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Sample records for stores regulates calcium

  1. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the ...

  2. Transgenic plants with increased calcium stores

    Science.gov (United States)

    Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Robertson, Dominique (Inventor); Boss, Wendy (Inventor)

    2004-01-01

    The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

  3. Forhastet regulering af de store

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2013-01-01

    Christiansborg gennemfører sandsynligvis en markant skærpet regulering af de store finansielle virksomheder. Det vil virke kontraktivt og medvirke til erhvervslivets kredittørke.......Christiansborg gennemfører sandsynligvis en markant skærpet regulering af de store finansielle virksomheder. Det vil virke kontraktivt og medvirke til erhvervslivets kredittørke....

  4. Calcium regulation and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Deepthi Rapaka

    2014-09-01

    Full Text Available Activation of the neuron induces transient fluctuations in [Ca2+]i. This transient rise in [Ca2+]i is dependent on calcium entry via calcium channels and release of calcium from intracellular stores, finally resulting in increase in calcium levels, which activates calcium regulatory proteins to restore the resting calcium levels by binding to the calcium-binding proteins, sequestration into the endoplasmic reticulum and the mitochondria, and finally extrusion of calcium spike potential from the cell by adenosine triphosphate-driven Ca2+ pumps and the Na+/Ca2+ exchanger. Improper regulation of calcium signaling, sequentially, likely contributes to synaptic dysfunction and excitotoxic and/or apoptotic death of the vulnerable neuronal populations. The cognitive decline associated with normal aging is not only due to neuronal loss, but is fairly the result of synaptic connectivity. Many evidences support that Ca2+ dyshomeostasis is implicated in normal brain aging. Thus the chief factor associated with Alzheimer’s disease was found to be increase in the levels of free intracellular calcium, demonstrating that the excessive levels might lead to cell death, which provides a key target for the calcium channel blockers might be used as the neuroprotective agents in Alzheimer’s disease.

  5. The functions of store-operated calcium channels.

    Science.gov (United States)

    Putney, James W; Steinckwich-Besançon, Natacha; Numaga-Tomita, Takuro; Davis, Felicity M; Desai, Pooja N; D'Agostin, Diane M; Wu, Shilan; Bird, Gary S

    2017-06-01

    Store-operated calcium channels provide calcium signals to the cytoplasm of a wide variety of cell types. The basic components of this signaling mechanism include a mechanism for discharging Ca 2+ stores (commonly but not exclusively phospholipase C and inositol 1,4,5-trisphosphate), a sensor in the endoplasmic reticulum that also serves as an activator of the plasma membrane channel (STIM1 and STIM2), and the store-operated channel (Orai1, 2 or 3). The advent of mice genetically altered to reduce store-operated calcium entry globally or in specific cell types has provided important tools to understand the functions of these widely encountered channels in specific and clinically important physiological systems. This review briefly discusses the history and cellular properties of store-operated calcium channels, and summarizes selected studies of their physiological functions in specific physiological or pathological contexts. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Published by Elsevier B.V.

  6. A pupal transcriptomic screen identifies Ral as a target of store-operated calcium entry in Drosophila neurons

    OpenAIRE

    Richhariya, Shlesha; Jayakumar, Siddharth; Abruzzi, Katharine; Rosbash, Michael; Hasan, Gaiti

    2017-01-01

    Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervou...

  7. Single molecule microscopy on Store-Operated Calcium channels

    International Nuclear Information System (INIS)

    Madl, J.

    2011-01-01

    Store-Operated Calcium Entry is essential for many signaling processes in non-excitable cells. The best studied Store-Operated Calcium current is the Calcium-Release-Activated-Calcium (CRAC) current in T-cells and mast cells, with Orai1 representing the essential pore forming subunit. Functional CRAC channels in store-depleted cells are composed of four Orai1 subunits. However, the stoichiometric composition in resting cells is still discussed controversially: both a tetrameric and a dimeric stoichiometry of resting-state Orai1 have been reported for immobilized or immobile Orai1 proteins. The aim of this thesis was to design a more versatile approach that allows reliable determination of the subunit stoichiometry of mobile Orai1 channels. The motive for this approach is that mobile sub-fractions of the entire Orai1 population provide the cleanest pool of data, devoid of contributions e.g. from immobile Orai1 clusters or Orai1-loaded vesicles attached to the plasma membrane. Moreover, resting-state Orai1 is predominantly mobile, and mobility appears critical for the lateral redistribution which occurs upon store depletion. The method per se is based on single molecule fluorescence microscopy and brightness analysis. Orai1 proteins were fused to a monomeric variant of Green Fluorescent Protein (mGFP) and over-expressed in a human cell line (T24). The 1:1 labeling stoichiometry allows using the brightness of individual Orai1-mGFP channels as a direct measure of the pore stoichiometry. Due to over-expression a potential mixing with endogenous Orai1 can be neglected. However, over-expression of Orai1-mGFP results in channel densities that are too high to allow for resolving single channels using diffraction limited optical microscopy. In order to overcome this challenge, I developed an experimental strategy that allows reduction of the density of actively fluorescent Orai1-mGFP channels without altering the labeling stoichiometry. In order to reduce the surface density

  8. Two-photon activation of endogenous store-operated calcium channels without optogenetics

    Science.gov (United States)

    Cheng, Pan; Tang, Wanyi; He, Hao

    2018-02-01

    Store-operated calcium (SOC) channels, regulated by intracellular Ca2+ store, are the essential pathway of calcium signaling and participate in a wide variety of cellular activities such as gene expression, secretion and immune response1. However, our understanding and regulation of SOC channels are mainly based on pharmacological methods. Considering the unique advantages of optical control, optogenetic control of SOC channels has been developed2. However, the process of genetic engineering to express exogenous light-sensitive protein is complicated, which arouses concerns about ethic difficulties in some research of animal and applications in human. In this report, we demonstrate rapid, robust and reproducible two-photon activation of endogenous SOC channels by femtosecond laser without optogenetics. We present that the short-duration two-photon scanning on subcellular microregion induces slow Ca2+ influx from extracellular medium, which can be eliminated by removing extracellular Ca2+. Block of SOC channels using various pharmacological inhibitors or knockdown of SOC channels by RNA interference reduce the probability of two-photon activated Ca2+ influx. On the contrary, overexpression of SOC channels can increase the probability of Ca2+ influx by two-photon scanning. These results collectively indicate Ca2+ influx through two-photon activated SOC channels. Different from classical pathway of SOC entry activated by Ca2+ store depletion, STIM1, the sensor protein of Ca2+ level in endoplasmic reticulum, does not show any aggregation or migration in this two-photon activated Ca2+ influx, which rules out the possibility of intracellular Ca2+ store depletion. Thereby, we propose this all-optical method of two-photon activation of SOC channels is of great potential to be widely applied in the research of cell calcium signaling and related biological research.

  9. Regulation of cardiomyocyte autophagy by calcium.

    Science.gov (United States)

    Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo-Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F G; Hill, Joseph A; Lavandero, Sergio

    2016-04-15

    Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy. Copyright © 2016 the American Physiological Society.

  10. Hydrostatic Pressure–Induced Release of Stored Calcium in Cultured Rat Optic Nerve Head Astrocytes

    Science.gov (United States)

    Mandal, Amritlal; Delamere, Nicholas A.

    2010-01-01

    Purpose. Elevated intraocular pressure is associated with glaucomatous optic nerve damage. Other investigators have shown functional changes in optic nerve head astrocytes subjected to elevated hydrostatic pressure (HP) for 1 to 5 days. Recently, the authors reported ERK1/2, p90RSK and NHE1 phosphorylation after 2 hours. Here they examine calcium responses at the onset of HP to determine what precedes ERK1/2 phosphorylation. Methods. Cytoplasmic calcium concentration ([Ca2+]i) was measured in cultured rat optic nerve astrocytes loaded with fura-2. The cells were placed in a closed imaging chamber and subjected to an HP increase of 15 mm Hg. Protein phosphorylation was detected by Western blot analysis. Results. The increase of HP caused an immediate slow increase in [Ca2+]i. The response persisted in calcium-free solution and when nickel chloride (4 mM) was added to suppress channel-mediated calcium entry. Previous depletion of the ER calcium stores by cyclopiazonic acid abolished the HP-induced calcium level increase. The HP-induced increase persisted in cells exposed to xestospongin C, an inhibitor of IP3R-mediated calcium release. In contrast, ryanodine receptor (RyR) antagonist ruthenium red (10 μM) or dantrolene (25 μM) inhibited the HP-induced calcium increase. The HP-induced calcium increase was abolished when ryanodine-sensitive calcium stores were pre-depleted with caffeine (3 mM). HP caused ERK1/2 phosphorylation. The magnitude of the ERK1/2 phosphorylation response was reduced by ruthenium red and dantrolene. Conclusions. Increasing HP causes calcium release from a ryanodine-sensitive cytoplasmic store and subsequent ERK1/2 activation. Calcium store release appears to be a required early step in the initial astrocyte response to an HP increase. PMID:20071675

  11. Enhanced Store-Operated Calcium Entry in Platelets is Associated with Peripheral Artery Disease in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Weijie Xia

    2015-11-01

    Full Text Available Background/Aims: Platelet dysfunction plays an important role in thrombosis in diabetes with peripheral artery disease (PAD. Store-operated calcium entry (SOCE and stromal interaction molecule 1 (STIM1 regulate platelet activity by modulating calcium influx. We hypothesized that enhanced SOCE in platelets is associated with diabetes with PAD. Methods: We studied the activity of platelets from healthy participants and from type 2 diabetic patients. Platelet calcium influx and protein expression of STIM1 and sarcoendoplasmic reticulum Ca2+-ATPase 3 (SERCA3 were investigated. Results: Compared with platelets from diabetic patients without PAD, platelets from diabetic patients with PAD exhibited significantly increased SOCE . Menthol administration completely inhibited calcium influx in platelets from diabetic patients without PAD, but this effect was blunted in those from diabetic patients with PAD. Furthermore, the increase in SOCE was correlated with the ankle brachial index (ABI in diabetic patients. High glucose significantly up-regulated STIM1 and SERCA3 protein expression and induced the phosphorylation of phospholipase C (PLC in platelets from healthy participants. This effect was attenuated in the presence of menthol or U73122, an inhibitor of PLC. Similarly, significant increases in STIM1 and SERCA3 protein expression were found in platelets from diabetic patients compared to those from healthy participants. Conclusion: Platelets from diabetic patients with PAD exhibited enhanced Store-operated calcium influx, which was associated with elevated STIM1/SERCA3 expression via a PLC-dependent pathway and was inhibited by menthol.

  12. Exopolysaccharides regulate calcium flow in cariogenic biofilms

    Science.gov (United States)

    Varenganayil, Muth M.; Decho, Alan W.

    2017-01-01

    Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS) provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya’s agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC) by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR) spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC). Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries. PMID:29023506

  13. Exopolysaccharides regulate calcium flow in cariogenic biofilms.

    Directory of Open Access Journals (Sweden)

    Monika Astasov-Frauenhoffer

    Full Text Available Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya's agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC. Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries.

  14. Calcium dips enhance volatile emission of cold-stored 'Fuji Kiku-8' apples.

    Science.gov (United States)

    Ortiz, Abel; Echeverría, Gemma; Graell, Jordi; Lara, Isabel

    2009-06-10

    Despite the relevance of volatile production for overall quality of apple (Malus x domestica Borkh.) fruit, only a few studies have focused on the effects of calcium treatments on this quality attribute. In this work, 'Fuji Kiku-8' apples were harvested at commercial maturity, dipped in calcium chloride (2%, w/v), stored at 1 degrees C and 92% relative humidity for 4 or 7 months under either air or ultralow oxygen (ULO; 1 kPa of O(2)/2 kPa of CO(2)), and placed subsequently at 20 degrees C. Ethylene production, standard quality parameters, emission of volatile compounds, and the activities of some related enzymes were assessed 7 days thereafter. Calcium concentration was higher in CaCl(2)-treated than in untreated fruit, suggesting that the treatment was effective in introducing calcium into the tissues. Higher calcium contents were concomitant with higher flesh firmness and titratable acidity after storage. Furthermore, calcium treatment led to increased production of volatiles in middle-term stored apples, probably arising from enhanced supply of precursors for ester production as a consequence of increased pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) activities. After long-term storage, higher volatile emission might have arisen also from the enhancement of alcohol o-acyltransferase (AAT) activity, which was increased as a result of calcium treatment. In addition to storage period, the effects of calcium treatment were also partially dependent on storage atmosphere and more noticeable for fruit stored in air.

  15. A pupal transcriptomic screen identifies Ral as a target of store-operated calcium entry in Drosophila neurons.

    Science.gov (United States)

    Richhariya, Shlesha; Jayakumar, Siddharth; Abruzzi, Katharine; Rosbash, Michael; Hasan, Gaiti

    2017-02-14

    Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase. Disruption of Ral function in neurons impaired flight, whereas ectopic expression of Ral in SOCE-compromised neurons restored flight. Through live imaging of calcium transients from cultured pupal neurons, we confirmed that Ral does not participate in SOCE, but acts downstream of it. These results identify neuronal SOCE as a mechanism that regulates expression of specific genes during development of the pupal nervous system and emphasizes the relevance of SOCE-regulated gene expression to flight circuit maturation.

  16. Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain

    DEFF Research Database (Denmark)

    Verma, A; Hirsch, D J; Hanley, M R

    1990-01-01

    ATP dependent Ca2+ accumulation into oxalate-loaded rat brain microsomes is potently inhibited by thapsigargin with an IC50 of 2 nM and maximal inhibition at 10 nM. Approximately 15% of the total A23187-releasable microsomal calcium store is insensitive to thapsigargin concentrations up to 100 mi...

  17. Regulation of intracellular calcium in resting and stimulated rat basophilic leukemia cells

    International Nuclear Information System (INIS)

    Mohr, F.C.

    1988-01-01

    Intracellular calcium regulation was studied in a cell line of mast cells, the rat basophilic leukemia (RBL) cells with the purpose of determining (1) The properties of the plasma membrane calcium permeability pathway and (2) The role of intracellular calcium stores. The first set of experiments showed that depolarization did not induce calcium entry or secretion in resting cells and did inhibit antigen-stimulated calcium uptake and secretion. In the second set of experiments the ionic basis of antigen-induced depolarization was studied using the fluorescent potential-sensitive probe bis-oxonol. The properties of the calcium entry pathway were more consistent with a calcium channel than a calcium transport mechanism such as Na:Ca exchange. The third set of experiments examined the effects of the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) on RBL cells. CCCP inhibited antigen-stimulated 45 Ca uptake and secretion by depolarizing the plasma membrane

  18. Depletion of intracellular calcium stores facilitates the influx of extracellular calcium in platelet derived growth factor stimulated A172 glioblastoma cells.

    Science.gov (United States)

    Vereb, G; Szöllösi, J; Mátyus, L; Balázs, M; Hyun, W C; Feuerstein, B G

    1996-05-01

    Calcium signaling in non-excitable cells is the consequence of calcium release from intracellular stores, at times followed by entry of extracellular calcium through the plasma membrane. To study whether entry of calcium depends upon the level of saturation of intracellular stores, we measured calcium channel opening in the plasma membrane of single confluent A172 glioblastoma cells stimulated with platelet derived growth factor (PDGF) and/or bradykinin (BK). We monitored the entry of extracellular calcium by measuring manganese quenching of Indo-1 fluorescence. PDGF raised intracellular calcium concentration ([Ca2+]i) after a dose-dependent delay (tdel) and then opened calcium channels after a dose-independent delay (tch). At higher doses (> 3 nM), BK increased [Ca2+]i after a tdel approximately 0 s, and tch decreased inversely with both dose and peak [Ca2+]i. Experiments with thapsigargin (TG), BK, and PDGF indicated that BK and PDGF share intracellular Ca2+ pools that are sensitive to TG. When these stores were depleted by treatment with BK and intracellular BAPTA, tdel did not change, but tch fell to almost 0 s in PDGF stimulated cells, indicating that depletion of calcium stores affects calcium channel opening in the plasma membrane. Our data support the capacitative model for calcium channel opening and the steady-state model describing quantal Ca2+ release from intracellular stores.

  19. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

  20. On the Role of Store-Operated Calcium Entry in Acute and Chronic Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Agnese Secondo

    2018-03-01

    Full Text Available In both excitable and non-excitable cells, calcium (Ca2+ signals are maintained by a highly integrated process involving store-operated Ca2+ entry (SOCE, namely the opening of plasma membrane (PM Ca2+ channels following the release of Ca2+ from intracellular stores. Upon depletion of Ca2+ store, the stromal interaction molecule (STIM senses Ca2+ level reduction and migrates from endoplasmic reticulum (ER-like sites to the PM where it activates the channel proteins Orai and/or the transient receptor potential channels (TRPC prompting Ca2+ refilling. Accumulating evidence suggests that SOCE dysregulation may trigger perturbation of intracellular Ca2+ signaling in neurons, glia or hematopoietic cells, thus participating to the pathogenesis of diverse neurodegenerative diseases. Under acute conditions, such as ischemic stroke, neuronal SOCE can either re-establish Ca2+ homeostasis or mediate Ca2+ overload, thus providing a non-excitotoxic mechanism of ischemic neuronal death. The dualistic role of SOCE in brain ischemia is further underscored by the evidence that it also participates to endothelial restoration and to the stabilization of intravascular thrombi. In Parkinson’s disease (PD models, loss of SOCE triggers ER stress and dysfunction/degeneration of dopaminergic neurons. Disruption of neuronal SOCE also underlies Alzheimer’s disease (AD pathogenesis, since both in genetic mouse models and in human sporadic AD brain samples, reduced SOCE contributes to synaptic loss and cognitive decline. Unlike the AD setting, in the striatum from Huntington’s disease (HD transgenic mice, an increased STIM2 expression causes elevated synaptic SOCE that was suggested to underlie synaptic loss in medium spiny neurons. Thus, pharmacological inhibition of SOCE is beneficial to synapse maintenance in HD models, whereas the same approach may be anticipated to be detrimental to cortical and hippocampal pyramidal neurons. On the other hand, up-regulation of

  1. Mitochondrial enzymes and endoplasmic reticulum calcium stores as targets of oxidative stress in neurodegenerative diseases.

    Science.gov (United States)

    Gibson, Gary E; Huang, Hsueh-Meei

    2004-08-01

    Considerable evidence indicates that oxidative stress accompanies age-related neurodegenerative diseases. Specific mechanisms by which oxidative stress leads to neurodegeneration are unknown. Two targets of oxidative stress that are known to change in neurodegenerative diseases are the mitochondrial enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC) and endoplasmic reticulum calcium stores. KGDHC activities are diminished in all common neurodegenerative diseases and the changes are particularly well documented in Alzheimer's disease (AD). A second change that occurs in cells from AD patients is an exaggerated endoplasmic reticulum calcium store [i.e., bombesin-releasable calcium stores (BRCS)]. H(2)O(2), a general oxidant, changes both variables in the same direction as occurs in disease. Other oxidants selectively alter these variables. Various antioxidants were used to help define the critical oxidant species that modifies these responses. All of the antioxidants diminish the oxidant-induced carboxy-dichlorofluorescein (cDCF) detectable reactive oxygen species (ROS), but have diverse actions on these cellular processes. For example, alpha-keto-beta-methyl-n-valeric acid (KMV) diminishes the H(2)O(2) effects on BRCS, while trolox and DMSO exaggerate the response. Acute trolox treatment does not alter H(2)O(2)-induced changes in KGDHC, whereas chronic treatment with trolox increases KGDHC almost threefold. The results suggest that KGDHC and BRCS provide targets by which oxidative stress may induce neurodegeneration and a useful tool for selecting antioxidants for reversing age-related neurodegeneration.

  2. Stores

    CERN Multimedia

    2004-01-01

    Following the introduction of Condensators, resistors and potentiometers from the Farnell electronic-catalogue into CERN Stores' catalogue, following products are now available: PRODUCT FAMILY GROUP SCEM Oscillators and quartz crystals 07.94.10 / 07.94.12 Diodes 08.51.14 / 08.51.54 Thyristors 08.51.60 / 08.51.66 Opto-electronics 08.52 Transistors 08.53 Integrated circuits 08.54 / 08.55 These articles can be procured in the same way as any other stores item, by completing a Material Request. N.B. Individual Farnell order codes can be used as keywords to facilitate searches in the CERN Stores Catalogue.

  3. Blockade of store-operated calcium entry alleviates high glucose-induced neurotoxicity via inhibiting apoptosis in rat neurons.

    Science.gov (United States)

    Xu, Zhenkuan; Xu, Wenzhe; Song, Yan; Zhang, Bin; Li, Feng; Liu, Yuguang

    2016-07-25

    Altered store-operated calcium entry (SOCE) has been suggested to be involved in many diabetic complications. However, the association of altered SOCE and diabetic neuronal damage remains unclear. This study aimed to investigate the effects of altered SOCE on primary cultured rat neuron injury induced by high glucose. Our data demonstrated that high glucose increased rat neuron injury and upregulated the expression of store-operated calcium channel (SOC). Inhibition of SOCE by a pharmacological inhibitor and siRNA knockdown of stromal interaction molecule 1 weakened the intracellular calcium overload, restored mitochondrial membrane potential, downregulated cytochrome C release and inhibited cell apoptosis. As well, treatment with the calcium chelator BAPTA-AM prevented cell apoptosis by ameliorating the high glucose-increased intracellular calcium level. These findings suggest that SOCE blockade may alleviate high glucose-induced neuronal damage by inhibiting apoptosis. SOCE might be a promising therapeutic target in diabetic neurotoxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Calcium regulates caveolin-1 expression at the transcriptional level

    International Nuclear Information System (INIS)

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming; Li, Yan; Liu, Dan; Zhang, Xue-Cheng; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2012-01-01

    Highlights: ► Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. ► An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. ► Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. ► Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca 2+ /calcineurin/NFAT.

  5. Brain calcium - Role in temperature regulation.

    Science.gov (United States)

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

    1973-01-01

    Perfusion of the preoptic-anterior hypothalamus with excess calcium ion in ground squirrels produces a drop in core temperature. The magnitude of the drop is directly dependent on ambient temperature. Respiration, heart rate, and oxygen consumption are also reduced during perfusion of calcium ion. It is concluded that the depression of body temperature during calcium ion perfusion is due to generalized depression of the neurons of the preoptic-anterior hypothalamus.

  6. Oxidative stress increases internal calcium stores and reduces a key mitochondrial enzyme.

    Science.gov (United States)

    Gibson, Gary E; Zhang, Hui; Xu, Hui; Park, Larry C H; Jeitner, Thomas M

    2002-03-16

    Fibroblasts from patients with genetic and non-genetic forms of Alzheimer's disease (AD) show many abnormalities including increased bombesin-releasable calcium stores (BRCS), diminished activities of the mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC), and an altered ability to handle oxidative stress. The link between genetic mutations (and the unknown primary event in non-genetic forms) and these other cellular abnormalities is unknown. To determine whether oxidative stress could be a convergence point that produces the other AD-related changes, these experiments tested in fibroblasts the effects of H(2)O(2), in the presence or absence of select antioxidants, on BRCS and KGDHC. H(2)O(2) concentrations that elevated carboxy-dichlorofluorescein (c-H(2)DCF)-detectable ROS increased BRCS and decreased KGDHC activity. These changes are in the same direction as those in fibroblasts from AD patients. Acute treatments with the antioxidants Trolox, or DMSO decreased c-H(2)DCF-detectable ROS by about 90%, but exaggerated the H(2)O(2)-induced increases in BRCS by about 4-fold and did not alter the reduction in KGDHC. Chronic pretreatments with Trolox more than doubled the BRCS, tripled KGDHC activities, and reduced the effects of H(2)O(2). Pretreatment with DMSO or N-acetyl cysteine diminished the BRCS and either had no effect, or exaggerated the H(2)O(2)-induced changes in these variables. The results demonstrate that BRCS and KGDHC are more sensitive to H(2)O(2) derived species than c-H(2)DCF, and that oxidized derivatives of the antioxidants exaggerate the actions of H(2)O(2). The findings support the hypothesis that select abnormalities in oxidative processes are a critical part of a cascade that leads to the cellular abnormalities in cells from AD patients.

  7. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-05-01

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774. © AlphaMed Press 2018.

  8. The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Javier Avila-Medina

    2018-03-01

    Full Text Available Cardiac, skeletal, and smooth muscle cells shared the common feature of contraction in response to different stimuli. Agonist-induced muscle's contraction is triggered by a cytosolic free Ca2+ concentration increase due to a rapid Ca2+ release from intracellular stores and a transmembrane Ca2+ influx, mainly through L-type Ca2+ channels. Compelling evidences have demonstrated that Ca2+ might also enter through other cationic channels such as Store-Operated Ca2+ Channels (SOCCs, involved in several physiological functions and pathological conditions. The opening of SOCCs is regulated by the filling state of the intracellular Ca2+ store, the sarcoplasmic reticulum, which communicates to the plasma membrane channels through the Stromal Interaction Molecule 1/2 (STIM1/2 protein. In muscle cells, SOCCs can be mainly non-selective cation channels formed by Orai1 and other members of the Transient Receptor Potential-Canonical (TRPC channels family, as well as highly selective Ca2+ Release-Activated Ca2+ (CRAC channels, formed exclusively by subunits of Orai proteins likely organized in macromolecular complexes. This review summarizes the current knowledge of the complex role of Store Operated Calcium Entry (SOCE pathways and related proteins in the function of cardiac, skeletal, and vascular smooth muscle cells.

  9. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian

    2012-03-06

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E 2 elevated [Ca 2+] i and increased Ca 2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E 2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E 2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E 2 induces the non-genomic responses Ca 2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E 2 responses. © 2012 Springer Science+Business Media, LLC.

  10. 43. Calmodulin regulating calcium sensitivity of Na channels

    Directory of Open Access Journals (Sweden)

    R. Vegiraju

    2016-07-01

    Full Text Available By extrapolating information from existing research and observing previous assumptions regarding the structure of the Na Channel, this experiment was conducted under the hypothesis that the Na Channel is in part regulated by the calmodulin protein, as a result proving calcium sensitivity of the Na Channel. Furthermore, we assume that there is a one to one stoichiometry between the Na Channel and the Calmodulin. There has been extensive research into the functionality and structure of sodium ion channels (Na channels, as several diseases are associated with the lack of regulation of sodium ions, that is caused by the disfunction of these Na channels. However, one highly controversial matter in the field is the importance of the protein calmodulin (CaM and calcium in Na channel function. Calmodulin is a protein that is well known for its role as a calcium binding messenger protein, and that association is believed to play an indirect role in regulating the Na channel through the Na channel’s supposed calcium sensitivity. While there are proponents for both sides, there has been relatively little research that provides strong evidence for either case. In this experiment, the effect of calmodulin on NaV 1.5 is tested by preparing a set of cardiac cells (of the human specie with the NaV 1.5 C-Termini and CaM protein, which were then to be placed in solutions with varying concentrations of calcium. We took special care to test multiple concentrations of calcium, as previous studies have tested very low concentrations, with Manu Ben-Johny’s team from the John Hopkins laboratory in particular testing up to a meager 50 micromolar, despite producing a well-respected paper (By comparison, the average Na channel can naturally sustain a concentration of almost 1-2 millimolar and on some occasions, reaching even higher concentrations. After using light scattering and observing the signals given off by the calcium interacting with these Nav1.5/Ca

  11. Buffer regulation of calcium puff sequences

    International Nuclear Information System (INIS)

    Fraiman, Daniel; Dawson, Silvina Ponce

    2014-01-01

    Puffs are localized Ca 2+ signals that arise in oocytes in response to inositol 1,4,5-trisphosphate (IP 3 ). They are the result of the liberation of Ca 2+ from the endoplasmic reticulum through the coordinated opening of IP 3 receptor/channels clustered at a functional release site. The presence of buffers that trap Ca 2+ provides a mechanism that enriches the spatio–temporal dynamics of cytosolic calcium. The expression of different types of buffers along the cell's life provides a tool with which Ca 2+ signals and their responses can be modulated. In this paper we extend the stochastic model of a cluster of IP 3 R-Ca 2+ channels introduced previously to elucidate the effect of buffers on sequences of puffs at the same release site. We obtain analytically the probability laws of the interpuff time and of the number of channels that participate of the puffs. Furthermore, we show that under typical experimental conditions the effect of buffers can be accounted for in terms of a simple inhibiting function. Hence, by exploring different inhibiting functions we are able to study the effect of a variety of buffers on the puff size and interpuff time distributions. We find the somewhat counter-intuitive result that the addition of a fast Ca 2+ buffer can increase the average number of channels that participate of a puff. (paper)

  12. Buffer regulation of calcium puff sequences.

    Science.gov (United States)

    Fraiman, Daniel; Dawson, Silvina Ponce

    2014-02-01

    Puffs are localized Ca(2 +) signals that arise in oocytes in response to inositol 1,4,5-trisphosphate (IP3). They are the result of the liberation of Ca(2 +) from the endoplasmic reticulum through the coordinated opening of IP3 receptor/channels clustered at a functional release site. The presence of buffers that trap Ca(2 +) provides a mechanism that enriches the spatio-temporal dynamics of cytosolic calcium. The expression of different types of buffers along the cell's life provides a tool with which Ca(2 +) signals and their responses can be modulated. In this paper we extend the stochastic model of a cluster of IP3R-Ca(2 +) channels introduced previously to elucidate the effect of buffers on sequences of puffs at the same release site. We obtain analytically the probability laws of the interpuff time and of the number of channels that participate of the puffs. Furthermore, we show that under typical experimental conditions the effect of buffers can be accounted for in terms of a simple inhibiting function. Hence, by exploring different inhibiting functions we are able to study the effect of a variety of buffers on the puff size and interpuff time distributions. We find the somewhat counter-intuitive result that the addition of a fast Ca(2 +) buffer can increase the average number of channels that participate of a puff.

  13. Calcium regulates the expression of a Dictyostelium discoideum ...

    Indian Academy of Sciences (India)

    In a screen for calcium-regulated gene expression during growth and development of Dictyostelium discoideum we have identified an asparaginyl tRNA synthetase (ddAsnRS) gene, the second tRNA synthetase gene identified in this organism. The ddAsnRS gene shows many unique features. One, it is repressed by ...

  14. Nitrogen enrichment regulates calcium sources in forests

    Science.gov (United States)

    Hynicka, Justin D.; Pett-Ridge, Julie C.; Perakis, Steven

    2016-01-01

    Nitrogen (N) is a key nutrient that shapes cycles of other essential elements in forests, including calcium (Ca). When N availability exceeds ecosystem demands, excess N can stimulate Ca leaching and deplete Ca from soils. Over the long term, these processes may alter the proportion of available Ca that is derived from atmospheric deposition vs. bedrock weathering, which has fundamental consequences for ecosystem properties and nutrient supply. We evaluated how landscape variation in soil N, reflecting long-term legacies of biological N fixation, influenced plant and soil Ca availability and ecosystem Ca sources across 22 temperate forests in Oregon. We also examined interactions between soil N and bedrock Ca using soil N gradients on contrasting basaltic vs. sedimentary bedrock that differed 17-fold in underlying Ca content. We found that low-N forests on Ca-rich basaltic bedrock relied strongly on Ca from weathering, but that soil N enrichment depleted readily weatherable mineral Ca and shifted forest reliance toward atmospheric Ca. Forests on Ca-poor sedimentary bedrock relied more consistently on atmospheric Ca across all levels of soil N enrichment. The broad importance of atmospheric Ca was unexpected given active regional uplift and erosion that are thought to rejuvenate weathering supply of soil minerals. Despite different Ca sources to forests on basaltic vs. sedimentary bedrock, we observed consistent declines in plant and soil Ca availability with increasing N, regardless of the Ca content of underlying bedrock. Thus, traditional measures of Ca availability in foliage and soil exchangeable pools may poorly reflect long-term Ca sources that sustain soil fertility. We conclude that long-term soil N enrichment can deplete available Ca and cause forests to rely increasingly on Ca from atmospheric deposition, which may limit ecosystem Ca supply in an increasingly N-rich world.

  15. The regulation of OXPHOS by extramitochondrial calcium.

    Science.gov (United States)

    Gellerich, Frank N; Gizatullina, Zemfira; Trumbeckaite, Sonata; Nguyen, Huu P; Pallas, Thilo; Arandarcikaite, Odeta; Vielhaber, Stephan; Seppet, Enn; Striggow, Frank

    2010-01-01

    Despite extensive research, the regulation of mitochondrial function is still not understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic task in co-ordinating the cellular work load and the regeneration of ATP by mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by the supply of glutamate to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier. Since this activation is not affected by ruthenium red, glutamate transport into mitochondria is controlled exclusively by extramitochondrial Ca2+. Therefore, this discovery shows that besides intramitochondrial also extramitochondrial Ca2+ regulates oxidative phosphorylation. This new mechanism acts as a mitochondrial "gas pedal", supplying the OXPHOS with substrate on demand. These results are in line with recent findings of Satrustegui and Palmieri showing that aralar as part of the malate-aspartate shuttle is involved in the Ca2+-dependent transport of reducing hydrogen equivalents (from NADH) into mitochondria. This review summarises results and evidence as well as hypothetical interpretations of data supporting the view that at the surface of mitochondria different regulatory Ca2+-binding sites exist and can contribute to cellular energy homeostasis. Moreover, on the basis of our own data, we propose that these surface Ca2+-binding sites may act as targets for neurotoxic proteins such as mutated huntingtin and others. The binding of these proteins to Ca2+-binding sites can impair the regulation by Ca2+, causing energetic depression and neurodegeneration. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Subcellular location of astrocytic calcium stores favors extrasynaptic neuron-astrocyte communication.

    Science.gov (United States)

    Patrushev, Ilya; Gavrilov, Nikolay; Turlapov, Vadim; Semyanov, Alexey

    2013-11-01

    Neuron-astrocyte interactions are important for brain computations and synaptic plasticity. Perisynaptic astrocytic processes (PAPs) contain a high density of transporters that are responsible for neurotransmitter clearance. Metabotropic glutamate receptors are thought to trigger Ca(2+) release from Ca(2+) stores in PAPs in response to synaptic activity. Our ultrastructural study revealed that PAPs are actually devoid of Ca(2+) stores and have a high surface-to-volume ratio favorable for uptake. Astrocytic processes containing Ca(2+) stores were located further away from the synapses and could therefore respond to changes in ambient glutamate. Thus, the anatomic data do not support communication involving Ca(2+) stores in tripartite synapses, but rather point to extrasynaptic communication. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid Precursor Protein Knock-In Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Zhang, Hua; Wu, Lili; Pchitskaya, Ekaterina; Zakharova, Olga; Saito, Takashi; Saido, Takaomi; Bezprozvanny, Ilya

    2015-09-30

    Alzheimer's disease (AD) is the most common reason for elderly dementia in the world. We proposed that memory loss in AD is related to destabilization of mushroom postsynaptic spines involved in long-term memory storage. We demonstrated previously that stromal interaction molecule 2 (STIM2)-regulated neuronal store-operated calcium entry (nSOC) in postsynaptic spines play a key role in stability of mushroom spines by maintaining activity of synaptic Ca(2+)/calmodulin kinase II (CaMKII). Furthermore, we demonstrated previously that the STIM2-nSOC-CaMKII pathway is downregulated in presenilin 1 M146V knock-in (PS1-M146V KI) mouse model of AD, leading to loss of hippocampal mushroom spines in this model. In the present study, we demonstrate that hippocampal mushroom postsynaptic spines are also lost in amyloid precursor protein knock-in (APPKI) mouse model of AD. We demonstrated that loss of mushroom spines occurs as a result of accumulation of extracellular β-amyloid 42 in APPKI culture media. Our results indicate that extracellular Aβ42 acts by overactivating mGluR5 receptor in APPKI neurons, leading to elevated Ca(2+) levels in endoplasmic reticulum, compensatory downregulation of STIM2 expression, impaired synaptic nSOC, and reduced CaMKII activity. Pharmacological inhibition of mGluR5 or overexpression of STIM2 rescued synaptic nSOC and prevented mushroom spine loss in APPKI hippocampal neurons. Our results indicate that downregulation of synaptic STIM2-nSOC-CaMKII pathway causes loss of mushroom synaptic spines in both presenilin and APPKI mouse models of AD. We propose that modulators/activators of this pathway may have a potential therapeutic value for treatment of memory loss in AD. Significance statement: A direct connection between amyloid-induced synaptic mushroom spine loss and neuronal store-operated calcium entry pathway is shown. These results provide strong support for the calcium hypothesis of neurodegeneration and further validate the synaptic

  18. Activation of PKA and Epac proteins by cyclic AMP depletes intracellular calcium stores and reduces calcium availability for vasoconstriction.

    Science.gov (United States)

    Cuíñas, Andrea; García-Morales, Verónica; Viña, Dolores; Gil-Longo, José; Campos-Toimil, Manuel

    2016-06-15

    We investigated the implication of PKA and Epac proteins in the endothelium-independent vasorelaxant effects of cyclic AMP (cAMP). Cytosolic Ca(2+) concentration ([Ca(2+)]c) was measured by fura-2 imaging in rat aortic smooth muscle cells (RASMC). Contraction-relaxation experiments were performed in rat aortic rings deprived of endothelium. In extracellular Ca(2+)-free solution, cAMP-elevating agents induced an increase in [Ca(2+)]c in RASMC that was reproduced by PKA and Epac activation and reduced after depletion of intracellular Ca(2+) reservoirs. Arginine-vasopressin (AVP)-evoked increase of [Ca(2+)]c and store-operated Ca(2+) entry (SOCE) were inhibited by cAMP-elevating agents, PKA or Epac activation in these cells. In aortic rings, the contractions induced by phenylephrine in absence of extracellular Ca(2+) were inhibited by cAMP-elevating agents, PKA or Epac activation. In these conditions, reintroduction of Ca(2+) induced a contraction that was inhibited by cAMP-elevating agents, an effect reduced by PKA inhibition and reproduced by PKA or Epac activators. Our results suggest that increased cAMP depletes intracellular, thapsigargin-sensitive Ca(2+) stores through activation of PKA and Epac in RASMC, thus reducing the amount of Ca(2+) released by IP3-generating agonists during the contraction of rat aorta. cAMP rise also inhibits the contraction induced by depletion of intracellular Ca(2+), an effect mediated by reduction of SOCE after PKA or Epac activation. Both effects participate in the cAMP-induced endothelium-independent vasorelaxation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Interactions of Mitochondria/Metabolism and Calcium Regulation in Alzheimer's Disease: A Calcinist Point of View.

    Science.gov (United States)

    Gibson, Gary E; Thakkar, Ankita

    2017-06-01

    Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry. Similar anomalies in calcium result when AD-like changes in mitochondrial enzymes or oxidative stress are induced experimentally. The calcium abnormalities can be directly linked to the altered tau phosphorylation, amyloid precursor protein processing and synaptic dysfunction that are defining features of AD. A better understanding of these changes is required before using calcium abnormalities as therapeutic targets.

  20. Complex actions of ionomycin in cultured cerebellar astrocytes affecting both calcium-induced calcium release and store-operated calcium entry

    DEFF Research Database (Denmark)

    Müller, Margit S; Obel, Linea Lykke Frimodt; Waagepetersen, Helle S

    2013-01-01

    The polyether antibiotic ionomycin is a common research tool employed to raise cytosolic Ca(2+) in almost any cell type. Although initially thought to directly cause physicochemical translocation of extracellular Ca(2+) into the cytosol, a number of studies have demonstrated that the mechanism of......(2+), consisting of an initial peak and a subsequent sustained plateau. The response was dependent on concentration and exposure time. While the plateau phase was abolished in the absence of extracellular Ca(2+), the peak phase persisted. The peak amplitude could be lowered significantly...... by application of dantrolene, demonstrating involvement of Ca(2+)-induced Ca(2+)-release (CICR). The plateau phase was markedly reduced when store-operated Ca(2+)-entry (SOCE) was blocked with 2-aminoethoxydiphenyl borate. Our results show that ionomycin directly affects internal Ca(2+) stores in astrocytes...

  1. Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

    Science.gov (United States)

    Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

    2016-01-01

    The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

  2. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry

    Directory of Open Access Journals (Sweden)

    Irina V. Gorudko

    2013-07-01

    Myeloperoxidase (MPO is a heme-containing enzyme released from activated leukocytes into the extracellular space during inflammation. Its main function is the production of hypohalous acids that are potent oxidants. MPO can also modulate cell signaling and inflammatory responses independently of its enzymatic activity. Because MPO is regarded as an important risk factor for cardiovascular diseases associated with increased platelet activity, we studied the effects of MPO on human platelet functional properties. Laser scanning confocal microscopy was used to reveal carbohydrate-independent MPO binding to human platelet membrane. Adding MPO to platelets did not activate their aggregation under basal conditions (without agonist. In contrast, MPO augmented agonist-induced platelet aggregation, which was not prevented by MPO enzymatic activity inhibitors. It was found that exposure of platelets to MPO leads to actin cytoskeleton reorganization and an increase in their elasticity. Furthermore, MPO evoked a rise in cytosolic Ca2+ through enhancement of store-operated Ca2+ entry (SOCE. Together, these findings indicate that MPO is not a direct agonist but rather a mediator that binds to human platelets, induces actin cytoskeleton reorganization and affects the mechanical stiffness of human platelets, resulting in potentiating SOCE and agonist-induced human platelet aggregation. Therefore, an increased activity of platelets in vascular disease can, at least partly, be provided by MPO elevated concentrations.

  3. Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

    Science.gov (United States)

    Zhang, Lili; Lu, Xiangru; Gui, Le; Wu, Yan; Sims, Stephen M; Wang, Guoping; Feng, Qingping

    2016-08-01

    Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  4. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  5. Role of vitamin D3 active metabolites in the regulation of calcium metabolism in hypokinetic rats

    International Nuclear Information System (INIS)

    Sergeev, I.N.; Afonin, B.V.; Blazhevich, N.V.

    1985-01-01

    The rats exposed to prolonged hypokinesia showed hypocalciemia, lower PTH and higher calcitonin concentrations in the serum, decreased calcium absorption in the small intestine, and a trend toward nephro- and arteriocalcinosis. Prophylactic administration of 24, 25-hydroxy D 3 , 1, 25-hydroxy D 3 and their combinations enhanced calcium absorption and alleviated hypocalciemia. The changes in the hormonal regulation of calcium homeostasis can be viewed as a factor responsible for calcium metabolic disorders associated with hypokinesia

  6. Calcium and cargoes as regulators of myosin 5a activity

    International Nuclear Information System (INIS)

    Sellers, James R.; Thirumurugan, Kavitha; Sakamoto, Takeshi; Hammer, John A.; Knight, Peter J.

    2008-01-01

    Myosin 5a is a two-headed actin-dependent motor that transports various cargoes in cells. Its enzymology and mechanochemistry have been extensively studied in vitro. It is a processive motor that takes multiple 36 nm steps on actin. The enzymatic activity of myosin 5 is regulated by an intramolecular folding mechanism whereby its lever arms fold back against the coiled-coil tail such that the motor domains directly bind the globular tail domains. We show that the structure seen in individual folded molecules is consistent with electron density map of two-dimensional crystals of the molecule. In this compact state, the actin-activated MgATPase activity of the molecule is markedly inhibited and the molecule cannot move processively on surface bound actin filaments. The actin-activated MgATPase activity of myosin 5a is activated by increasing the calcium concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro. However, calcium binding to the calmodulin light chains results in dissociation of some of the calmodulin which disrupts the ability of myosin 5a to move on actin filaments in vitro. Thus we propose that the physiologically relevant activation pathway in vivo involves binding of cargo-receptor proteins

  7. TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Serotonin and the regulation of calcium transport in dairy cows.

    Science.gov (United States)

    Hernandez, L L

    2017-12-01

    The mammary gland regulates maternal metabolism during lactation. Numerous factors within the tissue send signals to shift nutrients to the mammary gland for milk synthesis. Serotonin is a monoamine that has been well documented to regulate several aspects of lactation among species. Maintenance of maternal calcium homeostasis during lactation is a highly evolved process that is elegantly regulated by the interaction of the mammary gland with the bone, gut, and kidney tissues. It is well documented that dietary calcium is insufficient to maintain maternal calcium concentrations during lactation, and mammals must rely on bone resorption to maintain normocalcemia. Our recent work focused on the ability of the mammary gland to function as an accessory parathyroid gland during lactation. It was demonstrated that serotonin acts to stimulate parathyroid hormone-related protein (PTHrP) in the mammary gland during lactation. The main role of mammary-derived PTHrP during mammalian lactation is to stimulate bone resorption to maintain maternal calcium homeostasis during lactation. In addition to regulating PTHrP, it was shown that serotonin appears to directly affect calcium transporters and pumps in the mammary gland. Our current working hypothesis regarding the control of calcium during lactation is as follows: serotonin directly stimulates PTHrP production in the mammary gland through interaction with the sonic hedgehog signaling pathway. Simultaneously, serotonin directly increases calcium movement into the mammary gland and, subsequently, milk. These 2 direct actions of serotonin combine to induce a transient maternal hypocalcemia required to further stimulate PTHrP production and calcium mobilization from bone. Through these 2 routes, serotonin is able to improve maternal calcium concentrations. Furthermore, we have shown that Holstein and Jersey cows appear to regulate calcium in different manners and also respond differently to serotonergic stimulation of the calcium

  8. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Zi-xuan [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Rao, Wei [Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Huan [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Nan-ding [Department of Cardiology, Xi' an Traditional Chinese Medicine Hospital, Xi' an, 710032 (China); Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Zong-ren, E-mail: zongren@fmmu.edu.cn [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China)

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  9. Effect of calcium and salicylic acid on quality retention in relation to antioxidative enzymes in radish stored under refrigerated conditions.

    Science.gov (United States)

    Devi, Jomika; Bhatia, Surekha; Alam, M S; Dhillon, Tarsem Singh

    2018-03-01

    Effect of post harvest treatments with calcium chloride (CaCl 2 ) and salicylic acid (SA) on physiological and biochemical parameters in relation to activities of antioxidative enzymes were investigated in radish. Radish of variety Punjab Safed Mooli 2 was harvested, washed and treated with CaCl 2 (1, 1.5 and 2%) or SA (1, 1.5 and 2 mM). Treated as well as untreated radish were placed in open trays and stored under refrigerated (5 ± 1 °C, 90% RH) conditions for 42 days. Treatment of radish with CaCl 2 and SA slowed down changes in physiological weight, colour, total soluble solids, ascorbic acid, titrable acidity, total phenolics and antioxidant activity. Treated samples exhibited higher enhancement in activities of antioxidant enzymes viz. catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), peroxidase (POD), dehydroascorbate reductase (DHAR) and monodehydro-ascorbate reductase (MDHAR) than untreated samples. However SA was found to be more effective in slowing down the metabolic activities of radish as compared to CaCl 2 treatment. Among all the treatments, 1.5 mM SA maintained the quality parameters to greater extent probably by reducing the oxidative stress to larger extent due to highest activities of antioxidative enzymes and can be used to enhance the shelf life of radish during refrigerated storage.

  10. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    International Nuclear Information System (INIS)

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren

    2015-01-01

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion

  11. Thioredoxin h regulates calcium dependent protein kinases in plasma membranes.

    Science.gov (United States)

    Ueoka-Nakanishi, Hanayo; Sazuka, Takashi; Nakanishi, Yoichi; Maeshima, Masayoshi; Mori, Hitoshi; Hisabori, Toru

    2013-07-01

    Thioredoxin (Trx) is a key player in redox homeostasis in various cells, modulating the functions of target proteins by catalyzing a thiol-disulfide exchange reaction. Target proteins of cytosolic Trx-h of higher plants were studied, particularly in the plasma membrane, because plant plasma membranes include various functionally important protein molecules such as transporters and signal receptors. Plasma membrane proteins from Arabidopsis thaliana cell cultures were screened using a resin Trx-h1 mutant-immobilized, and a total of 48 candidate proteins obtained. These included two calcium-sensing proteins: a phosphoinositide-specific phospholipase 2 (AtPLC2) and a calcium-dependent protein kinase 21 (AtCPK21). A redox-dependent change in AtCPK21 kinase activity was demonstrated in vitro. Oxidation of AtCPK21 resulted in a decrease in kinase activity to 19% of that of untreated AtCPK21, but Trx-h1 effectively restored the activity to 90%. An intramolecular disulfide bond (Cys97-Cys108) that is responsible for this redox modulation was then identified. In addition, endogenous AtCPK21 was shown to be oxidized in vivo when the culture cells were treated with H2 O2 . These results suggest that redox regulation of AtCPK21 by Trx-h in response to external stimuli is important for appropriate cellular responses. The relationship between the redox regulation system and Ca(2+) signaling pathways is discussed. © 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  12. Store-operated calcium entry is required for sustained contraction and Ca2+ oscillations of airway smooth muscle.

    Science.gov (United States)

    Chen, Jun; Sanderson, Michael J

    2017-05-15

    Airway hyper-responsiveness in asthma is driven by excessive contraction of airway smooth muscle cells (ASMCs). Agonist-induced Ca 2+ oscillations underlie this contraction of ASMCs and the magnitude of this contraction is proportional to the Ca 2+ oscillation frequency. Sustained contraction and Ca 2+ oscillations require an influx of extracellular Ca 2+ , although the mechanisms and pathways mediating this Ca 2+ influx during agonist-induced ASMC contraction are not well defined. By inhibiting store-operated calcium entry (SOCE) or voltage-gated Ca 2+ channels (VGCCs), we show that SOCE, rather than Ca 2+ influx via VGCCs, provides the major Ca 2+ entry pathway into ASMCs to sustain ASMCs contraction and Ca 2+ oscillations. SOCE may therefore serve as a potential target for new bronchodilators to reduce airway hyper-responsiveness in asthma. Asthma is characterized by airway hyper-responsiveness: the excessive contraction of airway smooth muscle. The extent of this airway contraction is proportional to the frequency of Ca 2+ oscillations within airway smooth muscle cells (ASMCs). Sustained Ca 2+ oscillations require a Ca 2+ influx to replenish Ca 2+ losses across the plasma membrane. Our previous studies implied store-operated calcium entry (SOCE) as the major pathway for this Ca 2+ influx. In the present study, we explore this hypothesis, by examining the effects of SOCE inhibitors (GSK7975A and GSK5498A) as well as L-type voltage-gated Ca 2+ channel inhibitors (nifedipine and nimodipine) on airway contraction and Ca 2+ oscillations and SOCE-mediated Ca 2+ influx in ASMCs within mouse precision-cut lung slices. We found that both GSK7975A and GSK5498A were able to fully relax methacholine-induced airway contraction by abolishing the Ca 2+ oscillations, in a manner similar to that observed in zero extracellular Ca 2+ ([Ca 2+ ] e ). In addition, GSK7975A and GSK5498A inhibited increases in intracellular Ca 2+ ([Ca 2+ ] i ) in ASMCs with depleted Ca 2+ -stores in

  13. Low stored energy 100 kV regulator for ion sources at LANSCE

    International Nuclear Information System (INIS)

    Jacobson, E.G.; Haffner, R.L.; Ingalls, W.B.; Meyer, B.J.; Stelzer, J.E.

