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Sample records for calcium sensor ncs

  1. Fission yeast homolog of neuronal calcium sensor-1 (Ncs1p) regulates sporulation and confers calcium tolerance.

    PubMed

    Hamasaki-Katagiri, Nobuko; Molchanova, Tatiana; Takeda, Kazuyo; Ames, James B

    2004-03-26

    The neuronal calcium sensor (NCS) proteins (e.g. recoverin, neurocalcins, and frequenin) are expressed at highest levels in excitable cells, and some of them regulate desensitization of G protein-coupled receptors. Here we present NMR analysis and genetic functional studies of an NCS homolog in fission yeast (Ncs1p). Ncs1p binds three Ca2+ ions at saturation with an apparent affinity of 2 microm and Hill coefficient of 1.9. Analysis of NMR and fluorescence spectra of Ncs1p revealed significant Ca2+-induced protein conformational changes indicative of a Ca2+-myristoyl switch. The amino-terminal myristoyl group is sequestered inside a hydrophobic cavity of the Ca2+-free protein and becomes solvent-exposed in the Ca2+-bound protein. Subcellular fractionation experiments showed that myristoylation and Ca2+ binding by Ncs1p are essential for its translocation from cytoplasm to membranes. The ncs1 deletion mutant (ncs1Delta) showed two distinct phenotypes: nutrition-insensitive sexual development and a growth defect at high levels of extracellular Ca2+ (0.1 m CaCl(2)). Analysis of Ncs1p mutants lacking myristoylation (Ncs1p(G2A)) or deficient in Ca2+ binding (Ncs1p(E84Q/E120Q/E168Q)) revealed that Ca2+ binding was essential for both phenotypes, while myristoylation was less critical. Exogenous cAMP, a key regulator for sexual development, suppressed conjugation and sporulation of ncs1Delta, suggesting involvement of Ncs1p in the adenylate cyclase pathway turned on by the glucose-sensing G protein-coupled receptor Git3p. Starvation-independent sexual development of ncs1Delta was also complemented by retinal recoverin, which controls Ca2+-regulated desensitization of rhodopsin. In contrast, the Ca2+-intolerance of ncs1Delta was not affected by cAMP or recoverin, suggesting that the two ncs1Delta phenotypes are mechanistically independent. We propose that Schizosaccharomyces pombe Ncs1p negatively regulates sporulation perhaps by controlling Ca2+-dependent desensitization

  2. Datasets depicting mobility retardation of NCS proteins observed upon incubation with calcium, but not with magnesium, barium or strontium.

    PubMed

    Viviano, Jeffrey; Krishnan, Anuradha; Scully, Jenna; Wu, Hao; Venkataraman, Venkat

    2016-06-01

    In this data article we show the specificity of the Ca(2+)-induced mobility shift in three proteins that belong to the neuronal calcium sensor (NCS) protein family: Hippocalcin, GCAP1 and GCAP2. These proteins did not display a shift in mobility in native gels when incubated with divalent cations other than Ca(2+) - such as Mg(2+), Ba(2+), and Sr(2+), even at 10× concentrations. The data is similar to that obtained with another NCS protein, neurocalcin delta (Viviano et al., 2016, "Electrophoretic Mobility Shift in Native Gels Indicates Calcium-dependent Structural Changes of Neuronal Calcium Sensor Proteins", [1]). PMID:27222862

  3. Datasets depicting mobility retardation of NCS proteins observed upon incubation with calcium, but not with magnesium, barium or strontium

    PubMed Central

    Viviano, Jeffrey; Krishnan, Anuradha; Scully, Jenna; Wu, Hao; Venkataraman, Venkat

    2016-01-01

    In this data article we show the specificity of the Ca2+-induced mobility shift in three proteins that belong to the neuronal calcium sensor (NCS) protein family: Hippocalcin, GCAP1 and GCAP2. These proteins did not display a shift in mobility in native gels when incubated with divalent cations other than Ca2+ – such as Mg2+, Ba2+, and Sr2+, even at 10× concentrations. The data is similar to that obtained with another NCS protein, neurocalcin delta (Viviano et al., 2016, “Electrophoretic Mobility Shift in Native Gels Indicates Calcium-dependent Structural Changes of Neuronal Calcium Sensor Proteins”, [1]). PMID:27222862

  4. Paclitaxel accelerates spontaneous calcium oscillations in cardiomyocytes by interacting with NCS-1 and the InsP3R

    PubMed Central

    Zhang, Kun; Heidrich, Felix M.; DeGray, Brenda; Boehmerle, Wolfgang; Ehrlich, Barbara E.

    2010-01-01

    Paclitaxel (Taxol) is a microtubule-stabilizing compound that is used for cancer chemotherapy. However, Taxol administration is limited by serious side effects including cardiac arrhythmia, which cannot be explained by its microtubule-stabilizing effect. Recently, neuronal calcium sensor 1 (NCS-1), a calcium binding protein that modulates the inositol-1,4,5-trisphosphate receptor (InsP3R), was described as a binding partner of Taxol and as a substrate of calpain. We examined calcium signaling processes in cardiomyocytes after treatment with Taxol to investigate the basis of Taxol-induced cardiac arrhythmia. After treating isolated neonatal rat ventricular myocytes with a therapeutic concentration of Taxol for several hours live cell imaging experiments showed that the frequency of spontaneous calcium oscillations significantly increased. This effect was not mimicked by other tubulin-stabilizing agents. However, it was prevented by inhibiting the InsP3R. Taxol treated cells had increased expression of NCS-1, an effect also detectable after Taxol administration in vivo. Short hairpin RNA mediated knock down of NCS-1 decreased InsP3R dependent intracellular calcium release, whereas Taxol treatment, that increased NCS-1 levels, increased InsP3R dependent calcium release. The effects of Taxol were ryanodine receptor independent. At the single channel level Taxol and NCS-1 mediated an increase in InsP3R activity. Calpain activity was not affected by Taxol in cardiomyocytes suggesting a calpain independent signaling pathway. In short, our study shows that Taxol impacts calcium signaling and calcium oscillations in cardiomyocytes through NCS-1 and the InsP3R. PMID:20801127

  5. Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics.

    PubMed

    Wang, Baisheng; Boeckel, Göran R; Huynh, Larry; Nguyen, Lien; Cao, Wenxiang; De La Cruz, Enrique M; Kaftan, Edward J; Ehrlich, Barbara E

    2016-01-01

    Neuronal calcium sensor-1 (NCS-1 Var1) is a calcium-binding protein expressed in most tissues. We examined a poorly characterized variant of NCS-1 (Var2), identified only in humans where the N-terminal 22 amino acid residues of native NCS-1(MGKSNSKLKPEVVEELTRKTY) were replaced with 4 different residues (MATI). Because alterations in the level of expression of NCS-1 Var1 and the expression of NCS-1 variants have been correlated with several neurological diseases, the relative expression and functional role of NCS-1 Var2 was examined. We found that NCS-1 Var2 mRNA levels are not found in mouse tissues and are expressed at levels ~1000-fold lower than NCS-1 Var1 in three different human cell lines (SHSY5Y, HEK293, MB231). Protein expression of both variants was only identified in cell lines overexpressing exogenous NCS-1 Var2. The calcium binding affinity is ~100 times weaker in purified NCS-1 Var2 than NCS-1 Var1. Because truncation of NCS-1 Var1 has been linked to functional changes in neurons, we determined whether the differing properties of the NCS-1 variants could potentially contribute to the altered cell function. In contrast to previous reports showing that overexpression of NCS-1 Var1 increases calcium-dependent processes, functional differences in cells overexpressing NCS-1 Var2 were undetectable in assays for cell growth, cell death and drug (paclitaxel) potency. Our results suggest that NCS-1 Var1 is the primary functional version of NCS-1. PMID:27575489

  6. Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics

    PubMed Central

    Wang, Baisheng; Boeckel, Göran R.; Huynh, Larry; Nguyen, Lien; Cao, Wenxiang; De La Cruz, Enrique M.; Kaftan, Edward J.

    2016-01-01

    Neuronal calcium sensor-1 (NCS-1 Var1) is a calcium-binding protein expressed in most tissues. We examined a poorly characterized variant of NCS-1 (Var2), identified only in humans where the N-terminal 22 amino acid residues of native NCS-1(MGKSNSKLKPEVVEELTRKTY) were replaced with 4 different residues (MATI). Because alterations in the level of expression of NCS-1 Var1 and the expression of NCS-1 variants have been correlated with several neurological diseases, the relative expression and functional role of NCS-1 Var2 was examined. We found that NCS-1 Var2 mRNA levels are not found in mouse tissues and are expressed at levels ~1000-fold lower than NCS-1 Var1 in three different human cell lines (SHSY5Y, HEK293, MB231). Protein expression of both variants was only identified in cell lines overexpressing exogenous NCS-1 Var2. The calcium binding affinity is ~100 times weaker in purified NCS-1 Var2 than NCS-1 Var1. Because truncation of NCS-1 Var1 has been linked to functional changes in neurons, we determined whether the differing properties of the NCS-1 variants could potentially contribute to the altered cell function. In contrast to previous reports showing that overexpression of NCS-1 Var1 increases calcium-dependent processes, functional differences in cells overexpressing NCS-1 Var2 were undetectable in assays for cell growth, cell death and drug (paclitaxel) potency. Our results suggest that NCS-1 Var1 is the primary functional version of NCS-1. PMID:27575489

  7. Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder

    PubMed Central

    D'Onofrio, Stasia; Kezunovic, Nebojsa; Hyde, James R.; Luster, Brennon; Messias, Erick; Urbano, Francisco J.

    2014-01-01

    Reduced levels of gamma-band activity are present in schizophrenia and bipolar disorder patients. In the same disorders, increased neuronal calcium sensor protein-1 (NCS-1) expression was reported in a series of postmortem studies. These disorders are also characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). The discovery of gamma-band activity in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, revealed that such activity was mediated by high-threshold calcium channels that are regulated by NCS-1. We hypothesized that NCS-1 normally regulates gamma-band oscillations through these calcium channels and that excessive levels of NCS-1, such as would be expected with overexpression, decrease gamma-band activity. We found that PPN neurons in rat brain slices manifested gamma-band oscillations that were increased by low levels of NCS-1 but suppressed by high levels of NCS-1. Our results suggest that NCS-1 overexpression may be responsible for the decrease in gamma-band activity present in at least some schizophrenia and bipolar disorder patients. PMID:25376789

  8. The neuronal calcium sensor family of Ca2+-binding proteins.

    PubMed Central

    Burgoyne, R D; Weiss, J L

    2001-01-01

    Ca(2+) plays a central role in the function of neurons as the trigger for neurotransmitter release, and many aspects of neuronal activity, from rapid modulation to changes in gene expression, are controlled by Ca(2+). These actions of Ca(2+) must be mediated by Ca(2+)-binding proteins, including calmodulin, which is involved in Ca(2+) regulation, not only in neurons, but in most other cell types. A large number of other EF-hand-containing Ca(2+)-binding proteins are known. One family of these, the neuronal calcium sensor (NCS) proteins, has a restricted expression in retinal photoreceptors or neurons and neuroendocrine cells, suggesting that they have specialized roles in these cell types. Two members of the family (recoverin and guanylate cyclase-activating protein) have established roles in the regulation of phototransduction. Despite close sequence similarities, the NCS proteins have distinct neuronal distributions, suggesting that they have different functions. Recent work has begun to demonstrate the physiological roles of members of this protein family. These include roles in the modulation of neurotransmitter release, control of cyclic nucleotide metabolism, biosynthesis of polyphosphoinositides, regulation of gene expression and in the direct regulation of ion channels. In the present review we describe the known sequences and structures of the NCS proteins, information on their interactions with target proteins and current knowledge about their cellular and physiological functions. PMID:11115393

  9. Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.

    PubMed

    Ng, Enoch; Varaschin, Rafael K; Su, Ping; Browne, Caleb J; Hermainski, Joanna; Le Foll, Bernard; Pongs, Olaf; Liu, Fang; Trudeau, Louis-Eric; Roder, John C; Wong, Albert H C

    2016-03-15

    Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior. PMID:26738968

  10. Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation.

    PubMed

    Boehmerle, Wolfgang; Zhang, Kun; Sivula, Michael; Heidrich, Felix M; Lee, Yashang; Jordt, Sven-Eric; Ehrlich, Barbara E

    2007-06-26

    Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP(3))-mediated Ca(2+) signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP(3) receptor (InsP(3)R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca(2+) signaling. When NCS-1 protein levels recovered, so did InsP(3)-mediated Ca(2+) signaling. Inhibition of the Ca(2+)-activated protease mu-calpain prevented alterations in phosphoinositide-mediated Ca(2+) signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by mu-calpain in vitro and that mu-calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates mu-calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP(3)mediated Ca(2+) signaling. These findings provide a previously undescribed approach to understanding and treating Taxol-induced peripheral neuropathy. PMID:17581879

  11. Characterisation of the Interaction of the C-Terminus of the Dopamine D2 Receptor with Neuronal Calcium Sensor-1

    PubMed Central

    Lian, Lu-Yun; Pandalaneni, Sravan R.; Patel, Pryank; McCue, Hannah V.; Haynes, Lee P.; Burgoyne, Robert D.

    2011-01-01

    NCS-1 is a member of the neuronal calcium sensor (NCS) family of EF-hand Ca2+ binding proteins which has been implicated in several physiological functions including regulation of neurotransmitter release, membrane traffic, voltage gated Ca2+ channels, neuronal development, synaptic plasticity, and learning. NCS-1 binds to the dopamine D2 receptor, potentially affecting its internalisation and controlling dopamine D2 receptor surface expression. The D2 receptor binds NCS-1via a short 16-residue cytoplasmic C-terminal tail. We have used NMR and fluorescence spectroscopy to characterise the interactions between the NCS-1/Ca2+ and D2 peptide. The data show that NCS-1 binds D2 peptide with a Kd of ∼14.3 µM and stoichiometry of peptide binding to NCS-1 of 2∶1. NMR chemical shift mapping confirms that D2 peptide binds to the large, solvent-exposed hydrophobic groove, on one face of the NCS-1 molecule, with residues affected by the presence of the peptide spanning both the N and C-terminal portions of the protein. The NMR and mutagenesis data further show that movement of the C-terminal helix 11 of NCS-1 to fully expose the hydrophobic groove is important for D2 peptide binding. Molecular docking using restraints derived from the NMR chemical shift data, together with the experimentally-derived stoichiometry, produced a model of the complex between NCS-1 and the dopamine receptor, in which two molecules of the receptor are able to simultaneously bind to the NCS-1 monomer. PMID:22114693

  12. Interaction of ARF-1.1 and neuronal calcium sensor-1 in the control of the temperature-dependency of locomotion in Caenorhabditis elegans

    PubMed Central

    Todd, Paul A. C.; McCue, Hannah V.; Haynes, Lee P.; Barclay, Jeff W.; Burgoyne, Robert D.

    2016-01-01

    Neuronal calcium sensor-1 (NCS-1) mediates changes in cellular function by regulating various target proteins. Many potential targets have been identified but the physiological significance of only a few has been established. Upon temperature elevation, Caenorhabditis elegans exhibits reversible paralysis. In the absence of NCS-1, worms show delayed onset and a shorter duration of paralysis. This phenotype can be rescued by re-expression of ncs-1 in AIY neurons. Mutants with defects in four potential NCS-1 targets (arf-1.1, pifk-1, trp-1 and trp-2) showed qualitatively similar phenotypes to ncs-1 null worms, although the effect of pifk-1 mutation on time to paralysis was considerably delayed. Inhibition of pifk-1 also resulted in a locomotion phenotype. Analysis of double mutants showed no additive effects between mutations in ncs-1 and trp-1 or trp-2. In contrast, double mutants of arf-1.1 and ncs-1 had an intermediate phenotype, consistent with NCS-1 and ARF-1.1 acting in the same pathway. Over-expression of arf-1.1 in the AIY neurons was sufficient to rescue partially the phenotype of both the arf-1.1 and the ncs-1 null worms. These findings suggest that ARF-1.1 interacts with NCS-1 in AIY neurons and potentially pifk-1 in the Ca2+ signaling pathway that leads to inhibited locomotion at an elevated temperature. PMID:27435667

  13. Interaction of ARF-1.1 and neuronal calcium sensor-1 in the control of the temperature-dependency of locomotion in Caenorhabditis elegans.

    PubMed

    Todd, Paul A C; McCue, Hannah V; Haynes, Lee P; Barclay, Jeff W; Burgoyne, Robert D

    2016-01-01

    Neuronal calcium sensor-1 (NCS-1) mediates changes in cellular function by regulating various target proteins. Many potential targets have been identified but the physiological significance of only a few has been established. Upon temperature elevation, Caenorhabditis elegans exhibits reversible paralysis. In the absence of NCS-1, worms show delayed onset and a shorter duration of paralysis. This phenotype can be rescued by re-expression of ncs-1 in AIY neurons. Mutants with defects in four potential NCS-1 targets (arf-1.1, pifk-1, trp-1 and trp-2) showed qualitatively similar phenotypes to ncs-1 null worms, although the effect of pifk-1 mutation on time to paralysis was considerably delayed. Inhibition of pifk-1 also resulted in a locomotion phenotype. Analysis of double mutants showed no additive effects between mutations in ncs-1 and trp-1 or trp-2. In contrast, double mutants of arf-1.1 and ncs-1 had an intermediate phenotype, consistent with NCS-1 and ARF-1.1 acting in the same pathway. Over-expression of arf-1.1 in the AIY neurons was sufficient to rescue partially the phenotype of both the arf-1.1 and the ncs-1 null worms. These findings suggest that ARF-1.1 interacts with NCS-1 in AIY neurons and potentially pifk-1 in the Ca(2+) signaling pathway that leads to inhibited locomotion at an elevated temperature. PMID:27435667

  14. Modulation of CaV2.1 channels by neuronal calcium sensor-1 induces short-term synaptic facilitation.

    PubMed

    Yan, Jin; Leal, Karina; Magupalli, Venkat G; Nanou, Evanthia; Martinez, Gilbert Q; Scheuer, Todd; Catterall, William A

    2014-11-01

    Facilitation and inactivation of P/Q-type Ca2+ currents mediated by Ca2+/calmodulin binding to Ca(V)2.1 channels contribute to facilitation and rapid depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin from its binding site and differentially modulate P/Q-type Ca2 + currents, resulting in diverse patterns of short-term synaptic plasticity. Neuronal calcium sensor-1 (NCS-1, frequenin) has been shown to enhance synaptic facilitation, but the underlying mechanism is unclear. We report here that NCS-1 directly interacts with IQ-like motif and calmodulin-binding domain in the C-terminal domain of Ca(V)2.1 channel. NCS-1 reduces Ca2 +-dependent inactivation of P/Q-type Ca2+ current through interaction with the IQ-like motif and calmodulin-binding domain without affecting peak current or activation kinetics. Expression of NCS-1 in presynaptic superior cervical ganglion neurons has no effect on synaptic transmission, eliminating effects of this calcium sensor protein on endogenous N-type Ca2+ currents and the endogenous neurotransmitter release machinery. However, in superior cervical ganglion neurons expressing wild-type Ca(V)2.1 channels, co-expression of NCS-1 induces facilitation of synaptic transmission in response to paired pulses and trains of depolarizing stimuli, and this effect is lost in Ca(V)2.1 channels with mutations in the IQ-like motif and calmodulin-binding domain. These results reveal that NCS-1 directly modulates Ca(V)2.1 channels to induce short-term synaptic facilitation and further demonstrate that CaS proteins are crucial in fine-tuning short-term synaptic plasticity. PMID:25447945

  15. Single-Molecule Folding Mechanisms of the apo- and Mg2+-Bound States of Human Neuronal Calcium Sensor-1

    PubMed Central

    Naqvi, Mohsin M.; Heidarsson, Pétur O.; Otazo, Mariela R.; Mossa, Alessandro; Kragelund, Birthe B.; Cecconi, Ciro

    2015-01-01

    Neuronal calcium sensor-1 (NCS-1) is the primordial member of a family of proteins responsible primarily for sensing changes in neuronal Ca2+ concentration. NCS-1 is a multispecific protein interacting with a number of binding partners in both calcium-dependent and independent manners, and acting in a variety of cellular processes in which it has been linked to a number of disorders such as schizophrenia and autism. Despite extensive studies on the Ca2+-activated state of NCS proteins, little is known about the conformational dynamics of the Mg2+-bound and apo states, both of which are populated, at least transiently, at resting Ca2+ conditions. Here, we used optical tweezers to study the folding behavior of individual NCS-1 molecules in the presence of Mg2+ and in the absence of divalent ions. Under tension, the Mg2+-bound state of NCS-1 unfolds and refolds in a three-state process by populating one intermediate state consisting of a folded C-domain and an unfolded N-domain. The interconversion at equilibrium between the different molecular states populated by NCS-1 was monitored in real time through constant-force measurements and the energy landscapes underlying the observed transitions were reconstructed through hidden Markov model analysis. Unlike what has been observed with the Ca2+-bound state, the presence of Mg2+ allows both the N- and C-domain to fold through all-or-none transitions with similar refolding rates. In the absence of divalent ions, NCS-1 unfolds and refolds reversibly in a two-state reaction involving only the C-domain, whereas the N-domain has no detectable transitions. Overall, the results allowed us to trace the progression of NCS-1 folding along its energy landscapes and provided a solid platform for understanding the conformational dynamics of similar EF-hand proteins. PMID:26153708

  16. Temperature-Dependent Conformational Properties of Human Neuronal Calcium Sensor-1 Protein Revealed by All-Atom Simulations.

    PubMed

    Zhu, Yuzhen; Ma, Buyong; Qi, Ruxi; Nussinov, Ruth; Zhang, Qingwen

    2016-04-14

    Neuronal calcium sensor-1 (NCS-1) protein has orthologues from Saccharomyces cerevisiae to human with highly conserved amino acid sequences. NCS-1 is an important factor controlling the animal's response to temperature change. This leads us to investigate the temperature effects on the conformational dynamics of human NCS-1 at 310 and 316 K by all-atom molecular dynamics (MD) simulations and dynamic community network analysis. Four independent 500 ns MD simulations show that secondary structure content at 316 K is similar to that at 310 K, whereas the global protein structure is expanded. Loop 3 (L3) adopts an extended state occuping the hydrophobic crevice, and the number of suboptimal communication paths between residue D176 and V190 is reduced at 316 K. The dynamic community network analysis suggests that the interdomain correlation is weakened, and the intradomain coupling is strengthened at 316 K. The elevated temperature reduces the number of the salt bridges, especially in C-domain. This study suggests that the elevated temperature affects the conformational dynamics of human NCS-1 protein. Comparison of the structural dynamics of R102Q mutant and Δ176-190 truncated NCS-1 suggests that the structural and dynamical response of NCS-1 protein to elevated temperature may be one of its intrinsic functional properties. PMID:27007011

  17. Neuronal calcium sensor proteins are direct targets of the insulinotropic agent repaglinide.

    PubMed Central

    Okada, Miki; Takezawa, Daisuke; Tachibanaki, Shuji; Kawamura, Satoru; Tokumitsu, Hiroshi; Kobayashi, Ryoji

    2003-01-01

    The NCS (neuronal calcium sensor) proteins, including neurocalcins, recoverins and visinin-like proteins are members of a family of Ca2+-sensitive regulators, each with three Ca2+-binding EF-hand motifs. In plants, lily CCaMK [chimaeric Ca2+/CaM (calmodulin)-dependent protein kinase] and its PpCaMK ( Physcomitrella patens CCaMK) homologue are characterized by a visinin-like domain with three EF-hands. In the present study, in an effort to discover NCS antagonists, we screened a total of 43 compounds using Ca2+-dependent drug affinity chromatography and found that the insulinotropic agent repaglinide targets the NCS protein family. Repaglinide was found to bind to NCS proteins, but not to CaM or S100 proteins, in a Ca2+-dependent manner. Furthermore, the drug antagonized the inhibitory action of recoverin in a rhodopsin kinase assay with IC50 values of 400 microM. Moreover, repaglinide tightly bound to the visinin-like domain of CCaMK and PpCaMK in a Ca2+-dependent manner and antagonized the regulatory function of the domain with IC50 values of 55 and 4 microM for CCaMK and PpCaMK respectively. Although both repaglinide and a potent insulin secretagogue, namely glibenclamide, blocked K(ATP) channels with similar potency, glibenclamide had no antagonizing effect on the Ca2+-stimulated CCaMK and PpCaMK autophosphorylation, mediated by their visinin-like domain. In addition, a typical CaM antagonist, trifluoperazine, had no effect on the CCaMK and PpCaMK autophosphorylation. Repaglinide appears to be the first antagonist of NCS proteins and visinin-like domain-bearing enzymes. It may serve as a useful tool for evaluating the physiological functions of the NCS protein family. In addition, since repaglinide selectively targets NCS proteins among the EF-hand Ca2+-binding proteins, it is a potential lead compound for the development of more potent NCS antagonists. PMID:12844348

  18. Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions*

    PubMed Central

    Pandalaneni, Sravan; Karuppiah, Vijaykumar; Saleem, Muhammad; Haynes, Lee P.; Burgoyne, Robert D.; Mayans, Olga; Derrick, Jeremy P.; Lian, Lu-Yun

    2015-01-01

    Neuronal calcium sensor-1 (NCS-1) is the primordial member of the neuronal calcium sensor family of EF-hand Ca2+-binding proteins. It interacts with both the G-protein-coupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its internalization and surface expression, and the cognate kinases GRK1 and GRK2. Determination of the crystal structures of Ca2+/NCS-1 alone and in complex with peptides derived from D2R and GRK1 reveals that the differential recognition is facilitated by the conformational flexibility of the C-lobe-binding site. We find that two copies of the D2R peptide bind within the hydrophobic crevice on Ca2+/NCS-1, but only one copy of the GRK1 peptide binds. The different binding modes are made possible by the C-lobe-binding site of NCS-1, which adopts alternative conformations in each complex. C-terminal residues Ser-178–Val-190 act in concert with the flexible EF3/EF4 loop region to effectively form different peptide-binding sites. In the Ca2+/NCS-1·D2R peptide complex, the C-terminal region adopts a 310 helix-turn-310 helix, whereas in the GRK1 peptide complex it forms an α-helix. Removal of Ser-178–Val-190 generated a C-terminal truncation mutant that formed a dimer, indicating that the NCS-1 C-terminal region prevents NCS-1 oligomerization. We propose that the flexible nature of the C-terminal region is essential to allow it to modulate its protein-binding sites and adapt its conformation to accommodate both ligands. This appears to be driven by the variability of the conformation of the C-lobe-binding site, which has ramifications for the target specificity and diversity of NCS-1. PMID:25979333

  19. Fast Kinetics of Calcium Signaling and Sensor Design

    PubMed Central

    Tang, Shen; Reddish, Florence; Zhuo, You; Yang, Jenny J.

    2015-01-01

    Fast calcium signaling is regulated by numerous calcium channels exhibiting high spatiotemporal profiles which are currently measured by fluorescent calcium sensors. There is still a strong need to improve the kinetics of genetically encoded calcium indicators (sensors) to capture calcium dynamics in the millisecond time frame. In this review, we summarize several major fast calcium signaling pathways and discuss the recent developments and application of genetically encoded calcium indicators to detect these pathways. A new class of genetically encoded calcium indicators designed with site-directed mutagenesis on the surface of beta-barrel fluorescent proteins to form a pentagonal bipyramidal-like calcium binding domain dramatically accelerates calcium binding kinetics. Furthermore, novel genetically encoded calcium indicators with significantly increased fluorescent lifetime change are advantageous in deep-field imaging with high light-scattering and notable morphology change. PMID:26151819

  20. EVALUATION OF CALCIUM SENSORS IN FRESH AND SALTWATER

    EPA Science Inventory

    The Orion Calcium Ion Electrode No. 93-20 was evaluated for suitability as a calcium ion sensor for monitoring or in-situ marine applications by testing for the following parameters: accuracy, precision, temperature dependence, short- and long-term stability, durability, sensitiv...

  1. NATIONAL COMORBIDITY SURVEY (NCS)

    EPA Science Inventory

    The National Comorbidity Survey (NCS) was a collaborative epidemiologic investigation designed to study the prevalence and correlates of DSM III-R disorders and patterns and correlates of service utilization for these disorders. The NCS was the first survey to administer a struct...