    1998-01-01

    To minimize accelerating column damage caused by uncontrolled energy release during arc-downs, it is desirable to minimize the available stored electrical energy. For the Los Alamos Neutron Science Center (LANSCE) H - ion sources, the stored energy includes, in addition to the charge in the power supply output capacitance, the charge on the electronics racks. They are supported and insulated from ground by PVC pipe and have a capacitance to ground of approximately 900 pf. In 1988 (LANSCE) personnel designed a high-voltage current source using a low-stored-energy power supply and planar triode with the goal of eliminating uncontrolled release of charge stored in the power supply. Construction and testing were performed intermittently as resources permitted until 1993. When work on the Short Pulse Spallation Source (SPSS) started on the LANSCE Ion Source Test Stand (ISTS) it was recognized that a higher current power supply would be needed and work resumed on the regulator circuitry. A 120 kV power supply having low output capacitance, and a planar triode have been used to supply 40 mA, 120 Hz, 12% duty-factor current for the ISTS beam. The triode's cathode current is controlled by circuitry operating both at power-supply voltage level and at ground level via a fiber optic link. Voltage droop is approximately 600 V during the 1 ms beam pulse. The authors present the status of the regulator and its special challenges

  14. Calcium

    Science.gov (United States)

    ... You can get decent amounts of calcium from baked beans, navy beans, white beans, and others. Canned fish. You're in luck if you like sardines and canned salmon with bones. Almond milk. Working Calcium Into Your ...

  15. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model.

    Science.gov (United States)

    Wu, Jun; Ryskamp, Daniel A; Liang, Xia; Egorova, Polina; Zakharova, Olga; Hung, Gene; Bezprozvanny, Ilya

    2016-01-06

    YAC128 HD mice feature age-dependent MSN spine loss, mirroring YAC128 MSN spine loss in vivo. This finding establishes a system for mechanistic studies of synaptic instability in HD. We use it to demonstrate that sensitization of type 1 inositol (1,4,5)-trisphosphate receptors by mHtt, which depletes endoplasmic reticulum calcium, contributes to synaptotoxic enhancement of STIM2-dependent store-operated calcium (SOC) entry. Treatment with EVP4593, a neuroprotective inhibitor of neuronal SOC channels, rescues YAC128 MSN spine loss both in vitro and in vivo. These results suggest that enhanced neuronal SOC causes synaptic loss in HD-afflicted MSNs. Copyright © 2016 the authors 0270-6474/16/360125-17$15.00/0.

  16. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  17. Effect of freeze-thawing on the long-term stability of calcium levofolinate in 5% dextrose stored on polyolefin infusion bags.

    Science.gov (United States)

    Lebitasy, M; Hecq, J-D; Athanassopoulos, A; Vanbeckbergen, D; Jamart, J; Galanti, L

    2009-08-01

    Calcium levofolinate infusions could be prepared in advance by a centralized intravenous additive service (CIVAS) to improve safety and time management. To investigate the effect of freezing, microwave thawing and long-term storage at 5 +/- 3 degrees C on the stability of calcium levofolinate in 5% dextrose solution. Solutions of 250 mL of 5% dextrose in polyolefin bags (n = 5) containing approximately 400 mg of calcium levofolinate were prepared under aseptic conditions and frozen for 95 days at -20 degrees C. The solutions were then thawed using microwaves and stored at 5 +/- 3 degrees C for 1 month. The calcium levofolinate concentrations were measured by high performance liquid chromatography (HPLC). Visual inspection was performed and pH was measured periodically during the storage at 5 +/- 3 degrees C. Stability of the solution was defined as a concentration remaining superior to 90% of the initial concentration by regression analysis as recommended by the Food and Drug Administration (FDA). No colour change or precipitation in the solutions was observed. Calcium levofolinate infusions were stable when stored at 5 +/- 3 degrees C during 1 month after freeze-thaw treatment. Throughout this period, the lower confidence limit of the estimated regression line of concentration-time profile remained above 90% of the initial concentration. Slight change in pH values from 6.52 +/- 0.01 to 6.50 +/- 0.01 during storage time did not affect retention time on HPLC and has no clinical consequence, the solutions remaining in the acceptable range for perfusion (4 calcium levofolinate in 5% dextrose infusion may be prepared, frozen in advance by CIVAS, and then microwave thawed before use. Such treatment extends long-term stability and releases pharmacist's time for major activities such as checking medication order errors.

  18. Discrete-State Stochastic Models of Calcium-Regulated Calcium Influx and Subspace Dynamics Are Not Well-Approximated by ODEs That Neglect Concentration Fluctuations

    Science.gov (United States)

    Weinberg, Seth H.; Smith, Gregory D.

    2012-01-01

    Cardiac myocyte calcium signaling is often modeled using deterministic ordinary differential equations (ODEs) and mass-action kinetics. However, spatially restricted “domains” associated with calcium influx are small enough (e.g., 10−17 liters) that local signaling may involve 1–100 calcium ions. Is it appropriate to model the dynamics of subspace calcium using deterministic ODEs or, alternatively, do we require stochastic descriptions that account for the fundamentally discrete nature of these local calcium signals? To address this question, we constructed a minimal Markov model of a calcium-regulated calcium channel and associated subspace. We compared the expected value of fluctuating subspace calcium concentration (a result that accounts for the small subspace volume) with the corresponding deterministic model (an approximation that assumes large system size). When subspace calcium did not regulate calcium influx, the deterministic and stochastic descriptions agreed. However, when calcium binding altered channel activity in the model, the continuous deterministic description often deviated significantly from the discrete stochastic model, unless the subspace volume is unrealistically large and/or the kinetics of the calcium binding are sufficiently fast. This principle was also demonstrated using a physiologically realistic model of calmodulin regulation of L-type calcium channels introduced by Yue and coworkers. PMID:23509597

  19. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  20. Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility.

    Directory of Open Access Journals (Sweden)

    Jian Sun

    2016-05-01

    Full Text Available A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling.

  1. Regulating Intracellular Calcium in Plants: From Molecular Genetics to Physiology

    International Nuclear Information System (INIS)

    Sze, Heven

    2008-01-01

    To grow, develop, adapt, and reproduce, plants have evolved mechanisms to regulate the uptake, translocation and sorting of calcium ions into different cells and subcellular compartments. Yet how plants accomplish this remarkable feat is still poorly understood. The spatial and temporal changes in intracellular (Ca2+) during growth and during responses to hormonal and environmental stimuli indicate that Ca2+ influx and efflux transporters are diverse and tightly regulated in plants. The specific goals were to determine the biological roles of multiple Ca pumps (ECAs) in the model plant Arabidopsis thaliana. We had pioneered the use of K616 yeast strain to functionally express plant Ca pumps, and demonstrated two distinct types of Ca pumps in plants (Sze et al., 2000. Annu Rev Plant Biol. 51,433). ACA2 represented one type that was auto-inhibited by the N-terminal region and stimulated by calmodulin. ECA1 represented another type that was not sensitive to calmodulin and phylogenetically distinct from ACAs. The goal to determine the biological roles of multiple ECA-type Ca pumps in Arabidopsis has been accomplished. Although we demonstrated ECA1 was a Ca pump by functional expression in yeast, the in vivo roles of ECAs was unclear. A few highlights are described. ECA1 and/or ECA4 are Ca/Mn pumps localized to the ER and are highly expressed in all cell types. Using homozygous T-DNA insertional mutants of eca1, we demonstrated that the ER-bound ECA1 supports growth and confers tolerance of plants growing on medium low in Ca or containing toxic levels of Mn. This is the first genetic study to determine the in vivo function of a Ca pump in plants. A phylogenetically distinct ECA3 is also a Ca/Mn pump that is localized to endosome, such as post-Golgi compartments. Although it is expressed at lower levels than ECA1, eca3 mutants are impaired in Ca-dependent root growth and in pollen tube elongation. Increased secretion of wall proteins in mutants suggests that Ca and Mn

  2. Intracellular calcium levels can regulate Importin-dependent nuclear import

    International Nuclear Information System (INIS)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A.

    2014-01-01

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca 2+ on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery

  3. Intracellular calcium levels can regulate Importin-dependent nuclear import

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

    2014-07-18

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.

  4. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Wang, Xiaorui; Wang, Yue

    2010-01-01

    the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast......BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define...... neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium...

  5. Calcium in drinking water: effect on iron stores in Danish blood donors-results from the Danish Blood Donor Study.

    Science.gov (United States)

    Rigas, Andreas S; Ejsing, Benedikte H; Sørensen, Erik; Pedersen, Ole B; Hjalgrim, Henrik; Erikstrup, Christian; Ullum, Henrik

    2018-03-25

    Studies confirm that calcium inhibits iron absorption. Danish tap water comes from groundwater, which contains varying amounts of calcium depending on the subsoil. We investigated the association of calcium in drinking water with iron levels in Danish blood donors. We used data on Danish blood donors including dietary and lifestyle habits, blood donation history, and physiologic characteristics including measures of ferritin levels along with information on area of residence from The Danish Blood Donor Study. Data on calcium levels in groundwater ("water hardness") were obtained through the Geological Survey of Denmark and Greenland. We performed multiple linear and logistic regression analyses to evaluate the effect of water hardness on ferritin levels and risk of having iron deficiency (defined as ferritin levels water hardness and ferritin levels in both men and women. Risk of iron deficiency was correspondingly increased in both men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.14-2.12) and women (OR, 1.20; 95% CI, 1.03-1.40) with increasing water hardness. In analyses restricted to individuals who received supplemental iron tablets no significant association between groundwater hardness and ferritin levels was observed. As measured by ferritin levels, residential drinking water calcium content is associated with blood donors- iron levels and risk of iron deficiency. However, effect sizes are small. © 2018 AABB.

  6. Calcium-Mediated Regulation of Proton-Coupled Sodium Transport - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Schumaker, Karen S [Professor

    2013-10-24

    The long-term goal of our experiments was to understand mechanisms that regulate energy coupling by ion currents in plants. Activities of living organisms require chemical, mechanical, osmotic or electrical work, the energy for which is supplied by metabolism. Adenosine triphosphate (ATP) has long been recognized as the universal energy currency, with metabolism supporting the synthesis of ATP and the hydrolysis of ATP being used for the subsequent work. However, ATP is not the only energy currency in living organisms. A second and very different energy currency links metabolism to work by the movement of ions passing from one side of a membrane to the other. These ion currents play a major role in energy capture and they support a range of physiological processes from the active transport of nutrients to the spatial control of growth and development. In Arabidopsis thaliana (Arabidopsis), the activity of a plasma membrane Na+/H+ exchanger, SALT OVERLY SENSITIVE1 (SOS1), is essential for regulation of sodium ion homeostasis during plant growth in saline conditions. Mutations in SOS1 result in severely reduced seedling growth in the presence of salt compared to the growth of wild type. SOS1 is a secondary active transporter coupling movement of sodium ions out of the cell using energy stored in the transplasma membrane proton gradient, thereby preventing the build-up of toxic levels of sodium in the cytosol. SOS1 is regulated by complexes containing the SOS2 and CALCINEURIN B-LIKE10 (CBL10) or SOS3 proteins. CBL10 and SOS3 (also identified as CBL4) encode EF-hand calcium sensors that interact physically with and activate SOS2, a serine/threonine protein kinase. The CBL10/SOS2 or SOS3/SOS2 complexes then activate SOS1 Na+/H+ exchange activity. We completed our studies to understand how SOS1 activity is regulated. Specifically, we asked: (1) how does CBL10 regulate SOS1 activity? (2) What role do two putative CBL10-interacting proteins play in SOS1 regulation? (3) Are

  7. SNF1-related protein kinases 2 are negatively regulated by a plant-specific calcium sensor.

    Science.gov (United States)

    Bucholc, Maria; Ciesielski, Arkadiusz; Goch, Grażyna; Anielska-Mazur, Anna; Kulik, Anna; Krzywińska, Ewa; Dobrowolska, Grażyna

    2011-02-04

    SNF1-related protein kinases 2 (SnRK2s) are plant-specific enzymes involved in environmental stress signaling and abscisic acid-regulated plant development. Here, we report that SnRK2s interact with and are regulated by a plant-specific calcium-binding protein. We screened a Nicotiana plumbaginifolia Matchmaker cDNA library for proteins interacting with Nicotiana tabacum osmotic stress-activated protein kinase (NtOSAK), a member of the SnRK2 family. A putative EF-hand calcium-binding protein was identified as a molecular partner of NtOSAK. To determine whether the identified protein interacts only with NtOSAK or with other SnRK2s as well, we studied the interaction of an Arabidopsis thaliana orthologue of the calcium-binding protein with selected Arabidopsis SnRK2s using a two-hybrid system. All kinases studied interacted with the protein. The interactions were confirmed by bimolecular fluorescence complementation assay, indicating that the binding occurs in planta, exclusively in the cytoplasm. Calcium binding properties of the protein were analyzed by fluorescence spectroscopy using Tb(3+) as a spectroscopic probe. The calcium binding constant, determined by the protein fluorescence titration, was 2.5 ± 0.9 × 10(5) M(-1). The CD spectrum indicated that the secondary structure of the protein changes significantly in the presence of calcium, suggesting its possible function as a calcium sensor in plant cells. In vitro studies revealed that the activity of SnRK2 kinases analyzed is inhibited in a calcium-dependent manner by the identified calcium sensor, which we named SCS (SnRK2-interacting calcium sensor). Our results suggest that SCS is involved in response to abscisic acid during seed germination most probably by negative regulation of SnRK2s activity.

  8. Epithelial calcium channels: from identification to function and regulation.

    NARCIS (Netherlands)

    Hoenderop, J.G.J.; Nilius, B.; Bindels, R.J.M.

    2003-01-01

    The epithelial calcium channels TRPV5 and TRPV6 have been studied extensively in the epithelial tissues controlling Ca(2+) homeostasis and exhibit a range of distinctive properties that distinguish them from other transient receptor potential (TRP) channels. These two novel members of the

  9. The effects of calcium regulation of endosperm reserve protein ...

    African Journals Online (AJOL)

    The effects of steep liquor calcium ion on sorghum endosperm reserve protein mobilization were evaluated using two improved Nigeria sorghum cultivars (ICSV 400 and KSV 8). The key protein modification factors evaluated were free amino nitrogen (FAN), total non protein nitrogen (TNPN) and soluble protein of cold water ...

  10. Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate-Aspartate NADH Shuttle

    DEFF Research Database (Denmark)

    Satrústegui, Jorgina; Bak, Lasse K

    2015-01-01

    that MAS is regulated by fluctuations in cytosolic Ca(2+) levels, and that this regulation is required to maintain a tight coupling between neuronal activity and mitochondrial respiration and oxidative phosphorylation. At cytosolic Ca(2+) fluctuations below the threshold of the mitochondrial calcium...

  11. Computer simulation studies in fluid and calcium regulation and orthostatic intolerance

    Science.gov (United States)

    1985-01-01

    The systems analysis approach to physiological research uses mathematical models and computer simulation. Major areas of concern during prolonged space flight discussed include fluid and blood volume regulation; cardiovascular response during shuttle reentry; countermeasures for orthostatic intolerance; and calcium regulation and bone atrophy. Potential contributions of physiologic math models to future flight experiments are examined.

  12. Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man

    International Nuclear Information System (INIS)

    Kanis, J.A.; Cundy, T.; Bartlett, M.; Smith, R.; Heynen, G.; Warner, G.T.; Russell, R.G.G.

    1978-01-01

    Small doses (1 to 10 μg daily) of 24,25-dihydroxycholecalciferol (24,25-(OH) 2 D 3 ), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders of mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH) 2 D 3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH) 2 D 3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent. (author)

  13. TRPC1, STIM1, and ORAI influence signal-regulated intracellular and endoplasmic reticulum calcium dynamics in human myometrial cells.

    Science.gov (United States)

    Murtazina, Dilyara A; Chung, Daesuk; Ulloa, Aida; Bryan, Emily; Galan, Henry L; Sanborn, Barbara M

    2011-08-01

    To explore the relationship between signal-stimulated increases in intracellular calcium ([Ca(2+)](i)) and depletion and refilling of the endoplasmic reticulum (ER) Ca(2+) stores ([Ca(2+)](L)) in human myometrial cells, we measured simultaneous changes in [Ca(2+)](i) and [Ca(2+)](L) using Fura-2 and Mag-fluo-4, respectively, in PHM1-41 immortalized and primary cells derived from pregnant myometrium and in primary cells derived from nonpregnant tissue. Signal- and extracellular Ca(2+)-dependent increases in [Ca(2+)](i) (SRCE) and ER refilling stimulated by oxytocin and cyclopiazonic acid were not inhibited by voltage-operated channel blocker nifedipine or mibefradil, inhibition of Na(+)/Ca(2+) exchange with KB-R7943, or zero extracellular Na(+) in PHM1-41 cells. Gadolinium-inhibited oxytocin- and cyclopiazonic acid-induced SRCE and slowed ER store refilling. TRPC1 mRNA knockdown specifically inhibited oxytocin-stimulated SRCE but had no statistically significant effect on ER store refilling and no effect on either parameter following cyclopiazonic acid treatment. Dominant negative STIMΔERM expression attenuated oxytocin- and thapsigargin-stimulated SRCE. Both STIM1 and ORAI1-ORAI3 mRNA knockdowns significantly attenuated oxytocin- and cyclopiazonic acid-stimulated SRCE. The data also suggest that reduction in STIM1 or ORAI1-ORAI3 mRNA can impede the rate of ER store refilling following removal of SERCA inhibition. These data provide evidence for both distinct and overlapping influences of TRPC1, STIM1, and ORAI1-ORAI3 on SRCE and ER store refilling in human myometrial cells that may contribute to the regulation of myometrial Ca(2+) dynamics. These findings have important implications for understanding the control of myometrial Ca(2+) dynamics in relation to myometrial contractile function.

  14. Regulation of Energy Stores and Feeding by Neuronal and Peripheral CREB Activity in Drosophila

    Science.gov (United States)

    Iijima, Koichi; Zhao, LiJuan; Shenton, Christopher; Iijima-Ando, Kanae

    2009-01-01

    The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores and increased sensitivity to starvation. Expression of DN-CREB in the fat body also reduced glycogen levels, while it did not affect starvation sensitivity, presumably due to increased lipid levels in these flies. Interestingly, blocking CREB activity in the fat body increased food intake. These flies did not show a significant change in overall body size, suggesting that disruption of CREB activity in the fat body caused an obese-like phenotype. Using a transgenic CRE-luciferase reporter, we further demonstrated that disruption of the adipokinetic hormone receptor, which is functionally related to mammalian glucagon and β-adrenergic signaling, in the fat body reduced CRE-mediated transcription in flies. This study demonstrates that CREB activity in either neuronal or peripheral tissues regulates energy balance in Drosophila, and that the key signaling pathway regulating CREB activity in peripheral tissue is evolutionarily conserved. PMID:20041126

  15. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    Science.gov (United States)

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  16. Regulation of Bicarbonate Secretion in Marine Fish Intestine by the Calcium-Sensing Receptor

    Directory of Open Access Journals (Sweden)

    Sílvia F. Gregório

    2018-04-01

    Full Text Available In marine fish, high epithelial intestinal HCO3− secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR in the regulation of HCO3− secretion in the intestine of the sea bream (Sparus aurata L.. Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine. CaSR expression reflected intestinal fluid calcium concentration. In addition, anterior intestine tissue was mounted in Ussing chambers to test the putative regulation of HCO3− secretion in vitro using the anterior intestine. HCO3− secretion was sensitive to varying calcium levels in luminal saline and to calcimimetic compounds known to activate/block the CaSR i.e., R 568 and NPS-2143. Subsequent experiments were performed in intestinal sacs to measure water absorption and the sensitivity of water absorption to varying luminal levels of calcium and calcimimetics were exposed as well. It appears, that CaSR mediates HCO3− secretion and water absorption in marine fish as shown by responsiveness to calcium levels and calcimimetic compounds.

  17. A role for calcium in the regulation of ATP-binding cassette, sub-family C, member 3 (ABCC3) gene expression in a model of epidermal growth factor-mediated breast cancer epithelial-mesenchymal transition.

    Science.gov (United States)

    Stewart, Teneale A; Azimi, Iman; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2015-03-13

    Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. T-type voltage-gated calcium channels regulate the tone of mouse efferent arterioles

    DEFF Research Database (Denmark)

    Poulsen, Christian B; Al-Mashhadi, Rozh H; Cribbs, Leanne L

    2011-01-01

    Voltage-gated calcium channels are important for the regulation of renal blood flow and the glomerular filtration rate. Excitation-contraction coupling in afferent arterioles is known to require activation of these channels and we studied their role in the regulation of cortical efferent arteriolar...... tone. We used microdissected perfused mouse efferent arterioles and found a transient vasoconstriction in response to depolarization with potassium; an effect abolished by removal of extracellular calcium. The T-type voltage-gated calcium channel antagonists mibefradil and nickel blocked this potassium...... by immunocytochemistry to be located in mouse efferent arterioles, human pre- and postglomerular vasculature, and Ca(v)3.2 in rat glomerular arterioles. Inhibition of endothelial nitric oxide synthase by L-NAME or its deletion by gene knockout changed the potassium-elicited transient constriction to a sustained response...

  19. Intracellular sphingosine releases calcium from lysosomes.

    Science.gov (United States)

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

    2015-11-27

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

  20. Tight junction regulates epidermal calcium ion gradient and differentiation

    International Nuclear Information System (INIS)

    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya; Sasaki, Hiroyuki

    2011-01-01

    Research highlights: → We disrupted epidermal tight junction barrier in reconstructed epidermis. → It altered Ca 2+ distribution and consequentially differentiation state as well. → Tight junction should affect epidermal homeostasis by maintaining Ca 2+ gradient. -- Abstract: It is well known that calcium ions (Ca 2+ ) induce keratinocyte differentiation. Ca 2+ distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca 2+ gradient since it is considered the only permeability barrier in the skin. However, the epidermal tight junction (TJ) in the granulosum has recently been suggested to restrict molecular movement to assist the SC as a secondary barrier. The objective of this study was to clarify the contribution of the TJ to Ca 2+ gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca 2+ flux increased and the gradient changed in ion-capture cytochemistry images. Alterations of ultrastructures and proliferation/differentiation markers revealed that both hyperproliferation and precocious differentiation occurred regionally in the epidermis. These results suggest that the TJ plays a crucial role in maintaining epidermal homeostasis by controlling the Ca 2+ gradient.

  1. Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium Sensor Protein Regulation of Presynaptic Calcium Channels.

    Science.gov (United States)

    Nanou, Evanthia; Lee, Amy; Catterall, William A

    2018-05-02

    Activity-dependent regulation controls the balance of synaptic excitation to inhibition in neural circuits, and disruption of this regulation impairs learning and memory and causes many neurological disorders. The molecular mechanisms underlying short-term synaptic plasticity are incompletely understood, and their role in inhibitory synapses remains uncertain. Here we show that regulation of voltage-gated calcium (Ca 2+ ) channel type 2.1 (Ca V 2.1) by neuronal Ca 2+ sensor (CaS) proteins controls synaptic plasticity and excitation/inhibition balance in a hippocampal circuit. Prevention of CaS protein regulation by introducing the IM-AA mutation in Ca V 2.1 channels in male and female mice impairs short-term synaptic facilitation at excitatory synapses of CA3 pyramidal neurons onto parvalbumin (PV)-expressing basket cells. In sharp contrast, the IM-AA mutation abolishes rapid synaptic depression in the inhibitory synapses of PV basket cells onto CA1 pyramidal neurons. These results show that CaS protein regulation of facilitation and inactivation of Ca V 2.1 channels controls the direction of short-term plasticity at these two synapses. Deletion of the CaS protein CaBP1/caldendrin also blocks rapid depression at PV-CA1 synapses, implicating its upregulation of inactivation of Ca V 2.1 channels in control of short-term synaptic plasticity at this inhibitory synapse. Studies of local-circuit function revealed reduced inhibition of CA1 pyramidal neurons by the disynaptic pathway from CA3 pyramidal cells via PV basket cells and greatly increased excitation/inhibition ratio of the direct excitatory input versus indirect inhibitory input from CA3 pyramidal neurons to CA1 pyramidal neurons. This striking defect in local-circuit function may contribute to the dramatic impairment of spatial learning and memory in IM-AA mice. SIGNIFICANCE STATEMENT Many forms of short-term synaptic plasticity in neuronal circuits rely on regulation of presynaptic voltage-gated Ca 2+ (Ca V

  2. Intercellular calcium signaling is regulated by morphogens during Drosophila wing development

    OpenAIRE

    Chen, Danny; Levis, Megan; Arredondo-Walsh, Ninfamaria; Zartman, Jeremiah; Brodskiy, Pavel; Wu, Qinfeng; Huizar, Francisco; Soundarrajan, Dharsan; Narciso, Cody; Chen, Jianxu; Liang, Peixian

    2017-01-01

    Organ development is driven by a set of patterned inductive signals. However, how these signals are integrated to coordinate tissue patterning is still poorly understood. Calcium ions (Ca2+) are critical signaling components involved in signal integration and are regulated by a core Ca2+ signaling toolkit. Ca2+ signaling encodes a significant fraction of information in cells through both amplitude and frequency-dependent regulation of transcription factors and key regulatory enzymes. A range ...

  3. Long term effects on wet stored calcium rich fly ash with bearing on ground improvement work; Laangtidspaaverkan av kalkrika flygaskor vid vaatlagring foer anvaendning inom markstabilisering

    Energy Technology Data Exchange (ETDEWEB)

    Lagerlund, Johan; Jansing, Christiane

    2012-02-15

    Generation of electricity and heat by means of thermal power demands a product that can be ignited. This combustible material is usually coal, oil, gas, biomass and waste. If using solid fuels as coal, biomass and waste a by product known as ash is formed in the process; FA, (FA) and bottom ash. Roughly 600 Mt ashes are annually produced throughout the world and 70 weight % of these ashes are FA, 25 weight % bottom ashes and 5 weight % slag. 41 weight % of all ashes are annually reused in some form. Given the environmental impact of combustion i.e. CO{sub 2} emissions, a widened use of biomass fuels and co-combustion is expected in the near future. This will however create new problems when reusing ashes and FA in particular. The reuse of FA within the concrete industry stand for a total of about 25 % but the reuse of non-coal derived FA in the concrete industry is prohibited. Non-coal derived FA usually has higher amounts of calcium oxide, which acts expansively in concrete. Less than 20 % of biomass or co-combustion FA are reused today in Europe. A new standard, the EN 450, is however under construction. This standard will deal with the reuse of noncoal derived FA within the cement and concrete industry. In Sweden, coal is very seldom used as a fuel. More common is the use of biomass, peat and waste. It means that the FA are all non-coal derived and thus derived from reuse within the cement and concrete industry. Beside their non-coal origin, the main part of the FA is produced during November- March. This means that it might be hard to find available FA all year around, making the reuse of FA less attractive. Hence, FA must be stored prior to use. Little research have been made on the storage of calcium rich FA from biomass and co-combustion. Storing FA in a cheap way requires an addition of water to prevent from dusting when stockpiled outdoors. Addition of water in calcium rich FA will however cause an hardening of the material, thus causing detrimental

  4. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

    Full Text Available Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood into the ductal lumen (milk. Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1, which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2 and basolateral (CaSR, ORAI-1 membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2. Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2 are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation.

  5. Effect of Calcium Salt on Soft Rot, Bitter Pit and Physico-Chemical Properties of Stored Apples

    International Nuclear Information System (INIS)

    Jan, I.; Rab, A.; Sajid, M.; Iqbal, A.; Shinwari, Z. K.; Hamayun, M.

    2016-01-01

    Postharvest losses are one of the main problems in leading fruit producing countries. Therefore, an attempt has been made to decrease the postharvest losses during apple storage. To achieve this objective, fruits were dipped in 0, 3, 6 and 9 percent CaCl/sub 2/ solution for the period of 3, 6, 9 and 12 minutes and were stored for 150 days at 5 ± 1 C with 60-70 percent relative humidity. After the storage time, fruits were analysed for percent weight loss, total sugar, bitter pit incidence, soft rot, ascorbic acid and firmness. The ascorbic acid contents and firmness of the fruits significantly increased, when the fruits were dipped in 9% CaCl/sub 2/ solution as compared to control (dipped in water). Whereas, weight loss, total sugar, bitter pit and soft rot incidences were reduced with increased concentration of CaCl/sub 2/. The firmness of the fruits dipped for 3 minutes in a CaCl/sub 2/ solution was significantly lower in comparison to the fruits dipped for 12 minutes in a CaCl/sub 2/ solution. Likewise, the weight loss, bitter pit and the soft rot incidence reduced with increase in dipping duration in CaCl/sub 2/ solution from 3 minutes to 12 minutes. (author)

  6. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

    Directory of Open Access Journals (Sweden)

    Natalia Gustavsson

    Full Text Available BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. CONCLUSIONS: Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  7. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

    Science.gov (United States)

    Gustavsson, Natalia; Wang, Xiaorui; Wang, Yue; Seah, Tingting; Xu, Jun; Radda, George K; Südhof, Thomas C; Han, Weiping

    2010-11-09

    Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X) mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  8. LRRK2 regulates voltage-gated calcium channel function.

    Directory of Open Access Journals (Sweden)

    Cade eBedford

    2016-05-01

    Full Text Available Voltage-gated Ca2+ (CaV channels enable Ca2+ influx in response to membrane depolarization. CaV2.1 channels are localized to the presynaptic membrane of many types of neurons where they are involved in triggering neurotransmitter release. Several signaling proteins have been identified as important CaV2.1 regulators including protein kinases, G-proteins and Ca2+ binding proteins. Recently, we discovered that leucine rich repeat kinase 2 (LRRK2, a protein associated with inherited Parkinson’s disease, interacts with specific synaptic proteins and influences synaptic transmission. Since synaptic proteins functionally interact with CaV2.1 channels and synaptic transmission is triggered by Ca2+ entry via CaV2.1, we investigated whether LRRK2 could impact CaV2.1 channel function. CaV2.1 channel properties were measured using whole cell patch clamp electrophysiology in HEK293 cells transfected with CaV2.1 subunits and various LRRK2 constructs. Our results demonstrate that both wild type LRRK2 and the G2019S LRRK2 mutant caused a significant increase in whole cell Ca2+ current density compared to cells expressing only the CaV2.1 channel complex. In addition, LRRK2 expression caused a significant hyperpolarizing shift in voltage-dependent activation while having no significant effect on inactivation properties. These functional changes in CaV2.1 activity are likely due to a direct action of LRRK2 as we detected a physical interaction between LRRK2 and the β3 CaV channel subunit via coimmunoprecipitation. Furthermore, effects on CaV2.1 channel function are dependent on LRRK2 kinase activity as these could be reversed via treatment with a LRRK2 inhibitor. Interestingly, LRRK2 also augmented endogenous voltage-gated Ca2+ channel function in PC12 cells suggesting other CaV channels could also be regulated by LRRK2. Overall, our findings support a novel physiological role for LRRK2 in regulating CaV2.1 function that could have implications for how

  9. Regulation of calcium release from the endoplasmic reticulum by the serine hydrolase ABHD2.

    Science.gov (United States)

    Yun, Bogeon; Lee, HeeJung; Powell, Roger; Reisdorph, Nichole; Ewing, Heather; Gelb, Michael H; Hsu, Ku-Lung; Cravatt, Benjamin F; Leslie, Christina C

    2017-09-02

    The serine hydrolase inhibitors pyrrophenone and KT195 inhibit cell death induced by A23187 and H 2 O 2 by blocking the release of calcium from the endoplasmic reticulum and mitochondrial calcium uptake. The effect of pyrrophenone and KT195 on these processes is not due to inhibition of their known targets, cytosolic phospholipase A 2 and α/β-hydrolase domain-containing (ABHD) 6, respectively, but represent off-target effects. To identify targets of KT195, fibroblasts were treated with KT195-alkyne to covalently label protein targets followed by click chemistry with biotin azide, enrichment on streptavidin beads and tryptic peptide analysis by mass spectrometry. Although several serine hydrolases were identified, α/β-hydrolase domain-containing 2 (ABHD2) was the only target in which both KT195 and pyrrophenone competed for binding to KT195-alkyne. ABHD2 is a serine hydrolase with a predicted transmembrane domain consistent with its pull-down from the membrane proteome. Subcellular fractionation showed localization of ABHD2 to the endoplasmic reticulum but not to mitochondria or mitochondrial-associated membranes. Knockdown of ABHD2 with shRNA attenuated calcium release from the endoplasmic reticulum, mitochondrial calcium uptake and cell death in fibroblasts stimulated with A23187. The results describe a novel mechanism for regulating calcium transfer from the endoplasmic reticulum to mitochondria that involves the serine hydrolase ABHD2. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Redox regulation of calcium release in skeletal and cardiac muscle

    Directory of Open Access Journals (Sweden)

    CECILIA HIDALGO

    2002-01-01

    Full Text Available In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist and Mg2+ (endogenous inhibitor on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 µM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 µM [Ca2+]. In 10 µM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] ­ 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 µM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed

  11. Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

    Science.gov (United States)

    Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David

    2013-01-01

    Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539

  12. Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

    DEFF Research Database (Denmark)

    Quinn, S.J.; Thomsen, A.R.B.; Pang, J.L.

    2013-01-01

    , however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D [1,25(OH)D] despite no change in FGF23...... correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus...

  13. Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Orthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Liu, Xi [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Lian, Xiaojie [College of Mechanics, Taiyuan University of Technology, Taiyuan 030024 (China); Guo, Zhongwu [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Jiang, Hong-Jiang [Wendeng Hospital of Traditional Chinese Orthopedics and Traumatology, Shandong 264400 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2013-04-01

    Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.0% (wt.), which is near to the theoretic crystal water value of CSH. From scanning electron microscopy (SEM) micrographs, sheet crystal structure of CSD was observed to transform into rod-like crystal structure of CSH. Most interesting and important of all, CSD as setting accelerator was also introduced into CSH powder to regulate self-setting properties of injectable CSH paste, and thus the self-setting time of CSH paste can be regulated from near 30 min to less than 5 min by adding various amounts of setting accelerator. Because CSD is not only the reactant of preparing CSH but also the final solidified product of CSH, the setting accelerator has no significant effect on the other properties of materials, such as mechanical properties. In vitro biocompatibility and in vivo histology studies have demonstrated that the materials have good biocompatibility and good efficacy in bone regeneration. All these will further improve the workability of CSH in clinic applications. Highlights: ► Calcium sulfate hemihydrate (CSH) can be an injectable bone cement. ► CSH was produced by hydrothermal synthesis of calcium sulfate dihydrate (CSD). ► CSD was introduced into CSH powder to regulate self-setting properties of CSH. ► Setting accelerator has no significant effect on the other properties of materials. ► Injectable CSH has good biocompatibility and good efficacy in bone regeneration.

  14. Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties

    International Nuclear Information System (INIS)

    Chen, Zonggang; Liu, Huanye; Liu, Xi; Lian, Xiaojie; Guo, Zhongwu; Jiang, Hong-Jiang; Cui, Fu-Zhai

    2013-01-01

    Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.0% (wt.), which is near to the theoretic crystal water value of CSH. From scanning electron microscopy (SEM) micrographs, sheet crystal structure of CSD was observed to transform into rod-like crystal structure of CSH. Most interesting and important of all, CSD as setting accelerator was also introduced into CSH powder to regulate self-setting properties of injectable CSH paste, and thus the self-setting time of CSH paste can be regulated from near 30 min to less than 5 min by adding various amounts of setting accelerator. Because CSD is not only the reactant of preparing CSH but also the final solidified product of CSH, the setting accelerator has no significant effect on the other properties of materials, such as mechanical properties. In vitro biocompatibility and in vivo histology studies have demonstrated that the materials have good biocompatibility and good efficacy in bone regeneration. All these will further improve the workability of CSH in clinic applications. Highlights: ► Calcium sulfate hemihydrate (CSH) can be an injectable bone cement. ► CSH was produced by hydrothermal synthesis of calcium sulfate dihydrate (CSD). ► CSD was introduced into CSH powder to regulate self-setting properties of CSH. ► Setting accelerator has no significant effect on the other properties of materials. ► Injectable CSH has good biocompatibility and good efficacy in bone regeneration

  15. Filamin A Modulates Store-Operated Ca2+ Entry by Regulating STIM1 (Stromal Interaction Molecule 1)-Orai1 Association in Human Platelets.

    Science.gov (United States)

    Lopez, Jose J; Albarrán, Letizia; Jardín, Isaac; Sanchez-Collado, Jose; Redondo, Pedro C; Bermejo, Nuria; Bobe, Regis; Smani, Tarik; Rosado, Juan A

    2018-02-01

    Here, we provide evidence for the role of FLNA (filamin A) in the modulation of store-operated calcium entry (SOCE). SOCE is a major mechanism for calcium influx controlled by the intracellular Ca 2+ stores. On store depletion, the endoplasmic reticulum calcium sensor STIM1 (stromal interaction molecule 1) redistributes into puncta at endoplasmic reticulum/plasma membrane junctions, a process supported by the cytoskeleton, where it interacts with the calcium channels; however, the mechanism for fine-tuning SOCE is not completely understood. Our results demonstrate that STIM1 interacts with FLNA on calcium store depletion in human platelets. The interaction is dependent on the phosphorylation of FLNA at Ser 2152 by the cAMP-dependent protein kinase. Impairment of FLNA phosphorylation and knockdown of FLNA expression using siRNA increased SOCE in platelets. Similarly, SOCE was significantly greater in FLNA-deficient melanoma M2 cells than in the FLNA-expressing M2 subclone A7. Expression of FLNA in M2 cells attenuated SOCE, an effect prevented when the cells were transfected with the nonphosphorylatable FLNA S2152A mutant. Transfection of M2 cells with the STIM1(K684,685E) mutant reduced the STIM1-FLNA interaction. In platelets, attenuation of FLNA expression using siRNA resulted in enhanced association of STIM1 with the cytoskeleton, greater STIM1-Orai1 interaction, and SOCE. Introduction of an anti-FLNA (2597-2647) antibody attenuated the STIM1-FLNA interaction and enhanced thrombin-induced platelet aggregation. Our results indicate that FLNA modulates SOCE and then the correct platelet function, by fine-tuning the distribution of STIM1 in the cytoskeleton and the interaction with Orai1 channels. © 2017 American Heart Association, Inc.

  16. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Vickram Tejwani

    2013-05-01

    Full Text Available The elderly chronic kidney disease (CKD population is growing. Both aging and CKD can disrupt calcium (Ca2+ homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD. CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD.

  17. Inhibition of calmodulin - regulated calcium pump activity in rat brain by toxaphene

    International Nuclear Information System (INIS)

    Trottman, C.H.; Moorthy, K.S.

    1986-01-01

    In vivo effects of toxaphene on calcium pump activity in rat brain synaptosomes was studied. Male Sprague-Dawley rats were dosed with toxaphene at 0,25,50, and 100 mg/kg/day for 3 days and sacrificed 24 h after last dose. Ca 2+ -ATPase activity and 45 Ca uptake were determined in brain P 2 fraction. Toxaphene inhibited both Ca 2+ -ATPase activity and 45 Ca 2+ uptake and the inhibition was dose dependent. Both substrate and Ca 2+ activation kinetics of Ca 2+ -ATPase indicated non-competitive type of inhibition as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The inhibited Ca 2+ -ATPase activity and Ca 2+ uptake were restored to normal level by exogenously added calmodulin which increased both velocity and affinity. The inhibition of Ca 2+ -ATPase activity and Ca 2+ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium transport mechanisms by decreasing regulator protein calmodulin levels

  18. Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention.

    Directory of Open Access Journals (Sweden)

    Ziying Han

    2015-10-01

    Full Text Available Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg and arenaviruses (Lassa and Junín viruses, are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1 and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.

  19. Physiological studies in heterozygous calcium sensing receptor (CaSR gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo

    Directory of Open Access Journals (Sweden)

    Kovacs Christopher S

    2004-04-01

    Full Text Available Abstract Background The calcium sensing receptor (CaSR regulates serum calcium by suppressing secretion of parathyroid hormone; it also regulates renal tubular calcium excretion. Inactivating mutations of CaSR raise serum calcium and reduce urine calcium excretion. Thyroid C-cells (which make calcitonin express CaSR and may, therefore, be regulated by it. Since calcium stimulates release of calcitonin, the higher blood calcium caused by inactivation of CaSR should increase serum calcitonin, unless CaSR mutations alter the responsiveness of calcitonin to calcium. To demonstrate regulatory effects of CaSR on calcitonin release, we studied calcitonin responsiveness to calcium in normal and CaSR heterozygous-ablated (Casr+/- mice. Casr+/- mice have hypercalcemia and hypocalciuria, and live normal life spans. Each mouse received either 500 μl of normal saline or one of two doses of elemental calcium (500 μmol/kg or 5 mmol/kg by intraperitoneal injection. Ionized calcium was measured at baseline and 10 minutes, and serum calcitonin was measured on the 10 minute sample. Results At baseline, Casr+/- mice had a higher blood calcium, and in response to the two doses of elemental calcium, had greater increments and peak levels of ionized calcium than their wild type littermates. Despite significantly higher ionized calcium levels, the calcitonin levels of Casr+/- mice were consistently lower than wild type at any ionized calcium level, indicating that the dose-response curve of calcitonin to increases in ionized calcium had been significantly blunted or shifted to the right in Casr+/- mice. Conclusions These results confirm that the CaSR is a physiological regulator of calcitonin; therefore, in response to increases in ionized calcium, the CaSR inhibits parathyroid hormone secretion and stimulates calcitonin secretion.

  20. Regulation of dsr genes encoding proteins responsible for the oxidation of stored sulfur in Allochromatium vinosum.

    Science.gov (United States)

    Grimm, Frauke; Dobler, Nadine; Dahl, Christiane

    2010-03-01

    Sulfur globules are formed as obligatory intermediates during the oxidation of reduced sulfur compounds in many environmentally important photo- and chemolithoautotrophic bacteria. It is well established that the so-called Dsr proteins are essential for the oxidation of zero-valent sulfur accumulated in the globules; however, hardly anything is known about the regulation of dsr gene expression. Here, we present a closer look at the regulation of the dsr genes in the phototrophic sulfur bacterium Allochromatium vinosum. The dsr genes are expressed in a reduced sulfur compound-dependent manner and neither sulfite, the product of the reverse-acting dissimilatory sulfite reductase DsrAB, nor the alternative electron donor malate inhibit the gene expression. Moreover, we show the oxidation of sulfur to sulfite to be the rate-limiting step in the oxidation of sulfur to sulfate as sulfate production starts concomitantly with the upregulation of the expression of the dsr genes. Real-time RT-PCR experiments suggest that the genes dsrC and dsrS are additionally expressed from secondary internal promoters, pointing to a special function of the encoded proteins. Earlier structural analyses indicated the presence of a helix-turn-helix (HTH)-like motif in DsrC. We therefore assessed the DNA-binding capability of the protein and provide evidence for a possible regulatory function of DsrC.

  1. Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

    Science.gov (United States)

    Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

    2015-02-01

    Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The effect of intracellular calcium level regulators on the synthesis of pollen tube callose in Oenothera biennis L.

    Directory of Open Access Journals (Sweden)

    Elżbieta Bednarska

    2014-01-01

    Full Text Available It is shown that callose synthesis in the Oenothera biennis pollen tube is regulated by the endogenous Ca2+ level. Calcium antagonists reduced the amount of callose in the wall above the tip of the pollen tube (Verapamil - calcium channels blocker and at the tube tip after stopping tube growth (La3+ - a Ca2+ substitute. Ruthenium red and ionophore A 23187, which raise the Ca 21 level in the cytoplasm, induced callose synthesis at the tip of pollen tube.

  3. Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

    Directory of Open Access Journals (Sweden)

    Dan Lv

    Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

  4. Expression of the calcium-binding proteins MRP8 and MRP14 in monocytes is regulated by a calcium-induced suppressor mechanism.

    OpenAIRE

    Roth, J; Goebeler, M; Wrocklage, V; van den Bos, C; Sorg, C

    1994-01-01

    MRP8 and MRP14 are two calcium-binding proteins of the S-100 family the expression of which is restricted to distinct stages of monocytic differentiation. Heteromeric MRP8/MRP14 complexes have been shown to represent their biologically active forms. However, it is not as yet clear whether biochemical modification of complexes, or regulation on the transcriptional level, are responsible for the control of MRP8/MRP14 expression. Employing Western-blot analysis and metabolic labelling we have de...

  5. Transcriptional expression analysis of genes involved in regulation of calcium translocation and storage in finger millet (Eleusine coracana L. Gartn.).

    Science.gov (United States)

    Mirza, Neelofar; Taj, Gohar; Arora, Sandeep; Kumar, Anil

    2014-10-25

    Finger millet (Eleusine coracana) variably accumulates calcium in different tissues, due to differential expression of genes involved in uptake, translocation and accumulation of calcium. Ca(2+)/H(+) antiporter (CAX1), two pore channel (TPC1), CaM-stimulated type IIB Ca(2+) ATPase and two CaM dependent protein kinase (CaMK1 and 2) homologs were studied in finger millet. Two genotypes GP-45 and GP-1 (high and low calcium accumulating, respectively) were used to understand the role of these genes in differential calcium accumulation. For most of the genes higher expression was found in the high calcium accumulating genotype. CAX1 was strongly expressed in the late stages of spike development and could be responsible for accumulating high concentrations of calcium in seeds. TPC1 and Ca(2+) ATPase homologs recorded strong expression in the root, stem and developing spike and signify their role in calcium uptake and translocation, respectively. Calmodulin showed strong expression and a similar expression pattern to the type IIB ATPase in the developing spike only and indicating developing spike or even seed specific isoform of CaM affecting the activity of downstream target of calcium transportation. Interestingly, CaMK1 and CaMK2 had expression patterns similar to ATPase and TPC1 in various tissues raising a possibility of their respective regulation via CaM kinase. Expression pattern of 14-3-3 gene was observed to be similar to CAX1 gene in leaf and developing spike inferring a surprising possibility of CAX1 regulation through 14-3-3 protein. Our results provide a molecular insight for explaining the mechanism of calcium accumulation in finger millet. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells.

    Science.gov (United States)

    Long, Tingting; Su, Juan; Tang, Wen; Luo, Zhongling; Liu, Shuang; Liu, Zhaoqian; Zhou, Honghao; Qi, Min; Zeng, Weiqi; Zhang, Jianglin; Chen, Xiang

    2013-10-01

    Intracellular free calcium is a ubiquitous second messenger regulating a multitude of normal and pathogenic cellular responses, including the development of melanoma. Upstream signaling pathways regulating the intracellular free calcium concentration ([Ca2+]i) may therefore have a significant impact on melanoma growth and metastasis. In this study, we demonstrate that the endoplasmic reticulum (ER)-associated protein calcium-modulating cyclophilin ligand (CAML) is bound to Basigin, a widely expressed integral plasma membrane glycoprotein and extracellular matrix metalloproteinase inducer (EMMPRIN, or CD147) implicated in melanoma proliferation, invasiveness, and metastasis. This interaction between CAML and Basigin was first identified using yeast two-hybrid screening and further confirmed by co-immunoprecipitation. In human A375 melanoma cells, CAML and Basigin were co-localized to the ER. Knockdown of Basigin in melanoma cells by siRNA significantly decreased resting [Ca2+]i and the [Ca2+]i increase induced by the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (TG), indicating that the interaction between CAML and Basigin regulates ER-dependent [Ca2+]i signaling. Meanwhile upregulating the [Ca2+]i either by TG or phorbol myristate acetate (PMA) could stimulate the production of MMP-9 in A375 cells with the expression of Basigin. Our study has revealed a previously uncharacterized [Ca2+]i signaling pathway that may control melanoma invasion, and metastasis. Disruption of this pathway may be a novel therapeutic strategy for melanoma treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.

    Science.gov (United States)

    Zhang, Jingwei; Dalbay, Melis T; Luo, Xiaoman; Vrij, Erik; Barbieri, Davide; Moroni, Lorenzo; de Bruijn, Joost D; van Blitterswijk, Clemens A; Chapple, J Paul; Knight, Martin M; Yuan, Huipin

    2017-07-15

    The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery

  8. Calcium-regulated in vivo protein phosphorylation in Zea mays L. root tips

    Science.gov (United States)

    Raghothama, K. G.; Reddy, A. S.; Friedmann, M.; Poovaiah, B. W.

    1987-01-01

    Calcium dependent protein phosphorylation was studied in corn (Zea mays L.) root tips. Prior to in vivo protein phosphorylation experiments, the effect of calcium, ethyleneglycol-bis-(beta-aminoethyl ether)-N-N' -tetraacetic acid (EGTA) and calcium ionophore (A-23187) on phosphorus uptake was studied. Calcium increased phosphorus uptake, whereas EGTA and A-23187 decreased it. Consequently, phosphorus concentration in the media was adjusted so as to attain similar uptake in different treatments. Phosphoproteins were analyzed by two-dimensional gel electrophoresis. Distinct changes in phosphorylation were observed following altered calcium levels. Calcium depletion in root tips with EGTA and A-23187 decreased protein phosphorylation. However, replenishment of calcium following EGTA and ionophore pretreatment enhanced phosphorylation of proteins. Preloading of the root tips with 32P in the presence of EGTA and A-23187 followed by a ten minute calcium treatment, resulted in increased phosphorylation indicating the involvement of calcium, calcium and calmodulin-dependent kinases. Calmodulin antagonist W-7 was effective in inhibiting calcium-promoted phosphorylation. These studies suggest a physiological role for calcium-dependent phosphorylation in calcium-mediated processes in plants.

  9. Calcium regulation in long-term changes of neuronal excitability in the hippocampal formation

    Energy Technology Data Exchange (ETDEWEB)

    Mody, I.

    1985-01-01

    The regulation of calcium (Ca/sup 2 +/) was examined during long-term changes of neuronal excitability in the mammalian CNS. The preparations under investigation included the kindling model of epilepsy, a genetic form of epilepsy and long-term potentiation (LTP) of neuronal activity. The study also includes a discussion of the possible roles of a neuron-specific calcium-binding protein (CaBP). The findings are summarized as follows: (1) CaBP was found to have an unequal distribution in various cortical areas of the rat with higher levels in ventral structures. (2) The decline in CaBP was correlated to the number of evoked afterdischarges (AD's) during kindling-induced epilepsy. (3) Marked changes in CaBP levels were also found in the brains of the epileptic strain of mice (El). The induction of seizures further decreased the levels of CaBP in the El mice, indicating a possible genetic impairment of neuronal Ca/sup 2 +/ homeostasis in the El strain. (4) The levels of total hippocampal Ca/sup 2 +/ and Zn/sup 2 +/ were measured by atomic absorption spectrophotometry in control and commissural-kindled animals. (5) To measure Ca/sup 2 +/-homeostasis, the kinetic analysis of /sup 45/Ca uptake curves was undertaken in the in vitro hippocampus. (6) The kinetic analysis of /sup 45/Ca uptake curves revealed that Ca/sup 2 +/-regulation of the hippocampus is impaired following amygdala- and commissural kindling. (7). A novel form of long-term potentiation (LTP) of neuronal activity in the CA1 region of the hippocampus is described. The findings raise the possibility that the Ca/sup 2 +/ necessary for induction of LTP may be derived from an intraneuronal storage site.

  10. Calcium mobilization in HeLa cells induced by nitric oxide.

    Science.gov (United States)

    Huang, Yimei; Zheng, Liqin; Yang, Hongqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

    2014-01-01

    Nitric oxide (NO) has been proposed to be involved in tumor growth and metastasis. However, the mechanism by which nitric oxide modulates cancer cell growth and metastasis on cellular and molecular level is still not fully understood. This work utilized confocal microscopy and fluorescence microplate reader to investigate the effects of exogenous NO on the mobilization of calcium, which is one of the regulators of cell migration, in HeLa cells. The results show that NO elevates calcium in concentration-dependent manner in HeLa cells. And the elevation of calcium induced by NO is due to calcium influx and calcium release from intracellular calcium stores. Moreover, calcium release from intracellular stores is dominant. Furthermore, calcium release from mitochondria is one of the modulation pathways of NO. These findings would contribute to recognizing the significance of NO in cancer cell proliferation and metastasis. © Wiley Periodicals, Inc.

  11. Calcium regulation in frog peripheral nerve by the blood-nerve barrier

    International Nuclear Information System (INIS)

    Wadhwani, K.C.

    1986-01-01

    The objectives of this research were: (a) to investigate the characteristics of calcium transport across the perineurium and the endoneurial capillaries, and (b) to gain a better understanding of the extent of calcium homeostasis in the endoneurial space. To study the nature of calcium transport across the perineurium, the flux of radiotracer 45 Ca was measured through the perineurial cylinder, isolated from the frog sciatic nerve, and through the perineurium into the nerve in situ. To study the nature of calcium transport across the endoneurial capillaries, the permeability-surface area product (PA) of 45 Ca was determined as a function of the calcium concentration in the blood. To study calcium homeostasis, the calcium content of the frog sciatic nerve was determined as a function of chronic changes in plasma [Ca

  12. Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes.

    Science.gov (United States)

    Li, Yuwei; Ahrens, Molly J; Wu, Amy; Liu, Jennifer; Dudley, Andrew T

    2011-01-01

    For tissues that develop throughout embryogenesis and into postnatal life, the generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity. Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways. We present an integrated model for the regulation of proliferation potential by CamkII activity that has important implications for studies of growth control and adult progenitor/stem cell populations.

  13. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium

    Directory of Open Access Journals (Sweden)

    Adela Banciu

    2018-05-01

    human uterine myometrium and their gene expression regulation by beta-estradiol in pregnant conditions. Further exploration of the calcium signaling in TCs and its modulation by estrogen hormones will contribute to the understanding of labor and pregnancy mechanisms and to the development of effective strategies to reduce the risk of premature birth.

  14. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.

    Science.gov (United States)

    Banciu, Adela; Banciu, Daniel Dumitru; Mustaciosu, Cosmin Catalin; Radu, Mihai; Cretoiu, Dragos; Xiao, Junjie; Cretoiu, Sanda Maria; Suciu, Nicolae; Radu, Beatrice Mihaela

    2018-05-09

    myometrium and their gene expression regulation by beta-estradiol in pregnant conditions. Further exploration of the calcium signaling in TCs and its modulation by estrogen hormones will contribute to the understanding of labor and pregnancy mechanisms and to the development of effective strategies to reduce the risk of premature birth.

  15. Ultrasound enhances calcium absorption of jujube fruit by regulating the cellular calcium distribution and metabolism of cell wall polysaccharides.

    Science.gov (United States)

    Zhi, Huanhuan; Liu, Qiqi; Xu, Juan; Dong, Yu; Liu, Mengpei; Zong, Wei

    2017-12-01

    Ultrasound has been applied in fruit pre-washing processes. However, it is not sufficient to protect fruit from pathogenic infection throughout the entire storage period, and sometimes ultrasound causes tissue damage. The goal of this study was to investigate the effects of calcium chloride (CaCl 2 , 10 g L -1 ) and ultrasound (350 W at 40 kHz), separately and in combination, on jujube fruit quality, antioxidant status, tissue Ca 2+ content and distribution along with cell wall metabolism at 20 °C for 6 days. All three treatments significantly maintained fruit firmness and peel color, reduced respiration rate, decay incidence, superoxide anion, hydrogen peroxide and malondialdehyde and preserved higher enzymatic (superoxide dismutase, catalase and peroxidase) and non-enzymatic (ascorbic acid and glutathione) antioxidants compared with the control. Moreover, the combined treatment was more effective in increasing tissue Ca 2+ content and distribution, inhibiting the generation of water-soluble and CDTA-soluble pectin fractions, delaying the solubilization of Na 2 CO 3 -soluble pectin and having lower activities of cell wall-modifying enzymes (polygalacturonase and pectate lyase) during storage. These results demonstrated that the combination of CaCl 2 and ultrasound has potential commercial application to extend the shelf life of jujube fruit by facilitating Ca 2+ absorption and stabilizing the cell wall structure. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

    Science.gov (United States)

    Jayakumar, Siddharth; Hasan, Gaiti

    2018-01-01

    All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

  17. Calcium regulates cell death in cancer: Roles of the mitochondria and mitochondria-associated membranes (MAMs).

    Science.gov (United States)

    Danese, Alberto; Patergnani, Simone; Bonora, Massimo; Wieckowski, Mariusz R; Previati, Maurizio; Giorgi, Carlotta; Pinton, Paolo

    2017-08-01

    Until 1972, the term 'apoptosis' was used to differentiate the programmed cell death that naturally occurs in organismal development from the acute tissue death referred to as necrosis. Many studies on cell death and programmed cell death have been published and most are, at least to some degree, related to cancer. Some key proteins and molecular pathways implicated in cell death have been analyzed, whereas others are still being actively researched; therefore, an increasing number of cellular compartments and organelles are being implicated in cell death and cancer. Here, we discuss the mitochondria and subdomains of the endoplasmic reticulum (ER) that interact with mitochondria, the mitochondria-associated membranes (MAMs), which have been identified as critical hubs in the regulation of cell death and tumor growth. MAMs-dependent calcium (Ca 2+ ) release from the ER allows selective Ca 2+ uptake by the mitochondria. The perturbation of Ca 2+ homeostasis in cancer cells is correlated with sustained cell proliferation and the inhibition of cell death through the modulation of Ca 2+ signaling. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Calcium regulation of EGF-induced ERK5 activation: role of Lad1-MEKK2 interaction.

    Directory of Open Access Journals (Sweden)

    Zhong Yao

    Full Text Available The ERK5 cascade is a MAPK pathway that transmits both mitogenic and stress signals, yet its mechanism of activation is not fully understood. Using intracellular calcium modifiers, we found that ERK5 activation by EGF is inhibited both by the depletion and elevation of intracellular calcium levels. This calcium effect was found to occur upstream of MEKK2, which is the MAP3K of the ERK5 cascade. Co-immunoprecipitation revealed that EGF increases MEKK2 binding to the adaptor protein Lad1, and this interaction was reduced by the intracellular calcium modifiers, indicating that a proper calcium concentration is required for the interactions and transmission of EGF signals to ERK5. In vitro binding assays revealed that the proper calcium concentration is required for a direct binding of MEKK2 to Lad1. The binding of these proteins is not affected by c-Src-mediated phosphorylation on Lad1, but slightly affects the Tyr phosphorylation of MEKK2, suggesting that the interaction with Lad1 is necessary for full Tyr phosphorylation of MEKK2. In addition, we found that changes in calcium levels affect the EGF-induced nuclear translocation of MEKK2 and thereby its effect on the nuclear ERK5 activity. Taken together, these findings suggest that calcium is required for EGF-induced ERK5 activation, and this effect is probably mediated by securing proper interaction of MEKK2 with the upstream adaptor protein Lad1.

  19. Regulation of myofibrillar accumulation in chick muscle cultures - Evidence for the involvement of calcium and lysosomes in non-uniform turnover of contractile proteins

    Science.gov (United States)

    Silver, Geri; Etlinger, Joseph D.

    1985-01-01

    The effects of calcium on the synthesis and the degradation of individual myofibrillar proteins were investigated using primary chick-leg skeletal muscle cultures labeled with S-35-methionine (for protein accumulation experiments) or Ca(2+)-45 (for calcium efflux experiments). It was found that the turnover of individual contractile proteins is regulated nonuniformly by a calcium-dependent mechanism involving lysosomes. The results also indicate that contractile proteins are released from the myofibril before their breakdown to amino acids.

  20. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

    Science.gov (United States)

    Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

    2017-11-16

    Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3

  1. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration

    Directory of Open Access Journals (Sweden)

    Rubén Aquino-Martínez

    2017-11-01

    Full Text Available Abstract Background Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca2+-containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO4 on MSC migration. In addition, to evaluate the influence of CaSO4 on MSC differentiation and the potential molecular mechanisms involved. Methods A circular calvarial bone defect (5 mm diameter was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO4 treatment was also evaluated by qPCR. Results CaSO4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO4-containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO4 effects on MSC migration. Conclusions Specific CaSO4 concentrations induce bone regeneration of calvarial defects in part by acting on the host’s undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO4 regulates BMP-2-induced

  2. Calcium controls the formation of vacuoles from mitochondria to regulate microspore development in wheat.

    Science.gov (United States)

    Li, Dong Xiao; Hu, Hai Yan; Li, Gan; Ru, Zhen Gang; Tian, Hui Qiao

    2017-09-01

    Potassium antimonite was used to investigate the localisation of calcium in developing wheat anthers to examine the relationship between Ca 2+ and pollen development. During anther development, calcium precipitate formation increased in anther wall cells prior to microspore mother cell meiosis and appeared in microspores, suggesting the presence of a calcium influx from anther wall cells into the locule. Initially, the precipitates in microspore cytoplasm primarily accumulated in the mitochondria and destroyed their inner membranes (cisterns) to become small vacuoles, which expanded and fused, ultimately becoming a large vacuole during microspore vacuolisation. After microspore division and large vacuole decomposition, many calcium precipitates again accumulated in the small vacuoles, indicating that calcium from the large vacuole moved back into the cytoplasm of bicellular pollen.

  3. Calcium Regulates Molecular Interactions of Otoferlin with Soluble NSF Attachment Protein Receptor (SNARE) Proteins Required for Hair Cell Exocytosis*

    Science.gov (United States)

    Ramakrishnan, Neeliyath A.; Drescher, Marian J.; Morley, Barbara J.; Kelley, Philip M.; Drescher, Dennis G.

    2014-01-01

    Mutations in otoferlin, a C2 domain-containing ferlin family protein, cause non-syndromic hearing loss in humans (DFNB9 deafness). Furthermore, transmitter secretion of cochlear inner hair cells is compromised in mice lacking otoferlin. In the present study, we show that the C2F domain of otoferlin directly binds calcium (KD = 267 μm) with diminished binding in a pachanga (D1767G) C2F mouse mutation. Calcium was found to differentially regulate binding of otoferlin C2 domains to target SNARE (t-SNARE) proteins and phospholipids. C2D–F domains interact with the syntaxin-1 t-SNARE motif with maximum binding within the range of 20–50 μm Ca2+. At 20 μm Ca2+, the dissociation rate was substantially lower, indicating increased binding (KD = ∼10−9) compared with 0 μm Ca2+ (KD = ∼10−8), suggesting a calcium-mediated stabilization of the C2 domain·t-SNARE complex. C2A and C2B interactions with t-SNAREs were insensitive to calcium. The C2F domain directly binds the t-SNARE SNAP-25 maximally at 100 μm and with reduction at 0 μm Ca2+, a pattern repeated for C2F domain interactions with phosphatidylinositol 4,5-bisphosphate. In contrast, C2F did not bind the vesicle SNARE protein synaptobrevin-1 (VAMP-1). Moreover, an antibody targeting otoferlin immunoprecipitated syntaxin-1 and SNAP-25 but not synaptobrevin-1. As opposed to an increase in binding with increased calcium, interactions between otoferlin C2F domain and intramolecular C2 domains occurred in the absence of calcium, consistent with intra-C2 domain interactions forming a “closed” tertiary structure at low calcium that “opens” as calcium increases. These results suggest a direct role for otoferlin in exocytosis and modulation of calcium-dependent membrane fusion. PMID:24478316

  4. VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration.

    Science.gov (United States)

    Fearnley, Gareth W; Bruns, Alexander F; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-04-24

    Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response. © 2015. Published by The Company of Biologists Ltd.

  5. VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2015-07-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response.

  6. Effects of Ginger and Its Constituents on Airway Smooth Muscle Relaxation and Calcium Regulation

    Science.gov (United States)

    Siviski, Matthew E.; Zhang, Yi; Xu, Carrie; Hoonjan, Bhupinder; Emala, Charles W.

    2013-01-01

    The prevalence of asthma has increased in recent years, and is characterized by airway hyperresponsiveness and inflammation. Many patients report using alternative therapies to self-treat asthma symptoms as adjuncts to short-acting and long-acting β-agonists and inhaled corticosteroids (ICS). As many as 40% of patients with asthma use herbal therapies to manage asthma symptoms, often without proven efficacy or known mechanisms of action. Therefore, investigations of both the therapeutic and possible detrimental effects of isolated components of herbal treatments on the airway are important. We hypothesized that ginger and its active components induce bronchodilation by modulating intracellular calcium ([Ca2+]i) in airway smooth muscle (ASM). In isolated human ASM, ginger caused significant and rapid relaxation. Four purified constituents of ginger were subsequently tested for ASM relaxant properties in both guinea pig and human tracheas: [6]-gingerol, [8]-gingerol, and [6]-shogaol induced rapid relaxation of precontracted ASM (100–300 μM), whereas [10]-gingerol failed to induce relaxation. In human ASM cells, exposure to [6]-gingerol, [8]-gingerol, and [6]-shogaol, but not [10]-gingerol (100 μM), blunted subsequent Ca2+ responses to bradykinin (10 μM) and S-(−)-Bay K 8644 (10 μM). In A/J mice, the nebulization of [8]-gingerol (100 μM), 15 minutes before methacholine challenge, significantly attenuated airway resistance, compared with vehicle. Taken together, these novel data show that ginger and its isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax ASM, and [8]-gingerol attenuates airway hyperresponsiveness, in part by altering [Ca2+]i regulation. These purified compounds may provide a therapeutic option alone or in combination with accepted therapeutics, including β2-agonists, in airway diseases such as asthma. PMID:23065130

  7. Transcellular transport of calcium

    Energy Technology Data Exchange (ETDEWEB)

    Terepka, A R; Coleman, J R; Armbrecht, H J; Gunter, T E

    1976-01-01

    Studies of two calcium transporting epithelia, embryonic chick chorioallantoic membrane and the small intestine of rat and chick, have strongly suggested that the transfer of calcium across a cell involves processes distinctly different from intracellular calcium ion regulation. In the proposed model, transcellular calcium transport is considered as a specialized process developed only by certain cells in those tissues charged with bulk transfer of calcium. The overall effect of the endocytotic mechanism is bulk calcium movement across a cell, protection of mitochondria from exposure to high concentrations of calcium, and the avoidance of wide and potentially toxic fluctuations in cytosol ionic calcium levels. (MFB)

  8. Effects of calcium oxide treatment at varying moisture concentrations on the chemical composition, in situ degradability, in vitro digestibility and gas production kinetics of anaerobically stored corn stover.

    Science.gov (United States)

    Shi, H T; Cao, Z J; Wang, Y J; Li, S L; Yang, H J; Bi, Y L; Doane, P H

    2016-08-01

    The objective of this study was to determine the optimum conditions for calcium oxide (CaO) treatment of anaerobically stored corn stover by in situ and in vitro methods. Four ruminally cannulated, non-lactating, non-pregnant Holstein cows were used to determine the in situ effective degradabilities of dry matter (ISDMD), organic matter (ISOMD), neutral detergent fibre (ISNDFD), in vitro organic matter disappearance (IVOMD) and gas production in 72 h (GP72h ) of corn stover. A completely randomized design involving a 3 × 3 factorial arrangement was adopted. Ground corn stover was treated with different levels of CaO (3%, 5% and 7% of dry stover) at varying moisture contents (40%, 50% and 60%) and stored under anaerobic conditions for 15 days before analysis. Compared with untreated corn stover, the CaO-treated stover had increased ash and calcium (Ca) contents but decreased aNDF and OM contents. The moisture content, CaO level and their interaction affected (p  0.01) in these in situ degradability parameters were observed between the stover treated with 5% CaO at 60% moisture content and those treated with 7% CaO at 60% moisture content. Corn stover treated with 5% CaO at 50% moisture had the maximum IVOMD and GP72 h among the treatments, and there was no difference (p > 0.01) between 50% and 60% moisture. Results from this study suggested that 5% CaO applied at 60% moisture could be an effective and economical treatment combination. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  9. Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

    Science.gov (United States)

    Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

    2018-02-01

    Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian; Wu, Junhua

    2012-01-01

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses

  11. MiRNA-135a regulates the expression of small conductance calcium-activated potassium (SK3) channels in epilepsy-like conditions

    NARCIS (Netherlands)

    Honrath, Birgit; Norwood, Braxton; Tanrioever, Gaye; Kuter, Katarzyna; Henshall, David C; Aksel-Aksoy, Ayla; Schratt, Gerhard; Pasterkamp, Jeroen; Dencher, Norbert A.; Nieweg, Katja; Culmsee, Carsten; Dolga, Amalia Mihalea

    2017-01-01

    Background Excessive and hypersynchronous neuronal discharges are key characteristics in the pathophysiology of neurological disorders such as epilepsy. Owing to their ability of regulating neuronal excitability, small conductance calcium-activated potassium (SK) channels have been implicated in

  12. Differential expression of calcium/calmodulin-regulated SlSRs in response to abiotic and biotic stresses in tomato fruit.

    Science.gov (United States)

    Yang, Tianbao; Peng, Hui; Whitaker, Bruce D; Jurick, Wayne M

    2013-07-01

    Calcium has been shown to enhance stress tolerance, maintain firmness and reduce decay in fruits. Previously we reported that seven tomato SlSRs encode calcium/calmodulin-regulated proteins, and that their expressions are developmentally regulated during fruit development and ripening, and are also responsive to ethylene. To study their expressions in response to stresses encountered during postharvest handling, tomato fruit at the mature-green stage was subjected to chilling and wounding injuries, infected with Botrytis cinerea and treated with salicylic acid or methyl jasmonate. Gene expression studies revealed that the seven SlSRs differentially respond to different stress signals. SlSR2 was the only gene upregulated by all the treatments. SlSR4 acted as a late pathogen-induced gene; it was upregulated by salicylic acid and methyl jasmonate, but downregulated by cold treatment. SlSR3L was cold- and wound-responsive and was also induced by salicylic acid. SlSR1 and SlSR1L were repressed by cold, wounding and pathogen infection, but were upregulated by salicylic acid and methyl jasmonate. Overall, results of these expression studies indicate that individual SlSRs have distinct roles in responses to the specific stress signals, and SlSRs may act as a coordinator(s) connecting calcium-mediated signaling with other stress signal transduction pathways during fruit ripening and storage. © 2013 Scandinavian Plant Physiology Society.

  13. A Descriptive Longitudinal Study of Changes in Vape Shop Characteristics and Store Policies in Anticipation of the 2016 FDA Regulations of Tobacco Products, Including E-Cigarettes

    Directory of Open Access Journals (Sweden)

    Sheila Yu

    2018-02-01

    Full Text Available After proposing the “Deeming Rule” in 2014, the U.S. Food and Drug Administration (FDA began regulating the manufacturing, marketing, and sales of electronic cigarette (e-cigarette products as tobacco products in 2016. The current study conducted vape shop store observations and surveyed Los Angeles–area shop employees (assessing their beliefs, awareness, and perceptions of e-cigarettes and related FDA regulations at two time points one year apart to better understand what vape shop retailers would do given FDA’s soon-to-be-enacted Deeming Rule. The study also compared retailer beliefs/awareness/actions and store characteristics immediately after the Deeming Rule proposal versus a year after the Rule had been proposed, right before its enactment. Two data collection waves occurred before the Deeming Rule enactment, with Year 1 surveying 77 shops (2014 and Year 2 surveying 61 shops (2015–2016. Between the data collection points, 16 shops had closed. Among the shops that were open at both time points, the majority (95% in Year 1; 74% in Year 2 were aware of some FDA regulations or other policies applying to vape shops. However, overall awareness of FDA regulations and state/local policies governing e-cigarettes significantly decreased from Year 1 to Year 2. At both time points, all shops offered customers free puffs of nicotine-containing e-liquids (prohibited by the then upcoming Deeming Rule. Perceptions of e-cigarette safety also significantly decreased between the years. Exploring vape shop retailer perceptions and store policies (i.e., free puffs/samples displays, perceptions of e-cigarette safety, etc. over time will help the FDA assess the needs of the vape shop community and develop more effective retailer education campaigns and materials targeted to increase compliance with the newly enacted regulations.

  14. A Descriptive Longitudinal Study of Changes in Vape Shop Characteristics and Store Policies in Anticipation of the 2016 FDA Regulations of Tobacco Products, Including E-Cigarettes.

    Science.gov (United States)

    Yu, Sheila; Escobedo, Patricia; Garcia, Robert; Cruz, Tess Boley; Unger, Jennifer B; Baezconde-Garbanati, Lourdes; Meza, Leah; Sussman, Steve

    2018-02-11

    After proposing the "Deeming Rule" in 2014, the U.S. Food and Drug Administration (FDA) began regulating the manufacturing, marketing, and sales of electronic cigarette (e-cigarette) products as tobacco products in 2016. The current study conducted vape shop store observations and surveyed Los Angeles-area shop employees (assessing their beliefs, awareness, and perceptions of e-cigarettes and related FDA regulations) at two time points one year apart to better understand what vape shop retailers would do given FDA's soon-to-be-enacted Deeming Rule. The study also compared retailer beliefs/awareness/actions and store characteristics immediately after the Deeming Rule proposal versus a year after the Rule had been proposed, right before its enactment. Two data collection waves occurred before the Deeming Rule enactment, with Year 1 surveying 77 shops (2014) and Year 2 surveying 61 shops (2015-2016). Between the data collection points, 16 shops had closed. Among the shops that were open at both time points, the majority (95% in Year 1; 74% in Year 2) were aware of some FDA regulations or other policies applying to vape shops. However, overall awareness of FDA regulations and state/local policies governing e-cigarettes significantly decreased from Year 1 to Year 2. At both time points, all shops offered customers free puffs of nicotine-containing e-liquids (prohibited by the then upcoming Deeming Rule). Perceptions of e-cigarette safety also significantly decreased between the years. Exploring vape shop retailer perceptions and store policies (i.e., free puffs/samples displays, perceptions of e-cigarette safety, etc.) over time will help the FDA assess the needs of the vape shop community and develop more effective retailer education campaigns and materials targeted to increase compliance with the newly enacted regulations.

  15. Myofilament calcium sensitivity: Role in regulation of in vivo cardiac contraction and relaxation

    Directory of Open Access Journals (Sweden)

    Jae-Hoon Chung

    2016-12-01

    Full Text Available Myofilament calcium sensitivity is an often-used indicator of cardiac muscle function, often assessed in disease states such as hypertrophic cardiomyopathy (HCM and dilated cardiomyopathy (DCM. While calcium sensitivity measurement provides important insights into the mechanical force-generating capability of a muscle at steady-state, the dynamic behavior of the muscle cannot be sufficiently assessed with a force-pCa curve alone. The dissociation constant (Kd of the force-pCa curve depends on the ratio of the apparent on-rate (kon and apparent off-rate (koff of calcium on TnC and as a stand-alone parameter cannot provide an accurate depiction of the dynamic contraction and relaxation behavior without the additional quantification of kon or koff, or actually measuring dynamic twitch kinetics in an intact muscle. In this review, we examine the effect of length, frequency, and beta-adrenergic stimulation on myofilament calcium sensitivity and dynamic contraction, the effect of membrane permeabilization on calcium sensitivity, and the dynamic consequences of various myofilament protein mutations with potential implications in contractile and relaxation behavior.

  16. Biphasic regulation of intracellular calcium by gemfibrozil contributes to inhibiting L6 myoblast differentiation: implications for clinical myotoxicity.

    Science.gov (United States)

    Liu, Aiming; Yang, Julin; Gonzalez, Frank J; Cheng, Gary Q; Dai, Renke

    2011-02-18

    Gemfibrozil is the most myotoxic fibrate drug commonly used for dyslipidemia, but the mechanism is poorly understood. The current study revealed that gemfibrozil inhibits myoblast differentiation through the regulation of intracellular calcium ([Ca(2+)]i) as revealed in L6 myoblasts by use of laser scan confocal microscopy and flow cytometry using Fluo-4 AM as a probe. Gemfibrozil at 20-400 μM, could regulate [Ca(2+)]i in L6 cells in a biphasic manner, and sustained reduction was observed when the concentration reached 200 μM. Inhibition of L6 differentiation by gemfibrozil was concentration-dependent with maximal effect noted between 200 and 400 μM, as indicated by creatine kinase activities and the differentiation index, respectively. In differentiating L6 myoblasts, gemfibrozil at concentrations below 400 μM led to no significant signs of apoptosis or cytotoxicity, whereas differentiation, inhibited by 200 μM gemfibrozil, was only partially recovered. A good correlation was noted between gemfibrozil concentrations that regulate [Ca(2+)]i and inhibit L6 myoblasts differentiation, and both are within the range of total serum concentrations found in the clinic. These data suggest a potential pharmacodynamic effect of gemfibrozil on myogenesis as a warning sign, in addition to the complex pharmacokinetic interactions. It is also noteworthy that mobilization of [Ca(2+)]i by gemfibrozil may trigger complex biological responses besides myocyte differentiation. Information revealed in this study explores the mechanism of gemfibrozil-induced myotoxicity through the regulation of intracellular calcium.

  17. The Appetite-Inducing Peptide, Ghrelin, Induces Intracellular Store-Mediated Rises in Calcium in Addiction and Arousal-Related Laterodorsal Tegmental Neurons in Mouse Brain Slices

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behaviora...

  18. Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rui-Xing Wang

    2015-03-01

    Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

  19. Calcium channel agonists and antagonists regulate protein phosphorylation in intact synaptosomes

    International Nuclear Information System (INIS)

    Robinson, P.J.; Lovenberg, Walter

    1986-01-01

    Protein phosphorylation in intact synaptosomes is highly sensitive to alterations in calcium fluxes and was used to probe the possible mechanism of action of the calcium channel agonist BAY K 8644 and antagonists verapamil and nifedipine. These agents (at 1μM) all increased the basal phosphorylation of a specific set of 4 synaptosomal phosphoproteins termed P139, P124, P96 and P60, but did not alter depolarization-dependent protein phosphorylation. The increases could not be explained by a direct stimulation of protein kinases and appears unrelated to the known effects of these + drugs on K + -stimulated neuro-transmitter release. This finding may reveal a possible new mechanism of action for drugs which interact with calcium channels. (Author)

  20. Regulation of granule cell excitability by a low-threshold calcium spike in turtle olfactory bulb

    DEFF Research Database (Denmark)

    Pinato, Giulietta; Midtgaard, Jens

    2003-01-01

    of the cell usually increased their amplitude so that they more easily boosted Na spike initiation. The LTS persisted in the presence of TTX but was antagonized by blockers of T-type calcium channels. The voltage dependence, kinetics, and inactivation properties of the LTS were characteristic of a low......-threshold calcium spike. The threshold of the LTS was slightly above the resting potential but well below the Na spike threshold, and the LTS was often evoked in isolation in normal medium. Tetraethylammonium (TEA) and 4-aminopyridine (4-AP) had only minimal effects on the LTS but revealed the presence of a high...

  1. Molecular imaging of in vivo calcium ion expression in area postrema of total sleep deprived rats: Implications for cardiovascular regulation by TOF-SIMS analysis

    Science.gov (United States)

    Mai, Fu-Der; Chen, Li-You; Ling, Yong-Chien; Chen, Bo-Jung; Wu, Un-In; Chang, Hung-Ming

    2010-05-01

    Excessive calcium influx in chemosensitive neurons of area postrema (AP) is detrimental for sympathetic activation and participates in the disruption of cardiovascular activities. Since total sleep deprivation (TSD) is a stressful condition known to harm the cardiovascular function, the present study is aimed to determine whether the in vivo calcium expression in AP would significantly alter following TSD by the use of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and calretinin (a specific calcium sensor protein in AP neurons) immunohistochemistry. The results indicated that in normal rats, the calcium intensity was estimated to be 0.5 × 10 5 at m/ z 40.08. However, following TSD, the intensity for calcium ions was greatly increased to 1.2 × 10 5. Molecular imaging revealed that after TSD, various strongly expressed calcium signals were distributed throughout AP with clear identified profiles instead of randomly scattered within this region in normal rats. Immunohistochemical staining corresponded well with ionic image in which a majority of calcium-enriched gathering co-localized with calretinin positive neurons. The functional significance of TSD-induced calcium augmentation was demonstrated by increased heart rate and mean arterial pressure, clinical markers for cardiovascular dysfunction. Considering AP-mediated sympathetic activation is important for cardiovascular regulation, exaggerated calcium influx in AP would render this neurocircuitry more vulnerable to over-excitation, which might serve as the underlying mechanism for the development of TSD-relevant cardiovascular deficiency.

  2. G Protein Regulation of Neuronal Calcium Channels: Back to the Future

    Czech Academy of Sciences Publication Activity Database

    Proft, Juliane; Weiss, Norbert

    2015-01-01

    Roč. 87, č. 6 (2015), s. 890-906 ISSN 0026-895X R&D Projects: GA ČR GA15-13556S Institutional support: RVO:61388963 Keywords : voltage gated calcium channels Cav * G proteins * GPCR Subject RIV: CE - Biochemistry Impact factor: 3.931, year: 2015

  3. Characterization of a calcium/calmodulin-dependent protein kinase homolog from maize roots showing light-regulated gravitropism

    Science.gov (United States)

    Lu, Y. T.; Hidaka, H.; Feldman, L. J.

    1996-01-01

    Roots of many species respond to gravity (gravitropism) and grow downward only if illuminated. This light-regulated root gravitropism is phytochrome-dependent, mediated by calcium, and inhibited by KN-93, a specific inhibitor of calcium/calmodulin-dependent protein kinase II (CaMK II). A cDNA encoding MCK1, a maize homolog of mammalian CaMK, has been isolated from roots of maize (Zea mays L.). The MCK1 gene is expressed in root tips, the site of perception for both light and gravity. Using the [35S]CaM gel-overlay assay we showed that calmodulin-binding activity of the MCK1 is abolished by 50 microM KN-93, but binding is not affected by 5 microM KN-93, paralleling physiological findings that light-regulated root gravitropism is inhibited by 50 microM KN-93, but not by 5 microM KN-93. KN-93 inhibits light-regulated gravitropism by interrupting transduction of the light signal, not light perception, suggesting that MCK1 may play a role in transducing light. This is the first report suggesting a physiological function for a CaMK homolog in light signal transduction.

  4. The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice.

    Science.gov (United States)

    Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying

    2017-08-01

    Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.

  5. Signaling domain of Sonic Hedgehog as cannibalistic calcium-regulated zinc-peptidase.

    Directory of Open Access Journals (Sweden)

    Rocio Rebollido-Rios

    2014-07-01

    Full Text Available Sonic Hedgehog (Shh is a representative of the evolutionary closely related class of Hedgehog proteins that have essential signaling functions in animal development. The N-terminal domain (ShhN is also assigned to the group of LAS proteins (LAS = Lysostaphin type enzymes, D-Ala-D-Ala metalloproteases, Sonic Hedgehog, of which all members harbor a structurally well-defined Zn2+ center; however, it is remarkable that ShhN so far is the only LAS member without proven peptidase activity. Another unique feature of ShhN in the LAS group is a double-Ca2+ center close to the zinc. We have studied the effect of these calcium ions on ShhN structure, dynamics, and interactions. We find that the presence of calcium has a marked impact on ShhN properties, with the two calcium ions having different effects. The more strongly bound calcium ion significantly stabilizes the overall structure. Surprisingly, the binding of the second calcium ion switches the putative catalytic center from a state similar to LAS enzymes to a state that probably is catalytically inactive. We describe in detail the mechanics of the switch, including the effect on substrate co-ordinating residues and on the putative catalytic water molecule. The properties of the putative substrate binding site suggest that ShhN could degrade other ShhN molecules, e.g. by cleavage at highly conserved glycines in ShhN. To test experimentally the stability of ShhN against autodegradation, we compare two ShhN mutants in vitro: (1 a ShhN mutant unable to bind calcium but with putative catalytic center intact, and thus, according to our hypothesis, a constitutively active peptidase, and (2 a mutant carrying additionally mutation E177A, i.e., with the putative catalytically active residue knocked out. The in vitro results are consistent with ShhN being a cannibalistic zinc-peptidase. These experiments also reveal that the peptidase activity depends on pH.

  6. Cell-specific vacuolar calcium storage mediated by CAX1 regulates apoplastic calcium concentration, gas exchange, and plant productivity in Arabidopsis.

    Science.gov (United States)

    Conn, Simon J; Gilliham, Matthew; Athman, Asmini; Schreiber, Andreas W; Baumann, Ute; Moller, Isabel; Cheng, Ning-Hui; Stancombe, Matthew A; Hirschi, Kendal D; Webb, Alex A R; Burton, Rachel; Kaiser, Brent N; Tyerman, Stephen D; Leigh, Roger A

    2011-01-01

    The physiological role and mechanism of nutrient storage within vacuoles of specific cell types is poorly understood. Transcript profiles from Arabidopsis thaliana leaf cells differing in calcium concentration ([Ca], epidermis 60 mM) were compared using a microarray screen and single-cell quantitative PCR. Three tonoplast-localized Ca(2+) transporters, CAX1 (Ca(2+)/H(+)-antiporter), ACA4, and ACA11 (Ca(2+)-ATPases), were identified as preferentially expressed in Ca-rich mesophyll. Analysis of respective loss-of-function mutants demonstrated that only a mutant that lacked expression of both CAX1 and CAX3, a gene ectopically expressed in leaves upon knockout of CAX1, had reduced mesophyll [Ca]. Reduced capacity for mesophyll Ca accumulation resulted in reduced cell wall extensibility, stomatal aperture, transpiration, CO(2) assimilation, and leaf growth rate; increased transcript abundance of other Ca(2+) transporter genes; altered expression of cell wall-modifying proteins, including members of the pectinmethylesterase, expansin, cellulose synthase, and polygalacturonase families; and higher pectin concentrations and thicker cell walls. We demonstrate that these phenotypes result from altered apoplastic free [Ca(2+)], which is threefold greater in cax1/cax3 than in wild-type plants. We establish CAX1 as a key regulator of apoplastic [Ca(2+)] through compartmentation into mesophyll vacuoles, a mechanism essential for optimal plant function and productivity.

  7. Calcium oscillations in wounded fibroblast monolayers are spatially regulated through substrate mechanics

    Science.gov (United States)

    Lembong, Josephine; Sabass, Benedikt; Stone, Howard A.

    2017-08-01

    The maintenance of tissue integrity is essential for the life of multicellular organisms. Healing of a skin wound is a paradigm for how various cell types localize and repair tissue perturbations in an orchestrated fashion. To investigate biophysical mechanisms associated with wound localization, we focus on a model system consisting of a fibroblast monolayer on an elastic substrate. We find that the creation of an edge in the monolayer causes cytosolic calcium oscillations throughout the monolayer. The oscillation frequency increases with cell density, which shows that wound-induced calcium oscillations occur collectively. Inhibition of myosin II reduces the number of oscillating cells, demonstrating a coupling between actomyosin activity and calcium response. The spatial distribution of oscillating cells depends on the stiffness of the substrate. For soft substrates with a Young’s modulus E ~ 360 Pa, oscillations occur on average within 0.2 mm distance from the wound edge. Increasing substrate stiffness leads to an average localization of oscillations away from the edge (up to ~0.6 mm). In addition, we use traction force microscopy to determine stresses between cells and substrate. We find that an increase of substrate rigidity leads to a higher traction magnitude. For E    ~8 kPa, traction magnitude is on average almost uniform beneath the monolayer. Thus, the spatial occurrence of calcium oscillations correlates with the cell-substrate traction. Overall, the experiments with fibroblasts demonstrate a collective, chemomechanical localization mechanism at the edge of a wound with a potential physiological role.

  8. Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition

    Czech Academy of Sciences Publication Activity Database

    Bilkova, E.; Pleskot, Roman; Rissanen, S.; Sun, S.; Czogalla, A.; Cwiklik, Lukasz; Róg, T.; Vattulainen, I.; Cremer, P. S.; Jungwirth, P.; Coskun, U.

    2017-01-01

    Roč. 139, č. 11 (2017), s. 4019-4024 ISSN 0002-7863 R&D Projects: GA ČR GA13-19073S Institutional support: RVO:61389030 ; RVO:61388955 Keywords : membrane * calcium ions * PIP2 * molecular dynamics Subject RIV: EB - Genetics ; Molecular Biology; CF - Physical ; Theoretical Chemistry (UFCH-W) OBOR OECD: Cell biology Impact factor: 13.858, year: 2016

  9. Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition

    Czech Academy of Sciences Publication Activity Database

    Bilkova, E.; Pleskot, Roman; Rissanen, S.; Sun, S.; Czogalla, A.; Cwiklik, Lukasz; Róg, T.; Vattulainen, I.; Cremer, P. S.; Jungwirth, Pavel; Coskun, U.

    2017-01-01

    Roč. 139, č. 11 (2017), s. 4019-4024 ISSN 0002-7863 R&D Projects: GA ČR(CZ) GA16-01074S Institutional support: RVO:61388963 Keywords : membrane * calcium ions * PIP2 * molecular dynamics Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 13.858, year: 2016 http://pubs.acs.org/doi/full/10.1021/jacs.6b11760

  10. Injectable calcium sulfate/mineralized collagen-based bone repair materials with regulable self-setting properties.

    Science.gov (United States)

    Chen, Zonggang; Liu, Huanye; Liu, Xi; Cui, Fu-Zhai

    2011-12-15

    An injectable and self-setting bone repair materials (nano-hydroxyapatite/collagen/calcium sulfate hemihydrate, nHAC/CSH) was developed in this study. The nano-hydroxyapatite/collagen (nHAC) composite, which is the mineralized fibril by self-assembly of nano-hydrocyapatite and collagen, has the same features as natural bone in both main hierarchical microstructure and composition. It is a bioactive osteoconductor due to its high level of biocompatibility and appropriate degradation rate. However, this material lacks handling characteristics because of its particle or solid-preformed block shape. Herein, calcium sulfate hemihydrate (CSH) was introduced into nHAC to prepare an injectable and self-setting in situ bone repair materials. The morphology of materials was observed using SEM. Most important and interesting of all, calcium sulfate dihydrate (CSD), which is not only the reactant of preparing CSH but also the final solidified product of CSH, was introduced into nHAC as setting accelerator to regulate self-setting properties of injectable nHAC/CSH composite, and thus the self-setting time of nHAC/CSH composite can be regulated from more than 100 min to about 30 min and even less than 20 min by adding various amount of setting accelerator. The compressive properties of bone graft substitute after final setting are similar to those of cancellous bone. CSD as an excellent setting accelerator has no significant effect on the mechanical property and degradability of bone repair materials. In vitro biocompatibility and in vivo histology studies demonstrated that the nHAC/CSH composite could provide more adequate stimulus for cell adhesion and proliferation, embodying favorable cell biocompatibility and a strong ability to accelerate bone formation. It can offer a satisfactory biological environment for growing new bone in the implants and for stimulating bone formation. Copyright © 2011 Wiley Periodicals, Inc.

  11. Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.

    Science.gov (United States)

    Ozcan, Lale; Wong, Catherine C L; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A; Yates, John R; Accili, Domenico; Tabas, Ira

    2012-05-02

    Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Membrane junctions in Xenopus eggs: their distribution suggests a role in calcium regulation.

    Science.gov (United States)

    Gardiner, D M; Grey, R D

    1983-04-01

    We have observed the presence of membrane junctions formed between the plasma membrane and cortical endoplasmic reticulum of mature, unactivated eggs of xenopus laevis. The parallel, paired membranes of the junction are separated by a 10-mn gap within which electron-dense material is present. This material occurs in patches with an average center-to-center distance of approximately 30 nm. These junctions are rare in immature (but fully grown) oocytes (approximately 2 percent of the plasma membrane is associated with junctions) and increase dramatically during progesterone-induced maturation. Junctions in the mature, unactivated egg are two to three times more abundant in the animal hemisphere (25-30 percent of the plasma membrane associated with junction) as compared with the vegetal hemisphere (10-15 percent). Junction density decreases rapidly to values characteristic of immature oocytes in response to egg activation. The plasma membrane-ER junctions of xenopus eggs are strikingly similar in structure to membrane junctions in muscle cells thought to be essential in the triggering of intracellular calcium release from the sarcoplasmic reticulum. In addition, the junctions' distinctive, animal-vegetal polarity of distribution, their dramatic appearance during maturation, and their disapperance during activation are correlated with previously documented patterns of calcium-mediated events in anuran eggs. We discuss several lines of evidence supporting the hypothesis that these junctions in xenopus eggs are sites that transduce extracellular events into intracellular calcium release during fertilization and activation of development.

  13. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Lee Na-Young

    2010-08-01

    Full Text Available Abstract Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells, as in vitro blood-placental barrier (BPB model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC activator in TR-TBT cells. Also, calcium ion (Ca2+ was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α, lipopolysaccharide (LPS and diethyl maleate (DEM significantly increased taurine uptake, but H2O2 and nitric oxide (NO donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus.

  14. Phospholipid mediated activation of calcium dependent protein kinase 1 (CaCDPK1 from chickpea: a new paradigm of regulation.

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Dixit

    Full Text Available Phospholipids, the major structural components of membranes, can also have functions in regulating signaling pathways in plants under biotic and abiotic stress. The effects of adding phospholipids on the activity of stress-induced calcium dependent protein kinase (CaCDPK1 from chickpea are reported here. Both autophosphorylation as well as phosphorylation of the added substrate were enhanced specifically by phosphatidylcholine and to a lesser extent by phosphatidic acid, but not by phosphatidylethanolamine. Diacylgylerol, the neutral lipid known to activate mammalian PKC, stimulated CaCDPK1 but at higher concentrations. Increase in V(max of the enzyme activity by these phospholipids significantly decreased the K(m indicating that phospholipids enhance the affinity towards its substrate. In the absence of calcium, addition of phospholipids had no effect on the negligible activity of the enzyme. Intrinsic fluorescence intensity of the CaCDPK1 protein was quenched on adding PA and PC. Higher binding affinity was found with PC (K(½ = 114 nM compared to PA (K(½ = 335 nM. We also found that the concentration of PA increased in chickpea plants under salt stress. The stimulation by PA and PC suggests regulation of CaCDPK1 by these phospholipids during stress response.

  15. Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

    Science.gov (United States)

    Hahn, Hyung Jin; Youn, Hae Jeong; Cha, Hwa Jun; Kim, Karam; An, Sungkwan

    2016-01-01

    Background We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. Objective We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. Methods To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. Results Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. Conclusion These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation. PMID:27489424

  16. Glucose Regulates Cyclin D2 Expression in Quiescent and Replicating Pancreatic β-Cells Through Glycolysis and Calcium Channels

    Science.gov (United States)

    Salpeter, Seth J.; Klochendler, Agnes; Weinberg-Corem, Noa; Porat, Shay; Granot, Zvi; Shapiro, A. M. James; Magnuson, Mark A.; Eden, Amir; Grimsby, Joseph; Glaser, Benjamin

    2011-01-01

    Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G2-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication. PMID:21521747

  17. Regulation of photosynthesis by end-product accumulation in leaves of plants storing starch, sucrose, and hexose sugars.

    Science.gov (United States)

    Goldschmidt, E E; Huber, S C

    1992-08-01

    In the present study, leaves of different plant species were girdled by the hot wax collar method to prevent export of assimilates. Photosynthetic activity of girdled and control leaves was evaluated 3 to 7 days later by two methods: (a) carbon exchange rate (CER) of attached leaves was determined under ambient CO(2) concentrations using a closed gas system, and (b) maximum photosynthetic capacity (A(max)) was determined under 3% CO(2) with a leaf disc O(2) electrode. Starch, hexoses, and sucrose were determined enzymically. Typical starch storers like soybean (Glycine max L.) (up to 87.5 milligrams of starch per square decimeter in girdled leaves), cotton (Gossypium hirsutum L.), and cucumber (Cucumis sativus L.) responded to 7 days of girdling by increased (80-100%) stomatal resistance (r(s)) and decreased A(max) (>50%). On the other hand, spinach (Spinacia oleracea L.), a typical sucrose storer (up to 160 milligrams of sucrose per square decimeter in girdled leaves), showed only a slight reduction in CER and almost no change in A(max). Intermediate plants like tomato (Lycopersicon esculentum Mill.), sunflower (Helianthus annuus L.), broad bean (Vicia faba L.), bean (Phaseolus vulgaris L.), and pea (Pisum sativum L.), which upon girdling store both starch and sucrose, responded to the girdle by a considerable reduction in CER but only moderate inhibition of A(max), indicating that the observed reduction in CER was primarily a stomatal response. Both the wild-type tobacco (Nicotiana sylvestris) (which upon girdling stored starch and hexoses) and the starchless mutant (which stored only hexoses, up to 90 milligrams per square decimeter) showed 90 to 100% inhibition of CER and approximately 50% inhibition of A(max). In general, excised leaves (6 days) behaved like girdled leaves of the respective species, showing 50% reduction of A(max) in wild-type and starchless N. sylvestris but only slight decline of A(max) in spinach. The results of the present study

  18. 17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3.

    LENUS (Irish Health Repository)

    Muchekehu, Ruth W

    2008-09-01

    We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3\\

  19. Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel

    Energy Technology Data Exchange (ETDEWEB)

    Gaudioso, Christelle; Carlier, Edmond; Youssouf, Fahamoe [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Clare, Jeffrey J. [Eaton Pharma Consulting, Eaton Socon, Cambridgeshire PE19 8EF (United Kingdom); Debanne, Dominique [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Alcaraz, Gisele, E-mail: gisele.alcaraz@univmed.fr [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France)

    2011-07-29

    Highlights: {yields} Both Ca{sup ++}-Calmodulin (CaM) and Ca{sup ++}-free CaM bind to the C-terminal region of Nav1.1. {yields} Ca{sup ++} and CaM have both opposite and convergent effects on I{sub Nav1.1}. {yields} Ca{sup ++}-CaM modulates I{sub Nav1.1} amplitude. {yields} CaM hyperpolarizes the voltage-dependence of activation, and increases the inactivation rate. {yields} Ca{sup ++} alone antagonizes CaM for both effects, and depolarizes the voltage-dependence of inactivation. -- Abstract: Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a stably transfected HEK-293 cell line. The C-terminal region of the channel, as a fusion protein or in the yeast two-hybrid system, interacted with CaM via a consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1 cells showed that CaM overexpression increased peak current in a calcium-dependent way. CaM had no effect on the voltage-dependence of fast inactivation, and accelerated the inactivation kinetics. Elevating Ca{sup ++} depolarized the voltage-dependence of fast inactivation and slowed down the fast inactivation kinetics, and for high concentrations this effect competed with the acceleration induced by CaM alone. Similarly, the depolarizing action of calcium antagonized the hyperpolarizing shift of the voltage-dependence of activation due to CaM overexpression. Fluorescence spectroscopy measurements suggested that Ca{sup ++} could bind the Nav1.1 C-terminal region with micromolar affinity.

  20. Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation.

    Science.gov (United States)

    Huang, Hsueh-Meei; Zhang, Hui; Xu, Hui; Gibson, Gary E

    2003-01-20

    Mitochondrial dysfunction occurs in many neurodegenerative diseases. The alpha-ketoglutarate dehydrogenase complex (KGDHC) catalyzes a key and arguably rate-limiting step of the tricarboxylic acid cycle (TCA). A reduction in the activity of the KGDHC occurs in brains and cells of patients with many of these disorders and may underlie the abnormal mitochondrial function. Abnormalities in calcium homeostasis also occur in fibroblasts from Alzheimer's disease (AD) patients and in cells bearing mutations that lead to AD. Thus, the present studies test whether the reduction of KGDHC activity can lead to the alterations in mitochondrial function and calcium homeostasis. alpha-Keto-beta-methyl-n-valeric acid (KMV) inhibits KGDHC activity in living N2a cells in a dose- and time-dependent manner. Surprisingly, concentration of KMV that inhibit in situ KGDHC by 80% does not alter the mitochondrial membrane potential (MMP). However, similar concentrations of KMV induce the release of cytochrome c from mitochondria into the cytosol, reduce basal [Ca(2+)](i) by 23% (Pcalcium release from the endoplasmic reticulum (ER) by 46% (P<0.005). This result suggests that diminished KGDHC activities do not lead to the Ca(2+) abnormalities in fibroblasts from AD patients or cells bearing PS-1 mutations. The increased release of cytochrome c with diminished KGDHC activities will be expected to activate other pathways including cell death cascades. Reductions in this key mitochondrial enzyme will likely make the cells more vulnerable to metabolic insults that promote cell death.

  1. Regulation of proteolysis in Bacillus subtilis: effects of calcium ions and energy poisons

    International Nuclear Information System (INIS)

    O'Hara, M.B.; Hageman, J.H.

    1987-01-01

    Bacillus subtilis cells carry out extensive intracellular proteolysis (k = 0.15-0.23/h) during sporulation. Protein degradation was measured in cells growing in chemically defined sporulation medium, by following the release of [ 14 C]-leucine from the cells during spore formation. Sodium arsenate, carbonyl cyanide 3-chlorophenyl hydrazone, and sodium azide strongly inhibited proteolysis without altering cell viability greatly, which suggested that bulk proteolysis in B. subtilis is energy dependent. The authors have tested the hypothesis that the energy requirement may be for pumping in Ca 2+ . When [Ca 2+ ] was -6 , rates of proteolysis in sporulating cells were reduced 4-8 times that in cells in calcium ion- sufficient medium. Further, omission of Ca 2+ from the medium prevented the increase in the activity of the major intracellular serine protease. However, the presence of energy poisons in the media at levels which inhibited proteolysis, had no detectable effect on the uptake of by cells [ 45 Ca]. The authors concluded that B. subtilis cells required both metabolic energy and calcium ions for normal proteolysis

  2. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

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

  3. Intracellular Ca2+ Regulation in Calcium Sensitive Phenotype of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    HERMANSYAH

    2010-03-01

    Full Text Available Intracellular cytosolic Ca2+ concentration accumulation plays an essential information in Saccharomyces cerevisiae i.e. to explain cellular mechanism of Ca2+ sensitive phenotype. Disruption both S. cerevisiae PPase PTP2 and MSG5 genes showed an inhibited growth in the presence of Ca2+. On the other hand, by using Luminocounter with apoaequorin system, a method based upon luminescent photoprotein aequorin, intracellular Ca2+ concentration was accumulated as a consequence of calcium sensitive phenotype of S. cerevisiae. This fact indicated that PPase ptp2Δ and msg5Δ were involved in intracellular Ca2+ transport in addition their already known pathways i.e Mitogen Activated Protein Kinase cell wall integrity pathway, high osmolarity glycerol (HOG pathway, and pheromone response FUS3 pathway.

  4. Bruton's tyrosine kinase mediates the synergistic signalling between TLR9 and the B cell receptor by regulating calcium and calmodulin.

    Directory of Open Access Journals (Sweden)

    Elaine F Kenny

    Full Text Available B cells signal through both the B cell receptor (BCR which binds antigens and Toll-like receptors (TLRs including TLR9 which recognises CpG DNA. Activation of TLR9 synergises with BCR signalling when the BCR and TLR9 co-localise within an auto-phagosome-like compartment. Here we report that Bruton's tyrosine kinase (BTK is required for synergistic IL6 production and up-regulation of surface expression of MHC-class-II, CD69 and CD86 in primary murine and human B cells. We show that BTK is essential for co-localisation of the BCR and TLR9 within a potential auto-phagosome-like compartment in the Namalwa human B cell line. Downstream of BTK we find that calcium acting via calmodulin is required for this process. These data provide new insights into the role of BTK, an important target for autoimmune diseases, in B cell activation.