  2. Direct single-molecule observation of calcium-dependent misfolding in human neuronal calcium sensor-1.

    PubMed

    Heidarsson, Pétur O; Naqvi, Mohsin M; Otazo, Mariela R; Mossa, Alessandro; Kragelund, Birthe B; Cecconi, Ciro

    2014-09-01

    Neurodegenerative disorders are strongly linked to protein misfolding, and crucial to their explication is a detailed understanding of the underlying structural rearrangements and pathways that govern the formation of misfolded states. Here we use single-molecule optical tweezers to monitor misfolding reactions of the human neuronal calcium sensor-1, a multispecific EF-hand protein involved in neurotransmitter release and linked to severe neurological diseases. We directly observed two misfolding trajectories leading to distinct kinetically trapped misfolded conformations. Both trajectories originate from an on-pathway intermediate state and compete with native folding in a calcium-dependent manner. The relative probability of the different trajectories could be affected by modulating the relaxation rate of applied force, demonstrating an unprecedented real-time control over the free-energy landscape of a protein. Constant-force experiments in combination with hidden Markov analysis revealed the free-energy landscape of the misfolding transitions under both physiological and pathological calcium concentrations. Remarkably for a calcium sensor, we found that higher calcium concentrations increased the lifetimes of the misfolded conformations, slowing productive folding to the native state. We propose a rugged, multidimensional energy landscape for neuronal calcium sensor-1 and speculate on a direct link between protein misfolding and calcium dysregulation that could play a role in neurodegeneration. PMID:25157171

  3. Direct single-molecule observation of calcium-dependent misfolding in human neuronal calcium sensor-1

    PubMed Central

    Heidarsson, Pétur O.; Naqvi, Mohsin M.; Otazo, Mariela R.; Mossa, Alessandro; Kragelund, Birthe B.; Cecconi, Ciro

    2014-01-01

    Neurodegenerative disorders are strongly linked to protein misfolding, and crucial to their explication is a detailed understanding of the underlying structural rearrangements and pathways that govern the formation of misfolded states. Here we use single-molecule optical tweezers to monitor misfolding reactions of the human neuronal calcium sensor-1, a multispecific EF-hand protein involved in neurotransmitter release and linked to severe neurological diseases. We directly observed two misfolding trajectories leading to distinct kinetically trapped misfolded conformations. Both trajectories originate from an on-pathway intermediate state and compete with native folding in a calcium-dependent manner. The relative probability of the different trajectories could be affected by modulating the relaxation rate of applied force, demonstrating an unprecedented real-time control over the free-energy landscape of a protein. Constant-force experiments in combination with hidden Markov analysis revealed the free-energy landscape of the misfolding transitions under both physiological and pathological calcium concentrations. Remarkably for a calcium sensor, we found that higher calcium concentrations increased the lifetimes of the misfolded conformations, slowing productive folding to the native state. We propose a rugged, multidimensional energy landscape for neuronal calcium sensor-1 and speculate on a direct link between protein misfolding and calcium dysregulation that could play a role in neurodegeneration. PMID:25157171

  4. The calcium sensor synaptotagmin 7 is required for synaptic facilitation.

    PubMed

    Jackman, Skyler L; Turecek, Josef; Belinsky, Justine E; Regehr, Wade G

    2016-01-01

    It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release, and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed. Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. PMID:26738595

  5. Network Characterization Service (NCS)

    SciTech Connect

    Jin, Guojun; Yang, George; Crowley, Brian; Agarwal, Deborah

    2001-06-06

    Distributed applications require information to effectively utilize the network. Some of the information they require is the current and maximum bandwidth, current and minimum latency, bottlenecks, burst frequency, and congestion extent. This type of information allows applications to determine parameters like optimal TCP buffer size. In this paper, we present a cooperative information-gathering tool called the network characterization service (NCS). NCS runs in user space and is used to acquire network information. Its protocol is designed for scalable and distributed deployment, similar to DNS. Its algorithms provide efficient, speedy and accurate detection of bottlenecks, especially dynamic bottlenecks. On current and future networks, dynamic bottlenecks do and will affect network performance dramatically.

  6. The calcium sensor synaptotagmin 7 is required for synaptic facilitation

    PubMed Central

    Jackman, Skyler L.; Turecek, Josef; Belinsky, Justine E.

    2015-01-01

    It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner1. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release2. Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses3, but the underlying mechanism remains a mystery. Among the proposed mechanisms is that a specialized calcium sensor for facilitation transiently increases the probability of release2,4 and is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed5,6. Here we show that synaptotagmin 7 (syt7) is a calcium sensor that is required for facilitation at multiple central synapses. In syt7 knockout mice, facilitation is eliminated even though the initial probability of release and presynaptic residual calcium signals are unaltered. Expression of wild-type syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated syt7 with a calcium-insensitive C2A domain did not. By revealing the role of syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. PMID:26738595

  7. Assembly and Calcium Binding Properties of Quantum Dot-Calmodulin Calcium Sensor.

    PubMed

    Eun, Su-yong; Nguyen-ta, Kim; Yoo, Hoon; Silva, Gabriel A; Kim, Soon-jong

    2016-02-01

    We have developed the first nanoengineered quantum dot molecular complex designed to measure changes of calcium ion (Ca2+) concentration at high spatial and temporal resolutions in real time. The sensor is ratiometric and composed of three components: a quantum dot (QD) emitting at 620 nm as a fluorescence donor, an organic dye (Alexa Fluor 647) as a fluorescence acceptor, and a calmodulin-M13 (CaM-M13) protein part as a calcium sensing component. In this work, we have determined the maximal number of CaM-M13 required for saturating a single QD particle to be approximately 16. The dissociation constant, Kd of the QD-based calcium ion sensor was also estimated to be around 30 microM. PMID:27433729

  8. Demonstration of Binding of Neuronal Calcium Sensor-1 to the Cav2.1 P/Q-Type Calcium Channel

    PubMed Central

    2014-01-01

    In neurons, entry of extracellular calcium (Ca2+) into synaptic terminals through Cav2.1 (P/Q-type) Ca2+ channels is the driving force for exocytosis of neurotransmitter-containing synaptic vesicles. This class of Ca2+ channel is, therefore, pivotal during normal neurotransmission in higher organisms. In response to channel opening and Ca2+ influx, specific Ca2+-binding proteins associate with cytoplasmic regulatory domains of the P/Q channel to modulate subsequent channel opening. Channel modulation in this way influences synaptic plasticity with consequences for higher-level processes such as learning and memory acquisition. The ubiquitous Ca2+-sensing protein calmodulin (CaM) regulates the activity of all types of mammalian voltage-gated Ca2+ channels, including the P/Q class, by direct binding to specific regulatory motifs. More recently, experimental evidence has highlighted a role for additional Ca2+-binding proteins, particularly of the CaBP and NCS families in the regulation of P/Q channels. NCS-1 is a protein found from yeast to humans and that regulates a diverse number of cellular functions. Physiological and genetic evidence indicates that NCS-1 regulates P/Q channel activity, including calcium-dependent facilitation, although a direct physical association between the proteins has yet to be demonstrated. In this study, we aimed to determine if there is a direct interaction between NCS-1 and the C-terminal cytoplasmic tail of the Cav2.1 α-subunit. Using distinct but complementary approaches, including in vitro binding of bacterially expressed recombinant proteins, fluorescence spectrophotometry, isothermal titration calorimetry, nuclear magnetic resonance, and expression of fluorescently tagged proteins in mammalian cells, we show direct binding and demonstrate that CaM can compete for it. We speculate about how NCS-1/Cav2.1 association might add to the complexity of calcium channel regulation mediated by other known calcium-sensing proteins and how

  9. Neuronal calcium sensor-1 and cocaine addiction: A genetic association study in African-Americans and European Americans

    PubMed Central

    Multani, Pushpinder K.; Clarke, Toni-Kim; Narasimhan, Sneha; Ambrose-Lanci, Lisa; Kampman, Kyle M.; Pettinati, Helen M.; Oslin, David W.; O’Brien, Charles P.; Berrettini, Wade H.; Lohoff, Falk W.

    2013-01-01

    Genes involved in drug reward pathways are plausible candidates for susceptibility to substance use disorders. Given the prominent role of dopamine in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role in the pathophysiology of cocaine addiction (CA). In this study, we investigated whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611, rs1342043) was attempted using a replication sample of African American (AA) ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry (cases n = 336, controls n = 656). Secondary sex specific analysis was also carried out for each SNP in both AA and EA individuals. Genotyping of the discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA in AAs; however, this marker could not be confirmed in either the AA or EA replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043 showed a significant association with CA (genotypic p = 0.0001, allelic p = 0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p = 0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to susceptibility of CA in individuals of African descent. PMID:22999924

  10. Self-directed exploration provides a Ncs1-dependent learning bonus

    PubMed Central

    Mun, Ho-Suk; Saab, Bechara J.; Ng, Enoch; McGirr, Alexander; Lipina, Tatiana V.; Gondo, Yoichi; Georgiou, John; Roder, John C.

    2015-01-01

    Understanding the mechanisms of memory formation is fundamental to establishing optimal educational practices and restoring cognitive function in brain disease. Here, we show for the first time in a non-primate species, that spatial learning receives a special bonus from self-directed exploration. In contrast, when exploration is escape-oriented, or when the full repertoire of exploratory behaviors is reduced, no learning bonus occurs. These findings permitted the first molecular and cellular examinations into the coupling of exploration to learning. We found elevated expression of neuronal calcium sensor 1 (Ncs1) and dopamine type-2 receptors upon self-directed exploration, in concert with increased neuronal activity in the hippocampal dentate gyrus and area CA3, as well as the nucleus accumbens. We probed further into the learning bonus by developing a point mutant mouse (Ncs1P144S/P144S) harboring a destabilized NCS-1 protein, and found this line lacked the equivalent self-directed exploration learning bonus. Acute knock-down of Ncs1 in the hippocampus also decoupled exploration from efficient learning. These results are potentially relevant for augmenting learning and memory in health and disease, and provide the basis for further molecular and circuit analyses in this direction. PMID:26639399

  11. The Neuronal Calcium Sensor Protein Acrocalcin: A Potential Target of Calmodulin Regulation during Development in the Coral Acropora millepora

    PubMed Central

    Reyes-Bermudez, Alejandro; Miller, David J.; Sprungala, Susanne

    2012-01-01

    To understand the calcium-mediated signalling pathways underlying settlement and metamorphosis in the Scleractinian coral Acropora millepora, a predicted protein set derived from larval cDNAs was scanned for the presence of EF-hand domains (Pfam Id: PF00036). This approach led to the identification of a canonical calmodulin (AmCaM) protein and an uncharacterised member of the Neuronal Calcium Sensor (NCS) family of proteins known here as Acrocalcin (AmAC). While AmCaM transcripts were present throughout development, AmAC transcripts were not detected prior to gastrulation, after which relatively constant mRNA levels were detected until metamorphosis and settlement. The AmAC protein contains an internal CaM-binding site and was shown to interact in vitro with AmCaM. These results are consistent with the idea that AmAC is a target of AmCaM in vivo, suggesting that this interaction may regulate calcium-dependent processes during the development of Acropora millepora. PMID:23284743

  12. Soil calcium and pH monitoring sensor system.

    PubMed

    Lemos, Sherlan G; Nogueira, Ana Rita A; Torre-Neto, André; Parra, Aleix; Alonso, Julian

    2007-06-13

    An agrarian sensorial system based on temperature, moisture, and all solid-state ion-selective potentiometric sensors was developed with the objective of monitoring the behavior of H+ and Ca2+ ions in soil and in real conditions, contributing with a new tool that tries to complement the current precision agriculture technology. The evaluation of the sensorial system to pH monitoring presented a good correlation between the results obtained by the system and the standard methodology, allowing us to notice the soil buffer capacity at different soil depths. With regard to calcium, the sensor system also presented an agreement between its results and those obtained by flame atomic absorption spectrometry, using a calibration model based on multiple linear regressions that allows the correct determination of Ca2+ concentrations in soil depths where the relative moisture is different. In this way, using well-known potentiometric sensors in a complex, discontinued, and heterogeneous matrix, such as soil, the sensorial system proved to be a useful task for agrochemical field applications. PMID:17500528

  13. Network Adaptive Deadband: NCS Data Flow Control for Shared Networks

    PubMed Central

    Díaz-Cacho, Miguel; Delgado, Emma; Prieto, José A. G.; López, Joaquín

    2012-01-01

    This paper proposes a new middleware solution called Network Adaptive Deadband (NAD) for long time operation of Networked Control Systems (NCS) through the Internet or any shared network based on IP technology. The proposed middleware takes into account the network status and the NCS status, to improve the global system performance and to share more effectively the network by several NCS and sensor/actuator data flows. Relationship between network status and NCS status is solved with a TCP-friendly transport flow control protocol and the deadband concept, relating deadband value and transmission throughput. This creates a deadband-based flow control solution. Simulation and experiments in shared networks show that the implemented network adaptive deadband has better performance than an optimal constant deadband solution in the same circumstances. PMID:23208556

  14. Protein-specific localization of a rhodamine-based calcium-sensor in living cells.

    PubMed

    Best, Marcel; Porth, Isabel; Hauke, Sebastian; Braun, Felix; Herten, Dirk-Peter; Wombacher, Richard

    2016-06-28

    A small synthetic calcium sensor that can be site-specifically coupled to proteins in living cells by utilizing the bio-orthogonal HaloTag labeling strategy is presented. We synthesized an iodo-derivatized BAPTA chelator with a tetramethyl rhodamine fluorophore that allows further modification by Sonogashira cross-coupling. The presented calcium sensitive dye shows a 200-fold increase in fluorescence upon calcium binding. The derivatization with an aliphatic linker bearing a terminal haloalkane-function by Sonogashira cross-coupling allows the localization of the calcium sensor to Halo fusion proteins which we successfully demonstrate in in vitro and in vivo experiments. The herein reported highly sensitive tetramethyl rhodamine based calcium indicator, which can be selectively localized to proteins, is a powerful tool to determine changes in calcium levels inside living cells with spatiotemporal resolution. PMID:27072883

  15. Protein intake and calcium absorption – Potential role of the calcium sensor receptor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary protein induces calcium excretion but the source of this calcium is unclear. Evidence from short-term studies indicates that protein promotes bone resorption, but many epidemiologic studies do not corroborate this. Evidence is also mixed on weather protein promotes calcium absorption. Stud...

  16. Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling

    PubMed Central

    Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Pergel, Enikő; Bősze, Zsuzsanna; Bender, Balázs; Vajdovich, Péter; Tóvári, József; Homolya, László; Szakács, Gergely; Héja, László; Enyedi, Ágnes; Sarkadi, Balázs; Apáti, Ágota; Orbán, Tamás I.

    2015-01-01

    In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na+/Ca2+ exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies. PMID:26234466

  17. Biosensor and chemical sensor probes for calcium and other metal ions

    DOEpatents

    Vo-Dinh, Tuan; Viallet, Pierre

    1996-01-01

    The present invention relates to chemical sensor and biosensor probes for measuring low concentration of metals and metal ions in complex samples such as biological fluids, living cells, and environmental samples. More particularly the present invention relates to a gel-based Indo-1 and Fura-2 chemical sensor probes for the measurement of low concentrations of calcium, cadmium, magnesium and the like. Also disclosed is a detector device using the sensors of the present invention.

  18. Activation of the Endoplasmic Reticulum Calcium Sensor STIM1 and Store-Operated Calcium Entry by Rotavirus Requires NSP4 Viroporin Activity

    PubMed Central

    Hyser, Joseph M.; Utama, Budi; Crawford, Sue E.; Broughman, James R.

    2013-01-01

    Rotavirus nonstructural protein 4 (NSP4) induces dramatic changes in cellular calcium homeostasis. These include increased endoplasmic reticulum (ER) permeability, resulting in decreased ER calcium stores and activation of plasma membrane (PM) calcium influx channels, ultimately causing a 2- to 4-fold elevation in cytoplasmic calcium. Elevated cytoplasmic calcium is absolutely required for virus replication, but the underlying mechanisms responsible for calcium influx remain poorly understood. NSP4 is an ER-localized viroporin, whose activity depletes ER calcium, which ultimately leads to calcium influx. We hypothesized that NSP4-mediated depletion of ER calcium activates store-operated calcium entry (SOCE) through activation of the ER calcium sensor stromal interaction molecule 1 (STIM1). We established and used a stable yellow fluorescent protein-expressing STIM1 cell line (YFP-STIM1) as a biosensor to assess STIM1 activation (puncta formation) by rotavirus infection and NSP4 expression. We found that STIM1 is constitutively active in rotavirus-infected cells and that STIM1 puncta colocalize with the PM-localized Orai1 SOCE calcium channel. Expression of wild-type NSP4 activated STIM1, resulting in PM calcium influx, but an NSP4 viroporin mutant failed to induce STIM1 activation and did not activate the PM calcium entry pathway. Finally, knockdown of STIM1 significantly reduced rotavirus yield, indicating STIM1 plays a critical role in virus replication. These data demonstrate that while rotavirus may ultimately activate multiple calcium channels in the PM, calcium influx is predicated on NSP4 viroporin-mediated activation of STIM1 in the ER. This is the first report of viroporin-mediated activation of SOCE, reinforcing NSP4 as a robust model to understand dysregulation of calcium homeostasis during virus infections. PMID:24109210

  19. Fast calcium sensor proteins for monitoring neural activity

    PubMed Central

    Badura, Aleksandra; Sun, Xiaonan Richard; Giovannucci, Andrea; Lynch, Laura A.; Wang, Samuel S.-H.

    2014-01-01

    Abstract. A major goal of the BRAIN Initiative is the development of technologies to monitor neuronal network activity during active information processing. Toward this goal, genetically encoded calcium indicator proteins have become widely used for reporting activity in preparations ranging from invertebrates to awake mammals. However, slow response times, the narrow sensitivity range of Ca2+ and in some cases, poor signal-to-noise ratio still limit their usefulness. Here, we review recent improvements in the field of neural activity-sensitive probe design with a focus on the GCaMP family of calcium indicator proteins. In this context, we present our newly developed Fast-GCaMPs, which have up to 4-fold accelerated off-responses compared with the next-fastest GCaMP, GCaMP6f. Fast-GCaMPs were designed by destabilizing the association of the hydrophobic pocket of calcium-bound calmodulin with the RS20 binding domain, an intramolecular interaction that protects the green fluorescent protein chromophore. Fast-GCaMP6f-RS06 and Fast-GCaMP6f-RS09 have rapid off-responses in stopped-flow fluorimetry, in neocortical brain slices, and in the intact cerebellum in vivo. Fast-GCaMP6f variants should be useful for tracking action potentials closely spaced in time, and for following neural activity in fast-changing compartments, such as axons and dendrites. Finally, we discuss strategies that may allow tracking of a wider range of neuronal firing rates and improve spike detection. PMID:25558464

  20. CBL1, a calcium sensor that differentially regulates salt, drought, and cold responses in Arabidopsis.

    PubMed

    Cheong, Yong Hwa; Kim, Kyung-Nam; Pandey, Girdhar K; Gupta, Rajeev; Grant, John J; Luan, Sheng

    2003-08-01

    Although calcium is a critical component in the signal transduction pathways that lead to stress gene expression in higher plants, little is known about the molecular mechanism underlying calcium function. It is believed that cellular calcium changes are perceived by sensor molecules, including calcium binding proteins. The calcineurin B-like (CBL) protein family represents a unique group of calcium sensors in plants. A member of the family, CBL1, is highly inducible by multiple stress signals, implicating CBL1 in stress response pathways. When the CBL1 protein level was increased in transgenic Arabidopsis plants, it altered the stress response pathways in these plants. Although drought-induced gene expression was enhanced, gene induction by cold was inhibited. In addition, CBL1-overexpressing plants showed enhanced tolerance to salt and drought but reduced tolerance to freezing. By contrast, cbl1 null mutant plants showed enhanced cold induction and reduced drought induction of stress genes. The mutant plants displayed less tolerance to salt and drought but enhanced tolerance to freezing. These studies suggest that CBL1 functions as a positive regulator of salt and drought responses and a negative regulator of cold response in plants. PMID:12897256

  1. Submicron fiber optic sensors for calcium ions and pH with internal calibration

    NASA Astrophysics Data System (ADS)

    Plaschke, Markus; Geyer, Michael; Reichert, Johannes; Ache, Hans-Joachim

    1997-05-01

    Submicron optical sensors can be prepared by immobilization of fluorescent indicators on tapered fiber tips. However, fluorescence intensity based sensing depends on many parameters (e.g. light source, collection geometry, quenching effects, etc.) and therefore quantification is usually complicated. Ratio measurements are established as a common method to quantify fluorescence signals using a sensing and a reference dye. The sensors described in this work are based on a new immobilization concept which consists of the encapsulation of dextran-linked fluorescence indicators in an organic hydrogel. This concept allows co-immobilization and stable encapsulation of different indicators. The calcium- and pH-sensors presented contain dextran-coupled fluorescein- derivatives as indicators (Calcium GreenTM and fluorescein) and a rhodamine-derivative (Texas RedR) as reference dye, co-immobilized in PolyHEMA. These sensors exhibit a signal stability of several weeks (when stored in buffer solution), fast response times and calibration curves which are not affected by immobilization. Due to the ratio measurement signal reproducibility was less than or equal to 5%. The working lifetime of submicron sensors was limited only by photobleaching of the indicators which can be minimized by reduction of the laser power. The dynamic range and short response times of these sensors suggest applications in physiological fluids, cell cultures or micro-bioreactors.

  2. Calcium

    MedlinePlus

    ... of calcium dietary supplements are carbonate and citrate. Calcium carbonate is inexpensive, but is absorbed best when taken ... antacid products, such as Tums® and Rolaids®, contain calcium carbonate. Each pill or chew provides 200–400 mg ...

  3. Calcium Sensors as Key Hubs in Plant Responses to Biotic and Abiotic Stresses

    PubMed Central

    Ranty, Benoît; Aldon, Didier; Cotelle, Valérie; Galaud, Jean-Philippe; Thuleau, Patrice; Mazars, Christian

    2016-01-01

    The Ca2+ ion is recognized as a crucial second messenger in signaling pathways coupling the perception of environmental stimuli to plant adaptive responses. Indeed, one of the earliest events following the perception of environmental changes (temperature, salt stress, drought, pathogen, or herbivore attack) is intracellular variation of free calcium concentrations. These calcium variations differ in their spatio-temporal characteristics (subcellular location, amplitude, kinetics) with the nature and strength of the stimulus and, for this reason, they are considered as signatures encrypting information from the initial stimulus. This information is believed to drive a specific response by decoding via calcium-binding proteins. Based on recent examples, we illustrate how individual calcium sensors from the calcium-dependent protein kinase and calmodulin-like protein families can integrate inputs from various environmental changes. Focusing on members of these two families, shown to be involved in plant responses to both abiotic and biotic stimuli, we discuss their role as key hubs and we put forward hypotheses explaining how they can drive the signaling pathways toward the appropriate plant responses. PMID:27014336

  4. Differential Nanosecond Protein Dynamics in Homologous Calcium Sensors.

    PubMed

    Robin, Jörg; Brauer, Jens; Sulmann, Stefan; Marino, Valerio; Dell'Orco, Daniele; Lienau, Christoph; Koch, Karl-Wilhelm

    2015-10-16

    Shaping the temporal response of photoreceptors is facilitated by a well-balanced second messenger cascade, in which two neuronal Ca(2+)-sensor proteins operate in a sequential relay mechanism. Although they share structurally similar sensing units, they differentially activate the same target protein. Here, as a prototypical case in Ca(2+)-mediated signal processing, we investigate differential cellular responsiveness in protein conformational dynamics on a nanosecond time scale. For this, we have site-specifically labeled cysteine residues in guanylate cyclase-activating protein GCAP1 by the fluorescent dye Alexa647 and probed its local environment via time-resolved fluorescence spectroscopy. Fluorescence lifetime and rotational anisotropy measurements reveal a distinct structural movement of the polypeptide chain around position 106 upon release of Ca(2+). This is supported by analyzing the diffusional dye motion in a wobbling-in-a-cone model and by molecular dynamics simulations. We conclude that GCAP1 and its cellular cognate GCAP2 operate by distinctly different switching mechanisms despite their high structural homology. PMID:26204433

  5. Calcium

    MedlinePlus

    ... body stores more than 99 percent of its calcium in the bones and teeth to help make and keep them ... in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with soft bones that you eat, such as canned sardines and ...

  6. Beetroot-pigment-derived colorimetric sensor for detection of calcium dipicolinate in bacterial spores.

    PubMed

    Gonçalves, Letícia Christina Pires; Da Silva, Sandra Maria; DeRose, Paul C; Ando, Rômulo Augusto; Bastos, Erick Leite

    2013-01-01

    In this proof-of-concept study, we describe the use of the main red beet pigment betanin for the quantification of calcium dipicolinate in bacterial spores, including Bacillus anthracis. In the presence of europium(III) ions, betanin is converted to a water-soluble, non-luminescent orange 1∶1 complex with a stability constant of 1.4 × 10(5) L mol(-1). The addition of calcium dipicolinate, largely found in bacterial spores, changes the color of the aqueous solution of [Eu(Bn)(+)] from orange to magenta. The limit of detection (LOD) of calcium dipicolinate is around 2.0 × 10(-6) mol L(-1) and the LOD determined for both spores, B. cereus and B. anthracis, is (1.1 ± 0.3)× 10(6) spores mL(-1). This simple, green, fast and low cost colorimetric assay was selective for calcium dipicolinate when compared to several analogous compounds. The importance of this work relies on the potential use of betalains, raw natural pigments, as colorimetric sensors for biological applications. PMID:24019934

  7. Nanodevice-induced conformational and functional changes in a prototypical calcium sensor protein

    NASA Astrophysics Data System (ADS)

    Marino, Valerio; Astegno, Alessandra; Pedroni, Marco; Piccinelli, Fabio; Dell'Orco, Daniele

    2013-12-01

    Calcium (Ca2+) plays a major role in a variety of cellular processes. Fine changes in its concentration are detected by calcium sensor proteins, which adopt specific conformations to regulate their molecular targets. Here, two distinct nanodevices were probed as biocompatible carriers of Ca2+-sensors and the structural and functional effects of protein-nanodevice interactions were investigated. The prototypical Ca2+-sensor recoverin (Rec) was incubated with 20-25 nm CaF2 nanoparticles (NPs) and 70-80 nm liposomes with lipid composition similar to that found in photoreceptor cells. Circular dichroism and fluorescence spectroscopy were used to characterize changes in the protein secondary and tertiary structure and in thermal stability upon interaction with the nanodevice, both in the presence and in the absence of free Ca2+. Variations in the hydrodynamic diameter of the complex were measured by dynamic light scattering and the residual capability of the protein to act as a Ca2+-sensor in the presence of NPs was estimated spectroscopically. The conformation, thermal stability and Ca2+-sensing capability of Rec were all significantly affected by the presence of NPs, while liposomes did not significantly perturb Rec conformation and function, allowing reversible binding. NP-bound Rec maintained an all-helical fold but showed lower thermal stability and high cooperativity of unfolding. Our analysis can be proficiently used to validate the biocompatibility of other nanodevices intended for biomedical applications involving Ca2+-sensors.Calcium (Ca2+) plays a major role in a variety of cellular processes. Fine changes in its concentration are detected by calcium sensor proteins, which adopt specific conformations to regulate their molecular targets. Here, two distinct nanodevices were probed as biocompatible carriers of Ca2+-sensors and the structural and functional effects of protein-nanodevice interactions were investigated. The prototypical Ca2+-sensor recoverin (Rec

  8. Calcium

    MedlinePlus

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

  9. Arabidopsis CML38, a Calcium Sensor That Localizes to Ribonucleoprotein Complexes under Hypoxia Stress.

    PubMed

    Lokdarshi, Ansul; Conner, W Craig; McClintock, Carlee; Li, Tian; Roberts, Daniel M

    2016-02-01

    During waterlogging and the associated oxygen deprivation stress, plants respond by the induction of adaptive programs, including the redirected expression of gene networks toward the synthesis of core hypoxia-response proteins. Among these core response proteins in Arabidopsis (Arabidopsis thaliana) is the calcium sensor CML38, a protein related to regulator of gene silencing calmodulin-like proteins (rgsCaMs). CML38 transcripts are up-regulated more than 300-fold in roots within 6 h of hypoxia treatment. Transfer DNA insertional mutants of CML38 show an enhanced sensitivity to hypoxia stress, with lowered survival and more severe inhibition of root and shoot growth. By using yellow fluorescent protein (YFP) translational fusions, CML38 protein was found to be localized to cytosolic granule structures similar in morphology to hypoxia-induced stress granules. Immunoprecipitation of CML38 from the roots of hypoxia-challenged transgenic plants harboring CML38pro::CML38:YFP followed by liquid chromatography-tandem mass spectrometry analysis revealed the presence of protein targets associated with messenger RNA ribonucleoprotein (mRNP) complexes including stress granules, which are known to accumulate as messenger RNA storage and triage centers during hypoxia. This finding is further supported by the colocalization of CML38 with the mRNP stress granule marker RNA Binding Protein 47 (RBP47) upon cotransfection of Nicotiana benthamiana leaves. Ruthenium Red treatment results in the loss of CML38 signal in cytosolic granules, suggesting that calcium is necessary for stress granule association. These results confirm that CML38 is a core hypoxia response calcium sensor protein and suggest that it serves as a potential calcium signaling target within stress granules and other mRNPs that accumulate during flooding stress responses. PMID:26634999

  10. Arabidopsis CML38, a Calcium Sensor That Localizes to Ribonucleoprotein Complexes under Hypoxia Stress1[OPEN

    PubMed Central

    McClintock, Carlee; Li, Tian

    2016-01-01

    During waterlogging and the associated oxygen deprivation stress, plants respond by the induction of adaptive programs, including the redirected expression of gene networks toward the synthesis of core hypoxia-response proteins. Among these core response proteins in Arabidopsis (Arabidopsis thaliana) is the calcium sensor CML38, a protein related to regulator of gene silencing calmodulin-like proteins (rgsCaMs). CML38 transcripts are up-regulated more than 300-fold in roots within 6 h of hypoxia treatment. Transfer DNA insertional mutants of CML38 show an enhanced sensitivity to hypoxia stress, with lowered survival and more severe inhibition of root and shoot growth. By using yellow fluorescent protein (YFP) translational fusions, CML38 protein was found to be localized to cytosolic granule structures similar in morphology to hypoxia-induced stress granules. Immunoprecipitation of CML38 from the roots of hypoxia-challenged transgenic plants harboring CML38pro::CML38:YFP followed by liquid chromatography-tandem mass spectrometry analysis revealed the presence of protein targets associated with messenger RNA ribonucleoprotein (mRNP) complexes including stress granules, which are known to accumulate as messenger RNA storage and triage centers during hypoxia. This finding is further supported by the colocalization of CML38 with the mRNP stress granule marker RNA Binding Protein 47 (RBP47) upon cotransfection of Nicotiana benthamiana leaves. Ruthenium Red treatment results in the loss of CML38 signal in cytosolic granules, suggesting that calcium is necessary for stress granule association. These results confirm that CML38 is a core hypoxia response calcium sensor protein and suggest that it serves as a potential calcium signaling target within stress granules and other mRNPs that accumulate during flooding stress responses. PMID:26634999

  11. Polyaniline-graphene oxide nanocomposite sensor for quantification of calcium channel blocker levamlodipine.

    PubMed

    Jain, Rajeev; Sinha, Ankita; Khan, Ab Lateef

    2016-08-01

    A novel polyaniline-graphene oxide nanocomposite (PANI/GO/GCE) sensor has been fabricated for quantification of a calcium channel blocker drug levamlodipine (LAMP). Fabricated sensor has been characterized by electrochemical impedance spectroscopy, square wave and cyclic voltammetry, Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The developed PANI/GO/GCE sensor has excellent analytical performance towards electrocatalytic oxidation as compared to PANI/GCE, GO/GCE and bare GCE. Under optimized experimental conditions, the fabricated sensor exhibits a linear response for LAMP for its oxidation over a concentration range from 1.25μgmL(-1) to 13.25μgmL(-1) with correlation coefficient of 0.9950 (r(2)), detection limit of 1.07ngmL(-1) and quantification limit of 3.57ngmL(-1). The sensor shows an excellent performance for detecting LAMP with reproducibility of 2.78% relative standard deviation (RSD). The proposed method has been successfully applied for LAMP determination in pharmaceutical formulation with a recovery from 99.88% to 101.75%. PMID:27157745

  12. Synaptotagmin-7 Is an Asynchronous Calcium Sensor for Synaptic Transmission in Neurons Expressing SNAP-23

    PubMed Central

    Weber, Jens P.; Toft-Bertelsen, Trine L.; Mohrmann, Ralf; Delgado-Martinez, Ignacio; Sørensen, Jakob B.

    2014-01-01

    Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs). Use of neurons from double-knock-out (SNAP-25, synaptotagmin-7) mice in combination with viral transduction showed that SNAP-23-driven release is triggered by endogenous synaptotagmin-7. In the absence of synaptotagmin-7 release became even more asynchronous, and the spontaneous release rate increased even more, indicating that synaptotagmin-7 acts to synchronize release and suppress spontaneous release. However, compared to synaptotagmin-1, synaptotagmin-7 is a both leaky and asynchronous calcium sensor. In the presence of SNAP-25, consequences of the elimination of synaptotagmin-7 were small or absent, indicating that the protein pairs SNAP-25/synaptotagmin-1 and SNAP-23/synaptotagmin-7 might act as mutually exclusive calcium sensors. Expression of fusion proteins between pHluorin (pH-sensitive GFP) and synaptotagmin-1 or -7 showed that vesicles that fuse using the SNAP-23/synaptotagmin-7 combination contained synaptotagmin-1, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity. PMID:25422940

  13. Monitoring of hardening and hygroscopic induced strains in a calcium phosphate bone cement using FBG sensor.

    PubMed

    Bimis, A; Karalekas, D; Bouropoulos, N; Mouzakis, D; Zaoutsos, S

    2016-07-01

    This study initially deals with the investigation of the induced strains during hardening stage of a self-setting calcium phosphate bone cement using fiber-Bragg grating (FBG) optical sensors. A complementary Scanning Electron Microscopy (SEM) investigation was also conducted at different time intervals of the hardening period and its findings were related to the FBG recordings. From the obtained results, it is demonstrated that the FBG response is affected by the microstructural changes taking place when the bone cement is immersed into the hardening liquid media. Subsequently, the FBG sensor was used to monitor the absorption process and hygroscopic response of the hardened and dried biocement when exposed to a liquid/humid environment. From the FBG-based calculated hygric strains as a function of moisture concentration, the coefficient of moisture expansion (CME) of the examined bone cement was obtained, exhibiting two distinct linear regions. PMID:26807773

  14. 47 CFR 216.1 - NCS Directives.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL COMMUNICATIONS..., has developed a system of official documents of a referential nature. The documents include NCS... procedures of a continuing nature. The Directives are issued by the Executive Office of the President...

  15. 47 CFR 216.1 - NCS Directives.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL COMMUNICATIONS..., has developed a system of official documents of a referential nature. The documents include NCS... procedures of a continuing nature. The Directives are issued by the Executive Office of the President...

  16. 47 CFR 216.1 - NCS Directives.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL COMMUNICATIONS..., has developed a system of official documents of a referential nature. The documents include NCS... procedures of a continuing nature. The Directives are issued by the Executive Office of the President...

  17. 47 CFR 216.1 - NCS Directives.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL COMMUNICATIONS..., has developed a system of official documents of a referential nature. The documents include NCS... procedures of a continuing nature. The Directives are issued by the Executive Office of the President...

  18. 47 CFR 216.1 - NCS Directives.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL COMMUNICATIONS..., has developed a system of official documents of a referential nature. The documents include NCS... procedures of a continuing nature. The Directives are issued by the Executive Office of the President...

  19. Synthesis of an azido-tagged low affinity ratiometric calcium sensor

    PubMed Central

    Caldwell, Stuart T.; Cairns, Andrew G.; Olson, Marnie; Chalmers, Susan; Sandison, Mairi; Mullen, William; McCarron, John G.; Hartley, Richard C.

    2015-01-01

    Changes in high localised concentrations of Ca2+ ions are fundamental to cell signalling. The synthesis of a dual excitation, ratiometric calcium ion sensor with a Kd of 90 μM, is described. It is tagged with an azido group for bioconjugation, and absorbs in the blue/green and emits in the red region of the visible spectrum with a large Stokes shift. The binding modulating nitro group is introduced to the BAPTA core prior to construction of a benzofuran-2-yl carboxaldehyde by an allylation–oxidation–cyclisation sequence, which is followed by condensation with an azido-tagged thiohydantoin. The thiohydantoin unit has to be protected with an acetoxymethyl (AM) caging group to allow CuAAC click reaction and incorporation of the KDEL peptide endoplasmic reticulum (ER) retention sequence. PMID:26709317

  20. Calmodulin and STIM proteins: Two major calcium sensors in the cytoplasm and endoplasmic reticulum.

    PubMed

    Marshall, Christopher B; Nishikawa, Tadateru; Osawa, Masanori; Stathopulos, Peter B; Ikura, Mitsuhiko

    2015-04-24

    The calcium (Ca(2+)) ion is a universal signalling messenger which plays vital physiological roles in all eukaryotes. To decode highly regulated intracellular Ca(2+) signals, cells have evolved a number of sensor proteins that are ideally adapted to respond to a specific range of Ca(2+) levels. Among many such proteins, calmodulin (CaM) is a multi-functional cytoplasmic Ca(2+) sensor with a remarkable ability to interact with and regulate a plethora of structurally diverse target proteins. CaM achieves this 'multi-talented' functionality through two EF-hand domains, each with an independent capacity to bind targets, and an adaptable flexible linker. By contrast, stromal interaction molecule-1 and -2 (STIMs) have evolved for a specific role in endoplasmic reticulum (ER) Ca(2+) sensing using EF-hand machinery analogous to CaM; however, whereas CaM structurally adjusts to dissimilar binding partners, STIMs use the EF-hand machinery to self-regulate the stability of the Ca(2+) sensing domain. The molecular mechanisms underlying the Ca(2+)-dependent signal transduction by CaM and STIMs have revealed a remarkable repertoire of actions and underscore the flexibility of nature in molecular evolution and adaption to discrete Ca(2+) levels. Recent genomic sequencing efforts have uncovered a number of disease-associated mutations in both CaM and STIM1. This article aims to highlight the most recent key structural and functional findings in the CaM and STIM fields, and discusses how these two Ca(2+) sensor proteins execute their biological functions. PMID:25998729

  1. PyNCS: a microkernel for high-level definition and configuration of neuromorphic electronic systems.

    PubMed

    Stefanini, Fabio; Neftci, Emre O; Sheik, Sadique; Indiveri, Giacomo

    2014-01-01

    Neuromorphic hardware offers an electronic substrate for the realization of asynchronous event-based sensory-motor systems and large-scale spiking neural network architectures. In order to characterize these systems, configure them, and carry out modeling experiments, it is often necessary to interface them to workstations. The software used for this purpose typically consists of a large monolithic block of code which is highly specific to the hardware setup used. While this approach can lead to highly integrated hardware/software systems, it hampers the development of modular and reconfigurable infrastructures thus preventing a rapid evolution of such systems. To alleviate this problem, we propose PyNCS, an open-source front-end for the definition of neural network models that is interfaced to the hardware through a set of Python Application Programming Interfaces (APIs). The design of PyNCS promotes modularity, portability and expandability and separates implementation from hardware description. The high-level front-end that comes with PyNCS includes tools to define neural network models as well as to create, monitor and analyze spiking data. Here we report the design philosophy behind the PyNCS framework and describe its implementation. We demonstrate its functionality with two representative case studies, one using an event-based neuromorphic vision sensor, and one using a set of multi-neuron devices for carrying out a cognitive decision-making task involving state-dependent computation. PyNCS, already applicable to a wide range of existing spike-based neuromorphic setups, will accelerate the development of hybrid software/hardware neuromorphic systems, thanks to its code flexibility. The code is open-source and available online at https://github.com/inincs/pyNCS. PMID:25232314

  2. PyNCS: a microkernel for high-level definition and configuration of neuromorphic electronic systems

    PubMed Central

    Stefanini, Fabio; Neftci, Emre O.; Sheik, Sadique; Indiveri, Giacomo

    2014-01-01

    Neuromorphic hardware offers an electronic substrate for the realization of asynchronous event-based sensory-motor systems and large-scale spiking neural network architectures. In order to characterize these systems, configure them, and carry out modeling experiments, it is often necessary to interface them to workstations. The software used for this purpose typically consists of a large monolithic block of code which is highly specific to the hardware setup used. While this approach can lead to highly integrated hardware/software systems, it hampers the development of modular and reconfigurable infrastructures thus preventing a rapid evolution of such systems. To alleviate this problem, we propose PyNCS, an open-source front-end for the definition of neural network models that is interfaced to the hardware through a set of Python Application Programming Interfaces (APIs). The design of PyNCS promotes modularity, portability and expandability and separates implementation from hardware description. The high-level front-end that comes with PyNCS includes tools to define neural network models as well as to create, monitor and analyze spiking data. Here we report the design philosophy behind the PyNCS framework and describe its implementation. We demonstrate its functionality with two representative case studies, one using an event-based neuromorphic vision sensor, and one using a set of multi-neuron devices for carrying out a cognitive decision-making task involving state-dependent computation. PyNCS, already applicable to a wide range of existing spike-based neuromorphic setups, will accelerate the development of hybrid software/hardware neuromorphic systems, thanks to its code flexibility. The code is open-source and available online at https://github.com/inincs/pyNCS. PMID:25232314

  3. Calcium Binding Promotes Conformational Flexibility of the Neuronal Ca2+ Sensor Synaptotagmin

    PubMed Central

    Bykhovskaia, Maria

    2015-01-01

    Synaptotagmin 1 (Syt1) is a synaptic vesicle protein that serves as a calcium sensor of neuronal secretion. It is established that calcium binding to Syt1 triggers vesicle fusion and release of neuronal transmitters, however, the dynamics of this process is not fully understood. To investigate how Ca2+ binding affects Syt1 conformational dynamics, we performed prolonged molecular dynamics (MD) simulations of Ca2+-unbound and Ca2+-bound forms of Syt1. MD simulations were performed at a microsecond scale and combined with Monte Carlo sampling. We found that in the absence of Ca2+ Syt1 structure in the solution is represented by an ensemble of conformational states with tightly coupled domains. To investigate the effect of Ca2+ binding, we used two different strategies to generate a molecular model of a Ca2+-bound form of Syt1. First, we employed subsequent replacements of monovalent cations transiently captured within Syt1 Ca2+-binding pockets by Ca2+ ions. Second, we performed MD simulations of Syt1 at elevated Ca2+ levels. All the simulations produced Syt1 structures bound to four Ca2+ ions, two ions chelated at the binding pocket of each domain. MD simulations of the Ca2+-bound form of Syt1 revealed that Syt1 conformational flexibility drastically increased upon Ca2+ binding. In the presence of Ca2+, the separation between domains increased, and interdomain rotations became more frequent. These findings suggest that Ca2+ binding to Syt1 may induce major changes in the Syt1 conformational state, which in turn may initiate the fusion process. PMID:25992729

  4. FINAL REPORT: NATIONAL CHILDREN'S STUDY (NCS) ESTIMATING SUBJECT BURDEN FOR POTENTIAL NCS MEASUREMENTS

    EPA Science Inventory

    Purpose The National Children's Study (NCS), a large longitudinal cohort study of environmental exposures among children, is currently in the planning stage. Prior to enrollment of 100,000 pregnant women across the United Sates for this study, a better understanding of the partic...

  5. Functional heterogeneity of the four voltage sensors of a human L-type calcium channel

    PubMed Central

    Pantazis, Antonios; Savalli, Nicoletta; Sigg, Daniel; Neely, Alan; Olcese, Riccardo

    2014-01-01

    Excitation-evoked Ca2+ influx is the fastest and most ubiquitous chemical trigger for cellular processes, including neurotransmitter release, muscle contraction, and gene expression. The voltage dependence and timing of Ca2+ entry are thought to be functions of voltage-gated calcium (CaV) channels composed of a central pore regulated by four nonidentical voltage-sensing domains (VSDs I–IV). Currently, the individual voltage dependence and the contribution to pore opening of each VSD remain largely unknown. Using an optical approach (voltage-clamp fluorometry) to track the movement of the individual voltage sensors, we discovered that the four VSDs of CaV1.2 channels undergo voltage-evoked conformational rearrangements, each exhibiting distinct voltage- and time-dependent properties over a wide range of potentials and kinetics. The voltage dependence and fast kinetic components in the activation of VSDs II and III were compatible with the ionic current properties, suggesting that these voltage sensors are involved in CaV1.2 activation. This view is supported by an obligatory model, in which activation of VSDs II and III is necessary to open the pore. When these data were interpreted in view of an allosteric model, where pore opening is intrinsically independent but biased by VSD activation, VSDs II and III were each found to supply ∼50 meV (∼2 kT), amounting to ∼85% of the total energy, toward stabilizing the open state, with a smaller contribution from VSD I (∼16 meV). VSD IV did not appear to participate in channel opening. PMID:25489110

  6. Porous polymer film calcium ion chemical sensor and method of using the same

    DOEpatents

    Porter, Marc D.; Chau, Lai-Kwan

    1991-02-12

    A method of measuring calcium ions is disclosed wherein a calcium sensitive reagent, calcichrome, is immobilized on a porour polymer film. The reaction of the calcium sensitive reagent to the Ca(II) is then measured and concentration determined as a function of the reaction.

  7. Porous polymer film calcium ion chemical sensor and method of using the same

    DOEpatents

    Porter, M.D.; Chau, L.K.

    1991-02-12

    A method of measuring calcium ions is disclosed wherein a calcium sensitive reagent, calcichrome, is immobilized on a porous polymer film. The reaction of the calcium sensitive reagent to the Ca(II) is then measured and concentration determined as a function of the reaction. 1 figure.

  8. Structural basis for a hand-like site in the calcium sensor CatchER with fast kinetics

    SciTech Connect

    Zhang, Ying; Reddish, Florence; Tang, Shen; Zhuo, You; Wang, Yuan-Fang; Yang, Jenny J.; Weber, Irene T.

    2013-12-01

    High-resolution crystal structures of the designed calcium sensor CatchER revealed snapshots of calcium and gadolinium ions binding within the designed site in agreement with its fast kinetics. Calcium ions, which are important signaling molecules, can be detected in the endoplasmic reticulum by an engineered mutant of green fluorescent protein (GFP) designated CatchER with a fast off-rate. High resolution (1.78–1.20 Å) crystal structures were analyzed for CatchER in the apo form and in complexes with calcium or gadolinium to probe the binding site for metal ions. While CatchER exhibits a 1:1 binding stoichiometry in solution, two positions were observed for each of the metal ions bound within the hand-like site formed by the carboxylate side chains of the mutated residues S147E, S202D, Q204E, F223E and T225E that may be responsible for its fast kinetic properties. Comparison of the structures of CatchER, wild-type GFP and enhanced GFP confirmed that different conformations of Thr203 and Glu222 are associated with the two forms of Tyr66 of the chromophore which are responsible for the absorbance wavelengths of the different proteins. Calcium binding to CatchER may shift the equilibrium for conformational population of the Glu222 side chain and lead to further changes in its optical properties.

  9. Tonoplast calcium sensors CBL2 and CBL3 control plant growth and ion homeostasis through regulating V-ATPase activity in Arabidopsis

    PubMed Central

    Tang, Ren-Jie; Liu, Hua; Yang, Yang; Yang, Lei; Gao, Xiao-Shu; Garcia, Veder J; Luan, Sheng; Zhang, Hong-Xia

    2012-01-01

    Plant responses to developmental and environmental cues are often mediated by calcium (Ca2+) signals that are transmitted by diverse calcium sensors. The calcineurin B-like (CBL) protein family represents calcium sensors that decode calcium signals through specific interactions with a group of CBL-interacting protein kinases. We report functional analysis of Arabidopsis CBL2 and CBL3, two closely related CBL members that are localized to the vacuolar membrane through the N-terminal tonoplast-targeting sequence. While cbl2 or cbl3 single mutant did not show any phenotypic difference from the wild type, the cbl2 cbl3 double mutant was stunted with leaf tip necrosis, underdeveloped roots, shorter siliques and fewer seeds. These defects were reminiscent of those in the vha-a2 vha-a3 double mutant deficient in vacuolar H+-ATPase (V-ATPase). Indeed, the V-ATPase activity was reduced in the cbl2 cbl3 double mutant, connecting tonoplast CBL-type calcium sensors to the regulation of V-ATPase. Furthermore, cbl2 cbl3 double mutant was compromised in ionic tolerance and micronutrient accumulation, consistent with the defect in V-ATPase activity that has been shown to function in ion compartmentalization. Our results suggest that calcium sensors CBL2 and CBL3 serve as molecular links between calcium signaling and V-ATPase, a central regulator of intracellular ion homeostasis. PMID:23184060

  10. Calcium sensor kinase activates potassium uptake systems in gland cells of Venus flytraps

    PubMed Central

    Scherzer, Sönke; Böhm, Jennifer; Krol, Elzbieta; Shabala, Lana; Kreuzer, Ines; Larisch, Christina; Bemm, Felix; Al-Rasheid, Khaled A. S.; Shabala, Sergey; Rennenberg, Heinz; Neher, Erwin; Hedrich, Rainer

    2015-01-01

    The Darwin plant Dionaea muscipula is able to grow on mineral-poor soil, because it gains essential nutrients from captured animal prey. Given that no nutrients remain in the trap when it opens after the consumption of an animal meal, we here asked the question of how Dionaea sequesters prey-derived potassium. We show that prey capture triggers expression of a K+ uptake system in the Venus flytrap. In search of K+ transporters endowed with adequate properties for this role, we screened a Dionaea expressed sequence tag (EST) database and identified DmKT1 and DmHAK5 as candidates. On insect and touch hormone stimulation, the number of transcripts of these transporters increased in flytraps. After cRNA injection of K+-transporter genes into Xenopus oocytes, however, both putative K+ transporters remained silent. Assuming that calcium sensor kinases are regulating Arabidopsis K+ transporter 1 (AKT1), we coexpressed the putative K+ transporters with a large set of kinases and identified the CBL9-CIPK23 pair as the major activating complex for both transporters in Dionaea K+ uptake. DmKT1 was found to be a K+-selective channel of voltage-dependent high capacity and low affinity, whereas DmHAK5 was identified as the first, to our knowledge, proton-driven, high-affinity potassium transporter with weak selectivity. When the Venus flytrap is processing its prey, the gland cell membrane potential is maintained around −120 mV, and the apoplast is acidified to pH 3. These conditions in the green stomach formed by the closed flytrap allow DmKT1 and DmHAK5 to acquire prey-derived K+, reducing its concentration from millimolar levels down to trace levels. PMID:25997445

  11. Calcium sensor kinase activates potassium uptake systems in gland cells of Venus flytraps.

    PubMed

    Scherzer, Sönke; Böhm, Jennifer; Krol, Elzbieta; Shabala, Lana; Kreuzer, Ines; Larisch, Christina; Bemm, Felix; Al-Rasheid, Khaled A S; Shabala, Sergey; Rennenberg, Heinz; Neher, Erwin; Hedrich, Rainer

    2015-06-01

    The Darwin plant Dionaea muscipula is able to grow on mineral-poor soil, because it gains essential nutrients from captured animal prey. Given that no nutrients remain in the trap when it opens after the consumption of an animal meal, we here asked the question of how Dionaea sequesters prey-derived potassium. We show that prey capture triggers expression of a K(+) uptake system in the Venus flytrap. In search of K(+) transporters endowed with adequate properties for this role, we screened a Dionaea expressed sequence tag (EST) database and identified DmKT1 and DmHAK5 as candidates. On insect and touch hormone stimulation, the number of transcripts of these transporters increased in flytraps. After cRNA injection of K(+)-transporter genes into Xenopus oocytes, however, both putative K(+) transporters remained silent. Assuming that calcium sensor kinases are regulating Arabidopsis K(+) transporter 1 (AKT1), we coexpressed the putative K(+) transporters with a large set of kinases and identified the CBL9-CIPK23 pair as the major activating complex for both transporters in Dionaea K(+) uptake. DmKT1 was found to be a K(+)-selective channel of voltage-dependent high capacity and low affinity, whereas DmHAK5 was identified as the first, to our knowledge, proton-driven, high-affinity potassium transporter with weak selectivity. When the Venus flytrap is processing its prey, the gland cell membrane potential is maintained around -120 mV, and the apoplast is acidified to pH 3. These conditions in the green stomach formed by the closed flytrap allow DmKT1 and DmHAK5 to acquire prey-derived K(+), reducing its concentration from millimolar levels down to trace levels. PMID:25997445

  12. Crystal Structures of the GCaMP Calcium Sensor Reveal the Mechanism of Fluorescence Signal Change and Aid Rational Design

    SciTech Connect

    Akerboom, Jasper; Velez Rivera, Jonathan D.; Rodriguez Guilbe, María M.; Alfaro Malavé, Elisa C.; Hernandez, Hector H.; Tian, Lin; Hires, S. Andrew; Marvin, Jonathan S.; Looger, Loren L.; Schreiter, Eric R.

    2009-03-16

    The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca{sup 2+}-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaM and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.

  13. Redox Modulation of Cellular Signaling and Metabolism Through Reversible Oxidation of Methionine Sensors in Calcium Regulatory Proteins

    SciTech Connect

    Bigelow, Diana J.; Squier, Thomas C.

    2005-01-17

    Adaptive responses associated with environmental stressors are critical to cell survival. These involve the modulation of central signaling protein functions through site-specific and enzymatically reversible oxidative modifications of methionines to coordinate cellular metabolism, energy utilization, and calcium signaling. Under conditions when cellular redox and antioxidant defenses are overwhelmed, the selective oxidation of critical methionines within selected protein sensors functions to down-regulate energy metabolism and the further generation of reactive oxygen species (ROS). Mechanistically, these functional changes within protein sensors take advantage of the helix-breaking character of methionine sulfoxide. Thus, depending on either the ecological niche of the organism or the cellular milieu of different organ systems, cellular metabolism can be fine-tuned to maintain optimal function in the face of variable amounts of collateral oxidative damage. The sensitivity of several calcium regulatory proteins to oxidative modification provides cellular sensors that link oxidative stress to cellular response and recovery. Calmodulin (CaM) is one such critical calcium regulatory protein, which is functionally sensitive to methionine oxidation. Helix destabilization resulting from the oxidation of either Met{sup 144} or Met{sup 145} results in the nonproductive association between CaM and target proteins. The ability of oxidized CaM to stabilize its target proteins in an inhibited state with an affinity similar to that of native (unoxidized) CaM permits this central regulatory protein to function as a cellular rheostat that down-regulates energy metabolism in response to oxidative stress. Likewise, oxidation of a methionine within a critical switch region of the regulatory protein phospholamban is expected to destabilize the phosphorylationdependent helix formation necessary for the release of enzyme inhibition, resulting in a down-regulation of the Ca-ATPase in

  14. Polymorphism in Cs[AgZn(NCS)4].

    PubMed

    Güneş, Minna; Valkonen, Jussi

    2002-12-01

    The title compound, caesium silver zinc tetrathiocyanate, crystallizes in two polymorphic forms, in space groups P2(1)/n and C2/c. Both structures form a continuous three-dimensional network. The structure in C2/c contains a delocalized Ag atom in a binuclear-like anion, where two [Ag(NCS)(4)] units (delocalized Ag as an average) share two common NCS(-) ligands. PMID:12466595

  15. The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory

    PubMed Central

    Reinhard, Judith R.; Kriz, Alexander; Galic, Milos; Angliker, Nico; Rajalu, Mathieu; Vogt, Kaspar E.; Ruegg, Markus A.

    2016-01-01

    Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns of high neuronal activity and is required for learning and memory. Here we identify a mechanism that requires the calcium-binding protein Copine-6 to translate the initial calcium signals into changes in spine structure. We show that Copine-6 is recruited from the cytosol of dendrites to postsynaptic spine membranes by calcium transients that precede LTP. Cpne6 knockout mice are deficient in hippocampal LTP, learning and memory. Hippocampal neurons from Cpne6 knockouts lack spine structural plasticity as do wild-type neurons that express a Copine-6 calcium mutant. The function of Copine-6 is based on its binding, activating and recruiting the Rho GTPase Rac1 to cell membranes. Consistent with this function, the LTP deficit of Cpne6 knockout mice is rescued by the actin stabilizer jasplakinolide. These data show that Copine-6 links activity-triggered calcium signals to spine structural plasticity necessary for learning and memory. PMID:27194588

  16. The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory.

    PubMed

    Reinhard, Judith R; Kriz, Alexander; Galic, Milos; Angliker, Nico; Rajalu, Mathieu; Vogt, Kaspar E; Ruegg, Markus A

    2016-01-01

    Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns of high neuronal activity and is required for learning and memory. Here we identify a mechanism that requires the calcium-binding protein Copine-6 to translate the initial calcium signals into changes in spine structure. We show that Copine-6 is recruited from the cytosol of dendrites to postsynaptic spine membranes by calcium transients that precede LTP. Cpne6 knockout mice are deficient in hippocampal LTP, learning and memory. Hippocampal neurons from Cpne6 knockouts lack spine structural plasticity as do wild-type neurons that express a Copine-6 calcium mutant. The function of Copine-6 is based on its binding, activating and recruiting the Rho GTPase Rac1 to cell membranes. Consistent with this function, the LTP deficit of Cpne6 knockout mice is rescued by the actin stabilizer jasplakinolide. These data show that Copine-6 links activity-triggered calcium signals to spine structural plasticity necessary for learning and memory. PMID:27194588

  17. Overlapping functions of stonin 2 and SV2 in sorting of the calcium sensor synaptotagmin 1 to synaptic vesicles

    PubMed Central

    Kaempf, Natalie; Kochlamazashvili, Gaga; Puchkov, Dmytro; Maritzen, Tanja; Bajjalieh, Sandra M.; Kononenko, Natalia L.; Haucke, Volker

    2015-01-01

    Neurotransmission involves the calcium-regulated exocytic fusion of synaptic vesicles (SVs) and the subsequent retrieval of SV membranes followed by reformation of properly sized and shaped SVs. An unresolved question is whether each SV protein is sorted by its own dedicated adaptor or whether sorting is facilitated by association between different SV proteins. We demonstrate that endocytic sorting of the calcium sensor synaptotagmin 1 (Syt1) is mediated by the overlapping activities of the Syt1-associated SV glycoprotein SV2A/B and the endocytic Syt1-adaptor stonin 2 (Stn2). Deletion or knockdown of either SV2A/B or Stn2 results in partial Syt1 loss and missorting of Syt1 to the neuronal surface, whereas deletion of both SV2A/B and Stn2 dramatically exacerbates this phenotype. Selective missorting and degradation of Syt1 in the absence of SV2A/B and Stn2 impairs the efficacy of neurotransmission at hippocampal synapses. These results indicate that endocytic sorting of Syt1 to SVs is mediated by the overlapping activities of SV2A/B and Stn2 and favor a model according to which SV protein sorting is guarded by both cargo-specific mechanisms as well as association between SV proteins. PMID:26015569

  18. Development of calcium zirconate-based hydrogen sensors with oxide reference electrodes for molten aluminum

    NASA Astrophysics Data System (ADS)

    Krishnan, Vivek

    Hydrogen is a major cause of gas porosity in aluminum and is frequently removed from the melt prior to casting. The degassing process can be better controlled if the hydrogen content in the melt is known. Thus, gas sensors which can make continuous in situ measurements in molten aluminum are needed. Current online hydrogen sensing systems are complex designs which are prohibitively expensive. Solid electrolyte based potentiometric sensors have been developed as an attractive alternate. These sensors have traditionally used a gas phase as the reference electrode. The present design has a condensed-phase reference electrode to avoid the need for transport of the reference gas into and out of the melt. The use of an oxide rather than a hydride phase reference is expected to considerably lower device cost and improve shelf life and reliability. The sensor element consists of a solid electrolyte tube based on 10 mol% Indoped CaZrO3, which was synthesized using both solid oxide and oxalate co-precipitation techniques. Precursor oxalate powders prepared using polymeric surfactants (PEG) were characterized using SEM, XRD, FTIR and particle size analysis. PEG was found to reduce particle size and also influence the process of perovskite formation. The oxalate co-precipitation technique enabled powder synthesis at reduced processing time and temperature. Closed-one-end tubes were slip cast and densified for use as solid electrolytes. Impedance spectroscopy and D.C. resistance measurements were made at temperatures between 650 and 900°C. Undoped CaZrO3 was found to be a p-type conductor in air. Indoped CaZrO3 acted as a proton conductor in air and argon+H2O, whereas the material was found to be a p-type conductor in pure argon. While bulk conduction was found to be homogenous with activation energies matching those from D.C. measurements, conduction across the grain boundary was found to be heterogeneous. Potentiometric sensors using In-doped CaZrO3 as the electrolyte, and

  19. Toxicity of 33 NCS to freshwater fish and sea lamprey

    USGS Publications Warehouse

    Marking, Leif L.; King, Everett L.; Walker, Charles R.; Howell, John H.