  5. The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1.

    Directory of Open Access Journals (Sweden)

    Bo Yang

    Full Text Available Breaking the balance between proliferation and differentiation in animal cells can lead to cancer, but the mechanisms maintaining this balance remain largely undefined. The calcium activated chloride channel A1 (CLCA1 is a member of the calcium sensitive chloride conductance family of proteins and is expressed mainly in the colon, small intestine and appendix. We show that CLCA1 plays a functional role in differentiation and proliferation of Caco-2 cells and of intestinal tissue. Caco-2 cells spontaneously differentiate either in confluent culture or when treated with butyrate, a molecule present naturally in the diet. Here, we compared CLCA1 expressional levels between patients with and without colorectal cancer (CRC and determined the functional role of CLCA1 in differentiation and proliferation of Caco-2 cells. We showed that: 1 CLCA1 and CLCA4 expression were down-regulated significantly in CRC patients; 2 CLCA1 expression was up-regulated in Caco-2 cells induced to differentiate by confluent culture or by treatment with sodium butyrate (NaBT; 3 Knockdown of CLCA1 with siRNA significantly inhibited cell differentiation and promoted cell proliferation in Caco-2 confluent cultures, and 4 In Caco-2 3D culture, suppression of CLCA1 significantly increased cell proliferation and compromised NaBT-induced inhibition of proliferation. In conclusion, CLCA1 may contribute to promoting spontaneous differentiation and reducing proliferation of Caco-2 cells and may be a target of NaBT-induced inhibition of proliferation and therefore a potential diagnostic marker for CRC prognosis.

  6. Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Calcium Binding Properties and Allosteric Regulation of Downstream Regulatory Element Antagonist Modulator (DREAM).

    Science.gov (United States)

    Zhang, Jun; Li, Jing; Craig, Theodore A; Kumar, Rajiv; Gross, Michael L

    2017-07-18

    Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca 2+ -binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca 2+ but detaches from DRE under Ca 2+ stimulation, allowing gene expression. The Ca 2+ binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca 2+ binding properties and the subsequent conformational changes of full-length DREAM. We demonstrate that all EF-hands undergo large conformation changes upon calcium binding even though the EF-1 hand is not capable of binding to Ca 2+ . Moreover, EF-2 is a lower-affinity site compared to EF-3 and -4 hands. Comparison of HDX profiles between wild-type DREAM and two EF-1 mutated constructs illustrates that the conformational changes in the EF-1 hand are induced by long-range structural interactions. HDX analyses also reveal a conformational change in an N-terminal leucine-charged residue-rich domain (LCD) remote from Ca 2+ -binding EF-hands. This LCD domain is responsible for the direct interaction between DREAM and cAMP response element-binding protein (CREB) and regulates the recruitment of the co-activator, CREB-binding protein. These long-range interactions strongly suggest how conformational changes transmit the Ca 2+ signal to CREB-mediated gene transcription.

  7. Direct interaction of CaVβ with actin up-regulates L-type calcium currents in HL-1 cardiomyocytes.

    Science.gov (United States)

    Stölting, Gabriel; de Oliveira, Regina Campos; Guzman, Raul E; Miranda-Laferte, Erick; Conrad, Rachel; Jordan, Nadine; Schmidt, Silke; Hendriks, Johnny; Gensch, Thomas; Hidalgo, Patricia

    2015-02-20

    Expression of the β-subunit (CaVβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. CaVβ binds to the α1 pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although CaVβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between CaVβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by CaVβ2 that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of CaVβ2-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. CaVβ mediated L-type up-regulation, and CaVβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of CaVβ that is directly involved in vesicular trafficking. We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Direct Interaction of CaVβ with Actin Up-regulates L-type Calcium Currents in HL-1 Cardiomyocytes*

    Science.gov (United States)

    Stölting, Gabriel; de Oliveira, Regina Campos; Guzman, Raul E.; Miranda-Laferte, Erick; Conrad, Rachel; Jordan, Nadine; Schmidt, Silke; Hendriks, Johnny; Gensch, Thomas; Hidalgo, Patricia

    2015-01-01

    Expression of the β-subunit (CaVβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. CaVβ binds to the α1 pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although CaVβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between CaVβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by CaVβ2 that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of CaVβ2-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. CaVβ mediated L-type up-regulation, and CaVβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of CaVβ that is directly involved in vesicular trafficking. We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. PMID:25533460

  9. The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins.

    Science.gov (United States)

    Takahara, Terunao; Inoue, Kuniko; Arai, Yumika; Kuwata, Keiko; Shibata, Hideki; Maki, Masatoshi

    2017-10-13

    Mobilization of intracellular calcium is essential for a wide range of cellular processes, including signal transduction, apoptosis, and vesicular trafficking. Several lines of evidence have suggested that apoptosis-linked gene 2 (ALG-2, also known as PDCD6 ), a calcium-binding protein, acts as a calcium sensor linking calcium levels with efficient vesicular trafficking, especially at the endoplasmic reticulum (ER)-to-Golgi transport step. However, how ALG-2 regulates these processes remains largely unclear. Here, we report that M APK1- i nteracting and s pindle- s tabilizing (MISS)- l ike (MISSL), a previously uncharacterized protein, interacts with ALG-2 in a calcium-dependent manner. Live-cell imaging revealed that upon a rise in intracellular calcium levels, GFP-tagged MISSL (GFP-MISSL) dynamically relocalizes in a punctate pattern and colocalizes with ALG-2. MISSL knockdown caused disorganization of the components of the ER exit site, the ER-Golgi intermediate compartment, and Golgi. Importantly, knockdown of either MISSL or ALG-2 attenuated the secretion of se creted a lkaline p hosphatase (SEAP), a model secreted cargo protein, with similar reductions in secretion by single- and double-protein knockdowns, suggesting that MISSL and ALG-2 act in the same pathway to regulate the secretion process. Furthermore, ALG-2 or MISSL knockdown delayed ER-to-Golgi transport of procollagen type I. We also found that ALG-2 and MISSL interact with microtubule-associated protein 1B (MAP1B) and that MAP1B knockdown reverts the reduced secretion of SEAP caused by MISSL or ALG-2 depletion. These results suggest that a change in the intracellular calcium level plays a role in regulation of the secretory pathway via interaction of ALG-2 with MISSL and MAP1B. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

    Science.gov (United States)

    Dimitrov, Vassil; Salehi-Tabar, Reyhaneh; An, Beum-Soo; White, John H

    2014-10-01

    Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last ∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids.

    Science.gov (United States)

    Mannowetz, Nadja; Miller, Melissa R; Lishko, Polina V

    2017-05-30

    The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that ( i ) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and ( ii ) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.

  12. Calcium-Induced calcium release during action potential firing in developing inner hair cells.

    Science.gov (United States)

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

    2015-03-10

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  13. ZmCPK1, a calcium-independent kinase member of the Zea mays CDPK gene family, functions as a negative regulator in cold stress signalling.

    Science.gov (United States)

    Weckwerth, Philipp; Ehlert, Britta; Romeis, Tina

    2015-03-01

    Calcium-dependent protein kinases (CDPKs) have been shown to play important roles in plant environmental stress signal transduction. We report on the identification of ZmCPK1 as a member of the maize (Zea mays) CDPK gene family involved in the regulation of the maize cold stress response. Based upon in silico analysis of the Z. mays cv. B73 genome, we identified that the maize CDPK gene family consists of 39 members. Two CDPK members were selected whose gene expression was either increased (Zmcpk1) or decreased (Zmcpk25) in response to cold exposure. Biochemical analysis demonstrated that ZmCPK1 displays calcium-independent protein kinase activity. The C-terminal calcium-binding domain of ZmCPK1 was sufficient to mediate calcium independency of a previously calcium-dependent enzyme in chimeric ZmCPK25-CPK1 proteins. Furthermore, co-transfection of maize mesophyll protoplasts with active full-length ZmCPK1 suppressed the expression of a cold-induced marker gene, Zmerf3 (ZmCOI6.21). In accordance, heterologous overexpression of ZmCPK1 in Arabidopsis thaliana yielded plants with altered acclimation-induced frost tolerance. Our results identify ZmCPK1 as a negative regulator of cold stress signalling in maize. © 2014 John Wiley & Sons Ltd.

  14. The calcium sensor synaptotagmin 1 is expressed and regulated in hippocampal postsynaptic spines

    DEFF Research Database (Denmark)

    Hussain, Suleman; Egbenya, Daniel Lawer; Lai, Yi-Chen

    2017-01-01

    vesicles and at the postsynaptic density. We further investigated whether postsynaptic synaptotagmin 1 is regulated during synaptic plasticity. In a rat model of chronic temporal lobe epilepsy, we found that presynaptic and postsynaptic concentrations of the protein are reduced compared to control animals...

  15. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

    Science.gov (United States)

    Ngkelo, Anta; Richart, Adèle; Kirk, Jonathan A; Bonnin, Philippe; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Le Gall, Sylvain; Renault, Nisa; Guerin, Coralie; Ranek, Mark J; Kervadec, Anaïs; Danelli, Luca; Gautier, Gregory; Blank, Ulrich; Launay, Pierre; Camerer, Eric; Bruneval, Patrick; Menasche, Philippe; Heymes, Christophe; Luche, Elodie; Casteilla, Louis; Cousin, Béatrice; Rodewald, Hans-Reimer; Kass, David A; Silvestre, Jean-Sébastien

    2016-06-27

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. ©2016 Ngkelo et al.

  16. Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

    Science.gov (United States)

    Lin, C S; Boltz, R C; Blake, J T; Nguyen, M; Talento, A; Fischer, P A; Springer, M S; Sigal, N H; Slaughter, R S; Garcia, M L

    1993-03-01

    The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

  17. LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

    Science.gov (United States)

    Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

    2016-07-01

    Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

  18. A voltage-gated calcium channel regulates lysosomal fusion with endosomes and autophagosomes and is required for neuronal homeostasis.

    Directory of Open Access Journals (Sweden)

    Xuejun Tian

    2015-03-01

    Full Text Available Autophagy helps deliver sequestered intracellular cargo to lysosomes for proteolytic degradation and thereby maintains cellular homeostasis by preventing accumulation of toxic substances in cells. In a forward mosaic screen in Drosophila designed to identify genes required for neuronal function and maintenance, we identified multiple cacophony (cac mutant alleles. They exhibit an age-dependent accumulation of autophagic vacuoles (AVs in photoreceptor terminals and eventually a degeneration of the terminals and surrounding glia. cac encodes an α1 subunit of a Drosophila voltage-gated calcium channel (VGCC that is required for synaptic vesicle fusion with the plasma membrane and neurotransmitter release. Here, we show that cac mutant photoreceptor terminals accumulate AV-lysosomal fusion intermediates, suggesting that Cac is necessary for the fusion of AVs with lysosomes, a poorly defined process. Loss of another subunit of the VGCC, α2δ or straightjacket (stj, causes phenotypes very similar to those caused by the loss of cac, indicating that the VGCC is required for AV-lysosomal fusion. The role of VGCC in AV-lysosomal fusion is evolutionarily conserved, as the loss of the mouse homologues, Cacna1a and Cacna2d2, also leads to autophagic defects in mice. Moreover, we find that CACNA1A is localized to the lysosomes and that loss of lysosomal Cacna1a in cerebellar cultured neurons leads to a failure of lysosomes to fuse with endosomes and autophagosomes. Finally, we show that the lysosomal CACNA1A but not the plasma-membrane resident CACNA1A is required for lysosomal fusion. In summary, we present a model in which the VGCC plays a role in autophagy by regulating the fusion of AVs with lysosomes through its calcium channel activity and hence functions in maintaining neuronal homeostasis.

  19. The effect of growth regulators on the uptake and distribution of calcium in Golden Delicious apples

    International Nuclear Information System (INIS)

    Steenkamp, J.; De Villiers, O.T.

    1979-01-01

    45 Ca, applied to the roots of Golden Delicious apple seedlings, was readily absorbed and transported to the leaves. Application of NAAm to the leaves of seedlings significantly increased the uptake of 45 Ca, whereas the growth regulators GA 3 , kinetin, SADH, CEPA and 2,4,5-TP had no such effect. Application of NAAm to intact fruits and fruit discs also significantly increased the uptake of 45 Ca [af

  20. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

    Science.gov (United States)

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

    2018-01-01

    into the sarcoplasmic reticulum is a major mechanism by which SNS suppresses alternans in the guinea pig heart. Conclusions : SNS suppresses calcium and action potential alternans in the intact guinea pig heart by an action mediated through accelerated Ca handling and via increased I Ks .

  1. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

    International Nuclear Information System (INIS)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S.; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-01-01

    The voltage-gated calcium channel (Ca v ) β 1a subunit (Ca v β 1a ) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca v β 1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca v β 1a NH 2 -terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca v β 1a /YFP shows that TnT3 facilitates Ca v β 1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca v β 1a is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca v β 1a . • We mapped TnT3 and Ca v β 1a interaction domain. • TnT3 facilitates Ca v β 1a nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation

  2. Eukaryotic translation initiation factor 3 subunit e controls intracellular calcium homeostasis by regulation of cav1.2 surface expression.

    Directory of Open Access Journals (Sweden)

    Pawel Buda

    Full Text Available Inappropriate surface expression of voltage-gated Ca(2+channels (CaV in pancreatic ß-cells may contribute to the development of type 2 diabetes. First, failure to increase intracellular Ca(2+ concentrations at the sites of exocytosis impedes insulin release. Furthermore, excessive Ca(2+ influx may trigger cytotoxic effects. The regulation of surface expression of CaV channels in the pancreatic β-cells remains unknown. Here, we used real-time 3D confocal and TIRFM imaging, immunocytochemistry, cellular fractionation, immunoprecipitation and electrophysiology to study trafficking of L-type CaV1.2 channels upon β-cell stimulation. We found decreased surface expression of CaV1.2 and a corresponding reduction in L-type whole-cell Ca(2+ currents in insulin-secreting INS-1 832/13 cells upon protracted (15-30 min stimulation. This internalization occurs by clathrin-dependent endocytosis and could be prevented by microtubule or dynamin inhibitors. eIF3e (Eukaryotic translation initiation factor 3 subunit E is part of the protein translation initiation complex, but its effect on translation are modest and effects in ion channel trafficking have been suggested. The factor interacted with CaV1.2 and regulated CaV1.2 traffic bidirectionally. eIF3e silencing impaired CaV1.2 internalization, which resulted in an increased intracellular Ca(2+ load upon stimulation. These findings provide a mechanism for regulation of L-type CaV channel surface expression with consequences for β-cell calcium homeostasis, which will affect pancreatic β-cell function and insulin production.

  3. Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone formation correlates with intracellular calcium homeostasis regulation.

    Science.gov (United States)

    Zhao, Rui; Xie, Pengfei; Zhang, Kun; Tang, Zhurong; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

    2017-09-01

    Adequate bone substitutes osseointegration has been difficult to achieve in osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic osteoblasts, had a smaller crystal size and lower crystallinity than that of the normal. To date, little is known regarding the interaction of synthetic hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction. The present study investigated the biological effects of HANPs on osteoblastic cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy ones (SHM-OB). A selective effect of different concentrations of HANPs on the two cell lines was observed that the osteoporotic osteoblasts had a higher tolerance. Reductions in cell proliferation, ALP activity, collagen secretion and osteoblastic gene expressions were found in the SHM-OB when administered with HANPs concentration higher than 25µg/ml. In contrast, those of the OVX-OB suffered no depression but benefited from 25 to 250µg/ml HANPs in a dose-dependent manner. We demonstrated that the different effects of HANPs on osteoblasts were associated with the intracellular calcium influx into the endoplasmic reticulum. The in vivo bone defect model further confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more and mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. Collectively, the observed epigenetic regulation of osteoblastic cell function by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials. In this study, we investigated the biological effects of hydroxyapatite nanoparticles (HANPs) on osteoporotic rat bone and the derived osteoblast. Our findings revealed a previously unrecognized phenomenon that the osteoporotic individuals could benefit from higher concentrations of HANPs, as compared with the healthy individuals. The in

  4. Distinct Calcium Signaling Pathways Regulate Calmodulin Gene Expression in Tobacco1

    Science.gov (United States)

    van der Luit, Arnold H.; Olivari, Claudio; Haley, Ann; Knight, Marc R.; Trewavas, Anthony J.

    1999-01-01

    Cold shock and wind stimuli initiate Ca2+ transients in transgenic tobacco (Nicotiana plumbaginifolia) seedlings (named MAQ 2.4) containing cytoplasmic aequorin. To investigate whether these stimuli initiate Ca2+ pathways that are spatially distinct, stress-induced nuclear and cytoplasmic Ca2+ transients and the expression of a stress-induced calmodulin gene were compared. Tobacco seedlings were transformed with a construct that encodes a fusion protein between nucleoplasmin (a major oocyte nuclear protein) and aequorin. Immunocytochemical evidence indicated targeting of the fusion protein to the nucleus in these plants, which were named MAQ 7.11. Comparison between MAQ 7.11 and MAQ 2.4 seedlings confirmed that wind stimuli and cold shock invoke separate Ca2+ signaling pathways. Partial cDNAs encoding two tobacco calmodulin genes, NpCaM-1 and NpCaM-2, were identified and shown to have distinct nucleotide sequences that encode identical polypeptides. Expression of NpCaM-1, but not NpCaM-2, responded to wind and cold shock stimulation. Comparison of the Ca2+ dynamics with NpCaM-1 expression after stimulation suggested that wind-induced NpCaM-1 expression is regulated by a Ca2+ signaling pathway operational predominantly in the nucleus. In contrast, expression of NpCaM-1 in response to cold shock is regulated by a pathway operational predominantly in the cytoplasm. PMID:10557218

  5. Micromolar-Affinity Benzodiazepine Receptors Regulate Voltage-Sensitive Calcium Channels in Nerve Terminal Preparations

    Science.gov (United States)

    Taft, William C.; Delorenzo, Robert J.

    1984-05-01

    Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance.

  6. Calcium regulates ATP-sensitive microtubule binding by Chlamydomonas outer arm dynein.

    Science.gov (United States)

    Sakato, Miho; King, Stephen M

    2003-10-31

    The Chlamydomonas outer dynein arm contains three distinct heavy chains (alpha, beta, and gamma) that exhibit different motor properties. The LC4 protein, which binds 1-2 Ca2+ with KCa = 3 x 10-5 m, is associated with the gamma heavy chain and has been proposed to act as a sensor to regulate dynein motor function in response to alterations in intraflagellar Ca2+ levels. Here we genetically dissect the outer arm to yield subparticles containing different motor unit combinations and assess the microtubule-binding properties of these complexes both prior to and following preincubation with tubulin and ATP, which was used to inhibit ATP-insensitive (structural) microtubule binding. We observed that the alpha heavy chain exhibits a dominant Ca2+-independent ATP-sensitive MT binding activity in vitro that is inhibited by attachment of tubulin to the structural microtubule-binding domain. Furthermore, we show that ATP-sensitive microtubule binding by a dynein subparticle containing only the beta and gamma heavy chains does not occur at Ca2+ concentrations below pCa 6 but is maximally activated above pCa 5. This activity was not observed in mutant dyneins containing small deletions in the microtubule-binding region of the beta heavy chain or in dyneins that lack both the alpha heavy chain and the motor domain of the beta heavy chain. These findings strongly suggest that Ca2+ binding directly to a component of the dynein complex regulates ATP-sensitive interactions between the beta heavy chain and microtubules and lead to a model for how individual motor units are controlled within the outer dynein arm.

  7. Tobacco advertising in retail stores.

    Science.gov (United States)

    Cummings, K M; Sciandra, R; Lawrence, J

    1991-01-01

    Recent studies have described tobacco advertising in the print media, on billboards, and through sponsorship of cultural and sporting events. However, little attention has been given to another common and unavoidable source of tobacco advertising, that which is encountered in retail stores. In July 1987, we conducted a survey of 61 packaged goods retail stores in Buffalo, NY, to assess the prevalence and type of point-of-sale tobacco advertising. In addition, store owners or managers were surveyed to determine their store's policy regarding tobacco advertising, receipt of monetary incentives from distributors for displaying tobacco ads, and willingness to display antitobacco ads. Six types of stores were involved in the study: 10 supermarkets, 10 privately owned grocery stores, 9 chain convenience food stores that do not sell gasoline, 11 chain convenience food stores that sell gasoline, 11 chain pharmacies, and 10 private pharmacies. Two-thirds of the stores displayed tobacco posters, and 87 percent had promotional items advertising tobacco products, primarily cigarettes. Larger stores, and those that were privately owned, tended to display more posters and promotional items. Eighty percent of tobacco product displays were for cigarettes, 16 percent for smokeless tobacco products, and 4 percent for cigars and pipe tobacco. Convenience stores selling gasoline had the most separate tobacco product displays. Of tobacco product displays, 24 percent were located adjacent to candy and snack displays. Twenty-nine of the 61 store owners or managers indicated that their store had a policy regulating the display of tobacco ads and tobacco product displays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1910192

  8. A sensor for calcium uptake

    Science.gov (United States)

    Collins, Sean; Meyer, Tobias

    2011-01-01

    Mitochondria — the cell’s power plants — increase their energy production in response to calcium signals in the cytoplasm. A regulator of the elusive mitochondrial calcium channel has now been identified. PMID:20844529

  9. Calcium – how and why?

    Indian Academy of Sciences (India)

    Unknown

    biological processes because of its unusual physical and chemical properties. 1. History of calcium ... cellular roles of calcium has established the importance of this ion ..... Ca2+ ion, for example in regulating enzyme activity (Price. 1975 ...

  10. Bell-shaped calcium-response curves of lns(l,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum

    Science.gov (United States)

    Bezprozvanny, Llya; Watras, James; Ehrlich, Barbara E.

    1991-06-01

    RELEASE of calcium from intracellular stores occurs by two pathways, an inositol 1,4,5-trisphosphate (InsP3)-gated channel1-3 and a calcium-gated channel (ryanodine receptor)4-6. Using specific antibodies, both receptors were found in Purkinje cells of cerebellum7,8. We have now compared the functional properties of the channels corresponding to the two receptors by incorporating endoplasmic reticulum vesicles from canine cerebellum into planar bilayers. InsP3-gated channels were observed most frequently. Another channel type was activated by adenine nucleotides or caffeine, inhibited by ruthenium red, and modified by ryanodine, characteristics of the ryanodine receptor/channel6. The open probability of both channel types displayed a bell-shaped curve for dependence on calcium. For the InsP3-gated channel, the maximum probability of opening occurred at 0.2 µM free calcium, with sharp decreases on either side of the maximum. Maximum activity for the ryanodine receptor/channel was maintained between 1 and 100 µM calcium. Thus, within the physiological range of cytoplasmic calcium, the InsP3-gated channel itself allows positive feed-back and then negative feedback for calcium release, whereas the ryanodine receptor/channel behaves solely as a calcium-activated channel. The existence in the same cell of two channels with different responses to calcium and different ligand sensitivities provides a basis for complex patterns of intracellular calcium regulation.

  11. Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells.

    Science.gov (United States)

    Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S

    2016-04-15

    The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca(2+)] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca(2+)-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca(2+) entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca(2+)-dependent up-regulation of AQP5. These important findings reveal that the Ca(2+)-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells*

    Science.gov (United States)

    Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S.

    2016-01-01

    The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca2+] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca2+-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca2+ entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca2+-dependent up-regulation of AQP5. These important findings reveal that the Ca2+-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture. PMID:26903518

  13. Regulation of Calcium on Peanut Photosynthesis Under Low Night Temperature Stress

    Institute of Scientific and Technical Information of China (English)

    LIU Yi-fei; HAN Xiao-ri; ZHAN Xiu-mei; YANG Jin-feng; WANG Yu-zhi; SONG Qiao-bo; CHEN Xin

    2013-01-01

    The effects of different levels of CaCl2 on photosynthesis under low night temperature (8°C) stress in peanuts were studied in order to ifnd out the appropriate concentration of Ca2+ through the artiifcial climate chamber potted culture test. The results indicated that Ca2+, by means of improving the stomatal conductivity of peanut leaves under low night temperature stress, may mitigate the decline of photosynthetic rate in the peanut leaves. The regulation with 15 mmol L-1 CaCl2 (Ca15) was the most effective, compared with other treatments. Subsequently, the improvement of Ca2+ on peanut photosynthesis under low night temperature stress was validated further through spraying withCa15, Ca2+ chelator (ethylene glycol bis(2-aminoethyl) tetraacetic acid; EGTA) and calmodulin antagonists (trilfuonerazine; TFP).And CaM (Ca2+-modulin) played an important role in the nutritional signal transduction for Ca2+ mitigating photosynthesis limitations in peanuts under low night temperature stress.

  14. Vacuolar ATPase regulates surfactant secretion in rat alveolar type II cells by modulating lamellar body calcium.

    Directory of Open Access Journals (Sweden)

    Narendranath Reddy Chintagari

    2010-02-01

    Full Text Available Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase is the enzyme responsible for pumping H(+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1, an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca(2+ chelator, BAPTA-AM, the protein kinase C (PKC inhibitor, staurosporine, and the Ca(2+/calmodulin-dependent protein kinase II (CaMKII, KN-62. Baf A1 induced Ca(2+ release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca(2+ pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca(2+ mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion.

  15. Sensory Flask Cells in Sponge Larvae Regulate Metamorphosis via Calcium Signaling.

    Science.gov (United States)

    Nakanishi, Nagayasu; Stoupin, Daniel; Degnan, Sandie M; Degnan, Bernard M

    2015-12-01

    The Porifera (sponges) is one of the earliest phyletic lineages to branch off the metazoan tree. Although the body-plan of sponges is among the simplest in the animal kingdom and sponges lack nervous systems that communicate environmental signals to other cells, their larvae have sensory systems that generate coordinated responses to environmental cues. In eumetazoans (Cnidaria and Bilateria), the nervous systems of larvae often regulate metamorphosis through Ca(2+)-dependent signal transduction. In sponges, neither the identity of the receptor system that detects an inductive environmental cue (hereafter "metamorphic cues") nor the signaling system that mediates settlement and metamorphosis are known. Using a combination of behavioral assays and surgical manipulations, we show here that specialized epithelial cells-referred to as flask cells-enriched in the anterior third of the Amphimedon queenslandica larva are most likely to be the sensory cells that detect the metamorphic cues. Surgical removal of the region enriched in flask cells in a larva inhibits the initiation of metamorphosis. The flask cell has an apical sensory apparatus with a cilium surrounded by an apical F-actin-rich protrusion, and numerous vesicles, hallmarks of eumetazoan sensory-neurosecretory cells. We demonstrate that these flask cells respond to metamorphic cues by elevating intracellular Ca(2+) levels, and that this elevation is necessary for the initiation of metamorphosis. Taken together, these analyses suggest that sponge larvae have sensory-secretory epithelial cells capable of converting exogenous cues into internal signals via Ca(2+)-mediated signaling, which is necessary for the initiation of metamorphosis. Similarities in the morphology, physiology, and function of the sensory flask cells in sponge larvae with the sensory/neurosecretory cells in eumetazoan larvae suggest this sensory system predates the divergence of Porifera and Eumetazoa. © The Author 2015. Published by Oxford

  16. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    Science.gov (United States)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  17. Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.

    Science.gov (United States)

    Wasilewska, Barbara; Najdzion, Janusz; Równiak, Maciej; Bogus-Nowakowska, Krystyna; Hermanowicz, Beata; Kolenkiewicz, Małgorzata; Żakowski, Witold; Robak, Anna

    2016-03-01

    In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed. Copyright © 2015 Elsevier GmbH. All rights reserved.

  18. Store and forward teledermatology

    Directory of Open Access Journals (Sweden)

    Kanthraj Garehatty

    2007-01-01

    Full Text Available Store and forward and real time or videoconferences are the two types of teledermatology services practiced. Dermatology and radio-diagnosis are visual specialties suited for store-and-forward teledermatology (SAFT. Advances in information technology, electronic instruments and biotechnology have revolutionized and brought changes in SAFT. Cellular phone, digital camera, personal digital assistants, Wi-Fi, Wi-Max and computer- aided-design software are incorporated to deliver the quality health care to remote geographic regions. Complete SAFT care equivalent to face-to-face consultation (Gold standard is essential. Health care providers in rural areas are the ′eyes′ for the consultants. Consultants to guide them should have a rapid periodic audit of visual parameters and dimensions of lesions. Given this background, this article reviews advances in 1 capture, store and transfer of images. 2 Computer Aided measurements of generalized and localized lesions and 3 the integration model to meet all the above two requirements in a centralized location. This process enables diagnosis, management, periodic assessment and complete follow-up care to achieve patient and physician satisfaction. Preservation of privacy and confidentiality of digital images is important. Uniform rules and regulations are required. Indian space research organization (ISRO, Government of India has demonstrated telemedicine pilot projects utilizing the satellite communication and mobile telemedicine units to be useful in meeting the health care needs of remote and rural India. we have to join hands with them to meet dermatology problems in rural areas.

  19. Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins.

    NARCIS (Netherlands)

    Hsu, Y.J.; Dimke, H.; Schoeber, J.P.H.; Hsu, S.C.; Lin, S.H.; Chu, P.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2010-01-01

    Although gender differences in the renal handling of calcium have been reported, the overall contribution of androgens to these differences remains uncertain. We determined here whether testosterone affects active renal calcium reabsorption by regulating calcium transport proteins. Male mice had

  20. Expression of voltage-activated calcium channels in the early zebrafish embryo.

    Science.gov (United States)

    Sanhueza, Dayán; Montoya, Andro; Sierralta, Jimena; Kukuljan, Manuel

    2009-05-01

    Increases in cytosolic calcium concentrations regulate many cellular processes, including aspects of early development. Calcium release from intracellular stores and calcium entry through non-voltage-gated channels account for signalling in non-excitable cells, whereas voltage-gated calcium channels (CaV) are important in excitable cells. We report the expression of multiple transcripts of CaV, identified by its homology to other species, in the early embryo of the zebrafish, Danio rerio, at stages prior to the differentiation of excitable cells. CaV mRNAs and proteins were detected as early as the 2-cell stages, which indicate that they arise from both maternal and zygotic transcription. Exposure of embryos to pharmacological blockers of CaV does not perturb early development significantly, although late effects are appreciable. These results suggest that CaV may have a role in calcium homeostasis and control of cellular process during early embryonic development.

  1. Calcium supplements

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007477.htm Calcium supplements To use the sharing features on this page, please enable JavaScript. WHO SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the ...

  2. Structural dynamics of the cell nucleus: basis for morphology modulation of nuclear calcium signaling and gene transcription.

    Science.gov (United States)

    Queisser, Gillian; Wiegert, Simon; Bading, Hilmar

    2011-01-01

    Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons.

  3. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

    Directory of Open Access Journals (Sweden)

    Masako Isokawa

    2016-01-01

    Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

  4. Calcium metabolism in birds.

    Science.gov (United States)

    de Matos, Ricardo

    2008-01-01

    Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

  5. Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation.

    Science.gov (United States)

    Lagadec, Patricia; Balaguer, Thierry; Boukhechba, Florian; Michel, Grégory; Bouvet-Gerbettaz, Sébastien; Bouler, Jean-Michel; Scimeca, Jean-Claude; Rochet, Nathalie

    2017-07-15

    Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction. Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms

  6. Calcium Occupancy of N-terminal Sites within Calmodulin Induces Inhibition of the Ryanodine Receptor Calcium Release Channel

    Energy Technology Data Exchange (ETDEWEB)

    Boschek, Curt B; Jones, Terry E; Squier, Thomas C; Bigelow, Diana J

    2007-08-01

    Calmodulin (CaM) regulates calcium release from intracellular stores in skeletal muscle through its association with the ryanodine receptor (RyR1) calcium release channel, where CaM association enhances channel opening at resting calcium levels and its closing at micromolar calcium levels associated with muscle contraction. A high-affinity CaM-binding sequence (RyRp) has been identified in RyR1, which corresponds to a 30-residue sequence (i.e., K3614 – N3643) located within the central portion of the primary sequence. However, it is currently unclear whether the identified CaM-binding sequence a) senses calcium over the physiological range of calcium-concentrations associated with RyR1 regulation or b) plays a structural role unrelated to the calcium-dependent modulation of RyR1 function. Therefore, we have measured the calcium-dependent activation of the individual domains of CaM in association with RyRp and their relationship to the CaM-dependent regulation of RyR1. These measurements utilize an engineered CaM, permitting the site-specific incorporation of N-(1-pyrene) maleimide at either T34C (PyN-CaM) or T110C (PyC-CaM) in the N- and C-domains, respectively. Consistent with prior measurements, we observe a high-affinity association between both apo- and calcium-activated CaM and RyRp. Upon association with RyRp, fluorescence changes in PyN-CaM or PyC-CaM permit the measurement of the calcium-activation of these individual domains. Fluorescence changes upon calcium-activation of PyC-CaM in association with RyRp are indicative of high-affinity calcium-dependent activation of the C-terminal domain of CaM bound to RyRp at resting calcium levels and the activation of the N-terminal domain at levels of calcium associated cellular activation. In comparison, occupancy of calcium-binding sites in the N-domain of CaM mirrors the calcium-dependence of RyR1 inhibition observed at activating calcium levels, where [Ca]1/2 = 4.3 0.4 μM, suggesting a direct regulation of Ry

  7. L-type calcium channels play a critical role in maintaining lens transparency by regulating phosphorylation of aquaporin-0 and myosin light chain and expression of connexins.

    Science.gov (United States)

    Maddala, Rupalatha; Nagendran, Tharkika; de Ridder, Gustaaf G; Schey, Kevin L; Rao, Ponugoti Vasantha

    2013-01-01

    Homeostasis of intracellular calcium is crucial for lens cytoarchitecture and transparency, however, the identity of specific channel proteins regulating calcium influx within the lens is not completely understood. Here we examined the expression and distribution profiles of L-type calcium channels (LTCCs) and explored their role in morphological integrity and transparency of the mouse lens, using cDNA microarray, RT-PCR, immunoblot, pharmacological inhibitors and immunofluorescence analyses. The results revealed that Ca (V) 1.2 and 1.3 channels are expressed and distributed in both the epithelium and cortical fiber cells in mouse lens. Inhibition of LTCCs with felodipine or nifedipine induces progressive cortical cataract formation with time, in association with decreased lens weight in ex-vivo mouse lenses. Histological analyses of felodipine treated lenses revealed extensive disorganization and swelling of cortical fiber cells resembling the phenotype reported for altered aquaporin-0 activity without detectable cytotoxic effects. Analysis of both soluble and membrane rich fractions from felodipine treated lenses by SDS-PAGE in conjunction with mass spectrometry and immunoblot analyses revealed decreases in β-B1-crystallin, Hsp-90, spectrin and filensin. Significantly, loss of transparency in the felodipine treated lenses was preceded by an increase in aquaporin-0 serine-235 phosphorylation and levels of connexin-50, together with decreases in myosin light chain phosphorylation and the levels of 14-3-3ε, a phosphoprotein-binding regulatory protein. Felodipine treatment led to a significant increase in gene expression of connexin-50 and 46 in the mouse lens. Additionally, felodipine inhibition of LTCCs in primary cultures of mouse lens epithelial cells resulted in decreased intracellular calcium, and decreased actin stress fibers and myosin light chain phosphorylation, without detectable cytotoxic response. Taken together, these observations reveal a crucial

  8. Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway.

    Science.gov (United States)

    Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

    2015-01-01

    Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype.

  9. TO STORES USERS

    CERN Multimedia

    SPL Division

    2001-01-01

    Stores users are informed that the Stores (Central, Emergency window, Raw materials, Chemical products and Prévessin Self service stores) will be closed on Friday, 7 December owing to migration of the Stores computers to Windows 2000. Thank you for your understanding.

  10. Calcium absorption

    International Nuclear Information System (INIS)

    Carlmark, B.; Reizenstein, P.; Dudley, R.A.

    1976-01-01

    The methods most commonly used to measure the absorption and retention of orally administered calcium are reviewed. Nearly all make use of calcium radioisotopes. The magnitude of calcium absorption and retention depends upon the chemical form and amount of calcium administered, and the clinical and nutritional status of the subject; these influences are briefly surveyed. (author)

  11. Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

    Science.gov (United States)

    Chonchol, Michel; Levi, Moshe

    2015-01-01

    Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

  12. Ginkgolide B Exerts Cardioprotective Properties against Doxorubicin-Induced Cardiotoxicity by Regulating Reactive Oxygen Species, Akt and Calcium Signaling Pathways In Vitro and In Vivo.

    Science.gov (United States)

    Gao, Junqing; Chen, Tao; Zhao, Deqiang; Zheng, Jianpu; Liu, Zongjun

    2016-01-01

    The aim of this study was to evaluate the effect of Ginkgolide B (GB) on doxorubicin (DOX) induced cardiotoxicity in vitro and in vivo. Rat cardiomyocyte cell line H9c2 was pretreated with GB and subsequently subjected to doxorubicin treatment. Cell viability and cell apoptosis were assessed by MTT assay and Hoechst staining, respectively. Reactive oxygen species (ROS), Akt phosphorylation and intracellular calcium were equally determined in order to explore the underlying molecular mechanism. To verify the in vivo therapeutic effect of GB, we established a mouse model of cardiotoxicity and determined left ventricle ejection fraction (LVEF) and left ventricular mass (LVM). The in vitro experimental results indicated that pretreatment with GB significantly decreases the viability and apoptosis of H9c2 cells by decreasing ROS and intracellular calcium levels and activating Akt phosphorylation. In the in vivo study, we recorded an improved LVEF and a decreased LVM in the group of cardiotoxic rats treated with GB. Altogether, our findings anticipate that GB exerts a cardioprotective effect through possible regulation of the ROS, Akt and calcium pathways. The findings suggest that combination of GB with DOX in chemotherapy could help avoid the cardiotoxic side effects of GB.

  13. Poly(acrylic acid-regulated Synthesis of Rod-Like Calcium Carbonate Nanoparticles for Inducing the Osteogenic Differentiation of MC3T3-E1 Cells

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2016-05-01

    Full Text Available Calcium carbonate, especially with nanostructure, has been considered as a good candidate material for bone regeneration due to its excellent biodegradability and osteoconductivity. In this study, rod-like calcium carbonate nanoparticles (Rod-CC NPs with desired water dispersibility were achieved with the regulation of poly (acrylic acid. Characterization results revealed that the Rod-CC NPs had an average length of 240 nm, a width of 90 nm with an average aspect ratio of 2.60 and a negative ζ-potential of −22.25 ± 0.35 mV. The degradation study illustrated the nanoparticles degraded 23% at pH 7.4 and 45% at pH 5.6 in phosphate-buffered saline (PBS solution within three months. When cultured with MC3T3-E1 cells, the Rod-CC NPs exhibited a positive effect on the proliferation of osteoblast cells. Alkaline phosphatase (ALP activity assays together with the osteocalcin (OCN and bone sialoprotein (BSP expression observations demonstrated the nanoparticles could induce the differentiation of MC3T3-E1 cells. Our study developed well-dispersed rod-like calcium carbonate nanoparticles which have great potential to be used in bone regeneration.

  14. Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

    DEFF Research Database (Denmark)

    Kolko, M; Kiilgaard, J F; Wang, J

    2009-01-01

    Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used...... the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE...

  15. Calcium plays a key role in paraoxon-induced apoptosis in EL4 cells by regulating both endoplasmic reticulum- and mitochondria-associated pathways.

    Science.gov (United States)

    Li, Lan; Du, Yi; Ju, Furong; Ma, Shunxiang; Zhang, Shengxiang

    2016-01-01

    Paraoxon (POX) is one of the most toxic organophosphorus pesticides, but its toxic mechanisms associated with apoptosis remain unclear. The aim of this study was to investigate calcium-associated mechanisms in POX-induced apoptosis in EL4 cells. EL4 cells were exposed to POX for 0-16 h. EGTA was used to chelate Ca(2+ ) in extracellular medium, and heparin and procaine were used to inhibit Ca(2+ )efflux from the endoplasmic reticulum (ER). Z-ATAD-FMK was used to inhibit caspase-12 activity. The apoptotic rate assay, western blotting and immunocytochemistry (ICC) were used to reveal the mechanisms of POX-induced apoptosis. POX significantly increased the expression and activation of caspase-12 and caspase-3, enhanced expression of calpain 1 and calpain 2, and induced the release of cyt c, but did not change the expression of Grp 78. Inhibiting caspase-12 activity alleviated POX-induced upregulation of calpain 1 and caspase-3, promoted POX-induced upregulation of calpain 2, and reduced POX-induced cyt c release, suggesting that there was a cross-talk between the ER-associated pathway and mitochondria-associated apoptotic signals. Attenuating intracellular calcium concentration with EGTA, heparin or procaine decreased POX-induced upregulation of calpain 1, calpain 2, caspase-12 and caspase-3, and reduced POX-induced cyt c release. After pretreatment with EGTA or procaine, POX significantly promoted expression of Grp 78. Calcium played a key role in POX-induced apoptosis in EL4 cells by regulating both ER- and mitochondria-associated pathways. The cross-talk of ER- and mitochondria-associated pathways was accomplished through calcium signal.

  16. Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Sørensen, Belinda Halling; Sauter, Daniel Rafael Peter

    2015-01-01

    to be an essential component of both VRAC and VSOAC. Reduced VRAC and VSOAC activities are seen in drug resistant cancer cells. ANO1 is a calcium-activated chloride channel expressed on the plasma membrane of e.g. secretory epithelia. ANO1 is amplified and highly expressed in a large number of carcinomas. The gene...... functions as well as their role in cancer and drug resistance....

  17. Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7.

    Science.gov (United States)

    Ji, Li; Zhu, Huayuan; Chen, Hong; Fan, Wenyong; Chen, Junjie; Chen, Jing; Zhu, Guoqing; Wang, Juejin

    2015-12-01

    Neuropeptide W (NPW), an endogenous ligand for the G protein-coupled receptor 7 (GPR7), was first found to make important roles in central nerve system. In periphery, NPW was also present and regulated intracellular calcium homeostasis by L-type calcium channels. This study was designed to discover the effects of NPW-GPR7 on the function of CaV1.2 calcium channels in the vascular smooth muscle cells (VSMCs) and vasotone of arterial vessels. By whole-cell patch clamp, we studied the effects of NPW-23, the active form of NPW, on the CaV1.2 channels in the heterologously transfected human embryonic kidney 293 cells and VSMCs isolated from rat. Living system was used to explore the physiological function of NPW-23 in arterial myogenic tone. To investigate the pathological relevance, NPW mRNA level of mesenteric arteries was measured in the hypertensive and normotensive rats. NPW's receptor GPR7 was coexpressed with CaV1.2 channels in arterial smooth muscle. NPW-23 increased the ICa,L in transfected human embryonic kidney 293 cells and VSMCs via GPR7, which could be abrogated by phospholipase C (PLC)/protein kinase C (PKC) inhibitors, not protein kinase A or protein kinase G inhibitor. After NPW-23 application, the expression of pan phospho-PKC was increased; moreover, intracellular diacylglycerol level, the second messenger catalyzed by PLC, was increased 1.5-2-fold. Application with NPW-23 increased pressure-induced vasotone of the rat mesenteric arteries. Importantly, the expression of NPW was decreased in the hypertensive rats. NPW-23 regulates ICa,L via GPR7, which is mediated by PLC/PKC signaling, and such a mechanism plays a role in modulating vascular myogenic tone, which may involve in the development of vascular hypertension.

  18. Plasma membrane calcium ATPase 4 (PMCA4) co-ordinates calcium and nitric oxide signaling in regulating murine sperm functional activity.

    Science.gov (United States)

    Olli, Kristine E; Li, Kun; Galileo, Deni S; Martin-DeLeon, Patricia A

    2018-01-01

    Reduced sperm motility (asthenospermia) and resulting infertility arise from deletion of the Plasma Membrane Ca 2+ -ATPase 4 (Pmca4) gene which encodes the highly conserved Ca 2+ efflux pump, PMCA4. This is the major Ca 2+ clearance protein in murine sperm. Since the mechanism underlying asthenospermia in PMCA4's absence or reduced activity is unknown, we investigated if sperm PMCA4 negatively regulates nitric oxide synthases (NOSs) and when absent NO, peroxynitrite, and oxidative stress levels are increased. Using co-immunoprecipitation (Co-IP) and Fluorescence Resonance Energy Transfer (FRET), we show an association of PMCA4 with the NOSs in elevated cytosolic [Ca 2+ ] in capacitated and Ca 2+ ionophore-treated sperm and with neuronal (nNOS) at basal [Ca 2+ ] (ucapacitated sperm). FRET efficiencies for PMCA4-eNOS were 35% and 23% in capacitated and uncapacitated sperm, significantly (p < 0.01) different, with the molecules being <10 nm apart. For PMCA4-nNOS, this interaction was seen only for capacitated sperm where FRET efficiency was 24%, significantly (p < 0.05) higher than in uncapacitated sperm (6%). PMCA4 and the NOSs were identified as interacting partners in a quaternary complex that includes Caveolin1, which co-immunoprecipitated with eNOS in a Ca 2+ -dependent manner. In Pmca4 -/- sperm NOS activity was elevated twofold in capacitated/uncapacitated sperm (vs. wild-type), accompanied by a twofold increase in peroxynitrite levels and significantly (p < 0.001) increased numbers of apoptotic germ cells. The data support a quaternary complex model in which PMCA4 co-ordinates Ca 2+ and NO signaling to maintain motility, with increased NO levels resulting in asthenospermia in Pmca4 -/- males. They suggest the involvement of PMCA4 mutations in human asthenospermia, with diagnostic relevance. © 2017 Wiley Periodicals, Inc.

  19. The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels

    International Nuclear Information System (INIS)

    King, Taj D.; Gandy, Johanna C.; Bijur, Gautam N.

    2006-01-01

    The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is constitutively active, however its activity is markedly diminished following phosphorylation of Ser21 of GSK3α and Ser9 of GSK3β. Although several kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively much less is known about the mechanisms that cause the dephosphorylation of GSK3 at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH-SY5Y cells, which increases intracellular calcium concentrations caused a transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3 at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and significantly blocked the KCl-induced dephosphorylation of GSK3β, but not GSK3α. The phosphorylation of Akt was not affected by the overexpression of inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of cells with the GSK3 inhibitors lithium and SB216763 increased the levels of SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels

  20. Voltage-Gated Calcium Channels

    Science.gov (United States)

    Zamponi, Gerald Werner

    Voltage Gated Calcium Channels is the first comprehensive book in the calcium channel field, encompassing over thirty years of progress towards our understanding of calcium channel structure, function, regulation, physiology, pharmacology, and genetics. This book balances contributions from many of the leading authorities in the calcium channel field with fresh perspectives from risings stars in the area, taking into account the most recent literature and concepts. This is the only all-encompassing calcium channel book currently available, and is an essential resource for academic researchers at all levels in the areas neuroscience, biophysics, and cardiovascular sciences, as well as to researchers in the drug discovery area.

  1. Dendritic spine changes in the development of alcohol addiction regulated by α-calcium/calmodulin-dependent protein kinase II

    Directory of Open Access Journals (Sweden)

    Zofia Mijakowska

    2014-03-01

    Full Text Available Introduction Alcohol has many adverse effects on the brain. Among them are dendritic spine morphology alterations, which are believed to be the basis of alcohol addiction. Autophosphorylation of α-calcium/calmodulin-dependent protein kinase II (αCaMKII has been shown to regulate spine morphology in vitro. Here we show that αCaMKII can also regulate addiction related behaviour and dendritic spine morphology changes caused by alcohol consumption in vivo. Method 12 αCaMKII-autophosphorylation deficient female mice (T286A and 12 wild type littermates were used in the study. T286A strain was created by Giese et al. (1998. Mice were housed and tested in two IntelliCages from NewBehavior (www.newbehavior.com. IntelliCage is an automated learning system. After 95 days of alcohol drinking interrupted by tests for motivation, persistence in alcohol seeking and probability of relapse, mice were ascribed to ‘high’ or ‘low’ drinkers group according to their performance in the tests. Additional criterion was the amount of alcohol consumed during the whole experiment. Result of each test was evaluated separately. 1/3 of the mice that scored highest in each criterion were considered ‘positive’ for this trait. ‘Positive’ animals were given 1 point, negative 0 points. Mice that were positive in at least 2 criteria were ascribed to ‘high’ drinkers (‘+’ group. Remaining mice – to ‘low’ drinkers (‘–‘. This method of behavioral phenotyping, developed by Radwanska and Kaczmarek (2012, is inspired by DSM-IV. Since the results of this evaluation are discrete (i.e. by definition all the animals score between 0 to +4, we developed also a continuous method of addiction rating, which we call ‘addiction index’. The result of the second method is a sum of the standardized (z-score results of the above mentioned tests. We use it to examine the correlations between addiction-like behavior and spine parameters. Control group (12 WT, 8

  2. NACS Store Planning Manual.

    Science.gov (United States)

    College Store Journal, 1979

    1979-01-01

    Topics discussed by the NACS Store Planning/Renovation Committees in this updated version of the college store renovation manual include: short- and long-range planning, financial considerations, professional planning assistance, the store's image and business character, location considerations, building requirements, space requirements, fixtures,…

  3. Calcium - ionized

    Science.gov (United States)

    ... diuretics Thrombocytosis (high platelet count) Tumors Vitamin A excess Vitamin D excess Lower-than-normal levels may be due to: Hypoparathyroidism Malabsorption Osteomalacia Pancreatitis Renal failure Rickets Vitamin D deficiency Alternative Names Free calcium; Ionized calcium ...

  4. Calcium Carbonate

    Science.gov (United States)

    ... Calcium is needed by the body for healthy bones, muscles, nervous system, and heart. Calcium carbonate also ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  5. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  6. Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.

    Science.gov (United States)

    Evstratova, Alesya; Tóth, Katalin

    2011-12-01

    The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca(2+) wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca(2+) waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca(2+) signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca(2+) release from CA3 pyramidal cell internal stores.

  7. Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

    Science.gov (United States)

    Zatz, M; Mullen, D A

    1988-11-01

    We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

  8. Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca2+ Regulation

    Science.gov (United States)

    Shanks, Julia; Herring, Neil; Johnson, Errin; Liu, Kun; Li, Dan

    2017-01-01

    Reduced cardiomyocyte excitation–contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague–Dawley, Wistar Kyoto, and spontaneously hypertensive rats. Neurons were infected with Ad-mCherry or Ad-mCherry-hATP2Aa (SERCA2a). Intracellular Ca2+ changes were measured using fura-2AM in response to KCl, caffeine, thapsigargin, and carbonylcyanide-p-trifluoromethoxyphenylhydrazine to mobilize intracellular Ca2+ stores. The effect of SERCA2a on neurotransmitter release was measured using [3H]-norepinephrine overflow from 340 to 360 g Sprague–Dawley rat atria in response to right stellate ganglia stimulation. Upregulation of SERCA2a resulted in greater neurotransmitter release in response to stellate stimulation compared with control (empty: 98.7±20.5 cpm, n=7; SERCA: 186.5±28.41 cpm, n=8; Pneurons, SERCA2a overexpression facilitated greater depolarization-induced Ca2+ transients (empty: 0.64±0.03 au, n=57; SERCA: 0.75±0.03 au, n=68; Pneurons resulted in increased neurotransmission and increased Ca2+ loading into intracellular stores. Whether the increased Ca2+ transient and neurotransmission after SERCA2A overexpression contributes to enhanced sympathoexcitation in heart failure patients remains to be determined. PMID:28223472

  9. Calcium Signaling in Taste Cells

    Science.gov (United States)

    Medler, Kathryn F.