    1970-01-01

    The chemical 33NCS (3'-chloro-3-nitrosalicylanilide) was evaluated as a fish control agent and as a larvicide for sea lampreys at the Fish Control Laboratories of the Bureau of Sport Fisheries and Wildlife and the Hammond Bay Biological Station of the Bureau of Commercial Fisheries. The chemical is rapidly toxic to many species. Sea lampreys, bowfin, and channel catfish are the most sensitive species. Carp are more sensitive than trouts or sunfishes. Use of 33NCS in selective control of freshwater fishes or sea lampreys requires precise control because its toxicity is strongly influenced by variations in water quality.

  20. CO2/HCO3−- and Calcium-regulated Soluble Adenylyl Cyclase as a Physiological ATP Sensor*

    PubMed Central

    Zippin, Jonathan H.; Chen, Yanqiu; Straub, Susanne G.; Hess, Kenneth C.; Diaz, Ana; Lee, Dana; Tso, Patrick; Holz, George G.; Sharp, Geoffrey W. G.; Levin, Lonny R.; Buck, Jochen

    2013-01-01

    The second messenger molecule cAMP is integral for many physiological processes. In mammalian cells, cAMP can be generated from hormone- and G protein-regulated transmembrane adenylyl cyclases or via the widely expressed and structurally and biochemically distinct enzyme soluble adenylyl cyclase (sAC). sAC activity is uniquely stimulated by bicarbonate ions, and in cells, sAC functions as a physiological carbon dioxide, bicarbonate, and pH sensor. sAC activity is also stimulated by calcium, and its affinity for its substrate ATP suggests that it may be sensitive to physiologically relevant fluctuations in intracellular ATP. We demonstrate here that sAC can function as a cellular ATP sensor. In cells, sAC-generated cAMP reflects alterations in intracellular ATP that do not affect transmembrane AC-generated cAMP. In β cells of the pancreas, glucose metabolism generates ATP, which corresponds to an increase in cAMP, and we show here that sAC is responsible for an ATP-dependent cAMP increase. Glucose metabolism also elicits insulin secretion, and we further show that sAC is necessary for normal glucose-stimulated insulin secretion in vitro and in vivo. PMID:24100033

  1. Fluorescence Lifetime Readouts of Troponin-C-Based Calcium FRET Sensors: A Quantitative Comparison of CFP and mTFP1 as Donor Fluorophores

    PubMed Central

    Laine, Romain; Stuckey, Daniel W.; Manning, Hugh; Warren, Sean C.; Kennedy, Gordon; Carling, David

    2012-01-01

    We have compared the performance of two Troponin-C-based calcium FRET sensors using fluorescence lifetime read-outs. The first sensor, TN-L15, consists of a Troponin-C fragment inserted between CFP and Citrine while the second sensor, called mTFP-TnC-Cit, was realized by replacing CFP in TN-L15 with monomeric Teal Fluorescent Protein (mTFP1). Using cytosol preparations of transiently transfected mammalian cells, we have measured the fluorescence decay profiles of these sensors at controlled concentrations of calcium using time-correlated single photon counting. These data were fitted to discrete exponential decay models using global analysis to determine the FRET efficiency, fraction of donor molecules undergoing FRET and calcium affinity of these sensors. We have also studied the decay profiles of the donor fluorescent proteins alone and determined the sensitivity of the donor lifetime to temperature and emission wavelength. Live-cell fluorescence lifetime imaging (FLIM) of HEK293T cells expressing each of these sensors was also undertaken. We confirmed that donor fluorescence of mTFP-TnC-Cit fits well to a two-component decay model, while the TN-L15 lifetime data was best fitted to a constrained four-component model, which was supported by phasor analysis of the measured lifetime data. If the constrained global fitting is employed, the TN-L15 sensor can provide a larger dynamic range of lifetime readout than the mTFP-TnC-Cit sensor but the CFP donor is significantly more sensitive to changes in temperature and emission wavelength compared to mTFP and, while the mTFP-TnC-Cit solution phase data broadly agreed with measurements in live cells, this was not the case for the TN-L15 sensor. Our titration experiment also indicates that a similar precision in determination of calcium concentration can be achieved with both FRET biosensors when fitting a single exponential donor fluorescence decay model to the fluorescence decay profiles. We therefore suggest that m

  2. Calredoxin represents a novel type of calcium-dependent sensor-responder connected to redox regulation in the chloroplast.

    PubMed

    Hochmal, Ana Karina; Zinzius, Karen; Charoenwattanasatien, Ratana; Gäbelein, Philipp; Mutoh, Risa; Tanaka, Hideaki; Schulze, Stefan; Liu, Gai; Scholz, Martin; Nordhues, André; Offenborn, Jan Niklas; Petroutsos, Dimitris; Finazzi, Giovanni; Fufezan, Christian; Huang, Kaiyao; Kurisu, Genji; Hippler, Michael

    2016-01-01

    Calcium (Ca(2+)) and redox signalling play important roles in acclimation processes from archaea to eukaryotic organisms. Herein we characterized a unique protein from Chlamydomonas reinhardtii that has the competence to integrate Ca(2+)- and redox-related signalling. This protein, designated as calredoxin (CRX), combines four Ca(2+)-binding EF-hands and a thioredoxin (TRX) domain. A crystal structure of CRX, at 1.6 Å resolution, revealed an unusual calmodulin-fold of the Ca(2+)-binding EF-hands, which is functionally linked via an inter-domain communication path with the enzymatically active TRX domain. CRX is chloroplast-localized and interacted with a chloroplast 2-Cys peroxiredoxin (PRX1). Ca(2+)-binding to CRX is critical for its TRX activity and for efficient binding and reduction of PRX1. Thereby, CRX represents a new class of Ca(2+)-dependent 'sensor-responder' proteins. Genetically engineered Chlamydomonas strains with strongly diminished amounts of CRX revealed altered photosynthetic electron transfer and were affected in oxidative stress response underpinning a function of CRX in stress acclimation. PMID:27297041

  3. Excited-state structural dynamics of a dual-emission calmodulin-green fluorescent protein sensor for calcium ion imaging.

    PubMed

    Oscar, Breland G; Liu, Weimin; Zhao, Yongxin; Tang, Longteng; Wang, Yanli; Campbell, Robert E; Fang, Chong

    2014-07-15

    Fluorescent proteins (FPs) have played a pivotal role in bioimaging and advancing biomedicine. The versatile fluorescence from engineered, genetically encodable FP variants greatly enhances cellular imaging capabilities, which are dictated by excited-state structural dynamics of the embedded chromophore inside the protein pocket. Visualization of the molecular choreography of the photoexcited chromophore requires a spectroscopic technique capable of resolving atomic motions on the intrinsic timescale of femtosecond to picosecond. We use femtosecond stimulated Raman spectroscopy to study the excited-state conformational dynamics of a recently developed FP-calmodulin biosensor, GEM-GECO1, for calcium ion (Ca(2+)) sensing. This study reveals that, in the absence of Ca(2+), the dominant skeletal motion is a ∼ 170 cm(-1) phenol-ring in-plane rocking that facilitates excited-state proton transfer (ESPT) with a time constant of ∼ 30 ps (6 times slower than wild-type GFP) to reach the green fluorescent state. The functional relevance of the motion is corroborated by molecular dynamics simulations. Upon Ca(2+) binding, this in-plane rocking motion diminishes, and blue emission from a trapped photoexcited neutral chromophore dominates because ESPT is inhibited. Fluorescence properties of site-specific protein mutants lend further support to functional roles of key residues including proline 377 in modulating the H-bonding network and fluorescence outcome. These crucial structural dynamics insights will aid rational design in bioengineering to generate versatile, robust, and more sensitive optical sensors to detect Ca(2+) in physiologically relevant environments. PMID:24987121

  4. Calredoxin represents a novel type of calcium-dependent sensor-responder connected to redox regulation in the chloroplast

    PubMed Central

    Hochmal, Ana Karina; Zinzius, Karen; Charoenwattanasatien, Ratana; Gäbelein, Philipp; Mutoh, Risa; Tanaka, Hideaki; Schulze, Stefan; Liu, Gai; Scholz, Martin; Nordhues, André; Offenborn, Jan Niklas; Petroutsos, Dimitris; Finazzi, Giovanni; Fufezan, Christian; Huang, Kaiyao; Kurisu, Genji; Hippler, Michael

    2016-01-01

    Calcium (Ca2+) and redox signalling play important roles in acclimation processes from archaea to eukaryotic organisms. Herein we characterized a unique protein from Chlamydomonas reinhardtii that has the competence to integrate Ca2+- and redox-related signalling. This protein, designated as calredoxin (CRX), combines four Ca2+-binding EF-hands and a thioredoxin (TRX) domain. A crystal structure of CRX, at 1.6 Å resolution, revealed an unusual calmodulin-fold of the Ca2+-binding EF-hands, which is functionally linked via an inter-domain communication path with the enzymatically active TRX domain. CRX is chloroplast-localized and interacted with a chloroplast 2-Cys peroxiredoxin (PRX1). Ca2+-binding to CRX is critical for its TRX activity and for efficient binding and reduction of PRX1. Thereby, CRX represents a new class of Ca2+-dependent ‘sensor-responder' proteins. Genetically engineered Chlamydomonas strains with strongly diminished amounts of CRX revealed altered photosynthetic electron transfer and were affected in oxidative stress response underpinning a function of CRX in stress acclimation. PMID:27297041

  5. Genome-wide identification and analyses of the rice calmodulin and related potential calcium sensor proteins

    PubMed Central

    Boonburapong, Bongkoj; Buaboocha, Teerapong

    2007-01-01

    Background A wide range of stimuli evoke rapid and transient increases in [Ca2+]cyt in plant cells which are transmitted by protein sensors that contain EF-hand motifs. Here, a group of Oryza sativa L. genes encoding calmodulin (CaM) and CaM-like (CML) proteins that do not possess functional domains other than the Ca2+-binding EF-hand motifs was analyzed. Results By functional analyses and BLAST searches of the TIGR rice database, a maximum number of 243 proteins that possibly have EF-hand motifs were identified in the rice genome. Using a neighbor-joining tree based on amino acid sequence similarity, five loci were defined as Cam genes and thirty two additional CML genes were identified. Extensive analyses of the gene structures, the chromosome locations, the EF-hand motif organization, expression characteristics including analysis by RT-PCR and a comparative analysis of Cam and CML genes in rice and Arabidopsis are presented. Conclusion Although many proteins have unknown functions, the complexity of this gene family indicates the importance of Ca2+-signals in regulating cellular responses to stimuli and this family of proteins likely plays a critical role as their transducers. PMID:17263873

  6. Bio-NCs - the marriage of ultrasmall metal nanoclusters with biomolecules

    NASA Astrophysics Data System (ADS)

    Goswami, Nirmal; Zheng, Kaiyuan; Xie, Jianping

    2014-10-01

    Ultrasmall metal nanoclusters (NCs) have attracted increasing attention due to their fascinating physicochemical properties. Today, functional metal NCs are finding growing acceptance in biomedical applications. To achieve a better performance in biomedical applications, metal NCs can be interfaced with biomolecules, such as proteins, peptides, and DNA, to form a new class of biomolecule-NC composites (or bio-NCs in short), which typically show synergistic or novel physicochemical and physiological properties. This feature article focuses on the recent studies emerging at the interface of metal NCs and biomolecules, where the interactions could impart unique physicochemical properties to the metal NCs, as well as mutually regulate biological functions of the bio-NCs. In this article, we first provide a broad overview of key concepts and developments in the novel biomolecule-directed synthesis of metal NCs. A special focus is placed on the key roles of biomolecules in metal NC synthesis. In the second part, we describe how the encapsulated metal NCs affect the structure and function of biomolecules. Followed by that, we discuss several unique synergistic effects observed in the bio-NCs, and illustrate them with examples highlighting their potential biomedical applications. Continued interdisciplinary efforts are required to build up in-depth knowledge about the interfacial chemistry and biology of bio-NCs, which could further pave their ways toward biomedical applications.

  7. Single-column purification of the tag-free, recombinant form of the neuronal calcium sensor protein, hippocalcin expressed in Escherichia coli.

    PubMed

    Krishnan, Anuradha; Viviano, Jeffrey; Morozov, Yaroslav; Venkataraman, Venkat

    2016-07-01

    Hippocalcin is a 193 aa protein that is a member of the neuronal calcium sensor protein family, whose functions are regulated by calcium. Mice that lack the function of this protein are compromised in the long term potentiation aspect of memory generation. Recently, mutations in the gene have been linked with dystonia in human. The protein has no intrinsic enzyme activity but is known to bind to variety of target proteins. Very little information is available on how the protein executes its critical role in signaling pathways, except that it is regulated by binding of calcium. Further delineation of its function requires large amounts of pure protein. In this report, we present a single-step purification procedure that yields high quantities of the bacterially expressed, recombinant protein. The procedure may be adapted to purify the protein from inclusion bodies or cytosol in its myristoylated or non-myristoylated forms. MALDI-MS (in source decay) analyses demonstrates that the myristoylation occurs at the glycine residue. The protein is also biologically active as measured through tryptophan fluorescence, mobility shift and guanylate cyclase activity assays. Thus, further analyses of hippocalcin, both structural and functional, need no longer be limited by protein availability. PMID:27001424

  8. Examination of tapered plastic multimode fiber-based sensor performance with silver coating for different concentrations of calcium hypochlorite by soft computing methodologies--a comparative study.

    PubMed

    Zakaria, Rozalina; Sheng, Ong Yong; Wern, Kam; Shamshirband, Shahaboddin; Wahab, Ainuddin Wahid Abdul; Petković, Dalibor; Saboohi, Hadi

    2014-05-01

    A soft methodology study has been applied on tapered plastic multimode sensors. This study basically used tapered plastic multimode fiber [polymethyl methacrylate (PMMA)] optics as a sensor. The tapered PMMA fiber was fabricated using an etching method involving deionized water and acetone to achieve a waist diameter and length of 0.45 and 10 mm, respectively. In addition, a tapered PMMA probe, which was coated by silver film, was fabricated and demonstrated using a calcium hypochlorite (G70) solution. The working mechanism of such a device is based on the observation increment in the transmission of the sensor that is immersed in solutions at high concentrations. As the concentration was varied from 0 to 6 ppm, the output voltage of the sensor increased linearly. The silver film coating increased the sensitivity of the proposed sensor because of the effective cladding refractive index, which increases with the coating and thus allows more light to be transmitted from the tapered fiber. In this study, the polynomial and radial basis function (RBF) were applied as the kernel function of the support vector regression (SVR) to estimate and predict the output voltage response of the sensors with and without silver film according to experimental tests. Instead of minimizing the observed training error, SVR_poly and SVR_rbf were used in an attempt to minimize the generalization error bound so as to achieve generalized performance. An adaptive neuro-fuzzy interference system (ANFIS) approach was also investigated for comparison. The experimental results showed that improvements in the predictive accuracy and capacity for generalization can be achieved by the SVR_poly approach in comparison to the SVR_rbf methodology. The same testing errors were found for the SVR_poly approach and the ANFIS approach. PMID:24979634

  9. Calcium supplements

    MedlinePlus

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

  10. Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

    SciTech Connect

    J Wingard; J Ladner; M Vanarotti; A Fisher; H Robinson; K Buchanan; D Engman; J Ames

    2011-12-31

    The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically with flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..

  11. Fluorescent gold nanoclusters based photoelectrochemical sensors for detection of H2O2 and glucose.

    PubMed

    Zhang, Jianxiu; Tu, Liping; Zhao, Shuang; Liu, Guohua; Wang, Yangyun; Wang, Yong; Yue, Zhao

    2015-05-15

    In this work, low-toxicity fluorescent gold nanoclusters (AuNCs) based photoelectrochemical sensors were developed for H2O2 and glucose detection. Herein, the processes used to fabricate the sensors and the photoelectrochemical performances of the sensors under different conditions were presented. Based on the energy band levels of the AuNCs and electron tunneling processes, a detailed photoelectrochemical sensing model was given. The designed sensors were then used for H2O2 and glucose detection without any extra modification of the AuNCs or complex enzyme immobilization. The results demonstrate that the AuNCs allow for H2O2 sensing based on their capacity for both fluorescence and catalysis. Indeed, it was observed that H2O2 was catalyzed by the AuNCs and reduced by photoinduced electrons derived from excited AuNCs. Furthermore, an enhancement in photocurrent amplitude followed the increase in the concentrations of H2O2 and glucose. The effects of the types of ligands surrounding the AuNCs and the applied potential on the output photocurrent were well studied to optimize the measurement conditions. The sensitivity and LOD of MUA-AuNCs at -500 mV were 4.33 nA/mM and 35 μM, respectively. All experimental results indicated that AuNCs could not only serve as a promising photoelectrical material for building the photoelectrochemical biosensors but as catalysts for H2O2 sensing. PMID:25190086

  12. Structural basis for a hand-like site in the calcium sensor CatchER with fast kinetics

    PubMed Central

    Zhang, Ying; Reddish, Florence; Tang, Shen; Zhuo, You; Wang, Yuan-Fang; Yang, Jenny J.; Weber, Irene T.

    2013-01-01

    Calcium ions, which are important signaling molecules, can be detected in the endoplasmic reticulum by an engineered mutant of green fluorescent protein (GFP) designated CatchER with a fast off-rate. High resolution (1.78–1.20 Å) crystal structures were analyzed for CatchER in the apo form and in complexes with calcium or gadolinium to probe the binding site for metal ions. While CatchER exhibits a 1:1 binding stoichiometry in solution, two positions were observed for each of the metal ions bound within the hand-like site formed by the carboxylate side chains of the mutated residues S147E, S202D, Q204E, F223E and T225E that may be responsible for its fast kinetic properties. Comparison of the structures of CatchER, wild-type GFP and enhanced GFP confirmed that different conformations of Thr203 and Glu222 are associated with the two forms of Tyr66 of the chromophore which are responsible for the absorbance wavelengths of the different proteins. Calcium binding to CatchER may shift the equilibrium for conformational population of the Glu222 side chain and lead to further changes in its optical properties. PMID:24311573

  13. Calcium - ionized

    MedlinePlus

    ... at both ionized calcium and calcium attached to proteins. You may need to have a separate ionized calcium test if you have factors that increase or decrease total calcium levels. These may include abnormal blood levels ...

  14. Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to short-term synaptic plasticity in hippocampal neurons.

    PubMed

    Nanou, Evanthia; Sullivan, Jane M; Scheuer, Todd; Catterall, William A

    2016-01-26

    Short-term synaptic plasticity is induced by calcium (Ca(2+)) accumulating in presynaptic nerve terminals during repetitive action potentials. Regulation of voltage-gated CaV2.1 Ca(2+) channels by Ca(2+) sensor proteins induces facilitation of Ca(2+) currents and synaptic facilitation in cultured neurons expressing exogenous CaV2.1 channels. However, it is unknown whether this mechanism contributes to facilitation in native synapses. We introduced the IM-AA mutation into the IQ-like motif (IM) of the Ca(2+) sensor binding site. This mutation does not alter voltage dependence or kinetics of CaV2.1 currents, or frequency or amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs); however, synaptic facilitation is completely blocked in excitatory glutamatergic synapses in hippocampal autaptic cultures. In acutely prepared hippocampal slices, frequency and amplitude of mEPSCs and amplitudes of evoked EPSCs are unaltered. In contrast, short-term synaptic facilitation in response to paired stimuli is reduced by ∼ 50%. In the presence of EGTA-AM to prevent global increases in free Ca(2+), the IM-AA mutation completely blocks short-term synaptic facilitation, indicating that synaptic facilitation by brief, local increases in Ca(2+) is dependent upon regulation of CaV2.1 channels by Ca(2+) sensor proteins. In response to trains of action potentials, synaptic facilitation is reduced in IM-AA synapses in initial stimuli, consistent with results of paired-pulse experiments; however, synaptic depression is also delayed, resulting in sustained increases in amplitudes of later EPSCs during trains of 10 stimuli at 10-20 Hz. Evidently, regulation of CaV2.1 channels by CaS proteins is required for normal short-term plasticity and normal encoding of information in native hippocampal synapses. PMID:26755594

  15. Calcium Oscillations

    PubMed Central

    Dupont, Geneviève; Combettes, Laurent; Bird, Gary S.; Putney, James W.

    2011-01-01

    Calcium signaling results from a complex interplay between activation and inactivation of intracellular and extracellular calcium permeable channels. This complexity is obvious from the pattern of calcium signals observed with modest, physiological concentrations of calcium-mobilizing agonists, which typically present as sequential regenerative discharges of stored calcium, a process referred to as calcium oscillations. In this review, we discuss recent advances in understanding the underlying mechanism of calcium oscillations through the power of mathematical modeling. We also summarize recent findings on the role of calcium entry through store-operated channels in sustaining calcium oscillations and in the mechanism by which calcium oscillations couple to downstream effectors. PMID:21421924

  16. Calcium aluminate silicate Ca2Al2SiO7 single crystal applicable to piezoelectric sensors at high temperature

    NASA Astrophysics Data System (ADS)

    Takeda, Hiroaki; Hagiwara, Manabu; Noguchi, Hiroaki; Hoshina, Takuya; Takahashi, Tomoko; Kodama, Nobuhiro; Tsurumi, Takaaki

    2013-06-01

    Ca2Al2SiO7 (CAS) bulk single crystals were grown by the Czochralski method. Material constants of the crystal were determined over the driving temperature range of a typical combustion pressure sensor. The electrical resistivity at 800 °C was found to be of the order of 108 Ωcm. We constructed a measurement system for the direct piezoelectric effect at high temperature, and characterized the crystals in a simulated engine cylinder combustion environment. Output charge signal against applied stress was detected at 700 °C. These observations suggest that CAS crystals are superior candidate materials for high temperature for stress sensing.

  17. A calcium sensor - protein kinase signaling module diversified in plants and is retained in all lineages of Bikonta species.

    PubMed

    Beckmann, Linda; Edel, Kai H; Batistič, Oliver; Kudla, Jörg

    2016-01-01

    Calcium (Ca(2+)) signaling is a universal mechanism of signal transduction and involves Ca(2+) signal formation and decoding of information by Ca(2+) binding proteins. Calcineurin B-like proteins (CBLs), which upon Ca(2+) binding activate CBL-interacting protein kinases (CIPKs) regulate a multitude of physiological processes in plants. Here, we combine phylogenomics and functional analyses to investigate the occurrence and structural conservation of CBL and CIPK proteins in 26 species representing all major clades of eukaryotes. We demonstrate the presence of at least singular CBL-CIPK pairs in representatives of Archaeplastida, Chromalveolates and Excavates and their general absence in Opisthokonta and Amoebozoa. This denotes CBL-CIPK complexes as evolutionary ancient Ca(2+) signaling modules that likely evolved in the ancestor of all Bikonta. Furthermore, we functionally characterize the CBLs and CIPK from the parabasalid human pathogen Trichomonas vaginalis. Our results reveal strict evolutionary conservation of functionally important structural features, preservation of biochemical properties and a remarkable cross-kingdom protein-protein interaction potential between CBLs and CIPKs from Arabidopsis thaliana and T. vaginalis. Together our findings suggest an ancient evolutionary origin of a functional CBL-CIPK signaling module close to the root of eukaryotic evolution and provide insights into the initial evolution of signaling networks and Ca(2+) signaling specificity. PMID:27538881

  18. A calcium sensor – protein kinase signaling module diversified in plants and is retained in all lineages of Bikonta species

    PubMed Central

    Beckmann, Linda; Edel, Kai H.; Batistič, Oliver; Kudla, Jörg

    2016-01-01

    Calcium (Ca2+) signaling is a universal mechanism of signal transduction and involves Ca2+ signal formation and decoding of information by Ca2+ binding proteins. Calcineurin B-like proteins (CBLs), which upon Ca2+ binding activate CBL-interacting protein kinases (CIPKs) regulate a multitude of physiological processes in plants. Here, we combine phylogenomics and functional analyses to investigate the occurrence and structural conservation of CBL and CIPK proteins in 26 species representing all major clades of eukaryotes. We demonstrate the presence of at least singular CBL-CIPK pairs in representatives of Archaeplastida, Chromalveolates and Excavates and their general absence in Opisthokonta and Amoebozoa. This denotes CBL-CIPK complexes as evolutionary ancient Ca2+ signaling modules that likely evolved in the ancestor of all Bikonta. Furthermore, we functionally characterize the CBLs and CIPK from the parabasalid human pathogen Trichomonas vaginalis. Our results reveal strict evolutionary conservation of functionally important structural features, preservation of biochemical properties and a remarkable cross-kingdom protein-protein interaction potential between CBLs and CIPKs from Arabidopsis thaliana and T. vaginalis. Together our findings suggest an ancient evolutionary origin of a functional CBL-CIPK signaling module close to the root of eukaryotic evolution and provide insights into the initial evolution of signaling networks and Ca2+ signaling specificity. PMID:27538881

  19. Calcium - urine

    MedlinePlus

    ... best treatment for the most common type of kidney stone , which is made of calcium. This type of ... the kidneys into the urine, which causes calcium kidney stones Sarcoidosis Taking too much calcium Too much production ...

  20. Calcium Carbonate

    MedlinePlus

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

  1. The National Comorbidity Survey Adolescent Supplement (NCS-A): I. Background and Measures

    PubMed Central

    Merikangas, Kathleen R.; Avenevoli, Shelli; Costello, E. Jane; Koretz, Doreen; Kessler, Ronald C.

    2009-01-01

    Objective This paper presents an overview of the background and measures used in the National Comorbidity Survey Replication Adolescent Supplement (NCS-A). Methods The NCS-A is a national psychiatric epidemiological survey of adolescents ages 13–17. Results The NCS-A was designed to provide the first nationally representative estimates of the prevalence, correlates and patterns of service use for DSM-V mental disorders among US adolescents and to lay the groundwork for follow-up studies of risk-protective factors, consequences, and early expressions of adult mental disorders. The core NCS-A diagnostic interview, the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), is a fully-structured research diagnostic interview designed for use by trained lay interviewers. A multi-construct, multi-method, multi-informant battery was also included to assess risk and protective factors and barriers to service use. Design limitations due to the NCS-A evolving as a supplement to an ongoing survey of mental disorders of US adults include restricted age range of youth, cross-sectional assessment, and lack of full parental/surrogate informant reports on youth mental disorders and correlates. Conclusions Despite these limitations, the NCS-A contains unparalleled information that can be used to generate national estimates of prevalence and correlates of adolescent mental disorders, risk and protective factors, patterns of service use, and barriers to receiving treatment for these disorders. The retrospective NCS-A data on the development of psychopathology can additionally complement data from longitudinal studies based on more geographically restricted samples and serve as a useful baseline for future prospective studies of the onset and progression of mental disorders in adulthood. PMID:19242382

  2. Electrochemical sensors using gold submicron particles modified electrodes based on calcium complexes formed with alizarin red S for determination of Ca(2+) in isolated rat heart mitochondria.

    PubMed

    Yang, Jin-Xiang; He, Yan-Bin; Lai, Li-Na; Li, Jun-Bo; Song, Xiao-Liang

    2015-04-15

    A simple glassy carbon electrode (GCE) modified with gold submicron particles (AuSPs), characterized by a mean diameter of about0.15-0.20μm has been developed. Herein, the complexation reaction of Ca(2+) with alizarin red S (ARS), in 0.1M KOH, has been followed by electrochemical methods using the modified electrode which is able to catalyze the electro-reduction of ARS. When the stoichiometry ratio of Ca(2+) and ARS is 1:2, a new reduction peak at a higher negative potential of -0.975V appeared, and the peak of ARS at -0.815V disappeared. The peak current of ARS in alkaline solution is proportional to the concentration of Ca(2+) in the range 6.0×10(-7)-1.2×10(-4)M with a limit of detection (LOD) of 5.1×10(-7)M. Furthermore, the complex site of Ca(2+) with ARS was analysized by the experimental UV-vis and infrared spectrums and those calculated electronic and vibrational spectroscopies with density functional theory (DFT). The good accordance between theoretical and experimental data confirms that chelation of calcium ion preferentially occurs at the deprotonated catechol site. Then, we implemented an electrochemical assay for the investigation of Ca(2+) in preparations of isolated rat heart mitochondria, which demonstrates the submicron particles modified electrode is a simple and rapid sensor for determining the Ca(2+) in the biological samples. PMID:25497981

  3. Preparation and characterization of bioactive calcium silicate and poly(epsilon-caprolactone) nanocomposite for bone tissue regeneration.

    PubMed

    Wei, Jie; Heo, S J; Liu, Changsheng; Kim, D H; Kim, S E; Hyun, Y T; Shin, Ji-Wang; Shin, Jung-Woog

    2009-09-01

    A novel biocomposite of nanosized calcium silicate (n-CS) and poly(epsilon-caprolactone) (PCL) was successfully fabricated directly using n-CS slurry, not dried n-CS powder, in a solvent-casting method. The in vitro bioactivity of the composite was evaluated by investigating the apatite-forming ability in simulated body fluid. A proliferation assay with mouse L929 fibroblasts was used to test the in vitro biocompatibility. The composition, hydrophilicity, and mechanical properties were also evaluated. Results suggest that the incorporation of n-CS could significantly improve the hydrophilicity, compressive strength, and elastic modulus of n-CS/PCL composites, with the enhancements mainly dependent on n-CS content. The n-CS/PCL composites exhibit excellent in vitro bioactivity, with surface apatite formation for 40% (w/w) n-CS (C40) exceeding that of 20% (w/w) n-CS (C20) at 7 and 14 days. The Ca/P ratios of apatite formed on C20 and C40 surfaces were 1.58 and 1.61, respectively, indicating nonstoichiometric apatite with defective structure. Composites demonstrated significantly better cell attachment and proliferation than that of PCL alone, with C40 demonstrating the best bioactivity. The apatite layers that formed on the composite surfaces facilitated cell attachment (4 h) and proliferation during the early stages (1 and 4 days). Collectively, these results suggest that the incorporation of n-CS produces biocomposites with enhanced bioactivity and biocompatibility. PMID:18563819

  4. Fast doping of Cu into ZnSe NCs by hydrazine promoted cation exchange in aqueous solution at room temperature.

    PubMed

    Shao, Haibao; Wang, Chunlei; Xu, Shuhong; Wang, Zhuyuan; Yin, Haihong; Cui, Yiping

    2015-03-01

    Controllable doping is an effective way of tuning the properties of semiconductor nanocrystals (NCs). In this work, a simple strategy of fast doping Cu ions into ZnSe NCs under ambient conditions was proposed. The principle of doping is based on hydrazine (N2H4) promoted cation exchange reaction. By direct addition of Cu ion stock solution into the preformed ZnSe NCs, Cu doped ZnSe NCs can be obtained. Furthermore, the emission of doped NCs can be tuned by changing the amount of impurity ion addition. The cation exchange reaction is facilitated by three factors: 1) N2H4 addition, 2) fast impurity ions, and 3) partial stabilizer removal. The proposed cation exchange reaction in aqueous solution could be an alternate route for NC doping as well as synthesis of ionic NCs. PMID:25605441

  5. Chloroplast Structure and Function Is Altered in the NCS2 Maize Mitochondrial Mutant 1

    PubMed Central

    Roussell, Deborah L.; Thompson, Deborah L.; Pallardy, Steve G.; Miles, Donald; Newton, Kathleen J.

    1991-01-01

    The nonchromosomal stripe 2 (NCS2) mutant of maize (Zea mays L.) has a DNA rearrangement in the mitochondrial genome that segregates with the abnormal growth phenotype. Yet, the NCS2 characteristic phenotype includes striped sectors of pale-green tissue on the leaves. This suggests a chloroplast abnormality. To characterize the chloroplasts present in the mutant sectors, we examined the chloroplast structure by electron microscopy, chloroplast function by radiolabeled carbon dioxide fixation and fluorescence induction kinetics, and thylakoid protein composition by polyacrylamide gel electrophoresis. The data from these analyses suggest abnormal or prematurely arrested chloroplast development. Deleterious effects of the NCS2 mutant mitochondria upon the cells of the leaf include structural and functional alterations in the both the bundle sheath and mesophyll chloroplasts. ImagesFigure 1Figure 2Figure 3Figure 5Figure 6 PMID:16668157

  6. NICMOS Small ΔT Dewar / NCS PID Model for Orbit Night Power Reduction

    NASA Astrophysics Data System (ADS)

    Wheeler, T.; Robinson, M.

    2005-10-01

    Without SM4 and the installation of new Ni-HB2B batteries, HST is facing a future with decreasing battery capacity. This ISR explores one option for reducing HST’s battery load during orbit night while maintaining the science capability of the NICMOS. Modulating the NCS setpoint temperature, i.e., increasing it during orbit night and decreasing it during orbit day, can accomplish this. A linear NICMOS small ΔT thermal model was developed based on flight data serendipitously obtained during Proposal 10097, NICMOS Temperature Setpoint Darks, to predict camera one’s temperature, NCS compressor speed, and total NCS power for modulations of +/-1, +/-2, and +/-3K. The results are presented.

  7. Toxicity of 33NCS (3'-chloro-3-nitrosalicylanilide) to freshwater fish and sea lampreys

    USGS Publications Warehouse

    Marking, Leif L.; King, Everett L.; Walker, Charles R.; Howell, John H.

    1970-01-01

    The chemical 33NCS (3'-chloro-3-nitrosalicylanilide) was evaluated as a fish control agent and as a larvicide for sea lampreys at the Fish Control Laboratories of the Bureau of Sport Fisheries and Wildlife and the Hammond Bay Biological Station of the Bureau of Commercial Fisheries. The chemical is rapidly toxic to many species. Sea lampreys, bowfin, and channel catfish are the most sensitive species. Carp are more sensitive than trouts or sunfishes. Use of 33NCS in selective control of freshwater fishes or sea lampreys requires precise control because its toxicity is strongly influenced by variations in water quality.

  8. Atomic Resolution of Calcium and Oxygen Sublattices of Calcite in Ambient Conditions by Atomic Force Microscopy Using qPlus Sensors with Sapphire Tips.

    PubMed

    Wastl, Daniel S; Judmann, Michael; Weymouth, Alfred J; Giessibl, Franz J

    2015-01-01

    Characterization and imaging at the atomic scale with atomic force microscopy in biocompatible environments is an ongoing challenge. We demonstrate atomically resolved imaging of the calcite (101̅4) surface plane using stiff quartz cantilevers ("qPlus sensors", stiffness k = 1280 N/m) equipped with sapphire tips in ambient conditions without any surface preparation. With 10 atoms in one surface unit cell, calcite has a highly complex surface structure comprising three different chemical elements (Ca, C, and O). We obtain true atomic resolution of calcite in air at relative humidity ranging from 20% to 40%, imaging atomic steps and single atomic defects. We observe a great durability of sapphire tips with their Mohs hardness of 9, only one step below diamond. Depending on the state of the sapphire tip, we resolve either the calcium or the oxygen sublattice. We determine the tip termination by comparing the experimental images with simulations and discuss the possibility of chemical tip identification in air. The main challenges for imaging arise from the presence of water layers, which form on almost all surfaces and have the potential to dissolve the crystal surface. Frequency shift versus distance spectra show the presence of at least three ordered hydration layers. The measured height of the first hydration layer corresponds well to X-ray diffraction data and molecular dynamic simulations, namely, ∼220 pm. For the following hydration layers we measure ∼380 pm for the second and third layer, ending up in a total hydration layer thickness of at least 1 nm. Understanding the influence of water layers and their structure is important for surface segregation, surface reactions including reconstructions, healing of defects, and corrosion. PMID:25816927

  9. In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore.

    PubMed

    Hang, Vu Thi Thu; Oh, Tae Jin; Yamaguchi, Tokutaro; Sohng, Jae Kyung

    2010-10-01

    Neocarzinostatin (NCS) is an enediyne antibiotic produced by Streptomyces carzinostaticus. The NCS chromophore consists of an enediyne core, a sugar moiety, and a naphthoic acid (NA) moiety. The latter plays a key role in binding the NCS chromophore to its apoprotein to protect and stabilize the bioactive NCS chromophore. In this study, we expressed three genes: ncsB (naphthoic acid synthase), ncsB3 (P450 hydroxylase), and ncsB1 (O-methyltransferase), in Streptomyces lividans TK24. The three genes were sufficient to produce 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid. Production was analyzed and confirmed by LC-MS and nuclear magnetic resonance. Here, we report the functional characterization of ncsB3 and thereby elucidate the complete biosynthetic pathway of NA moiety of the NCS chromophore. PMID:20735485

  10. Calcium-binding proteins and development

    NASA Technical Reports Server (NTRS)

    Beckingham, K.; Lu, A. Q.; Andruss, B. F.; McIntire, L. V. (Principal Investigator)

    1998-01-01

    The known roles for calcium-binding proteins in developmental signaling pathways are reviewed. Current information on the calcium-binding characteristics of three classes of cell-surface developmental signaling proteins (EGF-domain proteins, cadherins and integrins) is presented together with an overview of the intracellular pathways downstream of these surface receptors. The developmental roles delineated to date for the universal intracellular calcium sensor, calmodulin, and its targets, and for calcium-binding regulators of the cytoskeleton are also reviewed.

  11. Identity of the Perchlorate Parent Salt(s) at the Phoenix Mars Landing Site Based on Reanalysis of the Calcium Sensor Response

    NASA Astrophysics Data System (ADS)

    Kounaves, S. P.; Folds, K. E.; Hansen, V. M.; Weber, A. W.; Carrier, B. L.; Chaniotakis, N. A.

    2012-12-01

    In 2008 the first comprehensive wet chemical analyses of the martian soil were performed by the Wet Chemistry Laboratory (WCL) on board the Phoenix Mars lander [1-4]. In addition to being dominated by Ca2+ and Mg2+ carbonates, SO4=, and other minor soluble species, the soil contained about 0.6 %wt perchlorate (ClO4-). Its discovery on Mars has broad implications for that planet's water cycle, astrobiology, human habitability, and possible formation of liquid brines. One remaining important question raised by the WCL discovery of ClO4- on Mars is the identity of the parent perchlorate salt. New refined analysis of the Phoenix WCL sensor data and laboratory analyses and equilibrium modeling, indicate that the identity and ratios of the ClO4- parent salts are different than initially proposed. The analyses performed by the Phoenix WCL, along with previous mission results [5], indicated that K+, Na+, Mg2+, Ca2+, or Fe2/3+, either singly or as a mixture, were possible candidate counter cations that could be associated with the amount of ClO4- present in solution. If we assumed 100% association of the ClO4- in the soil, then Ca2+ or Mg2+ could account for 100% in each case, since there is in effect a more than sufficient supply of these two counter cations. For other cations, measured concentrations limit the ClO4- salt potentially present, with Na+ accounting for < 30%, K+ < 5%, and Fe2/3+ < 3%. Clearly, Mg(ClO4)2 or Ca(ClO4)2 could constitute as much as 100% of the perchlorate salt present in the soil, either alone or in combination. To definitively identify the parent salt of the ClO4- detected by WCL, we have; (1) reexamined the original Phoenix WCL data in terms of the perchlorate and calcium sensor response; (2) performed a set of laboratory analyses using a WCL testbed to better understand the behavior of the sensor responses on Mars; and (3) have modeled possible chemical equilibrium and the effect of the perchlorate parent salt on other minerals present. The new

  12. Syntheses, structures and properties of homo- and heterobimetallic complexes of the type [Zn(tren)NCS] 2[M(NCS) 4] [tren = tris(2-aminoethyl)amine; M = Zn, Cu

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Soumi; Bhar, Kishalay; Das, Sumitra; Chantrapromma, Suchada; Fun, Hoong-Kun; Ghosh, Barindra Kumar

    2010-04-01

    A 2:2:1:6 molar ratio of Zn(ClO 4) 2·6H 2O, tris(2-aminoethyl)amine (tren), Zn(ClO 4) 2·6H 2O/Cu(ClO 4) 2·6H 2O and NH 4NCS in methanol-water solution mixtures affords homo-/heterobimetallic compounds of the type [Zn(tren)NCS] 2[M(NCS) 4] (M = Zn, 1; M = Cu, 2) which have been characterized using microanalytical, spectroscopic, magnetic and other physicochemical results. The structures of the compounds are determined by X-ray diffraction measurements. Structural analyses reveal that 1 and 2 are isomorphous and consist of two discrete [Zn(tren)NCS] + cations and a [M(NCS) 4] 2- (M = Zn/Cu) anion. Zinc(II) centers in the [Zn(tren)NCS] + units adopt distorted trigonal bipyramidal geometry with ZnN 5 chromophores coordinated through four N atoms of tren and one N atom of terminal thiocyanate. Each metal(II) center in [M(NCS) 4] 2- has a distorted tetrahedral coordination environment with an MN 4 chromophore ligated by four N atoms of the terminal thiocyanates. In solid state, doubly N-H…S hydrogen bonded 1D chains of [Zn(tren)NCS] + cations are interconnected by tetrahedral [Zn(NCS) 4] 2-/[Cu(NCS) 4] 2- anions through cooperative N-H…S and N-H…N (in 1) and N-H…S and C-H…S (in 2) hydrogen bonds resulting in 3D network structures. Establishment of such networks seems to be aiding the crystallization.

  13. Calcium - urine

    MedlinePlus

    ... into the urine, which causes calcium kidney stones Sarcoidosis Taking too much calcium Too much production of ... Milk-alkali syndrome Proximal renal tubular acidosis Rickets Sarcoidosis Vitamin D Update Date 5/3/2015 Updated ...

  14. Calcium supplements

    MedlinePlus

    ... SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the human body. It helps build and protect your teeth ... absorb calcium. You can get vitamin D from sunlight exposure to your skin and from your diet. Ask your provider whether ...

  15. Heterogeneous Nature of Relaxation Dynamics of Room-Temperature Ionic Liquids (EMIm)2[Co(NCS)4] and (BMIm)2[Co(NCS)4

    DOE PAGESBeta

    Hensel-Bielowka, Stella; Wojnarowska, Zaneta; Dzida, Marzena; Zorębski, Edward; Zorębski, Michał; Geppert-Rybczyńska, Monika; Peppel, Tim; Grzybowska, Katarzyna; Wang, Yangyang; Sokolov, Alexei P.; et al

    2015-08-11

    Dynamic crossover above Tg has been recognized as a characteristic feature of molecular dynamics of liquids approaching glass transition. Experimentally, it is manifested as a change in Vogel–Fulcher–Tammann dependence or a breakdown of the Stokes–Einstein and related relations. In this study, we report the exception from this rather general pattern of behavior. By means of dielectric, ultrasonic, rheological, and calorimetric methods, dynamics of two good ionic conductors (BMIm)2[Co(NCS)4] and (EMIm)2[Co(NCS)4] of less common stoichiometry (2:1) was studied in a very broad temperature range. However, none of the mentioned dynamic changes was observed in the entire studied temperature range. On themore » contrary, the single VFT and the same fractional Walden coefficient were found for conductivity and viscosity changes over 12 decades. Finally and moreover, ultrasonic studies revealed that the data at temperatures which cover the normal liquid region cannot be fitted by a single exponential decay, and the Cole–Cole function should be used instead.« less

  16. Improvement in γ-hydroxybutyrate-induced contextual fear memory deficit by systemic administration of NCS-382.

    PubMed

    Ishiwari, Keita; Sircar, Ratna

    2016-06-15

    Low, nonsedative doses of γ-hydroxybutyric acid (GHB) produce short-term anterograde amnesia in humans and memory impairments in experimental animals. We have previously shown that acute systemic treatment of GHB in adolescent female rats impairs the acquisition, but not the expression, of contextual fear memory while sparing both the acquisition and the expression of auditory cued fear memory. In the brain, GHB binds to specific GHB-binding sites as well as to γ-aminobutyric acid type B (GABAB) receptors. Although many of the behavioral effects of GHB at high doses have been attributed to its effects on the GABAB receptor, it is unclear which receptor mediates its relatively low-dose memory-impairing effects. The present study examined the ability of the putative GHB receptor antagonist NCS-382 to block the disrupting effects of GHB on fear memory in adolescent rat. Groups of rats received either a single dose of NCS-382 (3-10 mg/kg, intraperitoneally) or vehicle, followed by an injection of either GHB (100 mg/kg, intraperitoneally) or saline. All rats were trained in the fear paradigm, and tested for contextual fear memory and auditory cued fear memory. NCS-382 dose-dependently reversed deficits in the acquisition of contextual fear memory induced by GHB in adolescent rats, with 5 mg/kg of NCS-382 maximally increasing freezing to the context compared with the group administered GHB alone. When animals were tested for cued fear memory, treatment groups did not differ in freezing responses to the tone. These results suggest that low-dose amnesic effects of GHB are mediated by GHB receptors. PMID:27105320

  17. Improvement in γ-hydroxybutyrate-induced contextual fear memory deficit by systemic administration of NCS-382

    PubMed Central

    Ishiwari, Keita

    2016-01-01

    Low, nonsedative doses of γ-hydroxybutyric acid (GHB) produce short-term anterograde amnesia in humans and memory impairments in experimental animals. We have previously shown that acute systemic treatment of GHB in adolescent female rats impairs the acquisition, but not the expression, of contextual fear memory while sparing both the acquisition and the expression of auditory cued fear memory. In the brain, GHB binds to specific GHB-binding sites as well as to γ-aminobutyric acid type B (GABAB) receptors. Although many of the behavioral effects of GHB at high doses have been attributed to its effects on the GABAB receptor, it is unclear which receptor mediates its relatively low-dose memory-impairing effects. The present study examined the ability of the putative GHB receptor antagonist NCS-382 to block the disrupting effects of GHB on fear memory in adolescent rat. Groups of rats received either a single dose of NCS-382 (3–10 mg/kg, intraperitoneally) or vehicle, followed by an injection of either GHB (100 mg/kg, intraperitoneally) or saline. All rats were trained in the fear paradigm, and tested for contextual fear memory and auditory cued fear memory. NCS-382 dose-dependently reversed deficits in the acquisition of contextual fear memory induced by GHB in adolescent rats, with 5 mg/kg of NCS-382 maximally increasing freezing to the context compared with the group administered GHB alone. When animals were tested for cued fear memory, treatment groups did not differ in freezing responses to the tone. These results suggest that low-dose amnesic effects of GHB are mediated by GHB receptors. PMID:27105320

  18. The National Children’s Study (NCS) Establishment and Protection of the Inferential Base

    PubMed Central

    Ellenberg, Jonas H.

    2014-01-01

    SUMMARY The National Children’s Study is a unique study of environment and health that will follow a cohort of 100,000 women from prior to or early in pregnancy and then their children until 21 years of age. The NCS cohort will be a national multi-stage probability sample, using a U.S. Census Bureau geographic sampling frame unrelated to factors that might influence selection into the sample (e.g. access to health care). I present the case for the use of a national probability sample as the design base for the NCS, arguing that selection of the original cohort should be as free from selection bias as possible. The dangers of using a selected or non probability sample approach are demonstrated by an example of its use in outlining the clinical management of children with febrile seizures, an infrequent disorder, which was so wrong for decades. In addition I stress the importance of and the NCS approach to avoiding selection bias that might occur after the initial selection of the cohort. Selection of and maintenance of an unselected cohort is an important element for the validity of inferences in this major undertaking. PMID:20527009

  19. A Calcium-Relay Mechanism in Vertebrate Phototransduction

    PubMed Central

    2013-01-01

    Calcium-signaling in cells requires a fine-tuned system of calcium-transport proteins involving ion channels, exchangers, and ion-pumps but also calcium-sensor proteins and their targets. Thus, control of physiological responses very often depends on incremental changes of the cytoplasmic calcium concentration, which are sensed by calcium-binding proteins and are further transmitted to specific target proteins. This Review will focus on calcium-signaling in vertebrate photoreceptor cells, where recent physiological and biochemical data indicate that a subset of neuronal calcium sensor proteins named guanylate cyclase-activating proteins (GCAPs) operate in a calcium-relay system, namely, to make gradual responses to small changes in calcium. We will further integrate this mechanism in an existing computational model of phototransduction showing that it is consistent and compatible with the dynamics that are characteristic for the precise operation of the phototransduction pathways. PMID:23472635

  20. Calcium antagonists.

    PubMed

    Grossman, Ehud; Messerli, Franz H

    2004-01-01

    Calcium antagonists were introduced for the treatment of hypertension in the 1980s. Their use was subsequently expanded to additional disorders, such as angina pectoris, paroxysmal supraventricular tachycardias, hypertrophic cardiomyopathy, Raynaud phenomenon, pulmonary hypertension, diffuse esophageal spasms, and migraine. Calcium antagonists as a group are heterogeneous and include 3 main classes--phenylalkylamines, benzothiazepines, and dihydropyridines--that differ in their molecular structure, sites and modes of action, and effects on various other cardiovascular functions. Calcium antagonists lower blood pressure mainly through vasodilation and reduction of peripheral resistance. They maintain blood flow to vital organs, and are safe in patients with renal impairment. Unlike diuretics and beta-blockers, calcium antagonists do not impair glucose metabolism or lipid profile and may even attenuate the development of arteriosclerotic lesions. In long-term follow-up, patients treated with calcium antagonists had development of less overt diabetes mellitus than those who were treated with diuretics and beta-blockers. Moreover, calcium antagonists are able to reduce left ventricular mass and are effective in improving anginal pain. Recent prospective randomized studies attested to the beneficial effects of calcium antagonists in hypertensive patients. In comparison with placebo, calcium antagonist-based therapy reduced major cardiovascular events and cardiovascular death significantly in elderly hypertensive patients and in diabetic patients. In several comparative studies in hypertensive patients, treatment with calcium antagonists was equally effective as treatment with diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors. From these studies, it seems that a calcium antagonist-based regimen is superior to other regimens in preventing stroke, equivalent in preventing ischemic heart disease, and inferior in preventing congestive heart failure

  1. Oral administration of iron-saturated bovine lactoferrin–loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

    PubMed Central

    Mahidhara, Ganesh; Kanwar, Rupinder K; Roy, Kislay; Kanwar, Jagat R

    2015-01-01

    We determined the anticancer efficacy and internalization mechanism of our polymeric–ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts. PMID:26124661

  2. Calcium in diet

    MedlinePlus

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

  3. Calcium - ionized

    MedlinePlus

    ... levels. These may include abnormal blood levels of albumin or immunoglobulins. Normal Results Children: 4.8 to ... 2016:chap 245. Read More Acute kidney failure Albumin - blood (serum) test Bone tumor Calcium blood test ...

  4. Calcium Test

    MedlinePlus

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

  5. Calcium Calculator

    MedlinePlus

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

  6. Phosphorylation of Calcineurin B-like (CBL) Calcium Sensor Proteins by Their CBL-interacting Protein Kinases (CIPKs) Is Required for Full Activity of CBL-CIPK Complexes toward Their Target Proteins*

    PubMed Central

    Hashimoto, Kenji; Eckert, Christian; Anschütz, Uta; Scholz, Martin; Held, Katrin; Waadt, Rainer; Reyer, Antonella; Hippler, Michael; Becker, Dirk; Kudla, Jörg

    2012-01-01

    Calcineurin B-like proteins (CBLs) represent a family of calcium sensor proteins that interact with a group of serine/threonine kinases designated as CBL-interacting protein kinases (CIPKs). CBL-CIPK complexes are crucially involved in relaying plant responses to many environmental signals and in regulating ion fluxes. However, the biochemical characterization of CBL-CIPK complexes has so far been hampered by low activities of recombinant CIPKs. Here, we report on an efficient wheat germ extract-based in vitro transcription/translation protocol that yields active full-length wild-type CIPK proteins. We identified a conserved serine residue within the C terminus of CBLs as being phosphorylated by their interacting CIPKs. Remarkably, our studies revealed that CIPK-dependent CBL phosphorylation is strictly dependent on CBL-CIPK interaction via the CIPK NAF domain. The phosphorylation status of CBLs does not appear to influence the stability, localization, or CIPK interaction of these calcium sensor proteins in general. However, proper phosphorylation of CBL1 is absolutely required for the in vivo activation of the AKT1 K+ channel by CBL1-CIPK23 and CBL9-CIPK23 complexes in oocytes. Moreover, we show that by combining CBL1, CIPK23, and AKT1, we can faithfully reconstitute CBL-dependent enhancement of phosphorylation of target proteins by CIPKs in vitro. In addition, we report that phosphorylation of CBL1 by CIPK23 is also required for the CBL1-dependent enhancement of CIPK23 activity toward its substrate. Together, these data identify a novel general regulatory mechanism of CBL-CIPK complexes in that CBL phosphorylation at their flexible C terminus likely provokes conformational changes that enhance specificity and activity of CBL-CIPK complexes toward their target proteins. PMID:22253446

  7. Calcium Carbonate.

    PubMed

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

    2016-01-01

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

  8. Calcium orthophosphates

    PubMed Central

    Dorozhkin, Sergey V.

    2011-01-01

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

  9. Calcium Hydroxylapatite

    PubMed Central

    Yutskovskaya, Yana Alexandrovna; Philip Werschler, WM.

    2015-01-01

    Background: Calcium hydroxylapatite is one of the most well-studied dermal fillers worldwide and has been extensively used for the correction of moderate-to-severe facial lines and folds and to replenish lost volume. Objectives: To mark the milestone of 10 years of use in the aesthetic field, this review will consider the evolution of calcium hydroxylapatite in aesthetic medicine, provide a detailed injection protocol for a global facial approach, and examine how the unique properties of calcium hydroxylapatite provide it with an important place in today’s market. Methods: This article is an up-to-date review of calcium hydroxylapatite in aesthetic medicine along with procedures for its use, including a detailed injection protocol for a global facial approach by three expert injectors. Conclusion: Calcium hydroxylapatite is a very effective agent for many areas of facial soft tissue augmentation and is associated with a high and well-established safety profile. Calcium hydroxylapatite combines high elasticity and viscosity with an ability to induce long-term collagen formation making it an ideal agent for a global facial approach. PMID:25610523

  10. Modelling the protocol stack in NCS with deterministic and stochastic petri net

    NASA Astrophysics Data System (ADS)

    Hui, Chen; Chunjie, Zhou; Weifeng, Zhu

    2011-06-01

    Protocol stack is the basis of the networked control systems (NCS). Full or partial reconfiguration of protocol stack offers both optimised communication service and system performance. Nowadays, field testing is unrealistic to determine the performance of reconfigurable protocol stack; and the Petri net formal description technique offers the best combination of intuitive representation, tool support and analytical capabilities. Traditionally, separation between the different layers of the OSI model has been a common practice. Nevertheless, such a layered modelling analysis framework of protocol stack leads to the lack of global optimisation for protocol reconfiguration. In this article, we proposed a general modelling analysis framework for NCS based on the cross-layer concept, which is to establish an efficiency system scheduling model through abstracting the time constraint, the task interrelation, the processor and the bus sub-models from upper and lower layers (application, data link and physical layer). Cross-layer design can help to overcome the inadequacy of global optimisation based on information sharing between protocol layers. To illustrate the framework, we take controller area network (CAN) as a case study. The simulation results of deterministic and stochastic Petri-net (DSPN) model can help us adjust the message scheduling scheme and obtain better system performance.

  11. Visinin-like proteins (VSNLs): interaction partners and emerging functions in signal transduction of a subfamily of neuronal Ca2+-sensor proteins

    PubMed Central

    Braunewell, Karl-Heinz; Klein-Szanto, Andres J.

    2009-01-01

    The visinin-like protein (VSNL) subfamily, including the founder protein VILIP-1, VILIP-2, VILIP-3, hippocalcin and neurocalcin δ, constitute a highly homologous subfamily of neuronal calcium sensor (NCS) proteins. Comparative studies have shown that VSNLs are expressed predominantly in the brain with restricted expression patterns in different subsets of neurons, but are also found in peripheral organs. In addition, the proteins display differences in their calcium affinities, their membrane binding kinetics and in the intracellular targets to which they associate after calcium binding. Even though the proteins use a similar calcium-myristoyl switch mechanism to translocate to cellular membranes, they show calcium-dependent localization to different subcellular compartments when expressed in the same neuron. These distinct calcium-myristoyl switch properties might be explained by specificity for defined phospholipids and membrane-bound targets, which enable VSNLs to modulate various cellular signal transduction pathways, including cyclic nucleotide and MAPK signaling. An emerging theme is the direct or indirect effect of VSNLs on gene expression and the interaction with components of membrane trafficking complexes which may determine a role in membrane trafficking of different receptors and ion channels, such as glutamate receptors of the kainate and AMPA subtype, nicotinic ACh receptors and Ca2+-channels. One hypothesis is that the highly homologous VSNLs have evolved to fulfill specialized functions in membrane trafficking and thereby affect neuronal signaling and differentiation in defined subsets of neurons. VSNLs are involved in differentiation processes showing a tumor invasion suppressor function in peripheral organs. Finally, VSNLs play neuroprotective and neurotoxic roles and have been implicated in neurodegenerative diseases. PMID:18989702

  12. Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.

    PubMed

    Luo, Yinggang; Lin, Shuangjun; Zhang, Jian; Cooke, Heather A; Bruner, Steven D; Shen, Ben

    2008-05-23

    Neocarzinostatin, a clinical anticancer drug, is the archetypal member of the chromoprotein family of enediyne antitumor antibiotics that are composed of a nonprotein chromophore and an apoprotein. The neocarzinostatin chromophore consists of a nine-membered enediyne core, a deoxyaminosugar, and a naphthoic acid moiety. We have previously cloned and sequenced the neocarzinostatin biosynthetic gene cluster and proposed that the biosynthesis of the naphthoic acid moiety and its incorporation into the neocarzinostatin chromophore are catalyzed by five enzymes NcsB, NcsB1, NcsB2, NcsB3, and NcsB4. Here we report the biochemical characterization of NcsB1, unveiling that: (i) NcsB1 is an S-adenosyl-L-methionine-dependent O-methyltransferase; (ii) NcsB1 catalyzes regiospecific methylation at the 7-hydroxy group of its native substrate, 2,7-dihydroxy-5-methyl-1-naphthoic acid; (iii) NcsB1 also recognizes other dihydroxynaphthoic acids as substrates and catalyzes regiospecific O-methylation; and (iv) the carboxylate and its ortho-hydroxy groups of the substrate appear to be crucial for NcsB1 substrate recognition and binding, and O-methylation takes place only at the free hydroxy group of these dihydroxynaphthoic acids. These findings establish that NcsB1 catalyzes the third step in the biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore and further support the early proposal for the biosynthesis of the naphthoic acid and its incorporation into the neocarzinostatin chromophore with free naphthoic acids serving as intermediates. NcsB1 represents another opportunity that can now be exploited to produce novel neocarzinostatin analogs by engineering neocarzinostatin biosynthesis or applying directed biosynthesis strategies. PMID:18387946

  13. New, high-capacity, calcium-based sorbents: Calcium silicate sorbents. Final report

    SciTech Connect

    Kenney, M.E.; Chiang, Ray-Kuang

    1993-09-30

    A search is being carried out for new calcium-based SO{sub 2} sorbents for induct injection. More specifically, a search is being carried out for induct injection calcium silicate sorbents that are highly cost effective. The objectives of the past year were to study the sorption of SO{sub 2} by representative calcium silicates, to study the composition of the Ca(OH){sub 2}-fly ash sorbent, and to install a humidity sensor in the sorption system.

  14. [Mitochondria, calcium homeostasis and calcium signaling].