    2014-01-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. PMID:25450977

  10. Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels.

    Directory of Open Access Journals (Sweden)

    Alexander V Maltsev

    2017-08-01

    Full Text Available Intracellular Local Ca releases (LCRs from sarcoplasmic reticulum (SR regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s. Background Ca (in locations lacking LCRs quickly decays to resting Ca levels (<100 nM at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates.

  11. Toxoplasma DJ-1 Regulates Organelle Secretion by a Direct Interaction with Calcium-Dependent Protein Kinase 1

    Science.gov (United States)

    Child, Matthew A.; Garland, Megan; Foe, Ian; Madzelan, Peter; Treeck, Moritz; van der Linden, Wouter A.; Oresic Bender, Kristina; Weerapana, Eranthie; Wilson, Mark A.; Boothroyd, John C.; Reese, Michael L.

    2017-01-01

    ABSTRACT Human DJ-1 is a highly conserved and yet functionally enigmatic protein associated with a heritable form of Parkinson’s disease. It has been suggested to be a redox-dependent regulatory scaffold, binding to proteins to modulate their function. Here we present the X-ray crystal structure of the Toxoplasma orthologue Toxoplasma gondii DJ-1 (TgDJ-1) at 2.1-Å resolution and show that it directly associates with calcium-dependent protein kinase 1 (CDPK1). The TgDJ-1 structure identifies an orthologously conserved arginine dyad that acts as a phospho-gatekeeper motif to control complex formation. We determined that the binding of TgDJ-1 to CDPK1 is sensitive to oxidation and calcium, and that this interaction potentiates CDPK1 kinase activity. Finally, we show that genetic deletion of TgDJ-1 results in upregulation of CDPK1 expression and that disruption of the CDPK1/TgDJ-1 complex in vivo prevents normal exocytosis of parasite virulence-associated organelles called micronemes. Overall, our data suggest that TgDJ-1 functions as a noncanonical kinase-regulatory scaffold that integrates multiple intracellular signals to tune microneme exocytosis in T. gondii. PMID:28246362

  12. Regulation of the sodium/potassium/chloride cotransporter by calcium and cyclic AMP in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Higgins, B.L.; Smith, L.; Smith, J.B.

    1987-01-01

    The activity of the Na/K/Cl cotransporter in smooth muscle cells cultured from rat aorta was assayed by measuring the initial rate of furosemide-inhibitable 86 Rb influx or efflux. Five uM furosemide or 0.2 uM bumetanide inhibited influx by 50%. Furosemide-inhibitable 86 Rb influx depended on the presence of all 3 ions in the external medium. The dependence on Na and K was hyperbolic with apparent Km values of 45 and 5 mM, respectively. The dependence on Cl was sigmoidal. Assuming a stoichiometry of 1:1:2 for Na:K:Cl, a Km for Cl of 60 mM was obtained from a Hofstee plot of the data. Rapidly growing cells had 3 fold higher cotransport activity than quiescent cells. Angiotensin II (ANG) stimulated furosemide-inhibitable 86 Rb efflux by 2 fold. An ANG receptor antagonist prevented ANG from increasing cotransport activity. Two calcium ionophores, A23187 and ionomycin, increased cotransport activity by 2 fold. Phorbol myristate acetate had no effect on cotransport activity. Isoproterenol, dibutyryl cyclic AMP, cholera toxin, or methylisobutylxanthine inhibited furosemide-sensitive 86 Rb influx by 35 to 50%. From these findings they conclude that increasing cytoplasmic free calcium stimulates cotransport activity, whereas increasing cellular cyclic AMP inhibits the cotransporter

  13. Status of calcium regulating hormonal systems in delayed period in persons exposed to occupational exposure of low doses of ionizing radiations

    International Nuclear Information System (INIS)

    Dospolova, Zh.G.; Abylaev, Zh.A.

    1997-01-01

    Purpose of study is consideration of endocrine system participation in development of calcium exchange disorders in persons exposed to action of low dose radiation . By radio- immune method in blood serum of 150 liquidators of Chernobyl accident consequences the concentration the following hormones were determined: parathormone, T 3 , T 4 , TSH, cortisol, ACTH, testosteron, insulin. Content of these hormones have been studied in according to following radiation factors: value of absorbed doses of external irradiation, degree of radioactive contamination of zone and exposition duration. It was determined, that basically dishormone disorders development have been concerned with parathormone, cortisol, hormones of thyroid axis, and in some cases to ACTH and insulin. Liquidators' frequencies of normal and changed concentration of calcium regulating hormones are sited in tabular form. It was established, that examined persons in result hormone disorders have of decrease functions of pituitary glands (76.78 %), pancreas (55 %), thyroid gland (24.31 %) and sex glands (19.23 %) and simultaneously cases of increase functions of parathyroid gland (58.2 %), adrenal glands (52.32 %) and adeno-pituitary glands (17.39). It is concluded, that inter hormonal correlation disorders are accompanying with morphologic and functional futures of secretory activity changes

  14. Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

    International Nuclear Information System (INIS)

    Benson, D.W.; Hasselgren, P.O.; Hiyama, D.T.; James, J.H.; Li, S.; Rigel, D.F.; Fischer, J.E.

    1989-01-01

    Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle

  15. Calcium and ROS: A mutual interplay

    Science.gov (United States)

    Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

    2015-01-01

    Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

  16. Information for Stores Users

    CERN Multimedia

    Logistics Group

    2004-01-01

    As the FARNELL Catalogue CAPACITORS, RESISTORS and POTENTIOMETERS have now been integrated into the CERN Stores Catalogue (SCEM Groups 10 and 11) they can now be obtained via an EDH 'Material Request' like any other Stores item. N.B. The Farnell 'Order code' is one of the key-words that make it easier to find items in the Stores Catalogue. Logistics Group FI Department

  17. Distributed energy store railgun

    International Nuclear Information System (INIS)

    Marshall, R.A.

    1991-01-01

    This paper reports that when the limiting case of a distributed energy store railgun is analyzed, i.e., the case where the space between adjacent energy stores become indefinitely small, three important results are obtained. First, the shape of the current pulse delivered by each store is sinusoidal and an exponential tail. Second, the rail-to-rail voltage behind the rear-most active store approaches zero. Third, it is not possible to choose parameters in such a way that capacitor crowbars can be eliminated

  18. An Assessment of the Stability and the Potential for In-Situ Synthesis of Regulated Organic Compounds in High Level Radioactive Waste Stored at Hanford, Richland, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Wiemers, K.D.; Babad, H.; Hallen, R.T.; Jackson, L.P.; Lerchen, M.E.

    1999-01-04

    The stability assessment examined 269 non-detected regulated compounds, first seeking literature references of the stability of the compounds, then evaluating each compound based upon the presence of functional groups using professional judgment. Compounds that could potentially survive for significant periods in the tanks (>1 year) were designated as stable. Most of the functional groups associated with the regulated organic compounds were considered unstable under tank waste conditions. The general exceptions with respect to functional group stability are some simple substituted aromatic and polycyclic aromatic compounds that resist oxidation and the multiple substituted aliphatic and aromatic halides that hydrolyze or dehydrohalogenate slowly under tank waste conditions. One-hundred and eighty-one (181) regulated, organic compounds were determined as likely unstable in the tank waste environment.

  19. An Assessment of the Stability and the Potential for In-Situ Synthesis of Regulated Organic Compounds in High Level Radioactive Waste Stored at Hanford, Richland, Washington

    International Nuclear Information System (INIS)

    Wiemers, K.D.; Babad, H.; Hallen, R.T.; Jackson, L.P.; Lerchen, M.E.

    1999-01-01

    The stability assessment examined 269 non-detected regulated compounds, first seeking literature references of the stability of the compounds, then evaluating each compound based upon the presence of functional groups using professional judgment. Compounds that could potentially survive for significant periods in the tanks (>1 year) were designated as stable. Most of the functional groups associated with the regulated organic compounds were considered unstable under tank waste conditions. The general exceptions with respect to functional group stability are some simple substituted aromatic and polycyclic aromatic compounds that resist oxidation and the multiple substituted aliphatic and aromatic halides that hydrolyze or dehydrohalogenate slowly under tank waste conditions. One-hundred and eighty-one (181) regulated, organic compounds were determined as likely unstable in the tank waste environment

  20. Predicting Commissary Store Success

    Science.gov (United States)

    2014-12-01

    stores or if it is possible to predict that success. Multiple studies of private commercial grocery consumer preferences , habits and demographics have...appropriate number of competitors due to the nature of international cultures and consumer preferences . 2. Missing Data Four of the remaining stores

  1. Storing up trouble

    International Nuclear Information System (INIS)

    Townsley, M.

    1992-01-01

    Scottish Nuclear have applied for permission to build a temporary ground-level dry store for spent fuel at Torness. However, Nirex's failure to find a suitable site for a long-term repository could mean that the Torness store will be less temporary than planned. (author)

  2. Using calcium silicate to regulate the physicochemical and biological properties when using β-tricalcium phosphate as bone cement

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Chia-Tze; Huang, Tsui-Hsien [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chen, Yi-Jyun [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Dental Department, Taichung Hospital, Ministry of Health and Welfare, Taichung City, Taiwan (China); Hung, Chi-Jr [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Chi-Chang, E-mail: chichang31@gmail.com [Department of Chemical and Materials Engineering, Tunghai University, Taichung, Taiwan (China); Shie, Ming-You, E-mail: eviltacasi@gmail.com [Department of Chemical and Materials Engineering, Tunghai University, Taichung, Taiwan (China)

    2014-10-01

    β-Tricalcium phosphate (β-TCP) is an osteoconductive material. For this research we have combined it with a low degradation calcium silicate (CS) to enhance its bioactive and osteostimulative properties. To check its effectiveness, a series of β-TCP/CS composites with different ratios were prepared to make new bioactive and biodegradable biocomposites for bone repair. Regarding the formation of bone-like apatite, the diametral tensile strength as well as the ion release and weight loss of composites were compared both before and after immersions in simulated body fluid (SBF). In addition, we also examined the behavior of human dental pulp cells (hDPCs) cultured on β-TCP/CS composites. The results show that the apatite deposition ability of the β-TCP/CS composites improves as the CS content is increased. For composites with more than a 60% CS content, the samples become completely covered by a dense bone-like apatite layer. At the end of the immersion period, weight losses of 24%, 32%, 34%, 38%, 41%, and 45% were observed for the composites containing 0%, 20%, 40%, 80%, 80% and 100% β-TCP cements, respectively. In addition, the antibacterial activity of CS/β-TCP composite improves as the CS-content is increased. In vitro cell experiments show that the CS-rich composites promote human dental pulp cell (hDPC) proliferation and differentiation. However, when the CS quantity in the composite is less than 60%, the quantity of cells and osteogenesis protein of hDPCs is stimulated by Si released from the β-TCP/CS composites. The degradation of β-TCP and the osteogenesis of CS give strong reason to believe that these calcium-based composite cements will prove to be effective bone repair materials. - Highlights: • CS improved the physicochemical properties and osteogenic activity of β-TCP. • Higher CS in the composite, the shorter setting time and the higher DTS was found. • With a CS more than 40%, the osteogenesis and angiogenesis proteins were promoted by

  3. Information for stores users

    CERN Multimedia

    Logistics Group - FI Department

    2005-01-01

    The Farnell catalogue can now be accessed from the Material Request form on EDH in addition to the CERN Stores catalogue. Users can order Farnell equipment as well as standard Stores equipment at the same time using a single document, the EDH Materials Request form. The Materials Request form offers users items from both the internal 'Stores' catalogue and the external 'Farnell' catalogue, all of which may be ordered on the same form. The system automatically forwards orders for standard Stores equipment to the CERN Stores and those for Farnell equipment to Farnell. The delivery time is 48 hours in both cases. Requests for materials are routed for approval in accordance with the standard EDH routing procedures. Logistics Group FI Department

  4. Calcium transcriptionally regulates the biofilm machinery of Xylella fastidiosa to promote continued biofilm development in batch cultures.

    Science.gov (United States)

    Parker, Jennifer K; Chen, Hongyu; McCarty, Sara E; Liu, Lawrence Y; De La Fuente, Leonardo

    2016-05-01

    The functions of calcium (Ca) in bacteria are less characterized than in eukaryotes, where its role has been studied extensively. The plant-pathogenic bacterium Xylella fastidiosa has several virulence features that are enhanced by increased Ca concentrations, including biofilm formation. However, the specific mechanisms driving modulation of this feature are unclear. Characterization of biofilm formation over time showed that 4 mM Ca supplementation produced denser biofilms that were still developing at 96 h, while biofilm in non-supplemented media had reached the dispersal stage by 72 h. To identify changes in global gene expression in X. fastidiosa grown in supplemental Ca, RNA-Seq of batch culture biofilm cells was conducted at three 24-h time intervals. Results indicate that a variety of genes are differentially expressed in response to Ca, including genes related to attachment, motility, exopolysaccharide synthesis, biofilm formation, peptidoglycan synthesis, regulatory functions, iron homeostasis, and phages. Collectively, results demonstrate that Ca supplementation induces a transcriptional response that promotes continued biofilm development, while biofilm cells in nonsupplemented media are driven towards dispersion of cells from the biofilm structure. These results have important implications for disease progression in planta, where xylem sap is the source of Ca and other nutrients for X. fastidiosa. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  5. Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

    Science.gov (United States)

    Chen, L; Yue, J; Han, X; Li, J; Hu, Y

    2016-02-01

    Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

  6. Qualidade de pedúnculos de caju submetidos à aplicação pós-colheita de cálcio e armazenados sob refrigeração Quality of cashew pseudofruits treated with calcium at postharvest and stored under refrigeration

    Directory of Open Access Journals (Sweden)

    Raimundo Wilane de Figueiredo

    2007-04-01

    Full Text Available O objetivo deste trabalho foi avaliar os efeitos da aplicação de cálcio pós-colheita nas características químicas, físico-químicas e nos teores de cálcio em pedúnculos de cajueiro-anão precoce CCP-76, submetidos a armazenamento refrigerado sob atmosfera modificada. Os cajus foram imersos em água e em soluções com diferentes concentrações de cloreto de cálcio (0,5, 1 e 2% p/v, por dois minutos. Os cajus foram acondicionados em bandejas de isopor, envolvidos em filme de PVC e armazenados a 5±1°C e 88±3% de umidade relativa, durante 25 dias. Os teores de sólidos solúveis e açúcares solúveis diminuíram durante o armazenamento. Os pedúnculos de caju, independentemente da dose de cálcio, apresentaram tendência à diminuição da acidez e da vitamina C com o armazenamento, enquanto o pH apresentou um pequeno e gradual crescimento. Não houve variação nas antocianinas, nos pseudofrutos de caju tratados com cálcio. Verificaram-se pequenas reduções nas frações fenólicas menos polimerizadas, durante o armazenamento. O cálcio aplicado nas doses de 0,5 e 2% aumentou os teores de cálcio nos pedúnculos até o 15º dia, com diminuição posterior até o final do experimento.The objective of this work was to evaluate the effects of postharvest calcium applications on chemical and physico-chemical characteristics, quality atributes and calcium tissue concentration of early dwarf cashew pseudofruits (Anacardium occidentale L., stored under refrigeration and modified atmosphere. The cashews were immersed in water and in different calcium chloride solution concentrations (0.5, 1 and 2% (w/v for two minutes. Cashews were put in polysterene trays, packed in polyvinyl chloride (PVC and storaged at 5±1°C, 88±3% RH for 25 days. The total soluble solids (Brix and soluble sugars decreased during storage. The pseudofruits, independent of the chloride calcium concentration, showed a tendency to decrease the total titratable acidity

  7. Regulation of intracellular free calcium concentration during heterocyst differentiation by HetR and NtcA in Anabaena sp. PCC 7120.

    Science.gov (United States)

    Shi, Yunming; Zhao, Weixing; Zhang, Wei; Ye, Zi; Zhao, Jindong

    2006-07-25

    Calcium ions are important to some prokaryotic cellular processes, such as heterocyst differentiation of cyanobacteria. Intracellular free Ca(2+)concentration, [Ca(2+)](i), increases several fold in heterocysts and is regulated by CcbP, a Ca(2+)-binding protein found in heterocyst-forming cyanobacteria. We demonstrate here that CcbP is degraded by HetR, a serine-type protease that controls heterocyst differentiation. The degradation depends on Ca(2+) and appears to be specific because HetR did not digest other tested proteins. CcbP was found to bind two Ca(2+) per molecule with K(D) values of 200 nM and 12.8 microM. Degradation of CcbP releases bound Ca(2+) that contributes significantly to the increase of [Ca(2+)](i) during the process of heterocyst differentiation in Anabaena sp. strain PCC 7120. We suggest that degradation of CcbP is a mechanism of positive autoregulation of HetR. The down-regulation of ccbP in differentiating cells and mature heterocysts, which also is critical to the regulation of [Ca(2+)](i), depends on NtcA. Coexpression of ntcA and a ccbP promoter-controlled gfp in Escherichia coli diminished production of GFP, and the decrease is enhanced by alpha-ketoglutarate. It was also found that NtcA could bind a fragment of the ccbP promoter containing an NtcA-binding sequence in a alpha-ketoglutarate-dependent fashion. Therefore, [Ca(2+)](i) is regulated by a collaboration of HetR and NtcA in heterocyst differentiation in Anabaena sp. strain PCC 7120.

  8. Treatment of grapevines with prohexadione calcium as a growth regulator. The influence on production, winemaking and sensory characteristics of wines

    Directory of Open Access Journals (Sweden)

    Luis Vaquero-Fernández

    2009-09-01

    Significance and impact of study: ProCa as a growth regulator may be an option for a quality vitiviniculture. No previous studies have been published on applications of ProCa in grapevines in either Europe or in cv. Tempranillo. Additionally, studies with other varieties have not demonstrated sensory improvements in wines obtained from treated vines.

  9. Calcium waves.

    Science.gov (United States)

    Jaffe, Lionel F

    2008-04-12

    Waves through living systems are best characterized by their speeds at 20 degrees C. These speeds vary from those of calcium action potentials to those of ultraslow ones which move at 1-10 and/or 10-20 nm s(-1). All such waves are known or inferred to be calcium waves. The two classes of calcium waves which include ones with important morphogenetic effects are slow waves that move at 0.2-2 microm s(-1) and ultraslow ones. Both may be propagated by cycles in which the entry of calcium through the plasma membrane induces subsurface contraction. This contraction opens nearby stretch-sensitive calcium channels. Calcium entry through these channels propagates the calcium wave. Many slow waves are seen as waves of indentation. Some are considered to act via cellular peristalsis; for example, those which seem to drive the germ plasm to the vegetal pole of the Xenopus egg. Other good examples of morphogenetic slow waves are ones through fertilizing maize eggs, through developing barnacle eggs and through axolotl embryos during neural induction. Good examples of ultraslow morphogenetic waves are ones during inversion in developing Volvox embryos and across developing Drosophila eye discs. Morphogenetic waves may be best pursued by imaging their calcium with aequorins.

  10. Information for stores users

    CERN Multimedia

    2007-01-01

    From next week, the SFS UNIMARKET (tooling) catalogue will be accessible using the Material Request form on EDH in addition to the CERN Stores catalogue and those of existing suppliers. Users will now be able to place orders from the SFS catalogue using the Material Request form on EDH. Note: The system automatically forwards orders for standard Stores equipment and those for SFS equipment, placed using the same Material Request form, to the CERN Stores and SFS respectively. In both cases, the maximum delivery time will be 48 hours. Requests for equipment will be routed for approval in accordance with standard EDH routing procedures. Logistics Group FI Department

  11. INFORMATION FOR STORES USERS

    CERN Multimedia

    2007-01-01

    From next week, the SFS UNIMARKET (tooling) catalogue will be accessible using the Material Request form on EDH in addition to the CERN Stores catalogue and those of existing suppliers. Users will now be able to place orders from the SFS catalogue using the Material Request form on EDH. Note: The system automatically forwards orders for standard Stores equipment and those for SFS equipment, placed using the same Material Request form, to the CERN Stores and SFS respectively. In both cases, the maximum delivery time will be 48 hours. Requests for equipment will be routed for approval in accordance with standard EDH routing procedures. Logistics Group FI Department

  12. Information for stores users

    CERN Multimedia

    2006-01-01

    The Radiospares Catalogue is now accessible from the Material Request page on EDH in the same way as the CERN Stores Catalogue. This means that users can order Radiospares equipment by completing an EDH Materials Request form. N.B.: The system will automatically forward orders for standard Stores equipment to the CERN Stores and those for Radiospares equipment to Radiospares. In both cases the delivery time will be a maximum of 48 hours. Requests for materials will be routed for approval in accordance with the standard EDH routing procedures. Logistics Group FI Department

  13. INFORMATION FOR STORES USERS

    CERN Multimedia

    SPL Division

    1999-01-01

    You can now make Material Request from CERN Stores over the WEB :CERN Home/Administrative Tools/EDH/Material Requestor https://edh.cern.ch/Document/MAGVia the Stores Catalogue : CERN Home/Administrative Tools/Stores Catalogueor http://edhcat.cern.ch/In both cases, you need to enter your EDH login and password.For more details, you can consult the Quick Reference Guide on :http://edh.cern.ch/doc/quickrefguides.htmlor obtain a printed version from AIS Support at tel: 79933or e-mail to: ais.support@cern.chSPL DivisionLogistics Group

  14. 7 CFR 58.434 - Calcium chloride.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Calcium chloride. 58.434 Section 58.434 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.434 Calcium chloride. Calcium chloride, when used, shall meet the requirements of the Food...

  15. USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level.

    Directory of Open Access Journals (Sweden)

    Daniel Pouly

    Full Text Available The mammalian circadian clock influences most aspects of physiology and behavior through the transcriptional control of a wide variety of genes, mostly in a tissue-specific manner. About 20 clock-controlled genes (CCGs oscillate in virtually all mammalian tissues and are generally considered as core clock components. One of them is Ubiquitin-Specific Protease 2 (Usp2, whose status remains controversial, as it may be a cogwheel regulating the stability or activity of core cogwheels or an output effector. We report here that Usp2 is a clock output effector related to bodily Ca2+ homeostasis, a feature that is conserved across evolution. Drosophila with a whole-body knockdown of the orthologue of Usp2, CG14619 (dUsp2-kd, predominantly die during pupation but are rescued by dietary Ca2+ supplementation. Usp2-KO mice show hyperabsorption of dietary Ca2+ in small intestine, likely due to strong overexpression of the membrane scaffold protein NHERF4, a regulator of the Ca2+ channel TRPV6 mediating dietary Ca2+ uptake. In this tissue, USP2-45 is found in membrane fractions and negatively regulates NHERF4 protein abundance in a rhythmic manner at the protein level. In clock mutant animals (Cry1/Cry2-dKO, rhythmic USP2-45 expression is lost, as well as the one of NHERF4, confirming the inverse relationship between USP2-45 and NHERF4 protein levels. Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+.

  16. Information for stores users

    CERN Multimedia

    2006-01-01

    The Bossard catalogue is now accessible alongside the CERN Stores catalogue from the Material Request form on EDH. Users will thus be able to order Bossard equipment using the EDH Materials Request form. As a reminder, the system automatically forwards orders for standard Stores equipment to the CERN Stores and those for Bossard equipment to Bossard. In both cases the delivery time will be a maximum of 48 hours. Requests for materials will be routed for approval in accordance with the standard EDH routing procedures. Some items will remain available from the emergency desk in the event of urgent requests. These items will be visible in the Stores catalogue even if they cannot be purchased via the EDH material request form. Logistics Group FI Department

  17. Provenance Store Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Paulson, Patrick R.; Gibson, Tara D.; Schuchardt, Karen L.; Stephan, Eric G.

    2008-03-01

    Requirements for the provenance store and access API are developed. Existing RDF stores and APIs are evaluated against the requirements and performance benchmarks. The team’s conclusion is to use MySQL as a database backend, with a possible move to Oracle in the near-term future. Both Jena and Sesame’s APIs will be supported, but new code will use the Jena API

  18. Growth hormone secretagogues protect mouse cardiomyocytes from in vitro ischemia/reperfusion injury through regulation of intracellular calcium.

    Directory of Open Access Journals (Sweden)

    Yi Ma

    Full Text Available BACKGROUND: Ischemic heart disease is a leading cause of mortality. To study this disease, ischemia/reperfusion (I/R models are widely used to mimic the process of transient blockage and subsequent recovery of cardiac coronary blood supply. We aimed to determine whether the presence of the growth hormone secretagogues, ghrelin and hexarelin, would protect/improve the function of heart from I/R injury and to examine the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus. Ghrelin (10 nM or hexarelin (1 nM was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments. In freshly isolated cardiomyocytes from these hearts, single cell shortening, intracellular calcium ([Ca(2+](i transients and caffeine-releasable sarcoplasmic reticulum (SR Ca(2+ were measured. In addition, RT-PCR and Western blots were used to examine the expression level of GHS receptor type 1a (GHS-R1a, and phosphorylated phospholamban (p-PLB, respectively. Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+](i transient amplitude and caffeine-releasable SR Ca(2+ content after I/R through recovery of p-PLB. GHS-R1a antagonists, [D-Lys3]-GHRP-6 (200 nM and BIM28163 (100 nM, completely blocked the effects of GHS on both cell shortening and [Ca(2+](i transients. CONCLUSION/SIGNIFICANCE: Through activation of GHS-R1a, ghrelin and hexarelin produced a positive inotropic effect on ischemic cardiomyocytes and protected them from I/R injury probably by protecting or recovering p-PLB (and therefore SR Ca(2+ content to allow the maintenance or recovery of normal cardiac contractility. These observations provide supporting evidence for the potential therapeutic application of ghrelin and hexarelin in patients with cardiac I/R injury.

  19. Interaction proteins of invertase and invertase inhibitor in cold-stored potato tubers suggested a protein complex underlying post-translational regulation of invertase.

    Science.gov (United States)

    Lin, Yuan; Liu, Jun; Liu, Xun; Ou, Yongbin; Li, Meng; Zhang, Huiling; Song, Botao; Xie, Conghua

    2013-12-01

    The activity of vacuolar invertase (VI) is vital to potato cold-induced sweetening (CIS). A post-translational regulation of VI activity has been proposed which involves invertase inhibitor (VIH), but the mechanism for the interaction between VI and VIH has not been fully understood. To identify the potential partners of VI and VIH, two cDNA libraries were respectively constructed from CIS-resistant wild potato species Solanum berthaultii and CIS-sensitive potato cultivar AC035-01 for the yeast two-hybrid analysis. The StvacINV1 (one of the potato VIs) and StInvInh2B (one of the potato VIHs), previously identified to be associated with potato CIS, were used as baits to screen the two libraries. Through positive selection and sequencing, 27 potential target proteins of StvacINV1 and eight of StInvInh2B were clarified. The Kunitz-type protein inhibitors were captured by StvacINV1 in both libraries and the interaction between them was confirmed by bimolecular fluorescence complementation assay in tobacco cells, reinforcing a fundamental interaction between VI and VIH. Notably, a sucrose non-fermenting-1-related protein kinase 1 was captured by both the baits, suggesting that a protein complex could be necessary for fine turning of the invertase activity. The target proteins clarified in present research provide a route to elucidate the mechanism by which the VI activity can be subtly modulated. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. TRPV4 calcium-permeable channel is a novel regulator of oxidized LDL-induced macrophage foam cell formation.

    Science.gov (United States)

    Goswami, Rishov; Merth, Michael; Sharma, Shweta; Alharbi, Mazen O; Aranda-Espinoza, Helim; Zhu, Xiaoping; Rahaman, Shaik O

    2017-09-01

    Cardiovascular disease is the number one cause of death in United States, and atherosclerosis, a chronic inflammatory arterial disease, is the most dominant underlying pathology. Macrophages are thought to orchestrate atherosclerosis by generating lipid-laden foam cells and by secreting inflammatory mediators. Emerging data support a role for a mechanical factor, e.g., matrix stiffness, in regulation of macrophage function, vascular elasticity, and atherogenesis. However, the identity of the plasma membrane mechanosensor and the mechanisms by which pro-atherogenic signals are transduced/maintained are unknown. We have obtained evidence that TRPV4, an ion channel in the transient receptor potential vanilloid family and a known mechanosensor, is the likely mediator of oxidized low-density lipoprotein (oxLDL)-dependent macrophage foam cell formation, a critical process in atherogenesis. Specifically, we found that: i) genetic ablation of TRPV4 or pharmacologic inhibition of TRPV4 activity by a specific antagonist blocked oxLDL-induced macrophage foam cell formation, and ii) TRPV4 deficiency prevented pathophysiological range matrix stiffness or scratch-induced exacerbation of oxLDL-induced foam cell formation. Mechanistically, we found that: i) plasma membrane localization of TRPV4 was sensitized to the increasing level of matrix stiffness, ii) lack of foam cell formation in TRPV4 null cells was not due to lack of expression of CD36, a major receptor for oxLDL, and iii) TRPV4 channel activity regulated oxLDL uptake but not its binding on macrophages. Altogether, these findings identify a novel role for TRPV4 in regulating macrophage foam cell formation by modulating uptake of oxLDL. These findings suggest that therapeutic targeting of TRPV4 may provide a selective approach to the treatment of atherosclerosis. Copyright © 2017. Published by Elsevier Inc.

  1. Mg(2+),ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

    OpenAIRE

    T. О. Veklich; Iu. Iu. Mazur; S. О. Kosterin

    2015-01-01

    Plasma membrane Ca2+-pump is one of key proteins, which takes part in Ca2+ exchange in smooth muscle cells. It has a lot of diverse functions from control of basal cytoplasmal Ca2+ concentration to regulation of proteins involved in Ca2+-dependent signal pathway. Ca2+ pump function is often depen­dent on the isoform or even form of alternative splicing. Allowing for a variety of Ca2+-pump functions and properties, which were reviewed in detail in the first part of our review article cycle (U...

  2. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    Full Text Available The paper gives the review on the role of calcium in many physiological processes of plant organisms, including growth and development, protection from pathogenic influences, response to changing environmental factors, and many other aspects of plant physiology. Initial intake of calcium ions is carried out by Ca2+-channels of plasma membrane and they are further transported by the xylem owing to auxins’ attractive ability. The level of intake and selectivity of calcium transport to ove-ground parts of the plant is controlled by a symplast. Ca2+enters to the cytoplasm of endoderm cells through calcium channels on the cortical side of Kaspary bands, and is redistributed inside the stele by the symplast, with the use of Ca2+-АТPases and Ca2+/Н+-antiports. Owing to regulated expression and activity of these calcium transporters, calclum can be selectively delivered to the xylem. Important role in supporting calcium homeostasis is given to the vacuole which is the largest depo of calcium. Regulated quantity of calcium movement through the tonoplast is provided by a number of potential-, ligand-gated active transporters and channels, like Ca2+-ATPase and Ca2+/H+ exchanger. They are actively involved in the inactivation of the calcium signal by pumping Ca2+ to the depo of cells. Calcium ATPases are high affinity pumps that efficiently transfer calcium ions against the concentration gradient in their presence in the solution in nanomolar concentrations. Calcium exchangers are low affinity, high capacity Ca2+ transporters that are effectively transporting calcium after raising its concentration in the cell cytosol through the use of protons gradients. Maintaining constant concentration and participation in the response to stimuli of different types also involves EPR, plastids, mitochondria, and cell wall. Calcium binding proteins contain several conserved sequences that provide sensitivity to changes in the concentration of Ca2+ and when you

  3. Calcium and Nuclear Signaling in Prostate Cancer

    OpenAIRE

    Ivan V. Maly; Wilma A. Hofmann

    2018-01-01

    Recently, there have been a number of developments in the fields of calcium and nuclear signaling that point to new avenues for a more effective diagnosis and treatment of prostate cancer. An example is the discovery of new classes of molecules involved in calcium-regulated nuclear import and nuclear calcium signaling, from the G protein-coupled receptor (GPCR) and myosin families. This review surveys the new state of the calcium and nuclear signaling fields with the aim of identifying the un...

  4. Mg(2+,ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

    Directory of Open Access Journals (Sweden)

    T. О. Veklich

    2015-04-01

    Full Text Available Plasma membrane Ca2+-pump is one of key proteins, which takes part in Ca2+ exchange in smooth muscle cells. It has a lot of diverse functions from control of basal cytoplasmal Ca2+ concentration to regulation of proteins involved in Ca2+-dependent signal pathway. Ca2+ pump function is often depen­dent on the isoform or even form of alternative splicing. Allowing for a variety of Ca2+-pump functions and properties, which were reviewed in detail in the first part of our review article cycle (Ukr. Biochem. J., 2015; 87(1, the precise control of the mentioned pump activity is very important for cell functioning­. The other part of this article is dedicated to different regulation factors of smooth muscle plasma membrane Ca2+-pump activity: endogenous and exo­genous, biotic and abiotic factors. Special attention is given to literature data and own results about design and the search of selective plasma membrane Ca2+-pump inhibitor which would allow examining its functioning in smooth muscle cells more meticulously.

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

    Science.gov (United States)

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

    2016-09-14

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

  6. Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

    Directory of Open Access Journals (Sweden)

    Hu Wei

    2014-03-01

    Full Text Available C57BL/6 mice with dilated cardiomyopathy (DCM were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd, decreased left ventricular ejection fraction (LVEF as well as left ventricular short axis fractional shortening (LVFS, accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP and plasma angiotensin II (AngII concentration. Moreover, myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2 activity was decreased. The ratio of phosphorylated phospholamban (PLB to total PLB decreased significantly with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2 expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT1R and protein kinase C (PKCb2. The possible underlying mechanism might be the regulation of myocardial AT1R-PKCb2-Ca2+ handling proteins.

  7. The Nord interim store

    International Nuclear Information System (INIS)

    Leushacke, D.F.; Rittscher, D.

    1996-01-01

    In line with the decision taken in 1990 to shut down and decommission the Greifswald and Rheinsberg Nuclear Power Stations, the waste management concept of the Energiewerke Nord is based on direct and complete decommissioning of the six shut down reactor units within the next fifteen years. One key element of this concept is the construction and use of the Zwischenlager Nord (Nord Interim Store, ZLN) for holding the existing nuclear fuels and for interim and decay storage of the radioactive materials arising in decommissioning and demolition. The owner and operator of the store is Energiewerke Nord GmbH. The interim store has the functions of a processing and Energiewerke Nord GmbH. The interim store has the functions of a processing and treatment station and buffer store for the flows of residues arising. As a radioactive waste management station, it accommodates nuclear fuels, radioactive waste or residues which are not treated any further. It is used as a buffer store to allow the materials accumulating in disassembly to be stored temporarily before or after treatment in order to ensure continuous loading of the treatment plants. When operated as a processing station, the ZLN is able to handle nearly all types of radioactive waste and residues arising, except for nuclear fuels. These installations allow the treatment of radioactive residues to be separated from the demolition work both physically and in time. The possibilities of interium storage and buffer storage of untreated waste and waste packages make for high flexibility in logistics and waste management strategy. (orig.) [de

  8. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p

  9. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping

    2009-01-01

    Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most....... Also, we discuss potential roles of synaptotagmins in non-traditional endocrine systems....... synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin-calcium-sensor paradigm, that is, members of the synaptotagmin family function...... as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion...

  10. Inflammable materials stores

    International Nuclear Information System (INIS)

    Nandagopan, V.

    2017-01-01

    A new Inflammable Materials Stores has been constructed by A and SED, BARC near Gamma Field for storage of inflammable materials falling into Petroleum Class ‘A’ ‘B’ and “C” mainly comprising of oils and lubricants, Chemicals like Acetone, Petroleum Ether etc. which are regularly procured by Central Stores Unit (CSU) for issue to the various divisions of BARC. The design of the shed done by A and SED, BARC was duly got approved from Petroleum and Explosive Safety Organization (PESO) which is a mandatory requirement before commencement of the construction. The design had taken into account various safety factors which is ideally required for an inflammable materials stores

  11. The Androgen-Regulated Calcium-Activated Nucleotidase 1 (CANT1) Is Commonly Overexpressed in Prostate Cancer and Is Tumor-Biologically Relevant in Vitro

    Science.gov (United States)

    Gerhardt, Josefine; Steinbrech, Corinna; Büchi, Oralea; Behnke, Silvia; Bohnert, Annette; Fritzsche, Florian; Liewen, Heike; Stenner, Frank; Wild, Peter; Hermanns, Thomas; Müntener, Michael; Dietel, Manfred; Jung, Klaus; Stephan, Carsten; Kristiansen, Glen

    2011-01-01

    Previously, we identified the calcium-activated nucleotidase 1 (CANT1) transcript as up-regulated in prostate cancer. Now, we studied CANT1 protein expression in a large cohort of nearly 1000 prostatic tissue samples including normal tissue, prostatic intraepithelial neoplasia (PIN), primary carcinomas, metastases, and castrate-resistant carcinomas, and further investigated its functional relevance. CANT1 displayed predominantly a Golgi-type immunoreactivity with additional and variable cytoplasmic staining. In comparison to normal tissues, the staining intensity was significantly increased in PIN lesions and cancer. In cancer, high CANT1 levels were associated with a better prognosis, and castrate-resistant carcinomas commonly showed lower CANT1 levels than primary carcinomas. The functional role of CANT1 was investigated using RNA interference in two prostate cancer cell lines with abundant endogenous CANT1 protein. On CANT1 knockdown, a significantly diminished cell number and DNA synthesis rate, a cell cycle arrest in G1 phase, and a strong decrease of cell transmigration rate and wound healing capacity of CANT1 knockdown cells was found. However, on forced CANT1 overexpression, cell proliferation and migration remained unchanged. In summary, CANT1 is commonly overexpressed in the vast majority of primary prostate carcinomas and in the precursor lesion PIN and may represent a novel prognostic biomarker. Moreover, this is the first study to demonstrate a functional involvement of CANT1 in tumor biology. PMID:21435463

  12. Calcium-dependent protein kinase CPK31 interacts with arsenic transporter AtNIP1;1 and regulates arsenite uptake in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Ruijie Ji

    Full Text Available Although arsenite [As(III] is non-essential and toxic for plants, it is effectively absorbed through various transporters into the roots. Here we identified a calcium-dependent protein kinase (CPK31 response for As(III tolerance in Arabidopsis. We identified CPK31 as an interacting protein of a nodulin 26-like intrinsic protein (NIP1;1, an aquaporin involved in As(III uptake. Similarly to the nip1;1 mutants, the loss-of-function mutants of CPK31 improved the tolerance against As(III but not As(V, and accumulated less As(III in roots than that of the wild-type plants. The promoter-β-glucuronidase and quantitative Real-Time PCR analysis revealed that CPK31 displayed overlapping expression profiles with NIP1;1 in the roots, suggesting that they might function together in roots. Indeed, the cpk31 nip1;1 double mutants exhibited stronger As(III tolerance than cpk31 mutants, but similar to nip1;1 mutants, supporting the idea that CPK31 might serve as an upstream regulator of NIP1;1. Furthermore, transient CPK31 overexpression induced by dexamethasone caused the decrease in As(III tolerance of transgenic Arabidopsis lines. These findings reveal that CPK31 is a key factor in As(III response in plants.

  13. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells

    Science.gov (United States)

    Zhang, Hui-ming; Talbot, Mark J.; McCurdy, David W.; Patrick, John W.; Offler, Christina E.

    2015-01-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca2+ levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane–microtubule inter-relationship is discussed. PMID:26136268

  14. Information for Stores users

    CERN Multimedia

    FI Department

    2008-01-01

    The DISTRELEC catalogue (IT) is now available in EDH in addition to the CERN Stores catalogue and the catalogues of existing suppliers. Using an EDH materials request form, users can now order DISTRELEC equipment from amongst the following product groups: peripherals, multimedia, PC components, data media, communication and data cables and adapters. Non-authorised materials will be clearly indicated. As a reminder, the system automatically manages the distribution of standard Stores equipment and punch out equipment ordered on the same request form. In both cases, delivery will take a maximum of 48 hours. The approval of the EDH document will follow the usual EDH routing procedures. Logistics Group FI Department

  15. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic

    2013-05-01

    Full Text Available The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

  16. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  17. Protein kinase C regulates the activity of voltage-sensitive calcium channels of the rat chromaffin cells

    International Nuclear Information System (INIS)

    Wakade, A.R.; Malhotra, R.K.; Wakade, T.D.

    1986-01-01

    Phorbol dibutyrate (PB), an activator of protein kinase C was used as a tool to study the role of protein kinase C in the secretion of catecholamines (CA) from the perfused adrenal gland of rat. Secretion of CA evoked by splanchnic nerve stimulation, nicotine (N), carbamylcholine (C) and 35 mM K (K) was enhanced (about 2-fold) by 30 nM PB, but that evoked by muscarine (M) was not. In Ca-free and 1 mM EGTA Krebs solution, N and M did not evoke secretion, and PB also had no effect. If Ca concentration of the perfusion medium was maintained at 0.1 mM, N-evoked secretion was reduced over 80% but M-evoked secretion was still about 60% of the control value. Addition of PB to this medium did not modify secretion evoked by M, but N-evoked secretion was facilitated by 3-fold. Ca 45 flux data showed that N-, C-, and K-evoked secretion of CA was associated with 2- to 3-fold increase in Ca 45 uptake. However, M-evoked secretion did not cause Ca 45 uptake. These results suggest that N utilizes extracellular whereas M utilizes mostly intracellular Ca ions for the secretion of CA. PB alone did not affect Ca 45 uptake, but after stimulation with N, C and K, Ca 45 uptake was further enhanced by PB. It is concluded that protein kinase C phosphorylates membrane proteins that control opening and closing of Ca channels regulated by nicotine receptors and changes in membrane potentials

  18. Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

    Science.gov (United States)

    D'Amour, Pierre; Räkel, Agnès; Brossard, Jean-Hugues; Rousseau, Louise; Albert, Caroline; Cantor, Tom

    2006-01-01

    The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical. The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH. CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure. From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84). PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.

  19. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual

    Science.gov (United States)

    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward

    2013-01-01

    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

  20. Shaktismen - hinduismens store gudindetradition

    DEFF Research Database (Denmark)

    Olesen, Bjarne Wernicke

    2008-01-01

    Artiklen giver en introduktion til shaktismen - hinduismens store gudindetradition. Den ser på de vigtigste gudinder, begreber, traditioner og forestillinger, ligesom den giver et vue over forskningssituationen. Shaktismens opståen i sin klassiske form, dens hovedretninger, virkelighedsforståelse...

  1. Information for stores users

    CERN Multimedia

    FI Department

    2008-01-01

    From the beginning of March onwards, the LYRECO (stationery) catalogue will be accessible from the Material Request form on EDH in the same way as the CERN Stores catalogue and the existing individual supplier catalogues. Items will be delivered within a maximum of 48 hours. Logistics Group FI Department

  2. Store Security: Reducing Shoplifting.

    Science.gov (United States)

    Minsel, Robert; Garman, Jerry

    The major purpose of the course outline presented in the document is the reduction of stealing in retail stores. The teaching outline is formatted by juxtaposing the content outline of each substantive area next to relevant activities and methods. Some of the topics covered are psychology of shoplifting, tools used by shoplifters, Ohio's law on…

  3. Troponin T3 regulates nuclear localization of the calcium channel Ca{sub v}β{sub 1a} subunit in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Pereyra, Andrea S. [Department of Histology, National University of La Plata, 1900 La Plata (Argentina); Messi, Maria Laura; Wang, Zhong-Min [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Hereñú, Claudia [Department of Histology, National University of La Plata, 1900 La Plata (Argentina); Delbono, Osvaldo, E-mail: odelbono@wakehealth.edu [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2015-08-15

    The voltage-gated calcium channel (Ca{sub v}) β{sub 1a} subunit (Ca{sub v}β{sub 1a}) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca{sub v}β{sub 1a} subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca{sub v}β{sub 1a} NH{sub 2}-terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca{sub v}β{sub 1a}/YFP shows that TnT3 facilitates Ca{sub v}β{sub 1a} nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca{sub v}β{sub 1a} is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca{sub v}β{sub 1a}. • We mapped TnT3 and Ca{sub v}β{sub 1a} interaction domain. • TnT3 facilitates Ca{sub v}β{sub 1a} nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation.

  4. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

  5. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-κB translocation and ROS production in synoviocytes

    International Nuclear Information System (INIS)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang; Li, Junying

    2012-01-01

    Highlights: ► Moderate extracellular acidification regulates intracellular Ca 2+ mobilization. ► Moderate acidification activates NF-κB nuclear translocation in synoviocytes. ► Moderate acidification depresses the ROS production induced by capsaicin. ► Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca 2+ entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca 2+ entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca 2+ release from intracellular stores. The nuclear translocation of NF-κB was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-κB. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca 2+ mobilization, activating NF-κB nuclear translocation and depressing ROS production.

  6. STORE IN STORE FRANCHISING STRATEGY: THE TREND IN FRANCHISING NEGOTIATION

    OpenAIRE

    Rosado-Serrano, Alexander; Universidad de Puerto Rico

    2016-01-01

    The literature on franchising has traditionally focused on the effects and transformation it has promoted in the service sector, retailing, restaurants, hotels and other service-related industries. Store within a store research has been focused on the perspective of the manufacturer entering department stores. To date, little research has been carried out for the store in store strategy from the franchising perspective. This paper explores why big box retailers such as Walmart are adopting th...

  7. Differential effects of the steaming time and frequency for manufactured red Liriope platyphylla on nerve growth factor secretion ability, nerve growth factor receptor signaling pathway and regulation of calcium concentration.

    Science.gov (United States)

    Choi, Sun Il; Goo, Jun Seo; Kim, Ji Eun; Nam, So Hee; Hwang, In Sik; Lee, Hye Ryun; Lee, Young Ju; Son, Hong Joo; Lee, Hee Seob; Lee, Jong Sup; Kim, Hak Jin; Hwang, Dae Youn

    2012-11-01

    The herb Liriope platyphylla (LP) has been considered to have curative properties for diabetes, asthma and neurodegenerative disorders. To examine the effects of steaming time and frequency of manufactured red LP (RLP) on the nerve growth factor (NGF) secretion ability and NGF receptor signaling pathway, the NGF concentration, cell differentiation, NGF signaling pathway and calcium concentration were analyzed in neuronal cells treated with several types of LPs manufactured under different conditions. The maximum NGF secretion was observed in B35 cells treated with 50 µg/ml LP extract steamed for 9 h (9-SLP) and with two repeated steps (3 h steaming and 24 h air-dried) carried out 7 times (7-SALP). No significant changes in viability were detected in any of the cells treated with the various LPs, with the exception of 0-SLP and 0-SALP. In addition, PC12 cell differentiation was induced by treatment with the NGF-containing conditional medium (CM) collected from the RLP-treated cells. The levels of TrkA and extracellular signal-regulated kinase (ERK) phosphorylation in the high affinity NGF receptor signaling pathway were significantly higher in the cells treated with 3-SLP or 1-SALP/3-SALP CM compared with those treated with the vehicle CM. In the low affinity NGF receptor pathway, the expression levels of most components were higher in the 9-, 15- and 24-SALP CM-treated cells compared with the vehicle CM-treated cells. However, this level was significantly altered in cells treated with 3-SALP CM. Furthermore, an examination of the RLP function on calcium regulation revealed that only the LP- or RLP-treated cells exhibited changes in intracellular and extracellular calcium levels. RLP induced a significant decrease in the intracellular calcium levels and an increase in the extracellular calcium levels. These results suggest the possibility that steaming-processed LP may aid in the relief of neurodegenerative diseases through the NGF secretion ability and NGF

  8. Fuel element store

    International Nuclear Information System (INIS)

    Wieser, R.

    1987-01-01

    The spherical fuel elements are stored dry in cans. The cans themselves are stacked in parallel storage shafts, which are combined into a rectangular storage space. The storage space is made earthquake-proof by surrounding it with concrete. It consists of a ceiling assembled from several steel parts, which is connected to the floor by support elements. A cooling air ventilation station supplies the individual storage shaft and therefore the cans with cooling air via incoming and outgoing pipes. (DG) [de

  9. Air corrosion in storing

    International Nuclear Information System (INIS)

    Mazaudier, F.; Feron, D.; Baklouti, M.; Midoux, N.

    2001-01-01

    The air corrosiveness of a radioactive waste package has been estimated in a store inside which the environmental conditions are supposed to be rather close to the outside ones. It is expressed according to the ISO 9223 standard, from the humidification value and the amounts of sulfur dioxide and chlorine ions. A computer code has been perfected too; the thermal behaviour of the package can then been determined. (O.M.)

  10. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells.

    Science.gov (United States)

    Zhang, Hui-ming; Talbot, Mark J; McCurdy, David W; Patrick, John W; Offler, Christina E

    2015-09-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  11. Polyamine regulates tolerance to water stress in leaves of white clover associated with antioxidant defense and dehydrin genes via involvement in calcium messenger system and hydrogen peroxide signaling

    Directory of Open Access Journals (Sweden)

    Zhou eLi

    2015-10-01

    Full Text Available Endogenous polyamine (PA may play a critical role in tolerance to water stress in plants acting as a signaling molecule activator. Water stress caused increases in endogenous PA content in leaves, including putrescine (Put, spermidine (Spd, and spermine (Spm. Exogenous application of Spd could induce the instantaneous H2O2 burst and accumulation of cytosolic free Ca2+, and activate NADPH oxidase and CDPK gene expression in cells. To a great extent, PA biosynthetic inhibitor reduced the water stress-induced H2O2 accumulation, free cytosolic Ca2+ release, antioxidant enzyme activities and genes expression leading to aggravate water stress-induced oxidative damage, while these suppressing effects were alleviated by the addition of exogenous Spd, indicating PA was involved in water stress-induced H2O2 and cytosolic free Ca2+ production as well as stress tolerance. Dehydrin genes (Y2SK, Y2K, and SK2 were showed to be highly responsive to exogenous Spd. PA-induced antioxidant defense and dehydrin genes expression could be blocked by the scavenger of H2O2 and the inhibitors of H2O2 generation or Ca2+ channels blockers, a calmodulin antagonist, as well as the inhibitor of CDPK. These findings suggested that PA regulated tolerance to water stress in white clover associated with antioxidant defenses and dehydrins via involvement in the calcium messenger system and H2O2 signaling pathways. PA-induced H2O2 production required Ca2+ release, while PA-induced Ca2+ release was also essential for H2O2 production, suggesting an interaction between PA-induced H2O2 and Ca2+ signaling.

  12. Modulation of intracellular calcium homeostasis by trimethyltin chloride in human tumour cells: Neuroblastoma SY5Y and cervix adenocarcinoma HeLa S3

    International Nuclear Information System (INIS)

    Florea, Ana-Maria; Splettstoesser, Frank; Dopp, Elke; Rettenmeier, Albert W.; Buesselberg, Dietrich

    2005-01-01

    Physiological modifications of intracellular Ca 2+ ([Ca 2+ ] i ) levels trigger and/or regulate a diversity of cellular activities (e.g. neurotransmitter release, synaptic plasticity, muscular contraction, cell proliferation), while calcium overloads could result in cytotoxicity. Previously, we have shown that trimethyltin chloride (Me 3 SnCl; TMT) modulates calcium homeostasis in cervix adenocarcinoma (HeLa S3) cells [Florea, A.-M., Dopp, E., Buesselberg, D., 2005. TMT induces elevated calcium transients in HeLa cells: types and levels of response. Cell Calcium 37, 252-258]. Here we compare [Ca 2+ ] i -changes induced by trimethyltin chloride in neuroblastoma SY5Y and HeLa S3 cells using calcium-sensitive dyes (fluo-4/AM (fluo-4) and rhod-2/AM (rhod-2)) and laser scanning microscopy (LSM). TMT-induced calcium elevations in neuroblastoma SY5Y as well as in HeLa S3 cells. [Ca 2+ ] i rose to a sustained plateau or to transient spikes. Overall, the detected averaged increase of the maximum calcium elevation were: 0.5 μM ∼125.6%; 5 μM ∼130.1%; 500 μM ∼145% in HeLa S3 cells and 0.5 μM ∼133.3%; 5 μM ∼136.1%; 500 μM ∼147.1% in neuroblastoma SY5Y cells. The calcium rise derived from internal stores did not significantly depend on the presence of calcium in the external solution: ∼109% (no calcium added) versus ∼117% (2 mM calcium; 5 μM TMT) in HeLa cells. This difference was similar in neuroblastoma SY5Y cells, were ∼127% versus ∼136% increase (5 μM TMT) were measured. Staining of calcium stores with rhod-2 showed a TMT-induced [Ca 2+ ] i -decrease in the stores followed by an increase of the calcium concentration in the nuclei of the two cell lines tested. Our results suggest that toxic effects in human tumour cells after exposure to trimethyltin compounds might be due to an elevation of [Ca 2+ ] i

  13. Get Enough Calcium

    Science.gov (United States)

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... women, don't get enough calcium. How much calcium do I need every day? Women: If you ...

  14. Calcium - urine

    Science.gov (United States)

    ... Female urinary tract Male urinary tract Calcium urine test References Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier; ...

  15. Calcium regulation and muscle disease.

    NARCIS (Netherlands)

    Gommans, I.M.P.; Vlak, M.; Haan, A. de; Engelen, B.G.M. van

    2002-01-01

    Changes in intracellular Ca2+-concentration play an important role in the excitation-contraction-relaxation cycle of skeletal muscle. In this review we describe various inheritable muscle diseases to highlight the role of Ca2+-regulatory mechanisms. Upon excitation the ryanodine receptor releases

  16. Mucins and calcium phosphate precipitates additively stimulate cholesterol crystallization

    NARCIS (Netherlands)

    van den Berg, A. A.; van Buul, J. D.; Tytgat, G. N.; Groen, A. K.; Ostrow, J. D.

    1998-01-01

    Human biliary mucin and calcium binding protein (CBP) influence formation of both calcium salt precipitates and cholesterol crystals and colocalize in the center of cholesterol gallstones. We investigated how physiological concentrations of these proteins regulate cholesterol crystallization in

  17. Storing of free neutrons

    International Nuclear Information System (INIS)

    Trinks, U.

    1978-12-01

    The applied method makes use of the interaction between the magnetic moment μ vector of the neutron and a magnetic field B vector. By means of superconducting magnets there can easily be achieved potential walls of μ B approximately 2 x 10 -7 eV. The principle of magnetic storing was first used for the storage ring NESTOR and showed immediate success: the stored neutrons decreased exponentially with a time constant tau = (907 +- 70) sec corresponding to the natural lifetime of the neutrons within the statistical errors. This means that there occurred no measurable additional losses (e.g. by resonance excitation) Neutrons therefore could be observed in the storage ring during about 5 half-lives (in principle of course longer, too). The orbit dynamics for neutrons in the storage ring is smilar to that in circular accelerators for charged particles. It is so well understood that the problem of the storage ring for uncharged particles (with magnetic moment) may be considered to e solved. (orig./HSI) [de

  18. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Slade, A.M.; Nayler, W.G.; Meijler, F.L.

    1984-01-01

    Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture,

  19. Testis-specific isoform of Na/K-ATPase (ATP1A4) regulates sperm function and fertility in dairy bulls through potential mechanisms involving reactive oxygen species, calcium and actin polymerization.

    Science.gov (United States)

    Rajamanickam, G D; Kroetsch, T; Kastelic, J P; Thundathil, J C

    2017-07-01

    Traditional bull breeding soundness evaluation (BBSE) eliminates bulls that are grossly abnormal; however, bulls classified as satisfactory potential breeders still vary in field fertility, implying submicroscopic differences in sperm characteristics. The testis-specific isoform of Na/K-ATPase (ATP1A4) is involved in regulation of sperm motility and capacitation in bulls through well-established enzyme activity and signaling functions. The objective was to determine ATP1A4 content, activity and their relationship to post-thaw sperm function and field fertility, using semen samples from low-fertility (LF) and high-fertility (HF) Holstein bulls (n = 20 each) with known FERTSOL rates (measure of field fertility, based on non-return rate). Frozen-thawed sperm from HF bulls had increased ATP1A4 content and activity compared to LF bulls. Furthermore, post-thaw sperm from HF bulls had increased tyrosine phosphorylation, ROS, F-actin content, and low intracellular calcium compared to LF bulls. Subsequent incubation of HF bull sperm with ouabain (a specific ligand of Na/K-ATPase) further augmented the post-thaw increase in tyrosine phosphorylation, ROS production, and F-actin content, whereas the increase in intracellular calcium was still low compared to LF bull sperm. ATP1A4 content and activity, ROS, F-actin and calcium were significantly correlated with fertility. In conclusion, we inferred that ATP1A4 content and activity differed among dairy bulls with satisfactory semen characteristics and that ATP1A4 may regulate sperm function through mechanisms involving ROS, F-actin and calcium in frozen-thawed sperm of HF and LF dairy bulls. © 2017 American Society of Andrology and European Academy of Andrology.

  20. Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

    Science.gov (United States)

    Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

    2002-12-01

    Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes

  1. Store manager performance and satisfaction: effects on store employee performance and satisfaction, store customer satisfaction, and store customer spending growth.

    Science.gov (United States)

    Netemeyer, Richard G; Maxham, James G; Lichtenstein, Donald R

    2010-05-01

    Based on emotional contagion theory and the value-profit chain literatures, the present study posits a number of hypotheses that show how managers in the small store, small number of employees retail context may affect store employees, customers, and potentially store performance. With data from 306 store managers, 1,615 store customer-contact employees, and 57,656 customers of a single retail chain, the authors examined relationships among store manager job satisfaction and job performance, store customer-contact employee job satisfaction and job performance, customer satisfaction with the retailer, and a customer-spending-based store performance metric (customer spending growth over a 2-year period). Via path analysis, several hypothesized direct and interaction relations among these constructs are supported. The results suggest implications for academic researchers and retail managers. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  2. Superconducting energy store

    International Nuclear Information System (INIS)

    Elsel, W.

    1986-01-01

    The advantages obtained by the energy store device according to the invention with a superconducting solenoid system consist of the fact that only relatively short superconducting forward and return leads are required, which are collected into cables as far as possible. This limits the coolant losses of the cables. Only one relatively expensive connecting part with a transition of its conductors from room temperature to a low temperature is required, which, like the normal conducting current switch, is easily accessible. As the continuation has to be cooled independently of the upper part solenoid, cooling of this continuation part can prevent the introduction of large quantities of heat into the connected part solenoid. Due to the cooling of the forward and return conductors of the connecting cable with the coolant of the lower part solenoid, there are relatively few separations between the coolant spaces of the part solenoids. (orig./MM) [de

  3. Shopping in discount stores

    DEFF Research Database (Denmark)

    Zielke, Stephan

    2014-01-01

    quarters of intentions to shop in discount stores. Value perception has the strongest total effect, which is partly mediated by enjoyment, shame and guilt. Attributions influence the shopping intention indirectly via value perception and emotions. The inferior quality attribution has the strongest total......This paper analyzes the impact of price-related attributions, emotions and value perception on the intention to shop at grocery discounters in an integrated framework. Moderating effects of price consciousness are also analyzed. The results show that the proposed model explains almost three...... effect, followed by the efficiency of the business model attribution. The unfairness to stakeholders and the tricks in price communication attribution mostly influence the shopping intention for less price-conscious customers....

  4. The Hepatitis B Virus X Protein Elevates Cytosolic Calcium Signals by Modulating Mitochondrial Calcium Uptake

    Science.gov (United States)

    Yang, Bei

    2012-01-01

    Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduced HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication. PMID:22031934

  5. PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium

    International Nuclear Information System (INIS)

    Zhu Xuhui; Yao Honghong; Peng Fuwang; Callen, Shannon; Buch, Shilpa

    2009-01-01

    The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process. Furthermore, we also found that pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity by decreasing extracellular glutamate levels. We also demonstrated that extracellular calcium chelator EGTA was able to abolish PDGF-mediated neuroprotection, thereby underscoring the role of calcium signaling in PDGF-mediated neuroprotection. We also showed that Erk signaling pathway was critical for PDGF-mediated protection of cells. Additionally, blocking calcium entry with EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in the protection of cells against HIV Tat toxicity.

  6. The importance of store windows in creating store identity and store attractiveness

    Directory of Open Access Journals (Sweden)

    Renko Sanda

    2012-01-01

    Full Text Available While choosing the store, customer first notices the store window and it plays an important role in retailing strategy. Store's window is what customers see first in meeting with the store. Store window design can lead customer to enter the store, and can give a lot of information about store brands and products. Besides the analysis of the way how specific elements of the window design affect customers and their perception, the explanation of their attraction and rejection to customers is given. If we consider the importance of the topics, we can point out the lack of literature about store windows as the communication tool which allow store to communicate with its customers and to create its retailing strategy as well. There is the scientific contribution of this paper. The paper gives theoretical comprehensions completed with the results of the study about the importance of store windows for retailers as well as for customers. Therefore, for the purpose of this paper, a two-phase research study, including a qualitative and a quantitative approach, was used: 1 the qualitative study among retailers which indicated the most important elements of store windows, the level of financial sources invested in the window design, the basis for the decisions about store window design, etc.; 2 the quantitative study on the sample of consumers conducted with on-line questionnaire. Findings suggest that store window attractiveness is the main motif for store visits. The results of the research confirm that by means of store window and its elements (with special emphasis on price and pricing actions retail store sends messages to its consumers.

  7. Exploring the Potential of Transient Receptor Potential: Troubleshooting Troublesome Calcium Thoroughfares in Biomedicine

    Directory of Open Access Journals (Sweden)

    Ammad Ahmad Farooqi

    2010-12-01

    Full Text Available Transient Receptor Potential-Canonical (TRPC channels are the border guards residing in the supra-molecular assembly of plasma membrane. TRPCs represent a family of channels that have dual functions of store-operated and second messenger-operated channels in a diversity of cell types. Any disruption in the spatio-temporal organization drastically influences the calcium homeostasis. This review summarizes current interpretations on the infrastructure and characteristic divalent ions regulation in molecular anomalies. A specific targeting of these channels will enable us to get a step closer to personalized medicines.

  8. Ripk3 regulates cardiac microvascular reperfusion injury: The role of IP3R-dependent calcium overload, XO-mediated oxidative stress and F-action/filopodia-based cellular migration.

    Science.gov (United States)

    Zhou, Hao; Wang, Jin; Zhu, Pingjun; Hu, Shunying; Ren, Jun

    2018-05-01

    Ripk3-mediated cellular apoptosis is a major contributor to the pathogenesis of myocardial ischemia reperfusion (IR) injury. However, the mechanisms by which Ripk3 influences microvascular homeostasis and endothelial apoptosis are not completely understood. In this study, loss of Ripk3 inhibited endothelial apoptosis, alleviated luminal swelling, maintained microvasculature patency, reduced the expression of adhesion molecules and limited the myocardial inflammatory response. In vitro, Ripk3 deficiency protected endothelial cells from apoptosis and migratory arrest induced by HR injury. Mechanistically, Ripk3 had the ability to migrate onto the endoplasmic reticulum (ER), leading to ER damage, as evidenced by increased IP3R and XO expression. The higher IP3R content was associated with cellular calcium overload, and increased XO expression was involved in cellular oxidative injury. Furthermore, IP3R-mediated calcium overload and XO-dependent oxidative damage were able to initiate cellular apoptosis. More importantly, IP3R and XO also caused F-actin degradation into G-actin via post-transcriptional modification of cofilin, impairing the formation of the filopodia and limiting the migratory response of endothelial cells. Altogether, our data confirmed that Ripk3 was involved in microvascular IR injury via regulation of IP3R-mediated calcium overload, XO-dependent oxidative damage and filopodia-related cellular migration, ultimately leading to endothelial apoptosis and migratory inhibition. These findings provide a potential target for treating cardiac microcirculatory IR injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Subthreshold membrane potential oscillations in inferior olive neurons are dynamically regulated by P/Q- and T-type calcium channels: a study in mutant mice.

    Science.gov (United States)

    Choi, Soonwook; Yu, Eunah; Kim, Daesoo; Urbano, Francisco J; Makarenko, Vladimir; Shin, Hee-Sup; Llinás, Rodolfo R

    2010-08-15

    The role of P/Q- and T-type calcium channels in the rhythmic oscillatory behaviour of inferior olive (IO) neurons was investigated in mutant mice. Mice lacking either the CaV2.1 gene of the pore-forming alpha1A subunit for P/Q-type calcium channel, or the CaV3.1 gene of the pore-forming alpha1G subunit for T-type calcium channel were used. In vitro intracellular recording from IO neurons reveals that the amplitude and frequency of sinusoidal subthreshold oscillations (SSTOs) were reduced in the CaV2.1-/- mice. In the CaV3.1-/- mice, IO neurons also showed altered patterns of SSTOs and the probability of SSTO generation was significantly lower (15%, 5 of 34 neurons) than that of wild-type (78%, 31 of 40 neurons) or CaV2.1-/- mice (73%, 22 of 30 neurons). In addition, the low-threshold calcium spike and the sustained endogenous oscillation following rebound potentials were absent in IO neurons from CaV3.1-/- mice. Moreover, the phase-reset dynamics of oscillatory properties of single neurons and neuronal clusters in IO were remarkably altered in both CaV2.1-/- and CaV3.1-/- mice. These results suggest that both alpha1A P/Q- and alpha1G T-type calcium channels are required for the dynamic control of neuronal oscillations in the IO. These findings were supported by results from a mathematical IO neuronal model that incorporated T and P/Q channel kinetics.

  10. Calcium, essential for health

    Science.gov (United States)

    Martínez de Victoria, Emilio

    2016-07-12

    Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

  11. 38 CFR 74.27 - How will VA store information?

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) VETERANS SMALL BUSINESS REGULATIONS Records Management § 74.27 How will VA store information? VA... examination visits will be scanned onto portable media and fully secured in the Center for Veterans Enterprise...

  12. Calcium blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003477.htm Calcium blood test To use the sharing features on this page, please enable JavaScript. The calcium blood test measures the level of calcium in the blood. ...

  13. Calcium source (image)

    Science.gov (United States)

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

  14. Calcium Pyrophosphate Deposition (CPPD)

    Science.gov (United States)

    ... Patient / Caregiver Diseases & Conditions Calcium Pyrophosphate Deposition (CPPD) Calcium Pyrophosphate Deposition (CPPD) Fast Facts The risk of ... young people, too. Proper diagnosis depends on detecting calcium pyrophosphate crystals in the fluid of an affected ...

  15. Calcium carbonate overdose

    Science.gov (United States)

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Products that contain calcium carbonate are certain: Antacids (Tums, Chooz) Mineral supplements Hand lotions Vitamin and mineral supplements Other products may also contain ...

  16. Calcium and bones (image)

    Science.gov (United States)

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

  17. Calcium hydroxide poisoning

    Science.gov (United States)

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

  18. Immunoselection of cDNAs to avian intestinal calcium binding protein 28K and a novel calmodulin-like protein: assessment of mRNA regulation by the Vitamin D hormone

    International Nuclear Information System (INIS)

    Mangelsdorf, D.J.; Komm, B.S.; McDonnell, D.P.; Pike, J.W.; Haussler, M.R.

    1987-01-01

    Calcium's role in a variety of cellular processes has been well documented. The storage, distribution, and delivery of calcium are regulated by a family of binding proteins including troponin C, calmodulin, parvalbumin, and vitamin D dependent calcium binding protein (CaBP-28), all of which have evolved from a common ancestral gene. To evaluate vitamin D regulation of gene transcription, a CaBP-28 cDNA (767 base pairs) was isolated from a chicken intestine λgt11 library utilizing a polyvalent CaBP-28 antibody as a probe. Coincident with the identification of the CaBP-28 cDNA, a group of cDNAs also was isolated (with the anti-CaBP-28 antibody) that demonstrated 84% nucleotide homology and 99% deduced amino acid homology with chicken brain calmodulin (CaM). This new CaM-like cDNA was named neoCaM. There is little nucleotide homology between the CaBP-28 cDNA and neoCaM. The CaBP-28 cDNA hybridizes with three transcripts of 2000, 2900, and 3300 bases which are dramatically induced by 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], while the neoCaM cDNA recognizes three distinct (from CaBP-28) transcripts. Two of these mRNAs are 1400 and 1800 bases as described for brain CaM, but another large 4000-base transcript is detected with neoCaM. Neither the CaM nor the neoCaM transcript reveals any modulation by 1,25(OH) 2 D 3 . Herein, the authors discuss the possible significance of not only the isolation of both cDNAs with a single antibody but also the relation of neoCaM to other well-characterized CaM cDNAs

  19. Calcium in Urine Test

    Science.gov (United States)

    ... K. Brunner & Suddarth's Handbook of Laboratory and Diagnostic Tests. 2 nd Ed, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott Williams & Wilkins; c2014. Calcium, Serum; Calcium and Phosphates, Urine; ...

  20. Tobacco advertising in retail stores.

    OpenAIRE

    Cummings, K M; Sciandra, R; Lawrence, J

    1991-01-01

    Recent studies have described tobacco advertising in the print media, on billboards, and through sponsorship of cultural and sporting events. However, little attention has been given to another common and unavoidable source of tobacco advertising, that which is encountered in retail stores. In July 1987, we conducted a survey of 61 packaged goods retail stores in Buffalo, NY, to assess the prevalence and type of point-of-sale tobacco advertising. In addition, store owners or managers were sur...

  1. Calcium movements and the cellular basis of gravitropism

    Science.gov (United States)

    Roux, S. J.; Biro, R. L.; Hale, C. C.

    An early gravity-transduction event in oat coleoptiles which precedes any noticeable bending is the accumulation of calcium on their prospective slower-growing side. Sub-cellular calcium localization studies indicate that the gravity-stimulated redistribution of calcium results in an increased concentration of calcium in the walls of responding cells. Since calcium can inhibit the extension growth of plant cell walls, this selective accumulation of calcium in walls may play a role in inducing the asymmetry of growth which characterizes gravitropism. The active transport of calcium from cells into walls is performed by a calcium-dependent ATPase localized in the plasma membrane. Evidence is presented in support of the hypothesis that this calcium pump is regulated by a feed-back mechanism which includes the participation of calmodulin.

  2. Dorte Nors "Den store tomat"

    DEFF Research Database (Denmark)

    Michelsen, Jimmi

    2017-01-01

    Tekstgennemgang og undervisningsforløb til Dorte Nors "Den store tomat". Undervisningsforløbet er henvendt til elever i folkeskolens udskoling......Tekstgennemgang og undervisningsforløb til Dorte Nors "Den store tomat". Undervisningsforløbet er henvendt til elever i folkeskolens udskoling...

  3. Consumers’ preferences regarding department stores

    NARCIS (Netherlands)

    van Laarhoven, W.; Borgers, A.W.J.; van den Berg, P.E.W.

    2017-01-01

    The main reason for this research was the bankruptcy of one the Dutch oldest and largest chain of department stores at the end of 2015. The main goal of this research is to find what, from a consumers’ perspective, a department store should look like. A four storey (1500 m2 each) building was

  4. Regulation of ghrelin secretion and action.

    Science.gov (United States)

    Camiña, Jesus P; Carreira, Marcos C; Micic, Dragan; Pombo, Manuel; Kelestimur, Fahrettin; Dieguez, Carlos; Casanueva, Felipe F

    2003-10-01

    The pulsatile release of growth hormone (GH) from anterior pituitary gland is regulated by the interplay of at least two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. Furthermore, release of GH in vivo may also be controlled by a third type of receptor, the growth hormone secretagogue receptor, a G-protein-coupled receptor, called GHS receptor type 1a (GHSR1a), which was identified in the pituitary and the hypothalamus in humans using a nonpeptidyl growth hormone secretagogue (MK-0677). Ghrelin, the endogenous ligand for the GHS-R1a, is a 28-amino-acid peptide isolated from human stomach that is modified by a straight chain octanoyl group covalently linked to Ser3, which is essential for its endocrine activity. This hormone, predominantly expressed and secreted by the stomach, has a dual action on GH secretion and food intake, showing interdependency between these actions. The finding that fasting and food intake, respectively, increase and decrease the secretion of ghrelin suggests that this hormone may be the bridge connecting somatic growth and body composition with energy metabolism, and appears to play a role in the alteration of energy homeostasis and body weight in pathophysiological states such as hypothyroidism and hyperthyroidism. Despite this, little is known about the intracellular signaling through which ghrelin exerts its regulatory actions. Activation of intracellular calcium mobilization is one of the earliest known cellular signals elicited by ghrelin. In HEK- 293 cells expressing the GHS-R1a, ghrelin induces a biphasic cytosolic calcium elevation characterized by a spike phase of the response, which reflects Ins(1,4,5)P3- dependent calcium mobilization of intracellular stores, and a sustained phase of the response, which is due to calcium influx across the plasma membrane triggered by aperture of capacitative calcium channels

  5. Microtubule nucleation in mouse bone marrow-derived mast cells is regulated by the concerted action of GIT1/βPIX proteins and calcium

    Czech Academy of Sciences Publication Activity Database

    Sulimenko, Vadym; Hájková, Zuzana; Černohorská, Markéta; Sulimenko, Tetyana; Sládková, Vladimíra; Dráberová, Lubica; Vinopal, Stanislav; Dráberová, Eduarda; Dráber, Pavel

    2015-01-01

    Roč. 194, č. 9 (2015), s. 4099-4111 ISSN 0022-1767 R&D Projects: GA ČR GAP302/12/1673; GA ČR GPP302/11/P709; GA ČR(CZ) GA14-09807S; GA ČR GA15-22194S; GA MŠk(CZ) LD13015; GA MŠk LH12050; GA MZd NT14467 Institutional support: RVO:68378050 Keywords : Bone Marrow-Derived Mast Cells * Microtubule Nucleation * GIT1/beta PIX Proteins * Calcium Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.985, year: 2015

  6. Calcium sensing in exocytosis

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Wu, Bingbing; Han, Weiping

    2012-01-01

    an increase in intracellular calcium levels. Besides the triggering role, calcium signaling modulates the precise amount and kinetics of vesicle release. Thus, it is a central question to understand the molecular machineries responsible for calcium sensing in exocytosis. Here we provide an overview of our...... current understanding of calcium sensing in neurotransmitter release and hormone secretion....

  7. Calcium fluoride

    International Nuclear Information System (INIS)

    King, C.W.; Nestor, O.H.

    1989-01-01

    A new process for producing large, single, oriented crystals of calcium fluoride (CaF 2 ) has been developed which overcomes the limitations of current growing methods. This process has been reduced to practice and has yielded oriented crystals 17.5 x 17.5 x 5 cm 3 . Currently nearing completion is a system for producing 35 x 35 x 7.5 cm 3 single crystals. A scale up to one-meter-square is considered feasible. This crystal growing process makes possible the fabrication of very large CaF 2 windows. Suitability for very high power lasers, however, requires attention to properties beyond mere size. A process to generate higher purity growth stock (starting material) was also developed. The additional purification of the growth stock contributes to lower bulk absorption, the absence of color centers and increased radiation hardness. Also identified were several specific impurities which correlate with radiation hardness. A correlation was found between color centers induced by laser radiation and ionizing radiation. Other CaF 2 crystal properties such as tensile strength, absorption and laser damage thresholds were studied and are discussed

  8. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties

    Directory of Open Access Journals (Sweden)

    Christine Dorothee Schmeitz

    2013-09-01

    Full Text Available Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic or initiates apoptosis depends on extracellular triggers and intracellular signalling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modelling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.

  9. Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium.

    Science.gov (United States)

    Huang, Jian; Zhao, Lei; Yang, Ping; Chen, Zhen; Ruan, Xiong Z; Huang, Ailong; Tang, Ni; Chen, Yaxi

    2017-09-15

    Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS. We recently found that CD36 overexpression enhanced HBV replication. In this study, we further explored the mechanism by which CD36 overexpression promotes HBV replication. Our data showed that CD36 overexpression increased HBV replication, and CD36 knockdown inhibited HBV replication. RNA sequencing found some of the differentially expressed genes were involved in calcium ion homeostasis. CD36 overexpression elevated the cytosolic calcium level, and CD36 knockdown decreased the cytosolic calcium level. Calcium chelator BAPTA-AM could override the HBV replication increased by CD36 overexpression, and the calcium activator thapsigargin could improve the HBV replication reduced by CD36 knockdown. We further found that CD36 overexpression activated Src kinase, which plays an important role in the regulation of the store-operated Ca 2+ channel. An inhibitor of Src kinase (SU6656) significantly reduced the CD36-induced HBV replication. We identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. CD36 may represent a potential therapeutic target for the treatment of CHB patients with MS. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Divergent calcium signaling in RBCs from Tropidurus torquatus (Squamata – Tropiduridae strengthen classification in lizard evolution

    Directory of Open Access Journals (Sweden)

    Garcia Célia RS

    2007-08-01

    Full Text Available Abstract Background We have previously reported that a Teiid lizard red blood cells (RBCs such as Ameiva ameiva and Tupinambis merianae controls intracellular calcium levels by displaying multiple mechanisms. In these cells, calcium stores could be discharged not only by: thapsigargin, but also by the Na+/H+ ionophore monensin, K+/H+ ionophore nigericin and the H+ pump inhibitor bafilomycin as well as ionomycin. Moreover, these lizards possess a P2Y-type purinoceptors that mobilize Ca2+ from intracellular stores upon ATP addition. Results Here we report, that RBCs from the tropidurid lizard Tropidurus torquatus store Ca2+ in endoplasmic reticulum (ER pool but unlike in the referred Teiidae, these cells do not store calcium in monensin-nigericin sensitive pools. Moreover, mitochondria from T. torquatus RBCs accumulate Ca2+. Addition of ATP to a calcium-free medium does not increase the [Ca2+]c levels, however in a calcium medium we observe an increase in cytosolic calcium. This is an indication that purinergic receptors in these cells are P2X-like. Conclusion T. torquatus RBCs present different mechanisms from Teiid lizard red blood cells (RBCs, for controlling its intracellular calcium levels. At T. torquatus the ion is only stored at endoplasmic reticulum and mitochondria. Moreover activation of purinergic receptor, P2X type, was able to induce an influx of calcium from extracelullar medium. These studies contribute to the understanding of the evolution of calcium homeostasis and signaling in nucleated RBCs.

  11. Mucin 4 Gene Silencing Reduces Oxidative Stress and Calcium Oxalate Crystal Formation in Renal Tubular Epithelial Cells Through the Extracellular Signal-Regulated Kinase Signaling Pathway in Nephrolithiasis Rat Model

    Directory of Open Access Journals (Sweden)

    Ling Sun

    2018-05-01

    Full Text Available Background/Aims: Nephrolithiasis plagues a great number of patients all over the world. Increasing evidence shows that the extracellular signal-regulated kinase (ERK signaling pathway and renal tubular epithelial cell (RTEC dysfunction and attrition are central to the pathogenesis of kidney diseases. Mucin 4 (MUC4 is reported as an activator of ERK signaling pathway in epithelial cells. In this study, using rat models of calcium oxalate (CaOx nephrolithiasis, the present study aims to define the roles of MUC4 and ERK signaling pathway as contributors to oxidative stress and CaOx crystal formation in RTEC. Methods: Data sets of nephrolithiasis were searched using GEO database and a heat flow map was drawn. Then MUC4 function was predicted. Wistar rats were prepared for the purpose of model establishment of ethylene glycol and ammonium chloride induced CaOx nephrolithiasis. In order to assess the detailed regulatory mechanism of MUC4 silencing on the ERK signaling pathway and RTEC, we used recombinant plasmid to downregulate MUC4 expression in Wistar rat-based models. Samples from rat urine, serum and kidney tissues were reviewed to identify oxalic acid and calcium contents, BUN, Cr, Ca2+ and P3+ levels, calcium crystal formation in renal tubules and MUC4 positive expression rate. Finally, RT-qPCR, Western blot analysis, and ELISA were employed to access oxidative stress state and CaOx crystal formation in RTEC. Results: Initially, MUC4 was found to have an influence on the process of nephrolithiasis. MUC4 was upregulated in the CaOx nephrolithiasis model rats. We proved that the silencing of MUC4 triggered the inactivation of ERK signaling pathway. Following the silencing of MUC4 or the inhibition of ERK signaling pathway, the oxalic acid and calcium contents in rat urine, BUN, Cr, Ca2+ and P3+ levels in rat serum, p-ERK1/2, MCP-1 and OPN expressions in RTEC and H2O2 and MDA levels in the cultured supernatant were downregulated, but the GSH

  12. Allegheny County Supermarkets & Convenience Stores

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Location information for all Supermarkets and Convenience Stores in Allegheny County was produced using the Allegheny County Fee and Permit Data for 2016.

  13. Information from the central stores

    CERN Multimedia

    GS Department

    2010-01-01

    All items sold in the CERN shop (Bldg. 33) are now available in the central stores (Bldg. 73) and can be purchased on-line via EDH “Material Request” or at the “Emergency Desk” of the stores on the ground floor of Bldg. 73. These items are visible in the CERN catalogue under the “SCEM” codes beginning with 92. Department of General Infrastructure Services (GS) GS-SEM Group

  14. Hemoglobin Function in Stored Blood.

    Science.gov (United States)

    1974-08-01

    States during 1973. Several advantages over ACA) are important. Blood stored in CPD maintains higher ./ levels of 2,3-DPG (2,3- diphosphoglycerate ) and a...survival and ATP levels in stored blood is explained by the several functions of ATP which are necessary for cell viability. However, ATP levels do...not correlate with oxygen affinity during storage. Levels of 2,3-DPG determine oxygen affinity and thus hemoglobin function. (12,13) When normal levels

  15. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

    Energy Technology Data Exchange (ETDEWEB)

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

    2010-09-21

    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

  16. Calcium provision to oviparous and viviparous embryos of the reproductively bimodal lizard Lacerta (Zootoca) vivipara.

    Science.gov (United States)

    Stewart, James R; Ecay, Tom W; Heulin, Benoit

    2009-08-01

    Embryos of oviparous squamate reptiles typically obtain calcium from both yolk and eggshell but differ from other oviparous amniotes (turtles, birds and crocodilians) because they are heavily dependent on calcium-rich yolk. Eggs of viviparous squamates lack calcareous eggshells, and embryos receive calcium solely from yolk or from both yolk and placenta. The pattern of calcium mobilization by amniote embryos has been predicted to influence the evolution of viviparity if embryos are dependent on calcium from the eggshell and calcium placentotrophy evolves subsequent to viviparity. We studied the pattern of maternal provision and embryonic utilization of calcium of an oviparous and a viviparous population of the reproductively bimodal lizard Lacerta vivipara to test the hypotheses: (1) oviparous embryos are not dependent on eggshell calcium and (2) calcium content of viviparous hatchlings does not differ from oviparous hatchlings. Our findings do not support either of these hypotheses because oviparous females oviposited eggs with heavily calcified shells and calcium-poor yolk, and embryonic mobilization of shell calcium was greater than for other oviparous squamates. The calcium content of yolk from viviparous females did not differ from oviparous yolk, but viviparous eggs lacked calcareous eggshells. Uterine secretion by viviparous females compensated for the low calcium content of yolk, and placental calcium transfer was among the highest recorded for squamates. The pattern of calcium provision in these two populations suggests that dependence on uterine calcium, either stored temporarily in an eggshell or transferred directly across a placenta, did not constrain the evolution of reproductive mode in this lineage.

  17. El ion calcio: su regulación y función en la célula ß pancreática Ion calcium: its regulation and function in the pancreatic cell

    Directory of Open Access Journals (Sweden)

    Oscar Díaz Horta

    2003-12-01

    Full Text Available En el presente trabajo se realiza una revisión del conocimiento actual sobre la regulación de las concentraciones intracelulares del ion calcio, los principales mecanismos de entrada y salida de este a través de la membrana plasmática, con especial atención en el intercambiador Na+/Ca2+, y la función de este importante segundo mensajero en la secreción de insulina, así como la muerte celular programada de las células ß pancreáticas.The present paper made a review of the present knowledge on regulation of intracellular concentrations of calcium ion, the main mechanisms of inlet/outlet through the plasma membrane, with special attention to Na+/Ca2+, and the function of this important second messenger in insulin secretion and in programmed cell death of pancreatic cells.

  18. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to beta-palmitate and increased calcium absorption pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from IDACE, submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to beta...... (middle or beta) position of the glycerol backbone. Beta-palmitate is considered to be sufficiently characterised. The claimed effect is “beta palmitate enrichment contributes to increase calcium absorption”. The target population proposed by the applicant is infants from birth to 12 months of age......, the Panel took into account the biological plausibility of the mechanism by which beta-palmitate could exert the claimed effect and that three small human intervention studies in preterm and term infants provided some evidence that a higher degree of palmitic acid in the sn-2 position of formula...

  19. Calcium and Bone Metabolism Indices.

    Science.gov (United States)

    Song, Lu

    2017-01-01

    Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) control calcium homeostasis, whereas PTH, 1,25(OH) 2 D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic

  20. CORPORATE REBRANDING OF GRAMEDIA STORE (CORPORATE REBRANDING DI GRAMEDIA STORE

    Directory of Open Access Journals (Sweden)

    Natasha Helena Kairupan

    2016-10-01

    Full Text Available Abstract. The purposes of this research are to determine the stages of analysis, planning, and evaluation of corporate rebranding process of Gramedia Book Store to be Gramedia Store to rise stakeholder’s awareness. The method used is descriptive qualitative with positivism paradigm. The technique of collecting data through in-depth interview, observation, and literature study. The result of this research showed the analysis stage by analyzing the market through insights and foresights, brand audit through SWOT analysis, and identifying opportunities. The planning stage is by determine the purpose of the planning process and then determine the target audience, consist of external and internal customer. The planning of external customer by renaming and change of corporate identity, and marketing planning using communication channel (above the line and below the line. The planning of internal customer by Brand Induction, training, inspiration briefing at store, and innovation competition. The evaluation of rebranding process of Gramedia Store is having a focus group discussion with customer, media monitoring, and presentation to BOD. Keywords : Process, Corporate Rebranding, Stakeholder Awareness, Corporate Identity, Gramedia Store Abstrak.Tujuan penelitian ini adalah untuk mengetahui bagaimana tahapan analisis, perencanaan, dan evaluasi proses corporate rebranding Gramedia Book Store menjadi Gramedia Store untuk meningkatkan stakeholder awareness. Pendekatan yang digunakan adalah kualitatif dengan paradigma positivisme dan jenis studi deksriptif. Teknik pengumpulan data yang dilakukan melalui wawancara mendalam, observasi, dan studi pustaka. Berdasarkan hasil penelitian, tahapan analisis dilakukan dengan menganalisis pasar melalui insights dan foresights, audit merek dengan analisis SWOT, dan mengidentifikasi peluang. Dalam tahapan perencanaan dengan menentukan tujuan kemudian menentukan target audiens, yaitu eksternal dan internal. Perencanaan

  1. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-01-01

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

  2. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture.

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-09-18

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Comparing Relational and Ontological Triple Stores in Healthcare Domain

    Directory of Open Access Journals (Sweden)

    Ozgu Can

    2017-01-01

    Full Text Available Today’s technological improvements have made ubiquitous healthcare systems that converge into smart healthcare applications in order to solve patients’ problems, to communicate effectively with patients, and to improve healthcare service quality. The first step of building a smart healthcare information system is representing the healthcare data as connected, reachable, and sharable. In order to achieve this representation, ontologies are used to describe the healthcare data. Combining ontological healthcare data with the used and obtained data can be maintained by storing the entire health domain data inside big data stores that support both relational and graph-based ontological data. There are several big data stores and different types of big data sets in the healthcare domain. The goal of this paper is to determine the most applicable ontology data store for storing the big healthcare data. For this purpose, AllegroGraph and Oracle 12c data stores are compared based on their infrastructural capacity, loading time, and query response times. Hence, healthcare ontologies (GENE Ontology, Gene Expression Ontology (GEXO, Regulation of Transcription Ontology (RETO, Regulation of Gene Expression Ontology (REXO are used to measure the ontology loading time. Thereafter, various queries are constructed and executed for GENE ontology in order to measure the capacity and query response times for the performance comparison between AllegroGraph and Oracle 12c triple stores.

  4. TruStore: Implementing a Trusted Store for Android

    OpenAIRE

    Yury, Zhauniarovich; Olga, Gadyatskaya; Bruno, Crispo

    2013-01-01

    In the Android ecosystem, the process of verifying the integrity of downloaded apps is left to the user. Different from other systems, e.g., Apple, App Store, Google does not provide any certified vetting process for the Android apps. This choice has a lot of advantages but it is also the open door to possible attacks as the recent one shown by Bluebox. To address this issue, we present how to enable the deployment of application certification service, we called TruStores, for the Android pla...

  5. Regulation of physicochemical properties, osteogenesis activity, and fibroblast growth factor-2 release ability of β-tricalcium phosphate for bone cement by calcium silicate

    International Nuclear Information System (INIS)

    Su, Ching-Chuan; Kao, Chia-Tze; Hung, Chi-Jr; Chen, Yi-Jyun; Huang, Tsui-Hsien; Shie, Ming-You

    2014-01-01

    β-Tricalcium phosphate (β-TCP) is an osteoconductive material. For this research we have combined it with a low degradation calcium silicate (CS) to enhance its bioactive and osteostimulative properties. To check its effectiveness, a series of β-TCP/CS composites with different ratios were prepared to make new bioactive and biodegradable biocomposites for bone repair. Formation of bone-like apatite, the diametral tensile strength, and weight loss of composites were considered before and after immersion in simulated body fluid (SBF). In addition, we also examined the effects of fibroblast growth factor-2 (FGF-2) released from β-TCP/CS composites and in vitro human dental pulp cell (hDPC) and studied its behavior. The results showed that the apatite deposition ability of the β-TCP/CS composites was enhanced as the CS content was increased. For composites with more than 50% CS contents, the samples were completely covered by a dense bone-like apatite layer. At the end of the immersion point, weight losses of 19%, 24%, 33%, 42%, and 51% were observed for the composites containing 0%, 30%, 50%, 70% and 100% β-TCP cements, respectively. In vitro cell experiments show that the CS-rich composites promote human dental pulp cell (hDPC) proliferation and differentiation. However, when the CS quantity in the composite is less than 70%, the amount of cells and osteogenesis protein of hDPCs was stimulated by FGF-2 released from β-TCP/CS composites. The combination of FGF-2 in degradation of β-TCP and osteogenesis of CS gives a strong reason to believe that these calcium-based composite cements may prove to be promising bone repair materials. - Highlights: • CS improved physicochemical properties and osteogenic activity of β-TCP. • The higher the CS in the cement, the shorter the setting time and the higher the DTS. • The cell behavior was stimulated by FGF-2 released from composite containing 50% CS. • β-TCP/CS composite with FGF-2 has optimal properties for

  6. Calcium oxide/carbon dioxide reactivity in a packed bed reactor of a chemical heat pump for high-temperature gas reactors

    International Nuclear Information System (INIS)

    Kato, Yukitaka; Yamada, Mitsuteru; Kanie, Toshihiro; Yoshizawa, Yoshio

    2001-01-01

    The thermal performance of a chemical heat pump that uses a calcium oxide/carbon dioxide reaction system was discussed as a heat storage system for utilizing heat output from high temperature gas reactors (HTGR). Calcium oxide/carbon dioxide reactivity for the heat pump was measured using a packed bed reactor containing 1.0 kg of reactant. The reactor was capable of storing heat at 900 deg. C by decarbonation of calcium carbonate and generating up to 997 deg. C by carbonation of calcium oxide. The amount of stored heat in the reactor was 800-900 kJ kg -1 . The output temperature of the reactor could be controlled by regulating the carbonation pressure. The thermal storage performance of the reactor was superior to that of conventional sensible heat storage systems. A heat pump using this CaO/CO 2 reactor is expected to contribute to thermal load leveling and to realize highly efficient utilization of HTGR output due to the high heat storage density and high-quality temperature output of the heat pump

  7. Calcium and magnesium determination

    International Nuclear Information System (INIS)

    Bhattacharya, S.K.

    1982-01-01

    The roles of calcium and magnesium in human health and disease have been extensively studied. Calcium and magnesium have been determined in biological specimens by atomic absorption spectroscopy using stiochiometric nitrous oxide-acetylene flame

  8. Fenoprofen calcium overdose

    Science.gov (United States)

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

  9. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used ...

  10. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to lactose and increase in calcium absorption leading to an increase in calcium retention (ID 668) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to lactose and increase in calcium absorption leading to an increase in calcium retention. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member...... States or directly from stakeholders. The food constituent that is the subject of the health claim is lactose. The Panel considers that lactose is sufficiently characterised. The claimed effect is “calcium absorption”. The target population is assumed to be the general population. The Panel notes...... between the consumption of lactose and an increase in calcium absorption leading to an increase in calcium retention....

  11. Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology

    Directory of Open Access Journals (Sweden)

    Li XinMin

    2007-09-01

    Full Text Available Abstract Background Calcium (Ca2+ has recently been shown to selectively increase the activity of monoamine oxidase-A (MAO-A, a mitochondria-bound enzyme that generates peroxyradicals as a natural by-product of the deamination of neurotransmitters such as serotonin. It has also been suggested that increased intracellular free Ca2+ levels as well as MAO-A may be contributing to the oxidative stress associated with Alzheimer disease (AD. Results Incubation with Ca2+ selectively increases MAO-A enzymatic activity in protein extracts from mouse hippocampal HT-22 cell cultures. Treatment of HT-22 cultures with the Ca2+ ionophore A23187 also increases MAO-A activity, whereas overexpression of calbindin-D28K (CB-28K, a Ca2+-binding protein in brain that is greatly reduced in AD, decreases MAO-A activity. The effects of A23187 and CB-28K are both independent of any change in MAO-A protein or gene expression. The toxicity (via production of peroxyradicals and/or chromatin condensation associated with either A23187 or the AD-related β-amyloid peptide, which also increases free intracellular Ca2+, is attenuated by MAO-A inhibition in HT-22 cells as well as in primary hippocampal cultures. Conclusion These data suggest that increases in intracellular Ca2+ availability could contribute to a MAO-A-mediated mechanism with a role in AD-related oxidative stress.

  12. Orientation of the calcium channel beta relative to the alpha(12.2 subunit is critical for its regulation of channel activity.

    Directory of Open Access Journals (Sweden)

    Iuliia Vitko

    Full Text Available BACKGROUND: The Ca(vbeta subunits of high voltage-activated Ca(2+ channels control the trafficking and biophysical properties of the alpha(1 subunit. The Ca(vbeta-alpha(1 interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(12.2, then testing for Ca(vbeta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6. This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(vbeta with respect to alpha(12.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively. Again, the ability of Ca(vbeta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(vbeta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(vbeta subunit relative to the alpha(12.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(vbeta to regulate channel activity.

  13. Method of storing solidification products

    International Nuclear Information System (INIS)

    Tani, Yutaro.

    1985-01-01

    Purpose: To enable to efficiently and satisfactorily cool and store solidification products of liquid wastes generated from the reactor spent fuel reprocessing process by a simple facility. Method: Liquid wastes generated from the reactor spent fuel reprocessing process are caused to flow from the upper opening to the inside of a spherical canistor. The opening of the spherical canistor is welded with a lid by a remote control and the liquid wastes are tightly sealed within the spherical canistor as glass solidification products. Spherical canistors having the solidification products tightly sealed therein are sent into and stored in a hopper by the remote control. Further, a blower is driven upon storing to suck cooling air from the cooling air intake port to the inside of the hopper to absorb the decay heat of radioactive materials in the solidification products and the air is discharged from the duct and through the stack to the atmosphere. (Kawakami, Y.)

  14. Calcium en cardioplegie

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Meijler, F.L.

    1985-01-01

    Coronary perfusion with a calcium-free solution, followed by reperfusion with a calcium containing solution, may result in acute myocardial cell death and in irreversible loss of the e1ectrical and mechanical activity of the heart. This phenomenon is known as the calcium paradox. A number of

  15. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

    Science.gov (United States)

    Yamagishi, Yuya; Tessier-Lavigne, Marc

    2015-01-01

    Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled

  16. Method of storing fissile mateiral

    International Nuclear Information System (INIS)

    Onoshita, Toshio; Ishitobi, Masuhiro

    1989-01-01

    Upon storing nuclear fissile materials in a storing building, vessels packed with fissile materials are inserted into a containing chamber divided with partition walls comprising neutron absorbers and neutron moderators. Thus, released neutrons permeating the vessel are moderated by the neutron moderators and then absorbed by the neutron absorbers. Accordingly, the neutron absorbing effect by the neutron absorbers is improved, and irradiation of neutrons released from one of vessels to the other of vessels can be suppressed. Accordingly, it is possible to shorten the distance between the vessels in a contained state as much as possible, while securing the critical safety, to improve the containing density during storage. (T.M.)

  17. A new functional role for mechanistic/mammalian target of rapamycin complex 1 (mTORC1 in the circadian regulation of L-type voltage-gated calcium channels in avian cone photoreceptors.

    Directory of Open Access Journals (Sweden)

    Cathy Chia-Yu Huang

    Full Text Available In the retina, the L-type voltage-gated calcium channels (L-VGCCs are responsible for neurotransmitter release from photoreceptors and are under circadian regulation. Both the current densities and protein expression of L-VGCCs are significantly higher at night than during the day. However, the underlying mechanisms of circadian regulation of L-VGCCs in the retina are not completely understood. In this study, we demonstrated that the mechanistic/mammalian target of rapamycin complex (mTORC signaling pathway participated in the circadian phase-dependent modulation of L-VGCCs. The activities of the mTOR cascade, from mTORC1 to its downstream targets, displayed circadian oscillations throughout the course of a day. Disruption of mTORC1 signaling dampened the L-VGCC current densities, as well as the protein expression of L-VGCCs at night. The decrease of L-VGCCs at night by mTORC1 inhibition was in part due to a reduction of L-VGCCα1 subunit translocation from the cytosol to the plasma membrane. Finally, we showed that mTORC1 was downstream of the phosphatidylionositol 3 kinase-protein kinase B (PI3K-AKT signaling pathway. Taken together, mTORC1 signaling played a role in the circadian regulation of L-VGCCs, in part through regulation of ion channel trafficking and translocation, which brings to light a new functional role for mTORC1: the modulation of ion channel activities.

  18. Breastfeeding FAQs: Safely Storing Breast Milk

    Science.gov (United States)

    ... Search English Español Breastfeeding FAQs: Safely Storing Breast Milk KidsHealth / For Parents / Breastfeeding FAQs: Safely Storing Breast ... may have. How do I store my breast milk? You can freeze and/or refrigerate your pumped ( ...

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

    OpenAIRE

    Llach, Anna; Molina, Cristina E.; Alvarez Lacalle, Enrique; Tort, Lluis; Benítez, Raul; Hove, Leif

    2011-01-01

    Calcium release from the sarcoplasmic reticulum (SR) plays a central role in the regulation of cardiac contraction and rhythm in mammals and humans but its role is controversial in teleosts. Since the zebrafish is an emerging model for studies of cardiovascular function and regeneration we here sought to determine if basic features of SR calcium release are phylogenetically conserved. Confocal calcium imaging was used to detect spontaneous calcium release (calcium sparks and waves) from...

  20. Calcium and contribution to the normal development of bones: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2016-01-01

    Following an application from Specialised Nutrition Europe (formerly IDACE), submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked...

  1. Intracellular pH (pHin) and cytosolic calcium ([Ca2+]cyt) regulation via ATPases: studies in cell populations, single cells, and subcellular compartments

    Science.gov (United States)

    Rojas, Jose D.; Sanka, Shankar C.; Gyorke, Sandor; Wesson, Donald E.; Minta, Akwasi; Martinez-Zaguilan, Raul

    1999-07-01

    Changes in pHin and (Ca2+)cyt are important in the signal transduction mechanisms leading to many physiological responses including cell growth, motility, secretion/exocytosis, etc. The concentrations of these ions are regulated via primary and secondary ion transporting mechanisms. In diabetes, specific pH and Ca2+ regulatory mechanism might be altered. To study these ions, we employ fluorescence spectroscopy, and cell imagin spectroscopy/confocal microscopy. pH and Ca2+ indicators are loaded in the cytosol with acetoxymethyl ester forms of dyes, and in endosomal/lysosomal (E/L) compartments by overnight incubation of cells with dextran- conjugated ion fluorescent probes. We focus on specific pH and Ca2+ regulatory systems: plasmalemmal vacuolar- type H+-ATPases (pm V-ATPases) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA). As experimental models, we employ vascular smooth muscle (VSM) and microvascular endothelial cells. We have chosen these cells because they are important in blood flow regulation and in angiogenesis. These processes are altered in diabetes. In many cell types, ion transport processes are dependent on metabolism of glucose for maximal activity. Our main findings are: (a) glycolysis coupling the activity of SERCA is required for cytosolic Ca2+ homeostasis in both VSM and microvascular endothelial cells; (b) E/L compartments are important for pH and Ca2+ regulation via H+-ATPases and SERCA, respectively; and (c) pm-V- ATPases are important for pHin regulation in microvascular endothelial cells.

  2. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N

    2005-01-01

    Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL) secretion in various vertebrates including the tilapia, Oreochromis mossambicus. The mechanism by which GnRH regulates lactotroph cell function is poorly understood. Using the advantageous characteristics of the teleost...

  3. Calcium microdomains near R-type calcium channels control the induction of presynaptic LTP at parallel fiber to Purkinje cell synapses

    Science.gov (United States)

    Myoga, Michael H.; Regehr, Wade G.

    2011-01-01

    R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium-calmodulin sensitive potassium channel that in turn regulates postsynaptic hippocampal LTP. Here we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Although most presynaptic calcium influx is through N-type and P/Q-type calcium channels, blocking these channels does not disrupt PF-LTP, but blocking R-type calcium channels does. Moreover, global calcium signaling cannot account for the calcium dependence of PF-LTP because R-type channels contribute modestly to overall calcium entry. These findings indicate that within presynaptic terminals, R-type calcium channels produce calcium microdomains that evoke presynaptic LTP at moderate frequencies that do not greatly increase global calcium levels,. PMID:21471358

  4. Store operations to maintain cache coherence

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

    2017-08-01

    In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

  5. Store operations to maintain cache coherence

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

    2017-09-12

    In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

  6. Stores, Weight and Inertial System Facility

    Data.gov (United States)

    Federal Laboratory Consortium — This facility provides stores weight, center of gravity, and inertia measurements in support of weapon/aircraft compatibility testing. System provides store weight...

  7. Storing XML Documents in Databases

    NARCIS (Netherlands)

    A.R. Schmidt; S. Manegold (Stefan); M.L. Kersten (Martin); L.C. Rivero; J.H. Doorn; V.E. Ferraggine

    2005-01-01

    textabstractThe authors introduce concepts for loading large amounts of XML documents into databases where the documents are stored and maintained. The goal is to make XML databases as unobtrusive in multi-tier systems as possible and at the same time provide as many services defined by the XML

  8. Storing Peanuts in Grain Bags

    Science.gov (United States)

    A study was executed to determine the potential of storing farmers stock peanuts and shelled peanuts for crushing in hermetically sealed grain bags. The objectives of the study were to evaluate equipment for loading and unloading the grain bags, the capacity of the grain bags, and the changes in qu...

  9. Storing biomass in round bales

    Energy Technology Data Exchange (ETDEWEB)

    Summer, H.R.; Hellwig, R.E.; Monroe, G.E.

    1984-09-01

    Biomass fuels, in the form of crop residues, were stored outside in large round bales. The influence of rainfall on bale mass and the change in apparent average moisture content (A.A.M.C) was studied. Covering the bales with large sheets of polyethylene was found to be the most effective way of reducing moisture penetration.

  10. s larvae to stored cocoa

    African Journals Online (AJOL)

    olufunke oyedokun

    2015-04-22

    Apr 22, 2015 ... theobromine levels decrease, which in turn affects the colour, flavor (aroma) of the beans (Lagunes et al., 2007;. Rodriguez-Campos et al., 2011) and the organoleptic properties of the dried cocoa beans in store (Camu et al.,. 2008). Freshly harvested cocoa beans require fermentation for 5 - 7 days before ...

  11. Dependence of cerebral arterial contractions on intracellularly stored Ca++.

    Science.gov (United States)

    Sasaki, T; Kassell, N F; Zuccarello, M

    1986-01-01

    The purpose of the present study was to evaluate the dependence of the arterial contractions induced by different vasoactive agents upon intracellularly stored calcium in canine versus monkey cerebral arteries. The potency for inducing contractions in Ca++-free media was in the order of 9,11-epithio-11,12-metano-thromboxane A2 (STXA2) greater than prostaglandin F2 alpha (PGF2 alpha) much greater than serotonin greater than K+ in canine basilar arteries, and STXA2 greater than PGF2 alpha much greater than serotonin = K+ in monkey basilar arteries.

  12. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2005-01-01

    into biological effects in bone. Intercellular calcium waves are increases in intracellular calcium concentration in single cells, subsequently propagating to adjacent cells, and can be a possible mechanism for the coupling of bone formation to bone resorption. The aim of the present studies was to investigate...... whether bone cells are capable of communicating via intercellular calcium signals, and determine by which mechanisms the cells propagate the signals. First, we found that osteoblastic cells can propagate intercellular calcium transients upon mechanical stimulation, and that there are two principally...... different mechanisms for this propagation. One mechanism involves the secretion of a nucleotide, possibly ATP, acting in an autocrine action to purinergic P2Y2 receptors on the neighboring cells, leading to intracellular IP3 generation and subsequent release of calcium from intracellular stores. The other...

  13. Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Timmermann, D B; Lund, Trine Meldgaard; Belhage, B

    2001-01-01

    The physiological significance and subcellular distribution of voltage dependent calcium channels was defined using calcium channel blockers to inhibit potassium induced rises in cytosolic calcium concentration in cultured mouse neocortical neurons. The cytosolic calcium concentration was measured...... channels were differentially distributed in somata, neurites and nerve terminals. omega-conotoxin MVIIC (omega-CgTx MVIIC) inhibited approximately 40% of the Ca(2+)-rise in both somata and neurites and 60% of the potassium induced [3H]GABA release, indicating that the Q-type channel is the quantitatively...... most important voltage dependent calcium channel in all parts of the neuron. After treatment with thapsigargin the increase in cytosolic calcium was halved, indicating that calcium release from thapsigargin sensitive intracellular calcium stores is an important component of the potassium induced rise...

  14. Effective Factors in Environmental Health Status of Grocery Stores

    Directory of Open Access Journals (Sweden)

    Mehdi Asadi

    2012-08-01

    Full Text Available Aims of the Study: This study was carried out to determine the effective factors in environmental health status of grocery stores in the city of Qom (located in the center of Iran. Materials & Methods: In this cross-sectional study, 283 grocery stores from 3 different regions were selected randomly using stratified sampling. Data were gathered through observation, interview, and questionnaire. The questionnaire consisted of two sections: section 1 dealt with some shop managers’ features including the age, educational level, job satisfaction, passing “food and occupational hygiene training courses”, store ownership, duration of employment, and features of stores including their location (Region and environmental health condition. And section 2 dealt with the important aspects of regulations of Article 13. The data analyzed using statistical procedures such as Spearman Rank Correlation and Multivariate Regression Analysis. P-values less than 0.05 were considered as statistically significant. Results: Among the investigated factors, the manager’s educational level had a greater impact on the environmental health conditions of grocery stores. The ownership status of grocery stores, Job satisfaction and passing “food and occupational hygiene training courses” were next in the ranking, respectively (p <0.001 for all measures, except for shop ownership, for which p-value was <0.02. Conclusions: Planning and implementation of effective operational and strategic programs addressing the above mentioned issues seems to be necessary. Such programs will improve the health status of the stores over time.

  15. Effect of dietary calcium and phosphorus on intestinal calcium absorption and vitamin D metabolism

    International Nuclear Information System (INIS)

    Ribovich, M.L.; DeLuca, H.F.

    1978-01-01

    To understand better dietary regulation of intestinal calcium absorption, a quantitative assessment of the metabolites in plasma and duodenum of rats given daily doses of radioactive vitamin D 3 and diets differing in calcium and phosphorus content was made. All known vitamin D metabolites were ultimately identified by high-pressure liquid chromatography. In addition to the known metabolites (25-hydroxyvitamin D 3 , 24,25-dihydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , 25,26-dihydroxyvitamin D 3 , and 1,24,25-trihydroxyvitamin D 3 ), several new and unidentified metabolites were found. In addition to 1,25-dihydroxyvitamin D 3 and 1,24,25-trihydroxyvitamin D 3 , the levels of some of the unknown metabolites could be correlated with intestinal calcium transport. However, whether or not any of these metabolites plays a role in the stimulation of intestinal calcium absorption by low dietary calcium or low dietary phosphorus remains unknown

  16. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jorgensen, N R; Geist, S T; Civitelli, R

    1997-01-01

    mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein......Many cells coordinate their activities by transmitting rises in intracellular calcium from cell to cell. In nonexcitable cells, there are currently two models for intercellular calcium wave propagation, both of which involve release of inositol trisphosphate (IP3)- sensitive intracellular calcium...... stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied...

  17. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Recker, R.R.

    1985-01-01

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  18. Model/School Store Management Guide.

    Science.gov (United States)

    North Dakota State Board for Vocational Education, Bismarck.

    This teacher-coordinator manual assists in planning, organizing, directing, and evaluating student learning experiences associated with either a model store, school store, or combination. (A model store in a marketing laboratory simulates marketing functions; the school store markets merchandise to fellow students, faculty, and/or the public.)…

  19. Storing XML Documents in Databases

    OpenAIRE

    Schmidt, A.R.; Manegold, Stefan; Kersten, Martin; Rivero, L.C.; Doorn, J.H.; Ferraggine, V.E.

    2005-01-01

    textabstractThe authors introduce concepts for loading large amounts of XML documents into databases where the documents are stored and maintained. The goal is to make XML databases as unobtrusive in multi-tier systems as possible and at the same time provide as many services defined by the XML standards as possible. The ubiquity of XML has sparked great interest in deploying concepts known from Relational Database Management Systems such as declarative query languages, transactions, indexes ...

  20. Method of storing radioactive wastes

    International Nuclear Information System (INIS)

    Adachi, Toshio; Hiratake, Susumu.

    1980-01-01

    Purpose: To reduce the radiation doses externally irradiated from treated radioactive waste and also reduce the separation of radioactive nuclide due to external environmental factors such as air, water or the like. Method: Radioactive waste adhered with radioactive nuclide to solid material is molten to mix and submerge the radioactive nuclide adhered to the surface of the solid material into molten material. Then, the radioactive nuclide thus mixed is solidified to store the waste in solidified state. (Aizawa, K.)

  1. Specialty Store and Multi-Brand Store loyalty: An Indian consumer perspective

    Directory of Open Access Journals (Sweden)

    Sarabjot Singh

    2013-12-01

    Full Text Available In the competitive era of retailing, retailers need to understand the importance of store format preferences. The study aimed to understand consumer store loyalty; in-depth interview was conducted to examine consumer store loyalty antecedents for two retail formats: specialty stores and multi brand stores. The study conceptualizes store loyalty factors like program loyalty, trust and brand commitment. Trust and brand commitment act as mediating factors between store image and store loyalty formats, and also between brand image and store loyalty formats. The findings highlight how consumer store loyalty preference differ for these two formats.

  2. STIM and Orai isoform expression in pregnant human myometrium: a potential role in calcium signaling during pregnancy.

    Directory of Open Access Journals (Sweden)

    Evonne eChin-Smith

    2014-05-01

    Full Text Available Store-operated calcium (Ca2+ entry (SOCE can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3 have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at caesarean section from women at the time of preterm no labor (PTNL, preterm labor (PTL, term non-labor (TNL and term with labor (TL; primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM. STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy.

  3. Increasing T-type calcium channel activity by β-adrenergic stimulation contributes to β-adrenergic regulation of heart rates.

    Science.gov (United States)

    Li, Yingxin; Zhang, Xiaoxiao; Zhang, Chen; Zhang, Xiaoying; Li, Ying; Qi, Zhao; Szeto, Christopher; Tang, Mingxin; Peng, Yizhi; Molkentin, Jeffery D; Houser, Steven R; Xie, Mingxing; Chen, Xiongwen

    2018-04-01

    Cav3.1 T-type Ca 2+ channel current (I Ca-T ) contributes to heart rate genesis but is not known to contribute to heart rate regulation by the sympathetic/β-adrenergic system (SAS). We show that the loss of Cav3.1 makes the beating rates of the heart in vivo and perfused hearts ex vivo, as well as sinoatrial node cells, less sensitive to β-adrenergic stimulation; it also renders less conduction acceleration through the atrioventricular node by β-adrenergic stimulation. Increasing Cav3.1 in cardiomyocytes has the opposite effects. I Ca-T in sinoatrial nodal cells can be upregulated by β-adrenergic stimulation. The results of the present study add a new contribution to heart rate regulation by the SAS system and provide potential new mechanisms for the dysregulation of heart rate and conduction by the SAS in the heart. T-type Ca 2+ channel can be a target for heart disease treatments that aim to slow down the heart rate ABSTRACT: Cav3.1 (α 1G ) T-type Ca 2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular (AV) nodal cells and contributes to heart rate (HR) genesis and AV conduction. However, its role in HR regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear. In the present study, L- (I Ca-L ) and T-type (I Ca-T ) Ca 2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. I Ca-T was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of isoproterenol (ISO) were infused via the jugular vein and the HR was recorded. The EC 50 of the HR response to ISO was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by ISO was greater in TG mice but less in KO mice. In Langendorff-perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after

  4. Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons.

    Science.gov (United States)

    Llorente-Folch, Irene; Rueda, Carlos B; Amigo, Ignacio; del Arco, Araceli; Saheki, Takeyori; Pardo, Beatriz; Satrústegui, Jorgina

    2013-08-28

    Neuronal respiration is controlled by ATP demand and Ca2+ but the roles played by each are unknown, as any Ca2+ signal also impacts on ATP demand. Ca2+ can control mitochondrial function through Ca2+-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix after Ca2+ transport through the Ca2+ uniporter. We have studied the role of Ca2+ signaling in the regulation of mitochondrial respiration in intact mouse cortical neurons in basal conditions and in response to increased workload caused by increases in [Na+]cyt (veratridine, high-K+ depolarization) and/or [Ca2+]cyt (carbachol). Respiration in nonstimulated neurons on 2.5-5 mm glucose depends on ARALAR-malate aspartate shuttle (MAS), with a 46% drop in aralar KO neurons. All stimulation conditions induced increased OCR (oxygen consumption rate) in the presence of Ca2+, which was prevented by BAPTA-AM loading (to preserve the workload), or in Ca2+-free medium (which also lowers cell workload). SCaMC-3 limits respiration only in response to high workloads and robust Ca2+ signals. In every condition tested Ca2+ activation of ARALAR-MAS was required to fully stimulate coupled respiration by promoting pyruvate entry into mitochondria. In aralar KO neurons, respiration was stimulated by veratridine, but not by KCl or carbachol, indicating that the Ca2+ uniporter pathway played a role in the first, but not in the second condition, even though KCl caused an increase in [Ca2+]mit. The results suggest a requirement for ARALAR-MAS in priming pyruvate entry in mitochondria as a step needed to activate respiration by Ca2+ in response to moderate workloads.

  5. The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments

    Directory of Open Access Journals (Sweden)

    M. Garbuglia

    1999-10-01

    Full Text Available The Ca2+-modulated, dimeric proteins of the EF-hand (helix-loop-helix type, S100A1 and S100B, that have been shown to inhibit microtubule (MT protein assembly and to promote MT disassembly, interact with the type III intermediate filament (IF subunits, desmin and glial fibrillary acidic protein (GFAP, with a stoichiometry of 2 mol of IF subunit/mol of S100A1 or S100B dimer and an affinity of 0.5-1.0 µM in the presence of a few micromolar concentrations of Ca2+. Binding of S100A1 and S100B results in inhibition of desmin and GFAP assemblies into IFs and stimulation of the disassembly of preformed desmin and GFAP IFs. S100A1 and S100B interact with a stretch of residues in the N-terminal (head domain of desmin and GFAP, thereby blocking the head-to-tail process of IF elongation. The C-terminal extension of S100A1 (and, likely, S100B represents a critical part of the site that recognizes desmin and GFAP. S100B is localized to IFs within cells, suggesting that it might have a role in remodeling IFs upon elevation of cytosolic Ca2+ concentration by avoiding excess IF assembly and/or promoting IF disassembly in vivo. S100A1, that is not localized to IFs, might also play a role in the regulation of IF dynamics by binding to and sequestering unassembled IF subunits. Together, these observations suggest that S100A1 and S100B may be regarded as Ca2+-dependent regulators of the state of assembly of two important elements of the cytoskeleton, IFs and MTs, and, potentially, of MT- and IF-based activities.

  6. Understanding Retailers’ Acceptance of Virtual Stores

    OpenAIRE

    Irene Y.L. Chen

    2010-01-01

    The acceptance of e-commerce among consumers has stimulated the rise of virtual stores. Increasing traditional retailers or people who do not have sufficient capital for maintaining a brick-and-mortar store have considered using virtual stores to reach global market. In the e-commerce literature, there has been rich research evidence concerning consumers’ acceptance of virtual stores. However, rigorous academic research on retailers’ acceptance of virtual stores is relatively scarce today. Th...

  7. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  8. Dengue and Calcium

    OpenAIRE

    Shivanthan, Mitrakrishnan C; Rajapakse, Senaka

    2014-01-01

    Dengue is potentially fatal unless managed appropriately. No specific treatment is available and the mainstay of treatment is fluid management with careful monitoring, organ support, and correction of metabolic derangement. Evidence with regards to the role of calcium homeostasis in dengue is limited. Low blood calcium levels have been demonstrated in dengue infection and hypocalcemia maybe more pronounced in more severe forms. The cause of hypocalcemia is likely to be multifactorial. Calcium...

  9. Inventory of Tank Farm equipment stored or abandoned aboveground

    International Nuclear Information System (INIS)

    Hines, S.C.; Lakes, M.E.

    1994-01-01

    This document provides an inventory of Tank Farm equipment stored or abandoned aboveground and potentially subject to regulation. This inventory was conducted in part to ensure that Westinghouse Hanford Company (WHC) does not violate dangerous waste laws concerning storage of potentially contaminated equipment/debris that has been in contact with dangerous waste. The report identifies areas inventoried and provides photographs of equipment

  10. Drifting temperature climate control for archives and stores

    DEFF Research Database (Denmark)

    Klenz Larsen, Poul; Padfield, Tim; Ryhl-Svendsen, Morten

    2017-01-01

    The climate within museum stores and archives can be regulated by dehumidifying a building whose temperature is allowed to vary seasonally without explicit control. The ground beneath the building provides thermal inertia to hold the annual temperature cycle around 8 – 16°C, in northern Europe...

  11. 41 CFR 109-27.5004 - Sub-stores.

    Science.gov (United States)

    2010-07-01

    ... to the users, serve emergencies, provide economy in transportation, reduce shop and site stocks, and... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Sub-stores. 109-27.5004 Section 109-27.5004 Public Contracts and Property Management Federal Property Management Regulations...

  12. Fermentation of calcium-fortified soymilk with Lactobacillus: effects on calcium solubility, isoflavone conversion, and production of organic acids.

    Science.gov (United States)

    Tang, A L; Shah, N P; Wilcox, G; Walker, K Z; Stojanovska, L

    2007-11-01

    The objective of this study was to enhance calcium solubility and bioavailability from calcium-fortified soymilk by fermentation with 7 strains of Lactobacillus, namely, L. acidophilus ATCC 4962, ATCC33200, ATCC 4356, ATCC 4461, L. casei ASCC 290, L. plantarum ASCC 276, and L. fermentum VRI-003. The parameters that were used are viability, pH, calcium solubility, organic acid, and biologically active isoflavone aglycone content. Calcium-fortified soymilk made from soy protein isolate was inoculated with these probiotic strains, incubated for 24 h at 37 degrees C, then stored for 14 d at 4 degrees C. Soluble calcium was measured using atomic absorption spectrophotometry (AA). Organic acids and bioactive isoflavone aglycones, including diadzein, genistein, and glycetein, were measured using HPLC. Viability of the strains in the fermented calcium-fortified soymilk was > 8.5 log(10) CFU/g after 24 h fermentation and this was maintained for 14-d storage at 4 degrees C. After 24 h, there was a significant increase (P casei ASCC 290 demonstrated the highest increase with 89.3% and 87.0% soluble calcium after 24 h, respectively. The increase in calcium solubility observed was related to lowered pH associated with production of lactic and acetic acids. Fermentation significantly increased (P < 0.05) the level of conversion of isoflavones into biologically active aglycones, including diadzein, genistein, and glycetein. Our results show that fermenting calcium-fortified soymilk with the selected probiotics can potentially enhance the calcium bioavailability of calcium-fortified soymilk due to increased calcium solubility and bioactive isoflavone aglycone enrichment.

  13. The Voltage-Dependent Anion Channel 1 (AtVDAC1 Negatively Regulates Plant Cold Responses during Germination and Seedling Development in Arabidopsis and Interacts with Calcium Sensor CBL1

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Li

    2013-01-01

    Full Text Available The voltage-dependent anion channel (VDAC, a highly conserved major mitochondrial outer membrane protein, plays crucial roles in energy metabolism and metabolite transport. However, knowledge about the roles of the VDAC family in plants is limited. In this study, we investigated the expression pattern of VDAC1 in Arabidopsis and found that cold stress promoted the accumulation of VDAC1 transcripts in imbibed seeds and mature plants. Overexpression of VDAC1 reduced tolerance to cold stress in Arabidopsis. Phenotype analysis of VDAC1 T-DNA insertion mutant plants indicated that a vdac1 mutant line had faster germination kinetics under cold treatment and showed enhanced tolerance to freezing. The yeast two-hybrid system revealed that VDAC1 interacts with CBL1, a calcium sensor in plants. Like the vdac1, a cbl1 mutant also exhibited a higher seed germination rate. We conclude that both VDAC1 and CBL1 regulate cold stress responses during seed germination and plant development.

  14. Calcium Channel Blockers

    Science.gov (United States)

    ... Certain calcium channel blockers interact with grapefruit products. Kaplan NM, et al. Treatment of hypertension: Drug therapy. In: Kaplan's Clinical Hypertension. 11th ed. Philadelphia, Pa.: Wolters Kluwer ...

  15. Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease

    Directory of Open Access Journals (Sweden)

    Zippelius Annette

    2009-06-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca2+ elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT and G93A (SH-SY5YG93A expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. Conclusion In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations

  16. Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury

    DEFF Research Database (Denmark)

    Zhang, Ming Dong; Tortoriello, Giuseppe; Hsueh, Brian

    2014-01-01

    , and nerve injury-induced regulation of NECAB1/NECAB2 in mouse dorsal root ganglia (DRGs) and spinal cord. In DRGs, NECAB1/2 are expressed in around 70% of mainly small- and medium-sized neurons. Many colocalize with calcitonin gene-related peptide and isolectin B4, and thus represent nociceptors. NECAB1....../2 neurons are much more abundant in DRGs than the Ca2+-binding proteins (parvalbumin, calbindin, calretinin, and secretagogin) studied to date. In the spinal cord, the NECAB1/2 distribution is mainly complementary. NECAB1 labels interneurons and a plexus of processes in superficial layers of the dorsal horn....... In the dorsal horn, most NECAB1/2 neurons are glutamatergic. Both NECAB1/2 are transported into dorsal roots and peripheral nerves. Peripheral nerve injury reduces NECAB2, but not NECAB1, expression in DRG neurons. Our study identifies NECAB1/2 as abundant Ca2+-binding proteins in pain-related DRG neurons...

  17. The alpha hemolisina of Escherichia Coli induces increases in the calcium citoplasmico of neutrofilos and monocytes human beings

    International Nuclear Information System (INIS)

    Garcia, J.

    2000-01-01

    Escherichia coli alpha hemolysin (AH) and the calcium ionophores ionomycin and 4 Br A23187 caused increases in cell fluorescence, indicative of elevations in cytoplasmic calcium, in fura 2-loaded human polymorphonuclear leukocytes(PMN) and monocytes (MN). The increase in fluorescence caused by AH was dose dependent. Quelation of extracellular calcium with EGTA prevented fluorescence increases in PMN exposed to 2 HU50/ml AH, but did not prevent a small increase in 4 μM, ionomycin-treated PMN, indicating that ionomycin treatment under conditions of calcium quelation can mobilize calcium from internal stores, and that entry of external calcium accounts for most of the increases in cell fluorescence in cells treated with both AH and calcium ionophores. AH, as well as calcium ionophores and the chemotactic peptide FMLP caused rease of myeloperoxidase (MPO) from PMM suggesting that increments in intracellular calcium cause degramulation with release of granule contents (Author) [es

  18. Membrane mechanisms and intracellular signalling in cell volume regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Dunham, Philip B.

    1995-01-01

    Volume regulation, Signal transduction, Calcium-calmodulin, Stretch-activated channels, Eicosanoids, Macromolecular crowding, Cytoskeleton, Protein phosphorylation, dephosphorylation.......Volume regulation, Signal transduction, Calcium-calmodulin, Stretch-activated channels, Eicosanoids, Macromolecular crowding, Cytoskeleton, Protein phosphorylation, dephosphorylation....

  19. Transformações químicas, físicas e enzimáticas de goiabas 'PEDRO SATO' tratadas na pós-colheita com cloreto de cálcio e 1-metilciclopropeno e armazenadas sob refrigeração Chemical, physical and enzymatic transformations of guavas 'PEDRO SATO' treated at post-harvest with calcium chlorite and 1-methylciclopropone and stored under refrigeration

    Directory of Open Access Journals (Sweden)

    Lucilia Alves Linhares

    2007-06-01

    Full Text Available Com o objetivo de estudar o efeito dos tratamentos com cloreto de cálcio e com 1-MCP associando-se a refrigeração, na conservação e qualidade de goiabas 'Pedro Sato', conduziu-se o experimento em que frutos dessa cultivar foram tratados com solução de CaCl2 a 2% por 5 minutos e com 1-MCP na concentração de 150 nL/L por 12 horas em câmara hermeticamente fechada. Após os tratamentos, os frutos foram armazenados em câmara refrigerada a 10ºC e 90 ± 2% de umidade relativa, por um período de 25 dias. Os resultados indicaram que os tratamentos foram efetivos em manter a qualidade da fruta, salientando-se os frutos tratados com 1-MCP, que mantiveram uma melhor aparência interna e externa, apresentaram menor perda de massa, maior firmeza, menor síntese de vitamina C, menor solubilização de pectinas e menor atividade enzimática, aumentando desta forma a vida pós-colheita das goiabas.With the purpose of investigating the effect of the treatments with calcium chlorite and with 1-methylcyclopropene, associated with refrigeration, on the conservation and quality of guavas 'Pedro Sato', the experiment was carried out in which the fruit of thiscultivar was treated with a solution of 2% CaCl2 for 5 minutes and with 1-MCP at the concentration of 150 nL/L for 12 hours in a tightly sealed chamber. After the treatments, the fruit was stored in a refrigerated chamber at 10ºC and 90 ± 2% of relative humidity for a 25-days period. The results pointed out that the treatments were effective in maintaining fruit quality, stressing the 1-MCP-treated fruit, which kept a better internal and external appearance, presented less loss of mass, greater firmness, less synthesis of vitamin C, less pectin and less activity enzymatic activity, increasing in this way the post-harvest life of guavas.

  20. Cellular calcium mobilization

    International Nuclear Information System (INIS)

    Daniel, E.E.

    1984-01-01

    In vascular and other smooth muscles, occurrence of intracellular Ca stores which can be mobilized to support contraction may be a general phenomenon. The Ca stores are characterized by the requirement for release by high concentrations of agonists acting on plasma membrane receptors, by the failure of the released Ca2+ to recycle to the store, by the occurrence of rapid refilling of the store from the extracellular space, and by disappearance of the store when the plasma membrane is made leaky by saponin. In contrast to agonist-released Ca stores, those released by caffeine to support contraction in Ca2+-free solutions are more slowly lost and refilled, are not always emptied when the agonist-related store is emptied, and do not disappear after saponin treatment. Stores released by agonists have been suggested to be in the endoplasmic reticulum near the plasma membrane or at the inner aspect of the plasma membrane related to high affinity, pH-dependent Ca-binding sites. Caffeine-released stores are assumed to be in endoplasmic reticulum. Continued exposure of some tissues to Ca2+-free solutions unmasks what is considered to be a recycling Ca store releasable by agonists. Release of Ca2+ and its reaccumulation in this store appear to be slower than at the nonrecycling store. The contractions which persist for many hours in Ca2+-free solution are inhibited temporarily by Ca2+ restoration. Existence of a recycling store of releasable Ca2+ requires occurrence of mechanisms to abolish Ca2+ extrusion or leak-out of the cell and to ensure recycling to the same store

  1. Regulation of bovine kidney alpha-ketoglutarate dehydrogenase complex by calcium ion and adenine nucleotides. Effects on S0.5 for alpha-ketoglutarate.

    Science.gov (United States)

    Lawlis, V B; Roche, T E

    1981-04-28

    Regulation of bovine kidney alpha-ketoglutarate dehydrogenase complex by energy-linked metabolites was investigated. Ca2+, ADP, or inorganic phosphate markedly enhanced the activity of the complex, and ATP or, to a lesser extent, GTP decreased the activity of the complex. Initial velocity studies with alpha-ketoglutarate as the varied substrate demonstrated that these modulators induced large changes in S0.5 for alpha-ketoglutarate (based on analysis in Hill plots) with no change in the maximum velocity (as determined by double-reciprocal plots). For all conditions studied, the Hill coefficients were significantly less than 1.0 with slopes that were linear over wide ranges of alpha-ketoglutarate concentrations, indicating negative cooperativity that probably resulted from multiple site-site interactions. Ca2+ (maintained at 10 muM by a Ca2+ buffer) decreased the S0.5 for alpha-ketoglutarate 63-fold (from 25 to 0.40 mM); even in the presence of a positive effector, ADP or phosphate, Ca2+ decreased the S0.5 for alpha-ketoglutarate 7.8- or 28-fold, respectively. Consistent with a mechanism of action dependent of Ca2+, ADP (1.60 mM) or phosphate (20 mM) reduced the S0.5 for alpha-ketoglutarate in the presence of Ca2+ (i.e., 4.5- or 1.67-fold, respectively); however, these effectors elicited larger decreases in S0.5 in the absence of Ca2+ (i.e., 37- or 3.7-fold, respectively). ATP (1.6 mM) increased the S0.5 for alpha-ketoglutarate, and Ca2+ appreciably reduced the effect, lowering the S0.5 98-fold from 66 to 0.67 mM. Thus the activity of the kidney alpha-ketoglutarate dehydrogenase complex is poised to increase as the energy potential in mitochondria declines, and Ca2+ has a pronounced modulatory effect. Comparative studies on bovine heart alpha-ketoglutarate dehydrogenase complex and the effects of varying the ADP/ATP ratio in the presence or absence of Ca2+ or phosphate are also described.

  2. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  3. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

    2016-01-01

    Molar conductivity of saturated aqueous solutions of calcium d-saccharate, used as a stabilizer of beverages fortified with calcium d-gluconate, increases strongly upon dilution, indicating complex formation between calcium and d-saccharate ions, for which, at 25 °C, Kassoc = 1032 ± 80, ΔHassoc......° = -34 ± 6 kJ mol-1, and ΔSassoc° = -55 ± 9 J mol-1 K-1, were determined electrochemically. Calcium d-saccharate is sparingly soluble, with a solubility product, Ksp, of (6.17 ± 0.32) × 10-7 at 25 °C, only moderately increasing with the temperature: ΔHsol° = 48 ± 2 kJ mol-1, and ΔSassoc° = 42 ± 7 J mol-1...... K-1. Equilibria in supersaturated solutions of calcium d-saccharate seem only to adjust slowly, as seen from calcium activity measurements in calcium d-saccharate solutions made supersaturated by cooling. Solutions formed by isothermal dissolution of calcium d-gluconate in aqueous potassium d...

  4. A Dual Function Energy Store

    Directory of Open Access Journals (Sweden)

    Ron Tolmie

    2014-11-01

    Full Text Available Heat can be collected from local energy sources and concentrated into a relatively small volume, and at a useful working temperature, by using a heat pump as the concentrator. That heat can be stored and utilized at a later date for applications like space heating. The process is doing two things at the same time: storing heat and shifting the power demand. The concentration step can be done at night when there is normally a surplus of power and its timing can be directly controlled by the power grid operator to ensure that the power consumption occurs only when adequate power is available. The sources of heat can be the summer air, the heat extracted from buildings by their cooling systems, natural heat from the ground or solar heat, all of which are free, abundant and readily accessible. Such systems can meet the thermal needs of buildings while at the same time stabilizing the grid power demand, thus reducing the need for using fossil-fuelled peaking power generators. The heat pump maintains the temperature of the periphery at the ambient ground temperature so very little energy is lost during storage.

  5. Method of storing radioactive wastes

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, M; Kamiya, K; Sugimoto, Y

    1976-01-09

    A method is claimed to decrease the number of storage containers filled with radioactive wastes. A wire-netting containers having a capacity of 67 liters is filled with 60 kg of pellet-like radioactive solid material. The wire-netting container is held in the middle of a drum can, and asphalt is poured between the drum can and the wire-netting container and stored until radioactivity is attenuated. After storage, the stored body is heated to melt the asphalt and the wire-netting container is removed. Thereafter, the pellet-like radioactive solid material is taken out of the wire-netting container and combined with the other pellet-like radioactive solid material similarly taken out of the storage container, and the resultant material is filled into a wire-netting container having a capacity of 167 liters every 150 kg, and inserted again into the same drum can, into which recovered asphalt is poured for final storage.

  6. [Occupational risks in grocery stores].

    Science.gov (United States)

    Graziosi, Francesca; Bonfiglioli, Roberta; Violante, Francesco S

    2014-01-01

    This work provides an overview of the spectrum of possible occupational risk factors in the retail grocery store/supermarket workplace. Literature on this theme, obtained consulting PubMed database and Google Scholar, was checked. We also exjlore results from the National bInstitute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA). RESULTs: Contacts with objects, use of dangerous equipment (cutter, food slicer) and falls to the same level (slips, trips and falls) are the mainly described workplace hazards. Exposure to chemical (flour dust, components of detergents or disinfectants, volatile organic compounds and contact with nickel) and physical agents (cold exposure, nonionizing radiation and whole bpdy vibration) are reported by many authors. Relations between biomechanical and ergonomic risk factors and musculoskeletal disorders represent the main subjects of study. Few studies are found about biological agents (particularly among butchers). Data regarding psychosocial risks factors in this setting are still limited. Musculoskeletal disorders continue to be the most recurrent health problem between the grocery store workers (particularly low back pain and carpal tunnel syndrome among cashiers). Many technical documents and international Srecommendations are present to prevent these kinds of disorders. Psychosocial risk factors and risk of workplace violence should deserve further investigation.

  7. Protein kinase C interaction with calcium: a phospholipid-dependent process.

    LENUS (Irish Health Repository)

    Bazzi, M D

    1990-08-21

    The calcium-binding properties of calcium- and phospholipid-dependent protein kinase C (PKC) were investigated by equilibrium dialysis in the presence and the absence of phospholipids. Calcium binding to PKC displayed striking and unexpected behavior; the free proteins bound virtually no calcium at intracellular calcium concentrations and bound limited calcium (about 1 mol\\/mol of PKC) at 200 microM calcium. However, in the presence of membranes containing acidic phospholipids, PKC bound at least eight calcium ions per protein. The presence of 1 microM phorbol dibutyrate (PDBu) in the dialysis buffer had little effect on these calcium-binding properties. Analysis of PKC-calcium binding by gel filtration under equilibrium conditions gave similar results; only membrane-associated PKC bound significant amounts of calcium. Consequently, PKC is a member of what may be a large group of proteins that bind calcium in a phospholipid-dependent manner. The calcium concentrations needed to induce PKC-membrane binding were similar to those needed for calcium binding (about 40 microM calcium at the midpoint). However, the calcium concentration required for PKC-membrane binding was strongly influenced by the phosphatidylserine composition of the membranes. Membranes with higher percentages of phosphatidylserine required lower concentrations of calcium. These properties suggested that the calcium sites may be generated at the interface between PKC and the membrane. Calcium may function as a bridge between PKC and phospholipids. These studies also suggested that calcium-dependent PKC-membrane binding and PKC function could be regulated by a number of factors in addition to calcium levels and diacylglycerol content of the membrane.

  8. Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from Cicer arietinum.

    Science.gov (United States)

    Dixit, Ajay Kumar; Jayabaskaran, Chelliah

    2015-05-01

    Calcium plays a crucial role as a secondary messenger in all aspects of plant growth, development and survival. Calcium dependent protein kinases (CDPKs) are the major calcium decoders, which couple the changes in calcium level to an appropriate physiological response. The mechanism by which calcium regulates CDPK protein is not well understood. In this study, we investigated the interactions of Ca(2+) ions with the CDPK1 isoform of Cicer arietinum (CaCDPK1) using a combination of biophysical tools. CaCDPK1 has four different EF hands as predicted by protein sequence analysis. The fluorescence emission spectrum of CaCDPK1 showed quenching with a 5 nm red shift upon addition of calcium, indicating conformational changes in the tertiary structure. The plot of changes in intensity against calcium concentrations showed a biphasic curve with binding constants of 1.29 μM and 120 μM indicating two kinds of binding sites. Isothermal calorimetric (ITC) titration with CaCl2 also showed a biphasic curve with two binding constants of 0.027 μM and 1.7 μM. Circular dichroism (CD) spectra showed two prominent peaks at 208 and 222 nm indicating that CaCDPK1 is a α-helical rich protein. Calcium binding further increased the α-helical content of CaCDPK1 from 75 to 81%. Addition of calcium to CaCDPK1 also increased fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS) indicating exposure of hydrophobic surfaces. Thus, on the whole this study provides evidence for calcium induced conformational changes, exposure of hydrophobic surfaces and heterogeneity of EF hands in CaCDPK1. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Calcium and Egg Activation in Drosophila

    Science.gov (United States)

    Sartain, Caroline V.; Wolfner, Mariana F.

    2012-01-01

    Summary In many animals, a rise in intracellular calcium levels is the trigger for egg activation, the process by which an arrested mature oocyte transitions to prepare for embryogenesis. In nearly all animals studied to date, this calcium rise, and thus egg activation, is triggered by the fertilizing sperm. However in the insects that have been examined, fertilization is not necessary to activate their oocytes. Rather, these insects’ eggs activate as they transit through the female’s reproductive tract, regardless of male contribution. Recent studies in Drosophila have shown that egg activation nevertheless requires calcium and that the downstream events and molecules of egg activation are also conserved, despite the difference in initial trigger. Genetic studies have uncovered essential roles for the calcium-dependent enzyme calcineurin and its regulator calcipressin, and have hinted at roles for calmodulin, in Drosophila egg activation. Physiological and in vitro studies have led to a model in which mechanical forces that impact the Drosophila oocyte as it moves through the reproductive tract triggers the influx of calcium from the external environment, thereby initiating egg activation. Future research will aim to test this model, as well as to determine the spatiotemporal dynamics of cytoplasmic calcium flux and mode of signal propagation in this unique system. PMID:23218670

  10. Mitochondrial Ca2+ uniporter is critical for store-operated Ca2+ entry-dependent breast cancer cell migration

    International Nuclear Information System (INIS)

    Tang, Shihao; Wang, Xubu; Shen, Qiang; Yang, Xinyi; Yu, Changhui; Cai, Chunqing; Cai, Guoshuai; Meng, Xiaojing; Zou, Fei

    2015-01-01

    Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca 2+ uniporter (MCU), a regulator of mitochondrial Ca 2+ uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MCU is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)-induced store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE. - Highlights: • MCU is correlated to metastasis and invasive breast cancer. • MCU inhibition abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or TG-induced SOCE. • Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. • MCU plays a critical role in MDA-MB-231 cell migration by regulating SOCE

  11. Phagocytosis-induced /sup 45/calcium efflux in polymorphonuclear leucocytes

    Energy Technology Data Exchange (ETDEWEB)

    Barthelemy, A; Schell-Frederick, E [Brussels Univ. (Belgium). Institut de Recherche Interdisciplinaire; Paridaens, R [Brussels Univ. (Belgium). Faculte de Medicine

    1977-10-15

    The role of calcium ions in regulating the structure and function of non-muscle cells is a subject of intense study. Several lines of evidence that calcium may be essential in the function of polymorphonuclear leuocytes (PMNL) and an important control element in the process of phagocytosis. Direct studies of calcium distribution and fluxes have only recently been undertaken. To our knowledge, no report of calcium movements during normal phagocytosis has been published. In the context of an overall study of calcium dynamics in the PMNL, we report here initial studies on /sup 45/Ca efflux in prelabelled guinea pig PMNL. The results demonstrate the energy-dependence of resting calcium efflux and an increased efflux upon addition of phagocytic particles which is not dependent on particle internalization.

  12. The effects of calcium on the expression of genes involved in ...

    African Journals Online (AJOL)

    Calcium regulation of the genes involved in ethylene biosynthesis and ethylene receptors in flower abscission zones (AZ) of wild-type tomato (Lycopersicon esculentum Mill.) was investigated in this study. Calcium treatment delayed abscission of pedicel explants. However, verapamil (VP, calcium inhibitor) treatments ...

  13. 16-channel analog store and multiplexer unit

    Energy Technology Data Exchange (ETDEWEB)

    Brossard, M; Kulka, Z [Clermont-Ferrand-2 Univ., 63 - Aubiere (France). Lab. de Physique Corpusculaire

    1979-03-15

    A 16-channel analog store and multiplexer unit is described. The unit enables storing and selection of analog information which is then digitally encoded by single ADC. This solution becomes economically attractive particularly in multidetector pulse height analysis systems.

  14. Store Separations From a Supersonic Cone

    National Research Council Canada - National Science Library

    Simko, Richard J

    2006-01-01

    ... analyses of supersonic store separations. Also included in this research is a study of supersonic base pressure profiles, near-wake velocity profiles, wind tunnel shock interactions and force/moment studies on a conical store and parent vehicle...

  15. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free

  16. In-Store Media and Channel Management

    OpenAIRE

    Anthony Dukes; Yunchuan Liu

    2007-01-01

    In this paper, we study the interesting and complicated effects of retailer in-store media on distribution channel relationships. With the help of advanced technology, retailers can open in-store media in their stores and allow manufacturers to advertise through the instore media. We show that opening in-store media is a strategic decision for a retailer, and a retailer may strategically subsidize manufacturers on their advertising through instore media to better coordinate the channel. Even ...

  17. Consumer behaviour in Apple's App Store

    OpenAIRE

    Ayalew, Romel

    2011-01-01

    Mobile applications stores such as Apple’s App Store and Google’s Android Market revolutionized the distribution of applications for mobile devices. However, with thousands of application submissions, limited testing resources and the lack of an effective filtering mechanism, application stores suffer from information overload and a risk of releasing poor quality applications that could create confusion to consumers and may seriously affect the App store markets. Thus concern has been raised ...

  18. Corner stores: the perspective of urban youth.

    Science.gov (United States)

    Sherman, Sandra; Grode, Gabrielle; McCoy, Tara; Vander Veur, Stephanie S; Wojtanowski, Alexis; Sandoval, Brianna Almaguer; Foster, Gary D

    2015-02-01

    We examined the perspectives of low-income, urban youth about the corner store experience to inform the development of corner store interventions. Focus groups were conducted to understand youth perceptions regarding their early shopping experiences, the process of store selection, reasons for shopping in a corner store, parental guidance about corner stores, and what their ideal, or "dream corner store" would look like. Thematic analysis was employed to identify themes using ATLAS.ti (version 6.1, 2010, ATLAS.ti GmbH) and Excel (version 2010, Microsoft Corp). Focus groups were conducted in nine kindergarten-through-grade 8 (K-8) public schools in low-income neighborhoods with 40 fourth- to sixth-graders with a mean age of 10.9±0.8 years. Youth report going to corner stores with family members at an early age. By second and third grades, a growing number of youth reported shopping unaccompanied by an older sibling or adult. Youth reported that the products sold in stores were the key reason they choose a specific store. A small number of youth said their parents offered guidance on their corner store purchases. When youth were asked what their dream corner store would look like, they mentioned wanting a combination of healthy and less-healthy foods. These data suggest that, among low-income, urban youth, corner store shopping starts at a very young age and that product, price, and location are key factors that affect corner store selection. The data also suggest that few parents offer guidance about corner store purchases, and youth are receptive to having healthier items in corner stores. Corner store intervention efforts should target young children and their parents/caregivers and aim to increase the availability of affordable, healthier products. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  19. Retail brand architecture and consumer store loyalty

    DEFF Research Database (Denmark)

    Brunsø, Karen; Grunert, Klaus G.

    is to investigate the relationship between consumers perceived retail brand architecture, their store satisfaction and loyalty. Furthermore we use perceived store image as a mediating factor in our framework. In total 772 Danish households participated in a telephone interview and returned questionnaires by mail....... The major contribution of this research is to conceptualise and empirically investigate the role of brand architecture for perceived store image, store satisfaction and loyalty....

  20. Apparatus for storing protective suits

    International Nuclear Information System (INIS)

    Englemann, H.J.; Koller, J.; Schrader, H.R.; Schade, G.; Pedrerol, J.

    1975-01-01

    Arrangements are described for storing one or more protective suits when contaminated on the outside. In order to permit a person wearing a contaminated suit to leave a contaminated area safely, and without contaminating the environment, it has hitherto been the practice for the suit to be passed through a 'lock' and cleansed under decontaminating showers whilst still being worn. This procedure is time wasting and not always completely effective, and it may be necessary to provide a second suit for use whilst the first suit is being decontaminated. Repeated decontamination may also result in undue wear and tear. The arrangements described provide a 'lock' chamber in which a contaminated suit may be stowed away without its interior becoming contaminated, thus allowing repeated use by persons donning and shedding it. (U.K.)

  1. Alcoholic fermentation of stored sweet potatoes

    Energy Technology Data Exchange (ETDEWEB)

    Yutaka, Y; One, H

    1958-01-01

    Sweet potatoes were ground and stored in a ground hold. The stored sweet potatoes gave about 90% fermentation efficiency by the koji process. A lower fermentation efficiency by the amylo process was improved by adding 20 to 30 mg/100 ml of organic N. Inorganic N has no effect in improving the fermentation efficiency of the stored sweet potatoes by the amylo process.

  2. Cocaine- and amphetamine-regulated transcript peptide and calcium binding proteins immunoreactivity in the deep layers of the superior colliculus of the guinea pig: Implications for multisensory and visuomotor processing.

    Science.gov (United States)

    Najdzion, Janusz

    2018-03-01

    The superior colliculus (SC) of mammals is a midbrain center, that can be subdivided into the superficial (SCs) and deep layers (SCd). In contrast to the visual SCs, the SCd are involved in multisensory and motor processing. This study investigated the pattern of distribution and colocalization of cocaine- and amphetamine-regulated transcript peptide (CART) and three calcium-binding proteins (CaBPs) i.e. calbindin (CB), calretinin (CR) and parvalbumin (PV) in the SCd of the guinea pig. CART labeling was seen almost exclusively in the neuropil and fibers, which differed in regard to morphology and location. CART-positive neurons were very rare and restricted to a narrow area of the SCd. The most intense CART immunoreactivity was observed in the most dorsally located sublayer of the SCd, which is anatomically and functionally connected with the SCs. CART immunoreactivity in the remaining SCd was less intensive, but still relatively high. This characteristic pattern of immunoreactivity indicates that CART as a putative neurotransmitter or neuromodulator may play an important role in processing of visual information, while its involvement in the auditory and visuomotor processing is less significant, but still possible. CaBPs-positive neurons were morphologically diverse and widely distributed throughout all SCd. From studied CaBPs, CR showed a markedly different distribution compared to CB and PV. Overall, the patterns of distribution of CB and PV were similar in the entire SCd. Consequently, the complementarity of these patterns in the guinea pig was very weak. Double immunostaining revealed that CART did not colocalize with either CaBPs, which suggested that these neurochemical substances might not coexist in the multisensory and visuomotor parts of the SC. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast

    OpenAIRE

    Busti, Stefano; Mapelli, Valeria; Tripodi, Farida; Sanvito, Rossella; Magni, Fulvio; Coccetti, Paola; Rocchetti, Marcella; Nielsen, Jens; Alberghina, Lilia; Vanoni, Marco

    2016-01-01

    Calcium homeostasis is crucial to eukaryotic cell survival. By acting as an enzyme cofactor and a second messenger in several signal transduction pathways, the calcium ion controls many essential biological processes. Inside the endoplasmic reticulum (ER) calcium concentration is carefully regulated to safeguard the correct folding and processing of secretory proteins. By using the model organism Saccharomyces cerevisiae we show that calcium shortage leads to a slowdown of cell growth and met...

  4. Copycat snacks: Can students differentiate between school and store snacks?

    Science.gov (United States)

    Mann, Georgianna

    2018-02-01

    In 2014, the national Smart Snacks in School nutrition standards placed regulations on all snack foods sold in schools. Many food companies reformulated common snack food products for sale in schools, called "copycat snacks", which look similar to nutritionally different foods sold in stores. It is possible that these snacks create consumer confusion among students. The purpose of this study was to determine if middle school students could differentiate, in taste and appearance, between school (copycat) and store versions of common snacks. Seventy-six middle school students evaluated three different food products offered in schools: Froot Loops, Rice Krispy Treats, and Doritos. Students tasted snacks in a series of triangle tests for difference, one for each snack food, including school and store versions. Students were also presented with packages, school and store versions of the same products, and asked to determine the expected taste, purchase intentions, and perceived healthfulness. Students could determine taste differences between school and store Rice Krispy Treats yet could not differentiate between Froot Loop and Dorito varieties. Students rated store versions of all three snacks with greater expected taste, higher intention to purchase, and as less healthy. While it seems product confusion concerning copycat snacks may not be severe in this sample, snack food brands are still a prominent feature in schools. It is possible that these copycat snacks can confuse students' perceptions of healthy foods. Alternative packaging for school foods or reformation of store versions of snack foods may be viable solutions to this problem. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 7 CFR 1427.16 - Movement and protection of warehouse-stored cotton.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Movement and protection of warehouse-stored cotton. 1427.16 Section 1427.16 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY... Cotton Loan and Loan Deficiency Payments § 1427.16 Movement and protection of warehouse-stored cotton. (a...

  6. Pressure Systems Stored-Energy Threshold Risk Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Paulsen, Samuel S.

    2009-08-25

    Federal Regulation 10 CFR 851, which became effective February 2007, brought to light potential weaknesses regarding the Pressure Safety Program at the Pacific Northwest National Laboratory (PNNL). The definition of a pressure system in 10 CFR 851 does not contain a limit based upon pressure or any other criteria. Therefore, the need for a method to determine an appropriate risk-based hazard level for pressure safety was identified. The Laboratory has historically used a stored energy of 1000 lbf-ft to define a pressure hazard; however, an analytical basis for this value had not been documented. This document establishes the technical basis by evaluating the use of stored energy as an appropriate criterion to establish a pressure hazard, exploring a suitable risk threshold for pressure hazards, and reviewing the methods used to determine stored energy. The literature review and technical analysis concludes the use of stored energy as a method for determining a potential risk, the 1000 lbf-ft threshold, and the methods used by PNNL to calculate stored energy are all appropriate. Recommendations for further program improvements are also discussed

  7. The network-based energy management system for convenience stores

    Energy Technology Data Exchange (ETDEWEB)

    Wang, An-Ping; Hsu, Pau-Lo [Department of Electrical and Control Engineering, National Chiao-Tung University, 1001 Ta-Hsiue Road, Hsinchu City 310 (China)

    2008-07-01

    Convenience stores generally consume energy higher than other retailing merchants. As the problem of energy shortage becomes more serious during summer, almost all convenience stores sign a contract with power plants, which provides for fines if demand limiting occurs in Taiwan and many other countries. Therefore, a reliable and effective method to reduce their utility consumption is required for modern business and industry. This research integrates the remote sensors, the control network, and the embedded system technologies to construct a distributed energy management control system for dedicated convenience stores. Energy consumption can thus be reasonably managed with demand limits by measuring and analyzing the power consumption sources in four major subsystems of convenience stores, namely, (1) air-conditioning, (2) lighting, (3) heating, and (4) refrigeration. By applying the proposed demand prediction and control method, the demand limiting condition can be properly predicted, and the possible peak load can thus be eliminated via the network control mechanism. Moreover, by integrating the LonWork fieldbus and the WinCE operating system (OS), the proposed system has been successfully applied to a convenience store. The experimental results indicate that the proposed distributed energy management system suitably predicts the peak loading condition and successfully prevents its occurrence by switching the air-conditioning system without affecting the indoor temperature regulation. (author)

  8. DIHYDROPYRIDINE CALCIUM- CHANNELBLOCKERSFOR ...

    African Journals Online (AJOL)

    Furthermore, the controversy over the role of calci~-channel blockers as first-line ..... group trials while fully accounting for placebo effects as well as interindividual ..... Reducing calcium overload in the ischemic brain. N Engl JMed. 1999; 341 ...

  9. Calcium and Your Child

    Science.gov (United States)

    ... calcium-set tofu edamame (soybeans) broccoli, collard greens, kale, chard, Chinese cabbage, and other leafy greens almonds ... more dark green, leafy vegetables (such as broccoli, kale, collard greens, or Chinese cabbage) with meals. Kids ...

  10. [The dynamics of calcium distribution in stigma and style of lettuce (Lactuca sativa L.) before and after pollination].

    Science.gov (United States)

    Qiu, Yi Lan; Liu, Ru Shi; Xie, Chao Tian; Yang, Yan Hong; Gu, Li; Tian, Hui Qiao

    2005-08-01

    Potassium antimonite was used to deposit calcium in the stigma and style of lettuce (Lactuca sativa L.) before and after pollination. The stigma of lettuce is two splits. Abundant calcium granules are displayed in the wall of papillae on the receptive surface of stigma before and after pollination, which may facilitate pollen germination. However, a few calcium granules in the wall of epidermis cell on no-receptive surface. Calcium distribution in style presents a gradient in transmitting tissue and parenchyma cells from the top to the base of the style before pollination. After pollination, calcium in transmitting tissue distinctly increased and its gradient distribution became more evident. Pollen tubes grow in the intercellular gaps of transmitting tissue. When pollen tubes grew into transmitting tissue, calcium granules in parenchyma around transmitting tissue decreased, suggesting a calcium movement was controlled by pollen tubes. The calcium gradient distribution also appeared in the trachea of vascular bundle of style. In general, calcium in style displays a feature of time-special distribution: transmitting tissue doesn't need much more calcium that is only stored in the parenchyma before pollination. However, calcium in parenchyma cells may be transported to transmitting tissue and make the latter contain more calcium to form an evident calcium gradient and meet the requirement of pollen tubes directionally growing after pollination. This is the second sample of calcium gradient existing in style, which was found by using potassium antimonite method.

  11. Slow, stopped and stored light

    International Nuclear Information System (INIS)

    Welch, G.; Scully, M.

    2005-01-01

    Light that can been slowed to walking pace could have applications in telecommunications, optical storage and quantum computing. Whether we use it to estimate how far away a thunderstorm is, or simply take it for granted that we can have a conversation with someone on the other side of the world, we all know that light travels extremely fast. Indeed, special relativity teaches us that nothing in the universe can ever move faster than the speed of light in a vacuum: 299 792 458 ms sup - sup 1. However, there is no such limitation on how slowly light can travel. For the last few years, researchers have been routinely slowing light to just a few metres per second, and have recently even stopped it dead in its tracks so that it can be stored for future use. Slow-light has considerable popular appeal, deriving perhaps from the importance of the speed of light in relativity and cosmology. If everyday objects such as cars or people can travel faster than 'slow' light, for example, then it might appear that relativistic effects could be observed at very low speeds. Although this is not the case, slow light nonetheless promises to play an important role in optical technology because it allows light to be delayed for any period of time desired. This could lead to all-optical routers that would increase the bandwidth of the Internet, and applications in optical data storage, quantum information and even radar. (U.K.)

  12. Gas storing and processing device

    International Nuclear Information System (INIS)

    Kobayashi, Yoshihiro; Takano, Yosoko.

    1988-01-01

    Purpose: To increase the gas injection processing performance and obtain stable accumulation layers by increasing the thickness of the accumulation layers of amorphous alloy. Constitution: The gas storing processing device comprises a cylindrical vessel constituting an outer cathode for introducing gases to be processed, an inner cathode in which transition metal material and rare earth metal material as a sputtering target disposed in the vessel are combined by way of insulating material, an anode cover disposed to the upper portion of the vessel and an anode bottom disposed at the bottom thereof. It is adapted such that DC high voltage sources are connected respectively to the outer and the inner cathodes and sputtering voltage can be applied, removed and controlled independently to the transition metal and the rare earth metal of the inner cathode. This enables to control the composition ratio of the accumulation layers of amorphous alloy formed to the surface of the outer cathode, thereby enabling operation related with the gas injection ratio. (Sekiya, K.)

  13. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    James, W.P.T.; Branch, W.J.; Southgate, D.A.T.

    1978-01-01

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  14. Nutrition environments in corner stores in Philadelphia.

    Science.gov (United States)

    Cavanaugh, Erica; Mallya, Giridhar; Brensinger, Colleen; Tierney, Ann; Glanz, Karen

    2013-02-01

    To examine the availability, quality, and price of key types of healthy and less-healthy foods found in corner stores in low-income urban neighborhoods and the associations between store characteristics and store food environments. A sample of 246 corner stores was selected from all corner stores participating in the Philadelphia Healthy Corner Store Initiative (HCSI). The Nutrition Environment Measures Survey for Corner Stores (NEMS-CS) was used to assess the availability, quality, and price of foods and beverages in 11 common categories between February and May, 2011. NEMS-CS measures were completed in 233 stores, 94.7% of the 246 stores approached. The healthier options were significantly less available in all food categories and often more expensive. Baked goods, bread, chips and cereals were sold at nearly all stores, with significantly fewer offering low-fat baked goods (5.7%, pbread (56.2%, pfood environment and dietary choices among low-income urban populations. Availability of certain healthier foods could be improved. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. A model of propagating calcium-induced calcium release mediated by calcium diffusion

    NARCIS (Netherlands)

    Backx, P. H.; de Tombe, P. P.; van Deen, J. H.; Mulder, B. J.; ter Keurs, H. E.

    1989-01-01

    The effect of sudden local fluctuations of the free sarcoplasmic [Ca++]i in cardiac cells on calcium release and calcium uptake by the sarcoplasmic reticulum (SR) was calculated with the aid of a simplified model of SR calcium handling. The model was used to evaluate whether propagation of calcium

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

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate

  17. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2005-01-01

    different mechanisms for this propagation. One mechanism involves the secretion of a nucleotide, possibly ATP, acting in an autocrine action to purinergic P2Y2 receptors on the neighboring cells, leading to intracellular IP3 generation and subsequent release of calcium from intracellular stores. The other...... to osteoclasts as well. We demonstrated that paracrine action of ATP was responsible for the wave propagation, but now the purinergic P2X7 receptor was involved. Thus, the studies demonstrate that calcium signals can be propagated not only among osteoblasts, but also between osteoblasts and osteoclasts...

  18. Understanding Retailers’ Acceptance of Virtual Stores

    Directory of Open Access Journals (Sweden)

    Irene Y.L. Chen

    2010-09-01

    Full Text Available The acceptance of e-commerce among consumers has stimulated the rise of virtual stores. Increasing traditional retailers or people who do not have sufficient capital for maintaining a brick-and-mortar store have considered using virtual stores to reach global market. In the e-commerce literature, there has been rich research evidence concerning consumers’ acceptance of virtual stores. However, rigorous academic research on retailers’ acceptance of virtual stores is relatively scarce today. This study draws upon the theory of planned behavior and information richness theory to propose an integrated theoretical model. A field survey is used to collect data from e-tailers. The data are analyzed to examine the six relationships posited in the research model. Findings of this study provide a further research avenue for e-commerce, and implications for those who are managing or considering using virtual stores.

  19. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia.

    Science.gov (United States)

    Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana; Liantonio, Antonella

    2017-06-01

    Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca 2+ ] i , compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in

  20. Propagating separable equalities in an MDD store

    DEFF Research Database (Denmark)

    Hadzic, Tarik; Hooker, John N.; Tiedemann, Peter

    2008-01-01

    We present a propagator that achieves MDD consistency for a separable equality over an MDD (multivalued decision diagram) store in pseudo-polynomial time. We integrate the propagator into a constraint solver based on an MDD store introduced in [1]. Our experiments show that the new propagator pro...... provides substantial computational advantage over propagation of two inequality constraints, and that the advantage increases when the maximum width of the MDD store increases....

  1. Signature-based store checking buffer

    Science.gov (United States)

    Sridharan, Vilas; Gurumurthi, Sudhanva

    2015-06-02

    A system and method for optimizing redundant output verification, are provided. A hardware-based store fingerprint buffer receives multiple instances of output from multiple instances of computation. The store fingerprint buffer generates a signature from the content included in the multiple instances of output. When a barrier is reached, the store fingerprint buffer uses the signature to verify the content is error-free.

  2. Customers' willingness to purchase new store brands

    OpenAIRE

    Zielke, Stephan; Dobbelstein, Thomas

    2007-01-01

    Purpose – The purpose of this paper is to identify factors influencing customers’ willingness to purchase new store brands. Design/methodology/approach – The paper develops a 3 £ 3 design to investigate the impact of price and quality positioning on the willingness to purchase new store brands in five product groups. A total of 990 respondents completed a questionnaire about store brand perception, aspects of purchasing behavior and willingness to buy. Data are analyzed with analysis...

  3. Insect pests of stored grain products

    International Nuclear Information System (INIS)

    Chuaqui-Offermanns, N.

    1987-01-01

    The presence of insects in stored products is a worldwide recognized problem. In this report chemical and physical methods to control insect infestations in stored products are discussed. Special attention is given to the use of ionizing radiation to control insect pests in stored grains. The radiosensitivity of the most common insect pests at their different developmental stages is presented and discussed. The conclusions of this review are compiled in an executive summary. 62 refs

  4. Organizational choices and financial performance: the case of company-owned stores, franchisee-owned stores and stores-within-a-store among French fashion retailers

    OpenAIRE

    Paul Amadieu; Karine Picot-Coupey; Jean-Laurent Viviani

    2013-01-01

    This paper deals with the governance and financial performance issues in the context of French Fashion retail companies. In this study, we analyze the influence of the organizational choices on the financial performance at the network level. We consider three forms used in isolation (company-owned stores, franchisee-owned stores and stores-within-a-store), three dually-organized forms (dual forms mixing two of the three forms) as well as a combined form associating the three ones. We study a ...

  5. Store Image: Scale implementation Part 3

    Directory of Open Access Journals (Sweden)

    Ronel du Preez

    2008-10-01

    Full Text Available This paper is the final in the three-part series regarding store image. The purposes of this article are to (1 implement the developed scale to assess whether it illustrates acceptable psychometric properties of reliability and validity, (2 assess the model fit of the developed scale and (3 formulate recommendations for future research. Results indicated that the Apparel Store Image Scale (ASIS show acceptable reliability and model fit. A refined definition of store image was proposed together with a Final Model of Apparel Store Image. Recommendations for future research are made.

  6. How the Measurement of Store Choice Behaviour Moderates the Relationship between Distance and Store Choice Behaviour

    DEFF Research Database (Denmark)

    Hansen, Torben; Cumberland, Flemming; Solgaard, Hans Stubbe

    2013-01-01

    The influence of distance on consumer store choice behaviour has been considered in many studies. In that respect, frequency and budget share are frequently used methods of measurement to determine the consumer's store choice behavour. In this study, we propose that the significance of distance...... is influenced by the way in which store choice behaviour is conceptualized. A survey among 631 consuemrs was performed in order to examine the research proposition. Structural equation results suggest that the negative effect of distance on store choice behaviour is larger when store choice behaviour...... is measured as number of visits to a particular store than wehen store cjoice behaviour is measured as the percentage of budget spend at a particular store. Our results indicate that researchers should carefully consider the measurement of store choice behaviour when carrying out empirical research invlving...

  7. Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis

    DEFF Research Database (Denmark)

    Müller, Margit S; Fox, Rebecca; Schousboe, Arne

    2014-01-01

    Astrocytic glycogen, the only storage form of glucose in the brain, has been shown to play a fundamental role in supporting learning and memory, an effect achieved by providing metabolic support for neurons. We have examined the interplay between glycogenolysis and the bioenergetics of astrocytic...

  8. Depletion of calcium stores contributes to progesterone-induced attenuation of calcium signaling of G protein-coupled receptors

    Czech Academy of Sciences Publication Activity Database

    Gehrig-Burger, K.; Slaninová, Jiřina; Gimpl, G.

    2010-01-01

    Roč. 67, č. 16 (2010), s. 2815-2824 ISSN 1420-682X Institutional research plan: CEZ:AV0Z40550506 Keywords : non-genomic effect * oxytocin * bradykinin * progesterone Subject RIV: CC - Organic Chemistry Impact factor: 7.047, year: 2010

  9. Around the Corner to Better Health: A Milwaukee Corner Store Initiative.

    Science.gov (United States)

    Young, Staci; DeNomie, Melissa; Sabir, JoAnne; Gass, Eric; Tobin, Jessie

    2017-01-01

    To discuss successes and challenges of a collaborative pilot project to increase healthy food availability in corner stores in Milwaukee, Wisconsin. The Lindsay Heights Healthy Corner Store Initiative aimed to help corner stores sell high-quality produce by increasing supply of healthy foods and funding minor store upgrades to facilitate change. Evaluation research. Milwaukee, Wisconsin. Corner stores; youth and adult community members. (1) Supporting businesses in purchasing equipment to stock fresh produce, (2) connecting stores with produce sources, and (3) community outreach and marketing. Partnership capacity, youth engagement in food justice, and community members' usage of corner stores. Qualitative analysis; descriptive statistics. Storeowners reported more sold produce items per week and increased noticeable fresh produce upon entrance into the store. There was increased or improved store redesign, fresh produce signage, in-store cooking demonstrations, and small business development resources. Youth learned about new vegetables, increased kitchen skills and proper food storage, and the effects of obesity on overall health. Similar interventions must address infrastructure costs, cooperation with property owners, and local policies and regulations affecting business practices.

  10. Muscle glycogen stores and fatigue

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Westerblad, Håkan; Nielsen, Joachim

    2013-01-01

      Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle...... function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct...... pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation-contraction coupling and Ca2+ release from...

  11. Mathematical investigation of IP3-dependent calcium dynamics in astrocytes.

    Science.gov (United States)

    Handy, Gregory; Taheri, Marsa; White, John A; Borisyuk, Alla

    2017-06-01

    We study evoked calcium dynamics in astrocytes, a major cell type in the mammalian brain. Experimental evidence has shown that such dynamics are highly variable between different trials, cells, and cell subcompartments. Here we present a qualitative analysis of a recent mathematical model of astrocyte calcium responses. We show how the major response types are generated in the model as a result of the underlying bifurcation structure. By varying key channel parameters, mimicking blockers used by experimentalists, we manipulate this underlying bifurcation structure and predict how the distributions of responses can change. We find that store-operated calcium channels, plasma membrane bound channels with little activity during calcium transients, have a surprisingly strong effect, underscoring the importance of considering these channels in both experiments and mathematical settings. Variation in the maximum flow in different calcium channels is also shown to determine the range of stable oscillations, as well as set the range of frequencies of the oscillations. Further, by conducting a randomized search through the parameter space and recording the resulting calcium responses, we create a database that can be used by experimentalists to help estimate the underlying channel distribution of their cells.

  12. Building Store Satisfaction Centred on Customer Retention in Clothing Retailing: Store Design and Ease of Shopping

    Directory of Open Access Journals (Sweden)

    Gulden Turhan

    2016-01-01

    Full Text Available The study’s research model suggests that store design and ease of shopping are associated with customer retention through a mediated pathway in which store design and ease of shopping influence perceived store satisfaction, which in turn, influences customer retention. This survey was administered to two separate clothing stores offered to either females or males (in total, 533 participants. Using structural equation modelling methodology, data was analysed to explain the interrelations among the variables in the model. The results of an empirical study of a sample of store shoppers revealed that store design and ease of shopping influence customer retention in an indirect way through customer perception of satisfaction with the store. In building store satisfaction that is centred on customer retention, store design and shopping ease differ in their relative influences. This difference is high for females, but for men as low as to be considered negligible in males. As a result, improving customers’ perceptions of store design and ease of shopping is a way to ensure store satisfaction support customer retention. The results of the study provide a new insight into the relationships by suggesting indirect effects of shopping ease and store design on consumer retention by their impacts on store satisfaction, rather than direct effects.

  13. Building Store Satisfaction Centred on Customer Retention in Clothing Retailing: Store Design and Ease of Shopping

    Directory of Open Access Journals (Sweden)

    Gulden Turhan

    2014-01-01

    Full Text Available The study’s research model suggests that store design and ease of shopping are associated with customer retention through a mediated pathway in which store design and ease of shopping influence perceived store satisfaction, which in turn, influences customer retention. This survey was administered to two separate clothing stores offered to either females or males (in total, 533 participants. Using structural equation modelling methodology, data was analysed to explain the interrelations among the variables in the model. The results of an empirical study of a sample of store shoppers revealed that store design and ease of shopping influence customer retention in an indirect way through customer perception of satisfaction with the store. In building store satisfaction that is centred on customer retention, store design and shopping ease differ in their relative influences. This difference is high for females, but for men as low as to be considered negligible in males. As a result, improving customers’ perceptions of store design and ease of shopping is a way to ensure store satisfaction support customer retention. The results of the study provide a new insight into the relationships by suggesting indirect effects of shopping ease and store design on consumer retention by their impacts on store satisfaction, rather than direct effects.

  14. (G6PD) in stored blood

    African Journals Online (AJOL)

    Red blood cell viability in stored blood determines successful transfusion. Glucose-6-phosphate dehydrogenase (G6PD) activity has been shown to maintain red blood cell membrane integrity. This study was, therefore, aimed at estimating the G6PD activity in stored blood bags at the blood bank of the University of Nigeria ...

  15. Performance Determinants for Convenience Store Suppliers

    OpenAIRE

    Zainah Abdullah; Aznur Hajar Abdullah

    2012-01-01

    This paper examines the impact of information and communication technology (ICT) usage, internal relationship, supplier-retailer relationship, logistics services and inventory management on convenience store suppliers- performance. Data was collected from 275 convenience store managers in Malaysia using a set of questionnaire. The multiple linear regression results indicate that inventory management, supplier-retailer relationship, logistics services and internal relation...

  16. Apple iTunes music store

    OpenAIRE

    Lenzi, R.; Schmucker, M.; Spadoni, F.

    2003-01-01

    This technical report analyses the Apple iTunes Music Store and its success factors. Besides the technical aspects, user and customer aspects as well as content aspects are considered. Furthermore, iTunes Music Store's impact to online music distribution services is analysed and a short outlook to future music online distribution is given.

  17. Insect pest management in stored grain

    Science.gov (United States)

    Stored grain is vulnerable to attach by a variety of insect pests, that can generally be classified as external or internal feeders. Infestations primarily occur after grain is stored, though there is some evidence that infestations can occur in the field right before harvest. There are a variety of...

  18. Win-Win Strategies at Discount Stores

    NARCIS (Netherlands)

    B. Deleersnyder (Barbara); M.G. Dekimpe (Marnik); J-B.E.M. Steenkamp (Jan-Benedict); O. Koll (Oliver)

    2005-01-01

    textabstractAn important development that contributes to store brands’ growing success in the grocery market is the increasing number of discount stores that sell predominantly own, private-label, brands. To fight private labels, manufacturers of national brands feel increasingly compelled to

  19. Nudging consumer behaviour in retail stores

    DEFF Research Database (Denmark)

    Adam, Abdulfatah

    2016-01-01

    -effectiveness of alternative interventions in retail store settings. In cooperation with a supermarket chain in Denmark, we manipulated food locations inside the store so that relatively low energy dense products were placed favorable shelf locations. The underlying theory for the experiment was the behavioral approach (so...

  20. Consumers' store choice behavior for fresh food

    NARCIS (Netherlands)

    Meulenberg, M.T.G.; Trijp, van J.C.M.

    1991-01-01

    Consumers' preference for fresh food stores is analyzed. In particular the choice between supermarkets and specialized shops for purchasing fresh food is analyzed. Attention is given to the factors influencing this choice. For this purpose a number of research questions with respect to store choice

  1. Quantitative grading of store separation trajectories

    CSIR Research Space (South Africa)

    Jamison, Kevin A

    2017-09-01

    Full Text Available When a new store is integrated with an aircraft, it is necessary to verify that it separates safely for all possible release and emergency jettison scenarios. A large number of store separation analyses are required to comply with this requirement...

  2. Presenilin-mediated modulation of capacitative calcium entry.

    Science.gov (United States)

    Yoo, A S; Cheng, I; Chung, S; Grenfell, T Z; Lee, H; Pack-Chung, E; Handler, M; Shen, J; Xia, W; Tesco, G; Saunders, A J; Ding, K; Frosch, M P; Tanzi, R E; Kim, T W

    2000-09-01

    We studied a novel function of the presenilins (PS1 and PS2) in governing capacitative calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores. Abrogation of functional PS1, by either knocking out PS1 or expressing inactive PS1, markedly potentiated CCE, suggesting a role for PS1 in the modulation of CCE. In contrast, familial Alzheimer's disease (FAD)-linked mutant PS1 or PS2 significantly attenuated CCE and store depletion-activated currents. While inhibition of CCE selectively increased the amyloidogenic amyloid beta peptide (Abeta42), increased accumulation of the peptide had no effect on CCE. Thus, reduced CCE is most likely an early cellular event leading to increased Abeta42 generation associated with FAD mutant presenilins. Our data indicate that the CCE pathway is a novel therapeutic target for Alzheimer's disease.

  3. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R

    2005-01-01

    The regulation of bone turnover is a complex and finely tuned process. Many factors regulate bone remodeling, including hormones, growth factors, cytokines etc. However, little is known about the signals coupling bone formation to bone resorption, and how mechanical forces are translated...... into biological effects in bone. Intercellular calcium waves are increases in intracellular calcium concentration in single cells, subsequently propagating to adjacent cells, and can be a possible mechanism for the coupling of bone formation to bone resorption. The aim of the present studies was to investigate...... whether bone cells are capable of communicating via intercellular calcium signals, and determine by which mechanisms the cells propagate the signals. First, we found that osteoblastic cells can propagate intercellular calcium transients upon mechanical stimulation, and that there are two principally...

  4. Coupling between phosphate and calcium homeostasis: a mathematical model.

    Science.gov (United States)

    Granjon, David; Bonny, Olivier; Edwards, Aurélie

    2017-12-01

    We developed a mathematical model of calcium (Ca) and phosphate (PO 4 ) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO 4 balance. The model represents the exchanges of Ca and PO 4 between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO 4 -fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D 3 , fibroblast growth factor 23, and Ca 2+ -sensing receptors. Our results suggest that the Ca and PO 4 homeostatic systems are robust enough to handle small perturbations in the production rate of either PTH or vitamin D 3 The model predicts that large perturbations in PTH or vitamin D 3 synthesis have a greater impact on the plasma concentration of Ca 2+ ([Ca 2+ ] p ) than on that of PO 4 ([PO 4 ] p ); due to negative feedback loops, [PO 4 ] p does not consistently increase when the production rate of PTH or vitamin D 3 is decreased. Our results also suggest that, following a large PO 4 infusion, the rapidly exchangeable pool in bone acts as a fast, transient storage PO 4 compartment (on the order of minutes), whereas the intracellular pool is able to store greater amounts of PO 4 over several hours. Moreover, a large PO 4 infusion rapidly lowers [Ca 2+ ] p owing to the formation of CaPO 4 complexes. A large Ca infusion, however, has a small impact on [PO 4 ] p , since a significant fraction of Ca binds to albumin. This mathematical model is the first to include all major regulatory factors of Ca and PO 4 homeostasis. Copyright © 2017 the American Physiological Society.

  5. Store-operate-coherence-on-value

    Science.gov (United States)

    Chen, Dong; Heidelberger, Philip; Kumar, Sameer; Ohmacht, Martin; Steinmacher-Burow, Burkhard

    2014-11-18

    A system, method and computer program product for performing various store-operate instructions in a parallel computing environment that includes a plurality of processors and at least one cache memory device. A queue in the system receives, from a processor, a store-operate instruction that specifies under which condition a cache coherence operation is to be invoked. A hardware unit in the system runs the received store-operate instruction. The hardware unit evaluates whether a result of the running the received store-operate instruction satisfies the condition. The hardware unit invokes a cache coherence operation on a cache memory address associated with the received store-operate instruction if the result satisfies the condition. Otherwise, the hardware unit does not invoke the cache coherence operation on the cache memory device.

  6. Calcium ferrite formation from the thermolysis of calcium tris (maleato)

    Indian Academy of Sciences (India)

    For preparing calcium ferrite, calcium tris (maleato) ferrate(III) precursor was prepared by mixing aqueous solutions of iron(III) maleate, calcium maleate and maleic acid. Various physico-chemical techniques i.e. TG, DTG, DTA, Mössbauer, XRD, IR etc have been used to study the decomposition behaviour from ambient to ...

  7. Consumers' quality perception of national branded, national store branded, and imported store branded beef

    DEFF Research Database (Denmark)

    Banovic, Marija; Grunert, Klaus G.; Barreira, Maria Madalena

    2010-01-01

    This study investigated the differences in the consumers' quality perception of national branded, national store branded, and imported store branded beef. Partial Least Squares analysis is used for modelling the quality perception process. Results show that consumers perceived national branded...

  8. European Food Safety Authority; Response to comments on the Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific substantiation of a health claim related to beta-palmitate and increased calcium absorption pursuant to Article 14 of Regulation (EC

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, EFSA was asked to review the scientific comments received on the Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific substantiation of a health claim related to beta-palmitate and increased...... calcium absorption pursuant to Article 14 of Regulation (EC) No 1924/2006. Comments submitted to EFSA via the European Commission Services originated from the applicant (IDACE). EFSA has reviewed the comments and shared them with the chair of the NDA Panel, Prof. Albert Flynn, and the chair of the NDA...

  9. Beyond Promotion-Based Store Switching: Antecedents and Consequences of Systematic Multiple-Store Shopping

    OpenAIRE

    Gijsbrechts, E.; Campo, K.; Nisol, P.

    2005-01-01

    In this paper, we demonstrate that single-purpose multiple store shopping is not only driven by opportunistic, promotion-based motivations, but may also be part of a longer term shopping planning process based on stable store characteristics.Starting from a utility-maximizing shopping behavior model, we find that consumers systematically visit multiple stores to take advantage of two types of store complementarity.With 'fixed cost complementarity', consumers alternate visits to highly preferr...

  10. Using a Virtual Store As a Research Tool to Investigate Consumer In-store Behavior.

    Science.gov (United States)

    Ploydanai, Kunalai; van den Puttelaar, Jos; van Herpen, Erica; van Trijp, Hans

    2017-07-24

    People's responses to products and/or choice environments are crucial to understanding in-store consumer behaviors. Currently, there are various approaches (e.g., surveys or laboratory settings) to study in-store behaviors, but the external validity of these is limited by their poor capability to resemble realistic choice environments. In addition, building a real store to meet experimental conditions while controlling for undesirable effects is costly and highly difficult. A virtual store developed by virtual reality techniques potentially transcends these limitations by offering the simulation of a 3D virtual store environment in a realistic, flexible, and cost-efficient way. In particular, a virtual store interactively allows consumers (participants) to experience and interact with objects in a tightly controlled yet realistic setting. This paper presents the key elements of using a desktop virtual store to study in-store consumer behavior. Descriptions of the protocol steps to: 1) build the experimental store, 2) prepare the data management program, 3) run the virtual store experiment, and 4) organize and export data from the data management program are presented. The virtual store enables participants to navigate through the store, choose a product from alternatives, and select or return products. Moreover, consumer-related shopping behaviors (e.g., shopping time, walking speed, and number and type of products examined and bought) can also be collected. The protocol is illustrated with an example of a store layout experiment showing that shelf length and shelf orientation influence shopping- and movement-related behaviors. This demonstrates that the use of a virtual store facilitates the study of consumer responses. The virtual store can be especially helpful when examining factors that are costly or difficult to change in real life (e.g., overall store layout), products that are not presently available in the market, and routinized behaviors in familiar

  11. Children's Bone Health and Calcium

    Science.gov (United States)

    ... Twitter Pinterest Email Print Children's Bone Health and Calcium: Condition Information What is bone health and how ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  12. Buying in multiple stores : Shopping strategies beyond price promotions and their effects on Store Competition

    NARCIS (Netherlands)

    Gijsbrechts, E.; Campo, K.; Nisol, P.

    2013-01-01

    Grocery-store switching has typically been viewed as evidence of cherry-picking behavior, with consumers switching stores to benefit from temporary promotional offers. However, research reveals that it may also result from a longer-term planning process based on stable store characteristics. Even in

  13. The effect of mitochondrial inhibitors on calcium homeostasis in tumor mast cells

    International Nuclear Information System (INIS)

    Mohr, F.C.; Fewtrell, C.

    1990-01-01

    The depletion of intracellular ATP by mitochondrial inhibitors in a glucose-free saline solution inhibited antigen-stimulated 45Ca uptake, the rise in cytoplasmic calcium, measured by fura-2, and secretion in rat basophilic leukemia cells. Lowering the intracellular ATP concentration also released calcium from an intracellular store and made further 45Ca efflux from the cells unresponsive to subsequent antigen stimulation. Antigen-stimulated 45Ca efflux could be restored by the addition of glucose. The ATP-sensitive calcium store appeared to be the same store that releases calcium in response to antigen. In contrast, intracellular ATP was not lowered, and antigen-stimulated secretion was unaffected by mitochondrial inhibitors, provided that glucose was present in the bathing solution. Similarly, antigen-stimulated 45Ca uptake, 45Ca efflux, and the rise in free ionized calcium were unaffected by individual mitochondrial inhibitors in the presence of glucose. However, when the respiratory chain inhibitor antimycin A was used in combination with the ATP synthetase inhibitor oligomycin in the presence of glucose, antigen-stimulated 45Ca uptake was inhibited, whereas the rise in free ionized calcium and secretion were unaffected. Also, antigen-induced depolarization (an indirect measurement of Ca2+ influx across the plasma membrane) was not affected. The inhibition of antigen-stimulated 45Ca uptake could, however, be overcome if a high concentration of the Ca2+ buffer quin2 was present in the cells to buffer the incoming 45Ca. These results suggest that in fully functional rat basophilic leukemia cells the majority of the calcium entering in response to antigen stimulation is initially buffered by a calcium store sensitive to antimycin A and oligomycin, presumably the mitochondria

  14. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about 500...

  15. The interplay between HIF-1 and calcium signalling in cancer.

    Science.gov (United States)

    Azimi, Iman

    2018-04-01

    The interplay between hypoxia-inducible factor-1 (HIF-1) and calcium in cancer has begun to be unravelled with recent findings demonstrating the relationships between the two in different cancer types. This is an area of significance considering the crucial roles of both HIF-1 and calcium signalling in cancer progression and metastasis. This review summarises the experimental evidence of the crosstalk between HIF-1 and specific calcium channels, pumps and regulators in the context of cancer. HIF-1 as a master regulator of hypoxic transcriptional responses, mediates transcription of several calcium modulators. On the other hand, specific calcium channels and pumps regulate HIF-1 activity through controlling its transcription, translation, stabilisation, or nuclear translocation. Identifying the interplay between HIF-1 and components of the calcium signal will give new insights into mechanisms underlying cellular responses to physiological and pathophysiological cues, and may provide novel and more efficient therapeutic strategies for the control of cancer progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Antenatal calcium intake in Malaysia.

    Science.gov (United States)

    Mahdy, Zaleha Abdullah; Basri, Hashimah; Md Isa, Zaleha; Ahmad, Shuhaila; Shamsuddin, Khadijah; Mohd Amin, Rahmah

    2014-04-01

    To determine the adequacy of antenatal calcium intake in Malaysia, and the influencing factors. A cross-sectional study was conducted among postnatal women who delivered in two tertiary hospitals. Data were collected from antenatal cards, hospital documents and diet recall on daily milk and calcium intake during pregnancy. SPSS version 19.0 was used for statistical analyses. A total of 150 women were studied. The total daily calcium intake was 834 ± 43 mg (mean ± standard error of the mean), but the calcium intake distribution curve was skewed to the right with a median intake of 725 mg daily. When calcium intake from milk and calcium supplements was excluded, the daily dietary calcium intake was only 478 ± 25 mg. Even with inclusion of milk and calcium supplements, more than a third (n=55 or 36.7%) of the women consumed less than 600 mg calcium in their daily diet. The adequacy of daily calcium intake was not influenced by maternal age, ethnicity, income or maternal job or educational status as well as parity. The daily dietary calcium intake of the Malaysian antenatal population is far from adequate without the addition of calcium supplements and milk. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  17. The Plasma Membrane Calcium Pump

    Science.gov (United States)

    Rasmussen, H.

    1983-01-01

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

  18. Distributed energy store railguns experiment and analysis

    International Nuclear Information System (INIS)

    Holland, L.D.

    1984-01-01

    Electromagnetic acceleration of projectiles holds the potential for achieving higher velocities than yet achieved by any other means. A railgun is the simplest form of electromagnetic macroparticle accelerator and can generate the highest sustained accelerating force. The practical length of conventional railguns is limited by the impedance of the rails because current must be carried along the entire length of the rails. A railgun and power supply system called the distributed energy store railgun was proposed as a solution to this limitation. The distributed energy store railgun used multiple current sources connected to the rails of a railgun at points distributed along the bore. These current sources (energy stores) are turned on in sequence as the projectile moves down the bore so that current is fed to the railgun from behind the armature. In this system the length of the rails that carry the full armature current is less than the total length of the railgun. If a sufficient number of energy stores is used, this removes the limitation on the length of a railgun. An additional feature of distributed energy store type railguns is that they can be designed to maintain a constant pressure on the projectile being accelerated. A distributed energy store railgun was constructed and successfully operated. In addition to this first demonstration of the distributed energy store railgun principle, a theoretical model of the system was also constructed

  19. NASA Armstrong's Approach to Store Separation Analysis

    Science.gov (United States)

    Acuff, Chris; Bui, Trong

    2015-01-01

    Presentation will an overview of NASA Armstrong's store separation capabilities and how they have been applied recently. Objective of the presentation is to brief Generation Orbit and other potential partners on NASA Armstrong's store separation capabilities. It will include discussions on the use of NAVSEP and Cart3D, as well as some Python scripting work to perform the analysis, and a short overview of this methodology applied to the Towed Glider Air Launch System. Collaboration with potential customers in this area could lead to funding for the further development of a store separation capability at NASA Armstrong, which would boost the portfolio of engineering expertise at the center.

  20. Calcium and Nuclear Signaling in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ivan V. Maly

    2018-04-01

    Full Text Available Recently, there have been a number of developments in the fields of calcium and nuclear signaling that point to new avenues for a more effective diagnosis and treatment of prostate cancer. An example is the discovery of new classes of molecules involved in calcium-regulated nuclear import and nuclear calcium signaling, from the G protein-coupled receptor (GPCR and myosin families. This review surveys the new state of the calcium and nuclear signaling fields with the aim of identifying the unifying themes that hold out promise in the context of the problems presented by prostate cancer. Genomic perturbations, kinase cascades, developmental pathways, and channels and transporters are covered, with an emphasis on nuclear transport and functions. Special attention is paid to the molecular mechanisms behind prostate cancer progression to the malignant forms and the unfavorable response to anti-androgen treatment. The survey leads to some new hypotheses that connect heretofore disparate results and may present a translational interest.

  1. Calcium Biofortification: Three Pronged Molecular Approaches for Dissecting Complex Trait of Calcium Nutrition in Finger Millet (Eleusine coracana) for Devising Strategies of Enrichment of Food Crops.

    Science.gov (United States)

    Sharma, Divya; Jamra, Gautam; Singh, Uma M; Sood, Salej; Kumar, Anil

    2016-01-01

    Calcium is an essential macronutrient for plants and animals and plays an indispensable role in structure and signaling. Low dietary intake of calcium in humans has been epidemiologically linked to various diseases which can have serious health consequences over time. Major staple food-grains are poor source of calcium, however, finger millet [ Eleusine coracana (L.) Gaertn.], an orphan crop has an immense potential as a nutritional security crop due to its exceptionally high calcium content. Understanding the existing genetic variation as well as molecular mechanisms underlying the uptake, transport, accumulation of calcium ions (Ca 2+ ) in grains is of utmost importance for development of calcium bio-fortified crops. In this review, we have discussed molecular mechanisms involved in calcium accumulation and transport thoroughly, emphasized the role of molecular breeding, functional genomics and transgenic approaches to understand the intricate mechanism of calcium nutrition in finger millet. The objective is to provide a comprehensive up to date account of molecular mechanisms regulating calcium nutrition and highlight the significance of bio-fortification through identification of potential candidate genes and regulatory elements from finger millet to alleviate calcium malnutrition. Hence, finger millet could be used as a model system for explaining the mechanism of elevated calcium (Ca 2+ ) accumulation in its grains and could pave way for development of nutraceuticals or designer crops.

  2. Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential

    Directory of Open Access Journals (Sweden)

    Brinton Roberta

    2008-12-01

    Full Text Available Abstract Background Factors that regulate intracellular calcium concentration are known to play a critical role in brain function and neural development, including neural plasticity and neurogenesis. We previously demonstrated that the neurosteroid allopregnanolone (APα; 5α-pregnan-3α-ol-20-one promotes neural progenitor proliferation in vitro in cultures of rodent hippocampal and human cortical neural progenitors, and in vivo in triple transgenic Alzheimer's disease mice dentate gyrus. We also found that APα-induced proliferation of neural progenitors is abolished by a calcium channel blocker, nifedipine, indicating a calcium dependent mechanism for the proliferation. Methods In the present study, we investigated the effect of APα on the regulation of intracellular calcium concentration in E18 rat hippocampal neurons using ratiometric Fura2-AM imaging. Results Results indicate that APα rapidly increased intracellular calcium concentration in a dose-dependent and developmentally regulated manner, with an EC50 of 110 ± 15 nM and a maximal response occurring at three days in vitro. The stereoisomers 3β-hydroxy-5α-hydroxy-pregnan-20-one, and 3β-hydroxy-5β-hydroxy-pregnan-20-one, as well as progesterone, were without significant effect. APα-induced intracellular calcium concentration increase was not observed in calcium depleted medium and was blocked in the presence of the broad spectrum calcium channel blocker La3+, or the L-type calcium channel blocker nifedipine. Furthermore, the GABAA receptor blockers bicuculline and picrotoxin abolished APα-induced intracellular calcium concentration rise. Conclusion Collectively, these data indicate that APα promotes a rapid, dose-dependent, stereo-specific, and developmentally regulated increase of intracellular calcium concentration in rat embryonic hippocampal neurons via a mechanism that requires both the GABAA receptor and L-type calcium channel. These data suggest that AP

  3. Effect of calcium chloride and calcium lactate on quality and shelf-life of fresh-cut guava slices

    International Nuclear Information System (INIS)

    Raheem, M.I.U.; Huma, N.; Anjum, F.M.

    2013-01-01

    Present study was conducted to investigate the effectiveness of chemical treatments at low temperature on the quality of fresh-cut guava slices during 2011-12. Uniform sized guava slices were made free from seeds and treated with calcium chloride and calcium lactate with concentration 0.9%, 1.8%, 2.7% or 3.6%. After packing in plastic boxes, all treated samples were stored at 5 degree C + 2 degree C in a refrigerator for 24 days with 6 day interval between different removals. The results obtained from physico-chemical analysis showed decrease in firmness (111.67-12.67gf) and increase in browning (1.19-1.93nm) of guava slices compared to control with the passage of storage interval. Moreover, scores in taste (7.33-1.00), flavour (7.33-1.00), colour (7.50-1.00) and texture (7.67-1.00) of guava slices was also decreased with respect to interaction of treatments and storage period. Calcium chloride at the rate 2.7% showed significantly higher stability than other concentrations of calcium chloride and calcium lactate in delaying firmness and browning of fresh-cut guava slices along with maintaining their organoleptic properties for longer storage period. However, calcium chloride imparted undesirable bitterness to fresh-cut guava slices at the concentration of 3.6%. Based on the overall quality performance, 2.7% calcium chloride and 3.6% calcium lactate exhibited better results than other concentrations and control with storage life of 8 days at 5 degree C + 2 degree C. (author)

  4. Health food store recommendations: implications for breast cancer patients

    International Nuclear Information System (INIS)

    Mills, Edward; Ernst, Edzard; Singh, Rana; Ross, Cory; Wilson, Kumanan

    2003-01-01

    Many breast cancer patients use complementary and alternative medicine (CAM). We aimed to determine what advice health food store employees present to individuals seeking treatment options for breast cancer. Eight data gatherers asked employees of all retail health food stores in a major Canadian city, what they recommended for a patient with breast cancer. The data gatherers inquired about product safety, potential drug interactions, costs and efficacy. They also enquired about employee training related to the products. Thirty-four stores were examined. A total of 33 different products were recommended, none of which are supported by sufficient evidence of efficacy. The average cost of the products they recommended was $58.09 (CAD) (minimum $5.28, median $32.99, maximum $600) per month. Twenty-three employees (68%) did not ask whether the patient took prescription medications. Fifteen employees (44%) recommended visiting a healthcare professional (naturopaths (9), physicians (5), nutritionists (1). Three employees (8.8%) discussed potential adverse effects of the products. Eight employees (23.5%) discussed the potential for drug interactions. Two employees (5.9%) suggested a possible cure with the products and one employee (2.9%) suggested discontinuing Tamoxifen. Four employees (11.8%) recommended lifestyle changes and three employees (8.8%) recommended books for further reading on the products. This study draws attention to the heterogeneity of advice provided by natural health food stores to individuals seeking treatments for breast cancer, and the safety and cost implications of some of the products recommended. Physicians should enquire carefully about the use of natural health food products by patients with breast cancer. Regulators need to consider regulations to protect vulnerable patients from incurring significant costs in their purchasing of natural health food products lacking evidence of benefit and of questionable safety

  5. Movement of calcium signals and calcium-binding proteins: firewalls, traps and tunnels.

    Science.gov (United States)

    Barrow, S L; Sherwood, M W; Dolman, N J; Gerasimenko, O V; Voronina, S G; Tepikin, A V

    2006-06-01

    In the board game 'Snakes and Ladders', placed on the image of a pancreatic acinar cell, calcium ions have to move from release sites in the secretory region to the nucleus. There is another important contraflow - from calcium entry channels in the basal part of the cell to ER (endoplasmic reticulum) terminals in the secretory granule region. Both transport routes are perilous as the messenger can disappear in any place on the game board. It can be grabbed by calcium ATPases of the ER (masquerading as a snake but functioning like a ladder) and tunnelled through its low buffering environment, it can be lured into the whirlpools of mitochondria uniporters and forced to regulate the tricarboxylic acid cycle, and it can be permanently placed inside the matrix of secretory granules and released only outside the cell. The organelles could trade calcium (e.g. from the ER to mitochondria and vice versa) almost depriving this ion the light of the cytosol and noble company of cytosolic calcium buffers. Altogether it is a rich and colourful story.

  6. L-Type Calcium Channels Modulation by Estradiol.

    Science.gov (United States)

    Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

    2017-09-01

    Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

  7. Stored energy in irradiated silicon carbide

    Energy Technology Data Exchange (ETDEWEB)

    Snead, L.L.; Burchell, T.D. [Oak Ridge National Lab., TN (United States)

    1997-04-01

    This report presents a short review of the phenomenon of Wigner stored energy release from irradiated graphite and discusses it in relation to neutron irradiation of silicon carbide. A single published work in the area of stored energy release in SiC is reviewed and the results are discussed. It appears from this previous work that because the combination of the comparatively high specific heat of SiC and distribution in activation energies for recombining defects, the stored energy release of SiC should only be a problem at temperatures lower than those considered for fusion devices. The conclusion of this preliminary review is that the stored energy release in SiC will not be sufficient to cause catastrophic heating in fusion reactor components, though further study would be desirable.

  8. Boligmarkedet uden for de store byer

    DEFF Research Database (Denmark)

    Larsen, Jacob Norvig; Andersen, Hans Thor; Haldrup, Karin

    landet som helhed, hvor den østjyske millionby og hovedstaden er migrationens mål. Dermed må der på steder langt fra de store byers infrastruktur og arbejdspladser forventes faldende eller meget begrænset efterspørgsel efter boliger. Det gælder især gamle, dårligt vedligeholdte boliger og boliger med...... og lokalpolitiske planer og indsatser. Tre casestudier belyser, hvordan man i lokalsamfund i tre kommuner uden for de store byer aktivt tager den udfordring op, som følger af en generel strukturændring med øget urbanisering og aldrende befolkning i områderne uden for de store byer. Med blandt andet...... nye samarbejdsformer mellem private, frivillige og kommunale aktører og aktivitets- og beboerhuse som base for foreningsaktivitet er det flere steder lykkedes at tiltrække tilflyttere til samfund langt uden for de store byer....

  9. Infant Formula - Buying, Preparing, Storing, and Feeding

    Science.gov (United States)

    ... 000806.htm Infant Formula - buying, preparing, storing, and feeding To use the sharing features on this page, ... brush to get at hard-to-reach places. Feeding Formula to Baby Here is a guide to ...

  10. Retailing: Careers in the Department Store Industry.

    Science.gov (United States)

    Martin, Gail M.

    1982-01-01

    The retailing industry is overviewed and executive training programs are detailed. Jobs in retailing are described: merchandising, department manager, assistant buyer, buyer, merchandise manager, and store manager. Also discussed are operations, financial control, and personnel management. (CT)

  11. Human Resources Operational Data Store Core Services

    Data.gov (United States)

    Social Security Administration — This database contains only a very small subset of the Human Resources Operational Data Store data. It supports the SSA Employee and Office Data Retrieval (SEODR)...

  12. Apparatus and method for monitoring stored material

    International Nuclear Information System (INIS)

    Price, W.E.; Lewis, D.R.; Galloway, L.A.; Lowrey, C.B.

    1983-01-01

    Material, e.g. radioactive waste or other hazardous material, which is to be stored and monitored is placed within the innermost container of a series of nested containers and monitoring fluids are circulated in a closed loop of fluid flow through the spaces between the nested containers. Monitoring devices are used to analyse said monitoring fluids to detect leakage of the stored material from the innermost nested container and to detect the migration of external fluids into the series of nested containers. A computer based monitoring system continually checks the values of various parameters of the monitoring fluids to immediately detect and report the presence of stored material or external fluid in the monitoring fluids. The stored material may then be immediately retrieved from storage to repair leaks in the series of nested containers. (author)

  13. Mitochondrial Ca{sup 2+} uniporter is critical for store-operated Ca{sup 2+} entry-dependent breast cancer cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Shihao [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Guangzhou No.12 Hospital, Guangzhou (China); Wang, Xubu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Shen, Qiang [Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Yang, Xinyi; Yu, Changhui; Cai, Chunqing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Cai, Guoshuai [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Meng, Xiaojing, E-mail: xiaojingmeng@smu.edu.cn [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China)

    2015-02-27

    Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca{sup 2+} uniporter (MCU), a regulator of mitochondrial Ca{sup 2+} uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MCU is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)-induced store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE. - Highlights: • MCU is correlated to metastasis and invasive breast cancer. • MCU inhibition abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or TG-induced SOCE. • Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. • MCU plays a critical role in MDA-MB-231 cell migration by regulating SOCE.

  14. The transition between monostable and bistable states induced by time delay in intracellular calcium oscillation

    International Nuclear Information System (INIS)

    Duan, Wei-Long

    2013-01-01

    The revised role of the time delay of active processes with colored noises of transmission of intracellular Ca 2+ in intracellular calcium oscillation (ICO) is investigated by means of a first-order algorithm based on stochastic simulation. The simulation results indicate that time delay induces a double critical phenomenon and a transition between the monostable and bistable states of the ICO system. In addition, as the time delay increases, for a cytosolic Ca 2+ concentration with weak colored noises there appears a calcium burst, and the Ca 2+ concentration of the calcium store shows nonmonotonic variation. (paper)

  15. STRATEGI MARKET ENTRY CONVENIENCE STORE DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Respati Wulandari

    2017-04-01

    Full Text Available Penelitian ini bertujuan untuk menganalisa dan melihat strategi yang digunakan pada Convenience Store di Indonesia dengan mengambil 7-Eleven sebagai sumber field study dengan metode orientasi pasar. Pengaruh lifestyle menjadi indikator penunjang dalam perkembangan 7-Eleven ddengan menerapkan beberapa strategi yang mengena di market Indonesia, terutama bagi kalangan muda dimana diketahui memiliki indikasi terpenting dalam siklus lifestyle di Indonesia. Tujuan tercapai dengan mengetahui penerapan strategi yang digunakan sehingga dapat diterapkan dalam menjalankan strategi bisnis pada Convenience Store

  16. Torness delay is storing up trouble

    International Nuclear Information System (INIS)

    Cavenagh, Andrew.

    1994-01-01

    A recent decision by the Scottish Office to delay planning permission for the construction of a 50 million dry store for spent nuclear fuel at Torness Power Station is proving frustrating and inexplicable to many in the nuclear industry. The possible reasons for this apparent about face in government policy on spent fuel management are debated and the economic ramifications of the decision for British Nuclear Fuels Limited (BNFL), if the store were to go ahead, are outlined. (UK)

  17. Marketing practices of vapor store owners.

    Science.gov (United States)

    Cheney, Marshall; Gowin, Mary; Wann, Taylor Franklin

    2015-06-01

    We examined the marketing strategies for local vapor stores in a large metropolitan area in Oklahoma. Vapor store owners or managers (n = 33) participated in individual interviews regarding marketing practices in 2014. We asked owners about their marketing strategies and the groups they targeted. We transcribed the interviews and analyzed them for themes. Store owners used a variety of marketing strategies to bring new customers to their stores and keep current customers coming back. These marketing strategies showed many parallels to tobacco industry strategies. Most owners engaged in some form of traditional marketing practices (e.g., print media), but only a few used radio or television advertising because of budget constraints. Owners used social media and other forms of electronic communication, pricing discounts and specials, and loyalty programs. Owners also had booths at local events, sponsored community events, and hosted them in their stores. Owners attempted to target different groups of users, such as college students and long-term smokers. Local vapor store marketing practices closely resemble current and former tobacco industry marketing strategies. Surveillance of marketing practices should include local and Web-based strategies.

  18. Marketing Practices of Vapor Store Owners

    Science.gov (United States)

    Gowin, Mary; Wann, Taylor Franklin

    2015-01-01

    Objectives. We examined the marketing strategies for local vapor stores in a large metropolitan area in Oklahoma. Methods. Vapor store owners or managers (n = 33) participated in individual interviews regarding marketing practices in 2014. We asked owners about their marketing strategies and the groups they targeted. We transcribed the interviews and analyzed them for themes. Results. Store owners used a variety of marketing strategies to bring new customers to their stores and keep current customers coming back. These marketing strategies showed many parallels to tobacco industry strategies. Most owners engaged in some form of traditional marketing practices (e.g., print media), but only a few used radio or television advertising because of budget constraints. Owners used social media and other forms of electronic communication, pricing discounts and specials, and loyalty programs. Owners also had booths at local events, sponsored community events, and hosted them in their stores. Owners attempted to target different groups of users, such as college students and long-term smokers. Conclusions. Local vapor store marketing practices closely resemble current and former tobacco industry marketing strategies. Surveillance of marketing practices should include local and Web-based strategies. PMID:25880960

  19. Interaction of H2S with Calcium Permeable Channels and Transporters

    Directory of Open Access Journals (Sweden)

    Weihua Zhang

    2015-01-01

    Full Text Available A growing amount of evidence has suggested that hydrogen sulfide (H2S, as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC, T-type calcium channels (TTCC, sodium/calcium exchangers (NCX, transient receptor potential (TRP channels, β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.

  20. The Key Points of Building an Online Store

    OpenAIRE

    Etuaro, Mari

    2014-01-01

    Online shopping is becoming more popular in Finland and online shopping sales levels have increased. There has been concern that brick and mortar stores are losing their customers to online stores and that Finnish stores are losing their customers to international online stores. One solution to this concern is that Finnish brick and mortar stores also start selling online. But how to build online stores? The aim of this thesis was to study about building an online store based on theory and...