    PubMed

    Zavodnik, I B

    2016-03-01

    Са2+ is a very important and versatile intracellular signal which controls numerous biochemical and physiological (pathophysiological) processes in the cell. Good evidence exists that mitochondria are sensors, decoders and regulators of calcium signaling. Precise regulation of calcium signaling in the cell involves numerous molecular targets, which induce and decode changes of Са2+ concentrations in the cell (pumps, channels, Са2+-binding proteins, Са2+-dependent enzymes, localized in the cytoplasm and organelles). Mitochondrial Са2+ uniporter accumulates excess of Са2+ in mitochondria, while Na+/Са2+- and H+/Са2+-antiporters extrude Са2+ in the cytoplasm. Mitochondrial Са2+ overloading results in formation of mitochondria permeability transition pores which play an important role in cell death under many pathological conditions. Mitochondria regulate Са2+ homeostasis and control important cellular functions such as metabolism, proliferation, survival. Identification of cellular and mitochondrial Ca2+ transporters and understanding their functional mechanisms open up new prospects for their using as therapeutic targets. PMID:27420625

  15. Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER

    SciTech Connect

    Smart, Oliver S. Womack, Thomas O.; Flensburg, Claus; Keller, Peter; Paciorek, Włodek; Sharff, Andrew; Vonrhein, Clemens; Bricogne, Gérard

    2012-04-01

    Local structural similarity restraints (LSSR) provide a novel method for exploiting NCS or structural similarity to an external target structure. Two examples are given where BUSTER re-refinement of PDB entries with LSSR produces marked improvements, enabling further structural features to be modelled. Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct ‘target’ structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and @@target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -target enables the correct ligand-binding structure to be found, and http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.

  16. Calcium and bones

    MedlinePlus

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  17. Get Enough Calcium

    MedlinePlus

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

  18. Calcium carbonate overdose

    MedlinePlus

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

  19. Calcium cyanide

    Integrated Risk Information System (IRIS)

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

  20. Effect of salts, solvents and buffer on miRNA detection using DNA silver nanocluster (DNA/AgNCs) probes

    NASA Astrophysics Data System (ADS)

    Shah, Pratik; Cho, Seok Keun; Waaben Thulstrup, Peter; Bhang, Yong-Joo; Ahn, Jong Cheol; Choi, Suk Won; Rørvig-Lund, Andreas; Yang, Seong Wook

    2014-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs (size ˜21 nt to ˜25 nt) which regulate a variety of important cellular events in plants, animals and single cell eukaryotes. Especially because of their use in diagnostics of human diseases, efforts have been directed towards the invention of a rapid, simple and sequence selective detection method for miRNAs. Recently, we reported an innovative method for the determination of miRNA levels using the red fluorescent properties of DNA/silver nanoclusters (DNA/AgNCs). Our method is based on monitoring the emission drop of a DNA/AgNCs probe in the presence of its specific target miRNA. Accordingly, the accuracy and efficiency of the method relies on the sensitivity of hybridization between the probe and target. To gain specific and robust hybridization between probe and target, we investigated a range of diverse salts, organic solvents, and buffer to optimize target sensing conditions. Under the newly adjusted conditions, the target sensitivity and the formation of emissive DNA/AgNCs probes were significantly improved. Also, fortification of the Tris-acetate buffer with inorganic salts or organic solvents improved the sensitivity of the DNA/AgNC probes. On the basis of these optimizations, the versatility of the DNA/AgNCs-based miRNA detection method can be expanded.

  1. Effect of salts, solvents and buffer on miRNA detection using DNA silver nanocluster (DNA/AgNCs) probes.

    PubMed

    Shah, Pratik; Cho, Seok Keun; Thulstrup, Peter Waaben; Bhang, Yong-Joo; Ahn, Jong Cheol; Choi, Suk Won; Rørvig-Lund, Andreas; Yang, Seong Wook

    2014-01-31

    MicroRNAs (miRNAs) are small regulatory RNAs (size ~21 nt to ~25 nt) which regulate a variety of important cellular events in plants, animals and single cell eukaryotes. Especially because of their use in diagnostics of human diseases, efforts have been directed towards the invention of a rapid, simple and sequence selective detection method for miRNAs. Recently, we reported an innovative method for the determination of miRNA levels using the red fluorescent properties of DNA/silver nanoclusters (DNA/AgNCs). Our method is based on monitoring the emission drop of a DNA/AgNCs probe in the presence of its specific target miRNA. Accordingly, the accuracy and efficiency of the method relies on the sensitivity of hybridization between the probe and target. To gain specific and robust hybridization between probe and target, we investigated a range of diverse salts, organic solvents, and buffer to optimize target sensing conditions. Under the newly adjusted conditions, the target sensitivity and the formation of emissive DNA/AgNCs probes were significantly improved. Also, fortification of the Tris-acetate buffer with inorganic salts or organic solvents improved the sensitivity of the DNA/AgNC probes. On the basis of these optimizations, the versatility of the DNA/AgNCs-based miRNA detection method can be expanded. PMID:24393838

  2. 47 CFR 4.13 - Reports by the National Communications System (NCS) and by special offices and facilities, and...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Reports by the National Communications System (NCS) and by special offices and facilities, and related responsibilities of communications providers. 4.13 Section 4.13 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL DISRUPTIONS TO COMMUNICATIONS Reporting Requirements for...

  3. Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects

    PubMed Central

    Stefanello, Sílvio Terra; Dobrachinski, Fernando; de Carvalho, Nélson Rodrigues; Amaral, Guilherme Pires; Barcelos, Rômulo Pillon; Oliveira, Vitor Antunes; Oliveira, Cláudia Sirlene; Giordani, Camila Ferrazza Alves; Pereira, Maria Ester; Rodrigues, Oscar Endrigo Dorneles; Soares, Félix Alexandre Antunes

    2015-01-01

    Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration. PMID:26379436

  4. Calcium signaling and cell proliferation.

    PubMed

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. PMID:26275497

  5. Chemical sensors

    SciTech Connect

    Janata, J.; Josowicz, M.; DeVaney, D.M. )

    1994-06-15

    This review of chemical sensors contains the following topics of interest: books and reviews; reviews of sensors by their type; fabrication and selectivity; data processing; thermal sensors; mass sensors (fabrication, gas sensors, and liquid sensors); electrochemical sensors (potentiometric sensors, amperometric sensors, and conductometric sensors); and optical sensors (fabrication, liquid sensors, biosensors, and gas sensors). 795 refs., 1 tab.

  6. Magnetocaloric Evidence for FFLO Superconductivity in κ-(BEDT-TTF)2Cu(NCS)2

    NASA Astrophysics Data System (ADS)

    Fortune, Nathanael; Agosta, Charles; Hannahs, Scott; Park, Ju-Hyun; Gu, Shuyao; Liang, Lucy; Schleuter, John

    We present new magnetocaloric and calorimetric measurements of the high field superconducting state in the layered structure superconductor κ - (BEDT-TTF)2Cu(NCS)2. The strongly field-orientation dependent phase transition between the low field superconducting state and high field superconducting states is first order and is nearly temperature independent, occurring at the Clogston-Chandrasakar paramagnetic limit Hp. Magnetocaloric measurements dT / dH as a function of magnetic field reveal that the system becomes strongly paramagnetic at the cross over from the low field to high field state. At lower temperatures, we are able to resolve small changes at the phase boundary due to the absorption/release of latent heat when increasing/decreasing field, indicating that the high field state is higher entropy than the low field state. These results provide strong new evidence for the formation of paramagnetic spin domains within an inhomogeneous FFLO superconducting state. They also allow us to rule out alternative explanations involving the formation of spin density waves within a homogenous superconducting state. A portion of this work was performed at the National High Magnetic Field Laboratory, which is supported by National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida.

  7. Giant magnetoresistance in organic superconductors {kappa}-(BEDT-TTF){sub 2}Cu(NCS){sub 2}

    SciTech Connect

    Zuo, F.; Schlueter, J.A.; Kelly, M.E.; Williams, J.M.

    1997-08-01

    In this letter, the authors report transport measurements with field and current parallel to the {alpha} axis (perpendicular to the conducting plane) in the organic superconductor {kappa}-(BEDT-TTF){sub 2}Cu(NCS){sub 2}. The magnetoresistance displays a peak effect as a function of field and temperature with the peak fields increasing linearly with decreasing temperatures. The peak resistance is found to be greater than the normal state value extrapolated from both high and low field measurements. This is a first report of above normal resistance in a superconducting state. The results are in sharp contrast to the conventional dissipation mechanisms in the mixed state for anisotropic superconductors, as in the case of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8}. They propose a phenomenological model that the peak in the magnetoresistance is caused by a new scattering mechanism due to a strong coupling to the underlying crystal lattice of fluctuating vortices (vortex polarons). The model can semiquantitatively fit the data.

  8. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Estimation of Magnetic Interactions and Magnetic Structures in Charge-transfer Salts Based on [Cr(isoq)2(NCS)4]- (isoq = Isoquinoline)

    NASA Astrophysics Data System (ADS)

    Katsuhara, Mao; Mori, Takehiko

    2004-12-01

    Magnetic interactions J in [Cr(isoq)2(NCS)4]--based charge-transfer salts, (BDH-TTP)[Cr(isoq)2(NCS)4], (TMTTF)[Cr(isoq)2(NCS)4], and (BO)[Cr(isoq)2(NCS)4], are estimated on the basis of the extended Hückel molecular orbital calculations (BDH-TTP = 2,5-bis(1,3-dithiolan-2-ylidene)-1,3,4,6-tetrathiapentalene, BO = bis(ethylenedioxy)-tetrathiafulvalene, TMTTF = tetramethyltetrathiafulvalene, and isoq = isoquinoline). From this, experimental magnetic properties are discussed, and the magnetic structures are determined. (BDH-TTP)[Cr(isoq)2(NCS)4] is composed of two-dimensional array of antiferromagnetically coupled ferrimagnetic chains. These two-dimensional arrays, however, have net magnetic moment perpendicular to the sheets and give rise to weak ferromagnetism. (TMTTF)[Cr(isoq)2(NCS)4] and (BO)[Cr(isoq)2(NCS)4] have similar “body-centered” molecular arrangement. The TMTTF salt has considerable πd-interaction in two directions, and this compound actually shows a magnetic transition. The BO salt has large πd-interaction only in one direction, but the frustrating dd- and ππ-interactions are considerably large. Consequently, this compound does not exhibit a magnetic transition.

  10. Calcium in Plants

    PubMed Central

    WHITE, PHILIP J.; BROADLEY, MARTIN R.

    2003-01-01

    Calcium is an essential plant nutrient. It is required for various structural roles in the cell wall and membranes, it is a counter‐cation for inorganic and organic anions in the vacuole, and the cytosolic Ca2+ concentration ([Ca2+]cyt) is an obligate intracellular messenger coordinating responses to numerous developmental cues and environmental challenges. This article provides an overview of the nutritional requirements of different plants for Ca, and how this impacts on natural flora and the Ca content of crops. It also reviews recent work on (a) the mechanisms of Ca2+ transport across cellular membranes, (b) understanding the origins and specificity of [Ca2+]cyt signals and (c) characterizing the cellular [Ca2+]cyt‐sensors (such as calmodulin, calcineurin B‐like proteins and calcium‐dependent protein kinases) that allow plant cells to respond appropriately to [Ca2+]cyt signals. PMID:12933363

  11. Calcium and bones (image)

    MedlinePlus

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

  12. Calcium source (image)

    MedlinePlus

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

  13. Coronary Calcium Scan

    MedlinePlus

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

  14. Calcium hydroxide poisoning

    MedlinePlus

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

  15. AC susceptibility and critical current in the organic superconductor {kappa}-(ET){sub 2}Cu(NCS){sub 2}

    SciTech Connect

    Gonzalez, M.A.; Velez, M.; Vicent, J.L.; Schleuter, J.; Williams, J.M.; Crabtree, G.W.

    1994-05-01

    The AC susceptibility (X{prime}, X{double_prime}) has bee measured in a single crystal of the organic superconductor K-(ET){sub 2}Cu(NCS){sub 2} ({Tc} = 9.5 K) as a function of the DC magnetic field, for several frequencies (10 {sup 2} Hz

  16. First order vortex phase transition in the organic superconductor {kappa}-(BEDT-TTF){sub 2}Cu(NCS){sub 2}

    SciTech Connect

    Inada, M.; Sasaki, T.; Nishizaki, T.; Kobayashi, N.; Yamada, S.; Fukase, T.

    1999-12-01

    The local magnetic induction is measured in the quasi-two dimensional organic superconductor {kappa}-(BEDT-TTF){sub 2}Cu(NCS){sub 2} by using a micro Hall probe. The small step is observed on the temperature dependence of the local magnetic induction. This result implies the existence of the first-order phase transition of the vortex system in this organic superconductor as is already reported in high-{Tc} oxide and other organic superconductors.

  17. Synthesis and magnetic studies of the {π }-d ferrimagnet TTF[ Cr(NCS){4}(1,10'-phenanthroline)] , TTF = tetrathiafulvalene

    NASA Astrophysics Data System (ADS)

    Turner, S. S.; Carling, S. G.; Day, P.; Gómez-Garcia, C. J.; Coronado, E.

    2004-04-01

    A new synthesis route to the π -d ferrimagnet TTF[ Cr(NCS){4}(1,10'-phenanthroline)] is described along with recent magnetic investigations. In particular the variable frequency AC magnetisation of the protonated and fully deuterated samples indicate no frequency dependence and a Tc of 8.7 K. Single crystal heat capacity and muon spin relaxation experiments show a second magnetic transition at 2.4 K. Key words. Charge-transfer salts, conductivity, ferrimagnetism.

  18. Optimizing radiolabeling amine-functionalized silica nanoparticles using SarAr-NCS for applications in imaging and radiotherapy.

    PubMed

    Kong, Linggen; Mume, Eskender; Triani, Gerry; Smith, Suzanne V

    2013-05-01

    Silica nanoparticles functionalized with amine groups and in the size range of approximately 60-94 nm were produced by combining sol-gel processing and emulsion technology. Hexa-aza cage ligand SarAr-NCS was conjugated to the silica nanoparticles and subsequently radiolabeled with a solution of (57)Co(2+)-doped carrier Co(2+). The number of Co(2+) ions bound to the silica particles at pH 7 was used to determine the average number of available SarAr-NCS ligands conjugated to a silica particle. For organically modified silica particles of 94.0 and 59.5 nm diameter, the maximum number of metal binding sites was determined to be 11700 and 3270 sites per particle, respectively. For silica particles (63.5 nm peak diameter) produced using an water-in-oil emulsion, the calculated average was 4480 on the particle surface. The number of SarAr-NCS conjugated on the particles was easily controlled, potentially providing for a range of products for applications in the risk assessment of particles and theranostic imaging or radiotherapy when radiolabeled with a suitable radioisotope such as (64)Cu or (67)Cu. PMID:23581487

  19. A theoretical study on the interstellar synthesis of H{sub 2}NCS{sup +} and HNCSH{sup +} cations

    SciTech Connect

    Gronowski, Marcin; Kołos, Robert E-mail: rkolos@ichf.edu.pl

    2014-09-10

    HNCS and NCSH molecules, recently discovered in the interstellar medium, are likely formed via the dissociative recombination of H{sub 2}NCS{sup +} or HNCSH{sup +} isomeric ions. Interstellar synthesis of the latter is discussed on theoretical grounds. The analysis of relevant potential energy surfaces suggests a key role for chemical processes in which CSH{sup +} or HCS{sup +} cations (most likely formed in CS+H{sub 3}{sup +} collisions) react with NH{sub 2} or NH{sub 3}. The astrochemical kinetic database (kida.uva.2011), appended with 7 sulfur-bearing molecules and 48 corresponding reactions, has been applied to model the evolution of HNCS, NCSH, and their cationic precursors in a quiescent molecular cloud. Based on the model and on spectroscopic predictions, for an object like TMC-1, we expect the total intensity of H{sub 2}NCS{sup +} microwave lines to be comparable to that observed for HSCN. Theoretically derived molecular parameters, of interest for radio spectroscopy, are given for the most stable cations sharing the H{sub 2}NCS{sup +} stoichiometry.

  20. Nanocrystals of Fe(phen)2(NCS)2 and the size-dependent spin-crossover characteristics.

    PubMed

    Laisney, J; Tissot, A; Molnár, G; Rechignat, L; Rivière, E; Brisset, F; Bousseksou, A; Boillot, M-L

    2015-10-21

    We report on the size reduction of the neutral Fe(phen)2(NCS)2 prototypical compound exhibiting a cooperative spin-crossover associated with a first-order phase transition (at ca. 176 K). We use the [Fe(phen)3](NCS)2 ionic precursor and the solvent-assisted precipitation technique to prepare an array of crystalline objects with sizes varying over two orders of magnitude (from 15 up to 1400 nm). TEM, X-ray diffraction and IR measurements provide evidences for the formation of particles of neutral and ionic species, which results from the interplay between the relevant chemical equilibrium and the reaction kinetics (ligand extraction, complex precipitation), and the modulation of the latter by physico-chemical parameters. A thermal transformation of diamagnetic nanocrystals of [Fe(phen)3](NCS)2 leads to spin-crossover particles of Fe(phen)2(NCS)2 of a comparable size. Powders of nano-, micro- and polycrystals of Fe(phen)2(NCS)2 present X-ray diffractograms typical of the so-called polymorph II. The importance of size effects on the cooperative spin-crossover process was probed with magnetic, Mössbauer, Raman and IR spectroscopic measurements. Each sample exhibits spin-state switching of the Fe(ii) ions. The salient features are: a cooperativity preserved at the micrometric scale, a very limited downshift of the transition temperature and an asymmetric spreading of the thermal process (over ca. 100 K) with the size reduction. At temperatures close to room temperature, the process appears to be quasi complete whatever the size of the samples. This result, extracted from Raman data, was confirmed by Mössbauer measurements in the case of the largest objects (LS residue <5-10% for bulk and microparticles). Below 150 K, a very efficient low-spin to high-spin photoexcitation was induced by the Raman laser beam in all the samples which prevents the extraction of the high-spin fraction in this temperature range. However variable temperature IR spectra of the 29 nm particles

  1. Towards the chemical control of molecular packing: syntheses and crystal structures of three trans-[NiL4(NCS)2] complexes.

    PubMed

    Soliman, Saied M; Elzawy, Zahia B; Abu-Youssef, Morsy A M; Albering, Jörg; Gatterer, Karl; Ohrström, Lars; Kettle, Sidney F A

    2014-02-01

    Three nickel(II) isothiocyanato complexes of the formula trans-[NiL4(NCS)2] (L = ethylisonicotinate, methylisonicotinate and 4-benzoylpyridine) have been prepared: [Ni(ethylisonicotinate)4(NCS)2] (I), [Ni(methylisonicotinate)4(NCS)2] (II) and [Ni(4-benzoylpyridine)4(NCS)2] (III). All three complexes are monomeric and have a distorted octahedral geometry around Ni(II). Despite their apparent molecular similarity, the crystal density of (III) (1.454 g cm(-3)) is significantly higher than that of (I) and (II) (both 1.408 g cm(-3)), suggesting that the molecular packing is most efficient in (III). A study of the molecular Hirshfeld surfaces, together with density functional theory (DFT) calculations, provide insights into the origin of the molecular packing features, and it is suggested that the greater crystal density of (III) results from smaller intermolecular electrostatic repulsions. PMID:24441134

  2. A visual physiological temperature sensor developed with gelatin-stabilized luminescent silver nanoclusters.

    PubMed

    Lan, Jing; Zou, Hongyan; Liu, Zexi; Gao, Mingxuan; Chen, Binbin; Li, Yuanfang; Huang, Chengzhi

    2015-10-01

    A visual physiological temperature sensor was successfully developed with newly hydrothermally prepared fluorescent silver nanoclusters (AgNCs) at room temperature using gelatin as the protective and reducing agent. The as-prepared gelatin-stabilized AgNCs was water-soluble, uniform and exhibited a narrow distribution with an average size of 1.16 nm, showing a maximum emission band at 552 nm (2.45 eV) when excited at 445 nm (2.79 eV). The large Stokes shift of 110 nm of the gelatin-stabilized AgNCs makes it actually applicable with very low background and light scattering interferences. It was found that the as-prepared gelatin-stabilized AgNCs is temperature-sensitive over the range from 5°C to 45°C, and thus a visual physiological temperature sensor could be developed with the gelatin-AgNCs as under the irradiation of visible light. PMID:26078186

  3. Extracellular calcium sensing and extracellular calcium signaling

    NASA Technical Reports Server (NTRS)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    , localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

  4. DFT structural investigation on Fe(1,10-phenanthroline){sub 2} (NCS){sub 2} spin crossover molecule

    SciTech Connect

    Chiş, V.; Isai, R.; Droghetti, A.; Rungger, I.; Sanvito, S.; Morari, C.

    2013-11-13

    Understanding the coupling of spin crossover molecules to metallic surfaces is a key ingredient for harnessing of their remarkable features for future spintronics applications. Here we investigate the structural and electronic properties of deformed Fe(1,10-phenanthroline){sub 2} (NCS){sub 2} molecules, mimicking the possible effects arising from the interaction with a metallic substrate. We find a relatively large structural flexibility for this molecule, accompanied by small changes in their total energy. This suggests that the spin crossover activity can be modulated by the interaction with the substrate.

  5. Nature and mechanism of the photoinduced spin transition in [Fe(PM-BiA){sub 2}(NCS){sub 2}

    SciTech Connect

    Ichiyanagi, K.; Hebert, J.; Toupet, L.; Cailleau, H.; Collet, E.

    2006-02-01

    We report the investigation of a prototype cooperative photoinduced spin transition in [Fe(PM-BiA){sub 2}(NCS){sub 2}] by x-ray diffraction. The structural rearrangement accompanying the change of an electronic state between the low spin and the photoinduced out-of-equilibrium high spin phases is similar to the one occurring around the phase transition at thermal equilibrium. The cooperative behavior of the light-induced optical hysteresis and light-induced thermal hysteresis phenomena investigated here show a strong similarity with thermal hysteresis around first-order phase transitions, since they are driven by a domain nucleation process.

  6. Calcium/calmodulin-mediated signal network in plants

    NASA Technical Reports Server (NTRS)

    Yang, Tianbao; Poovaiah, B. W.

    2003-01-01

    Various extracellular stimuli elicit specific calcium signatures that can be recognized by different calcium sensors. Calmodulin, the predominant calcium receptor, is one of the best-characterized calcium sensors in eukaryotes. In recent years, completion of the Arabidopsis genome project and advances in functional genomics have helped to identify and characterize numerous calmodulin-binding proteins in plants. There are some similarities in Ca(2+)/calmodulin-mediated signaling in plants and animals. However, plants possess multiple calmodulin genes and many calmodulin target proteins, including unique protein kinases and transcription factors. Some of these proteins are likely to act as "hubs" during calcium signal transduction. Hence, a better understanding of the function of these calmodulin target proteins should help in deciphering the Ca(2+)/calmodulin-mediated signal network and its role in plant growth, development and response to environmental stimuli.

  7. Heterogeneous Nature of Relaxation Dynamics of Room-Temperature Ionic Liquids (EMIm)2[Co(NCS)4] and (BMIm)2[Co(NCS)4

    SciTech Connect

    Hensel-Bielowka, Stella; Wojnarowska, Zaneta; Dzida, Marzena; Zorębski, Edward; Zorębski, Michał; Geppert-Rybczyńska, Monika; Peppel, Tim; Grzybowska, Katarzyna; Wang, Yangyang; Sokolov, Alexei P.; Paluch, Marian

    2015-08-11

    Dynamic crossover above Tg has been recognized as a characteristic feature of molecular dynamics of liquids approaching glass transition. Experimentally, it is manifested as a change in Vogel–Fulcher–Tammann dependence or a breakdown of the Stokes–Einstein and related relations. In this study, we report the exception from this rather general pattern of behavior. By means of dielectric, ultrasonic, rheological, and calorimetric methods, dynamics of two good ionic conductors (BMIm)2[Co(NCS)4] and (EMIm)2[Co(NCS)4] of less common stoichiometry (2:1) was studied in a very broad temperature range. However, none of the mentioned dynamic changes was observed in the entire studied temperature range. On the contrary, the single VFT and the same fractional Walden coefficient were found for conductivity and viscosity changes over 12 decades. Finally and moreover, ultrasonic studies revealed that the data at temperatures which cover the normal liquid region cannot be fitted by a single exponential decay, and the Cole–Cole function should be used instead.

  8. Single-source-precursor synthesis of hafnium-containing ultrahigh-temperature ceramic nanocomposites (UHTC-NCs).

    PubMed

    Yuan, Jia; Hapis, Stefania; Breitzke, Hergen; Xu, Yeping; Fasel, Claudia; Kleebe, Hans-Joachim; Buntkowsky, Gerd; Riedel, Ralf; Ionescu, Emanuel

    2014-10-01

    Amorphous SiHfBCN ceramics were prepared from a commercial polysilazane (HTT 1800, AZ-EM), which was modified upon reactions with Hf(NEt2)4 and BH3·SMe2, and subsequently cross-linked and pyrolyzed. The prepared materials were investigated with respect to their chemical and phase composition, by means of spectroscopy techniques (Fourier transform infrared (FTIR), Raman, magic-angle spinning nuclear magnetic resonance (MAS NMR)), as well as X-ray diffraction (XRD) and transmission electron microscopy (TEM). Annealing experiments of the SiHfBCN samples in an inert gas atmosphere (Ar, N2) at temperatures in the range of 1300-1700 °C showed the conversion of the amorphous materials into nanostructured UHTC-NCs. Depending on the annealing atmosphere, HfC/HfB2/SiC (annealing in argon) and HfN/Si3N4/SiBCN (annealing in nitrogen) nanocomposites were obtained. The results emphasize that the conversion of the single-phase SiHfBCN into UHTC-NCs is thermodynamically controlled, thus allowing for a knowledge-based preparative path toward nanostructured ultrahigh-temperature stable materials with adjusted compositions. PMID:25231931

  9. Towards Understanding Quantum Monodromy in Quasi-Symmetric Molecules: Fassst Rotational Spectra of CH_3NCO and CH_3NCS

    NASA Astrophysics Data System (ADS)

    Kisiel, Zbigniew; Fortman, Sarah; Medvedev, Ivan R.; Winnewisser, Manfred; De Lucia, Frank C.; Koput, Jacek

    2010-06-01

    The recent studies of the rotational spectrum of the NCNCS molecule demonstrated the success of quantum monodromy in describing the quasilinear behavior of this molecule, inclusive of the abrupt transition of spectroscopic behavior from the bent to the linear molecule regime. Similar, quasisymmetric behaviour, is known to be present in symmetric top molecules, and has been studied at lowest-J transitions for two such molecules, CH_3NCO and CH_3NCS. Further progress requires more experimental data and presently we report FASSST rotational spectra of CH_3NCO and CH_3NCS. The spectra provide practically continuous 117-376 GHz coverage and are very rich, since the ladder of excited vibrational states associated with the qusilinear bending coordinate is multiplied by the nearly free internal rotation of the methyl group. Initial stages of the analysis leading up to an analysis in an extension of the framework used for NCNCS are described. B.P.Winnewisser, et al., Phys. Rev. Lett. 95. 243002 (2005). M.Winnewisser, et al., J. Mol. Struct. 798, 1 {2006}. B.P.Winnewisser, et al., Phys. Chem. Chem. Phys. DOI:10.1039/B922023B (2010). J.Koput, J. Mol. Spectrosc. 115, 131 (1986) J.Koput, J. Mol. Spectrosc. 118, 189 (1986)

  10. [Do cows drink calcium?].

    PubMed

    Geishauser, T; Lechner, S; Plate, I; Heidemann, B

    2008-03-01

    The objective of this study was to investigate how well cows drink the Propeller calcium drink, and it's effect on blood calcium concentration. Drinking was tested in 120 cows right after calving, before cows drank anything else. 60 cows each were offered 20 liters of Propeller calcium drink or 20 liters of water. Cows drank the Propeller as good as water. 72% of all cows drank all 20 liters, 18% drank on average 8.2 liters and 10% drank less than 1 liter. Blood calcium concentration was studied in 16 cows right after calving. Eight cows each were offered 20 liters of Propeller calcium drink or no calcium drink. Blood calcium significantly increased ten minutes after Propeller intake and stayed significantly elevated for 24 hours. Without calcium drink blood calcium levels decreased significantly. Advantages of the new Propeller calcium drink over calcium gels or boli could be that cows now drink calcium themselves and that the Propeller increases blood calcium concentration rapidly and long lasting. PMID:18429501

  11. Fenoprofen calcium overdose

    MedlinePlus

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

  12. Calcium channel blocker overdose

    MedlinePlus

    ... 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 ...

  13. Calcium and Vitamin D

    MedlinePlus

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

  14. Calcium and bones (image)

    MedlinePlus

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human body. Bones, like other tissues in the body, are continually being re-formed and incorporate calcium into their ...

  15. Fenoprofen calcium overdose

    MedlinePlus

    Fenoprofen calcium is a type of medicine called a nonsteroidal anti-inflammatory drug. It is a prescription pain medicine used to relieve symptoms of arthritis . Fenoprofen calcium overdose occurs when someone takes more than the ...

  16. Calcium and magnesium disorders.

    PubMed

    Goff, Jesse P

    2014-07-01

    Hypocalcemia is a clinical disorder that can be life threatening to the cow (milk fever) and predisposes the animal to various other metabolic and infectious disorders. Calcium homeostasis is mediated primarily by parathyroid hormone, which stimulates bone calcium resorption and renal calcium reabsorption. Parathyroid hormone stimulates the production of 1,25-dihydroxyvitamin D to enhance diet calcium absorption. High dietary cation-anion difference interferes with tissue sensitivity to parathyroid hormone. Hypomagnesemia reduces tissue response to parathyroid hormone. PMID:24980727

  17. Calcium and Mitosis

    NASA Technical Reports Server (NTRS)

    Hepler, P.

    1983-01-01

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

  18. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter describes the roles of calcium and vitamin D in bone health. Calcium is required for the bone formation phase of bone remodeling and it also affects bone mass through its impact on the remodeling rate. Typically, about 5 nmol (200 mg) of calcium is removed from the adult skeleton and ...

  19. Calcium and bones

    MedlinePlus

    Bone strength and calcium ... or if your body does not absorb enough calcium, your bones can get weak or will not grow properly. ... injury. As you age, your body still needs calcium to keep your bones dense and strong. Most experts recommend at least ...

  20. A "turn-on" silver nanocluster based fluorescent sensor for folate receptor detection and cancer cell imaging under visual analysis.

    PubMed

    Jiang, Hong; Xu, Gang; Sun, Yimin; Zheng, Weiwei; Zhu, Xiangxiang; Wang, Baojuan; Zhang, Xiaojun; Wang, Guangfeng

    2015-07-28

    A novel terminal protection based label-free and "turn-on" fluorescent sensor for detection of folate receptors (FRs) and HeLa cells is developed by fluorescence resonance energy transfer (FRET) between single-walled carbon nanotubes (SWCNTs) and silver nanoclusters (AgNCs). Multilevel visual analysis (m(2)VA) was firstly proposed and applied in optimizing the experimental parameters. PMID:26108636

  1. Multiscale experimental and theoretical investigations of spin crossover Fe(II) complexes: examples of [Fe(phen)2(NCS)2] and [Fe(PM-BiA)2(NCS)2].

    PubMed

    Matar, Samir F; Guionneau, Philippe; Chastanet, Guillaume

    2015-01-01

    For spin crossover (SCO) complexes, computation results are reported and confirmed with experiments at multiscale levels of the isolated molecule and extended solid on the one hand and theory on the other hand. The SCO phenomenon which characterizes organometallics based on divalent iron in an octahedral FeN6-like environment with high spin (HS) and low spin (LS) states involves the LS/HS switching at the cost of small energies provided by temperature, pressure or light, the latter connected with Light-Induced Excited Spin-State Trapping (LIESST) process. Characteristic infra red (IR) and Raman vibration frequencies are computed within density functional theory (DFT) framework. In [Fe(phen)2(NCS)2] a connection of selected frequencies is established with an ultra-fast light-induced LS → HS photoswitching mechanism. In the extended solid, density of state DOS and electron localization function (ELF) are established for both LS and HS forms, leading to characterizion of the compound as an insulator in both spin states with larger gaps for LS configuration, while keeping molecular features in the solid. In [Fe(PM-BiA)2(NCS)2], by combining DFT and classical molecular dynamics, the properties and the domains of existence of the different phases are obtained by expressing the potential energy surfaces in a short range potential for Fe-N interactions. Applying such Fe-N potentials inserted in a classical force field and carrying out molecular dynamics (MD) in so-called "semi-classical MD" calculations, lead to the relative energies of HS/LS configurations of the crystal and to the assessment of the experimental (P, T) phase diagram. PMID:25686037

  2. Multiscale Experimental and Theoretical Investigations of Spin Crossover FeII Complexes: Examples of [Fe(phen)2(NCS)2] and [Fe(PM-BiA)2(NCS)2

    PubMed Central

    Matar, Samir F.; Guionneau, Philippe; Chastanet, Guillaume

    2015-01-01

    For spin crossover (SCO) complexes, computation results are reported and confirmed with experiments at multiscale levels of the isolated molecule and extended solid on the one hand and theory on the other hand. The SCO phenomenon which characterizes organometallics based on divalent iron in an octahedral FeN6-like environment with high spin (HS) and low spin (LS) states involves the LS/HS switching at the cost of small energies provided by temperature, pressure or light, the latter connected with Light-Induced Excited Spin-State Trapping (LIESST) process. Characteristic infra red (IR) and Raman vibration frequencies are computed within density functional theory (DFT) framework. In [Fe(phen)2(NCS)2] a connection of selected frequencies is established with an ultra-fast light-induced LS → HS photoswitching mechanism. In the extended solid, density of state DOS and electron localization function (ELF) are established for both LS and HS forms, leading to characterizion of the compound as an insulator in both spin states with larger gaps for LS configuration, while keeping molecular features in the solid. In [Fe(PM-BiA)2(NCS)2], by combining DFT and classical molecular dynamics, the properties and the domains of existence of the different phases are obtained by expressing the potential energy surfaces in a short range potential for Fe–N interactions. Applying such Fe–N potentials inserted in a classical force field and carrying out molecular dynamics (MD) in so-called “semi-classical MD” calculations, lead to the relative energies of HS/LS configurations of the crystal and to the assessment of the experimental (P, T) phase diagram. PMID:25686037

  3. Calcium bioavailability from calcium fortified food products.

    PubMed

    Kohls, K

    1991-08-01

    The calcium balance of 12 presumed healthy human young adult subjects was assessed. Subjects consumed a constant laboratory-controlled diet supplemented with one of four calcium-fortified food products: orange juice (OJ), milk (M), experimental pasteurized processed cheese (T), soda (S), or a calcium carbonate plus vitamin D tablet (CC). Study length was 6 weeks with seven-day experimental periods (2-days allowed for adjustment with 5-days combined for purposes of analysis). All urine and fecal samples were collected by the subjects for the duration of the study. Blood samples were drawn at the end of each experimental period. Urine and fecal calcium contents were determined. Blood samples were analyzed for alkaline phosphatase. Results of this study indicate a higher fecal calcium content (mg/day) when subjects consumed CC and T, and when subjects consumed self-selected diets, than when given S, M, or OJ. Urinary calcium excretion was significantly lower when subjects consumed OJ than when they consumed M, T, or their self-selected diets. A significantly larger positive calcium balance was demonstrated when subjects consumed OJ as compared to T. Fecal transmit time did not vary significantly. Serum alkaline phosphatase was significantly lower when subjects consumed T than when they consumed self-selected diets. PMID:1765836

  4. Synthesis, crystal structure and luminescence properties of one inorganic-organic hybrid compound [FTMA] 2[Co(NCS) 4] (FTMA = ferrocenylmethyltrimethylammonium cation)

    NASA Astrophysics Data System (ADS)

    Bai, Yan; Zhang, Guo-Qiang; Dang, Dong-Bin; Ma, Peng-Tao; Niu, Jing-Yang

    2011-08-01

    A new inorganic-organic hybrid compound [FTMA] 2[Co(NCS) 4] (FTMA = ferrocenylmethyltrimethylammonium cation) has been synthesized and characterized by IR, UV, elemental analysis and X-ray crystallography. Co(II) atom has a distorted tetrahedral environment with four N atoms of four NCS - anions. In the solid state there are C-H⋯π interactions between adjacent ferrocenyl cations, which generate one-dimensional (1-D) supramolecular chain, and C-H⋯S hydrogen bonds between [FTMA] + cations and cobalt thiocyanate anions. The title compound shows strong purple fluorescence emission in the solid state at room temperature.

  5. Synthesis, crystal structure and luminescence properties of one inorganic-organic hybrid compound [FTMA]2[Co(NCS)4] (FTMA = ferrocenylmethyltrimethylammonium cation).

    PubMed

    Bai, Yan; Zhang, Guo-Qiang; Dang, Dong-Bin; Ma, Peng-Tao; Niu, Jing-Yang

    2011-08-01

    A new inorganic-organic hybrid compound [FTMA](2)[Co(NCS)(4)] (FTMA = ferrocenylmethyltrimethylammonium cation) has been synthesized and characterized by IR, UV, elemental analysis and X-ray crystallography. Co(II) atom has a distorted tetrahedral environment with four N atoms of four NCS(-) anions. In the solid state there are C-H⋯π interactions between adjacent ferrocenyl cations, which generate one-dimensional (1-D) supramolecular chain, and C-H⋯S hydrogen bonds between [FTMA](+) cations and cobalt thiocyanate anions. The title compound shows strong purple fluorescence emission in the solid state at room temperature. PMID:21530374

  6. Structural and Magnetic Behavior of a Quasi-1D Antiferromagnetic Chain Compound Cu(NCS)(2)(PYZ)

    SciTech Connect

    Bordallo, H. N.; Chapon, L. C.; Manson, Jamie L; Qualls, J. S.; Hall, D.; Argyriou, D. N.

    2003-01-01

    Synchrotron X-ray diffraction (XRD) and neutron powder diffraction (NPD) were used to determine the structure of Cu(NCS){sub 2}(pyz) (pyz=pyrazine=C{sub 4}N{sub 2}H{sub 4}), which consists of a stacking of Cu-pyz-Cu chains. While NPD measurements showed no evidence of long-range magnetic ordering, the temperature dependence of the magnetic susceptibility and magnetization suggests that the system can be adequately described on the local scale as a spin-1/2 antiferromagnet (AFM) chain with an intrachain exchange interaction J/k{sub B} = -8 K ({approx}0.7 meV). Comparison of isothermal magnetization data acquired up to 30 T at 1.6 K to a linear chain model shows excellent agreement, making this material a nearly ideal example of an isotropic Heisenberg AFM chain.

  7. Density functional plus dynamical mean-field theory of the spin-crossover molecule Fe(phen)2(NCS)2

    NASA Astrophysics Data System (ADS)

    Chen, Jia; Millis, Andrew J.; Marianetti, Chris A.

    2015-06-01

    We study the spin-crossover molecule Fe(phen) 2(NCS) 2 using density functional theory (DFT) plus dynamical mean-field theory, which allows access to observables not attainable with traditional quantum chemical or electronic structure methods. The temperature dependent magnetic susceptibility, electron addition and removal spectra, and total energies are calculated and compared to experiment. We demonstrate that the proper quantitative energy difference between the high-spin and low-spin state, as well as reasonably accurate values of the magnetic susceptibility can be obtained when using reasonable interaction parameters. Comparisons to DFT and DFT+U calculations demonstrate that dynamical correlations are critical to the energetics of the low-spin state. Additionally, we elucidate the differences between DFT+U and spin density functional theory (SDFT) plus U methodologies, demonstrating that DFT+U can recover SDFT+U results for an appropriately chosen on-site exchange interaction.

  8. Matrix-assisted relaxation in Fe(phen)2(NCS)2 spin-crossover microparticles, experimental and theoretical investigations

    NASA Astrophysics Data System (ADS)

    Enachescu, Cristian; Tanasa, Radu; Stancu, Alexandru; Tissot, Antoine; Laisney, Jérôme; Boillot, Marie-Laure

    2016-07-01

    In this study, we present the influence of the embedding matrix on the relaxation of Fe(phen)2(NCS)2 (phen = 1,10-phenanthroline) spin-transition microparticles as revealed by experiments and provide an explanation within the framework of an elastic model based on a Monte-Carlo method. Experiments show that the shape of the high-spin → low-spin relaxation curves is drastically changed when the particles are dispersed in glycerol. This effect was considered in the model by means of interactions between the microparticles and the matrix. A faster start of the relaxation for microparticles embedded in glycerol is due to an initial positive local pressure acting on the edge spin-crossover molecules from the matrix side. This local pressure diminishes and eventually becomes negative during relaxation, as an effect of the decrease of the volume of spin-crossover microparticles from high-spin to low-spin.

  9. Calculated impact of ferromagnetic substrate on the spin crossover in a Fe(1 ,10 -phenanthroline) 2(NCS) 2 molecule

    NASA Astrophysics Data System (ADS)

    Gueddida, S.; Alouani, M.

    2016-05-01

    Spin crossover in the Fe(1 ,10 -phenanthroline) 2(NCS) 2 (Fephen) molecule adsorbed on ferromagnetic cobalt (001) and (111) surfaces as well as a gold (001) surface has been studied using the projector augmented wave method in conjunction with the density functional theory within the generalized gradient approximation, including a Hubbard interaction U at the iron site and a van der Waals weak interaction between the molecule and the surface. It is shown that the energy difference between the high-spin (HS) and the low-spin (LS) states and the energy barrier of Fephen/Co(111) are significantly reduced compared to those of the adsorbed molecule on Cu(001) and Au(001). This makes the switching of the molecule from the HS to the LS state much easier than when the molecule is adsorbed on a copper or gold substrate. It is also shown that an indirect exchange mechanism is responsible for the ferromagnetic coupling between the Fe center of Fephen and the cobalt substrate and that, in the LS state, the Fephen/Co interface remains magnetically active due to small induced magnetic moments in the NCS group and iron center. This magnetic coupling between the molecule and the substrate decreases in an oscillatory fashion as a function of the number of copper layers inserted between the molecule and the cobalt substrate, in a manner similar to that of the interlayer magnetic exchange coupling. Finally, scanning tunneling microscopy images at the Fermi level show that the separation between the phen lobes is larger in the HS state than in the LS state and the work functions of cobalt, gold, and copper substrates are strongly reduced upon adsorption of the Fephen molecule.

  10. Sense and specificity in neuronal calcium signalling☆

    PubMed Central

    Burgoyne, Robert D.; Haynes, Lee P.

    2015-01-01

    Changes in the intracellular free calcium concentration ([Ca2 +]i) in neurons regulate many and varied aspects of neuronal function over time scales from microseconds to days. The mystery is how a single signalling ion can lead to such diverse and specific changes in cell function. This is partly due to aspects of the Ca2 + signal itself, including its magnitude, duration, localisation and persistent or oscillatory nature. The transduction of the Ca2 + signal requires Ca2 + binding to various Ca2 + sensor proteins. The different properties of these sensors are important for differential signal processing and determine the physiological specificity of Ca2 + signalling pathways. A major factor underlying the specific roles of particular Ca2 + sensor proteins is the nature of their interaction with target proteins and how this mediates unique patterns of regulation. We review here recent progress from structural analyses and from functional analyses in model organisms that have begun to reveal the rules that underlie Ca2 + sensor protein specificity for target interaction. We discuss three case studies exemplifying different aspects of Ca2 + sensor/target interaction. This article is part of a special issue titled the 13th European Symposium on Calcium. PMID:25447549

  11. Lifetime Prevalence of Mental Disorders in U.S. Adolescents: Results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A)

    ERIC Educational Resources Information Center

    Merikangas, Kathleen Ries; He, Jian-ping; Burstein, Marcy; Swanson, Sonja A.; Avenevoli, Shelli; Cui, Lihong; Benjet, Corina; Georgiades, Katholiki; Swendsen, Joel

    2010-01-01

    Objective: To present estimates of the lifetime prevalence of "DSM-IV" mental disorders with and without severe impairment, their comorbidity across broad classes of disorder, and their sociodemographic correlates. Method: The National Comorbidity Survey-Adolescent Supplement NCS-A is a nationally representative face-to-face survey of 10,123…

  12. From Too Much Freedom to Too Much Restriction: The Case of Teacher Autonomy from National Curriculum Statement (NCS) to Curriculum and Assessment Statement (CAPS)

    ERIC Educational Resources Information Center

    Ramatlapana, K.; Makonye, J. P.

    2012-01-01

    The major curricula revisions in South Africa in the last two decades or so have changed the curriculum landscape. These revisions are meant to effect among other issues, the socio-economic development for all through quality education. The latest curricula transition from National Curriculum Statement (NCS) to Curriculum and Assessment Policy…

  13. Spectra and relaxation dynamics of the pseudohalide (PS) vibrational bands for Ru(bpy)2(PS)2 complexes, PS = CN, NCS and N3

    NASA Astrophysics Data System (ADS)

    Compton, Ryan; Gerardi, Helen K.; Weidinger, Daniel; Brown, Douglas J.; Dressick, Walter J.; Heilweil, Edwin J.; Owrutsky, Jeffrey C.

    2013-08-01

    Static and transient infrared spectroscopy were used to investigate cis-Ru(bpy)2(N3)2 (bpy = 2,2‧-bipyridine), cis-Ru(bpy)2(NCS)2, and cis-Ru(bpy)2(CN)2 in solution. The NC stretching IR band for cis-Ru(bpy)2(NCS)2 appears at higher frequency (∼2106 cm-1 in DMSO) than for the free NCS- anion while the IR bands for the azide and cyanide complexes are closer to those of the respective free anions. The vibrational energy relaxation (VER) lifetime for the azide complex is found to be much shorter (∼5 ps) than for either the NCS or CN species (both ∼70 ps in DMSO) and the lifetimes resemble those for each corresponding free anion in solution. However, for cis-Ru(bpy)2(N3)2, it is determined that the transition frequency depends more on the solvent than the VER lifetime implying that intramolecular vibrational relaxation is predominant over solvent energy-extracting interactions. These results are compared to the behavior of other related metal complexes in solution.

  14. Two-bit memory and quantized storage phenomenon in conventional MOS structures with double-stacked Pt-NCs in an HfAlO matrix.

    PubMed

    Zhou, Guangdong; Wu, Bo; Liu, Xiaoqin; Li, Ping; Zhang, Shuangju; Sun, Bai; Zhou, Ankun

    2016-03-01

    A two-bit memory and quantized storage phenomenon are observed at room temperature for a device based on the traditional MOS structure with double-stacked Pt-nanocrystals (Pt-NCs). A 2.68 and 1.72 V flat band voltage shift (memory window) has been obtained when applying a ±7 V programming/erasing voltage to the structures with double-stacked Pt-NCs. The memory windows of 2.40 and 1.44 V can be retained after stress for 10(5) seconds, which correspond to 89.55% and 83.72% stored charges reserved. The quantized charge storage phenomenon characterized by current-voltage (J-V) hysteresis curves was detected at room temperature. The shrinkage of the memory window results from the decreasing tunneling probability, which strongly depends on the number of stacks. The traps, de-traps and quantum confinement effects of Pt-NCs may contribute to the improvement of dielectric characteristics and the two-bit memory behavior. The multi-bit memory and quantized storage behavior observed in the Pt-NCs stacks structure at room temperature might provide a feasible method for realizing the multi-bit storage in non-volatile flash memory devices. PMID:26864686

  15. Synthesis and structure of R{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (R = Rb or Cs)

    SciTech Connect

    Serezhkin, V. N.; Peresypkina, E. V.; Grigor’eva, V. A.; Virovets, A. V.; Serezhkina, L. B.

    2015-01-15

    Crystals Rb{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (I) and Cs{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (II) have been synthesized and studied by IR spectroscopy and X-ray diffraction. Crystals I are monoclinic, with the following parameters: a = 12.2118(5) Å, b = 10.2545(3) Å, c = 11.8754(4) Å, β = 110.287(1)°, sp. gr. C2/c, Z = 4, and R = 0.0523. Crystals II are orthorhombic, with a = 13.7309(3) Å, b = 10.5749(2) Å, c = 10.1891(2) Å, sp. gr. Pnma, Z = 4, and R = 0.0411. The basic structural units of crystals I and II are one-core complexes [UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}]{sup 2−}, which belong to the crystallochemical group cis-AB{sub 2}{sup 01}M{sub 2}{sup 1} (A = UO{sub 2}{sup 2+}, B{sup 01} = NO{sub 3}{sup −}, M{sup 1} = NCS{sup −}), which are combined into a framework via electrostatic interactions with ions of alkaline metals R (R = Rb or Cs). The structural features of crystals I and II, which condition the formation of [UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}]{sup 2−} complexes with a cis rather than a trans position of isothiocyanate ions in the coordination sphere of uranyl ions, are discussed.

  16. Calcium Stores in Vertebrate Photoreceptors

    PubMed Central

    Križaj, David

    2012-01-01

    This review lays out the emerging evidence for the fundamental role of Ca2+ stores and store-operated channels in the Ca2+ homeostasis of rods and cones. Calcium-induced calcium release (CICR) is a major contributor to steady-state and light-evoked photoreceptor Ca2+ homeostasis in the darkness whereas store-operated Ca2+ channels play a more significant role under sustained illumination conditions. The homeostatic response includes dynamic interactions between the plasma membrane, endoplasmic reticulum (ER), mitochondria and/or outer segment disk organelles which dynamically sequester, accumulate and release Ca2+. Coordinated activation of SERCA transporters, ryanodine receptors (RyR), inositol triphosphate receptors (IP3Rs) and TRPC channels amplifies cytosolic voltage-operated signals but also provides a memory trace of previous exposures to light. Store-operated channels, activated by the STIM1 sensor, prevent pathological decrease in [Ca2+]i mediated by excessive activation of PMCA transporters in saturating light. CICR and SOCE may also modulate the transmission of afferent and efferent signals in the outer retina. Thus, Ca2+ stores provide additional complexity, adaptability, tuneability and speed to photoreceptor signaling. PMID:22453974

  17. Lead in calcium supplements.

    PubMed

    Scelfo, G M; Flegal, A R

    2000-04-01

    Intercalibrated measurements of lead in calcium supplements indicate the importance of rigorous analytical techniques to accurately quantify contaminant exposures in complex matrices. Without such techniques, measurements of lead concentrations in calcium supplements may be either erroneously low, by as much as 50%, or below the detection limit needed for new public health criteria. In this study, we determined the lead content of 136 brands of supplements that were purchased in 1996. The calcium in the products was derived from natural sources (bonemeal, dolomite, or oyster shell) or was synthesized and/or refined (chelated and nonchelated calcium). The dried products were acid digested and analyzed for lead by high resolution-inductively coupled plasma-mass spectrometry. The method's limit of quantitation averaged 0.06 microg/g, with a coefficient of variation of 1.7% and a 90-100% lead recovery of a bonemeal standard reference material. Two-thirds of those calcium supplements failed to meet the 1999 California criteria for acceptable lead levels (1.5 microg/daily dose of calcium) in consumer products. The nonchelated synthesized and/or refined calcium products, specifically antacids and infant formulas, had the lowest lead concentrations, ranging from nondetectable to 2.9 microg Pb/g calcium, and had the largest proportion of brands meeting the new criteria (85% of the antacids and 100% of the infant formulas). PMID:10753088

  18. Lead in calcium supplements.

    PubMed Central

    Scelfo, G M; Flegal, A R

    2000-01-01

    Intercalibrated measurements of lead in calcium supplements indicate the importance of rigorous analytical techniques to accurately quantify contaminant exposures in complex matrices. Without such techniques, measurements of lead concentrations in calcium supplements may be either erroneously low, by as much as 50%, or below the detection limit needed for new public health criteria. In this study, we determined the lead content of 136 brands of supplements that were purchased in 1996. The calcium in the products was derived from natural sources (bonemeal, dolomite, or oyster shell) or was synthesized and/or refined (chelated and nonchelated calcium). The dried products were acid digested and analyzed for lead by high resolution-inductively coupled plasma-mass spectrometry. The method's limit of quantitation averaged 0.06 microg/g, with a coefficient of variation of 1.7% and a 90-100% lead recovery of a bonemeal standard reference material. Two-thirds of those calcium supplements failed to meet the 1999 California criteria for acceptable lead levels (1.5 microg/daily dose of calcium) in consumer products. The nonchelated synthesized and/or refined calcium products, specifically antacids and infant formulas, had the lowest lead concentrations, ranging from nondetectable to 2.9 microg Pb/g calcium, and had the largest proportion of brands meeting the new criteria (85% of the antacids and 100% of the infant formulas). Images Figure 1 Figure 2 PMID:10753088

  19. Spin crossover transition of Fe(phen)2(NCS)2: periodic dispersion-corrected density-functional study.

    PubMed

    Bučko, Tomáš; Hafner, Jürgen; Lebègue, Sébastien; Ángyán, János G

    2012-04-28

    Periodic dispersion corrected DFT calculations have been performed to study the spin-crossover transition of Fe(phen)(2)(NCS)(2) in the molecular and in the crystalline state. We show that London dispersion interactions play a crucial role in the cohesion of the crystals. Based on calculations of vibrational eigenstates of the isolated molecule and of the crystalline phase in both the low- and high-spin states, the transition entropies and enthalpies have been calculated. We demonstrate that, due to the stabilization of the low-spin state by intermolecular dispersion forces, the transition enthalpy at the transition temperature is larger for the crystalline phase in comparison with an isolated molecule. The effective coordination number of the nitrogen atoms of the ligands around the iron atom has been identified as the order parameter driving the quasi-reversible low-spin to high-spin transition in the crystal. Finally, using constrained geometry relaxations at fixed values of the coordination number, we computed the energy barrier of the LS to HS transition and found it to be in a reasonable agreement with the experimental value. PMID:22415338

  20. [Intensive care therapy of space-occupying large hemispheric infarction. Summary of the NCS/DGNI guidelines].

    PubMed

    Bösel, J; Schönenberger, S; Dohmen, C; Jüttler, E; Staykov, D; Zweckberger, K; Hacke, W; Schwab, S; Torbey, M T; Huttner, H B

    2015-08-01

    Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference. PMID:26108877

  1. Mixed-state magnetoresistance in organic superconductors {kappa}{endash}(BEDT-TTF){sub 2}Cu(NCS){sub 2}

    SciTech Connect

    Zuo, F.; Schlueter, J.A.; Kelly, M.E.; Williams, J.M.

    1996-11-01

    We report transport measurements with field and current parallel to the {ital a} axis (perpendicular to the conducting plane) in the organic superconductor {kappa}{endash}(BEDT-TTF){sub 2}Cu(NCS){sub 2}. The magnetoresistance displays a peak effect as a function of field and temperature with the peak fields increasing linearly with decreasing temperatures. The peak resistance is found to be greater than the normal-state value extrapolated from both high- and low-field measurements. The results are in sharp contrast to the conventional dissipation mechanisms in the mixed state for anisotropic superconductors, as in the case of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8}. We propose a phenomenological model that the peak in the magnetoresistance is caused by a scattering mechanism due to a strong coupling to the underlying crystal lattice of fluctuating vortices (vortex polarons). The model can semiquantitatively fit the data. {copyright} {ital 1996 The American Physical Society.}

  2. Decoding of calcium signal through calmodulin: calmodulin-binding proteins in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many abiotic and biotic stimuli such as heat, cold, drought, salt, light, wind, touch, wounding, symbionts and pathogens as well as growth, developmental and hormonal cues can quickly induce cytosolic calcium increases. Calmodulin, the most thoroughly studied calcium sensor, mediates interpretation...

  3. Comparative effects of oral aromatic and branched-chain amino acids on urine calcium and excretion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aromatic amino acids (AAAs) bind to the calcium sensor receptor (CaR) but branched-chain amino acids (B-CAAs) do not; by binding to this receptor, AAAs have an increased potential to affect calcium homeostasis. This study was conducted to determine and compare the effects of AAAs and B-CAAs on calci...

  4. [Calcium and health].

    PubMed

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

    2015-01-01

    An adequate intake of calcium is only not limited to avoid the risk of osteoporosis and its benefits in longterm bone health, but also it has been linked to protection against various major diseases, such as hypertension, cancer, kidney stones, insulin resistance, diabetes... and several investigations suggest its importance in preventing and controlling obesity. Studies conducted in Spanish representative samples show that a high percentage of adults and children (> 75%) don't achieve the recommended intake of calcium. Moreover, are growing trends among the population suggesting that calcium intake and dairy consumption (main food source of the mineral) are high, and even excessive, in many individuals. This misconception results in that the calcium intake is increasingly far from the recommended one. The maximum tolerable intake of the mineral is fixed at 2.500 mg/day, but this intake is unusual, and it's more disturbing and frequent, to find intakes below the recommended calcium intakes (1.000 and 1.200 mg/day in adults, men and women, respectively). Data from different studies highlight the risk of an inadequate calcium intake and the damages that may affect the health in a long term. It is not about transmitting indiscriminate guidelines in order to increase the intake of calcium / dairy, but the recommended intakes must be met to achieve both the nutritional and health benefits. Also activities for demystification of misconceptions are need, increasingly frequent, that may impair health population. PMID:25862324

  5. GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent thermotransduction cascade in the AFD neurons responsible for C. elegans thermotaxis

    PubMed Central

    Wang, Dong; O’Halloran, Damien

    2013-01-01

    Certain thermoreceptor neurons are sensitive to tiny thermal fluctuations (0.01°C or less) and maintain their sensitivity across a wide range of ambient temperatures through a process of adaptation, but understanding of the biochemical basis for this performance is rudimentary. Prior studies of the AFD thermoreceptor in Caenorhabditis elegans revealed a signaling cascade that depends on a trio of receptor guanylate cyclases (rGCs), GCY-8, GCY-18, and GCY-23, and gives rise to warming-activated thermoreceptor currents (ThRCs) carried by cyclic GMP–gated ion channels. The threshold for ThRC activation adapts to the ambient temperature through an unknown calcium-dependent process. Here, we use in vivo whole-cell patch-clamp recording from AFD to show that loss of GCY-8, but not of GCY-18 or GCY-23, reduces or eliminates ThRCs, identifying this rGC as a crucial signaling element. To learn more about thermotransduction and adaptation, we used behavioral screens and analysis of gene expression patterns to identify phosphodiesterases (PDEs) likely to contribute to thermotransduction. Deleting PDE-2 decouples the threshold for ThRC activation from ambient temperature, altering adaptation. We provide evidence that the conserved neuronal calcium sensor 1 protein also regulates the threshold for ThRC activation and propose a signaling network to account for ThRC activation and adaptation. Because PDEs play essential roles in diverse biological processes, including vertebrate phototransduction and olfaction, and regulation of smooth muscle contractility and cardiovascular function, this study has broad implications for understanding how extraordinary sensitivity and dynamic range is achieved in cyclic nucleotide–based signaling networks. PMID:24081984

  6. Handling packet dropouts and random delays for unstable delayed processes in NCS by optimal tuning of PIλDμ controllers with evolutionary algorithms.

    PubMed

    Pan, Indranil; Das, Saptarshi; Gupta, Amitava

    2011-10-01

    The issues of stochastically varying network delays and packet dropouts in Networked Control System (NCS) applications have been simultaneously addressed by time domain optimal tuning of fractional order (FO) PID controllers. Different variants of evolutionary algorithms are used for the tuning process and their performances are compared. Also the effectiveness of the fractional order PI(λ)D(μ) controllers over their integer order counterparts is looked into. Two standard test bench plants with time delay and unstable poles which are encountered in process control applications are tuned with the proposed method to establish the validity of the tuning methodology. The proposed tuning methodology is independent of the specific choice of plant and is also applicable for less complicated systems. Thus it is useful in a wide variety of scenarios. The paper also shows the superiority of FOPID controllers over their conventional PID counterparts for NCS applications. PMID:21621208

  7. Note: Inhibiting bottleneck corrosion in electrical calcium tests for ultra-barrier measurements

    NASA Astrophysics Data System (ADS)

    Nehm, F.; Müller-Meskamp, L.; Klumbies, H.; Leo, K.

    2015-12-01

    A major failure mechanism is identified in electrical calcium corrosion tests for quality assessment of high-end application moisture barriers. Accelerated calcium corrosion is found at the calcium/electrode junction, leading to an electrical bottleneck. This causes test failure not related to overall calcium loss. The likely cause is a difference in electrochemical potential between the aluminum electrodes and the calcium sensor, resulting in a corrosion element. As a solution, a thin, full-area copper layer is introduced below the calcium, shifting the corrosion element to the calcium/copper junction and inhibiting bottleneck degradation. Using the copper layer improves the level of sensitivity for the water vapor transmission rate (WVTR) by over one order of magnitude. Thin-film encapsulated samples with 20 nm of atomic layer deposited alumina barriers this way exhibit WVTRs of 6 × 10-5 g(H2O)/m2/d at 38 °C, 90% relative humidity.

  8. Calcium, channels, intracellular signaling and autoimmunity.

    PubMed

    Izquierdo, Jorge-Hernán; Bonilla-Abadía, Fabio; Cañas, Carlos A; Tobón, Gabriel J

    2014-01-01

    Calcium (Ca²⁺) is an important cation able to function as a second messenger in different cells of the immune system, particularly in B and T lymphocytes, macrophages and mastocytes, among others. Recent discoveries related to the entry of Ca²⁺ through the store-operated calcium entry (SOCE) has opened a new investigation area about the cell destiny regulated by Ca²⁺ especially in B and T lymphocytes. SOCE acts through calcium-release-activated calcium (CRAC) channels. The function of CRAC depends of two recently discovered regulators: the Ca²⁺ sensor in the endoplasmic reticulum or stromal interaction molecule (STIM-1) and one subunit of CRAC channels called Orai1. This review focuses on the role of Ca²⁺ signals in B and T lymphocytes functions, the signalling pathways leading to Ca²⁺ influx, and the relationship between Ca²⁺ signals and autoimmune diseases. PMID:24001934

  9. Get Enough Calcium

    MedlinePlus

    ... Previous section Overview 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of ... Foods and Vitamins 3 of 4 sections Take Action: Vitamin D Get enough vitamin D. Vitamin D ...

  10. Stoichiometry of Calcium Medicines

    ERIC Educational Resources Information Center

    Pinto, Gabriel

    2005-01-01

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

  11. Calcium in diet

    MedlinePlus

    ... level based on scientific research evidence. Adequate Intake (AI): This level is established when there is not ... enough calcium from the foods they eat. Infants (AI) 0 to 6 months: 200 milligrams per day ( ...

  12. Calcium pyrophosphate arthritis

    MedlinePlus

    ... that can cause attacks of arthritis. Like with gout, crystals form in the joints. But in calcium ... pyrophosphate arthritis can be misdiagnosed as: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis

  13. Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.

    PubMed

    Cooke, Heather A; Guenther, Elizabeth L; Luo, Yinggang; Shen, Ben; Bruner, Steven D

    2009-10-13

    The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization. PMID:19702337

  14. Locking-to-unlocking system is an efficient strategy to design DNA/silver nanoclusters (AgNCs) probe for human miRNAs

    PubMed Central

    Shah, Pratik; Choi, Suk Won; Kim, Ho-jin; Cho, Seok Keun; Bhang, Yong-Joo; Ryu, Moon Young; Thulstrup, Peter Waaben; Bjerrum, Morten Jannik; Yang, Seong Wook

    2016-01-01

    MicroRNAs (miRNAs), small non-coding RNA molecules, are important biomarkers for research and medical purposes. Here, we describe the development of a fast and simple method using highly fluorescent oligonucleotide-silver nanocluster probes (DNA/AgNCs) to efficiently detect specific miRNAs. Due to the great sequence diversity of miRNAs in humans and other organisms, a uniform strategy for miRNA detection is attractive. The concept presented is an oligonucleotide-based locking-to-unlocking system that can be endowed with miRNA complementarity while maintaining the same secondary structure. The locking-to-unlocking system is based on fold-back anchored DNA templates that consist of a cytosine-rich loop for AgNCs stabilization, an miRNA recognition site and an overlap region for hairpin stabilization. When an miRNA is recognized, fluorescence in the visible region is specifically extinguished in a concentration-dependent manner. Here, the exact composition of the fold-back anchor for the locking-to-unlocking system has been systematically optimized, balancing propensity for loop-structure formation, encapsulation of emissive AgNCs and target sensitivity. It is demonstrated that the applied strategy successfully can detect a number of cancer related miRNAs in RNA extracts from human cancer cell lines. PMID:26681688

  15. Locking-to-unlocking system is an efficient strategy to design DNA/silver nanoclusters (AgNCs) probe for human miRNAs.

    PubMed

    Shah, Pratik; Choi, Suk Won; Kim, Ho-Jin; Cho, Seok Keun; Bhang, Yong-Joo; Ryu, Moon Young; Thulstrup, Peter Waaben; Bjerrum, Morten Jannik; Yang, Seong Wook

    2016-04-01

    MicroRNAs (miRNAs), small non-coding RNA molecules, are important biomarkers for research and medical purposes. Here, we describe the development of a fast and simple method using highly fluorescent oligonucleotide-silver nanocluster probes (DNA/AgNCs) to efficiently detect specific miRNAs. Due to the great sequence diversity of miRNAs in humans and other organisms, a uniform strategy for miRNA detection is attractive. The concept presented is an oligonucleotide-based locking-to-unlocking system that can be endowed with miRNA complementarity while maintaining the same secondary structure. The locking-to-unlocking system is based on fold-back anchored DNA templates that consist of a cytosine-rich loop for AgNCs stabilization, an miRNA recognition site and an overlap region for hairpin stabilization. When an miRNA is recognized, fluorescence in the visible region is specifically extinguished in a concentration-dependent manner. Here, the exact composition of the fold-back anchor for the locking-to-unlocking system has been systematically optimized, balancing propensity for loop-structure formation, encapsulation of emissive AgNCs and target sensitivity. It is demonstrated that the applied strategy successfully can detect a number of cancer related miRNAs in RNA extracts from human cancer cell lines. PMID:26681688

  16. Molecular Basis of Substrate Promiscuity for the SAM-Dependent O-Methyltransferase NcsB1, Involved in the Biosynthesis of the Enediyne Antitumor Antibiotic Neocarzinostatin

    SciTech Connect

    Cooke, H.; Guenther, E; Luo, Y; Shen, B; Bruner, S

    2009-01-01

    The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization.

  17. Risk factors for twelve-month suicide attempts in the National Comorbidity Survey Replication (NCS-R)

    PubMed Central

    Borges, Guilherme; Angst, Jules; Nock, Matthew K.; Ruscio, Ayelet Meron; Walters, Ellen E.; Kessler, Ronald C.

    2007-01-01

    BACKGROUND Clinical judgments about the likelihood of suicide attempt would be aided by an index of risk factors that could be quickly assessed in diverse settings. We sought to develop such a risk index for 12-month suicide attempts among suicide ideators. METHOD The National Comorbidity Survey Replication (NCS-R), a household survey of adults ages 18+, assessed 12-month occurrence of suicide ideation, plans, and attempts in a subsample of 5692 respondents. Retrospectively assessed correlates include history of prior suicidality, socio-demographics, parental psychopathology, and 12-month DSM-IV disorders. RESULTS Twelve-month prevalence estimates of suicide ideation, plans, and attempts are 2.6%, 0.7%, and 0.4%. Although ideators with a plan are more likely to make an attempt (31.9%) than those without a plan (9.6%), 43% of attempts were described as unplanned. History of prior attempts is the strongest correlate of 12-month attempts. Other significant correlates include shorter duration of ideation, presence of a suicide plan, and several socio-demographic and parental psychopathology variables. Twelve-month disorders are not powerful correlates. A four-category summary index of correlates is strongly related to attempts among ideators (AUC = .88). The distribution (conditional probability of attempt) of the risk index is 19.0% very low (0.0%), 51.1% low (3.5%), 16.2% intermediate (21.3%), and 13.7% high (78.1%). Two-thirds (67.1%) of attempts were made by ideators in the high risk category. CONCLUSIONS A short, preliminary risk index based on retrospectively reported responses to fully structured questions is strongly correlated with 12-month suicide attempts among ideators, with a high concentration of attempts among high-risk ideators. PMID:16938149

  18. Pathological Gambling, Problem Gambling and Sleep Complaints: An Analysis of the National Comorbidity Survey: Replication (NCS-R)

    PubMed Central

    Siani, Aaron; Rosenthal, Richard J.; Fong, Timothy W.

    2012-01-01

    The purpose of this study is to investigate the relationship between sleep disturbances and gambling behavior. Data from the National Comorbidity Survey—Replication (NCS-R) was used to examine the relationship between three specific sleep complaints (difficulty initiating sleep [DIS], difficulty maintaining sleep [DMS], and early morning awakening [EMA]) and gambling behavior. Bivariate logistic regression models were used to control for potentially confounding psychiatric disorders and age. Almost half of respondents with problem gambling behavior (45.9%) and two thirds (67.7%) of respondents with pathological gambling behavior reported at least one sleep compliant. Compared to respondents with no gambling pathology, respondents with pathological gambling were significantly more likely to report at least one sleep complaint (Adjusted Odds Ratio [AOR] = 3.444, 95% CI = 1.538–7.713), to report all sleep complaints (AOR = 3.449, 95% CI = 1.503–7.914), and to report any individual complaint (DIS: OR = 2.300, 95% CI = 1.069–4.946; DMS: AOR = 4.604, 95% CI = 2.093–10.129; EMA: AOR = 3.968, 95% CI = 1.856–8.481). The relationship between problem gambling and sleep complaints were more modest (any sleep complaint: AOR = 1.794, 95% CI = 1.142–2.818; all three sleep complaints: AOR = 2.144, 95% CI = 1.169–3.931; DIS: AOR = 1.961, 95% CI = 1.204–3.194; DMS: AOR = 1.551, 95% CI = 0.951–2.529; EMA: AOR = 1.796, 95% CI = 1.099–2.935). Given the individual and societal ramifications linked with the presence of sleep problems, this study presents another health-related repercussion associated with gambling pathology rarely discussed in the literature. PMID:22396174

  19. Synthesis, characterization and crystal structure of a 1D thiocyanato bridged [Cu(en)2Zn(NCS)4]ṡH2O. Comparison of the three structures with the same [Cu(en)2Zn(NCS)4] unit - different in structural terms

    NASA Astrophysics Data System (ADS)

    Wrzeszcz, Grzegorz; Muzioł, Tadeusz M.; Tereba, Natalia

    2015-03-01

    In this paper we report the synthesis method and the structure of a one-dimensional thiocyanato bridged heterometallic compound, [Cu(en)2Zn(NCS)4]ṡH2O (1). Moreover, we compare the structure of (1) with the previously described structures of [Cu(en)2Zn(NCS)4]ṡ0.5H2O (2) and [Cu(en)2Zn(NCS)4]ṡCH3CN (3) Pryma et al. (2003) [7]. The compound (1) has been characterized by thermal decomposition, IR, Vis and EPR spectra, and magnetic studies. Structure has been determined by X-ray analysis. Described coordination polymer crystallizes in the orthorhombic Cmcm space group with a = 12.414(2), b = 10.3276(14), c = 14.967(2) Å, α = β = γ = 90°, V = 1918.8(5) Å3 and Z = 4. Each distorted tetrahedral zinc(II) centre (with N-bonded NCS-) links two tetragonally distorted octahedral copper(II) centres by two end-to-end thiocyanato bridges and vice versa forming a zigzag type of CuZn chain. The structures of (1), (2) and (3) differ in crystallographic system, space group and/or CuZn chain type as well as in details. Variable temperature magnetic susceptibility measurements show very weak antiferromagnetic interactions between the paramagnetic copper(II) ions for compound (1).

  20. NCS TECHNOLOGY WORKSHOP & REPORT

    EPA Science Inventory

    Innovative Technologies for Remote Collection of Data

  21. May 12-14, 2003
  22. Hyatt Harborside Hotel
  23. Boston, MA
  24. This meeting was held in conjunction with the National Children's ...

  1. Calcium decorated and doped phosphorene for gas adsorption

    NASA Astrophysics Data System (ADS)

    Lalitha, Murugan; Nataraj, Yuvarani; Lakshmipathi, Senthilkumar

    2016-07-01

    In this paper, we present the results from first-principles study based on the electronic structure and adsorption characteristics of CH4, CO2, H2 and NH3 adsorbed on Ca decorated/doped phosphorene. Our study finds that phosphorene exhibits n-type behaviour on decorating calcium, and p-type on doping calcium. Gas molecules are physisorbed on both pristine and calcium-mediated phosphorene, visible through their lower binding energy and charge transfer values. Ca decorated phosphorene is suitable for hydrogen storage due to its higher binding energy for H2. Ca doped structures shows increased binding affinity towards CH4 and NH3 in zigzag1 direction and armchair directions respectively. The extracts of our study implies that Ca doped phosphorene possess increased binding affinity towards gas molecules, and the results are highly helpful for gas adsorption and to design gas sensors based on calcium doped or decorated phosphorene.

  2. Current sensor

    DOEpatents

    Yakymyshyn, Christopher Paul; Brubaker, Michael Allen; Yakymyshyn, Pamela Jane

    2007-01-16

    A current sensor is described that uses a plurality of magnetic field sensors positioned around a current carrying conductor. The sensor can be hinged to allow clamping to a conductor. The current sensor provides high measurement accuracy for both DC and AC currents, and is substantially immune to the effects of temperature, conductor position, nearby current carrying conductors and aging.

  3. Modelling of calcium phosphates

    NASA Astrophysics Data System (ADS)

    Calderin Hidalgo, Lazaro Juan

    This work is a contribution to a large scale joint experimental and theoretical effort to understand the biological properties of silicon doped calcium phosphates undertaken by Queen's University and Millenium Biologix Corp. We have modeled calcium phosphates and silicon doped calcium phosphates in close relation to experiment in order to study possible location of silicon in the lattice. Density functional theory has been used to study the structural and dynamical properties of small systems of calcium phosphates to gain preliminary information on phosphates and the performance of the theoretical methods. The same methods were used to investigate structural and electronic properties of larger scale calcium phosphate systems, while a classical shell model was developed to investigate the dynamical properties of such large and complex systems. In the context of the shell model a method was devised to calculate the dynamical matrix corrected for the long range Coulomb interaction in the long wave length limit. It was necessary also to develop a theoretical expression for the dielectric function in the context of the shell model. Infrared spectra and thermal parameters were calculated based on these methods. We also propose some directions for future research.

  4. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    ERIC Educational Resources Information Center

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

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

  5. Calcium and olfactory transduction.

    PubMed

    Winegar, B D; Rosick, E R; Schafer, R

    1988-01-01

    1. Inorganic cations, organic calcium antagonists, and calmodulin antagonists were applied to olfactory epithelia of frogs (Rana pipiens) while recording electroolfactogram (EOG) responses. 2. Inorganic cations inhibited EOGs in a rank order, reflecting their calcium channel blocking potency: La3+ greater than Zn2+ greater than Cd2+ greater than Al3+ greater than Ca2+ greater than Sr2+ greater than Co2+ greater than Ba2+ greater than Mg2+. Barium ion significantly enhanced EOGs immediately following application. 3. Diltiazem and verapamil produced dose-dependent EOG inhibition. 4. Calmodulin antagonists inhibited EOGs without correlation to their anti-calmodulin potency. PMID:2904344

  6. Calcium metabolism in microgravity.

    PubMed

    Heer, M; Kamps, N; Biener, C; Korr, C; Boerger, A; Zittermann, A; Stehle, P; Drummer, C

    1999-09-01

    Unloading of weight bearing bones as induced by microgravity or immobilization has significant impacts on the calcium and bone metabolism and is the most likely cause for space osteoporosis. During a 4.5 to 6 month stay in space most of the astronauts develop a reduction in bone mineral density in spine, femoral neck, trochanter, and pelvis of 1%-1.6% measured by Dual Energy X-ray Absorption (DEXA). Dependent on the mission length and the individual turnover rates of the astronauts it can even reach individual losses of up to 14% in the femoral neck. Osteoporosis itself is defined as the deterioration of bone tissue leading to enhanced bone fragility and to a consequent increase in fracture risk. Thinking of long-term missions to Mars or interplanetary missions for years, space osteoporosis is one of the major concerns for manned spaceflight. However, decrease in bone density can be initiated differently. It either can be caused by increases in bone formation and bone resorption resulting in a net bone loss, as obtained in fast looser postmenopausal osteoporosis. On the other hand decrease in bone formation and increase in bone resorption also leads to bone losses as obtained in slow looser postmenopausal osteoporosis or in Anorexia Nervosa patients. Biomarkers of bone turnover measured during several missions indicated that the pattern of space osteoporosis is very similar to the pattern of Anorexia Nervosa patients or slow looser postmenopausal osteoporosis. However, beside unloading, other risk factors for space osteoporosis exist such as stress, nutrition, fluid shifts, dehydration and bone perfusion. Especially nutritional factors may contribute considerably to the development of osteoporosis. From earthbound studies it is known that calcium supplementation in women and men can prevent bone loss of 1% bone per year. Based on these results we studied the calcium intake during several European missions and performed an experiment during the German MIR 97 mission

  7. Structural aspects of calcium-release activated calcium channel function

    PubMed Central

    Stathopulos, Peter B; Ikura, Mitsuhiko

    2013-01-01

    Store-operated calcium (Ca2+) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca2+ levels by signaling Ca2+ release activated Ca2+ channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca2+ elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca2+ sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca2+ sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations. PMID:24213636

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

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

  10. Children's Bone Health and Calcium

    MedlinePlus

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

  11. Calcium carbonate with magnesium overdose

    MedlinePlus

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

  12. Calcium Content of Common Foods

    MedlinePlus

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

  13. Synthesis, characterization and crystal structures of the bidentate Schiff base N,N'-bis(2-nitrocinnamaldehyde)ethylenediamine and its complex with CuNCS and triphenylphosphane.

    PubMed

    Clegg, William; Harrington, Ross W; Barati, Kazem; Habibi, Mohammad Hossein; Montazerozohori, Morteza; Lalegani, Arash

    2015-07-01

    Reaction of copper(I) thiocyanate and triphenylphosphane with the bidentate Schiff base N,N'-bis(trans-2-nitrocinnamaldehyde)ethylenediamine {Nca2en, (1); systematic name (1E,1'E,2E,2'E)-N,N'-(ethane-1,2-diyl)bis[3-(2-nitrophenyl)prop-2-en-1-imine]}, C20H18N4O4, in a 1:1:1 molar ratio in acetonitrile resulted in the formation of the complex {(1E,1'E,2E,2'E)-N,N'-(ethane-1,2-diyl)bis[3-(2-nitrophenyl)prop-2-en-1-imine]-κ(2)N,N'}(thiocyanato-κN)(triphenylphosphane-κP)copper(I)], [Cu(NCS)(C20H18N4O4)(C18H15P)] or [Cu(NCS)(Nca2en)(PPh3)], (2). The Schiff base and copper(I) complex have been characterized by elemental analyses, IR, electronic and (1)H NMR spectroscopy, and X-ray crystallography [from synchrotron data for (1)]. The molecule of (1) lies on a crystallographic inversion centre, with a trans conformation for the ethylenediamine unit, and displays significant twists from coplanarity of its nitro group, aromatic ring, conjugated chain and especially ethylenediamine segments. It acts as a bidentate ligand coordinating via the imine N atoms to the Cu(I) atom in complex (2), in which the ethylenediamine unit necessarily adopts a somewhat flattened gauche conformation, resulting in a rather bowed shape overall for the ligand. The NCS(-) ligand is coordinated through its N atom. The geometry around the Cu(I) atom is distorted tetrahedral, with a small N-Cu-N bite angle of 81.56 (12)° and an enlarged opposite angle of 117.29 (9)° for SCN-Cu-P. Comparisons are made with the analogous Schiff base having no nitro substituents and with metal complexes of both ligands. PMID:26146396

  14. Synthesis, structural and electrical properties of [C{sub 2}H{sub 10}N{sub 2}][(SnCl(NCS){sub 2}]{sub 2}

    SciTech Connect

    Karoui, Sahel; Kamoun, Slaheddine; Jouini, Amor

    2013-01-15

    Synthesis, structural and electrical properties are given for a new organic stannous pseudo halide material. The structure of the [C{sub 2}H{sub 10}N{sub 2}][(SnCl(NCS){sub 2}]{sub 2} reveals that the adjacent Sn(II) centres are bridged by a pair of SCN{sup -} anions to form a 1-D array giving rise to the anionic chains (SnCl(NCS){sub 2}){sub n}{sup n-}. These chains are themselves interconnected by means of N-H Horizontal-Ellipsis Cl(S) hydrogen bonds originating from the organic cation [(NH{sub 3}){sub 2}(CH{sub 2}){sub 2}]{sup 2+}. The AC impedance measurements were performed as a function of both frequency and temperature. The electrical conduction and dielectric relaxation have been studied. The activation energy associated with the electrical relaxation determined from the electric modulus spectra was found close to that of the activation energy obtained for DC conductivity. The conduction mechanisms are attributed to the quantum mechanical tunneling model in phase I and to the proton hopping among hydrogen vacancies in phase II. - Graphical abstract: Atomic coordination in [C2H10N2][SnCl(NCS)2)2]. Highlights: Black-Right-Pointing-Pointer X-ray diffraction analysis shows the 1D network character of the structure. Black-Right-Pointing-Pointer DSC experiments show a phase transition at 336 K. Black-Right-Pointing-Pointer The AC conductivity is interpreted in terms of Jonsher's law. Black-Right-Pointing-Pointer Two conduction mechanisms are proposed for phase I and II.

  15. A Tiered Framework for Risk-Relevant Characterization and Ranking of Chemical Exposures: Applications to the National Children’s Study (NCS)

    PubMed Central

    Georgopoulos, Panos G.; Brinkerhoff, Christopher J.; Isukapalli, Sastry; Dellarco, Michael; Landrigan, Philip J.; Lioy, Paul J.

    2014-01-01

    A challenge for large-scale environmental health investigations such as the National Children’s Study (NCS), is characterizing exposures to multiple, co-occurring chemical agents with varying spatiotemporal concentrations and consequences modulated by biochemical, physiological, behavioral, socioeconomic, and environmental factors. Such investigations can benefit from systematic retrieval, analysis, and integration of diverse extant information on both contaminant patterns and exposure-relevant factors. This requires development, evaluation, and deployment of informatics methods that support flexible access and analysis of multiattribute data across multiple spatiotemporal scales. A new “Tiered Exposure Ranking” (TiER) framework, developed to support various aspects of risk-relevant exposure characterization, is described here, with examples demonstrating its application to the NCS. TiER utilizes advances in informatics computational methods, extant database content and availability, and integrative environmental/exposure/biological modeling to support both “discovery-driven” and “hypothesis-driven” analyses. “Tier 1” applications focus on “exposomic” pattern recognition for extracting information from multidimensional data sets, whereas second and higher tier applications utilize mechanistic models to develop risk-relevant exposure metrics for populations and individuals. In this article, “tier 1” applications of TiER explore identification of potentially causative associations among risk factors, for prioritizing further studies, by considering publicly available demographic/socioeconomic, behavioral, and environmental data in relation to two health endpoints (preterm birth and low birth weight). A “tier 2” application develops estimates of pollutant mixture inhalation exposure indices for NCS counties, formulated to support risk characterization for these endpoints. Applications of TiER demonstrate the feasibility of developing risk

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

    PubMed

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

    1991-08-01

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

  17. Zeeman-driven phase transition within the superconducting state of {kappa}-(BEDT-TTF){sub 2}Cu(NCS){sub 2}.

    SciTech Connect

    Wright, J. A.; Green, E.; kuhns, P.; Reyes, A.; Brooks, J.; Schlueter, J.; Kato, R.; Yamamoto, H.; Kobayashi, M.; Brown , S. E.

    2011-08-16

    {sup 13}C nuclear magnetic resonance measurements were performed on {kappa}-(BEDT-TTF){sub 2}Cu(NCS){sub 2}, with the external field placed parallel to the quasi-2D conducting layers. The absorption spectrum is used to determine the electronic spin polarization M{sub s} as a function of external field H at a temperature T = 0.35 K. A discontinuity in the derivative dM{sub s}/dH at an applied field of H{sub s} = 213 {+-} 3 kOe is taken as evidence for a Zeeman-driven transition within the superconducting state and stabilization of inhomogeneous superconductivity.

  18. Calcium biofortification of crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adequate intakes of vitamin D and calcium are essential preventative measures and essential components of any therapeutic regimen for osteoporosis. Vitamin D is also important for the prevention of falls. Current evidence suggests that a 25-hydroxyvitamin D level of 75 nmol/L (30 ng/ml) or higher ...

  20. High Blood Calcium (Hypercalcemia)

    MedlinePlus

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

  1. Calcium silicate insulation structure

    DOEpatents

    Kollie, Thomas G.; Lauf, Robert J.

    1995-01-01

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

  2. Diet and calcium stones.

    PubMed Central

    Hughes, J; Norman, R W

    1992-01-01

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

  3. The Plasma Membrane Calcium Pump

    NASA Technical Reports Server (NTRS)

    Rasmussen, H.

    1983-01-01

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

  4. Impregnating Coal With Calcium Carbonate

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  5. Photoelastic sensors

    SciTech Connect

    Kulakov, G.I.

    1985-07-01

    This paper presents the result of a study of photoelastic sensors which makes it possible to explain many mechanical and physical features of the operation of annular photoelastic borehole sensors and to plan ways of utilizing these features for interpreting the sensor readings.

  6. Voltage-Gated Calcium Channels

    NASA Astrophysics Data System (ADS)

    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.

  7. Structure-Function Relationship of a Plant NCS1 Member – Homology Modeling and Mutagenesis Identified Residues Critical for Substrate Specificity of PLUTO, a Nucleobase Transporter from Arabidopsis

    PubMed Central

    Witz, Sandra; Panwar, Pankaj; Schober, Markus; Deppe, Johannes; Pasha, Farhan Ahmad; Lemieux, M. Joanne; Möhlmann, Torsten

    2014-01-01

    Plastidic uracil salvage is essential for plant growth and development. So far, PLUTO, the plastidic nucleobase transporter from Arabidopsis thaliana is the only known uracil importer at the inner plastidic membrane which represents the permeability barrier of this organelle. We present the first homology model of PLUTO, the sole plant NCS1 member from Arabidopsis based on the crystal structure of the benzyl hydantoin transporter MHP1 from Microbacterium liquefaciens and validated by molecular dynamics simulations. Polar side chains of residues Glu-227 and backbones of Val-145, Gly-147 and Thr-425 are proposed to form the binding site for the three PLUTO substrates uracil, adenine and guanine. Mutational analysis and competition studies identified Glu-227 as an important residue for uracil and to a lesser extent for guanine transport. A differential response in substrate transport was apparent with PLUTO double mutants E227Q G147Q and E227Q T425A, both of which most strongly affected adenine transport, and in V145A G147Q, which markedly affected guanine transport. These differences could be explained by docking studies, showing that uracil and guanine exhibit a similar binding mode whereas adenine binds deep into the catalytic pocket of PLUTO. Furthermore, competition studies confirmed these results. The present study defines the molecular determinants for PLUTO substrate binding and demonstrates key differences in structure-function relations between PLUTO and other NCS1 family members. PMID:24621654

  8. Structure-function relationship of a plant NCS1 member--homology modeling and mutagenesis identified residues critical for substrate specificity of PLUTO, a nucleobase transporter from Arabidopsis.

    PubMed

    Witz, Sandra; Panwar, Pankaj; Schober, Markus; Deppe, Johannes; Pasha, Farhan Ahmad; Lemieux, M Joanne; Möhlmann, Torsten

    2014-01-01

    Plastidic uracil salvage is essential for plant growth and development. So far, PLUTO, the plastidic nucleobase transporter from Arabidopsis thaliana is the only known uracil importer at the inner plastidic membrane which represents the permeability barrier of this organelle. We present the first homology model of PLUTO, the sole plant NCS1 member from Arabidopsis based on the crystal structure of the benzyl hydantoin transporter MHP1 from Microbacterium liquefaciens and validated by molecular dynamics simulations. Polar side chains of residues Glu-227 and backbones of Val-145, Gly-147 and Thr-425 are proposed to form the binding site for the three PLUTO substrates uracil, adenine and guanine. Mutational analysis and competition studies identified Glu-227 as an important residue for uracil and to a lesser extent for guanine transport. A differential response in substrate transport was apparent with PLUTO double mutants E227Q G147Q and E227Q T425A, both of which most strongly affected adenine transport, and in V145A G147Q, which markedly affected guanine transport. These differences could be explained by docking studies, showing that uracil and guanine exhibit a similar binding mode whereas adenine binds deep into the catalytic pocket of PLUTO. Furthermore, competition studies confirmed these results. The present study defines the molecular determinants for PLUTO substrate binding and demonstrates key differences in structure-function relations between PLUTO and other NCS1 family members. PMID:24621654

  9. Fruit Calcium: Transport and Physiology.

    PubMed

    Hocking, Bradleigh; Tyerman, Stephen D; Burton, Rachel A; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium

  10. Fruit Calcium: Transport and Physiology

    PubMed Central

    Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium