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Sample records for calcium 39 target

  1. 44gSc from metal calcium targets for PET

    DEFF Research Database (Denmark)

    Severin, Gregory; Gagnon, K.; Engle, J. W.;

    2012-01-01

    A low-cost and efficient method for producing pre-clinical scale quantities of 44gSc is presented. Production involves proton irradiation of natural unenriched calcium metal followed by rapid separation of radioscandium from the target using hydroxmate functionalized resin.© 2012 American Institu...

  2. Target gene analyses of 39 amelogenesis imperfecta kindreds.

    Science.gov (United States)

    Chan, Hui-Chen; Estrella, Ninna M R P; Milkovich, Rachel N; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2011-12-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred.

  3. Novel frontiers in calcium signaling: A possible target for chemotherapy.

    Science.gov (United States)

    Bonora, Massimo; Giorgi, Carlotta; Pinton, Paolo

    2015-09-01

    Intracellular calcium (Ca(2+)) is largely known as a second messenger that is able to drive effects ranging from vesicle formation to muscle contraction, energy production and much more. In spite of its physiological regulation, Ca(2+) is a strategic tool for regulating apoptosis, especially during transmission between the endoplasmic reticulum and the mitochondria. Contact sites between these organelles are well-defined as signaling platforms where oncogenes and oncosuppressors can exert anti/pro-apoptotic activities. Recent advances from in vivo investigations into these regions highlight the role of the master oncosuppressor p53 in regulating Ca(2+) transmission and apoptosis, and we propose that Ca(2+) signals are relevant targets when developing new therapeutic approaches.

  4. Calcium-sensing receptor: a key target for extracellular calcium signaling in neurons

    Directory of Open Access Journals (Sweden)

    Brian L Jones

    2016-03-01

    Full Text Available Though both clinicians and scientists have long recognized the influence of extracellular calcium on the function of muscle and nervous tissue, recent insights reveal that the mechanisms allowing changes in extracellular calcium to alter cellular excitability have been incompletely understood. For many years the effects of calcium on neuronal signaling were explained only in terms of calcium entry through voltage-gated calcium channels and biophysical charge screening. More recently however, it has been recognized that the calcium-sensing receptor is prevalent in the nervous system and regulates synaptic transmission and neuronal activity via multiple signaling pathways. Here we review the multiplicity of mechanisms by which changes in extracellular calcium alter neuronal signaling and propose that multiple mechanisms are required to describe the full range of experimental observations.

  5. Calcium Mass Balance during Citrate Hemodialysis: A Randomized Controlled Trial Comparing Normal and Low Ionized Calcium Target Ranges

    Science.gov (United States)

    Orsag, Alesa; Ponikvar, Rafael; Buturovic-Ponikvar, Jadranka

    2016-01-01

    Background Regional citrate anticoagulation (RCA) during hemodialysis interferes with calcium homeostasis. Optimal ionized calcium (iCa) target range during RCA and consequent calcium balance are unknown. Methods In a randomized controlled trial (ACTRN12613001029785) 30 chronic hemodialysis patients were assigned to normal (1.1–1.2 mmol/) or low (0.95–1.05 mmol/l) iCa target range during a single hemodialysis with RCA. The primary outcome was calcium mass balance during the procedure, using a partial spent dialysate collection method; magnesium mass balance was also measured. Intact parathormone (iPTH), total calcium (tCa) and magnesium were measured before and after procedures. Results Mean iCa during procedures was significantly different in the two groups (1.12±0.06 in normal and 1.06±0.07 mmol/l in low iCa group, p <0.001), resulting in different tCa (2.18±0.22 vs. 1.95±0.17, p = 0.003) after the procedure. Mean delivered calcium during the procedure was 58.3±4.8 mmol in the normal and 51.5±8.2 mmol in the low iCa group (p = 0.010), which resulted in a significantly higher mean positive calcium mass balance of 14.6±8.3 mmol (584±333 mg) per procedure in normal as compared to 7.2±8.5 mmol (290±341 mg) in low iCa group (p = 0.024). Linear mixed effects model showed a significant interaction effect of time and iCa target range group on iPTH, i.e. a significant increase in iPTH in the low as compared to normal iCa target group (p = 0.008). Magnesium mass balance was mildly negative and comparable in both groups. Conclusions Low iCa target range resulted in a significantly less positive calcium mass balance, but in a significant increase in iPTH. To achieve a more neutral calcium balance, we recommend allowing a mild hypocalcemia during hemodialysis with RCA, especially when it is used for prolonged periods. PMID:28030601

  6. The ER mitochondria calcium cycle and ER stress response as therapeutic targets in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Vedrana eTadic

    2014-05-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Although the etiology remains unclear, disturbances in calcium homoeostasis and protein folding are essential features of neurodegeneration in this disorder. Here, we review recent research findings on the interaction between endoplasmic reticulum (ER and mitochondria, and its effect on calcium signaling and oxidative stress. We further provide insights into studies, providing evidence that structures of the ER mitochondria calcium cycle (ERMCC serve as a promising targets for therapeutic approaches for treatment of ALS.

  7. Targeting Calcium Signaling Induces Epigenetic Reactivation of Tumor Suppressor Genes in Cancer.

    Science.gov (United States)

    Raynal, Noël J-M; Lee, Justin T; Wang, Youjun; Beaudry, Annie; Madireddi, Priyanka; Garriga, Judith; Malouf, Gabriel G; Dumont, Sarah; Dettman, Elisha J; Gharibyan, Vazganush; Ahmed, Saira; Chung, Woonbok; Childers, Wayne E; Abou-Gharbia, Magid; Henry, Ryan A; Andrews, Andrew J; Jelinek, Jaroslav; Cui, Ying; Baylin, Stephen B; Gill, Donald L; Issa, Jean-Pierre J

    2016-03-15

    Targeting epigenetic pathways is a promising approach for cancer therapy. Here, we report on the unexpected finding that targeting calcium signaling can reverse epigenetic silencing of tumor suppressor genes (TSG). In a screen for drugs that reactivate silenced gene expression in colon cancer cells, we found three classical epigenetic targeted drugs (DNA methylation and histone deacetylase inhibitors) and 11 other drugs that induced methylated and silenced CpG island promoters driving a reporter gene (GFP) as well as endogenous TSGs in multiple cancer cell lines. These newly identified drugs, most prominently cardiac glycosides, did not change DNA methylation locally or histone modifications globally. Instead, all 11 drugs altered calcium signaling and triggered calcium-calmodulin kinase (CamK) activity, leading to MeCP2 nuclear exclusion. Blocking CamK activity abolished gene reactivation and cancer cell killing by these drugs, showing that triggering calcium fluxes is an essential component of their epigenetic mechanism of action. Our data identify calcium signaling as a new pathway that can be targeted to reactivate TSGs in cancer.

  8. Direct imaging of ER calcium with targeted-esterase induced dye loading (TED).

    Science.gov (United States)

    Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

    2013-05-07

    Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca(2+) indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca(2+) indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca(2+) indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca(2+) indicator and a hydrophilic fluorescent dye/Ca(2+) complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0.

  9. Manufacturing of calcium, lithium and molybdenum targets for use in nuclear physics experiments

    Science.gov (United States)

    Kheswa, N. Y.; Papka, P.; Buthelezi, E. Z.; Lieder, R. M.; Neveling, R.; Newman, R. T.

    2010-02-01

    This paper describes methods used in the manufacturing of chemically reactive targets such as calcium ( natCa), lithium-6 ( 6Li) and molybdenum-97 ( 97Mo) for nuclear physics experiments at the iThemba LABS cyclotron facility (Faure, South Africa). Due to the chemical properties of these materials a suitable and controlled environment was established in order to minimize oxygen contamination of targets. Calcium was prepared by means of vacuum evaporation while lithium was cold rolled to a desired thickness. In the case of molybdenum, the metallic powder was melted under vacuum using an e-gun followed by cold rolling of the metal bead to a desired thickness. In addition, latest developments toward the establishment of a dedicated nuclear physics target laboratory are discussed.

  10. Manufacturing of calcium, lithium and molybdenum targets for use in nuclear physics experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kheswa, N.Y., E-mail: kheswa@tlabs.ac.z [iThemba Laboratory for Accelerator Based Science, P.O. Box 722, Somerset West 7129, Western Cape (South Africa); Papka, P.; Buthelezi, E.Z.; Lieder, R.M.; Neveling, R.; Newman, R.T. [iThemba Laboratory for Accelerator Based Science, P.O. Box 722, Somerset West 7129, Western Cape (South Africa)

    2010-02-11

    This paper describes methods used in the manufacturing of chemically reactive targets such as calcium ({sup nat}Ca), lithium-6 ({sup 6}Li) and molybdenum-97 ({sup 97}Mo) for nuclear physics experiments at the iThemba LABS cyclotron facility (Faure, South Africa). Due to the chemical properties of these materials a suitable and controlled environment was established in order to minimize oxygen contamination of targets. Calcium was prepared by means of vacuum evaporation while lithium was cold rolled to a desired thickness. In the case of molybdenum, the metallic powder was melted under vacuum using an e-gun followed by cold rolling of the metal bead to a desired thickness. In addition, latest developments toward the establishment of a dedicated nuclear physics target laboratory are discussed.

  11. Superparamagnetic calcium ferrite nanoparticles synthesized using a simple sol-gel method for targeted drug delivery.

    Science.gov (United States)

    Sulaiman, N H; Ghazali, M J; Majlis, B Y; Yunas, J; Razali, M

    2015-01-01

    The calcium ferrite nano-particles (CaFe2O4 NPs) were synthesized using a sol-gel method for targeted drug delivery application. The proposed nano-particles were initially prepared by mixing calcium and iron nitrates that were added with citric acid in order to prevent agglomeration and subsequently calcined at a temperature of 550°C to obtain small particle size. The prepared nanoparticles were characterized by using an XRD (X-ray diffraction), which revealed the configuration of orthorhombic structures of the CaFe2O4 nano-particles. A crystallite size of ~13.59 nm was obtained using a Scherer's formula. Magnetic analysis using a VSM (Vibrating Sample Magnetometer analysis), revealed that the synthesized particles exhibited super-paramagnetic behavior having magnetization saturation of approximately 88.3emu/g. Detailed observation via the scanning electron microscopy (SEM) showed the calcium ferrite nano-particles were spherical in shape.

  12. Antibody-conjugated soybean oil-filled calcium phosphate nanoshells for targetted delivery of hydrophobic molecules.

    Science.gov (United States)

    Schmidt, H T; Kroczynski, M; Maddox, J; Chen, Y; Josephs, R; Ostafin, A E

    2006-11-01

    Hollow calcium phosphate nanoparticles capable of encapsulating poorly water-soluble molecules were produced by self-assembly. Previously reported were solid calcium phosphate nanoparticles and water-filled calcium phosphate nanocapsules suited for encapsulating mostly hydrophilic, but not hydrophobic compounds. Here, calcium phosphate was deposited around 100 nm diameter, 1,2-dioleoyl-sn-glycero-3-phosphate stabilized soybean oil nanoemulsions using either calcium chloride or NaOH titrations to achieve shell thickness between 20-70 nm. The surface was functionalized with carboxylic acid via the addition of carboxyethylphosphonic acid to attach Molecular Probes AB-594C antibody using sulpho-n-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with an efficiency of approximately 70%, while retaining near complete antibody function. Hydrophobic pyrene was encapsulated with an efficiency of 95%, at concentrations much higher than its water solubility limit, and exhibited spectral features characteristic of a hydrophobic environment. These materials can be used in the targeted delivery of many useful, yet poorly water-soluble pharmaceutical and nutraceutical compounds.

  13. Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

    Energy Technology Data Exchange (ETDEWEB)

    Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim, E-mail: joachimloo@ntu.edu.sg [Nanyang Technological University, School of Materials Science and Engineering (Singapore)

    2012-06-15

    Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

  14. Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors.

    Science.gov (United States)

    Eyckmans, Jeroen; Roberts, Scott J; Bolander, Johanna; Schrooten, Jan; Chen, Christopher S; Luyten, Frank P

    2013-06-01

    Although calcium phosphate-containing biomaterials are promising scaffolds for bone regenerative strategies, the osteoinductive capacity of such materials is poorly understood. In this study, we investigated whether endogenous mechanisms of in vivo calcium phosphate-driven, ectopic bone formation could be identified and used to induce enhanced differentiation in vitro of the same progenitor population. To accomplish this, human periosteum derived cells (hPDCs) were seeded on hydroxyapatite/collagen scaffolds (calcium phosphate rich matrix or CPRM), or on decalcified scaffolds (calcium phosphate depleted matrix or CPDM), followed by subcutaneous implantation in nude mice to trigger ectopic bone formation. In this system, osteoblast differentiation occurred in CPRM scaffolds, but not in CPDM scaffolds. Gene expression was assessed by human full-genome microarray at 20 h after seeding, and 2, 8 and 18 days after implantation. In both matrices, implantation of the cell constructs triggered a similar gene expression cascade, however, gene expression dynamics progressed faster in CPRM scaffolds than in CPDM scaffolds. The difference in gene expression dynamics was associated with differential activation of hub genes and molecular signaling pathways related to calcium signaling (CREB), inflammation (TNFα, NFkB, and IL6) and bone development (TGFβ, β-catenin, BMP, EGF, and ERK signaling). Starting from this set of pathways, a growth factor cocktail was developed that robustly enhanced osteogenesis in vitro and in vivo. Taken together, our data demonstrate that through the identification and subsequent stimulation of genes, proteins and signaling pathways associated with calcium phosphate mediated osteoinduction, a focused approach to develop targeted differentiation protocols in adult progenitor cells can be achieved.

  15. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

    Full Text Available Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1 is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for

  16. LFP-guided targeting of a cortical barrel column for in vivo two-photon calcium imaging.

    Science.gov (United States)

    Lee, Joon-Hyuk; Shin, Hee-Sup; Lee, Kwang-Hyung; Chung, Sooyoung

    2015-10-29

    Two-photon microscopy of bulk-loaded functional dyes is an outstanding physiological technique that enables simultaneous functional mapping of hundreds of brain cells in vivo at single-cell resolution. However, precise targeting of a specific cortical location is not easy due to its fine dimensionality. To enable precise targeting, intrinsic-signal optical imaging is often additionally performed. However, the intrinsic-signal optical imaging is not only time-consuming but also ineffective in ensuring precision. Here, we propose an alternative method for precise targeting based on local field potential (LFP) recording, a conventional electrophysiological method. The heart of this method lies in use of the same glass pipette to record LFPs and to eject calcium dye. After confirming the target area by LFP using a glass pipette, the calcium dye is ejected from the same pipette without a time delay or spatial adjustment. As a result, the calcium dye is loaded into the same ensemble of brain cells from which the LFP was obtained. As a validation of the proposed LFP-based method, we targeted and successfully loaded calcium dye into layer 2/3 of a mouse barrel column.

  17. MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter.

    Science.gov (United States)

    Pan, Lei; Huang, Bi-Jun; Ma, Xiu-E; Wang, Shi-Yi; Feng, Jing; Lv, Fei; Liu, Yuan; Liu, Yi; Li, Chang-Ming; Liang, Dan-Dan; Li, Jun; Xu, Liang; Chen, Yi-Han

    2015-03-10

    MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H2O2, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.

  18. Current data with inulin-type fructans and calcium, targeting bone health in adults.

    Science.gov (United States)

    Coxam, Véronique

    2007-11-01

    In humans, there is increasing evidence that the colon can absorb nutritionally significant amounts of calcium, and this process may be susceptible to dietary manipulation by fermentable substrates, especially inulin-type fructans. Inulin-type fructans can modulate calcium absorption because they are resistant to hydrolysis by mammalian enzymes and are fermented in the large intestine to produce short-chain fatty acids, which in turn reduce luminal pH and modify calcium speciation, and hence solubility, or exert a direct effect on the mucosal transport pathway. Quite a few intervention studies showed an improvement of calcium absorption in adolescents or young adults by inulin-type fructans. In the same way, a positive effect has been reported in older women.

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

    Energy Technology Data Exchange (ETDEWEB)

    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..

  20. The multifunctional role of calcium in the heart: a tempting target

    OpenAIRE

    Bourgonje, V J A

    2013-01-01

    The sole purpose of the heart is to pump blood through the body. In order to achieve this, it is important that the rhythm is regular and controlled, that the contractile force of the muscle is sufficient, and that the macrostructure of the heart retains the right balance, between for example wall thickness and volume of the lumen. Remarkably, calcium plays an important role in all these processes. This multifaceted role of calcium in the heart is mirrored in what happens in pathology. Distur...

  1. Systemic delivery of siRNA by hyaluronan-functionalized calcium phosphate nanoparticles for tumor-targeted therapy

    Science.gov (United States)

    Qiu, Chong; Wei, Wei; Sun, Jing; Zhang, Hai-Tao; Ding, Jing-Song; Wang, Jian-Cheng; Zhang, Qiang

    2016-06-01

    In this study, hyaluronan (HA)-functionalized calcium phosphate nanoparticles (CaP-AHA/siRNA NPs) were developed for an injectable and targetable delivery of siRNA, which were prepared by coating the alendronate-hyaluronan graft polymer (AHA) around the surface of calcium phosphate-siRNA co-precipitates. The prepared CaP-AHA/siRNA NPs had a uniform spherical core-shell morphology with an approximate size of 170 nm and zeta potential of -12 mV. The coating of hydrophilic HA improved the physical stability of nanoparticles over one month due to the strong interactions between phosphonate and calcium. In vitro experiments demonstrated that the negatively charged CaP-AHA/siRNA NPs could effectively deliver EGFR-targeted siRNA into A549 cells through CD44-mediated endocytosis and significantly down-regulate the level of EGFR expression. Also, the internalized CaP-AHA/siRNA NPs exhibited a pH-responsive release of siRNA, indicating that the acidification of lysosomes probably facilitated the disassembling of nanoparticles and the resultant ions sharply increased the inner osmotic pressure and thus expedited the release of siRNA from late lysosomes into the cytoplasm. Furthermore, in vivo tumor therapy demonstrated that high accumulation of CaP-AHA/siEGFR NPs in tumor led to a significant tumor growth inhibition with a specific EGFR gene silencing effect after intravenous administration in nude mice xenografted with A549 tumor, along with a negligible body weight loss. These results suggested that the CaP-AHA/siRNA NPs could be an effective and safe systemic siRNA delivery system for a RNAi-based tumor targeted therapy strategy.In this study, hyaluronan (HA)-functionalized calcium phosphate nanoparticles (CaP-AHA/siRNA NPs) were developed for an injectable and targetable delivery of siRNA, which were prepared by coating the alendronate-hyaluronan graft polymer (AHA) around the surface of calcium phosphate-siRNA co-precipitates. The prepared CaP-AHA/siRNA NPs had a uniform

  2. Calcium-dependent modulation and plasma membrane targeting of the AKT2 potassium channel by the CBL4/ CIPK6 calcium sensor/protein kinase complex

    Institute of Scientific and Technical Information of China (English)

    Katrin Held; Jean-Baptiste Thibaud; J(o)rg Kudla; Francois Pascaud; Christian Eckert; Pawel Gajdanowicz; Kenji Hashimoto; Claire Corratgé-Faillie; Jan Niklas Offenborn; Beno(i)t Lacombe; Ingo Dreyer

    2011-01-01

    Potassium (K+) channel function is fundamental to many physiological processes. However, components and mechanisms regulating the activity of plant K+ channels remain poorly understood. Here, we show that the calcium (Ca2+)sensor CBL4 together with the interacting protein kinase CIPK6 modulates the activity and plasma membrane (PM)targeting of the K+ channel AKT2 from Arabidopsis thaliana by mediating translocation of AKT2 to the PM in plant cells and enhancing AKT2 activity in oocytes. Accordingly, akt2, cbl4 and cipk6 mutants share similar developmental and delayed flowering pheuotypes. Moreover, the isolated regulatory C-terminal domain of CIPK6 is sufficient for mediating CBL4- and Ca2+-dependent channel translocation from the endoplasmic reticulum membrane to the PM by a novel targeting pathway that is dependent on dual lipid modifications of CBL4 by myristoylation and palmitoylation. Thus, we describe a critical mechanism of ion-channel regulation where a Ca2+ sensor modulates K+ channel activity by promoting a kinase interaction-dependent but phosphorylation-independent translocation of the channel to the PM.

  3. Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland)

    2011-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). The antagonist {sup 125}I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic {beta}-cells and mouse insulinomas, but it does not label human pancreatic {beta}-cells and insulinomas. High affinity displacement (IC{sub 50} approximately 2 nM) is observed in mouse {beta}-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist {sup 125}I-GLP-1(7-36)amide intensively labels mouse pancreatic {beta}-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amide. (orig.)

  4. 钙结合蛋白在前列腺癌中的下调表达及其临床意义%The clinical significance of decreased expression of calcium binding protein 39 in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    朱建国; 陈卫红; 徐述雄; 王元林; 孙兆林; 何慧婵; 钟惟德

    2013-01-01

    目的 探讨钙结合蛋白(CAB39)在前列腺癌中的作用及其临床意义.方法 应用蛋白组学二维荧光差异凝胶电泳(2D-DIGE)技术筛选出在局限性前列腺癌与癌旁组织差异性表达的CAB39蛋白,质谱分析(MS)鉴定、免疫组织化学技术检测CAB39蛋白在24例前列腺癌与癌旁组织中的表达,结合CAB39免疫组织化学评分和前列腺癌患者的临床病理参数进行分析.结果 CAB39蛋白在癌旁组织中的免疫组织化学染色阳性率高于前列腺癌组织(70.8%比33.3%,P<0.01),CAB39蛋白表达在前列腺癌患者年龄、血清前列腺特异抗原(PSA)水平、Gleason评分和肿瘤TNM分期各不同分组中的差异均无统计学意义(P>0.05).结论 CAB39蛋白在前列腺癌患者中下调表达,它可能是前列腺癌抑制因子.%Objective To explore the role and clinical significance of calcium binding protein 39 (CAB39) protein in prostate cancer (PCa).Methods Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) to screen CAB39 protein in PCa and adjacent tissues,and mass spectrometry analysis verification,to analyze the differentially expressed degree of CAB39 protein in 24 cases of PCa and adjacent tissues by immunohistochemical (IHC) technology,the combination of CAB39 IHC score and clinicopathological parameters of PCa patients were analyzed.Results Using the method of IHC,we found that the expression of CAB39 protein in adjacent tissues was significantly higher than that in PCa tissues (70.8% vs 33.3%,P <0.01).The expression of CAB39 protein in different age stages of PCa patients,serum PSA levels,Gleason score and TNM stage in tumor group had no significant difference(P >0.05).Conclusion CAB39 protein is down-regulated expression in PCa,it may be prostate tumor suppressor.

  5. Intracellular calcium mobilization as a target for the spasmolytic action of scopoletin.

    Science.gov (United States)

    Oliveira, E J; Romero, M A; Silva, M S; Silva, B A; Medeiros, I A

    2001-10-01

    The coumarin scopoletin was isolated in a pure form from the roots of Brunfelsia hopeana Benth. (Solanaceae). In isolated rat aortic rings, scopoletin (26-520 microM) inhibited to approximately the same extent the contractions induced by a variety of substances, including phenylephrine, potassium chloride, serotonin and PGF(2) (alpha). The effect of the coumarin on phenylephrine-induced contractions was not affected by endothelium removal or NO-synthase blockade by L-NAME (100 microM). Scopoletin (78 - 590 microM) antagonized in a concentration-dependent manner (IC(50) = 300 +/- 20 microM, n = 5), transient contractions in Ca(2+)-free media induced by noradrenaline, but not those induced by caffeine. Also, scopoletin did not interfere with the refilling of noradrenaline-sensitive intracellular calcium stores. It is suggested that the non-specific spasmolytic action of scopoletin can be attributed, at least in part, to its ability to inhibit the intracellular calcium mobilization from the noradrenaline-sensitive stores.

  6. Involvement of EZH2, SUV39H1, G9a and associated molecules in pathogenesis of urethane induced mouse lung tumors: Potential targets for cancer control

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Manuraj; Sahay, Satya; Tiwari, Prakash [Carcinogenesis Laboratory, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow –226001 (India); Upadhyay, Daya S. [Laboratory Animals Services, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow (India); Sultana, Sarwat [Dept. Medical Elementology and Toxicology, Jamia Hamdard, Hamdard Nagar, New Delhi (India); Gupta, Krishna P., E-mail: krishnag522@yahoo.co.in [Carcinogenesis Laboratory, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow –226001 (India)

    2014-10-15

    In the present study, we showed the correlation of EZH2, SUV39H1 or G9a expression and histone modifications with the urethane induced mouse lung tumorigenesis in the presence or absence of antitumor agent, inositol hexaphosphate (IP6). Tumorigenesis and the molecular events involved therein were studied at 1, 4, 12 or 36 weeks after the exposure. There were no tumors at 1 or 4 weeks but tumors started appearing at 12 weeks and grew further till 36 weeks after urethane exposure. Among the molecular events, upregulation of EZH2 and SUV39H1 expressions appeared to be time dependent, but G9a expression was altered significantly only at later stages of 12 or 36 weeks. Alteration in miR-138 expression supports the upregulation of its target, EZH2. H3K9me2, H3K27me3 or H4K20me3 was found to be altered at 12 or 36 weeks. However, ChIP analysis of p16 and MLH1 promoters showed their binding with H3K9me2 and H3K27me3 which was maximum at 36 weeks. Thus, histone modification and their interactions with gene promoter resulted in the reduced expression of p16 and MLH1. IP6 prevented the incidence and the size of urethane induced lung tumors. IP6 also prevented the urethane induced alterations in EZH2, SUV39H1, G9a expressions and histone modifications. Our results suggest that the alterations in the histone modification pathways involving EZH2 and SUV39H1 expressions are among the early events in urethane induced mouse lung tumorigenesis and could be exploited for cancer control. - Highlights: • Urethane induces mouse lung tumor in a time dependent manner. • EZH2, SUV39H1, G9a induced by urethane and progress with time • Downregulation of miRNA-138 supports the EZH2 upregulation. • Methylation of histones showed a consequence of upregulated EZH2, SUV39H1 and G9a. • IP6 inhibits urethane induced changes and prevents tumor development.

  7. The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro.

    Science.gov (United States)

    Gerő, Domokos; Torregrossa, Roberta; Perry, Alexis; Waters, Alicia; Le-Trionnaire, Sophie; Whatmore, Jacqueline L; Wood, Mark; Whiteman, Matthew

    2016-11-01

    The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30-300nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30-300nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications.

  8. Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery.

    Science.gov (United States)

    Agarwal, Tarun; Narayana, S N Gautham Hari; Pal, Kunal; Pramanik, Krishna; Giri, Supratim; Banerjee, Indranil

    2015-04-01

    The present study delineates preparation, characterization and application of calcium alginate (CA)-carboxymethyl cellulose (CMC) beads for colon-specific oral drug delivery. Here, we exploited pH responsive swelling, mucoadhesivity and colonic microflora-catered biodegradability of the formulations for colon-specific drug delivery. The CA-CMC beads were prepared by ionic gelation method and its physicochemical characterization was done by SEM, XRD, EDAX, DSC and texture analyzer. The swelling and mucoadhesivity of the beads was found higher at the simulated colonic environment. Variation was more prominent in compositions with lower CMC concentrations. CA-CMC formulations degraded slowly in simulated colonic fluid, however the degradation rate increased drastically in the presence of colonic microflora. In vitro release study of anticancer drug 5-fluorouracil (5-FU) showed a release (>90%) in the presence of colonic enzymes. A critical analysis of drug release profile along with FRAP (fluorescence recovery after photobleaching) study revealed that the presence of CMC in the formulation retarded the release rate of 5-FU. 5-FU-loaded formulations were tested against colon adenocarcinoma cells (HT-29). Cytotoxicity data, nuclear condensation-fragmentation and apoptosis analysis (by flow cytometry) together confirmed the therapeutic potential of the CA-CMC formulations. In conclusion, CA-CMC beads can be used for colon-specific drug delivery.

  9. Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation.

    Directory of Open Access Journals (Sweden)

    Zhiling Zhang

    Full Text Available Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca(2+ is less stable at acidic pH, enabling 'smart' drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca(2+ concentration, and Ca(2+ incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca(2+ binding affinity, enabling its use in a variety of biomedical applications.

  10. Does extracellular calcium determine what pool of GABA is the target for alpha-latrotoxin?

    Science.gov (United States)

    Storchak, L G; Linetska, M V; Himmelreich, N H

    2002-04-01

    Presynaptic neurotoxin alpha-latrotoxin, from the venom of Latrodectus mactans tredecimguttatus, causes massive [(3)H]GABA release from rat brain synaptosomes, irrespective of calcium presence in the extracellular medium. Whether the binding of alpha-latrotoxin to Ca(2+)-dependent (neurexin 1 alpha) or to Ca(2+)-independent (latrophilin) receptor triggers [(3)H]GABA release by the same mechanisms or different ones, inducing either exocytotic process or outflow by mobile membrane GABA transporter, is unknown. We examined alpha-latrotoxin-evoked [(3)H]GABA release from synaptosomes which cytosolic [(3)H]GABA pool was depleted either by applying competitive inhibitors of the GABA transporter, nipecotic acid and 2,4-diaminobutyric acid, or by permeation with digitonin. We also compared the effect of the GABA transporter inhibitors on depolarisation-evoked and alpha-latrotoxin-evoked [(3)H]GABA release using as depolarising agents 4-aminopyridine and high KCl in the Ca(2+)-containing and in Ca(2+)-free medium, respectively. Incubation of synaptosomes with nipecotic acid induced the essential acceleration of unstimulated [(3)H]GABA release and deep inhibition of high KCl-evoked Ca(2+)-independent [(3)H]GABA release. In contrast, at the similar conditions the effect of alpha-latrotoxin was greatly augmented with respect to the control response. Another way to assay what GABA pool was involved in alpha-latrotoxin-induced release lays in an analysis of the effects of depolarisation and alpha-latrotoxin in consecutive order. The preliminary 4-aminopyridine-stimulated [(3)H]GABA release attenuated the toxin effect. But when depolarisation occurred in Ca(2+)-free medium, no influence on alpha-latrotoxin effect was revealed. Employing digitonin-permeated synaptosomes, we have shown that alpha-latrotoxin could stimulate [3H]GABA release in the medium with 1mM EGTA, this effect of the toxin was blocked by concanavalin A and was ATP-dependent. The latter suggests that alpha

  11. Bone Is a Major Target of PTH/PTHrP Receptor Signaling in Regulation of Fetal Blood Calcium Homeostasis.

    Science.gov (United States)

    Hirai, Takao; Kobayashi, Tatsuya; Nishimori, Shigeki; Karaplis, Andrew C; Goltzman, David; Kronenberg, Henry M

    2015-08-01

    The blood calcium concentration during fetal life is tightly regulated within a narrow range by highly interactive homeostatic mechanisms that include transport of calcium across the placenta and fluxes in and out of bone; the mechanisms of this regulation are poorly understood. Our findings that endochondral bone-specific PTH/PTHrP receptor (PPR) knockout (KO) mice showed significant reduction of fetal blood calcium concentration compared with that of control littermates at embryonic day 18.5 led us to focus on bone as a possibly major determinant of fetal calcium homeostasis. We found that the fetal calcium concentration of Runx2 KO mice was significantly higher than that of control littermates, suggesting that calcium flux into bone had a considerable influence on the circulating calcium concentration. Moreover, Runx2:PTH double mutant fetuses showed calcium levels similar to those of Runx2 KO mice, suggesting that part of the fetal hypocalcemia in PTH KO mice was caused by the increment of the mineralized bone mass allowed by the formation of osteoblasts. Finally, Rank:PTH double mutant mice had a blood calcium concentration even lower than that of the either Rank KO or PTH KO mice alone at embryonic day 18.5. These observations in our genetic models suggest that PTH/PTHrP receptor signaling in bones has a significant role of the regulation of fetal blood calcium concentration and that both placental transport and osteoclast activation contribute to PTH's hypercalcemic action. They also show that PTH-independent deposition of calcium in bone is the major controller of fetal blood calcium level.

  12. Separation of cyclotron-produced 44Sc from a natural calcium target using a dipentyl pentylphosphonate functionalized extraction resin

    Science.gov (United States)

    Valdovinos, H.F.; Hernandez, R.; Barnhart, T.E.; Graves, S.; Cai, W.; Nickles, R.J.

    2014-01-01

    Significant interest in 44Sc as a radioactive synthon to label small molecules for positron emission tomography (PET) imaging has been recently observed. Despite the efforts of several research groups, the ideal 44Sc production and separation method remains elusive. Herein, we propose a novel separation method to obtain 44Sc from the proton irradiation of calcium targets based on extraction chromatography, which promises to greatly simplify current production methodologies. Using the commercially available Uranium and Tetravalent Actinides (UTEVA) extraction resin we were able to rapidly ( 80% of the activity generated at end of bombardment (EoB) in small ~1 M HCl fractions (400 μL). The chemical purity of the 44Sc eluates was evaluated through chelation with DOTA and DTPA, and by trace metal analysis using microwave induced plasma atomic emission spectrometry. The distribution coefficients (Kd) of Sc(III) and Ca(II) in UTEVA were determined in HCl medium in a range of concentrations from zero to 12.1 M The 44Sc obtained with our method proved to be suitable for the direct labeling of small biomolecules for PET imaging, with excellent specific activities and radiochemical purity. PMID:25464172

  13. Development and implementation of a high-throughput compound screening assay for targeting disrupted ER calcium homeostasis in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Kamran Honarnejad

    Full Text Available Disrupted intracellular calcium homeostasis is believed to occur early in the cascade of events leading to Alzheimer's disease (AD pathology. Particularly familial AD mutations linked to Presenilins result in exaggerated agonist-evoked calcium release from endoplasmic reticulum (ER. Here we report the development of a fully automated high-throughput calcium imaging assay utilizing a genetically-encoded FRET-based calcium indicator at single cell resolution for compound screening. The established high-throughput screening assay offers several advantages over conventional high-throughput calcium imaging technologies. We employed this assay for drug discovery in AD by screening compound libraries consisting of over 20,000 small molecules followed by structure-activity-relationship analysis. This led to the identification of Bepridil, a calcium channel antagonist drug in addition to four further lead structures capable of normalizing the potentiated FAD-PS1-induced calcium release from ER. Interestingly, it has recently been reported that Bepridil can reduce Aβ production by lowering BACE1 activity. Indeed, we also detected lowered Aβ, increased sAPPα and decreased sAPPβ fragment levels upon Bepridil treatment. The latter findings suggest that Bepridil may provide a multifactorial therapeutic modality for AD by simultaneously addressing multiple aspects of the disease.

  14. Vincristine-sulphate-loaded liposome-templated calcium phosphate nanoshell as potential tumor-targeting delivery system.

    Science.gov (United States)

    Thakkar, Hetal Paresh; Baser, Amit Kumar; Parmar, Mayur Prakashbhai; Patel, Ketul Harshadbhai; Ramachandra Murthy, Rayasa

    2012-06-01

    Vincristine-sulfate-loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate-coated liposomes show higher cell uptake than uncoated liposomes.

  15. The influence of target stoichiometry on early cell adhesion of co-sputtered calcium-phosphate surfaces.

    Science.gov (United States)

    Boyd, A R; O'Kane, C; O'Hare, P; Burke, G A; Meenan, B J

    2013-12-01

    The nature of the initial interaction between calcium phosphate (Ca-P) thin films and osteoblasts can be influenced by a number of different properties including the phase, crystallinity, stoichiometry and composition of the surface. There is still a strong interest in developing and studying Ca-P surfaces that have the ability to accurately control the osteoblast response. Radio frequency (RF) magnetron sputtering is a technique that allows for accurate control of the properties of deposited Ca-P coatings and has been studied extensively because of this fact. In this work, Ca-P coatings were co-deposited using RF magnetron sputtering in order to study the effect of changing the target stoichiometry on the initial in vitro behavior of MG63 osteoblast-like cells. The samples produced were analysed both as-deposited and after thermal annealing to 500 °C. After annealing XPS analyses of the samples co-deposited using tricalcium phosphate (TCP) materials gave a Ca/P ratio of 1.71 ± 0.01, as compared to those co-deposited from hydroxyapatite (HA) materials, with a Ca/P of 1.82 ± 0.06. In addition to this, the curve fitted XPS data indicated the presence of low levels of carbonate in the coatings. Despite this the XRD results for all of the annealed coatings were shown to be characteristic of pure HA with a preferred 002 orientation. The atomic force microscopy results also highlighted that both types of coatings had surface features of a similar size (200-220 nm). Both surfaces exhibited a degree of surface degradation, even after 1 h of cell culture. However, the TCP derived surfaces showed an enhanced osteoblastic cell response in terms of cell adhesion and cell proliferation in the earlier stages of cell culture than the surfaces deposited from HA. An improvement in the initial cell attachment and a potential for increased cell proliferation rates is viewed as a highly advantageous result in relation to controlling the osteoblast response on these surfaces.

  16. 1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components.

    Science.gov (United States)

    Lee, Seong Min; Riley, Erin M; Meyer, Mark B; Benkusky, Nancy A; Plum, Lori A; DeLuca, Hector F; Pike, J Wesley

    2015-07-17

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) plays an integral role in calcium homeostasis in higher organisms through its actions in the intestine, kidney, and skeleton. Interestingly, although several intestinal genes are known to play a contributory role in calcium homeostasis, the entire caste of key components remains to be identified. To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with vehicle or 1,25(OH)2D3 and evaluated 6 h later. RNA samples from the duodena were then subjected to RNA sequence analysis, and the data were analyzed bioinformatically. 1,25(OH)2D3 altered expression of large collections of genes in animals under either dietary condition. 45 genes were found common to both 1,25(OH)2D3-treated groups and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet. We then conducted a ChIP sequence analysis of binding sites for the vitamin D receptor (VDR) across the proximal intestine in vitamin D-sufficient normal mice treated with vehicle or 1,25(OH)2D3. The residual VDR cistrome was composed of 4617 sites, which was increased almost 4-fold following hormone treatment. Interestingly, the majority of the genes regulated by 1,25(OH)2D3 in each diet group as well as those found in common in both groups contained frequent VDR sites that likely regulated their expression. This study revealed a global network of genes in the intestine that both represent direct targets of vitamin D action in mice and are involved in calcium absorption.

  17. Calcium signaling and epilepsy.

    Science.gov (United States)

    Steinlein, Ortrud K

    2014-08-01

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

  18. Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors.

    Science.gov (United States)

    Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong; Li, He; Li, Yaogang; Duan, Yourong

    2016-01-19

    Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately -16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy.

  19. Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins.

    Science.gov (United States)

    Sewalt, Richard G A B; Lachner, Monika; Vargas, Mark; Hamer, Karien M; den Blaauwen, Jan L; Hendrix, Thijs; Melcher, Martin; Schweizer, Dieter; Jenuwein, Thomas; Otte, Arie P

    2002-08-01

    Polycomb group (PcG) proteins form multimeric chromatin-associated protein complexes that are involved in heritable repression of gene activity. Two distinct human PcG complexes have been characterized. The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity. The HPC/HPH PcG complex contains the HPH, RING1, BMI1, and HPC proteins. Here we show that vertebrate Polycomb homologs HPC2 and XPc2, but not M33/MPc1, interact with the histone lysine methyltransferase (HMTase) SUV39H1 both in vitro and in vivo. We further find that overexpression of SUV39H1 induces selective nuclear relocalization of HPC/HPH PcG proteins but not of the EED/EZH2 PcG proteins. This SUV39H1-dependent relocalization concentrates the HPC/HPH PcG proteins to the large pericentromeric heterochromatin domains (1q12) on human chromosome 1. Within these PcG domains we observe increased H3-K9 methylation. Finally, we show that H3-K9 HMTase activity is associated with endogenous HPC2. Our findings suggest a role for the SUV39H1 HMTase and histone H3-K9 methylation in the targeting of human HPC/HPH PcG proteins to modified chromatin structures.

  20. miR-185 plays an anti-hypertrophic role in the heart via multiple targets in the calcium-signaling pathways.

    Directory of Open Access Journals (Sweden)

    Jin Ock Kim

    Full Text Available MicroRNA (miRNA is an endogenous non-coding RNA species that either inhibits RNA translation or promotes degradation of target mRNAs. miRNAs often regulate cellular signaling by targeting multiple genes within the pathways. In the present study, using Gene Set Analysis, a useful bioinformatics tool to identify miRNAs with multiple target genes in the same pathways, we identified miR-185 as a key candidate regulator of cardiac hypertrophy. Using a mouse model, we found that miR-185 was significantly down-regulated in myocardial cells during cardiac hypertrophy induced by transverse aortic constriction. To confirm that miR-185 is an anti-hypertrophic miRNA, genetic manipulation studies such as overexpression and knock-down of miR-185 in neonatal rat ventricular myocytes were conducted. The results showed that up-regulation of miR-185 led to anti-hypertrophic effects, while down-regulation led to pro-hypertrophic effects, suggesting that miR-185 has an anti-hypertrophic role in the heart. Our study further identified Camk2d, Ncx1, and Nfatc3 as direct targets of miR-185. The activity of Nuclear Factor of Activated T-cell (NFAT and calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ was negatively regulated by miR-185 as assessed by NFAT-luciferase activity and western blotting. The expression of phospho-phospholamban (Thr-17, a marker of CaMKIIδ activity, was also significantly reduced by miR-185. In conclusion, miR-185 effectively blocked cardiac hypertrophy signaling through multiple targets, rendering it a potential drug target for diseases such as heart failure.

  1. Rice calcium-dependent protein kinase OsCPK17 targets plasma membrane intrinsic protein and sucrose phosphate synthase and is required for a proper cold stress response

    KAUST Repository

    Almadanim, M. Cecília

    2017-01-19

    Calcium-dependent protein kinases (CDPKs) are involved in plant tolerance mechanisms to abiotic stresses. Although CDPKs are recognized as key messengers in signal transduction, the specific role of most members of this family remains unknown. Here we test the hypothesis that OsCPK17 plays a role in rice cold stress response by analyzing OsCPK17 knockout, silencing, and overexpressing rice lines under low temperature. Altered OsCPK17 gene expression compromises cold tolerance performance, without affecting the expression of key cold stress-inducible genes. A comparative phosphoproteomic approach led to the identification of six potential in vivo OsCPK17 targets, which are associated with sugar and nitrogen metabolism, and with osmotic regulation. To test direct interaction, in vitro kinase assays were performed, showing that the sucrose phosphate synthase OsSPS4, and the aquaporin OsPIP2;1/OsPIP2;6 are phosphorylated by OsCPK17 in a calcium-dependent manner. Altogether, our data indicates that OsCPK17 is required for a proper cold stress response in rice, likely affecting the activity of membrane channels and sugar metabolism.

  2. Analysis list: Suv39h2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Suv39h2 Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Suv...39h2.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Suv39h2.5.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/mm9/target/Suv39h2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Suv39h

  3. Analysis list: Suv39h1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Suv39h1 Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Suv...39h1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Suv39h1.5.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/mm9/target/Suv39h1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Suv39h

  4. Development of new highly potent imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1.

    Science.gov (United States)

    Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Béatrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline

    2015-11-13

    Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were then identified, which were able to block TgCDPK1 enzymatic activity at low nanomolar concentrations, with a good selectivity profile against a panel of mammalian kinases. The potential of these inhibitors was confirmed in vitro on T. gondii growth, with EC50 values of 100 nM and 70 nM, respectively. These best candidates also displayed low toxicity to mammalian cells and were selected for further in vivo investigations on murine model of acute toxoplasmosis.

  5. [Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

    Science.gov (United States)

    Nagano, Nobuo; Tsutsui, Takaaki

    2016-06-01

    Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.

  6. Both the H2S biosynthesis inhibitor aminooxyacetic acid and the mitochondrially targeted H2S donor AP39 exert protective effects in a mouse model of burn injury.

    Science.gov (United States)

    Ahmad, Akbar; Szabo, Csaba

    2016-11-01

    Hydrogen sulfide (H2S) exerts beneficial as well as deleterious effects in various models of critical illness. Here we tested the effect of two different pharmacological interventions: (a) inhibition of H2S biosynthesis using the cystathionine-beta-synthase (CBS)/cystathionine-gamma-lyase (CSE) inhibitor aminooxyacetic acid (AOAA) and the mitochondrially targeted H2S donor [10-oxo-10-[4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy]decyl]triphenyl-phosphonium (AP39). A 30% body surface area burn injury was induced in anesthetized mice; animals were treated with vehicle, AOAA (10mg/kg i.p. once or once a day for 6days), or AP39 (0.3mg/kg/day once or once a day for 6days). In two separate groups, animals were sacrificed, at 24h post-burn or on Day 7 post-burn, blood and lungs were collected and the following parameters were evaluated: myeloperoxidase (MPO) and malondialdehyde (MDA) in lung homogenates, plasma cytokines (Luminex analysis) and circulating indicators of organ dysfunction (Vetscan analysis). Lung MPO levels (an index of neutrophil infiltration) and MDA levels (an index of oxidative stress) were significantly increased in response to burn injury both at 24h and at 7days; both AOAA and AP39 attenuated these increases. From a panel of inflammatory cytokines (TNFα, IL-1β, IL-6, IL-10, MCP-1, MIP-2, VEGF and IFNγ) in the plasma, IL-6 and IL-10 levels were markedly elevated at 24h and VEGF was slightly elevated. IL-6 remained highly elevated at 7days post-burn while IL-10 levels decreased, but remained slightly elevated over baseline 7days post-burn. The changes in cytokine levels were attenuated both by AP39 and AOAA at both time points studied. The burn-induced increases in the organ injury markers ALP and ALT, amylase and creatinine were reduced by both AOAA and AP39. We conclude that both H2S biosynthesis inhibition (using AOAA) and H2S donation (using AP39) suppresses inflammatory mediator production and reduces multi-organ injury in a murine model of burn

  7. Folate-targeted pH-responsive calcium zoledronate nanoscale metal-organic frameworks: Turning a bone antiresorptive agent into an anticancer therapeutic.

    Science.gov (United States)

    Au, Kin Man; Satterlee, Andrew; Min, Yuanzeng; Tian, Xi; Kim, Young Seok; Caster, Joseph M; Zhang, Longzhen; Zhang, Tian; Huang, Leaf; Wang, Andrew Z

    2016-03-01

    Zoledronate (Zol) is a third-generation bisphosphonate that is widely used as an anti-resorptive agent for the treatment of cancer bone metastasis. While there is preclinical data indicating that bisphosphonates such as Zol have direct cytotoxic effects on cancer cells, such effect has not been firmly established in the clinical setting. This is likely due to the rapid absorption of bisphosphonates by the skeleton after intravenous (i.v.) administration. Herein, we report the reformulation of Zol using nanotechnology and evaluation of this novel nanoscale metal-organic frameworks (nMOFs) formulation of Zol as an anticancer agent. The nMOF formulation is comprised of a calcium zoledronate (CaZol) core and a polyethylene glycol (PEG) surface. To preferentially deliver CaZol nMOFs to tumors as well as facilitate cellular uptake of Zol, we incorporated folate (Fol)-targeted ligands on the nMOFs. The folate receptor (FR) is known to be overexpressed in several tumor types, including head-and-neck, prostate, and non-small cell lung cancers. We demonstrated that these targeted CaZol nMOFs possess excellent chemical and colloidal stability in physiological conditions. The release of encapsulated Zol from the nMOFs occurs in the mid-endosomes during nMOF endocytosis. In vitro toxicity studies demonstrated that Fol-targeted CaZol nMOFs are more efficient than small molecule Zol in inhibiting cell proliferation and inducing apoptosis in FR-overexpressing H460 non-small cell lung and PC3 prostate cancer cells. Our findings were further validated in vivo using mouse xenograft models of H460 and PC3. We demonstrated that Fol-targeted CaZol nMOFs are effective anticancer agents and increase the direct antitumor activity of Zol by 80-85% in vivo through inhibition of tumor neovasculature, and inhibiting cell proliferation and inducing apoptosis.

  8. Fibroblast-like synoviocytes induce calcium mineral formation and deposition.

    Science.gov (United States)

    Sun, Yubo; Mauerhan, David R; Franklin, Atiya M; Zinchenko, Natalia; Norton, Harry James; Hanley, Edward N; Gruber, Helen E

    2014-01-01

    Calcium crystals are present in the synovial fluid of 65%-100% patients with osteoarthritis (OA) and 20%-39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s). The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

  9. Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

    Directory of Open Access Journals (Sweden)

    Yubo Sun

    2014-01-01

    Full Text Available Calcium crystals are present in the synovial fluid of 65%–100% patients with osteoarthritis (OA and 20%–39% patients with rheumatoid arthritis (RA. This study sought to investigate the role of fibroblast-like synoviocytes (FLSs in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s. The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

  10. Glatiramer acetate (copaxone modulates platelet activation and inhibits thrombin-induced calcium influx: possible role of copaxone in targeting platelets during autoimmune neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Sarah C Starossom

    Full Text Available BACKGROUND: Glatiramer acetate (GA, Copaxone, Copolymer-1 is an FDA approved drug for the treatment of MS and it is very effective in suppressing neuroinflammation in experimental autoimmune encephalitis (EAE, an animal model of MS. Although this drug was designed to inhibit pathogenic T cells, the exact mechanism of EAE/MS suppression by GA is still not well understood. Previously we presented evidence that platelets become activated and promote neuroinflammation in EAE, suggesting a possible pathogenic role of platelets in MS and EAE. We hypothesized that GA could inhibit neuroinflammation by affecting not only immune cells but also platelets. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of GA on the activation of human platelets in vitro: calcium influx, platelet aggregation and expression of activation markers. Our results in human platelets were confirmed by in-vitro and in-vivo studies of modulation of functions of platelets in mouse model. We found that GA inhibited thrombin-induced calcium influx in human and mouse platelets. GA also decreased thrombin-induced CD31, CD62P, CD63, and active form of αIIbβ3 integrin surface expression and formation of platelet aggregates for both mouse and human platelets, and prolonged the bleeding time in mice by 2.7-fold. In addition, we found that GA decreased the extent of macrophage activation induced by co-culture of macrophages with platelets. CONCLUSIONS: GA inhibited the activation of platelets, which suggests a new mechanism of GA action in suppression of EAE/MS by targeting platelets and possibly preventing their interaction with immune cells such as macrophages. Furthermore, the reduction in platelet activation by GA may have additional cardiovascular benefits to prevent thrombosis.

  11. Calcium supplements

    Science.gov (United States)

    ... do not help. Always tell your provider and pharmacist if you are taking extra calcium. Calcium supplements ... 2012:chap 251. The National Osteoporosis Foundation (NOF). Clinician's Guide to prevention and treatment of osteoporosis . National ...

  12. Analysis list: lin-39 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available lin-39 Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/lin-39....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/lin-39.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/li...n-39.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/lin-39.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  13. Calcium in diet

    Science.gov (United States)

    ... D is needed to help your body use calcium. Milk is fortified with vitamin D for this reason. ... of calcium dietary supplements include calcium citrate and calcium carbonate. Calcium citrate is the more expensive form of ...

  14. Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice.

    Science.gov (United States)

    Chow, Edwin C Y; Quach, Holly P; Vieth, Reinhold; Pang, K Sandy

    2013-05-01

    The vitamin D receptor (VDR) maintains a balance of plasma calcium and 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH)2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH)2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH)2D3 treatment in mice (2.5 μg/kg ip, singly or q2d × 4). After a single ip dose, plasma 1,25(OH)2D3 peaked at ∼0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH)2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH)2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH)2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH)2D3.

  15. Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

    Science.gov (United States)

    Li, Wei-Ming; Chiang, Chih-Sheng; Huang, Wei-Chen; Su, Chia-Wei; Chiang, Min-Yu; Chen, Jian-Yi; Chen, San-Yuan

    2015-12-28

    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers.

  16. Calcium Electroporation

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Effect of curd washing on the properties of reduced-calcium and standard-calcium Cheddar cheese.

    Science.gov (United States)

    Hou, Jia; McSweeney, Paul L H; Beresford, Thomas P; Guinee, Timothy P

    2014-10-01

    Washed (W) and nonwashed (NW) variants of standard (SCa) and reduced-calcium (RCa) Cheddar cheeses were made in triplicate, ripened for a 270-d period, and analyzed for composition and changes during maturation. Curd washing was applied to cheeses to give a target level of lactose plus lactic acid in cheese moisture of 3.9 g/100 g in the W cheese, compared with a value of 5.3 g/100 g of lactose plus lactic acid in cheese moisture in the control NW cheeses. The 4 cheese types were denoted standard calcium nonwashed (SCaNW), standard calcium washed (SCaW), reduced-calcium nonwashed (RCaNW), and reduced-calcium washed (RCaW). The mean calcium level was 760 mg/100 g in the SCaNW and SCaW and 660 mg/100 g in the RCaNW and RCaW cheeses. Otherwise the gross composition of all cheeses was similar, each with protein, fat, and moisture levels of ~26, 32, and 36 g/100 g, respectively. Curd washing significantly reduced the mean level of lactic acid in the SCaW cheese and residual lactose in both SCaW and RCaW cheeses. The mean pH of the standard-calcium cheese over the 270-d ripening period increased significantly with curd washing and ripening time, in contrast to the reduced-calcium cheese, which was not affected by the latter parameters. Otherwise curd washing had little effect on changes in populations of starter bacteria or nonstarter lactic acid bacteria, proteolysis, rheology, or color of the cheese during ripening. Descriptive sensory analysis at 270 d indicated that the SCaW cheese had a nuttier, sweeter, less fruity, and less rancid taste than the corresponding SCaNW cheese. In contrast, curd washing was not as effective in discriminating between the RCaW and RCaNW cheeses. The RCaW cheese had a more buttery, caramel odor and flavor, and a more bitter, less sweet, and nutty taste than the SCaW cheese, whereas the RCaNW had a more pungent and less fruity flavor, a less fruity odor, a saltier, more-bitter, and less acidic taste, and a more astringent mouthfeel than

  18. The 50-kDa protein of Apple chlorotic leaf spot virus interferes with intracellular and intercellular targeting and tubule-inducing activity of the 39-kDa protein of Grapevine berry inner necrosis virus.

    Science.gov (United States)

    Isogai, M; Saitou, Y; Takahashi, N; Itabashi, T; Terada, M; Satoh, H; Yoshikawa, N

    2003-03-01

    To understand why transgenic Nicotiana occidentalis plants expressing a functional movement protein (MP) of Apple chlorotic leaf spot virus (ACLSV) show specific resistance to Grapevine berry inner necrosis virus (GINV), the MPs of ACLSV (50KP) and GINV (39KP) were fused to green, yellow, or cyan fluorescent proteins (GFP, YFP, or CFP). These fusion proteins were transiently expressed in leaf cells of both transgenic (50KP) and nontransgenic (NT) plants, and the intracellular and intercellular trafficking and tubule-inducing activity of these proteins were compared. The results indicate that in epidermal cells and protoplasts from 50KP plant leaves, the trafficking and tubule-inducing activities of GINV-39KP were specifically blocked while those of ACLSV-50KP and Apple stem grooving virus MP (36KP) were not affected. Additionally, when 39KP-YFP and 50KP-CFP were coexpressed in the leaf epidermis of NT plants, the fluorescence of both proteins was confined to single cells, indicating that 50KP-CFP interferes with the cell-to-cell trafficking of 39KP-YFP and vice versa. Mutational analyses of 50KP showed that the deletion mutants that retained the activities described above still blocked cell-to-cell trafficking of 39KP, but the dysfunctional 50KP mutants could no longer impede cell-to-cell movement of 39KP. Transgenic plants expressing the functional 50KP deletion mutants showed specific resistance against GINV. In contrast, transgenic plants expressing the dysfunctional 50KP mutants did not show any resistance to the virus. From these results, we conclude that the specific resistance of 50KP plants to GINV is due to the ability of the 50KP to block intracellular and intercellular trafficking of GINV 39KP.

  19. Analysis list: unc-39 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available unc-39 Embryo,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/...unc-39.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/unc-39.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/target/unc-39.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/unc-39.Embryo....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/unc-39.Larvae.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  20. Calcium and bones

    Science.gov (United States)

    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. ...

  1. Calcium Test

    Science.gov (United States)

    ... if a person has symptoms of a parathyroid disorder , malabsorption , or an overactive thyroid. A total calcium level is often measured as part of a routine health screening. It is included in the comprehensive metabolic panel (CMP) and the basic metabolic panel (BMP) , ...

  2. Calcium Carbonate

    Science.gov (United States)

    ... doctor if you have or have ever had kidney disease or stomach conditions.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking calcium carbonate, call your doctor.

  3. Production of scandium-43 and -47 from a powdery calcium oxide target via the (nat/44)Ca(α,x)-channel.

    Science.gov (United States)

    Minegishi, Katsuyuki; Nagatsu, Kotaro; Fukada, Masami; Suzuki, Hisashi; Ohya, Tomoyuki; Zhang, Ming-Rong

    2016-10-01

    We produced (43)Sc and (47)Sc via the (nat/44)Ca(α,x)-channel using a vertical beam coupled with a ceramic target box. After activation, the powdery CaO target material was dissolved in HCl in the target box in situ and remotely recovered as a radio-Sc solution. The respective yields of (43)Sc and (47)Sc following isolation via a precipitation method with a typical 0.22µm sterile filter were 54.8MBq/µAh (1.48mCi/µAh) and 780kBq/µAh (21.1µCi/µAh) at the end of separation (approximately 1.5h from the EOB). In addition, we discuss the recycling of target Ca.

  4. Plasma membrane calcium pump (PMCA) isoform 4 is targeted to the apical membrane by the w-splice insert from PMCA2

    OpenAIRE

    Antalffy, Géza; Mauer, Amy S.; Pászty, Katalin; Hegedus, Luca; Padányi, Rita; Enyedi, Ágnes; STREHLER, EMANUEL E.

    2012-01-01

    Local Ca2+ signaling requires proper targeting of the Ca2+ signaling toolkit to specific cellular locales. Different isoforms of the plasma membrane Ca2+ pump (PMCA) are responsible for Ca2+ extrusion at the apical and basolateral membrane of polarized epithelial cells, but the mechanisms and signals for differential targeting of the PMCAs are not well understood. Recent work demonstrated that the alternatively spliced w-insert in PMCA2 directs this pump to the apical membrane. We now show th...

  5. GPR39 Zn2+-sensing receptor

    DEFF Research Database (Denmark)

    Młyniec, Katarzyna; Singewald, Nicolas; Holst, Birgitte;

    2015-01-01

    Zinc is a trace element released from glutamatergic terminals, and modulates the pre- and postsynaptic areas, giving a diverse biological response. Zinc is a natural ligand that inhibits the N-methyl-d-aspartate (NMDA) receptor and regulates the excessive release of glutamate. Moreover, zinc...... exhibits an antidepressant-like profile, as demonstrated in both preclinical and clinical studies. Recent reports indicate that the GPR39 Zn2+-sensing receptor is an important target for zinc “transmission” (its activation modulates/induces diverse biochemical pathways involved in neuroprotection......). Preclinical studies provide evidence that zinc deficiency leads to depressive-like behavior related to down-regulation of the GPR39 Zn2+-sensing receptor. Zinc binds to the GPR39 and triggers signals, leading to CRE-dependent gene transcription, resulting in increases in proteins such as brain...

  6. Health screening - women - ages 18 to 39

    Science.gov (United States)

    Health maintenance visit - women - ages 18 to 39; Physical exam - women - ages 18 to 39; Yearly exam - ... 39; Checkup - women - ages 18 to 39; Women's health - ages 18 to 39; Preventive care - women - ages ...

  7. Health screening - men - ages 18 to 39

    Science.gov (United States)

    Health maintenance visit - men - ages 18 to 39; Physical exam - men - ages 18 to 39; Yearly exam - ... 39; Checkup - men - ages 18 to 39; Men's health - ages 18 to 39; Preventive care exam - men - ...

  8. Altered calcium signaling in cancer cells.

    Science.gov (United States)

    Stewart, Teneale A; Yapa, Kunsala T D S; Monteith, Gregory R

    2015-10-01

    It is the nature of the calcium signal, as determined by the coordinated activity of a suite of calcium channels, pumps, exchangers and binding proteins that ultimately guides a cell's fate. Deregulation of the calcium signal is often deleterious and has been linked to each of the 'cancer hallmarks'. Despite this, we do not yet have a full understanding of the remodeling of the calcium signal associated with cancer. Such an understanding could aid in guiding the development of therapies specifically targeting altered calcium signaling in cancer cells during tumorigenic progression. Findings from some of the studies that have assessed the remodeling of the calcium signal associated with tumorigenesis and/or processes important in invasion and metastasis are presented in this review. The potential of new methodologies is also discussed. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

  9. Calcium channel as a potential anticancer agent.

    Science.gov (United States)

    Kriazhev, L

    2009-11-01

    Anticancer treatment in modern clinical practices includes chemotherapy and radiation therapy with or without surgical interventions. Efficiency of both methods varies greatly depending on cancer types and stages. Besides, chemo- and radiotherapy are toxic and damaging that causes serious side effects. This fact prompts the search for alternative methods of antitumor therapy. It is well known that prolonged or high increase of intracellular calcium concentration inevitably leads to the cell death via apoptosis or necrosis. However, stimulation of cell calcium level by chemical agents is hardly achievable because cells have very sophisticated machinery for maintaining intracellular calcium in physiological ranges. This obstacle can be overridden, nevertheless. It was found that calcium channels in so called calcium cells in land snails are directly regulated by extracellular calcium concentration. The higher the concentration the higher the calcium intake is through the channels. Bearing in mind that extracellular/intracellular calcium concentration ratio in human beings is 10,000-12,000 fold the insertion of the channel into cancer cells would lead to fast and uncontrollable by the cells calcium intake and cell death. Proteins composing the channel may be extracted from plasma membrane of calcium cells and sequenced by mass-spectrometry or N-terminal sequencing. Either proteins or corresponding genes could be used for targeted delivery into cancer cells.

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

    Science.gov (United States)

    Huang, Cathy Chia-Yu; Ko, Michael Lee; Ko, Gladys Yi-Ping

    2013-01-01

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

  11. Osteoblasts detect pericellular calcium concentration increase via neomycin-sensitive voltage gated calcium channels.

    Science.gov (United States)

    Sun, Xuanhao; Kishore, Vipuil; Fites, Kateri; Akkus, Ozan

    2012-11-01

    intracellular calcium occurs by the entry of extracellular calcium ions through VGCCs which are sensitive to neomycin. N-type and P-type VGCCs are potential candidates because they are observed in osteoblasts and they are sensitive to neomycin. The calcium channels identified in this study provide new insight into mechanisms underlying the targeted repair process which is essential to bone adaptation.

  12. Intracellular calcium is a target of modulation of apoptosis in MCF-7 cells in the presence of IgA adsorbed to polyethylene glycol

    Directory of Open Access Journals (Sweden)

    Honorio-França AC

    2016-02-01

    Full Text Available Adenilda Cristina Honorio-França,1 Gabriel Triches Nunes,1 Danny Laura Gomes Fagundes,1 Patrícia Gelli Feres de Marchi,1 Rubian Trindade da Silva Fernandes,1 Juliana Luzia França,1,2 Aline do Carmo França-Botelho,2 Lucélia Campelo Albuquerque Moraes,1 Fernando de Pilla Varotti,3 Eduardo Luzía França1,3 1Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças, Mato Grosso, Brazil; 2Institute of Health Sciences, University Center of Planalto de Araxá, Araxá, Minas Gerais, Brazil; 3Campus Centro Oeste Dona Lindu – Federal University of São João Del Rei, Divinópolis, Minas Gerais, Brazil Purpose: Clinical and epidemiological studies have indicated that breastfeeding has a protective effect on breast cancer risk. Protein-based drugs, including antibodies, are being developed to attain better forms of cancer therapy. Secretory IgA (SIgA is the antibody class in human breast milk, and its activity can be linked to the protective effect of breastfeeding. The aim of this study was to investigate the effect of polyethylene glycol (PEG microspheres with adsorbed SIgA on MCF-7 human breast cancer cells.  Methods: The PEG microspheres were characterized by flow cytometry and fluorescence microscopy. The MCF-7 cells were obtained from American Type Culture Collection. MCF-7 cells were pre-incubated for 24 hours with or without SIgA (100 ng/mL, PEG microspheres or SIgA adsorbed in PEG microspheres (100 ng/mL. Viability, intracellular calcium release, and apoptosis in MCF-7 cells were determined by flow cytometry.  Results: Fluorescence microscopy and flow cytometry analyses revealed that SIgA was able to adsorb to the PEG microspheres. The MCF-7 cells that were incubated with PEG microspheres with adsorbed SIgA showed decreased viability. MCF-7 cells that were incubated with SIgA or PEG microspheres with adsorbed SIgA had increased intracellular Ca2+ levels. In the presence of SIgA, an increase in the

  13. Calcium and Vitamin D

    Science.gov (United States)

    ... Cart Home › Patients › Treatment › Calcium/Vitamin D Calcium/Vitamin D Getting enough calcium and vitamin D is ... the-counter medications and calcium supplements. What is Vitamin D and What Does it Do? Vitamin D ...

  14. Imaging calcium in neurons.

    Science.gov (United States)

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  15. 32 CFR 3.9 - Follow-on production contracts.

    Science.gov (United States)

    2010-07-01

    ... proposed quantity and target prices for the follow-on production units as part of that competition. (3... matter of policy, establishing target prices for production units should only be considered when the risk... 32 National Defense 1 2010-07-01 2010-07-01 false Follow-on production contracts. 3.9 Section...

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

    Directory of Open Access Journals (Sweden)

    Cathy Chia-Yu Huang

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

  17. Electret properties of CR-39

    Energy Technology Data Exchange (ETDEWEB)

    Makovicka, L.; Moliton, A.; Guille, B.; Teyssier, J.L.

    1987-01-01

    The behaviour of CR-39 (a solid track detector) as an electret is compared with other classical electret materials (Teflon, Mylar). The initial charge obtained, principally by a corona method, and its decay have been studied; the result for the charge of CR-39 is similar to that for other polymer electrets and the decay is intermediate between that of Teflon and Mylar. Some results of X ray and neutron irradiations are then presented. They show significant responses of CR-39 subjected to X ray beams of approximately 10/sup -2/ Gy.

  18. ISS Expedition 39 Press Kit

    Data.gov (United States)

    National Aeronautics and Space Administration — Press kit for ISS mission Expedition 39 from 11/2013-05/2014. Press kits contain information about each mission overview, crew, mission timeline, benefits, and media...

  19. Use of genetically-encoded calcium indicators for live cell calcium imaging and localization in virus-infected cells.

    Science.gov (United States)

    Perry, Jacob L; Ramachandran, Nina K; Utama, Budi; Hyser, Joseph M

    2015-11-15

    Calcium signaling is a ubiquitous and versatile process involved in nearly every cellular process, and exploitation of host calcium signals is a common strategy used by viruses to facilitate replication and cause disease. Small molecule fluorescent calcium dyes have been used by many to examine changes in host cell calcium signaling and calcium channel activation during virus infections, but disadvantages of these dyes, including poor loading and poor long-term retention, complicate analysis of calcium imaging in virus-infected cells due to changes in cell physiology and membrane integrity. The recent expansion of genetically-encoded calcium indicators (GECIs), including blue and red-shifted color variants and variants with calcium affinities appropriate for calcium storage organelles like the endoplasmic reticulum (ER), make the use of GECIs an attractive alternative for calcium imaging in the context of virus infections. Here we describe the development and testing of cell lines stably expressing both green cytoplasmic (GCaMP5G and GCaMP6s) and red ER-targeted (RCEPIAer) GECIs. Using three viruses (rotavirus, poliovirus and respiratory syncytial virus) previously shown to disrupt host calcium homeostasis, we show the GECI cell lines can be used to detect simultaneous cytoplasmic and ER calcium signals. Further, we demonstrate the GECI expression has sufficient stability to enable long-term confocal imaging of both cytoplasmic and ER calcium during the course of virus infections.

  20. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

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

  1. Calcium - Function and effects

    NARCIS (Netherlands)

    Liang, Jianfen; He, Yifan; Gao, Qian; Wang, Xuan; Nout, M.J.R.

    2016-01-01

    Rice is the primary food source for more than half of the world population. Levels of calcium contents and inhibitor - phytic acid are summarized in this chapter. Phytic acid has a very strong chelating ability and it is the main inhibit factor for calcium in rice products. Calcium contents in br

  2. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

    Science.gov (United States)

    Liao, Yajin; Dong, Yuan; Cheng, Jinbo

    2017-01-01

    The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

  3. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

    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. Calcium And Zinc Deficiency In Preeclamptic Women

    Directory of Open Access Journals (Sweden)

    Sultana Ferdousi

    2011-12-01

    Full Text Available Background: Pre-eclampsia is the most common medical complication of pregnancy associated withincreased maternal and infant mortality and morbidity. Reduced serum calcium and zinc levels arefound associated with elevated blood pressure in preeclampsia. Objective: To observe serum calciumand zinc levels in preeclamptic women. Methods: This cross sectional study was carried out in theDepartment of Physiology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka betweenJuly 2009 to June 2010. In this study, 60 pregnant women of preeclampsia, aged 18-39 years withgestational period more than 20th weeks were included as the study (group B. For comparison ageand gestational period matched 30 normotensive pregnant women control (group A were also studied.All the subjects were selected from Obstetric and Gynae In and Out patient Department of BSMMUand Dhaka Medical College Hospital. Serum calcium was measured by Colorimetric method and serumzinc was measured by Spectrophotometric method. Data were analysed by independent sample t testand Pearson’s correlation coefficient test. Results: Mean serum calcium and zinc levels weresignificantly (p<0.001 lower in study group than those of control group. Again, serum calcium andzinc showed significant negative correlation with SBP and DBP in preeclamptic women. Conclusion:This study concludes that serum calcium and zinc deficiency may be one of the risk factor ofpreeclampsia. Therefore, early detection and supplementation to treat this deficiency may reduce theincidence of preeclampsia.

  5. Calcium is important forus.

    Institute of Scientific and Technical Information of China (English)

    高利平

    2005-01-01

    Calcium is important for our health.We must have it in our diet to stay well.A good place to get it is from dairy products like milk, cheese and ice cream.One pound of cheese has fifty times the calcium we should have every day.Other foods have less.For example,a pound of beans also has calcium.But it has only three times the amount we ought to have daily.

  6. The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.

    Directory of Open Access Journals (Sweden)

    Yi-Wen Hsieh

    Full Text Available The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWC(ON and AWC(OFF, by inhibiting a calcium-mediated signaling pathway in the future AWC(ON cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWC(ON fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWC(ON cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWC(ON identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWC(ON neurons. tir-1 expression is downregulated through its 3' UTR in AWC(ON, in which mir-71 is expressed at a higher level than in AWC(OFF. In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3' UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWC(ON identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation.

  7. The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.

    Science.gov (United States)

    Hsieh, Yi-Wen; Chang, Chieh; Chuang, Chiou-Fen

    2012-01-01

    The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWC(ON) and AWC(OFF), by inhibiting a calcium-mediated signaling pathway in the future AWC(ON) cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWC(ON) fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWC(ON) cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWC(ON) identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWC(ON) neurons. tir-1 expression is downregulated through its 3' UTR in AWC(ON), in which mir-71 is expressed at a higher level than in AWC(OFF). In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3' UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWC(ON) identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation.

  8. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  9. Acylhydrazones contribute to serum glucose homeostasis through dual physiological targets.

    Science.gov (United States)

    Frederico, Marisa Jádna Silva; Castro, Allisson Jhonatan Gomes; Mascarello, Alessandra; Mendes, Camila Pires; Kappel, Virgínia Dermachi; Stumpf, Taisa Regina; Leal, Paulo Cesar; Nunes, Ricardo José; Yunes, Rosendo Augusto; Silva, Fátima Regina Mena Barreto

    2012-01-01

    In this study the in vivo and in vitro antidiabetic effects of four acylhydrazone derivatives were investigated in rats. The secretagogue action, oral glucose tolerance, insulinogenic index and mechanism of action of these acylhydrazones in relation to calcium uptake in pancreatic islets were studied. Also, the insulinomimetic effect on glycemia in diabetic rats was verified. Of the acylhydrazones studied, 1 and 4 were able to increase glucose tolerance in an acute time-course. A powerful secretagogue effect was exhibited by 1 and glibenclamide with an insulinogenic index around 3.9 and 1.3-fold higher than that of the hyperglycemic group, respectively. Moreover, an acute and dose-dependent effect of glibenclamide and 1 on calcium uptake in pancreatic islets was observed. The rapid stimulatory effect of 1 on calcium uptake seems to be mediated, at least in part, by ATP-dependent K+ channels (K+-ATP) since the stimulatory effect of 1 was similar to that observed for glibenclamide but was not potentiated by sulphonylurea. Furthermore, both extracellular and calcium from stocks mediate the signal transduction of stimulatory effect of 1 on calcium uptake which may contribute to insulin secretion. In addition, the insulinomimetic effect of 1 was evidenced through the level of serum glucose lowering in alloxan-induced diabetic rats. Also, 1 induced a significant increase in glycogen content in vivo and glucose uptake in soleus muscle in vitro. The results of this study indicate dual physiological targets for the acylhydrazone 1, i.e., pancreatic islets and skeletal muscle, as a result of insulin secretagogue and insulinomimetic action.

  10. Calcium signaling in neurodegeneration

    Directory of Open Access Journals (Sweden)

    Dreses-Werringloer Ute

    2009-05-01

    Full Text Available Abstract Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular level of the versatility of this ion has made overwhelming progress in the past several years and has been extensively reviewed. In the brain, calcium is fundamental in the control of synaptic activity and memory formation, a process that leads to the activation of specific calcium-dependent signal transduction pathways and implicates key protein effectors, such as CaMKs, MAPK/ERKs, and CREB. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also maintains neuronal integrity and long-term cell survival. Emerging knowledge indicates that calcium homeostasis is not only critical for cell physiology and health, but also, when deregulated, can lead to neurodegeneration via complex and diverse mechanisms involved in selective neuronal impairments and death. The identification of several modulators of calcium homeostasis, such as presenilins and CALHM1, as potential factors involved in the pathogenesis of Alzheimer's disease, provides strong support for a role of calcium in neurodegeneration. These observations represent an important step towards understanding the molecular mechanisms of calcium signaling disturbances observed in different brain diseases such as Alzheimer's, Parkinson's, and Huntington's diseases.

  11. Knockdown of USP39 induces cell cycle arrest and apoptosis in melanoma.

    Science.gov (United States)

    Zhao, Yuan; Zhang, Bo; Lei, Yu; Sun, Jingying; Zhang, Yaohua; Yang, Sen; Zhang, Xuejun

    2016-10-01

    The spliceosome machinery composed of multimeric protein complexes guides precursor messenger RNAs (mRNAs) (pre-mRNAs) splicing in eukaryotic cells. Spliceosome components have been shown to be downregulated in cancer and could be a promising molecular target for anticancer therapy. The ubiquitin-specific protease 39 (USP39) is essential for pre-mRNA splicing, and upregulated USP39 expression is noted in a variety of cancers. However, the role of USP39 in the development and progression of melanoma remains unclear. In the present study, USP39 expression was found to be increased in melanoma tissues compared with that in nevus tissues. USP39 silencing via lentivirus-mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro. Moreover, USP39 knockdown suppressed melanoma tumor growth in a xenograft model. In addition, USP39 silencing was associated with the increased expressions of p21, p27, and Bax. Furthermore, the inhibition of USP39 expression decreased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, indicating that ERK signaling pathways might be involved in the regulation of melanoma cell proliferation by USP39. Our findings suggest that USP39 may play crucial roles in the development and pathogenesis of melanoma, and it may serve as a potential therapeutic target for melanoma.

  12. Effects of calcium ion, calpains, and calcium channel blockers on retinitis pigmentosa.

    Science.gov (United States)

    Nakazawa, Mitsuru

    2011-01-01

    Recent advances in molecular genetic studies have revealed many of the causative genes of retinitis pigmentosa (RP). These achievements have provided clues to the mechanisms of photoreceptor degeneration in RP. Apoptosis is known to be a final common pathway in RP and, therefore, a possible therapeutic target for photoreceptor rescue. However, apoptosis is not a single molecular cascade, but consists of many different reactions such as caspase-dependent and caspase-independent pathways commonly leading to DNA fractionation and cell death. The intracellular concentration of calcium ions is also known to increase in apoptosis. These findings suggest that calpains, one of the calcium-dependent proteinases, play some roles in the process of photoreceptor apoptosis and that calcium channel antagonists may potentially inhibit photoreceptor apoptosis. Herein, the effects of calpains and calcium channel antagonists on photoreceptor degeneration are reviewed.

  13. Effects of Calcium Ion, Calpains, and Calcium Channel Blockers on Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Mitsuru Nakazawa

    2011-01-01

    Full Text Available Recent advances in molecular genetic studies have revealed many of the causative genes of retinitis pigmentosa (RP. These achievements have provided clues to the mechanisms of photoreceptor degeneration in RP. Apoptosis is known to be a final common pathway in RP and, therefore, a possible therapeutic target for photoreceptor rescue. However, apoptosis is not a single molecular cascade, but consists of many different reactions such as caspase-dependent and caspase-independent pathways commonly leading to DNA fractionation and cell death. The intracellular concentration of calcium ions is also known to increase in apoptosis. These findings suggest that calpains, one of the calcium-dependent proteinases, play some roles in the process of photoreceptor apoptosis and that calcium channel antagonists may potentially inhibit photoreceptor apoptosis. Herein, the effects of calpains and calcium channel antagonists on photoreceptor degeneration are reviewed.

  14. 48 CFR 39.105 - Privacy.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Privacy. 39.105 Section 39... CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 39.105 Privacy. Agencies shall ensure that contracts for information technology address protection of privacy in accordance with the Privacy Act (5...

  15. 25 CFR 39.902 - Allocation.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Allocation. 39.902 Section 39.902 Indians BUREAU OF... Maintenance and Minor Repair Fund § 39.902 Allocation. (a) Interim Maintenance and Minor Repair funds shall be... determining school allocations shall be taken from the facilities inventory maintained by the Division...

  16. 34 CFR 104.39 - Private education.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Private education. 104.39 Section 104.39 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION... Preschool, Elementary, and Secondary Education § 104.39 Private education. (a) A recipient that...

  17. 45 CFR 84.39 - Private education.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Private education. 84.39 Section 84.39 Public... Secondary Education § 84.39 Private education. (a) A recipient that provides private elementary or secondary education may not, on the basis of handicap, exclude a qualified handicapped person if the person can,...

  18. 45 CFR 605.39 - Private education.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Private education. 605.39 Section 605.39 Public..., Elementary, and Secondary Education § 605.39 Private education. (a) A recipient that provides private elementary or secondary education may not, on the basis of handicap, exclude a qualified handicapped...

  19. 40 CFR 68.39 - Documentation.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Documentation. 68.39 Section 68.39... ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.39 Documentation. The owner or operator shall... passive mitigation that were assumed to limit the quantity that could be released. Documentation...

  20. 12 CFR 561.39 - Principal office.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Principal office. 561.39 Section 561.39 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING ALL SAVINGS ASSOCIATIONS § 561.39 Principal office. The term principal office means the...

  1. 14 CFR 33.39 - Lubrication system.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Lubrication system. 33.39 Section 33.39... STANDARDS: AIRCRAFT ENGINES Design and Construction; Reciprocating Aircraft Engines § 33.39 Lubrication system. (a) The lubrication system of the engine must be designed and constructed so that it...

  2. 10 CFR 39.71 - Security.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Security. 39.71 Section 39.71 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Security, Records, Notifications § 39.71 Security. (a) A logging supervisor must be physically present at a temporary jobsite...

  3. 14 CFR 437.39 - Flight rules.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Flight rules. 437.39 Section 437.39 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... Documentation § 437.39 Flight rules. An applicant must provide flight rules as required by § 437.71....

  4. 46 CFR 151.03-39 - Ocean.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Ocean. 151.03-39 Section 151.03-39 Shipping COAST GUARD... HAZARDOUS MATERIAL CARGOES Definitions § 151.03-39 Ocean. A designation for all vessels normally navigating the waters of any ocean or the Gulf of Mexico more than 20 nautical miles offshore....

  5. 28 CFR 0.39a - Functions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Functions. 0.39a Section 0.39a Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE 2-Office of Professional Responsibility § 0.39a Functions. (a) The Counsel shall: (1) Receive, review, investigate and refer...

  6. 19 CFR 143.39 - Penalties.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Penalties. 143.39 Section 143.39 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.39 Penalties. (a) Brokers. Brokers...

  7. 28 CFR 39.160 - Communications.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Communications. 39.160 Section 39.160... PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF JUSTICE § 39.160 Communications. (a) The agency shall take appropriate steps to ensure effective communication with applicants, participants, personnel...

  8. 14 CFR 35.39 - Endurance test.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Endurance test. 35.39 Section 35.39... STANDARDS: PROPELLERS Tests and Inspections § 35.39 Endurance test. Endurance tests on the propeller system... propellers must be subjected to one of the following tests: (1) A 50-hour flight test in level flight or...

  9. 46 CFR 67.39 - Corporation.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Corporation. 67.39 Section 67.39 Shipping COAST GUARD... Citizenship Requirements for Vessel Documentation § 67.39 Corporation. (a) For the purpose of obtaining a registry or a recreational endorsement, a corporation meets citizenship requirements if: (1) It...

  10. 45 CFR 233.39 - Age.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Age. 233.39 Section 233.39 Public Welfare... FINANCIAL ASSISTANCE PROGRAMS § 233.39 Age. (a) Condition for plan approval. A State plan under title I or XVI of the Social Security Act may not impose any age requirement of more than 65 years. (b)...

  11. Calcium and Your Child

    Science.gov (United States)

    ... for dinner. Create mini-pizzas by topping whole-wheat English muffins or bagels with pizza sauce, low- ... Minerals Do I Need to Drink Milk? Lactose Intolerance Becoming a Vegetarian Soy Foods and Health Calcium ...

  12. Stoichiometry of Calcium Medicines

    Science.gov (United States)

    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.

  13. Voltage-Gated Calcium Channels in Nociception

    Science.gov (United States)

    Yasuda, Takahiro; Adams, David J.

    Voltage-gated calcium channels (VGCCs) are a large and functionally diverse group of membrane ion channels ubiquitously expressed throughout the central and peripheral nervous systems. VGCCs contribute to various physiological processes and transduce electrical activity into other cellular functions. This chapter provides an overview of biophysical properties of VGCCs, including regulation by auxiliary subunits, and their physiological role in neuronal functions. Subsequently, then we focus on N-type calcium (Cav2.2) channels, in particular their diversity and specific antagonists. We also discuss the role of N-type calcium channels in nociception and pain transmission through primary sensory dorsal root ganglion neurons (nociceptors). It has been shown that these channels are expressed predominantly in nerve terminals of the nociceptors and that they control neurotransmitter release. To date, important roles of N-type calcium channels in pain sensation have been elucidated genetically and pharmacologically, indicating that specific N-type calcium channel antagonists or modulators are particularly useful as therapeutic drugs targeting chronic and neuropathic pain.

  14. Calcium and Calcium-Base Alloys

    Science.gov (United States)

    1949-01-01

    should be satisfactory, because the electrolytic process for •(!>: A. H. Everts and G. D. Baglev’, " Physical «nrt m<„.+„4 i «_ of Calcium«, Electrochem...Rev. Metalurgie , 3j2, (1), 129 (1935). 10 ^sm^mssss^ma^^ extension between two known loads, is preferable to the value of 3,700,000 p.B.i. obtained

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

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate ab

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

    Science.gov (United States)

    Gibson, Gary E; Thakkar, Ankita

    2017-02-08

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

  17. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

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

  18. Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

    DEFF Research Database (Denmark)

    Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars;

    2013-01-01

    BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... endothelial activation. Here, we tested whether CD133 MP might be shed in a CD39-dependent manner in a model of liver injury and could potentially serve as biomarkers of liver failure in the clinic. METHODS: Wild-type and Cd39-null mice were subjected to acetaminophen-induced liver injury. Mice were...

  19. Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia

    OpenAIRE

    Wilson, Rosamund J; Copley, J Brian

    2017-01-01

    Background Calcium-based and non-calcium-based phosphate binders have similar efficacy in the treatment of hyperphosphatemia; however, calcium-based binders may be associated with hypercalcemia, vascular calcification, and adynamic bone disease. Scope A post hoc analysis was carried out of data from a 16-week, Phase IV study of patients with end-stage renal disease (ESRD) who switched to lanthanum carbonate monotherapy from baseline calcium acetate/calcium carbonate monotherapy. Of the intent...

  20. [Microbial geochemical calcium cycle].

    Science.gov (United States)

    Zavarzin, G A

    2002-01-01

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

  1. Breast regression protein-39 (BRP-39) promotes dendritic cell maturation in vitro and enhances Th2 inflammation in murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    Qian xu; Shou-jie CHAI; Ying-ying QIAN; Min ZHANG; Kai WANG

    2012-01-01

    Aim: To determine the roles of breast regression protein-39 (BRP-39) in regulating dendritic cell maturation and in pathology of acute asthma.Methods: Mouse bone marrow-derived dendritic cells (BMDCs) were prepared,and infected with adenovirus over-expressing BRP-39.Ovalbumin (OVA)-induced murine model of acute asthma was made in female BALB/c mice by sensitizing and challenging with chicken OVA and Imject Alum.The transfected BMDCs were adoptively transferred into OVA-treated mice via intravenous injection.Airway hyperresponsiveness (AHR),inflammation and pulmonary histopathology were characterized.Results: The expression of BRP-39 mRNA and protein was significantly increased in lung tissues of OVA-treated mice.The BMDCs infected with adenovirus BRP-39 exhibited greater maturation and higher activity in vitro.Adoptive transfer of the cells into OVA-treated mice significantly augmented OVA-induced AHR and eosinophilic inflammation.Meanwhile,BRP-39 further enhanced the production of OVA-induced Th2 cytokines IL-4,IL-5,and IL-13,but significantly attenuated OVA-induced IFN-γ production in bronchoalveolar lavage fluid.Conclusion: In OVA-induced murine model of acute asthma,BRP-39 is over-expressed in lung tissue and augments Th2 inflammatory response and AHR.BRP-39 promotes dendritic cell maturation in vitro.Therefore,BRP-39 may be a potential therapeutic target of asthma.

  2. Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

    NARCIS (Netherlands)

    C.M. O'Seaghdha (Conall); H. Wu (Hongsheng); Q. Yang (Qiong); K. Kapur (Karen); I. Guessous (Idris); P. Zuber (Patrick); A. Köttgen (Anna); C. Stoudmann (Candice); A. Teumer (Alexander); Z. Kutalik (Zoltán); M. Mangino (Massimo); A. Dehghan (Abbas); W. Zhang (Weihua); G. Eiriksdottir (Gudny); G. Li (Guo); T. Tanaka (Toshiko); L. Portas (Laura); L.M. Lopez (Lorna); C. Hayward (Caroline); K. Lohman (Kurt); K. Matsuda (Koichi); S. Padmanabhan (Sandosh); D. Firsov (Dmitri); R. Sorice; S. Ulivi (Shelia); A.C. Brockhaus (A. Catharina); M.E. Kleber (Marcus); A. Mahajan (Anubha); F.D.J. Ernst (Florian); V. Gudnason (Vilmundur); L.J. Launer (Lenore); A. Mace (Aurelien); E.A. Boerwinkle (Eric); D.E. Arking (Dan); C. Tanikawa (Chizu); Y. Nakamura (Yusuke); M.J. Brown (Morris); J.-M. Gaspoz (Jean-Michel); J.-M. Theler (Jean-Marc); D.S. Siscovick (David); B.M. Psaty (Bruce); S.M. Bergmann (Sven); P. Vollenweider (Peter); V. Vitart (Veronique); A.F. Wright (Alan); T. Zemunik (Tatijana); M. Boban (Mladen); I. Kolcic (Ivana); P. Navarro (Pau); E.M. Brown (Edward); K. Estrada Gil (Karol); J. Ding (Jinhui); T.B. Harris (Tamara); S. Bandinelli (Stefania); D.G. Hernandez (Dena); A. Singleton (Andrew); S. Girotto; D. Ruggiero; A.P. d' Adamo (Adamo Pio); A. Robino (Antonietta); T. Meitinger (Thomas); C. Meisinger (Christa); G. Davies (Gail); J.M. Starr (John); J.C. Chambers (John); B.O. Boehm (Bernhard); B. Winkelmann; J. Huang (Jian); D. Murgia (Daniela); S.H. Wild (Sarah); H. Campbell (Harry); A.D. Morris (Andrew); O.H. Franco (Oscar); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); U. Vol̈ker (Uwe); M. Hannemann (Mario); R. Biffar (Reiner); W. Hoffmann (Wolfgang); S.-Y. Shin; P. Lescuyer (Pierre); H. Henry (Hughes); C. Schurmann (Claudia); P. Munroe (Patricia); P. Gasparini (Paolo); N. Pirastu (Nicola); M. Ciullo; C. Gieger (Christian); W. März (Winfried); L. Lind (Lars); T.D. Spector (Timothy); G.D. Smith; I. Rudan (Igor); J.F. Wilson (James); O. Polasek (Ozren); I.J. Deary (Ian); M. Pirastu (Mario); L. Ferrucci (Luigi); Y. Liu (Yongmei); B. Kestenbaum (Bryan); J.S. Kooner (Jaspal); J.C.M. Witteman (Jacqueline); M. Nauck (Matthias); W.H.L. Kao (Wen); H. Wallaschofski (Henri); O. Bonny (Olivier); C. Fox (Craig); M. Bochud (Murielle)

    2013-01-01

    textabstractCalcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 populati

  3. Protein ligand-tethered synthetic calcium indicator for localization control and spatiotemporal calcium imaging in plant cells.

    Science.gov (United States)

    Takaoka, Yousuke; Shigenaga, Miyuki; Imai, Masaki; Nukadzuka, Yuuki; Ishimaru, Yasuhiro; Saito, Kei; Yokoyama, Ryusuke; Nishitani, Kazuhiko; Ueda, Minoru

    2016-01-01

    In plant biology, calcium ions are involved in a variety of intriguing biological phenomena as a secondary messenger. However, most conventional calcium indicators are not applicable for plant cells because of the difficulty with their localization control in plant cells. We here introduce a method to monitor spatiotemporal Ca(2+) dynamics in living plant cells based on linking the synthetic calcium indicator Calcium Green-1 to a natural product-based protein ligand. In a proof-of-concept study using cultured BY-2 cells overexpressing the target protein for the ligand, the ligand-tethered probe accumulated in the cytosol and nucleus, and enabled real-time monitoring of the cytosolic and nucleus Ca(2+) dynamics under the physiological condition. The present strategy using ligand-tethered fluorescent sensors may be successfully applied to reveal the spatiotemporal dynamics of calcium ions in living plant cells.

  4. A Study of the Residual 39Ar Content in Argon from Underground Sources

    CERN Document Server

    Xu, J; Galbiati, C; Goretti, A; Guray, G; Hohman, T; Holtz, D; Ianni, A; Laubenstein, M; Loer, B; Love, C; Martoff, C J; Montanari, D; Mukhopadhyay, S; Nelson, A; Rountree, S D; Vogelaar, R B; Wright, A

    2012-01-01

    The discovery of argon from underground sources with significantly less 39Ar than atmospheric argon was an important step in the development of direct-detection dark matter experiments using argon as the active target. We report on the design and operation of a low background detector with a single phase liquid argon target that was built to study the 39Ar content of the underground argon. Underground argon from the Kinder Morgan CO2 plant in Cortez, Colorado was determined to have less than 0.65% of the 39Ar activity in atmospheric argon.

  5. Kinetics of the Carbonate Leaching for Calcium Metavanadate

    Directory of Open Access Journals (Sweden)

    Peiyang Shi

    2016-10-01

    Full Text Available The sodium salt roasting process was widely used for extracting vanadium due to its high yield rate of vanadium. However, the serious pollution was a problem. The calcium roasting process was environmentally friendly, but the yield rate of vanadium was relatively lower. Focusing on the calcium metavanadate produced in the calcium roasting process of vanadium minerals, the mechanism of the carbonate leaching for calcium metavanadate and its leaching kinetics of calcium metavanadate were studied. With the increase of the leaching agent content, the decrease of the particle size, the increase of the temperature and the increase of the reaction time, the leaching rate of vanadium increased, and the constant of reaction rate increased. In the carbonate leaching process, the calcium carbonate was globular and attached to the surface of calcium metavanadate. In the solution containing bicarbonate radical, lots of cracks formed in the dissolution process. However, the cracks were relatively fewer in the solution containing carbonate. In the present study, the carbonate leaching for calcium metavanadate was controlled by diffusion, the activation energy reached maximum and minimum in the sodium bicarbonate and the sodium carbonate solution, respectively. The activation energy value in the ammonium bicarbonate solution was between those two solutions. The kinetic equations of the carbonate leaching for calcium metavanadate were as follows: 1 − 2/3η − (1 − η2/3 = 4.39[Na2CO3]0.75/r0 × exp(−2527.06/Tt; 1 − 2/3η − (1 − η2/3 = 7.89[NaHCO3]0.53/r0 × exp(−2530.67/Tt; 1 − 2/3η − (1 − η2/3 = 6.78[NH4HCO3]0.69/r0 × exp(−2459.71/Tt.

  6. The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

    Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L...

  7. Inositol trisphosphate and calcium signalling

    Science.gov (United States)

    Berridge, Michael J.

    1993-01-01

    Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.

  8. Calcium pathway machinery at fertilization in echinoderms.

    Science.gov (United States)

    Ramos, Isabela; Wessel, Gary M

    2013-01-01

    Calcium signaling in cells directs diverse physiological processes. The calcium waves triggered by fertilization is a highly conserved calcium signaling event essential for egg activation, and has been documented in every egg tested. This activity is one of the few highly conserved events of egg activation through the course of evolution. Echinoderm eggs, as well as many other cell types, have three main intracellular Ca(2+) mobilizing messengers - IP3, cADPR and NAADP. Both cADPR and NAADP were identified as Ca(2+) mobilizing messengers using the sea urchin egg homogenate, and this experimental system, along with the intact urchin and starfish oocyte/egg, continues to be a vital tool for investigating the mechanism of action of calcium signals. While many of the major regulatory steps of the IP3 pathway are well resolved, both cADPR and NAADP remain understudied in terms of our understanding of the fundamental process of egg activation at fertilization. Recently, NAADP has been shown to trigger Ca(2+) release from acidic vesicles, separately from the ER, and a new class of calcium channels, the two-pore channels (TPCs), was identified as the likely targets for this messenger. Moreover, it was found that both cADPR and NAADP can be synthesized by the same family of enzymes, the ADP-rybosyl cyclases (ARCs). In this context of increasing amount of information, the potential coupling and functional roles of different messengers, intracellular stores and channels in the formation of the fertilization calcium wave in echinoderms will be critically evaluated.

  9. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    Science.gov (United States)

    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)

  10. Calcium and Calcium Supplements: Achieving the Right Balance

    Science.gov (United States)

    ... bone mass, which is a risk factor for osteoporosis. Many Americans don't get enough calcium in their diets. Children and adolescent girls are at particular risk, but so are adults age 50 and older. How much calcium you ...

  11. 10 CFR 39.37 - Physical inventory.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Physical inventory. 39.37 Section 39.37 Energy NUCLEAR... inventory. Each licensee shall conduct a semi-annual physical inventory to account for all licensed material received and possessed under the license. The licensee shall retain records of the inventory for 3...

  12. 34 CFR 300.39 - Special education.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Special education. 300.39 Section 300.39 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN...

  13. 7 CFR 981.39 - Duties.

    Science.gov (United States)

    2010-01-01

    ... growing, shipping, and marketing conditions with respect to almonds and to assemble data in connection... 7 Agriculture 8 2010-01-01 2010-01-01 false Duties. 981.39 Section 981.39 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements...

  14. 39 CFR 3002.2 - Statutory functions.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Statutory functions. 3002.2 Section 3002.2 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL ORGANIZATION § 3002.2 Statutory functions. (a) Areas of jurisdiction. The Commission has jurisdiction over changes in postal rates and fees under 39 U.S.C. 3622,...

  15. 19 CFR 148.39 - Rented automobiles.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Rented automobiles. 148.39 Section 148.39 Customs... automobiles. (a) Importation for temporary period. An automobile rented by a resident of the United States... (HTSUS) (19 U.S.C. 1202), without payment of duty. The automobile shall be used for the transportation...

  16. 9 CFR 3.9 - Feeding.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feeding. 3.9 Section 3.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling, Care, Treatment, and Transportation of Dogs and Cats...

  17. 7 CFR 2902.39 - Floor strippers.

    Science.gov (United States)

    2010-01-01

    ... Floor strippers. (a) Definition. Products that are formulated to loosen waxes, resins, or varnishes from floor surfaces. They can be in either liquid or gel form, and may also be used with or without... 7 Agriculture 15 2010-01-01 2010-01-01 false Floor strippers. 2902.39 Section 2902.39...

  18. Calcium, vitamin D and bone

    OpenAIRE

    Borg, Andrew A.

    2012-01-01

    Calcium, protein and vitamin D are the main nutrients relevant to bone health. This short article discusses the importance of vitamin D and its relation to calcium homeostasis. The various causes, clinical manifestations and treatment are outlined.

  19. Involvement of inositol 1,4,5-trisphosphate in nicotinic calcium responses in dystrophic myotubes assessed by near-plasma membrane calcium measurement.

    Science.gov (United States)

    Basset, Olivier; Boittin, François-Xavier; Dorchies, Olivier M; Chatton, Jean-Yves; van Breemen, Cornelis; Ruegg, Urs T

    2004-11-05

    In skeletal muscle cells, plasma membrane depolarization causes a rapid calcium release from the sarcoplasmic reticulum through ryanodine receptors triggering contraction. In Duchenne muscular dystrophy (DMD), a lethal disease that is caused by the lack of the cytoskeletal protein dystrophin, the cytosolic calcium concentration is known to be increased, and this increase may lead to cell necrosis. Here, we used myotubes derived from control and mdx mice, the murine model of DMD, to study the calcium responses induced by nicotinic acetylcholine receptor stimulation. The photoprotein aequorin was expressed in the cytosol or targeted to the plasma membrane as a fusion protein with the synaptosome-associated protein SNAP-25, thus allowing calcium measurements in a restricted area localized just below the plasma membrane. The carbachol-induced calcium responses were 4.5 times bigger in dystrophic myotubes than in control myotubes. Moreover, in dystrophic myotubes the carbachol-mediated calcium responses measured in the subsarcolemmal area were at least 10 times bigger than in the bulk cytosol. The initial calcium responses were due to calcium influx into the cells followed by a fast refilling/release phase from the sarcoplasmic reticulum. In addition and unexpectedly, the inositol 1,4,5-trisphosphate receptor pathway was involved in these calcium signals only in the dystrophic myotubes. This surprising involvement of this calcium release channel in the excitation-contraction coupling could open new ways for understanding exercise-induced calcium increases and downstream muscle degeneration in mdx mice and, therefore, in DMD.

  20. The Role of CaMKII in Calcium-Activated Death Pathways in Bone Marrow B Cells

    OpenAIRE

    2010-01-01

    Calcium is an essential signaling molecule in developing B cells, thus altering calcium dynamics represents a potential target for toxicant effects. GW7845, a tyrosine analog and potent peroxisome proliferator-activated receptor γ agonist, induces rapid mitogen-activated protein kinase (MAPK)–dependent apoptosis in bone marrow B cells. Changes in calcium dynamics are capable of mediating rapid initiation of cell death; therefore, we investigated the contribution of calcium to GW7845-induced a...

  1. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  2. Calcium carbonate overdose

    Science.gov (United States)

    Calcium carbonate is not very poisonous. Recovery is quite likely. But, long-term overuse is more serious than a single overdose, because it can cause kidney damage. Few people die from an antacid overdose. Keep all medicines in child-proof bottles and out ...

  3. High Blood Calcium (Hypercalcemia)

    Science.gov (United States)

    ... as well as kidney function and levels of calcium in your urine. Your provider may do other tests to further assess your condition, such as checking your blood levels of phosphorus (a mineral). Imaging studies also may be helpful, such as bone ...

  4. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about 500...

  5. Calcium aluminate in alumina

    Science.gov (United States)

    Altay, Arzu

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

  6. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...

  7. Bioceramics of calcium orthophosphates.

    Science.gov (United States)

    Dorozhkin, Sergey V

    2010-03-01

    A strong interest in use of ceramics for biomedical applications appeared in the late 1960's. Used initially as alternatives to metals in order to increase a biocompatibility of implants, bioceramics have become a diverse class of biomaterials, presently including three basic types: relatively bioinert ceramics, bioactive (or surface reactive) and bioresorbable ones. Furthermore, any type of bioceramics could be porous to provide tissue ingrowth. This review is devoted to bioceramics prepared from calcium orthophosphates, which belong to the categories of bioresorbable and bioactive compounds. During the past 30-40 years, there have been a number of major advances in this field. Namely, after the initial work on development of bioceramics that was tolerated in the physiological environment, emphasis was shifted towards the use of bioceramics that interacted with bones by forming a direct chemical bond. By the structural and compositional control, it became possible to choose whether the bioceramics of calcium orthophosphates was biologically stable once incorporated within the skeletal structure or whether it was resorbed over time. At the turn of the millennium, a new concept of calcium orthophosphate bioceramics, which is able to regenerate bone tissues, has been developed. Current biomedical applications of calcium orthophosphate bioceramics include replacements for hips, knees, teeth, tendons and ligaments, as well as repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jawbone, spinal fusion and bone fillers after tumor surgery. Potential future applications of calcium orthophosphate bioceramics will include drug-delivery systems, as well as they will become effective carriers of growth factors, bioactive peptides and/or various types of cells for tissue engineering purposes.

  8. Concurrent imaging of synaptic vesicle recycling and calcium dynamics.

    Directory of Open Access Journals (Sweden)

    Haiyan eLi

    2011-11-01

    Full Text Available Synaptic transmission involves the calcium-dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2, and a presynaptically-localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3 with a large dynamic range. The fluorescence of VGLUT1-mOr2 is quenched by the low pH of synaptic vesicles. Exocytosis upon electrical stimulation exposes the luminal mOr2 to the neutral extracellular pH and relieves fluorescence quenching. Re-acidification of the vesicle upon endocytosis again reduces fluorescence intensity. Changes in fluorescence intensity thus monitor synaptic vesicle exo- and endocytosis, as demonstrated previously for the green VGLUT1-pHluorin. To monitor changes in calcium, we fused the synaptic vesicle protein synaptophysin to the recently improved calcium indicator GCaMP3. SyGCaMP3 is targeted to presynaptic varicosities, and exhibits changes in fluorescence in response to electrical stimulation consistent with changes in calcium concentration. Using real-time imaging of both reporters expressed in the same synapses, we determine the time course of changes in VGLUT1 recycling in relation to changes in presynaptic calcium concentration. Inhibition of P/Q- and N-type calcium channels reduces calcium levels, as well as the rate of synaptic vesicle exocytosis and the fraction of vesicles released.

  9. Calcium and magnesium concentrations in mature human milk: influence of calcium intake, age and socioeconomic level.

    Science.gov (United States)

    Vítolo, M R; Valente Soares, L M; Carvalho, E B; Cardoso, C B

    2004-03-01

    Concentrations of calcium and magnesium were measured in mature milk, collected between 30 and 90 days after childbirth, from a group of 90 mothers between 14 and 39 years of age, exclusively breastfeeding. The group was divided into three sub-groups: low socioeconomic-level adolescents (LSAd), low socioeconomic-level adults (LSA), and high socioeconomic-level adults (HSA). Each mother's nutritional status was determined using the body-mass index (BMI) and her eating habits, obtained on the basis of a 24-h dietary recall. Adolescent and adult mothers in the low socioeconomic-level group had lower average calcium intake (LSAd = 618.4 +/- 555.2 mg and LSA = 679.4 +/- 411.4 mg) than adult mothers in the higher socioeconomic-level group (853.6 +/- 415.5 mg). The average concentration of calcium in the adolescent mothers' milk (LSAd) was significantly lower (5.30 +/- 1.42 mmol Ca/L, P = 0.01) than that of the two adult groups (LSA = 5.82 +/- 1.55 mmol Ca/L and HSA = 6.40 mmol Ca/L). The average magnesium concentrations for all groups did not show significant differences (LSAd = 1.06 +/- 0.18, LSA = 1.16 +/- 0.23 and HSA = 1.11 +/- 0.23 mmol Mg/L, for P= 0.16). These results indicate that magnesium concentrations in mature human milk do not seem to depend on maternal nutritional status. The condition of adolescence, however, associated with lower calcium intake by the mother, resulted in lower calcium concentrations in the milk secreted when compared to that of adult mothers.

  10. The 39-Item Parkinson's Disease Questionnaire (PDQ-39): Is it a Unidimensional Construct?

    Science.gov (United States)

    Hagell, Peter; Nilsson, Maria H

    2009-07-01

    The 39-item Parkinson's Disease Questionnaire, and particularly its summary index (PDQ-39SI) is a widely used patient-reported clinical trial endpoint. A basic assumption when summing items into a total score is that they represent a common variable. We therefore assessed the unidimensionality of the PDQ-39SI using Rasch and confirmatory factor analysis. Both analyses showed model misfit. Adjustment for differential item functioning and disordered response category thresholds did not improve model fit, and residual analyses showed deviation from unidimensionality. These data indicate multidimensionality and challenge the interpretation and validity of PDQ-39SI scores. Clinicians and investigators should use and interpret the PDQ-39SI with caution.

  11. Divalent Mn in calcium hydroxyapatite by pulse laser deposition.

    Science.gov (United States)

    Mayer, I; Peto, G; Karacs, A; Molnár, G; Popov, I

    2010-10-01

    Pulse laser deposition (PLD) was used to deposit Mn containing calcium hydroxyapatite (HAMn). The PLD process ensures that the composition of the target and the deposited layer is the same. In some cases additional effort should be made to preserve some volatile components, namely OH. This was ensured by water steam supply. Calcium hydroxyapatite deposited by this method has the same properties as the target in respect to lattice parameters and valence state of Mn, which ensures the fixation between hard tissue and metal implants. This fact makes PLD grown HAMn layer covering implants to be improved for practical use.

  12. 21 CFR 814.39 - PMA supplements.

    Science.gov (United States)

    2010-04-01

    ... sterilization procedures. (5) Changes in packaging. (6) Changes in the performance or design specifications..., § 814.39 was amended by adding paragraph (h), effective Aug. 16, 2010. For the convenience of the...

  13. Calcium signaling in taste cells.

    Science.gov (United States)

    Medler, Kathryn F

    2015-09-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

  14. Lipid body accumulation alters calcium signaling dynamics in immune cells.

    Science.gov (United States)

    Greineisen, William E; Speck, Mark; Shimoda, Lori M N; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J; Turner, Helen

    2014-09-01

    There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcɛRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signaling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcɛRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signaling pathway and its downstream targets.

  15. Role of magnesium on the biomimetic deposition of calcium phosphate

    Science.gov (United States)

    Sarma, Bimal K.; Sarma, Bikash

    2016-10-01

    Biomimetic depositions of calcium phosphate (CaP) are carried out using simulated body fluid (SBF), calcifying solution and newly developed magnesium containing calcifying solution. Calcium phosphate has a rich phase diagram and is well known for its excellent biocompatibility and bioactivity. The most common phase is hydroxyapatite (HAp), an integral component of human bone and tooth, widely used in orthopedic and dental applications. In addition, calcium phosphate nanoparticles show promise for the targeted drug delivery. The doping of calcium phosphate by magnesium, zinc, strontium etc. can change the protein uptake by CaP nanocrystals. This work describes the role of magnesium on the nucleation and growth of CaP on Ti and its oxide substrates. X-ray diffraction studies confirm formation of HAp nanocrystals which closely resemble the structure of bone apatite when grown using SBF and calcifying solution. It has been observed that magnesium plays crucial role in the nucleation and growth of calcium phosphate. A low magnesium level enhances the crystallinity of HAp while higher magnesium content leads to the formation of amorphous calcium phosphate (ACP) phase. Interestingly, the deposition of ACP phase is rapid when magnesium ion concentration in the solution is 40% of calcium plus magnesium ions concentration. Moreover, high magnesium content alters the morphology of CaP films.

  16. Fruit Calcium: Transport and Physiology

    Directory of Open Access Journals (Sweden)

    Bradleigh eHocking

    2016-04-01

    Full Text Available 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 fruit development, physical traits and disease susceptibility 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 ripening and 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 towards 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

  17. 49 CFR 1242.30 - Dismantling retired road property and depreciation (accounts XX-17-39, XX-18-39, XX-19-39, 62-17...

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Dismantling retired road property and depreciation (accounts XX-17-39, XX-18-39, XX-19-39, 62-17-00, 62-18-00, and 62-19-00). 1242.30 Section 1242.30....30 Dismantling retired road property and depreciation (accounts XX-17-39, XX-18-39, XX-19-39,...

  18. DISTILLATION OF CALCIUM

    Science.gov (United States)

    Barton, J.

    1954-07-27

    This invention relates to an improvement in the process for the purification of caicium or magnesium containing an alkali metal as impurity, which comprises distiiling a batch of the mixture in two stages, the first stage distillation being carried out in the presence of an inert gas at an absolute pressure substantially greater than the vapor pressure of calcium or maguesium at the temperature of distillation, but less than the vaper pressure at that temperature of the alkali metal impurity so that only the alkali metal is vaporized and condensed on a condensing surface. A second stage distilso that substantially only the calcium or magnesium distills under its own vapor pressure only and condenses in solid form on a lower condensing surface.

  19. Synthesis of calcium superoxide

    Science.gov (United States)

    Rewick, R. T.; Blucher, W. G.; Estacio, P. L.

    1972-01-01

    Efforts to prepare Ca(O2) sub 2 from reactions of calcium compounds with 100% O3 and with O(D-1) atoms generated by photolysis of O3 at 2537 A are described. Samples of Ca(OH) sub 2, CaO, CaO2, Ca metal, and mixtures containing suspected impurities to promote reaction have been treated with excess O3 under static and flow conditions in the presence and absence of UV irradiation. Studies with KO2 suggest that the superoxide anion is stable to radiation at 2537 A but reacts with oxygen atoms generated by the photolysis of O3 to form KO3. Calcium superoxide is expected to behave in an analogous.

  20. Tertiary dentinogenesis with calcium hydroxide: a review of proposed mechanisms.

    Science.gov (United States)

    Sangwan, P; Sangwan, A; Duhan, J; Rohilla, A

    2013-01-01

    Calcium hydroxide has been used extensively in dentistry for a century. Despite its widespread use as a pulp-capping agent, its mechanisms of action still remain ambiguous. Understanding its modes of action will lead to a broader understanding of the mechanisms associated with induced dentinogenesis and help in optimizing the currently available agents to target specific regenerative processes to obtain the best possible clinical outcomes. A literature search relating to mechanisms of dentinogenesis of calcium hydroxide up to December 2011 was carried out using pubmed and MEDLINE database searches as well as manual searching of cross-references from identified studies. Resulting suggestions regarding dentinogenic mechanisms of calcium hydroxide range from direct irritating action of the material to induction of release of biologically active molecules. The purpose of this article is to discuss various mechanisms through which calcium hydroxide may induce tertiary dentinogenesis in the light of observations made in included studies.

  1. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2005-01-01

    whether bone cells are capable of communicating via intercellular calcium signals, and determine by which mechanisms the cells propagate the signals. First, we found that osteoblastic cells can propagate intercellular calcium transients upon mechanical stimulation, and that there are two principally...... to osteoclasts as well. We demonstrated that paracrine action of ATP was responsible for the wave propagation, but now the purinergic P2X7 receptor was involved. Thus, the studies demonstrate that calcium signals can be propagated not only among osteoblasts, but also between osteoblasts and osteoclasts...... in response to mechanical stimulation. Thus, intercellular calcium signaling can be a mechanism by which mechanical stimuli on bone are translated into biological signals in bone cells, and propagated through the network of cells in bone. Further, the observations offer new pharmacological targets...

  2. Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.

    Science.gov (United States)

    Chameau, Pascal; Qin, Yongjun; Spijker, Sabine; Smit, August Benjamin; Smit, Guus; Joëls, Marian

    2007-01-01

    Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover, we addressed the putative gene targets that eventually lead to the enhanced calcium currents. Electrophysiological recordings were performed in nucleated patches that allow excellent voltage control. Calcium currents in these patches almost exclusively involve N- and L-type channels. We found that L- but not N-type calcium currents were largely enhanced after treatment with a high dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage dependency and kinetic properties of the currents were unaffected by the hormone. Nonstationary noise analysis suggests that the increased current is not caused by a larger unitary conductance, but rather to a doubling of the number of functional channels. Quantitative real-time PCR revealed that transcripts of the Ca(v)1 subunits encoding for the N- or L-type calcium channels are not upregulated in the mouse CA1 area; instead, a strong, direct, and consistent upregulation of the beta4 subunit was observed. This indicates that the corticosteroid-induced increase in number of L-type calcium channels is not caused by a simple transcriptional regulation of the pore-forming subunit of the channels.

  3. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

    This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Geneviève Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Université Libre de Bruxelles;Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbrück Center for Molecular Medicine, Berlin;Vivien Kirk is an Associate Professor in the Depar...

  4. Calcium signalling and calcium channels: evolution and general principles.

    Science.gov (United States)

    Verkhratsky, Alexei; Parpura, Vladimir

    2014-09-15

    Calcium as a divalent cation was selected early in evolution as a signaling molecule to be used by both prokaryotes and eukaryotes. Its low cytosolic concentration likely reflects the initial concentration of this ion in the primordial soup/ocean as unicellular organisms were formed. As the concentration of calcium in the ocean subsequently increased, so did the diversity of homeostatic molecules handling calcium. This includes the plasma membrane channels that allowed the calcium entry, as well as extrusion mechanisms, i.e., exchangers and pumps. Further diversification occurred with the evolution of intracellular organelles, in particular the endoplasmic reticulum and mitochondria, which also contain channels, exchanger(s) and pumps to handle the homeostasis of calcium ions. Calcium signalling system, based around coordinated interactions of the above molecular entities, can be activated by the opening of voltage-gated channels, neurotransmitters, second messengers and/or mechanical stimulation, and as such is all-pervading pathway in physiology and pathophysiology of organisms.

  5. Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia

    Science.gov (United States)

    Wilson, Rosamund J; Copley, J Brian

    2017-01-01

    Background Calcium-based and non-calcium-based phosphate binders have similar efficacy in the treatment of hyperphosphatemia; however, calcium-based binders may be associated with hypercalcemia, vascular calcification, and adynamic bone disease. Scope A post hoc analysis was carried out of data from a 16-week, Phase IV study of patients with end-stage renal disease (ESRD) who switched to lanthanum carbonate monotherapy from baseline calcium acetate/calcium carbonate monotherapy. Of the intent-to-treat population (N=2520), 752 patients with recorded dose data for calcium acetate (n=551)/calcium carbonate (n=201) at baseline and lanthanum carbonate at week 16 were studied. Elemental calcium intake, serum phosphate, corrected serum calcium, and serum intact parathyroid hormone levels were analyzed. Findings Of the 551 patients with calcium acetate dose data, 271 (49.2%) had an elemental calcium intake of at least 1.5 g/day at baseline, and 142 (25.8%) had an intake of at least 2.0 g/day. Mean (95% confidence interval [CI]) serum phosphate levels were 6.1 (5.89, 6.21) mg/dL at baseline and 6.2 (6.04, 6.38) mg/dL at 16 weeks; mean (95% CI) corrected serum calcium levels were 9.3 (9.16, 9.44) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Of the 201 patients with calcium carbonate dose data, 117 (58.2%) had an elemental calcium intake of at least 1.5 g/day, and 76 (37.8%) had an intake of at least 2.0 g/day. Mean (95% CI) serum phosphate levels were 5.8 (5.52, 6.06) mg/dL at baseline and 5.8 (5.53, 6.05) mg/dL at week 16; mean (95% CI) corrected serum calcium levels were 9.7 (9.15, 10.25) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Conclusion Calcium acetate/calcium carbonate phosphate binders, taken to control serum phosphate levels, may result in high levels of elemental calcium intake. This may lead to complications related to calcium balance. PMID:28182142

  6. Calibration of CR-39 with monoenergetic protons

    Science.gov (United States)

    Xiaojiao, Duan; Xiaofei, Lan; Zhixin, Tan; Yongsheng, Huang; Shilun, Guo; Dawei, Yang; Naiyan, Wang

    2009-10-01

    Calibration of solid state nuclear track detector CR-39 was carried out with very low-energy monoenergetic protons of 20-100 keV from a Cockcroft Walton accelerator. To reduce the beam of the proton from the accelerator, a novel method was adopted by means of a high voltage pulse generator. The irradiation time of the proton beam on each CR-39 sheet was shortened to one pulse with duration of 100 ns, so that very separated proton tracks around 104 cm-2 can be irradiated and observed and measured on the surface of the CR-39 detector after etching. The variations of track diameter with etching time as well as with proton energy response curve has been carefully calibrated for the first time in this very low energy region. The calibration shows that the optical limit for the observation of etched tracks of protons in CR-39 is about or a little lower that 20 keV, above which the proton tracks can be seen clearly and the response curve can be used to distinguish protons from the other ions and determine the energy of the protons. The extension of response curve of protons from traditionally 20 to 100 keV in CR-39 is significant in retrieving information of protons produced in the studies of nuclear physics, plasma physics, ultrahigh intensity laser physics and laser acceleration.

  7. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

    Science.gov (United States)

    Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E.; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y.; Simpson, Michael A.; Chong, W. K.; Jacques, Thomas S.; Woltjer, Randy L.; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M.; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R.; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A. M.; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S.; Yoganathan, Sangeetha; Dale, Russell C.; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A.; Enns, Caroline A.; Hayflick, Susan J.; Clayton, Peter T.; Mills, Philippa B.; Kurian, Manju A.; Wilson, Stephen W.

    2016-01-01

    Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism–dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates. PMID:27231142

  8. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

    Science.gov (United States)

    Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y; Simpson, Michael A; Chong, W K; Jacques, Thomas S; Woltjer, Randy L; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A M; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S; Yoganathan, Sangeetha; Dale, Russell C; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A; Enns, Caroline A; Hayflick, Susan J; Clayton, Peter T; Mills, Philippa B; Kurian, Manju A; Wilson, Stephen W

    2016-05-27

    Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.

  9. Effect of vitamin D/sub 3/, other drugs altering serum calcium or phosphorus concentrations, and desoxycorticosterone on the distribution of Tc-99m pyrophosphate between target and nontarget tissues. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Carr, E.A. Jr.; Carroll, M.; Montes, M.

    1981-06-01

    Radioactive imaging agents are chemically designed for selective distribution. Another approach to selectivity is to find stable compounds that favorably influence this distribution. Using a rat model of myocardial necrosis, the effects of various stable compounds on the ratio, uptake of Tc-99m pyrophosphate (PPi) by the target lesion/uptake by the principal nontarget, bone (L/B) were studied. Vitamin D/sub 3/s ability to increase L/B was mediated by the hypercalcemia and hyperphosphatemia that it caused. In contrast, pulse doses of desoxycorticosterone acetate (DOCA) at 7 and 6 h before killing increased uptake by lesion, with no change in serum (Ca) and minimal changes in serum (P), (Na), and (K). DOCA also increased the lesion-to-blood ratio. These results encourage further study of DOCA's effect and investigation of other stable drugs that may influence distribution of other imaging agents.

  10. Calcium – how and why?

    Indian Academy of Sciences (India)

    J K Jaiswal

    2001-09-01

    Calcium is among the most commonly used ions, in a multitude of biological functions, so much so that it is impossible to imagine life without calcium. In this article I have attempted to address the question as to how calcium has achieved this status with a brief mention of the history of calcium research in biology. It appears that during the origin and early evolution of life the Ca2+ ion was given a unique opportunity to be used in several biological processes because of its unusual physical and chemical properties.

  11. Calcium Phosphate Biomaterials: An Update

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Current calcium phosphate (CaP) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricalcium phosphate ( β-TCP ) , biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of composites (CaP/polymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses. This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity, osteoconductivity, osteoinductivity.

  12. Calcium measurement methods

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-09-01

    Full Text Available Rightly stressed by prof. Wolfgang Walz in the Preface to the series Neuromethods series, the “careful application of methods is probably the most important step in the process of scientific inquiry”. Thus, I strongly suggest to all those interested in calcium signaling and especially to the new-comers in the hot topic of neuroscience (which has so much space even in science-society debate for its implications in legal issues and in the judge-decision process to take profit from this so well edited book. I am saying this since prof. Verkhratsky and prof. Petersen......

  13. Calcium Nutrition and Extracellular Calcium Sensing: Relevance for the Pathogenesis of Osteoporosis, Cancer and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Meinrad Peterlik

    2013-01-01

    Full Text Available Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR. This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca2+ to function as a “first messenger” for various intracellular signaling cascades. Evidence demonstrates that Ca2+/CaSR signaling in functional linkage with vitamin D receptor (VDR-activated pathways (i promotes osteoblast differentiation and formation of mineralized bone; (ii targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; (iii evokes Ca2+ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca2+/CaSR signaling opens Ca2+-sensitive K+ conductance channels in vascular endothelial cells, and also participates in IP3-dependent regulation of cytoplasmic Ca2+, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca2+/CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease.

  14. Cosmic ray source abundance of calcium

    CERN Document Server

    Perron, C

    1978-01-01

    Re-examines the results of experiments in which ultra-high purity iron targets were irradiated by protons from the two CERN accelerators (600 MeV and 21 GeV); the spallation products were then chemically separated, and their isotopic composition determined by mass spectrometry. Ratios of cross-sections for calcium production by spallation of iron show that /sup 42/Ca, /sup 43/Ca and /sup 44/Ca have about the same abundance, about 10-15% that of iron, confirming earlier studies. (11 refs).

  15. Hybrid Calcium Phosphate Coatings for Titanium Implants

    Science.gov (United States)

    Kharapudchenko, E.; Ignatov, V.; Ivanov, V.; Tverdokhlebov, S.

    2017-01-01

    Hybrid multilayer coatings were obtained on titanium substrates by the combination of two methods: the micro-arc oxidation in phosphoric acid solution with the addition of calcium compounds to high supersaturated state and RF magnetron sputtering of the target made of synthetic hydroxyapatite. 16 different groups of coatings were formed on titanium substrates and in vitro studies were conducted in accordance with ISO 23317 in the solution simulating body fluid. The studies using SEM, XRD of the coatings of the samples before and after exposure to SBF were performed. The features of morphology, chemical and phase composition of the studied coatings are shown.

  16. 7 CFR 982.39 - Duties.

    Science.gov (United States)

    2010-01-01

    ... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE HAZELNUTS GROWN IN OREGON AND WASHINGTON Order Regulating Handling Hazelnut Control Board § 982.39 Duties. The Board shall have among others the... investigate the growing, shipping and marketing conditions with respect to hazelnuts, and assemble data...

  17. 39 CFR 262.3 - Information.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Information. 262.3 Section 262.3 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION RECORDS AND INFORMATION MANAGEMENT DEFINITIONS § 262.3 Information. Data combined with the knowledge of its context and having the potential...

  18. 39 CFR 3030.41 - Satisfaction.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Satisfaction. 3030.41 Section 3030.41 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL RULES FOR COMPLAINTS Settlement § 3030.41 Satisfaction. (a) If a complaint is resolved informally, in whole or in part, subsequent to Commission action...

  19. 39 CFR 551.6 - Pricing.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Pricing. 551.6 Section 551.6 Postal Service UNITED STATES POSTAL SERVICE POSTAGE PROGRAMS SEMIPOSTAL STAMP PROGRAM § 551.6 Pricing. (a) The Semipostal Authorization Act, as amended by Public Law 107-67, section 652, 115 Stat. 514 (2001), prescribes that the...

  20. 39 CFR 262.5 - Systems (Privacy).

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Systems (Privacy). 262.5 Section 262.5 Postal... DEFINITIONS § 262.5 Systems (Privacy). (a) Privacy Act system of records. A Postal Service system containing... individual. (c) Computer matching program. A “matching program,” as defined in the Privacy Act, 5 U.S.C....

  1. 39 CFR 3060.12 - Asset allocation.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Asset allocation. 3060.12 Section 3060.12 Postal... COMPETITIVE PRODUCTS ENTERPRISE § 3060.12 Asset allocation. Within 6 months of January 23, 2009, and for each... competitive products enterprise using a method of allocation based on appropriate revenue or cost...

  2. 39 CFR 265.10 - Annual report.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Annual report. 265.10 Section 265.10 Postal... Annual report. A report concerning the administration of the Freedom of Information Act and this part..., with the first such report, for fiscal year 1998, due on or before February 1, 1999. Data for...

  3. 39 CFR 3060.41 - Supporting documentation.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Supporting documentation. 3060.41 Section 3060.41 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL ACCOUNTING PRACTICES AND TAX RULES FOR THE THEORETICAL COMPETITIVE PRODUCTS ENTERPRISE § 3060.41 Supporting documentation. (a) In support of...

  4. 39 CFR 957.27 - Suspension.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Suspension. 957.27 Section 957.27 Postal Service... SUSPENSION FROM CONTRACTING § 957.27 Suspension. (a) Any firm or individual suspended under chapter 3, section 7 of the Postal Service Purchasing Manual who believes that the suspension has not been...

  5. 39 CFR 955.28 - Suspension.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Suspension. 955.28 Section 955.28 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE BEFORE THE POSTAL SERVICE BOARD OF CONTRACT APPEALS § 955.28 Suspension. (a) Whenever at any time it appears that the parties are in agreement as...

  6. 9 CFR 311.39 - Biological residues.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Biological residues. 311.39 Section... Biological residues. Carcasses, organs, or other parts of carcasses of livestock shall be condemned if it is determined that they are adulterated because of the presence of any biological residues....

  7. 10 CFR 39.61 - Training.

    Science.gov (United States)

    2010-01-01

    ... licensed materials, remote handling tools, and radiation survey instruments, as appropriate for the logging... COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Radiation Safety Requirements § 39.61 Training. (a) The licensee may not permit an individual to act as a logging supervisor until that...

  8. 41 CFR 101-39.303 - Maintenance.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Maintenance. 101-39.303... Maintenance. In order to ensure uninterrupted operation of GSA Interagency Fleet Management System (IFMS) vehicles, safety and preventive maintenance inspections will be performed at regularly scheduled...

  9. 39 CFR 261.2 - Authority.

    Science.gov (United States)

    2010-07-01

    .... Included is the authority to issue records management policy and to delegate or take appropriate action if... UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION RECORDS AND INFORMATION MANAGEMENT § 261.2... dispose of such property. (b) 39 CFR 262.2 assigns to the Postal Service Records Office, located under...

  10. 39 CFR 501.19 - Intellectual property.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Intellectual property. 501.19 Section 501.19... POSTAGE EVIDENCING SYSTEMS § 501.19 Intellectual property. Providers submitting Postage Evidencing Systems to the Postal Service for approval are responsible for obtaining all intellectual property...

  11. 49 CFR 230.39 - Broken staybolts.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Staybolts § 230.39 Broken staybolts. (a) Maximum allowable number of broken staybolts. No boiler shall be... inside the firebox or combustion chamber on a straight line. No boiler shall be allowed to remain...

  12. 39 CFR 266.10 - Computer matching.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Computer matching. 266.10 Section 266.10 Postal... Computer matching. (a) General. Any agency or Postal Service component that wishes to use records from a... records must submit its proposal to the Postal Service Manager Records Office. Computer matching...

  13. 39 CFR 3020.75 - Review.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Review. 3020.75 Section 3020.75 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL PRODUCT LISTS Proposal of the Commission To Modify the Product Lists Described Within the Mail Classification Schedule § 3020.75 Review. The Commission shall...

  14. 39 CFR 3020.55 - Review.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Review. 3020.55 Section 3020.55 Postal Service... the Product Lists Described Within the Mail Classification Schedule § 3020.55 Review. The Commission shall review the request, the Postal Service reply, and any public comment to determine whether...

  15. 39 CFR 3020.34 - Review.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Review. 3020.34 Section 3020.34 Postal Service... the Product Lists Described Within the Mail Classification Schedule § 3020.34 Review. The Commission shall review the request and responsive comments. The Commission shall either: (a) Approve the...

  16. 39 CFR 221.5 - Headquarters organization.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Headquarters organization. 221.5 Section 221.5 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION GENERAL ORGANIZATION § 221.5 Headquarters organization. (a) Postmaster General—(1) Appointment. The postmaster general (PMG), the...

  17. 39 CFR 221.6 - Field organization.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Field organization. 221.6 Section 221.6 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION GENERAL ORGANIZATION § 221.6 Field organization. (a) General. There are 8 areas, each with a vice president. (b) Area locations. Area...

  18. 39 CFR 7.2 - Open meetings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Open meetings. 7.2 Section 7.2 Postal Service... (ARTICLE VII) § 7.2 Open meetings. (a) It is the policy of the United States, established in section 2 of..., except as specifically permitted by statute, every portion of every meeting of the Board of Governors...

  19. 39 CFR 268.1 - General principles.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false General principles. 268.1 Section 268.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION PRIVACY OF INFORMATION-EMPLOYEE RULES OF CONDUCT § 268.1 General principles. In order to conduct its business, the Postal Service has...

  20. 39 CFR 602.1 - General principles.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false General principles. 602.1 Section 602.1 Postal Service UNITED STATES POSTAL SERVICE PROCUREMENT SYSTEM FOR THE U.S. POSTAL SERVICE: INTELLECTUAL PROPERTY RIGHTS OTHER THAN PATENTS INTELLECTUAL PROPERTY RIGHTS OTHER THAN PATENTS § 602.1 General principles....

  1. 39 CFR 601.100 - Purchasing policy.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Purchasing policy. 601.100 Section 601.100 Postal Service UNITED STATES POSTAL SERVICE PROCUREMENT SYSTEM FOR THE U.S. POSTAL SERVICE: INTELLECTUAL PROPERTY RIGHTS OTHER THAN PATENTS PURCHASING OF PROPERTY AND SERVICES § 601.100 Purchasing policy. The...

  2. 39 CFR 955.34 - Sanctions.

    Science.gov (United States)

    2010-07-01

    ... attorney, the standards include the rules of professional conduct and ethics of the jurisdictions in which... established for the purpose of the case; (2) Forbidding challenge of the accuracy of any evidence; (3... accordance with 39 CFR Part 951, referral to an appropriate licensing authority, or such other action...

  3. 39 CFR 3004.12 - Reading room.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Reading room. 3004.12 Section 3004.12 Postal... Reading room. (a) The Commission maintains a public reading room at its offices (901 New York Avenue, NW., Suite 200, Washington, DC 20268-0001) and an electronic reading room at http://www.prc.gov. The...

  4. Reference: 39 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available 39 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u12837954i Madson Michael...as C|Dunand Christophe|Li Xuemei|Madson Michael|Reiter Wolf-Dieter|Shoue Douglas A|Vanzin Gary F|Verma Rajeev

  5. 37 CFR 251.39 - Remedies.

    Science.gov (United States)

    2010-07-01

    ....39 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT ARBITRATION ROYALTY PANEL RULES AND PROCEDURES COPYRIGHT ARBITRATION ROYALTY PANEL RULES OF PROCEDURE Standards of... who engaged in the ethical violation— (1) Referral of the matter to the bar or...

  6. 39 CFR 3020.76 - Further proceedings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Further proceedings. 3020.76 Section 3020.76... the Product Lists Described Within the Mail Classification Schedule § 3020.76 Further proceedings. If the Commission determines that further proceedings are appropriate, a conference shall be scheduled...

  7. 39 CFR 3020.35 - Further proceedings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Further proceedings. 3020.35 Section 3020.35... proceedings. If the Commission determines that further proceedings are necessary, a conference shall be...) Explain the reasons for not going forward with additional proceedings and approve the request to...

  8. 39 CFR 3020.56 - Further proceedings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Further proceedings. 3020.56 Section 3020.56... proceedings. If the Commission determines that further proceedings are necessary, a conference shall be... reasons for not going forward with formal proceedings; or (d) Direct other action as the Commission...

  9. 39 CFR 3001.41 - Rulemaking proceedings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Rulemaking proceedings. 3001.41 Section 3001.41... Applicability § 3001.41 Rulemaking proceedings. (a) General notice. Before the adoption of any rule of general... it impracticable, unnecessary, or contrary to the public interest to give such notice, it may...

  10. 39 CFR 960.18 - Further proceedings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Further proceedings. 960.18 Section 960.18 Postal... JUSTICE ACT IN POSTAL SERVICE PROCEEDINGS Procedures for Considering Applications § 960.18 Further proceedings. (a) Ordinarily, the determination of an award will be made on the basis of the written...

  11. Molecular mechanisms of crystallization impacting calcium phosphate cements

    Science.gov (United States)

    Giocondi, Jennifer L.; El-Dasher, Bassem S.; Nancollas, George H.; Orme, Christine A.

    2010-01-01

    The biomineral calcium hydrogen phosphate dihydrate (CaHPO4·2H2O), known as brushite, is a malleable material that both grows and dissolves faster than most other calcium minerals, including other calcium phosphate phases, calcium carbonates and calcium oxalates. Within the body, this ready formation and dissolution can play a role in certain diseases, such as kidney stone and plaque formation. However, these same properties, along with brushite’s excellent biocompatibility, can be used to great benefit in making resorbable biomedical cements. To optimize cements, additives are commonly used to control crystallization kinetics and phase transformation. This paper describes the use of in situ scanning probe microscopy to investigate the role of several solution parameters and additives in brushite atomic step motion. Surprisingly, this work demonstrates that the activation barrier for phosphate (rather than calcium) incorporation limits growth kinetics and that additives such as magnesium, citrate and bisphosphonates each influence step motion in distinctly different ways. Our findings provide details of how, and where, molecules inhibit or accelerate kinetics. These insights have the potential to aid in designing molecules to target specific steps and to guide synergistic combinations of additives. PMID:20308110

  12. Who should receive calcium and vitamin D supplementation?

    Science.gov (United States)

    Verbrugge, Frederik H; Gielen, Evelien; Milisen, Koen; Boonen, Steven

    2012-09-01

    Combined calcium and vitamin D supplementation is recommended in the prevention and treatment of osteoporosis. Until recently, supplementation was perceived as harmless without adverse effects. However, recent meta-analyses have provided evidence suggesting that calcium supplements, whether or not in combination with vitamin D, may be associated with cardiovascular risks. Although this finding constitutes a safety signal that has to be taken seriously, these data have to be interpreted with some caution. Current data do not allow definite conclusions to be drawn, but require further independent confirmation, since in numerous large studies, combined calcium and vitamin D supplementation did not increase cardiovascular events, even in the most frail and elderly populations. Nevertheless, it seems appropriate to correct calcium deficiency preferably by enhancing dietary intake and to target supplementation on individuals at high risk of fracture or in whom calcium and vitamin D deficiency is highly prevalent. Other trials have shown an increased risk of falls and fractures with annual oral administration of high dose of vitamin D. Therefore, supplementation with more frequent, lower doses is preferred. Yet, the optimal dosing schedule is unknown and needs further study. In order to correct age-associated secondary hyperparathyroidism and to prevent osteoporotic fractures, a daily dose of 1,000-1,200 mg calcium and 800 IU vitamin D is recommended in elderly or institutionalised people, patients with established osteoporosis and individuals on glucocorticoids.

  13. Molecular mechanisms of crystallization impacting calcium phosphate cements.

    Science.gov (United States)

    Giocondi, Jennifer L; El-Dasher, Bassem S; Nancollas, George H; Orme, Christine A

    2010-04-28

    The biomineral calcium hydrogen phosphate dihydrate (CaHPO(4).2H(2)O), known as brushite, is a malleable material that both grows and dissolves faster than most other calcium minerals, including other calcium phosphate phases, calcium carbonates and calcium oxalates. Within the body, this ready formation and dissolution can play a role in certain diseases, such as kidney stone and plaque formation. However, these same properties, along with brushite's excellent biocompatibility, can be used to great benefit in making resorbable biomedical cements. To optimize cements, additives are commonly used to control crystallization kinetics and phase transformation. This paper describes the use of in situ scanning probe microscopy to investigate the role of several solution parameters and additives in brushite atomic step motion. Surprisingly, this work demonstrates that the activation barrier for phosphate (rather than calcium) incorporation limits growth kinetics and that additives such as magnesium, citrate and bisphosphonates each influence step motion in distinctly different ways. Our findings provide details of how, and where, molecules inhibit or accelerate kinetics. These insights have the potential to aid in designing molecules to target specific steps and to guide synergistic combinations of additives.

  14. Hybrid calcium phosphate coatings for implants

    Science.gov (United States)

    Malchikhina, Alena I.; Shesterikov, Evgeny V.; Bolbasov, Evgeny N.; Ignatov, Viktor P.; Tverdokhlebov, Sergei I.

    2016-08-01

    Monophasic biomaterials cannot provide all the necessary functions of bones or other calcined tissues. It is necessary to create for cancer patients the multiphase materials with the structure and composition simulating the natural bone. Such materials are classified as hybrid, obtained by a combination of chemically different components. The paper presents the physical, chemical and biological studies of coatings produced by hybrid technologies (HT), which combine primer layer and calcium phosphate (CaP) coating. The first HT type combines the method of vacuum arc titanium primer layer deposition on a stainless steel substrate with the following micro-arc oxidation (MAO) in phosphoric acid solution with addition of calcium compounds to achieve high supersaturated state. MAO CaP coatings feature high porosity (2-8%, pore size 5-7 µm) and surface morphology with the thickness greater than 5 µm. The thickness of Ti primer layer is 5-40 µm. Amorphous MAO CaP coating micro-hardness was measured at maximum normal load Fmax = 300 mN. It was 3.1 ± 0.8 GPa, surface layer elasticity modulus E = 110 ± 20 GPa, roughness Ra = 0.9 ± 0.1 µm, Rz = 7.5 ± 0.2 µm, which is less than the titanium primer layer roughness. Hybrid MAO CaP coating is biocompatible, able to form calcium phosphates from supersaturated body fluid (SBF) solution and also stimulates osteoinduction processes. The second HT type includes the oxide layer formation by thermal oxidation and then CaP target radio frequency magnetron sputtering (RFMS). Oxide-RFMS CaP coating is a thin dense coating with good adhesion to the substrate material, which can be used for metal implants. The RFMS CaP coating has thickness 1.6 ± 0.1 µm and consists of main target elements calcium and phosphorus and Ca/P ratio 2.4. The second HT type can form calcium phosphates from SBF solution. In vivo study shows that hybrid RFMS CaP coating is biocompatible and produces fibrointegration processes.

  15. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... in Balance › Vitamin D, Calcium, and Bone Health Vitamin D, Calcium, and Bone Health March 2012 Download ... also helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin ...

  16. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000490.htm Calcium, vitamin D, and your bones To use the sharing ... and maintain strong bones. How Much Calcium and Vitamin D do I Need? Amounts of calcium are ...

  17. Vitamin D and Intestinal Calcium Absorption

    OpenAIRE

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J.; Seth, Tanya

    2011-01-01

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D3 (1,25(OH)2D3) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium throu...

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

    OpenAIRE

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

    2013-01-01

    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate ...

  19. 21 CFR 184.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the...

  20. Launch Complex 39A, SWMU 008, Operations, Maintenance, and Monitoring Report, Kennedy Space Center, FL

    Science.gov (United States)

    Wilson, Deborah M.

    2016-01-01

    This Operations, Maintenance, and Monitoring Report (OMMR) presents the findings, observations, and results from Year 1 operation of the air sparging (AS) groundwater interim measure (IM) for High-Concentration Plumes (HCPs) and Low-Concentration Plumes (LCPs) within the perimeter fence line at Launch Complex 39A (LC39A) located at Kennedy Space Center (KSC), Florida. The objective of the LC39A groundwater IM is to actively decrease concentrations of trichloroethene (TCE), cis-1,2-dichloroethene (cDCE), and vinyl chloride (VC) in groundwater in the HCP and LCP within the pad perimeter fence line via AS to levels less than Florida Department of Environmental Protection (FDEP) Groundwater Cleanup Target Levels (GCTLs). The objective was developed because LC39A is currently being leased to Space Exploration Technologies (SpaceX), and the original IM for monitored natural attenuation (MNA) over an extended period of time was not suitable for future planned site use.

  1. Evolution of the Calcium Paradigm: The Relation between Vitamin D, Serum Calcium and Calcium Absorption

    Directory of Open Access Journals (Sweden)

    Borje E. Christopher Nordin

    2010-09-01

    Full Text Available Osteoporosis is the index disease for calcium deficiency, just as rickets/osteomalacia is the index disease for vitamin D deficiency, but there is considerable overlap between them. The common explanation for this overlap is that hypovitaminosis D causes malabsorption of calcium which then causes secondary hyperparathyroidism and is effectively the same thing as calcium deficiency. This paradigm is incorrect. Hypovitaminosis D causes secondary hyperparathyroidism at serum calcidiol levels lower than 60 nmol/L long before it causes malabsorption of calcium because serum calcitriol (which controls calcium absorption is maintained until serum calcidiol falls below 20 nmol/L. This secondary hyperparathyroidism, probably due to loss of a “calcaemic” action of vitamin D on bone first described in 1957, destroys bone and explains why vitamin D insufficiency is a risk factor for osteoporosis. Vitamin D thus plays a central role in the maintenance of the serum (ionised calcium, which is more important to the organism than the preservation of the skeleton. Bone is sacrificed when absorbed dietary calcium does not match excretion through the skin, kidneys and bowel which is why calcium deficiency causes osteoporosis in experimental animals and, by implication, in humans.

  2. Mars at Ls 39o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    18 April 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 39o during a previous Mars year. This month, Mars looks similar, as Ls 39o occurs in mid-April 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  3. Mars at Ls 39o: Tharsis

    Science.gov (United States)

    2006-01-01

    4 April 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 39o during a previous Mars year. This month, Mars looks similar, as Ls 39o occurs in mid-April 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  4. Optical and Magnetic Trapping of Potassium 39

    Science.gov (United States)

    Ensher, Jason; Cornell, Eric; Cataliotti, Francesco; Fort, Chiara; Marin, Francesco; Prevedelli, Marco; Inguscio, Massimo; Ricci, Leonardo; Tino, Guglielmo

    1998-05-01

    We present measurments of optical trapping and cooling and magnetic trapping of ^39K in a double-MOT apparatus. (Optics Lett. 21, 290(1996)) We have measured light-assisted collisional loss rates from our second MOT over a range of trap light intensities. At an intensity of 10 mW/cm^2 we find a loss rate parameter β of 2 x 10-11 cc/s. β increases with trap light intensity and is consistent with the values measured by Williamson and Walker (JOSA B 12, 1393 (1995)). We also present studies of the temperature of atoms in a MOT of ^39K. Under certain conditions of repump light intensity and trap light detuning we measure temperatures nearly as low as the Doppler Limit. Finally, we report on prelimiary results of magnetic trapping in which we have trapped several 10^7 atoms in a quadrupole magnetic trap.

  5. Limestone reaction in calcium aluminate cement–calcium sulfate systems

    Energy Technology Data Exchange (ETDEWEB)

    Bizzozero, Julien, E-mail: julien.bizzozero@gmail.com; Scrivener, Karen L.

    2015-10-15

    This paper reports a study of ternary blends composed of calcium aluminate cement, calcium sulfate hemihydrate and limestone. Compressive strength tests and hydration kinetics were studied as a function of limestone and calcium sulfate content. The phase evolution and the total porosity were followed and compared to thermodynamic simulation to understand the reactions involved and the effect of limestone on these binders. The reaction of limestone leads to the formation of hemicarboaluminate and monocarboaluminate. Increasing the ratio between sulfate and aluminate decreases the extent of limestone reaction.

  6. 39 CFR 6.2 - Special meetings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Special meetings. 6.2 Section 6.2 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE MEETINGS (ARTICLE VI) § 6.2 Special meetings. Consistent with the provisions of §§ 6.6 and 7.5 of these bylaws, the...

  7. Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases

    Institute of Scientific and Technical Information of China (English)

    Nasrin NFJATBAKHSH; Zhong-ping FENG

    2011-01-01

    Calcium ion entry through voltage-gated calcium channels is essential for cellular signalling in a wide variety of cells and multiple physiological processes. Perturbations of voltage-gated calcium channel function can lead to pathophysiological consequences. Calcium binding proteins serve as calcium sensors and regulate the calcium channel properties via feedback mechanisms. This review highlights the current evidences of calcium binding protein-mediated channel regulation in human diseases.

  8. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  9. Fibroblast growth factor-23 negates 1,25(OH)2D3-induced intestinal calcium transport by reducing the transcellular and paracellular calcium fluxes.

    Science.gov (United States)

    Khuituan, Pissared; Wongdee, Kannikar; Jantarajit, Walailuk; Suntornsaratoon, Panan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2013-08-01

    The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been known to stimulate intestinal calcium transport via both transcellular and paracellular pathways. Recently, we reported that the 1,25(OH)2D3-enhanced calcium transport in the mouse duodenum could be abolished by fibroblast growth factor (FGF)-23, but the targeted calcium transport pathway has been elusive. Herein, the 1,25(OH)2D3-enhanced calcium transport was markedly inhibited by FGF-23 and inhibitors of the basolateral calcium transporters, NCX1 and PMCA1b, suggesting the negative effect of FGF-23 on the transcellular calcium transport. Similar results could be observed in the intestinal epithelium-like Caco-2 monolayer. Although the Arrhenius plot indicated that FGF-23 decreased the potential barrier (e.g., activation energy) of the paracellular calcium movement, FGF-23 was found to modestly decrease the 1,25(OH)2D3-enhanced paracellular calcium transport and calcium permeability. Moreover, FGF-23 affected the 1,25(OH)2D3-induced change in duodenal water permeability as determined by tritiated water, but both 1,25(OH)2D3 and FGF-23 were without effects on the transepithelial fluxes of paracellular markers, (3)H-mannitol and (14)C-polyethylene glycol. It could be concluded that FGF-23 diminished the 1,25(OH)2D3-enhanced calcium absorption through the transcellular and paracellular pathways. Our findings have thus corroborated the presence of a bone-kidney-intestinal axis of FGF-23/vitamin D system in the regulation of calcium homeostasis.

  10. Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent.

    Science.gov (United States)

    Davis, F M; Azimi, I; Faville, R A; Peters, A A; Jalink, K; Putney, J W; Goodhill, G J; Thompson, E W; Roberts-Thomson, S J; Monteith, G R

    2014-05-01

    Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of

  11. 21 CFR 184.1187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium alginate. 184.1187 Section 184.1187 Food... Specific Substances Affirmed as GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005.... Calcium alginate is prepared by the neutralization of purified alginic acid with appropriate pH...

  12. Effect of calcium carbonate combined with calcitonin on hypercalcemia in hemodialysis patients.

    Science.gov (United States)

    Wei, Yong; Kong, Xiang Lei; Li, Wen Bin; Wang, Zun Song

    2014-12-01

    This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin.

  13. Evaluation of calcium ion release and change in pH on combining calcium hydroxide with different vehicles

    Directory of Open Access Journals (Sweden)

    Charu Grover

    2014-01-01

    of 99.53, 17.98, 74.93% respectively with a significant difference among all groups. Group 1 reached the highest Ca 2+ level (39.79% at the end of 1 day but showed almost complete release of calcium hydroxide at the end of 15 days. Group 3 showed least calcium ion release (17.98% at 15 days. Group 4 showed a sustained release of Ca +2 ions from 74% at 15 days to 95% at the end of 30 days. After the 1 st h; Group 1 showed the highest pH level (11.8. However, pH reduced to 7.8 at the end of 30 days in this group. Group 2 showed the highest pH value (10.35, followed by Group 4 (10.32 after 30 days. Conclusion: Chitosan can be used as a promising vehicle for calcium hydroxide to maintain an alkaline pH and to allow sustained release of calcium ions in the root canal system.

  14. 3-(9-Anthrylmethyl-1-benzylperimidinium hexafluorophosphate

    Directory of Open Access Journals (Sweden)

    Gui-Yu Wang

    2009-06-01

    Full Text Available In the title compound, C33H25N2+·PF6−, the naphthalene ring system is twisted with respect to the anthracene and benzene rings, making dihedral angles of 72.40 (3 and 71.39 (4°, respectively. The crystal structure is stabilized by intermolecular C—H...F hydrogen bonding. Four F atoms of the hexafluorophosphate anion are disordered over two sets of sites in a 0.645 (4:0.355 (4 ratio.

  15. Calcium Orthophosphate Cements and Concretes

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2009-03-01

    Full Text Available In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are a bioactive and biodegradable grafting material in the form of a powder and a liquid. Both phases form after mixing a viscous paste that after being implanted, sets and hardens within the body as either a non-stoichiometric calcium deficient hydroxyapatite (CDHA or brushite, sometimes blended with unreacted particles and other phases. As both CDHA and brushite are remarkably biocompartible and bioresorbable (therefore, in vivo they can be replaced with newly forming bone, calcium orthophosphate cements represent a good correction technique for non-weight-bearing bone fractures or defects and appear to be very promising materials for bone grafting applications. Besides, these cements possess an excellent osteoconductivity, molding capabilities and easy manipulation. Furthermore, reinforced cement formulations are available, which in a certain sense might be described as calcium orthophosphate concretes. The concepts established by calcium orthophosphate cement pioneers in the early 1980s were used as a platform to initiate a new generation of bone substitute materials for commercialization. Since then, advances have been made in the composition, performance and manufacturing; several beneficial formulations have already been introduced as a result. Many other compositions are in experimental stages. In this review, an insight into calcium orthophosphate cements and concretes, as excellent biomaterials suitable for both dental and bone grafting application, has been provided.

  16. High-calcium diet modulates effects of long-term prolactin exposure on the cortical bone calcium content in ovariectomized rats.

    Science.gov (United States)

    Charoenphandhu, Narattaphol; Tudpor, Kukiat; Thongchote, Kanogwun; Saengamnart, Wasana; Puntheeranurak, Supaporn; Krishnamra, Nateetip

    2007-02-01

    diet. The present results thus indicated that the adult cortical bones were potentially direct targets of prolactin. Moreover, the effects of high physiological prolactin on cortical bones were age dependent and were observed only under the modulation of high-calcium diet condition.

  17. Emanuel Strehler’s work on calcium pumps and calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Emanuel; E; Strehler

    2011-01-01

    Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders including heart disease, Alzheimer’s disease and stroke. Ca 2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca 2+ homeostasis in the cell, as well as on the mechanisms of localized Ca 2+ signaling. A longterm focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca 2+ levels, but also to local Ca 2+ signaling and vectorial Ca 2+ transport. A second major research arearevolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.

  18. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  19. Differential calcium signaling mediated by voltage-gated calcium channels in rat retinal ganglion cells and their unmyelinated axons.

    Directory of Open Access Journals (Sweden)

    Allison Sargoy

    Full Text Available Aberrant calcium regulation has been implicated as a causative factor in the degeneration of retinal ganglion cells (RGCs in numerous injury models of optic neuropathy. Since calcium has dual roles in maintaining homeostasis and triggering apoptotic pathways in healthy and injured cells, respectively, investigation of voltage-gated Ca channel (VGCC regulation as a potential strategy to reduce the loss of RGCs is warranted. The accessibility and structure of the retina provide advantages for the investigation of the mechanisms of calcium signalling in both the somata of ganglion cells as well as their unmyelinated axons. The goal of the present study was to determine the distribution of VGCC subtypes in the cell bodies and axons of ganglion cells in the normal retina and to define their contribution to calcium signals in these cellular compartments. We report L-type Ca channel α1C and α1D subunit immunoreactivity in rat RGC somata and axons. The N-type Ca channel α1B subunit was in RGC somata and axons, while the P/Q-type Ca channel α1A subunit was only in the RGC somata. We patch clamped isolated ganglion cells and biophysically identified T-type Ca channels. Calcium imaging studies of RGCs in wholemounted retinas showed that selective Ca channel antagonists reduced depolarization-evoked calcium signals mediated by L-, N-, P/Q- and T-type Ca channels in the cell bodies but only by L-type Ca channels in the axons. This differential contribution of VGCC subtypes to calcium signals in RGC somata and their axons may provide insight into the development of target-specific strategies to spare the loss of RGCs and their axons following injury.

  20. Factors affecting calcium balance in Chinese adolescents.

    Science.gov (United States)

    Yin, Jing; Zhang, Qian; Liu, Ailing; Du, Weijing; Wang, Xiaoyan; Hu, Xiaoqi; Ma, Guansheng

    2010-01-01

    Chinese dietary reference intakes (DRIs) for calcium were developed mainly from studies conducted amongst Caucasians, yet a recent review showed that reference calcium intakes for Asians are likely to be different from those of Caucasians (Lee and Jiang, 2008). In order to develop calcium DRIs for Chinese adolescents, it is necessary to explore the characteristics and potential influencing factors of calcium metabolic balance in Chinese adolescents. A total of 80 students (15.1+/-0.8 years) were recruited stratified by gender from a 1-year calcium supplementation study. Subjects were randomly designed to four groups and supplemented with calcium carbonate tablets providing elemental calcium at 63, 354, 660, and 966 mg/day, respectively. Subjects consumed food from a 3-day cycle menu prepared by staff for 10 days. Elemental calcium in samples of foods, feces, and urine was determined in duplicates by inductively coupled plasma atomic emission spectrometry. The total calcium intake ranged from 352 to 1323 mg/day. The calcium apparent absorption efficiency and retention in boys were significantly higher than that in girls (68.7% vs. 46.4%, 480 mg/day vs. 204 mg/day, PCalcium retention increased with calcium intakes, but did not reach a plateau. Calcium absorption efficiency in boys increased with calcium intake up to 665 mg/day, and decreased after that. In girls, calcium absorption efficiency decreased with calcium intake. Calcium absorption efficiency increased within 1 year after first spermatorrhea in boys, but decreased with pubertal development in girls. Sex, calcium intake, age, and pubertal development were the most important determinants of calcium absorption (R(2)=0.508, Pcalcium intake, age, and pubertal development are important factors for calcium retention and absorption during growth, which should be considered for the development of calcium DRIs for Chinese adolescents.

  1. Calcium Channel Expression and Applicability as Targeted Therapies in Melanoma

    Directory of Open Access Journals (Sweden)

    A. Macià

    2015-01-01

    Full Text Available The remodeling of Ca2+ signaling is a common finding in cancer pathophysiology serving the purpose of facilitating proliferation, migration, or survival of cancer cells subjected to stressful conditions. One particular facet of these adaptive changes is the alteration of Ca2+ fluxes through the plasma membrane, as described in several studies. In this review, we summarize the current knowledge about the expression of different Ca2+ channels in the plasma membrane of melanoma cells and its impact on oncogenic Ca2+ signaling. In the last few years, new molecular components of Ca2+ influx pathways have been identified in melanoma cells. In addition, new links between Ca2+ homeostasis and specific cell processes important in melanoma tumor progression have been unveiled. Thus, not only do Ca2+ channels appear to have a potential as prognostic markers, but their pharmacological blockade or gene silencing is hinted as interesting therapeutic approaches.

  2. ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Reigetsu Yoshikawa; Haruki Okamura; Yoshiro Nakano; Tomonori Morinaga; Tomoko Hashimoto-Tamaoki; Hidenori Yanagi; Chun-Shen Shen; Yoshinori Fujiwara; Masafumi Noda; Toshihiko Yagyu; Makoto Gega; Tsutomu Oshima; Takehira Yamamura

    2006-01-01

    AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC).METHODS: Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSKrelated markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then,we investigated the clinical implications of these markers in the prognosis of CRC patients.RESULTS: ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P < 0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value:90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P < 0.05).CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine.

  3. Mitochondrial calcium uptake.

    Science.gov (United States)

    Williams, George S B; Boyman, Liron; Chikando, Aristide C; Khairallah, Ramzi J; Lederer, W J

    2013-06-25

    Calcium (Ca(2+)) uptake into the mitochondrial matrix is critically important to cellular function. As a regulator of matrix Ca(2+) levels, this flux influences energy production and can initiate cell death. If large, this flux could potentially alter intracellular Ca(2+) ([Ca(2+)]i) signals. Despite years of study, fundamental disagreements on the extent and speed of mitochondrial Ca(2+) uptake still exist. Here, we review and quantitatively analyze mitochondrial Ca(2+) uptake fluxes from different tissues and interpret the results with respect to the recently proposed mitochondrial Ca(2+) uniporter (MCU) candidate. This quantitative analysis yields four clear results: (i) under physiological conditions, Ca(2+) influx into the mitochondria via the MCU is small relative to other cytosolic Ca(2+) extrusion pathways; (ii) single MCU conductance is ∼6-7 pS (105 mM [Ca(2+)]), and MCU flux appears to be modulated by [Ca(2+)]i, suggesting Ca(2+) regulation of MCU open probability (P(O)); (iii) in the heart, two features are clear: the number of MCU channels per mitochondrion can be calculated, and MCU probability is low under normal conditions; and (iv) in skeletal muscle and liver cells, uptake per mitochondrion varies in magnitude but total uptake per cell still appears to be modest. Based on our analysis of available quantitative data, we conclude that although Ca(2+) critically regulates mitochondrial function, the mitochondria do not act as a significant dynamic buffer of cytosolic Ca(2+) under physiological conditions. Nevertheless, with prolonged (superphysiological) elevations of [Ca(2+)]i, mitochondrial Ca(2+) uptake can increase 10- to 1,000-fold and begin to shape [Ca(2+)]i dynamics.

  4. Fabrication of patterned calcium cross-linked alginate hydrogel films and coatings through reductive cation exchange.

    Science.gov (United States)

    Bruchet, Marion; Melman, Artem

    2015-10-20

    Calcium cross-linked alginate hydrogels are widely used in targeted drug delivery, tissue engineering, wound treatment, and other biomedical applications. We developed a method for preparing homogeneous alginate hydrogels cross-linked with Ca(2+) cations using reductive cation exchange in homogeneous iron(III) cross-linked alginate hydrogels. Treatment of iron(III) cross-linked alginate hydrogels with calcium salts and sodium ascorbate results in reduction of iron(III) cations to iron(II) that are instantaneously replaced with Ca(2+) cations, producing homogeneous ionically cross-linking hydrogels. Alternatively, the cation exchange can be performed by photochemical reduction in the presence of calcium chloride using a sacrificial photoreductant. This approach allows fabrication of patterned calcium alginate hydrogels through photochemical patterning of iron(III) cross-linked alginate hydrogel followed by the photochemical reductive exchange of iron cations to calcium.

  5. Dopaminergic regulation of dendritic calcium: fast multisite calcium imaging.

    Science.gov (United States)

    Zhou, Wen-Liang; Oikonomou, Katerina D; Short, Shaina M; Antic, Srdjan D

    2013-01-01

    Optimal dopamine tone is required for the normal cortical function; however it is still unclear how cortical-dopamine-release affects information processing in individual cortical neurons. Thousands of glutamatergic inputs impinge onto elaborate dendritic trees of neocortical pyramidal neurons. In the process of ensuing synaptic integration (information processing), a variety of calcium transients are generated in remote dendritic compartments. In order to understand the cellular mechanisms of dopaminergic modulation it is important to know whether and how dopaminergic signals affect dendritic calcium transients. In this chapter, we describe a relatively inexpensive method for monitoring dendritic calcium fluctuations at multiple loci across the pyramidal dendritic tree, at the same moment of time (simultaneously). The experiments have been designed to measure the amplitude, time course and spatial extent of action potential-associated dendritic calcium transients before and after application of dopaminergic drugs. In the examples provided here the dendritic calcium transients were evoked by triggering the somatic action potentials (backpropagation-evoked), and puffs of exogenous dopamine were applied locally onto selected dendritic branches.

  6. Formation of calcium complexes by borogluconate in vitro and during calcium borogluconate infusion in sheep.

    Science.gov (United States)

    Farningham, D A

    1985-07-01

    The effect of borogluconate on plasma calcium fractions was studied in vitro and in vivo in sheep. In vitro calcium chloride was more effective in raising ionised plasma calcium than calcium borogluconate. Sodium borate or gluconate added to blood caused only small decreases in blood ionised calcium. However, together, a synergistic reduction in ionised calcium was observed. Following calcium borogluconate infusions into sheep, total plasma calcium rose primarily because of an increase in the unionised ultrafiltrable fraction. Other changes observed following the infusion were hypercalciuria, decreased glomerular filtration rate and acidosis. Sodium borogluconate administered subcutaneously lowered total plasma calcium. This probably resulted from enhanced calcium excretion. It is suggested that since the anionic component of calcium solutions alters the availability and retention of calcium, it is likely to affect clinical efficacy significantly.

  7. The calcium concentration of public drinking waters and bottled mineral waters in Spain and its contribution to satisfying nutritional needs

    Directory of Open Access Journals (Sweden)

    Isidro Vitoria

    2014-07-01

    Full Text Available Introduction: A sufficient intake of calcium enables correct bone mineralization. The bioavailability of calcium in water is similar to that in milk. Objective: To determine the concentration of calcium in public drinking water and bottled mineral water. Methods: We used ion chromatography to analyse the calcium concentrations of public drinking waters in a representative sample of 108 Spanish municipalities (21,290,707 people and of 109 natural mineral waters sold in Spain, 97 of which were produced in Spain and 12 of which were imported. Results: The average calcium concentration of public drinking waters was 38.96 ± 32.44 mg/L (range: 0.40159.68 mg/L. In 27 municipalities, the water contained 50-100 mg/L of calcium and in six municipalities it contained over 100 mg/L. The average calcium concentration of the 97 Spanish natural mineral water brands was 39.6 mg/L (range: 0.6-610.1 mg/L. Of these, 34 contained 50-100 mg/L of calcium and six contained over 100 mg/L. Of the 12 imported brands, 10 contained over 50 mg/L. Assuming water consumption is as recommended, water containing 50-100 mg/L of calcium provides 5.4-12.8% of the recommended intake of calcium for children aged one to thirteen, up to 13.6% for adolescents, 5.8-17.6% for adults, and up to 20.8% for lactating mothers. Water with 100-150 mg/L of calcium provides 10-31% of the recommended dietary allowance, depending on the age of the individual. Discussion: Public drinking water and natural mineral water consumption in a third of Spanish cities can be considered an important complementary source of calcium.

  8. [Calcium metabolism characteristics in microgravity].

    Science.gov (United States)

    Grigor'ev, A I; Larina, I M; Morukov, B V

    1999-06-01

    The results of research of calcium exchange parameters at cosmonauts taken part in long space flights (SF) onboard of orbital stations "SALUT" and "MIR" within 1978-1998 were generalized. The analysis of data received during observation of 44 cosmonauts (18 of them have taken part in long SF twice) was done. The observation was carried out before and after SF by duration 30-438 days. The content of a total calcium in blood serum was increased basically by the increase of its ionized fraction after flights of moderate (3-6 months) and large duration (6-14 months) along with the significant increase of PTH and decrease of calcitonin levels. The content of osteocalcin after SF was increased. Three cosmonauts participated in research of calcium kinetics using stable isotopes before, in time and after a 115-day SF. Reduction of intestinal absorption, excretion through a gastrointestinal tract, and increase of calcium excretion with urine were marked in time of SF. In early postflight period a level of intestinal absorption, on the average, was much lower than in SF, and the calcium removal through intestine was increased. Both renal and intestinal excretion of calcium were not normalized in 3.5-4.5 months after end of SF. Increase of resorbtive processes in bone tissues which induced negative bone balance during flight was observed in all test subjects, proceeding from estimations of speed of the basic calcium flows made on the basis of mathematical modeling. The conclusion about decrease in speed of bone tissue remodeling and strengthening of its resorption proves to be true by data of research of biochemical and endocrine markers.

  9. Calcium wave of tubuloglomerular feedback.

    Science.gov (United States)

    Peti-Peterdi, János

    2006-08-01

    ATP release from macula densa (MD) cells into the interstitium of the juxtaglomerular (JG) apparatus (JGA) is an integral component of the tubuloglomerular feedback (TGF) mechanism that controls the glomerular filtration rate. Because the cells of the JGA express a number of calcium-coupled purinergic receptors, these studies tested the hypothesis that TGF activation triggers a calcium wave that spreads from the MD toward distant cells of the JGA and glomerulus. Ratiometric calcium imaging of in vitro microperfused isolated JGA-glomerulus complex dissected from rabbits was performed with fluo-4/fura red and confocal fluorescence microscopy. Activation of TGF by increasing tubular flow rate at the MD rapidly produced a significant elevation in intracellular Ca(2+) concentration ([Ca(2+)](i)) in extraglomerular mesangial cells (by 187.6 +/- 45.1 nM) and JG renin granular cells (by 281.4 +/- 66.6 nM). Subsequently, cell-to-cell propagation of the calcium signal at a rate of 12.6 +/- 1.1 microm/s was observed upstream toward proximal segments of the afferent arteriole and adjacent glomeruli, as well as toward intraglomerular elements including the most distant podocytes (5.9 +/- 0.4 microm/s). The same calcium wave was observed in nonperfusing glomeruli, causing vasoconstriction and contractions of the glomerular tuft. Gap junction uncoupling, an ATP scavenger enzyme cocktail, and pharmacological inhibition of P(2) purinergic receptors, but not adenosine A(1) receptor blockade, abolished the changes in [Ca(2+)](i) and propagation of the calcium wave. These studies provided evidence that both gap junctional communication and extracellular ATP are integral components of the TGF calcium wave.

  10. Aggregation of Phosphoinositides at Phisiological Calcium Concentrations

    Science.gov (United States)

    Kazadi Badiambile, Adolphe; Forstner, Martin B.

    2012-02-01

    Phosphoinositides play a crucial role in many cellular functions such as calcium signaling, endocytosis, exocytosis and the targeting of proteins to specific membrane sites. To maintain functional specificity, it has been suggested that phosphoinositides are spatially organized in ``pools'' in the cellular plasma membrane. A possible mechanism that could induce and regulate such organization of phosphoinositides is their interaction with Ca2+ ions. Understanding the physicochemical mechanism that can regulate membrane structure is a crucial step in the development of adaptive biomimetic membrane systems. Using Langmuir monolayers, we investigated the effect of bivalent calcium and magnesium cations on the surface pressure-area/lipid isotherm of monolayers of phosphatidylinositol (PI), phosphatidylinositol bisphosphate (PIP2) and dioleoylphosphatidylglycerol (DOPG) and dipalmitoylphosphatidylcholine (DPPC). It is found that the decrease of area per lipid, i.e. the increase in aggregation, is dependent on both the lipid's head group charge, the bivalent cation and temperature. However, electrostatics are not sufficient to account for all experimental observations. Thus additional interactions between ions and phosphoinositides need to be considered.

  11. Building bones in babies: can and should we exceed the human milk-fed infant's rate of bone calcium accretion?

    Science.gov (United States)

    Abrams, Steven A

    2006-11-01

    Increasing calcium absorption and bone calcium accretion to levels above those achieved by human milk-fed, full-term infants is possible with infant formulas. However, no data support such a goal or suggest that it is beneficial to short- or long-term bone health. Small differences in the bioavailability of calcium between infant formulas are unlikely to have long-term consequences. Long-term studies of the effects of infant feeding type on ultimate bone mass are needed. For now, the vitamin-replete breast-fed infant's rate of calcium accretion during the first year of life should be the standard targeted for infant formulas.

  12. Calcium supplement: humanity's double-edged sword.

    Science.gov (United States)

    Bunyaratavej, Narong; Buranasinsup, Shutipen

    2011-10-01

    The principle aim of the present study is to investigate the dark side of calcium, pollutions in calcium preparation especially lead (Pb), mercury (Hg) and cadmium (Cd). The collected samples were the different calcium salts in the market and 18 preparations which were classified into 3 groups: Calcium carbonate salts, Chelated calcium and natural-raw calcium. All samples were analyzed for lead, cadmium and mercury by inductively Coupled Plasma Mass Spectrometry (ICP-MS) technique, in house method based on AOAC (2005) 999.10 by ICP-MS. The calcium carbonate and the natural-raw calcium in every sample contained lead at 0.023-0.407 mg/kg of calcium powder. Meanwhile, the natural-raw calcium such as oyster, coral and animal bone showed amount of lead at 0.106-0.384 mg/kg with small amounts of mercury and cadmium. The chelated calcium such as calcium gluconate, calcium lactate and calcium citrate are free of lead.

  13. CD39 and Immune Suppression%CD39分子和免疫抑制

    Institute of Scientific and Technical Information of China (English)

    遇晓

    2012-01-01

    CD39 is the main extracellular apyrase which expresses inherently in the human bodies and down-regulates in the autoimmune disease. Autoimmune disease pathology is over-immunologic response which damages autologous tissue. The key therapy is suppressing the immune reaction. Here is to make a review' on the function of immune suppression from hindering cell migration and antigen-presenting, changing the expression cytokines, suppressing cell proliferation and killing, so as to offer a new idea for the treatment of autoimmune diseases.%CD39分子是主要的细胞外ATP双磷酸酶,是人体内固有的免疫抑制因子,在自身免疫性疾病表达下降.自身免疫性疾病是机体过高的免疫应答反应造成自身组织损害的过程.抑制机体免疫反应是目前主要的治疗策略.现从CD39影响细胞迁移和抗原呈递、改变细胞因子的产生、抑制细胞增殖和杀伤功能等方面阐述CD39的免疫抑制功能,以期为自身免疫性疾病的治疗提供新的思路.

  14. Calcium and lithium ion production for laser ion source

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, M.; Palm, K.; Stifler, C.; Steski, D.; Ikeda, S.; Kumaki, M.; Kanesue, T.

    2015-08-23

    Calcium and lithium ion beams are required by NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL) to simulate the effects of cosmic radiation. To find out difficulties to provide such high reactive material as laser targets, the both species were experimentally tested. Plate-shaped lithium and calcium targets were fabricated to create ablation plasmas with a 6ns, 1064nm Nd:YAG laser. We found significant oxygen contamination in both the Ca and Li high-charge-state beams due to the rapid oxidation of the surfaces. A large-spot-size, low-power-density laser was then used to analyze the low-charge-state beams without scanning the targets. The low-charge-state Ca beam did not have any apparent oxygen contamination, showing the potential to clean the target entirely with a low-power beam once in the chamber. The Li target was clearly still oxidizing in the chamber after each low-power shot. To measure the rate of oxidation, we shot the low-power laser at the target repeatedly at 10sec, 30sec, 60sec, and 120sec interval lengths, showing a linear relation between the interval time and the amount of oxygen in the beam.

  15. Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives

    Directory of Open Access Journals (Sweden)

    Ellen C. Gleeson

    2015-04-01

    Full Text Available A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.

  16. Octupole strength in the neutron-rich calcium isotopes

    CERN Document Server

    Riley, L A; Agiorgousis, M L; Baugher, T R; Bazin, D; Bowry, M; Cottle, P D; DeVone, F G; Gade, A; Glowacki, M T; Gregory, S D; Haldeman, E B; Kemper, K W; Lunderberg, E; Noji, S; Recchia, F; Sadler, B V; Scott, M; Weisshaar, D; Zegers, R G T

    2016-01-01

    Low-lying excited states of the neutron-rich calcium isotopes $^{48-52}$Ca have been studied via $\\gamma$-ray spectroscopy following inverse-kinematics proton scattering on a liquid hydrogen target using the GRETINA $\\gamma$-ray tracking array. The energies and strengths of the octupole states in these isotopes are remarkably constant, indicating that these states are dominated by proton excitations.

  17. moco: Fast Motion Correction for Calcium Imaging.

    Science.gov (United States)

    Dubbs, Alexander; Guevara, James; Yuste, Rafael

    2016-01-01

    Motion correction is the first step in a pipeline of algorithms to analyze calcium imaging videos and extract biologically relevant information, for example the network structure of the neurons therein. Fast motion correction is especially critical for closed-loop activity triggered stimulation experiments, where accurate detection and targeting of specific cells in necessary. We introduce a novel motion-correction algorithm which uses a Fourier-transform approach, and a combination of judicious downsampling and the accelerated computation of many L 2 norms using dynamic programming and two-dimensional, fft-accelerated convolutions, to enhance its efficiency. Its accuracy is comparable to that of established community-used algorithms, and it is more stable to large translational motions. It is programmed in Java and is compatible with ImageJ.

  18. The symphony of autophagy and calcium signaling.

    Science.gov (United States)

    Yao, Zhiyuan; Klionsky, Daniel J

    2015-01-01

    Posttranslational regulation of macroautophagy (hereafter autophagy), including phosphorylating and dephosphorylating components of the autophagy-related (Atg) core machinery and the corresponding upstream transcriptional factors, is important for the precise modulation of autophagy levels. Several kinases that are involved in phosphorylating autophagy-related proteins have been identified in both yeast and mammalian cells. However, there has been much less research published with regard to the identification of the complementary phosphatases that function in autophagy. A recent study identified PPP3/calcineurin, a calcium-dependent phosphatase, as a regulator of autophagy, and demonstrated that one of the key targets of PPP3/calcineurin is TFEB, a master transcriptional factor that controls autophagy and lysosomal function in mammalian cells.

  19. moco: Fast Motion Correction for Calcium Imaging

    Directory of Open Access Journals (Sweden)

    Alexander eDubbs

    2016-02-01

    Full Text Available Motion correction is the first step in a pipeline of algorithms to analyze calcium imaging videos and extract biologically relevant information, for example the network structure of the neurons therein. Fast motion correction is especially critical for closed-loop activity triggered stimulation experiments, where accurate detection and targeting of specific cells in necessary. We introduce a novel motion-correction algorithm that uses a Fourier-transform approach, and a combination of judicious downsampling and the accelerated computation of many $L_2$ norms using dynamic programming and two-dimensional, fft-accelerated convolutions, to enhance its efficiency. Its accuracy is comparable to that of established community-used algorithms, and it is more stable to large translational motions. It is programmed in Java and is compatible with ImageJ.

  20. Nuclear calcium signaling induces expression of the synaptic organizers Lrrtm1 and Lrrtm2.

    Science.gov (United States)

    Hayer, Stefanie N; Bading, Hilmar

    2015-02-27

    Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as a signaling end point in synapse-to-nucleus communication. As an important regulator of neuronal gene expression, nuclear calcium is involved in the conversion of synaptic stimuli into functional and structural changes of neurons. Here we identify two synaptic organizers, Lrrtm1 and Lrrtm2, as targets of nuclear calcium signaling. Expression of both Lrrtm1 and Lrrtm2 increased in a synaptic NMDA receptor- and nuclear calcium-dependent manner in hippocampal neurons within 2-4 h after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis and required calcium/calmodulin-dependent protein kinases and the nuclear calcium signaling target CREB-binding protein. Analysis of reporter gene constructs revealed a functional cAMP response element in the proximal promoter of Lrrtm2, indicating that at least Lrrtm2 is regulated by the classical nuclear Ca(2+)/calmodulin-dependent protein kinase IV-CREB/CREB-binding protein pathway. These results suggest that one mechanism by which nuclear calcium signaling controls neuronal network function is by regulating the expression of Lrrtm1 and Lrrtm2.

  1. Microanalyses of the hydroxyl—poly—calcium sodium phosphate coatings produced by ion beam assisted deposition

    Institute of Scientific and Technical Information of China (English)

    LIUZhong-Yang; WANGChang-Xing; 等

    2002-01-01

    Thin calcium phosphate catings on titanium alloy substrates were prepared by Ar+ ion beam assisted deposition(IBAD) from hydroxyl-poly-calcium sodium phosphate(HPPA) target.The coatings were analyzed by XRD,FTIR,XPS,These analyses revealed that the as-deposited films were amorphous or no apparent crystallinity.No distinct absorption band of the hydroxyl group was observed in FTIR spectra of the coatings but new absorption bands were presented for CO3-2,The calcium to phosphorous ratio of these catings in different IBAD conditions varied from 0.46 to 3.36.

  2. 36 CFR 7.39 - Mesa Verde National Park.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Mesa Verde National Park. 7.39 Section 7.39 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.39 Mesa Verde National Park. (a) Visiting...

  3. 28 CFR 39.110 - Self-evaluation.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Self-evaluation. 39.110 Section 39.110... PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF JUSTICE § 39.110 Self-evaluation. (a) The agency... representing handicapped persons, to participate in the self-evaluation process by submitting comments...

  4. 14 CFR 120.39 - Testing for alcohol.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Testing for alcohol. 120.39 Section 120.39... AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS DRUG AND ALCOHOL TESTING PROGRAM... Under § 91.147 of This Chapter and Safety-Sensitive Employees § 120.39 Testing for alcohol. (a)...

  5. 29 CFR 1910.39 - Fire prevention plans.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Fire prevention plans. 1910.39 Section 1910.39 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Means of Egress § 1910.39 Fire prevention plans. (a) Application. An employer must have a fire prevention plan when an OSHA standard in this part requires one. The...

  6. 10 CFR 1.39 - Office of Human Resources.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Office of Human Resources. 1.39 Section 1.39 Energy... § 1.39 Office of Human Resources. The Office of Human Resources— (a) Plans and implements NRC policies... agency's human resources; (b) Provides labor relations and personnel policy guidance and...

  7. 42 CFR 60.39 - Death and disability claims.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Death and disability claims. 60.39 Section 60.39... ASSISTANCE LOAN PROGRAM The Lender and Holder § 60.39 Death and disability claims. (a) Death. The Secretary... death. (b) Disability. (1) The Secretary will discharge a borrower's liability on the loan in...

  8. 10 CFR 39.49 - Uranium sinker bars.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Uranium sinker bars. 39.49 Section 39.49 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.49 Uranium sinker bars. The licensee may use a uranium sinker bar in well logging applications only if it is...

  9. 29 CFR 785.39 - Travel away from home community.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Travel away from home community. 785.39 Section 785.39 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS... Principles Traveltime § 785.39 Travel away from home community. Travel that keeps an employee away from...

  10. 10 CFR 39.13 - Specific licenses for well logging.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Specific licenses for well logging. 39.13 Section 39.13 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Specific Licensing Requirements § 39.13 Specific licenses for well logging. The Commission will approve an application for a specific license for the...

  11. 49 CFR 176.39 - Inspection of cargo.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Inspection of cargo. 176.39 Section 176.39... Requirements § 176.39 Inspection of cargo. (a) Manned vessels. The carrier, its agents, and any person... thereafter, weather permitting, in order to ensure that the cargo is in a safe condition and that no...

  12. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    Science.gov (United States)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  13. Vitamin D and intestinal calcium absorption.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed.

  14. The Brugada syndrome mutation A39V does not affect surface expression of neuronal rat Cav1.2 channels

    Directory of Open Access Journals (Sweden)

    Simms Brett A

    2012-03-01

    Full Text Available Abstract Background A loss of function of the L-type calcium channel, Cav1.2, results in a cardiac specific disease known as Brugada syndrome. Although many Brugada syndrome channelopathies reduce channel function, one point mutation in the N-terminus of Cav1.2 (A39V has been shown to elicit disease a phenotype because of a loss of surface trafficking of the channel. This lack of cell membrane expression could not be rescued by the trafficking chaperone Cavβ. Findings We report that despite the striking loss of trafficking described previously in the cardiac Cav1.2 channel, the A39V mutation while in the background of the brain isoform traffics and functions normally. We detected no differences in biophysical properties between wild type Cav1.2 and A39V-Cav1.2 in the presence of either a cardiac (Cavβ2b, or a neuronal beta subunit (Cavβ1b. In addition, the A39V-Cav1.2 mutant showed a normal Cavβ2b mediated increase in surface expression in tsA-201 cells. Conclusions The Brugada syndrome mutation A39V when introduced into rat brain Cav1.2 does not trigger the loss-of-trafficking phenotype seen in a previous study on the human heart isoform of the channel.

  15. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille;

    2013-01-01

    electroporation and electrochemotherapy. METHODS: The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore...... survival at similar applied voltage parameters. The effect of calcium electroporation is independent of calcium compound. GENERAL SIGNIFICANCE: This study strongly supports the use of calcium electroporation as a potential cancer therapy and the results may aid in future clinical trials....

  16. Catalytic pyrolysis using UZM-39 aluminosilicate zeolite

    Science.gov (United States)

    Nicholas, Christpher P; Boldingh, Edwin P

    2013-12-17

    A new family of coherently grown composites of TUN and IMF zeotypes has been synthesized and show to be effective catalysts for catalytic pyrolysis of biomass. These zeolites are represented by the empirical formula. Na.sub.nM.sub.m.sup.n+R.sub.rQ.sub.qAl.sub1-xE.sub.xSi.sub.yO.s- ub.z where M represents zinc or a metal or metals from Group 1, Group 2, Group 3 or the lanthanide series of the periodic table, R is an A,.OMEGA.-dihalosubstituted paraffin such as 1,4-dibromobutane, Q is a neutral amine containing 5 or fewer carbon atoms such as 1-methylpyrrolidine and E is a framework element such as gallium. The process involves contacting a carbonaceous biomass feedstock with UZM-39 at pyrolysis conditions to produce pyrolysis gases comprising hydrocarbons. The catalyst catalyzes a deoxygenation reaction converting oxygenated hyrdocarbons into hydrocarbons removing the oxygen as carbon oxides and water. A portion of the pyrolysis gases is condensed to produce low oxygen biomass-derived pyrolysis oil.

  17. Catalytic pyrolysis using UZM-39 aluminosilicate zeolite

    Energy Technology Data Exchange (ETDEWEB)

    Nicholas, Christopher P; Boldingh, Edwin P

    2014-10-07

    A new family of coherently grown composites of TUN and IMF zeotypes has been synthesized and shown to be effective catalysts for catalytic pyrolysis of biomass. These zeolites are represented by the empirical formula. Na.sub.nM.sub.m.sup.n+R.sub.rQ.sub.qAl.sub.1-xE.sub.xSi.sub.yO.s- ub.z where M represents zinc or a metal or metals from Group 1, Group 2, Group 3 or the lanthanide series of the periodic table, R is an A,.OMEGA.-dihalosubstituted paraffin such as 1,4-dibromobutane, Q is a neutral amine containing 5 or fewer carbon atoms such as 1-methylpyrrolidine and E is a framework element such as gallium. The process involves contacting a carbonaceous biomass feedstock with UZM-39 at pyrolysis conditions to produce pyrolysis gases comprising hydrocarbons. The catalyst catalyzes a deoxygenation reaction converting oxygenated hydrocarbons into hydrocarbons and removing the oxygen as carbon oxides and water. A portion of the pyrolysis gases is condensed to produce low oxygen biomass-derived pyrolysis oil.

  18. The effect of calcium gluconate and other calcium supplements as a dietary calcium source on magnesium absorption in rats.

    Science.gov (United States)

    Chonan, O; Takahashi, R; Yasui, H; Watanuki, M

    1997-01-01

    The effects of commercially available calcium supplements (calcium carbonate, calcium gluconate, oyster shell preparation and bovine bone preparation) and gluconic acid on the absorption of calcium and magnesium were evaluated for 30 days in male Wistar rats. There were no differences in the apparent absorption ratio of calcium among rats fed each calcium supplement; however, the rats fed the calcium gluconate diet had a higher apparent absorption ratio of magnesium than the rats fed the other calcium supplements. Dietary gluconic acid also more markedly stimulated magnesium absorption than the calcium carbonate diet, and the bone (femur and tibia) magnesium contents of rats fed the gluconic acid diet were significantly higher than those of the rats fed the calcium carbonate diet. Furthermore, the weight of cecal tissue and the concentrations of acetic acid and butyric acid in cecal digesta of rats fed the calcium gluconate diet or the gluconic acid diet were significantly increased. We speculate that the stimulation of magnesium absorption in rats fed the calcium gluconate diet is a result of the gluconic acid component and the effect of gluconic acid on magnesium absorption probably results from cecal hypertrophy, magnesium solubility in the large intestine and the effects of volatile fatty acids on magnesium absorption.

  19. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

    Full Text Available At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 рА and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 µM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  20. Novel Zn2+ Modulated GPR39 Receptor Agonists Do Not Drive Acute Insulin Secretion in Rodents.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Type 2 diabetes (T2D occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion in vivo. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn2+ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO mice and Zucker fatty rats. It is concluded that Zn2+ modulated GPR39 agonists do not acutely stimulate insulin release in rodents.

  1. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Devkanya Dutta

    2000-12-01

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the store-operated calcium entry or capacitative calcium entry. Capacitative calcium current plays a key role in replenishing calcium stores and activating various physiological processes. Despite considerable efforts, very little is known about the molecular nature of the capacitative channel and the signalling pathway that activates it. This review summarizes our current knowledge about store operated calcium entry and suggests possible hypotheses for its mode of activation.

  2. The ins and outs of mitochondrial calcium.

    Science.gov (United States)

    Finkel, Toren; Menazza, Sara; Holmström, Kira M; Parks, Randi J; Liu, Julia; Sun, Junhui; Liu, Jie; Pan, Xin; Murphy, Elizabeth

    2015-05-22

    Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the setting of ischemia-reperfusion injury is thought to be a critical event in triggering cellular necrosis. For many decades, the details of how calcium entered the mitochondria remained a biological mystery. In the past few years, significant progress has been made in identifying the molecular components of the mitochondrial calcium uniporter complex. Here, we review how calcium enters and leaves the mitochondria, the growing insight into the topology, stoichiometry and function of the uniporter complex, and the early lessons learned from some initial mouse models that genetically perturb mitochondrial calcium homeostasis.

  3. Familial hypocalciuric hypercalcemia and calcium sensing receptor

    DEFF Research Database (Denmark)

    Mrgan, Monija; Nielsen, Sanne; Brixen, Kim

    2014-01-01

    Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign autosomal dominant disease characterized by hypercalcemia, normal to increased parathyroid hormone level, and a relatively low renal calcium excretion. Inactivation of the calcium-sensing receptor in heterozygous patients results in...

  4. Decalcification of calcium polycarbophil in rats.

    Science.gov (United States)

    Yamada, T; Saito, T; Takahara, E; Nagata, O; Tamai, I; Tsuji, A

    1997-03-01

    The in vivo decalcification of calcium polycarbophil was examined. The decalcification ratio of [45Ca]calcium polycarbophil in the stomach after oral dosing to rats was more than 70% at each designated time and quite closely followed in the in vitro decalcification curve, indicating that the greater part of the calcium ion is released from calcium polycarbophil under normal gastric acidic conditions. The residual radioactivity in rat gastrointestine was nearly equal to that after oral administration of either [45Ca]calcium chloride + polycarbophil. The serum level of radioactivity was nearly equal to that after oral dosing of [45Ca]calcium lactate. These results indicate that the greater part of orally administered calcium polycarbophil released calcium ions to produce polycarbophil in vivo.

  5. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  6. Variable efficacy of calcium carbonate tablets.

    Science.gov (United States)

    Kobrin, S M; Goldstein, S J; Shangraw, R F; Raja, R M

    1989-12-01

    Orally administered calcium carbonate tablets are commonly prescribed as a calcium supplement and for their phosphate-binding effects in renal failure patients. Two cases are reported in which a commercially available brand of calcium carbonate tablets appeared to be ineffective. Formal investigation of the bioavailability of this product revealed it to have impaired disintegration and dissolution and a lack of clinical efficacy. Recommendations that will enable physicians to avoid prescribing and pharmacists to avoid dispensing ineffective calcium carbonate tablets are proposed.

  7. Calcium regulation in endosymbiotic organelles of plants

    OpenAIRE

    Bussemer, Johanna; Vothknecht, Ute C.; Chigri, Fatima

    2009-01-01

    In plant cells calcium-dependent signaling pathways are involved in a large array of biological processes in response to hormones, biotic/abiotic stress signals and a variety of developmental cues. This is generally achieved through binding of calcium to diverse calcium-sensing proteins, which subsequently control downstream events by activating or inhibiting biochemical reactions. Regulation by calcium is considered as a eukaryotic trait and has not been described for prokaryotes. Neverthele...

  8. Teaching Calcium-Induced Calcium Release in Cardiomyocytes Using a Classic Paper by Fabiato

    Science.gov (United States)

    Liang, Willmann

    2008-01-01

    This teaching paper utilizes the materials presented by Dr. Fabiato in his review article entitled "Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum." In the review, supporting evidence of calcium-induced calcium release (CICR) is presented. Data concerning potential objections to the CICR theory are discussed as well. In…

  9. Calcium and Vitamin D in Obesity and Related Chronic Disease.

    Science.gov (United States)

    Pannu, Poonam K; Calton, Emily K; Soares, Mario J

    2016-01-01

    There is a pandemic of lifestyle-related diseases. In both developed and lesser developed countries of the world, an inadequacy of calcium intake and low vitamin D status is common. In this chapter, we explore a mechanistic framework that links calcium and vitamin D status to chronic conditions including obesity, systemic inflammation, endothelial dysfunction, dyslipidemia and cardiovascular disease, and type 2 diabetes mellitus. We also update the available clinical evidence, mainly from randomized controlled trials, to provide a synthesis of evidence in favor or against these hypotheses. There is consistent data to support calcium increasing whole body fat oxidation and increasing fecal fat excretion, while there is good cellular evidence for vitamin D reducing inflammation. Clinical trials support a marginal reduction in circulating lipids and some meta-analysis support an increase in insulin sensitivity following vitamin D. However, these mechanistic pathways and intermediate biomarkers of disease do not consistently transcribe into measurable health outcomes. Cementing the benefits of calcium and vitamin D for extraskeletal health needs a reexamination of the target 25(OH)D level to be achieved and the minimum duration of future trials.

  10. Feasibility of coronary calcium and stent image subtraction using 320-detector row CT angiography

    DEFF Research Database (Denmark)

    Fuchs, Andreas; Kühl, J Tobias; Chen, Marcus Y;

    2015-01-01

    . We defined target segments on CCTAconv as motion-free coronary segments with calcification or stent and low reader confidence. The effect of CCTAsub was assessed. No approval from the ethics committee was required according to Danish law. RESULTS: A total of 76 target segments were identified....... The use of coronary calcium image subtraction improved the reader confidence in 66% of these segments. In target segments, specificity (86% vs 65%; P

  11. 21 CFR 582.5217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phosphate. 582.5217 Section 582.5217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic)....

  12. 21 CFR 582.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phosphate. 582.1217 Section 582.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic)....

  13. 21 CFR 182.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium phosphate. 182.1217 Section 182.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Substances § 182.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic)....

  14. Abnormalities of serum calcium and magnesium

    Science.gov (United States)

    Neonatal hypocalcemia is defined as a total serum calcium concentration of <7 mg/dL or an ionized calcium concentration of <4 mg/dL (1mmol/L). In very low birth weight (VLBW) infants, ionized calcium values of 0.8 to 1 mmol/L are common and not usually associated with clinical symptoms. In larger in...

  15. Acute calcium homeostasis in MHS swine.

    Science.gov (United States)

    Harrison, G G; Morrell, D F; Brain, V; Jaros, G G

    1987-07-01

    To elucidate a pathogenesis for the reduction in bone calcium content observed in MHS individuals, we studied the acute calcium homeostasis of MHS swine. This was achieved by the serial measurement, with a calcium selective electrode, of calcium transients in Landrace MHS (five) and control Landrace/large white cross MH negative (five) swine following IV bolus injection of calcium gluconate 0.1 mmol X kg-1--a dose which induced an acute 45 per cent increase in plasma ionised calcium. Experimental animals were anaesthetised with ketamine 10 mg X kg-1 IM, thiopentone (intermittent divided doses) 15-25 mg X kg-1 (total) IV and N2O/O2 (FIO2 0.3) by IPPV to maintain a normal blood gas, acid/base state. The plasma ionised calcium decay curve observed in MHS swine did not differ from that of control normal swine. Further it was noted that the induced acute rise in plasma ionised calcium failed to trigger the MH syndrome in any MHS swine. It is concluded that the mechanisms of acute calcium homeostasis in MHS swine are normal. An explanation for the reduction in bone calcium content observed in MHS individuals must be sought, therefore, through study of the slow long-term component of the calcium regulatory process. In addition, the conventional strictures placed on the use, in MHS patients, of calcium gluconate are called in question.

  16. Multifaceted Role of Calcium in Cancer.

    Science.gov (United States)

    Sarode, Gargi S; Sarode, Sachin C; Patil, Shankargouda

    2017-01-01

    Role of calcium in bone remodeling and tooth remineral-ization is well known. However, calcium also plays a very imperative role in many biochemical reactions, which are essential for normal functioning of cells. The calcium associated tissue homeostasis encompasses activities like proliferation, cell death, cell motility, oxygen, and nutrient supply.

  17. 21 CFR 582.6219 - Calcium phytate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phytate. 582.6219 Section 582.6219 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium phytate. (a) Product. Calcium phytate. (b) Conditions of use. This substance is...

  18. 21 CFR 582.3189 - Calcium ascorbate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium ascorbate. 582.3189 Section 582.3189 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3189 Calcium ascorbate. (a) Product. Calcium ascorbate. (b) Conditions of use. This substance...

  19. 21 CFR 182.3189 - Calcium ascorbate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium ascorbate. 182.3189 Section 182.3189 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Calcium ascorbate. (a) Product. Calcium ascorbate. (b) Conditions of use. This substance is...

  20. 21 CFR 582.7187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium alginate. 582.7187 Section 582.7187 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium alginate. (a) Product. Calcium alginate. (b) Conditions of use. This substance is...

  1. Repair of Nerve Cell Membrance Damage by Calcium-Dependent, Membrane-Binding Proteins

    Science.gov (United States)

    2013-09-01

    signaling and amyloid toxicity in Alzheimer disease, J Biol Chem 285 (2010) 12463-12468. [14] H.A. Lashuel, P.T. Lansbury, Are amyloid diseases caused by...protein aggregates that mimic bacterial pore-forming toxins?, Q Rev Biophys 39 (2006) 167-201. [15] N. Arispe, E. Rojas, H.B. Pollard, Alzheimer ...disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum , Proc Natl Acad Sci U S A 90 (1993) 567

  2. Silver-doped calcium phosphate nanoparticles: synthesis, characterization, and toxic effects toward mammalian and prokaryotic cells.

    Science.gov (United States)

    Peetsch, Alexander; Greulich, Christina; Braun, Dieter; Stroetges, Christian; Rehage, Heinz; Siebers, Bettina; Köller, Manfred; Epple, Matthias

    2013-02-01

    Spherical silver-doped calcium phosphate nanoparticles were synthesized in a co-precipitation route from calcium nitrate/silver nitrate and ammonium phosphate in a continuous process and colloidally stabilized by carboxymethyl cellulose. Nanoparticles with 0.39 wt% silver content and a diameter of about 50-60 nm were obtained. The toxic effects toward mammalian and prokaryotic cells were determined by viability tests and determination of the minimal inhibitory and minimal bactericidal concentrations (MIC and MBC). Three mammalian cells lines, i.e. human mesenchymal stem cells (hMSC) and blood peripheral mononuclear cells (PBMC, monocytes and T-lymphocytes), and two prokaryotic strains, i.e. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used. Silver-doped calcium phosphate nanoparticles and silver acetate showed similar effect toward mammalian and prokaryotic cells with toxic silver concentrations in the range of 1-3 μg mL(-1).

  3. Exploration of As(III)/As(V) Uptake from Aqueous Solution by Synthesized Calcium Sulfate Whisker☆

    Institute of Scientific and Technical Information of China (English)

    Xiaojuan Chen; Liuchun Yang; Junfeng Zhang; Yan Huang

    2014-01-01

    Although common calcium-containing minerals such as calcite and gypsum may fix arsenic, the interaction be-tween modified calcic minerals and arsenic has seldom been reported. The uptake behavior of As(III)/As(V) from aqueous solutions by calcium sulfate whisker (CSW, dihydrate or anhydrite) synthesized through a cooling recrystal ization method was explored. A series of batch experiments were conducted to examine the effect of pH, reaction time, whisker dosage, and initial As concentration. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the samples prepared. The results showed that pH of the aqueous solution was an important parameter for As(III)/As(V) uptake, and an excellent removal efficiency could be achieved under strongly alkaline condition. The data from batch experiments for reaction of As(V) with calcium sulfate dihydrate whisker (CSDW) and calcium sulfate anhydrous whisker (CSAW) were well described with extended Langmuir EXT1 model, from which theoretic maximum adsorption capacity of 46.57 mg As(V)·(g CSDW)−1 and 39.18 mg As(V)·(g CSAW)−1 were obtained. Some calcium arsenate solids products, such as CaAsO3(OH) (weilite, syn), Ca3(AsO4)2 (calcium arsenate), CaO–As2O5, Ca–As–O, Ca5(AsO4)3OH·xH2O (calcium arsenate hydroxide hydrate), and CaH(AsO4)·2H2O (hydrogen calcium arsenic oxide hydrate), were detected at pH = 12.5 through XRD analysis. This indicates that the interaction mechanism between As(V) and CSW is a complex adsorption process combined with surface dissolution and chemical precipitation.

  4. Calcium Orthophosphate-Based Bioceramics

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2013-09-01

    Full Text Available Various types of grafts have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A bit later, such synthetic biomaterials were called bioceramics. In principle, bioceramics can be prepared from diverse materials but this review is limited to calcium orthophosphate-based formulations only, which possess the specific advantages due to the chemical similarity to mammalian bones and teeth. During the past 40 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the calcium orthophosphate-based implants remain biologically stable once incorporated into the skeletal structure or whether they were resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed and such formulations became an integrated part of the tissue engineering approach. Now calcium orthophosphate scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous and harbor different biomolecules and/or cells. Therefore, current biomedical applications of calcium orthophosphate bioceramics include bone augmentations, artificial bone grafts, maxillofacial reconstruction, spinal fusion, periodontal disease repairs and bone fillers after tumor surgery. Perspective future applications comprise drug delivery and tissue engineering purposes because calcium orthophosphates appear to be promising carriers of growth factors, bioactive peptides and various types of cells.

  5. STS-103 Discovery crawls to Launch Pad 39B

    Science.gov (United States)

    1999-01-01

    With the American flag flapping in the morning breeze, Space Shuttle Discovery across the turn basin makes its 4.2-mile (6.8 kilometer) crawl to Launch Pad 39B (background, left) atop the mobile launcher platform and crawler transporter. Once at the pad, the orbiter, external tank and solid rocket boosters will undergo final preparations for the STS-103 launch targeted for Dec. 6, 1999, at 2:37 a.m. EST. The mission is a 'call-up' due to the need to replace and repair portions of the Hubble Space Telescope. Although Hubble is operating normally and conducting its scientific observations, only three of its six gyroscopes are working properly. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The STS-103 crew members are Commander Curtis L. Brown Jr., Pilot Scott J. Kelly, Steven L. Smith, C. Michael Foale (Ph.D.), John M. Grunsfeld (Ph.D.), and Claude Nicollier of Switzerland and Jean-Frangois Clervoy of France, both with the European Space Agency.

  6. STS-103 crew on Pad 39-B during TCDT activities

    Science.gov (United States)

    1999-01-01

    Taking a break during emergency egress training at Launch Pad 39B are (left to right) STS-103 Mission Specialists Jean-Frangois Clervoy of France, Claude Nicollier of Switzerland, Commander Curtis L. Brown Jr., Pilot Scott J. Kelly, and Mission Specialists John M. Grunsfeld (Ph.D.), C. Michael Foale (Ph.D.) and Steven L. Smith. Clervoy and Nicollier are with the European Space Agency. The training is part of Terminal Countdown Demonstration Test (TCDT) activities that also include opportunities to inspect the mission payloads in the orbiter's payload bay and simulated countdown exercises. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope, including the gyroscopes that allow the telescope to point at stars, galaxies and planets. The STS-103 crew will be replacing a Fine Guidance Sensor, an older computer with a new enhanced model, an older data tape recorder with a solid-state digital recorder, a failed spare transmitter with a new one, and degraded insulation on the telescope with new thermal insulation. The crew will also install a Battery Voltage/Temperature Improvement Kit to protect the spacecraft batteries from overcharging and overheating when the telescope goes into a safe mode. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  7. Exporting calcium from cells.

    Science.gov (United States)

    Guerini, Danilo; Coletto, Luisa; Carafoli, Ernesto

    2005-01-01

    All eukaryotic cells import Ca2+ through a number of variously gated plasma membrane channels. Once inside cells, Ca2+ transmits information to a large number of (enzyme) targets. Eventually, it must be exported again, to prevent the overloading of the cytosol with Ca2+. Two systems export Ca2+ from cells: a high affinity, low capacity Ca2+-ATPase, and a lower affinity, but much larger capacity, Na+/Ca2+ exchanger. The ATPase (commonly called the Ca2+ pump) is the fine-tuner of cell Ca2+, as it functions well even if the concentration of the ion drops below the microM level. It is a large enzyme, with 10 transmembrane domains and a C-terminal cytosolic tail that contains regulatory sites, including a calmodulin-binding domain. Four distinct gene products plus a large number of splice variants have been described. Some are tissue specific, the isoform 2 being specifically expressed in the sensorial cells of the Corti organ in the inner-ear. Its genetic absence causes deafness in mice. Two different families of the Na+/Ca2+ exchanger exist, one of which, originally described in photoreceptors, transports K+ and Ca2+ in exchange for Na+. The exchanger is particularly active in excitable cells, e.g., heart, where the necessity cyclically arises to rapidly eject large amounts of Ca2+. In addition to heart, the exchanger is particularly important to neurons: the cleavage of the most important neuronal isoform (NCX3) by calpains activated by excitotoxic treatments generates Ca2+ overload and eventually cell death.

  8. Apatite Formation from Amorphous Calcium Phosphate and Mixed Amorphous Calcium Phosphate/Amorphous Calcium Carbonate.

    Science.gov (United States)

    Ibsen, Casper J S; Chernyshov, Dmitry; Birkedal, Henrik

    2016-08-22

    Crystallization from amorphous phases is an emerging pathway for making advanced materials. Biology has made use of amorphous precursor phases for eons and used them to produce structures with remarkable properties. Herein, we show how the design of the amorphous phase greatly influences the nanocrystals formed therefrom. We investigate the transformation of mixed amorphous calcium phosphate/amorphous calcium carbonate phases into bone-like nanocrystalline apatite using in situ synchrotron X-ray diffraction and IR spectroscopy. The speciation of phosphate was controlled by pH to favor HPO4 (2-) . In a carbonate free system, the reaction produces anisotropic apatite crystallites with large aspect ratios. The first formed crystallites are highly calcium deficient and hydrogen phosphate rich, consistent with thin octacalcium phosphate (OCP)-like needles. During growth, the crystallites become increasingly stoichiometric, which indicates that the crystallites grow through addition of near-stoichiometric apatite to the OCP-like initial crystals through a process that involves either crystallite fusion/aggregation or Ostwald ripening. The mixed amorphous phases were found to be more stable against phase transformations, hence, the crystallization was inhibited. The resulting crystallites were smaller and less anisotropic. This is rationalized by the idea that a local phosphate-depletion zone formed around the growing crystal until it was surrounded by amorphous calcium carbonate, which stopped the crystallization.

  9. The pharmacological properties of lipophilic calcium antagonists.

    Science.gov (United States)

    van Zwieten, P A

    1998-01-01

    Several types of calcium antagonists (CA) (verapamil, diltiazem, nifedipine and related drugs) may be used as antihypertensives. In practice, the dihydropyridines (nifedipine and related drugs) are the CA used most frequently as antihypertensives. Apart from the lowering of blood pressure CA may lead to other, theoretically beneficial, effects: regression of left ventricular and vascular hypertrophy, renal protection, weak natriuretic, weak antiplatelet, anti-ischaemic and antiatherogenic activity. Several new dihydropyridine CA have been introduced in recent years. The advantages of the newer compounds, such as amlodipine, felodipine, isradipine, lacidipine and lercanidipine, may include: vasoselectivity, hence little or no cardiodepressant activity; an improved kinetic profile, resulting in a slow onset and long duration of action, fewer side-effects such as reflex tachycardia and headache, owing to the slow onset of the antihypertensive action. For a few newer CA a predominant effect on specialized circulatory beds (renal, coronary and cerebral) has been claimed. The new CA, which are clearly lipophilic, deserve special attention. Owing to the lipophilic character of such compounds considerable concentration occurs in lipid-containing membrane depots. The CA thus concentrated are slowly released from these depots and, subsequently, reach their targets, the L-type calcium channels. This phenomenon explains both the slow onset and the long duration of action of these CA. Owing to the slow onset of action reflex tachycardia is virtually absent. The long duration of action allows satisfactory control of blood pressure in hypertensives by means of a single daily dose. A few lipophilic dihydropyridine CA are vasoselective. This property implies that at therapeutic, vasodilatory dosages no cardiodepressant activity occurs. Lercanidipine is a recently introduced example of a lipophilic and vasoselective dihydropyridine CA. It is an effective vasodilator

  10. Monoclonal antibody to native P39 protein from Borrelia burgdorferi.

    OpenAIRE

    Sullivan, T J; Hechemy, K E; Harris, H L; Rudofsky, U H; Samsonoff, W A; Peterson, A J; Evans, B. D.; Balaban, S L

    1994-01-01

    We have produced, by using a sonicate of Borrelia burgdorferi, a monoclonal antibody (MAb), NYSP39H, that is specific for the P39 protein band. This MAb reacted with 13 isolates of B. burgdorferi but not with eight different spirochetes (four borrelias, two leptospiras, and two treponemas). Surface labeling of B. burgdorferi with biotin and subsequent treatment with Nonidet P-40 showed that P39 was not biotinylated but was extracted with Nonidet P-40, indicating that it is present within the ...

  11. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX....... Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon......)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers...

  12. Calcium regulation in endosymbiotic organelles of plants.

    Science.gov (United States)

    Bussemer, Johanna; Vothknecht, Ute C; Chigri, Fatima

    2009-09-01

    In plant cells calcium-dependent signaling pathways are involved in a large array of biological processes in response to hormones, biotic/abiotic stress signals and a variety of developmental cues. This is generally achieved through binding of calcium to diverse calcium-sensing proteins, which subsequently control downstream events by activating or inhibiting biochemical reactions. Regulation by calcium is considered as a eukaryotic trait and has not been described for prokaryotes. Nevertheless, there is increasing evidence indicating that organelles of prokaryotic origin, such as chloroplasts and mitochondria, are integrated into the calcium-signaling network of the cell. An important transducer of calcium in these organelles appears to be calmodulin. In this review we want to give an overview over present data showing that endosymbiotic organelles harbour calcium-dependent biological processes with a focus on calmodulin-regulation.

  13. Store-operated calcium signaling in neutrophils.

    Science.gov (United States)

    Clemens, Regina A; Lowell, Clifford A

    2015-10-01

    Calcium signals in neutrophils are initiated by a variety of cell-surface receptors, including formyl peptide and other GPCRs, FcRs, and integrins. The predominant pathway by which calcium enters immune cells is termed SOCE, whereby plasma membrane CRAC channels allow influx of extracellular calcium into the cytoplasm when intracellular ER stores are depleted. The identification of 2 key families of SOCE regulators, STIM calcium "sensors" and ORAI calcium channels, has allowed for genetic manipulation of SOCE pathways and provided valuable insight into the molecular mechanism of calcium signaling in immune cells, including neutrophils. This review focuses on our current knowledge of the molecules involved in neutrophil SOCE and how study of these molecules has further informed our understanding of the role of calcium signaling in neutrophil activation.

  14. Drosophila mushroom body Kenyon cells generate spontaneous calcium transients mediated by PLTX-sensitive calcium channels.

    Science.gov (United States)

    Jiang, Shaojuan Amy; Campusano, Jorge M; Su, Hailing; O'Dowd, Diane K

    2005-07-01

    Spontaneous calcium oscillations in mushroom bodies of late stage pupal and adult Drosophila brains have been implicated in memory consolidation during olfactory associative learning. This study explores the cellular mechanisms regulating calcium dynamics in Kenyon cells, principal neurons in mushroom bodies. Fura-2 imaging shows that Kenyon cells cultured from late stage Drosophila pupae generate spontaneous calcium transients in a cell autonomous fashion, at a frequency similar to calcium oscillations in vivo (10-20/h). The expression of calcium transients is up regulated during pupal development. Although the ability to generate transients is a property intrinsic to Kenyon cells, transients can be modulated by bath application of nicotine and GABA. Calcium transients are blocked, and baseline calcium levels reduced, by removal of external calcium, addition of cobalt, or addition of Plectreurys toxin (PLTX), an insect-specific calcium channel antagonist. Transients do not require calcium release from intracellular stores. Whole cell recordings reveal that the majority of voltage-gated calcium channels in Kenyon cells are PLTX-sensitive. Together these data show that influx of calcium through PLTX-sensitive voltage-gated calcium channels mediates spontaneous calcium transients and regulates basal calcium levels in cultured Kenyon cells. The data also suggest that these calcium transients represent cellular events underlying calcium oscillations in the intact mushroom bodies. However, spontaneous calcium transients are not unique to Kenyon cells as they are present in approximately 60% of all cultured central brain neurons. This suggests the calcium transients play a more general role in maturation or function of adult brain neurons.

  15. Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design.

    Science.gov (United States)

    Slade, Daniel J; Fang, Pengfei; Dreyton, Christina J; Zhang, Ying; Fuhrmann, Jakob; Rempel, Don; Bax, Benjamin D; Coonrod, Scott A; Lewis, Huw D; Guo, Min; Gross, Michael L; Thompson, Paul R

    2015-04-17

    Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ions that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.

  16. Exon: CBRC-CFAM-39-0000 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-39-0000 ATGCATGTGCGTTGTACACCCATGTGGAGCCTTGtgcacgcatgtcatgccactgcatgcgtatgcattgtgcatgcatatg...ccactggatgcacctgcatgtatacaCATGTGGTAGGTGGGCATGTGTGTGATGCCACTGGATGCGTGTGCATTGTGCATGCATGTGGTGTATTGTGCATGTATGGGATG...CCACTGCATGCACCTGTATGTATACATACACACGTGGTACGTGGGCATGTGTGTGATGCCACtgcatacatatg...tgggcatgcgtgtgatgcaactggatgcgtgtgcattgtgcatgcatgTGGTGCATTGTGGATGCATGTGCATTATACACGCAAGTGGTGCATTGTGCATGCATG...tgcattgtgcatgcatatggtgcattgtggatgcatgtgcattatacacgcatatggtgcattgggcatgcatgtggtgccactgcatgcatgagagctgtgcatgcatacaAGATGAGGGCCAATTATTGA ...

  17. Calcium channel antagonists in hypertension.

    Science.gov (United States)

    Ambrosioni, E; Borghi, C

    1989-02-01

    The clinical usefulness of calcium entry-blockers for the treatment of high blood pressure is related to their capacity to act upon the primary hemodynamic derangement in hypertension: the increased peripheral vascular resistance. They can be used alone or in combination with other antihypertensive agents for the treatment of various forms of hypertensive disease. The calcium entry-blockers appear to be the most useful agents for the treatment of hypertension in the elderly and for the treatment of hypertension associated with ischemic heart disease, pulmonary obstructive disease, peripheral vascular disease, and supraventricular arrhythmias. They are effective in reducing blood pressure in pregnancy-associated hypertension and must be considered as first-line therapy for the treatment of hypertensive crisis.

  18. Novel strategies in drug discovery of the calcium-sensing receptor based on biased signaling

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Smajilovic, Sanela; Bräuner-Osborne, Hans

    2012-01-01

    A hallmark of chronic kidney disease is hyperphosphatemia due to renal phosphate retention. Prolonged parathyroid gland exposure to hyperphosphatemia leads to secondary hyperparathyroidism characterized by hyperplasia of the glands and excessive secretion of parathyroid hormone (PTH), which causes...... renal osteodystrophy. PTH secretion from the parathyroid glands is controlled by the calcium-sensing receptor (CaSR) that senses extracellular calcium. High extracellular calcium activates the CaSR causing inhibition of PTH secretion through multiple signaling pathways. Cinacalcet is the first drug...... targeting the CaSR and can be used to effectively control and reduce PTH secretion in PTH-related diseases. Cinacalcet is a positive allosteric modulator of the CaSR and affects PTH secretion from parathyroid glands by shifting the calcium-PTH concentration-response curve to the left. One major disadvantage...

  19. The calcium-alkali syndrome

    OpenAIRE

    Arroyo, Mariangeli; Fenves, Andrew Z.; Emmett, Michael

    2013-01-01

    The milk-alkali syndrome was a common cause of hypercalcemia, metabolic alkalosis, and renal failure in the early 20th century. It was caused by the ingestion of large quantities of milk and absorbable alkali to treat peptic ulcer disease. The syndrome virtually vanished after introduction of histamine-2 blockers and proton pump inhibitors. More recently, a similar condition called the calcium-alkali syndrome has emerged as a common cause of hypercalcemia and alkalosis. It is usually caused b...

  20. Calcium phosphate polymer hybrid materials

    OpenAIRE

    2011-01-01

    Calcium phosphate (CaP) is of strong interest to the medical field because of its potential for bone repair, gene transfection, etc.1-3 Nowadays, the majority of the commercially available materials are fabricated via “classical” materials science approaches, i.e. via high temperature or high pressure approaches, from rather poorly defined slurries, or from organic solvents.3,4 Precipitation of inorganics with (polymeric) additives from aqueous solution on the other hand enables the synthesis...

  1. Kalium-39-NMR in-vivo am Menschen bei 7Tesla: 39K-MR-Bildgebung und Auflösung der Quadrupolaufspaltung der 39K-Resonanz

    OpenAIRE

    Rösler, Manuela Barbara

    2015-01-01

    In dieser Arbeit wurde die Machbarkeit der In-vivo-39K-MR-Bildgebung am menschlichen Oberschenkel sowie am Kopf mit einer nominellen Auflösung von 1 cm3 in einer Messzeit von 30 min bei einer Grundmagnetfeldstärke von 7T gezeigt. Zur Optimierung der Sequenzparameter wurden sowohl die globalen Relaxationszeitkonstanten bestimmt. In Untersuchungsregionen mit hohem Muskelanteil, wie im Ober- und Unterschenkel, ist die Resonanz von 39K in ein Triplett aufgespalten. Die beiden Satellitenresona...

  2. CCN3 and calcium signaling

    Directory of Open Access Journals (Sweden)

    Li Chang Long

    2003-08-01

    Full Text Available Abstract The CCN family of genes consists presently of six members in human (CCN1-6 also known as Cyr61 (Cystein rich 61, CTGF (Connective Tissue Growth Factor, NOV (Nephroblastoma Overexpressed gene, WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins. Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions. In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.

  3. Store-Operated Calcium Channels.

    Science.gov (United States)

    Prakriya, Murali; Lewis, Richard S

    2015-10-01

    Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca(2+) sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca(2+) from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca(2+) depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.

  4. Kinetics of calcium sulfoaluminate formation from tricalcium aluminate, calcium sulfate and calcium oxide

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xuerun, E-mail: xuerunli@163.com; Zhang, Yu; Shen, Xiaodong, E-mail: xdshen@njut.edu.cn; Wang, Qianqian; Pan, Zhigang

    2014-01-15

    The formation kinetics of tricalcium aluminate (C{sub 3}A) and calcium sulfate yielding calcium sulfoaluminate (C{sub 4}A{sub 3}$) and the decomposition kinetics of calcium sulfoaluminate were investigated by sintering a mixture of synthetic C{sub 3}A and gypsum. The quantitative analysis of the phase composition was performed by X-ray powder diffraction analysis using the Rietveld method. The results showed that the formation reaction 3Ca{sub 3}Al{sub 2}O{sub 6} + CaSO{sub 4} → Ca{sub 4}Al{sub 6}O{sub 12}(SO{sub 4}) + 6CaO was the primary reaction < 1350 °C with and activation energy of 231 ± 42 kJ/mol; while the decomposition reaction 2Ca{sub 4}Al{sub 6}O{sub 12}(SO{sub 4}) + 10CaO → 6Ca{sub 3}Al{sub 2}O{sub 6} + 2SO{sub 2} ↑ + O{sub 2} ↑ primarily occurred beyond 1350 °C with an activation energy of 792 ± 64 kJ/mol. The optimal formation region for C{sub 4}A{sub 3}$ was from 1150 °C to 1350 °C and from 6 h to 1 h, which could provide useful information on the formation of C{sub 4}A{sub 3}$ containing clinkers. The Jander diffusion model was feasible for the formation and decomposition of calcium sulfoaluminate. Ca{sup 2+} and SO{sub 4}{sup 2−} were the diffusive species in both the formation and decomposition reactions. -- Highlights: •Formation and decomposition of calcium sulphoaluminate were studied. •Decomposition of calcium sulphoaluminate combined CaO and yielded C{sub 3}A. •Activation energy for formation was 231 ± 42 kJ/mol. •Activation energy for decomposition was 792 ± 64 kJ/mol. •Both the formation and decomposition were controlled by diffusion.

  5. Quality of life in aphasia: Greek adaptation of the stroke and aphasia quality of life scale - 39 item (SAQOL-39)

    OpenAIRE

    Kartsona, A.; Hilari, K.

    2007-01-01

    AIM: Health-related quality of life (HRQL) measures are becoming increasingly popular in evaluating health care interventions and services. The stroke and aphasia quality of life scale-39 item (SAQOL-39) is an English questionnaire that measures HRQL in people with aphasia. There is currently no measure to assess the HRQL of Greek-speaking people with aphasia. This study began the cross-cultural adaptation of the SAQOL-39 into Greek, by translating and linguistically validating the instrument...

  6. Plasma Calcium, Inorganic Phosphate and Magnesium During Hypocalcaemia Induced by a Standardized EDTA Infusion in Cows

    Directory of Open Access Journals (Sweden)

    Enemark JMD

    2001-06-01

    Full Text Available The intravenous Na2EDTA infusion technique allows effective specific chelation of circulating Ca2+ leading to a progressive hypocalcaemia. Methods previously used were not described in detail and results obtained by monitoring total and free ionic calcium were not comparable due to differences in sampling and analysis. This paper describes a standardized EDTA infusion technique that allowed comparison of the response of calcium, phosphorus and magnesium between 2 groups of experimental cows. The concentration of the Na2EDTA solution was 0.134 mol/l and the flow rate was standardized at 1.2 ml/kg per hour. Involuntary recumbency occurred when ionised calcium dropped to 0.39 – 0.52 mmol/l due to chelation. An initial fast drop of ionized calcium was observed during the first 20 min of infusion followed by a fluctuation leading to a further drop until recumbency. Pre-infusion [Ca2+] between tests does not correlate with the amount of EDTA required to induce involuntary recumbence. Total calcium concentration measured by atomic absorption remained almost constant during the first 100 min of infusion but declined gradually when the infusion was prolonged. The concentration of inorganic phosphate declined gradually in a fluctuating manner until recumbency. Magnesium concentration remained constant during infusion. Such electrolyte responses during infusion were comparable to those in spontaneous milk fever. The standardized infusion technique might be useful in future experimental studies.

  7. —Part I. Interaction of Calcium and Copper-Calcium Alloy with Electrolyte

    Science.gov (United States)

    Zaikov, Yurii P.; Batukhtin, Victor P.; Shurov, Nikolay I.; Ivanovskii, Leonid E.; Suzdaltsev, Andrey V.

    2014-06-01

    This paper describes the interaction between calcium and molten CaCl2 and the solubility of calcium in this melt, depending on the calcium content in the copper-calcium alloy that comes in contact with the molten CaCl2. The negative influence of the dissolved calcium on the current efficiency was verified. The negative effects of moisture and CaO impurities on the calcium current efficiency were demonstrated. The dependence of the current efficiency and the purity of the metal obtained by the electrolysis conditions were studied in a laboratory electrolyzer (20 to 80 A).

  8. Autogenous vein graft thrombosis following exposure to calcium-free solutions (calcium paradox).

    Science.gov (United States)

    Nozick, J H; Farnsworth, P; Montefusco, C M; Parsonnet, V; Ruigrok, T J; Zimmerman, A N

    1981-01-01

    The morphological and functional effects of calcium-free and calcium-containing solutions on canine jugular vein intima were examined under conditions which closely resemble those techniques currently employed in peripheral vascular and aortocoronary bypass surgery. Veins that had been exposed only to calcium-containing solutions remained patent for the duration of the experimental period. Vein perfusion with a calcium-free solution, however, resulted in disruption of the jugular vein intima once calcium ions were reintroduced. Autogenous as a femoral arterial graft became thrombosed within 60 minutes. It is therefore suggested that vein grafts of autogenous origin be irrigated with calcium-containing solutions to prevent intimal damage and thrombosis.

  9. Vitamin D-enhanced duodenal calcium transport.

    Science.gov (United States)

    Wongdee, Kannikar; Charoenphandhu, Narattaphol

    2015-01-01

    For humans and rodents, duodenum is a very important site of calcium absorption since it is exposed to ionized calcium released from dietary complexes by gastric acid. Calcium traverses the duodenal epithelium via both transcellular and paracellular pathways in a vitamin D-dependent manner. After binding to the nuclear vitamin D receptor, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] upregulates the expression of several calcium transporter genes, e.g., TRPV5/6, calbindin-D9k, plasma membrane Ca(2+)-ATPase1b, and NCX1, thereby enhancing the transcellular calcium transport. This action has been reported to be under the regulation of parathyroid-kidney-intestinal and bone-kidney-intestinal axes, in which the plasma calcium and fibroblast growth factor-23 act as negative feedback regulators, respectively. 1,25(OH)2D3 also modulates the expression of tight junction-related genes and convective water flow, presumably to increase the paracellular calcium permeability and solvent drag-induced calcium transport. However, vitamin D-independent calcium absorption does exist and plays an important role in calcium homeostasis under certain conditions, particularly in neonatal period, pregnancy, and lactation as well as in naturally vitamin D-impoverished subterranean mammals.

  10. The Role of Calcium in Osteoporosis

    Science.gov (United States)

    Arnaud, C. D.; Sanchez, S. D.

    1991-01-01

    Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

  11. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  12. 7 CFR 1773.39 - Utility plant and accumulated depreciation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Utility plant and accumulated depreciation. 1773.39... Procedures and Documentation § 1773.39 Utility plant and accumulated depreciation. (a) General. The audit of... depreciation reserves; (4) Examined direct purchases of special equipment and general plant; (5) Determined...

  13. Elective caesarean section at 38 weeks versus 39 weeks

    DEFF Research Database (Denmark)

    Glavind, Julie; Kindberg, S F; Uldbjerg, N;

    2013-01-01

    To investigate whether elective caesarean section before 39 completed weeks of gestation increases the risk of adverse neonatal or maternal outcomes.......To investigate whether elective caesarean section before 39 completed weeks of gestation increases the risk of adverse neonatal or maternal outcomes....

  14. 7 CFR 319.56-39 - Fragrant pears from China.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Fragrant pears from China. 319.56-39 Section 319.56-39... pears from China. Fragrant pears may be imported into the United States from China only under the... China. (2) All propagative material introduced into a registered production site must be certified...

  15. 31 CFR 103.39 - Person outside the United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Person outside the United States. 103.39 Section 103.39 Money and Finance: Treasury Regulations Relating to Money and Finance FINANCIAL RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS Records Required To Be Maintained §...

  16. 39 CFR 3.2 - Compensation of Board.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Compensation of Board. 3.2 Section 3.2 Postal... (ARTICLE III) § 3.2 Compensation of Board. Section 202(a)(1) of title 39 provides for the compensation of... meetings. Compensation is provided for not more than 42 days of meetings per year....

  17. 19 CFR 19.39 - Delivery for exportation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Delivery for exportation. 19.39 Section 19.39... Delivery for exportation. (a) Delivery to land border locations—(1) Land border locations. Land border... exportation from such locations shall be made to the purchaser only beyond the exit point, except as...

  18. 20 CFR 901.39 - Reply to answer.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Reply to answer. 901.39 Section 901.39 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF ACTUARIAL SERVICES UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 Suspension or Termination...

  19. 15 CFR 265.39 - Weapons and explosives.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Weapons and explosives. 265.39 Section..., GAITHERSBURG, MARYLAND, AND BOULDER AND FORT COLLINS, COLORADO Buildings and Grounds § 265.39 Weapons and... dangerous or deadly weapons or materials, or explosives, either openly or concealed, without the...

  20. Antimicrobial and immunomodulatory activities of PR-39 derived peptides.

    Directory of Open Access Journals (Sweden)

    Edwin J A Veldhuizen

    Full Text Available The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics.

  1. 28 CFR 71.39 - Appeal to authority head.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Appeal to authority head. 71.39 Section 71.39 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) IMPLEMENTATION OF THE PROVISIONS OF... appeal shall be stayed automatically pending resolution of the motion for reconsideration. (2) If...

  2. 48 CFR 39.102 - Management of risk.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Management of risk. 39.102... CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 39.102 Management of risk. (a) Prior to entering... monitored, funding availability, and program management risk. (c) Appropriate techniques should be...

  3. 14 CFR 147.39 - Display of certificate.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Display of certificate. 147.39 Section 147.39 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SCHOOLS AND OTHER CERTIFICATED AGENCIES AVIATION MAINTENANCE TECHNICIAN SCHOOLS Operating Rules §...

  4. 38 CFR 39.122 - Inspections, audits, and reports.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Inspections, audits, and reports. 39.122 Section 39.122 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Single Audit Act of 1984 (see part 41 of this chapter). (b) A State will make an annual report on VA...

  5. 38 CFR 39.25 - Inspections, audits, and reports.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Inspections, audits, and reports. 39.25 Section 39.25 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... State will make an annual report on VA Form 40-0241 (“State Cemetery Data”) signed by the...

  6. 33 CFR 157.39 - Machinery space bilges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Machinery space bilges. 157.39... Vessel Operation § 157.39 Machinery space bilges. (a) A tank vessel may discharge an oily mixture from a machinery space bilge that is combined with an oil cargo residue if the vessel discharges in compliance...

  7. 9 CFR 3.39 - Care in transit.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Care in transit. 3.39 Section 3.39 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling, Care, Treatment, and Transportation of...

  8. Rat pancreas secretes particulate ecto-nucleotidase CD39

    DEFF Research Database (Denmark)

    Sørensen, Christiane Elisabeth; Amstrup, Jan; Rasmussen, Hans N;

    2003-01-01

    In exocrine pancreas, acini release ATP and the excurrent ducts express several types of purinergic P2 receptors. Thereby, ATP, or its hydrolytic products, might play a role as a paracrine regulator between acini and ducts. The aim of the present study was to elucidate whether this acinar......-ductal signalling is regulated by nucleotidase(s), and to characterize and localize one of the nucleotidases within the rat pancreas. Using RT-PCR and Western blotting we show that pancreas expresses the full length ecto-nucleoside triphosphate diphosphohydrolase, CD39. Immunofluorescence shows CD39 localization...... relocalizes in clusters towards the lumen and is secreted. As a result, pancreatic juice collected from intact pancreas stimulated with CCK-8 contained nucleotidase activity, including that of CD39, and no detectable amounts of ATP. Anti-CD39 antibodies detected the full length (78 kDa) CD39 in pancreatic...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse...... models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice......, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D [1,25(OH)D] despite no change in FGF23...

  10. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Directory of Open Access Journals (Sweden)

    Bading Hilmar

    2007-07-01

    Full Text Available Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

  11. Fortification of all-purpose wheat-flour tortillas with calcium lactate, calcium carbonate, or calcium citrate is acceptable.

    Science.gov (United States)

    Romanchik-Cerpovicz, Joelle E; McKemie, Rebecca J

    2007-03-01

    Fortification helps provide adequate nutrients for individuals not meeting daily needs. Foods may be fortified with calcium to assist individuals with lactose intolerance and others preferring not to consume traditional forms of dairy. This study examined the quality of all-purpose wheat-flour tortillas fortified with calcium lactate, calcium carbonate, or calcium citrate. These tortillas were compared to similarly prepared nonfortified flour tortillas (control) and commercial nonfortified flour tortillas. Calcium-fortified tortillas contained 114 mg elemental calcium per standard serving (48 g tortilla), an 8.6-fold increase compared to nonfortified tortillas. Moisture contents and rollabilities of all tortillas were similar. Consumers (N=87) evaluated each tortilla in duplicate using a hedonic scale and reported liking the appearance, texture, flavor, aftertaste, and overall acceptability of all tortillas. However, the appearance of control tortillas was preferred over commercial tortillas (P<0.01), whereas the aftertaste of commercial tortillas or those fortified with calcium carbonate was preferred over the control (P<0.05). Despite these differences, consumers were equally willing to purchase both fortified and nonfortified tortillas, suggesting that appearance and aftertaste may not influence willingness to purchase. Overall, this study shows that fortification of flour tortillas with various forms of calcium is a feasible alternative calcium source.

  12. STS-103 crew pose in front of Pad 39B

    Science.gov (United States)

    1999-01-01

    During Terminal Countdown Demonstration Test (TDCT) activities at Launch Pad 39B, the STS-103 crew pose in front of the flame trench, which is situated underneath the Mobile Launcher Platform holding Space Shuttle Discovery. Standing left to right are Mission Specialists Claude Nicollier of Switzerland, who is with the European Space Agency (ESA), C. Michael Foale (Ph.D.), John M. Grunsfeld (Ph.D.), Pilot Scott J. Kelly, Commander Curtis L. Brown Jr., and Mission Specialists Jean-Frangois Clervoy of France, also with ESA, and Steven L. Smith. One of the solid rocket boosters and the external tank that are attached to Discovery can be seen in the photo. The flame trench is made of concrete and refractory brick, and contains an orbiter flame deflector on one side and solid rocket booster flame deflector on the other. The deflectors protect the flame trench floor and pad surface from the intense heat of launch. The TCDT provides the crew with emergency egress training, opportunities to inspect their mission payloads in the orbiter's payload bay, and simulated countdown exercises. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope, including the gyroscopes that allow the telescope to point at stars, galaxies and planets. The STS-103 crew will be replacing a Fine Guidance Sensor, an older computer with a new enhanced model, an older data tape recorder with a solid-state digital recorder, a failed spare transmitter with a new one, and degraded insulation on the telescope with new thermal insulation. The crew will also install a Battery Voltage/Temperature Improvement Kit to protect the spacecraft batteries from overcharging and overheating when the telescope goes into a safe mode. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  13. The calcium-dependent protein kinase 3 of toxoplasma influences basal calcium levels and functions beyond egress as revealed by quantitative phosphoproteome analysis.

    OpenAIRE

    Moritz Treeck; Sanders, John L.; Rajshekhar Y Gaji; Kacie A LaFavers; Child, Matthew A.; Gustavo Arrizabalaga; Elias, Joshua E.; John C Boothroyd

    2014-01-01

    Calcium-dependent protein kinases (CDPKs) are conserved in plants and apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress from the host cell in the presence of a calcium-ionophore. The targets and the pathways that the kinase controls, however, are not known. To identify pathways regulated by TgCDPK3, we measured relative phosphorylation site usage in wild type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry using stable isotope-labelin...

  14. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

    and dense gel structure and with little seperation of whey due to participation of calcium to the final gel structure. On the other hand, the combination of heat treatment and calcium addition to milk with pH values lower than 5.6 will still produce gel structures which are dominated by the decrease of p......Calcium is one of the several elements that can be found in milk distributed between the micellar and the serum milk phase. Calcium is important from a nutritional point of view, but its contribution to the functional and structural properties of dairy products has only recently been...... acknowledgement. The presence of calcium in a dynamic equilibrium between the serum and the micellar milk phase make the distribution susceptible to certain physicochemical conditions and to technological treatments of milk resulting in fluctuations in pH and temperature and also sensitive to addition of calcium...

  15. Overbased Calcium sulfonate Detergent Technology Overview

    Institute of Scientific and Technical Information of China (English)

    MA Qing-gao; MUIR Ronald J.

    2009-01-01

    Overbased calcium sulfonate is used widely as detergent in automotive and marine lubricants, as well as various industrial oil applications. In this paper, the process to produce overbased calcium sulfonate is overviewed. The sulfonate structure and molecular weight and its molecular weight distribution, the enclosed calcium carbonate nanoparticle size and crystalline structure, properties of the carrier oil, all influence its properties, such as stability, viscosity, and detergency of the system.

  16. [Calcium carbide of different crystal formation synthesized by calcium carbide residue].

    Science.gov (United States)

    Lu, Zhong-yuan; Kang, Ming; Jiang, Cai-rong; Tu, Ming-jing

    2006-04-01

    To recycle calcium carbide residue effectively, calcium carbide of different crystal form, including global aragonite, calcite and acicular calcium carbide was synthesized. Both the influence of pretreatment in the purity of calcium carbide, and the influence of temperatures of carbonization reaction, release velocity of carbon dioxide in the apparition of calcium carbide of different crystal form were studied with DTA-TG and SEM. The result shows that calcium carbide residue can take place chemistry reaction with ammonia chlorinate straight. Under the condition that pH was above 7, the purity of calcium carbide was above 97%, and the whiteness was above 98. Once provided the different temperatures of carbonization reaction and the proper release velocity of carbon dioxide, global aragonite, calcite and acicular calcium carbide were obtained.

  17. Red blood cell calcium homeostasis in patients with end-stage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Gafter, U.; Malachi, T.; Barak, H.; Djaldetti, M.; Levi, J. (Hasharon Hospital, Petah-Tiqva (Israel))

    1989-09-01

    Low cell calcium level is essential for preservation of red blood cell (RBC) membrane deformability and survival. RBCs from patients with end-stage renal disease (ESRD) demonstrate reduction in membrane deformability, possibly as a result of increased RBC cellular calcium level. To evaluate calcium homeostasis in RBCs from patients with ESRD, we measured cell calcium level, basal and calmodulin-stimulated calcium-stimulated Mg-dependent ATPase (CaATPase) activity, and calcium 45 efflux were measured before and after hemodialysis. The in vitro effect of uremic plasma and of urea on CaATPase activity of normal RBCs was tested, and 45Ca influx into RBCs of patients undergoing hemodialysis also was determined. A morphologic evaluation of red cells from patients with ESRD was performed with a scanning electron microscope. RBC calcium level in patients (mean +/- SEM 21.2 +/- 2.8 mumol/L of cells; n = 28) was higher than in controls (4.9 +/- 0.3 mumol/L of cells; n = 24; p less than 0.001). Hemodialysis had no effect on cell calcium level. Both basal and calmodulin-stimulated RBC CaATPase activities in patients with ESRD (n = 9) were reduced by approximately 50% (p less than 0.01), but after hemodialysis, enzyme activity returned to normal. 45Ca efflux from calcium-loaded cells, which was 2574.0 +/- 217.0 mumol/L of cells per 0.5 hours before hemodialysis, increased to 3140.7 +/- 206.8 mumol/L of cells per 0.5 hours after hemodialysis (p less than 0.005). In vitro incubation of normal RBCs with uremic plasma depressed CaATPase activity, but incubation with urea had no effect. RBCs of patients with ESRD revealed increased 45Ca influx, 7.63 +/- 1.15 mumol/L of cells per hour versus 4.61 +/- 0.39 mumol/L of cells per hour (p less than 0.025). RBCs of patients revealed a high incidence of spherocytosis and echynocytosis, which correlated with a high cell calcium level (r = 0.894, p less than 0.01).

  18. Calcium binding proteins and calcium signaling in prokaryotes.

    Science.gov (United States)

    Domínguez, Delfina C; Guragain, Manita; Patrauchan, Marianna

    2015-03-01

    With the continued increase of genomic information and computational analyses during the recent years, the number of newly discovered calcium binding proteins (CaBPs) in prokaryotic organisms has increased dramatically. These proteins contain sequences that closely resemble a variety of eukaryotic calcium (Ca(2+)) binding motifs including the canonical and pseudo EF-hand motifs, Ca(2+)-binding β-roll, Greek key motif and a novel putative Ca(2+)-binding domain, called the Big domain. Prokaryotic CaBPs have been implicated in diverse cellular activities such as division, development, motility, homeostasis, stress response, secretion, transport, signaling and host-pathogen interactions. However, the majority of these proteins are hypothetical, and only few of them have been studied functionally. The finding of many diverse CaBPs in prokaryotic genomes opens an exciting area of research to explore and define the role of Ca(2+) in organisms other than eukaryotes. This review presents the most recent developments in the field of CaBPs and novel advancements in the role of Ca(2+) in prokaryotes.

  19. Disease causing mutations of calcium channels.

    Science.gov (United States)

    Lorenzon, Nancy M; Beam, Kurt G

    2008-01-01

    Calcium ions play an important role in the electrical excitability of nerve and muscle, as well as serving as a critical second messenger for diverse cellular functions. As a result, mutations of genes encoding calcium channels may have subtle affects on channel function yet strongly perturb cellular behavior. This review discusses the effects of calcium channel mutations on channel function, the pathological consequences for cellular physiology, and possible links between altered channel function and disease. Many cellular functions are directly or indirectly regulated by the free cytosolic calcium concentration. Thus, calcium levels must be very tightly regulated in time and space. Intracellular calcium ions are essential second messengers and play a role in many functions including, action potential generation, neurotransmitter and hormone release, muscle contraction, neurite outgrowth, synaptogenesis, calcium-dependent gene expression, synaptic plasticity and cell death. Calcium ions that control cell activity can be supplied to the cell cytosol from two major sources: the extracellular space or intracellular stores. Voltage-gated and ligand-gated channels are the primary way in which Ca(2+) ions enter from the extracellular space. The sarcoplasm reticulum (SR) in muscle and the endoplasmic reticulum in non-muscle cells are the main intracellular Ca(2+) stores: the ryanodine receptor (RyR) and inositol-triphosphate receptor channels are the major contributors of calcium release from internal stores.

  20. Regulation of cardiomyocyte autophagy by calcium.

    Science.gov (United States)

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

    2016-04-15

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

  1. Altered calcium signaling following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    John Thomas Weber

    2012-04-01

    Full Text Available Cell death and dysfunction after traumatic brain injury (TBI is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI.

  2. Sintering of calcium phosphate bioceramics.

    Science.gov (United States)

    Champion, E

    2013-04-01

    Calcium phosphate ceramics have become of prime importance for biological applications in the field of bone tissue engineering. This paper reviews the sintering behaviour of these bioceramics. Conventional pressureless sintering of hydroxyapatite, Ca10(PO4)6(OH)2, a reference compound, has been extensively studied. Its physico-chemistry is detailed. It can be seen as a competition between two thermally activated phenomena that proceed by solid-state diffusion of matter: densification and grain growth. Usually, the objective is to promote the first and prevent the second. Literature data are analysed from sintering maps (i.e. grain growth vs. densification). Sintering trajectories of hydroxyapatite produced by conventional pressureless sintering and non-conventional techniques, including two-step sintering, liquid phase sintering, hot pressing, hot isostatic pressing, ultrahigh pressure, microwave and spark plasma sintering, are presented. Whatever the sintering technique may be, grain growth occurs mainly during the last step of sintering, when the relative bulk density reaches 95% of the maximum value. Though often considered very advantageous, most assisted sintering techniques do not appear very superior to conventional pressureless sintering. Sintering of tricalcium phosphate or biphasic calcium phosphates is also discussed. The chemical composition of calcium phosphate influences the behaviour. Similarly, ionic substitutions in hydroxyapatite or in tricalcium phosphate create lattice defects that modify the sintering rate. Depending on their nature, they can either accelerate or slow down the sintering rate. The thermal stability of compounds at the sintering temperature must also be taken into account. Controlled atmospheres may be required to prevent thermal decomposition, and flash sintering techniques, which allow consolidation at low temperature, can be helpful.

  3. Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels

    OpenAIRE

    2008-01-01

    Digitoxin and other cardiac glycosides are important, centuries-old drugs for treating congestive heart failure. However, the mechanism of action of these compounds is still being elucidated. Calcium is known to potentiate the toxicity of these drugs, and we have hypothesized that digitoxin might mediate calcium entry into cells. We report here that digitoxin molecules mediate calcium entry into intact cells. Multimers of digitoxin molecules also are able to form calcium channels in pure plan...

  4. The Role of Calcium in Prevention and Treatment of Osteoporosis.

    Science.gov (United States)

    Heaney, Robert P.

    1987-01-01

    Osteoporosis results from several factors. Calcium deficiency is only one, and high calcium intake will prevent only those cases in which calcium is the limiting factor. Calcium cannot reverse, but only arrest, bone loss. A high calcium intake for every member of the population is advocated. (Author/MT)

  5. Calcium imaging perspectives in plants.

    Science.gov (United States)

    Kanchiswamy, Chidananda Nagamangala; Malnoy, Mickael; Occhipinti, Andrea; Maffei, Massimo E

    2014-03-04

    The calcium ion (Ca2+) is a versatile intracellular messenger. It provides dynamic regulation of a vast array of gene transcriptions, protein kinases, transcription factors and other complex downstream signaling cascades. For the past six decades, intracellular Ca2+ concentration has been significantly studied and still many studies are under way. Our understanding of Ca2+ signaling and the corresponding physiological phenomenon is growing exponentially. Here we focus on the improvements made in the development of probes used for Ca2+ imaging and expanding the application of Ca2+ imaging in plant science research.

  6. The Electronic Structure of Calcium

    DEFF Research Database (Denmark)

    Jan, J.-P.; Skriver, Hans Lomholt

    1981-01-01

    The electronic structure of calcium under pressure is re-examined by means of self-consistent energy band calculations based on the local density approximation and using the linear muffin-tin orbitals (LMTO) method with corrections to the atomic sphere approximation included. At zero pressure.......149 Ryd, respectively, relative to the s band, give the best possible agreement. Under increasing pressure the s and p electrons are found to transfer into the d band, and Ca undergoes metal-semimetal-metal electronic transitions. Calculations of the bandstructure and the electronic pressure, including...

  7. ALG-2 oscillates in subcellular localization, unitemporally with calcium oscillations

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Berchtold, Martin Werner

    2007-01-01

    localization in an oscillatory fashion unitemporally with Ca2+ oscillations, whereas a Ca2+-binding deficient mutant of ALG-2 did not redistribute. Using tagged ALG-2 as bait we identified its novel target protein Sec31A and based on the partial colocalization of endogenous ALG-2 and Sec31A we propose that ALG......A variety of stimuli can trigger intracellular calcium oscillations. Relatively little is known about the molecular mechanisms decoding these events. We show that ALG-2, a Ca2+-binding protein originally isolated as a protein associated with apoptosis, is directly linked to Ca2+ signalling. We...

  8. Store-operated calcium channels and pro-inflammatory signals

    Institute of Scientific and Technical Information of China (English)

    Wei-chiao CHANG

    2006-01-01

    In non-excitable cells such as T lymphocytes,hepatocytes,mast cells,endothelia and epithelia,the major pathway for calcium(Ca2+)entry is through store-operated Ca2+ channels in the plasma membrane.These channels are activated by the emptying of intracellular Ca2+ stores,however,neither the gating mechanism nor the downstream targets of these channels has been clear established.Here,I review some of the proposed gating mechanisms of store-operated Ca2+ channels and the functional implications in regulating pro-inflammatory signals.

  9. Calcium

    Science.gov (United States)

    ... don't have enough of the intestinal enzyme lactase that helps digest the sugar (lactose) in dairy ... free dairy products are readily available, as are lactase drops that can be added to dairy products ...

  10. Calcium

    Science.gov (United States)

    ... tingling in the fingers, convulsions, and abnormal heart rhythms that can lead to death if not corrected. ... that includes weight-bearing physical activity (such as walking and running). Osteoporosis is a disease of the ...

  11. Calcium

    Science.gov (United States)

    ... for dinner. Create mini-pizzas by topping whole-wheat English muffins or bagels with pizza sauce and ... Fitness Center Vitamin D Smart Supermarket Shopping Lactose Intolerance Vitamins and Minerals Vitamin Chart Mineral Chart Food ...

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  13. 76 FR 51991 - Determination That PENTETATE CALCIUM TRISODIUM (Trisodium Calcium Diethylenetriaminepentaacetate...

    Science.gov (United States)

    2011-08-19

    ... new drug applications (ANDAs) for PENTETATE CALCIUM TRISODIUM (Ca-DTPA) solution for intravenous or... ANDA that does not refer to a listed drug. PENTETATE CALCIUM TRISODIUM (Ca-DTPA) solution for... HUMAN SERVICES Food and Drug Administration Determination That PENTETATE CALCIUM TRISODIUM...

  14. Effect of lowering dietary calcium intake on fractional whole body calcium retention

    Energy Technology Data Exchange (ETDEWEB)

    Dawson-Hughes, B.; Stern, D.T.; Shipp, C.C.; Rasmussen, H.M.

    1988-07-01

    Although fractional calcium absorption is known to vary inversely with calcium intake, the extent and timing of individual hormonal and calcium absorption responses to altered calcium intake have not been defined. We measured fractional whole body retention of orally ingested /sup 47/Ca, an index of calcium absorption, in nine normal women after they had eaten a 2000-mg calcium diet for 8 weeks and a 300-mg calcium diet for 1, 2, 4, and 8 weeks. After the diet change, serum intact PTH (32.2% increase; P = 0.005), serum 1,25-dihydroxyvitamin D (1,25-(OH)2D; 43.8% increase; P = 0.003), and fractional whole body calcium retention (42.8% increase; P = 0.004) increased within 1 week. Although the PTH and calcium retention responses remained fairly constant throughout the low calcium intake period, serum 1,25-(OH)2D concentrations declined toward baseline after week 1. Thus, the late increase in calcium retention may have resulted from calcium absorption that was independent of 1,25-(OH)2D stimulation.

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

    Science.gov (United States)

    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. Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Ajibade, Dare; Benn, Bryan S; Feng, Jingjing; Joshi, Sneha S

    2010-07-01

    Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action.

  17. Effect of calcium on adsorption capacity of powdered activated carbon.

    Science.gov (United States)

    Li, Gang; Shang, Junteng; Wang, Ying; Li, Yansheng; Gao, Hong

    2013-12-01

    We investigated the effect of calcium ion on the adsorption of humic acid (HA) (as a target pollutant) by powered activated carbon. The HA adsorption isotherms at different pH and kinetics of two different solutions including HA alone and HA doped Ca(2+), were performed. It was showed that the adsorption capacity of powdered activated carbon (PAC) for HA was markedly enhanced when Ca(2+) was doped into HA. Also, HA and Ca(2+) taken as nitrate were tested on the uptake of each other respectively and it was showed that the adsorbed amounts of both of them were significantly promoted when HA and calcium co-existed. Furthermore, the adsorbed amount of HA slightly decreased with the increasing of Ca(2+) concentration, whereas the amount of calcium increased with the increasing of HA concentration, but all above the amounts without addition. Finally, the change of pH before and after adsorption process is studied. In the two different solutions including HA alone and HA doped Ca(2+), pH had a small rise, but the extent of pH of later solution was bigger.

  18. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model

    Science.gov (United States)

    Liu, Baohua; Wang, Zimei; Zhang, Le; Ghosh, Shrestha; Zheng, Huiling; Zhou, Zhongjun

    2013-01-01

    A de novo G608G mutation in LMNA gene leads to Hutchinson–Gilford progeria syndrome. Mice lacking the prelamin A-processing metalloprotease, Zmpste24, recapitulate many of the progeroid features of Hutchinson–Gilford progeria syndrome. Here we show that A-type lamins interact with SUV39H1, and prelamin A/progerin exhibits enhanced binding capacity to SUV39H1, protecting it from proteasomal degradation and, consequently, increasing H3K9me3 levels. Depletion of Suv39h1 reduces H3K9me3 levels, restores DNA repair capacity and delays senescence in progeroid cells. Remarkably, loss of Suv39h1 in Zmpste24−/− mice delays body weight loss, increases bone mineral density and extends lifespan by ∼60%. Thus, increased H3K9me3 levels, possibly mediated by enhanced Suv39h1 stability in the presence of prelamin A/progerin, compromise genome maintenance, which in turn contributes to accelerated senescence in laminopathy-based premature aging. Our study provides an explanation for epigenetic alterations in Hutchinson–Gilford progeria syndrome and a potential strategy for intervention by targeting SUV39H1-mediated heterochromatin remodelling. PMID:23695662

  19. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model.

    Science.gov (United States)

    Liu, Baohua; Wang, Zimei; Zhang, Le; Ghosh, Shrestha; Zheng, Huiling; Zhou, Zhongjun

    2013-01-01

    A de novo G608G mutation in LMNA gene leads to Hutchinson-Gilford progeria syndrome. Mice lacking the prelamin A-processing metalloprotease, Zmpste24, recapitulate many of the progeroid features of Hutchinson-Gilford progeria syndrome. Here we show that A-type lamins interact with SUV39H1, and prelamin A/progerin exhibits enhanced binding capacity to SUV39H1, protecting it from proteasomal degradation and, consequently, increasing H3K9me3 levels. Depletion of Suv39h1 reduces H3K9me3 levels, restores DNA repair capacity and delays senescence in progeroid cells. Remarkably, loss of Suv39h1 in Zmpste24(-/-) mice delays body weight loss, increases bone mineral density and extends lifespan by ∼60%. Thus, increased H3K9me3 levels, possibly mediated by enhanced Suv39h1 stability in the presence of prelamin A/progerin, compromise genome maintenance, which in turn contributes to accelerated senescence in laminopathy-based premature aging. Our study provides an explanation for epigenetic alterations in Hutchinson-Gilford progeria syndrome and a potential strategy for intervention by targeting SUV39H1-mediated heterochromatin remodelling.

  20. Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

    Institute of Scientific and Technical Information of China (English)

    Mary; Louisa; Holton; Michael; Emerson; Ludwig; Neyses; Angel; L; Armesilla

    2010-01-01

    Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.

  1. Vitamin D signaling in calcium and bone homeostasis: a delicate balance.

    Science.gov (United States)

    Carmeliet, Geert; Dermauw, Veronique; Bouillon, Roger

    2015-08-01

    Loss-of-function mutations in genes involved in the vitamin D/vitamin D receptor system have clearly evidenced its critical role for mineral and skeletal homeostasis. Adequate levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D are therefore required and depend on sufficient sunlight exposure or dietary intake. Intestinal calcium absorption is a primary target of 1,25(OH)2D action and this pathway indirectly promotes calcium incorporation in bone. Severe vitamin D deficiency may thus decrease bone quality and leads to osteomalacia, whereas less severe deficiency increases the risk of osteoporosis and bone fractures. On the other hand, high vitamin D levels together with low dietary calcium intake will increase bone resorption and decrease bone mineralization in order to maintain normal serum calcium levels. Appropriate dietary calcium intake and sufficient serum vitamin D levels are thus important for skeletal health. Dosing of calcium and vitamin D supplements is still debated and requires further investigation.

  2. Calcium signaling in pluripotent stem cells.

    Science.gov (United States)

    Apáti, Ágota; Pászty, Katalin; Erdei, Zsuzsa; Szebényi, Kornélia; Homolya, László; Sarkadi, Balázs

    2012-04-28

    Pluripotent stem cells represent a new source of biological material allowing the exploration of signaling phenomena during normal cell development and differentiation. Still, the calcium signaling pathways and intracellular calcium responses to various ligands or stress conditions have not been sufficiently explored as yet in embryonic or induced pluripotent stem cells and in their differentiated offspring. This is partly due to the special culturing conditions of these cell types, the rapid morphological and functional changes in heterogeneous cell populations during early differentiation, and methodological problems in cellular calcium measurements. In this paper, we review the currently available data in the literature on calcium signaling in pluripotent stem cells and discuss the potential shortcomings of these studies. Various assay methods are surveyed for obtaining reliable data both in undifferentiated embryonic stem cells and in specific, stem cell-derived human tissues. In this paper, we present the modulation of calcium signaling in human embryonic stem cells (hESC) and in their derivates; mesenchymal stem cell like (MSCl) cells and cardiac tissues using the fluorescent calcium indicator Fluo-4 and confocal microscopy. LPA, trypsin and angiotensin II were effective in inducing calcium signals both in HUES9 and MSCl cells. Histamine and thrombin induced calcium signal exclusively in the MSCl cells, while ATP was effective only in HUES9 cells. There was no calcium signal evoked by GABA, even at relatively high concentrations. In stem cell-derived cardiomyocytes a rapid increase in the beating rate and an increase of the calcium signal peaks could be observed after the addition of adrenaline, while verapamil led to a strong decrease in cellular calcium and stopped spontaneous contractions in a relaxed state.

  3. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  4. Atmospheric environment for Space Shuttle Atlantis (STS-39) launch

    Science.gov (United States)

    Jasper, G. L.; Batts, G. W.

    1992-01-01

    A summary is presented of selected atmospheric conditions observed near space shuttle Atlantis STS-39 launch time on 28 April 1991, at Kennedy Space Center, FL. Values of ambient pressure, temperature, moisture, ground winds, visual observations (cloud), and winds aloft are included. The sequence of prelaunch Jimsphere measured vertical wind profiles is given. The final atmospheric tape, which consists of wind and thermodynamic parameters versus altitude, for STS-39 vehicle ascent was constructed. The STS-39 ascent atmospheric data tape was constructed by NASA-Marshall to provide an internally consistent data set for use in postflight performance assessments and represents the best estimate of the launch environment to the 400,000 ft altitude that was traversed by the STS-39 vehicle.

  5. 14 CFR 39.3 - Definition of airworthiness directives.

    Science.gov (United States)

    2010-01-01

    ... AIRCRAFT AIRWORTHINESS DIRECTIVES § 39.3 Definition of airworthiness directives. FAA's airworthiness directives are legally enforceable rules that apply to the following products: aircraft, aircraft engines, propellers, and appliances....

  6. 34 CFR 361.39 - State-imposed requirements.

    Science.gov (United States)

    2010-07-01

    ... AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE VOCATIONAL REHABILITATION SERVICES PROGRAM State Plan and Other Requirements for Vocational Rehabilitation Services Administration § 361.39 State... policies relating to the administration or operation of its vocational rehabilitation program that...

  7. Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy

    Directory of Open Access Journals (Sweden)

    R Heuberger

    2014-10-01

    Full Text Available In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied – preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE and cross-linked polyethylene (XLPE against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

  8. Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy.

    Science.gov (United States)

    Heuberger, R; Wahl, P; Krieg, J; Gautier, E

    2014-10-23

    In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied - preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE) and cross-linked polyethylene (XLPE) against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

  9. An Intracellular Calcium Oscillations Model Including Mitochondrial Calcium Cycling

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-Min; LIU Zeng-Rong

    2005-01-01

    @@ Calcium is a ubiquitous second messenger. Mitochondria contributes significantly to intracellular Ca2+ dynamics.The experiment of Kaftan et al. [J. Biol. Chem. 275(2000) 25465] demonstrated that inhibiting mitochondrial Ca2+ uptake can reduce the frequency of cytosolic Ca2+ concentration oscillations of gonadotropes. By considering the mitochondrial Ca2+ cycling we develop a three-variable model of intracellular Ca2+ oscillations based on the models of Atri et al. [Biophys. J. 65 (1993) 1727] and Falcke et al. [Biophys. J. 77 (1999) 37]. The model reproduces the fact that mitochondrial Ca2+ cycling increases the frequency of cytosolic Ca2+ oscillations, which accords with Kaftan's results. Moreover the model predicts that when the mitochondria overload with Ca2+, the cytosolic Ca2+ oscillations vanish, which may trigger apoptosis.

  10. PKA controls calcium influx into motor neurons during a rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    Han Wang

    Full Text Available Cyclic adenosine monophosphate (cAMP has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR signaling pathway that is dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that PKA is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active PKA transgenes reveals that knockdown of PKA activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive PKA activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that PKA activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active PKA increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that PKA activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels.

  11. 21 CFR 182.8217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium phosphate. 182.8217 Section 182.8217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b) Conditions of use. This...

  12. Bespuiten met calcium kan neusrot voorkomen

    NARCIS (Netherlands)

    Zandstra, G.B.; Marcelis, L.F.M.

    2000-01-01

    Oorzaak van neusrot bij paprika is een calciumtekort in de vrucht. Een bespuiting met calcium vlak na de bloei heeft een zeer gunstig effect. In bijgaande tabel gegevens over het effect van spuiten met calcium op het optreden van neusrot bij paprika

  13. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

    Rüdiger, Sten, E-mail: sten.ruediger@physik.hu-berlin.de

    2014-01-10

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  14. Oligofructose stimulates calcium absorption in adolescents

    NARCIS (Netherlands)

    Heuvel, E.G.H.M. van den; Muys, T.; Dokkum, W. van; Schaafsma, G.

    1999-01-01

    Background: In rats, nondigestible oligosaccharides stimulate calcium absorption. Recently, this effect was also found in human subjects. Objective: The objective of the study was to investigate whether consumption of 15 g oligofructose/d stimulates calcium absorption in male adolescents. Design: Tw

  15. ALG-2, a multifunctional calcium binding protein?

    DEFF Research Database (Denmark)

    Tarabykina, Svetlana; Mollerup, Jens; Winding Gojkovic, P.;

    2004-01-01

    ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article...

  16. Simulating complex calcium-calcineurin signaling network

    NARCIS (Netherlands)

    Cui, J.; Kaandorp, J.A.

    2008-01-01

    Understanding of processes in which calcium signaling is involved is of fundamental importance in systems biology and has many applications in medicine. In this paper we have studied the particular case of the complex calcium-calcineurin-MCIP-NFAT signaling network in cardiac myocytes, the understan

  17. Elements from chlorine to calcium nuclear reactions

    CERN Document Server

    Kunz, Wunibald

    1968-01-01

    Nuclear Tables: Part II Nuclear Reactions, Volume 3: The Elements from Chlorine to Calcium contains tabulations of the nuclear reaction values of elements chlorine, argon, potassium, and calcium. These tabulations provide the calculated Q-values of the elements and their isotopes. This book will be of value to general chemistry researchers.

  18. Adding calcium improves lithium ferrite core

    Science.gov (United States)

    Lessoff, H.

    1969-01-01

    Adding calcium increases uniformity of grain growth over a wide range of sintering temperatures and reduces porosity within the grain. Ferrite cores containing calcium have square hysteresis loops and high curie temperatures, making them useful in coincident current memories of digital electronic computers.

  19. Calcium, snails, and birds: a case study

    Directory of Open Access Journals (Sweden)

    R. Mänd

    2000-10-01

    Full Text Available Recent studies have shown that wild birds breeding in acidified areas have difficulties with obtaining sufficient calcium for their eggshells, and that the cause of it is the shortage of land snails. Many birds have to search for Ca-rich snail shells on a daily basis during egg production. Molluscs depend on litter calcium, which has decreased due to acidification of the environment. Calcium limitation may be a widespread phenomenon also in non-acidified, naturally Ca-poor areas. The problem is that while in the latter areas the time for development of specific adaptations may have been sufficient, then in acidified areas, on the contrary, calcium shortage is a recent phenomenon. Therefore, since the extent of calcium limitation in non-acidified areas is hard to derive from observational data, experimental approach is needed. We provide experimental evidence that specific calcium deficit does affect reproductive traits also in the birds breeding in naturally base-poor habitats. Our study was conducted in a heterogeneous woodland area in Estonia containing deciduous forest patches as well as base-poor pine forest with low snail abundance. Ca supplementation, using snail shell and chicken eggshell fragments, was carried out for pied flycatchers and great tits. Extra calcium affected positively several reproductive traits like egg volume and eggshell thickness, start of breeding, and fledglings’ parameters. The negative relationship between calcium availability and lay-date suggests that birds adjust their breeding tactics to conditions of Ca deficiency, for example, by postponing laying.

  20. Calcium Orthophosphates in Nature, Biology and Medicine

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2009-04-01

    Full Text Available The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. These materials are of the special significance because they represent the inorganic part of major normal (bones, teeth and dear antlers and pathological (i.e. those appearing due to various diseases calcified tissues of mammals. Due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists use this property extensively to construct artificial bone grafts that are either entirely made of or only surface-coated with the biologically relevant calcium orthophosphates. For example, self-setting hydraulic cements made of calcium orthophosphates are helpful in bone repair, while titanium substitutes covered by a surface layer of calcium orthophosphates are used for hip joint endoprostheses and as tooth substitutes. Porous scaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. In addition, technical grade calcium orthophosphates are very popular mineral fertilizers. Thus ere calcium orthophosphates are of great significance for humankind and, in this paper, an overview on the current knowledge on this subject is provided.

  1. CD39/adenosine pathway is involved in AIDS progression.

    Directory of Open Access Journals (Sweden)

    Maria Nikolova

    2011-07-01

    Full Text Available HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high FoxP3+CD127(low T cells (Treg play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS.

  2. Calcium and caffeine interaction in increased calcium balance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Sandra Tavares da Silva

    2013-06-01

    Full Text Available OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40 were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day. The animals were kept in individuals metabolic cages at a temperature of 24°±2ºC, light/dark cycles of 12/12 hours, and deionized water available ad libitum. On the 8th week of the experiment, food consumption was measured and 24-hour urine and 4-day feces were collected to determine calcium balance [Balance=Ca intake-(Urinary Ca+Fecal Ca]. RESULTS: Animals with adequate calcium intake presented higher balances and rates of calcium absorption and retention (p<0.05 than those with inadequate calcium intake, regardless of caffeine intake (p<0.05. Caffeine intake did not affect urinary calcium excretion but increased balance (p<0.05 in the groups with adequate calcium intake. CONCLUSION: Adequate calcium intake attenuated the negative effects of estrogen deficiency and improved calcium balance even in the presence of caffeine.

  3. Calcium Forms,Subcelluar Distribution and Ultrastructure of Pulp Cells as Influenced by Calcium Deficiency in Apple (Malus pumila) Fruits

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian-hui; ZHOU Wei

    2004-01-01

    Calcium in Red Fuji and Starkrimson apples during storage were fractionated by sequent extracting. Localization and distribution of calcium and influence of calcium nutrition on cell ultrastructure were observed by transmission electron microscopy combined with in situ precipitation of calcium with an improved method of potassium pyroantimonate technique. Results indicated that spraying calcium solution on surface of young fruits increased contents of calcium in all forms. During storage, contents of soluble calcium and pectic calcium declined and thosein calcium phosphate, calcium oxalate and calcium silicate increased. Calcium contents of Red Fuji in all forms were higher than those of Starkrimson, indicating that calcium accumulating capability of Red Fuji fruits preceded that of Starkrimson. Under transmission electron microscopy, calcium antimonite precipitates (CaAP) was mainly distributed in cell wall, tonoplast, nuclear membrane and nucleoplasm,much more CaAP deposited in vacuole. Calcium deficiency during storage leads to decrease of CaAP in locations mentioned above, disappearance of compartmentation, and entrance of CaAP to cytoplasm. Transformation from soluble calcium and pectic calcium to calcium phosphate,oxalate and damages of biomembranes structuraly and functionally resulted from calcium deficiency during storage were the crucial causation of physiological disorder.

  4. [Calcium and vitamin D in osteology].

    Science.gov (United States)

    Amling, M; Barvencik, F

    2015-06-01

    Calcium homeostasis is of paramount physiological and pathophysiological importance in health and disease. This article focuses on the skeletal relevance of calcium and vitamin D in daily clinical practice. Against the background of an endemic vitamin D deficiency in Germany and the increasing number of patients with drug-induced (proton pump inhibitor) enteral calcium uptake problems, it is of critical importance to understand that a vitamin D level of > 30 µg/l (> 75 nmol/l) is required for intact skeletal mineralization and that furthermore, a physiological gastric acid production is essential for a normal enteral uptake of calcium from foodstuffs. Therefore, a guideline-conform handling of vitamin D and calcium substitution is required not only for patients with rheumatoid diseases but also for any osteological therapy.

  5. Calcium ion currents mediating oocyte maturation events

    Directory of Open Access Journals (Sweden)

    Tosti Elisabetta

    2006-05-01

    Full Text Available Abstract During maturation, the last phase of oogenesis, the oocyte undergoes several changes which prepare it to be ovulated and fertilized. Immature oocytes are arrested in the first meiotic process prophase, that is morphologically identified by a germinal vesicle. The removal of the first meiotic block marks the initiation of maturation. Although a large number of molecules are involved in complex sequences of events, there is evidence that a calcium increase plays a pivotal role in meiosis re-initiation. It is well established that, during this process, calcium is released from the intracellular stores, whereas less is known on the role of external calcium entering the cell through the plasma membrane ion channels. This review is focused on the functional role of calcium currents during oocyte maturation in all the species, from invertebrates to mammals. The emerging role of specific L-type calcium channels will be discussed.

  6. Process for the preparation of calcium superoxide

    Science.gov (United States)

    Ballou, E. V.; Wood, P. C.; Wydeven, T. J.; Spitze, L. A. (Inventor)

    1978-01-01

    Calcium superoxide is prepared in high yields by spreading a quantity of calcium peroxide diperoxyhydrate on the surface of a container, positioning said container in a vacuum chamber on a support structure through which a coolant fluid can be circulated, partially evacuating said vacuum chamber, allowing the temperature of the diperoxyhydrate to reach the range of about 0 to about 40 C; maintaining the temperature selected for a period of time sufficient to complete the disproproriation of the diperoxyhydrate to calcium superoxide, calcium hydroxide, oxygen, and water; constantly and systematically removing the water as it is formed by sweeping the reacting material with a current of dry inert gas and/or by condensation of said water on a cold surface; backfilling the chamber with a dry inert gas; and finally, recovering the calcium superoxide produced.

  7. Application of Calcium Phosphate Materials in Dentistry

    Directory of Open Access Journals (Sweden)

    Jabr S. Al-Sanabani

    2013-01-01

    Full Text Available Calcium phosphate materials are similar to bone in composition and in having bioactive and osteoconductive properties. Calcium phosphate materials in different forms, as cements, composites, and coatings, are used in many medical and dental applications. This paper reviews the applications of these materials in dentistry. It presents a brief history, dental applications, and methods for improving their mechanical properties. Notable research is highlighted regarding (1 application of calcium phosphate into various fields in dentistry; (2 improving mechanical properties of calcium phosphate; (3 biomimetic process and functionally graded materials. This paper deals with most common types of the calcium phosphate materials such as hydroxyapatite and tricalcium phosphate which are currently used in dental and medical fields.

  8. The influence of electron discharge and magnetic field on calcium carbonate (CaCO3) precipitation

    Science.gov (United States)

    Putro, Triswantoro; Endarko

    2016-04-01

    The influences of electron discharge and magnetic field on calcium carbonate (CaCO3) precipitation in water have been successfully investigated. The study used three pairs of magnetic field 0.1 T whilst the electron discharge was generated from television flyback transformer type BW00607 and stainless steel SUS 304 as an electrode. The water sample with an initial condition of 230 mg/L placed in the reactor with flow rate 375 mL/minutes, result showed that the electron discharge can be reduced contain of calcium carbonate the water sample around 17.39% within 2 hours. Meanwhile for the same long period of treatment and flow rate, around 56.69% from initial condition of 520 mg/L of calcium carbonate in the water sample can be achieved by three pairs of magnetic field 0.1 T. When the combination of three pairs of magnetic field 0.1 T and the electron discharge used for treatment, the result showed that the combination of electron discharge and magnetic field methods can be used to precipitate calcium carbonate in the water sample 300 mg/L around 76.66% for 2 hours of treatment. The study then investigated the influence of the polar position of the magnetic field on calcium carbonate precipitation. Two positions of magnetic field were tested namely the system with alternated polar magnetics and the system without inversion of the polar magnetics. The influence of the polar position showed that the percentage reduction in levels of calcium carbonate in the water sample (360 mg/L) is significant different. Result showed that the system without inversion of the polar magnetics is generally lower than the system with alternated polar magnetics, with reduction level at 30.55 and 57.69%, respectively.

  9. Calcium-imaging with Fura-2 in isolated cerebral microvessels

    DEFF Research Database (Denmark)

    Hess, Jörg; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, cytoplasmic free calcium, Fura-2 fluorescence, image analysis, blood-brain barrier......Neuropathology, cytoplasmic free calcium, Fura-2 fluorescence, image analysis, blood-brain barrier...

  10. Diagnosis and assessment of skeletal related disease using calcium 41

    Science.gov (United States)

    Hillegonds, Darren J [Oakland, CA; Vogel, John S [San Jose, CA; Fitzgerald, Robert L [Encinitas, CA; Deftos, Leonard J [Del Mar, CA; Herold, David [Del Mar, CA; Burton, Douglas W [San Diego, CA

    2012-05-15

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  11. Support for calcium channel gene defects in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Lu Ake Tzu-Hui

    2012-12-01

    Full Text Available Abstract Background Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD. Calcium channel genes (CCG contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis. Methods A total of 2,176 single-nucleotide polymorphisms (SNP (703 genotyped and 1,473 imputed covering the genes that encode the α1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP. SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel. Results Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations. Conclusions These associations support a role for common CCG SNPs in ASD.

  12. Calcium-sensitive immunoaffinity chromatography

    DEFF Research Database (Denmark)

    Henriksen, Maiken L; Lindhardt Madsen, Kirstine; Skjoedt, Karsten

    2014-01-01

    Immunoaffinity chromatography is a powerful fractionation technique that has become indispensable for protein purification and characterization. However, it is difficult to retrieve bound proteins without using harsh or denaturing elution conditions, and the purification of scarce antigens...... to homogeneity may be impossible due to contamination with abundant antigens. In this study, we purified the scarce, complement-associated plasma protein complex, collectin LK (CL-LK, complex of collectin liver 1 and kidney 1), by immunoaffinity chromatography using a calcium-sensitive anti-collectin-kidney-1 m...... chromatography was superior to the traditional immunoaffinity chromatographies and resulted in a nine-fold improvement of the purification factor. The technique is applicable for the purification of proteins in complex mixtures by single-step fractionation without the denaturation of eluted antigens...

  13. Target Space $\

    CERN Document Server

    Huggett, Nick

    2015-01-01

    This paper investigates the significance of T-duality in string theory: the indistinguishability with respect to all observables, of models attributing radically different radii to space -- larger than the observable universe, or far smaller than the Planck length, say. Two interpretational branch points are identified and discussed. First, whether duals are physically equivalent or not: by considering a duality of the familiar simple harmonic oscillator, I argue that they are. Unlike the oscillator, there are no measurements 'outside' string theory that could distinguish the duals. Second, whether duals agree or disagree on the radius of 'target space', the space in which strings evolve according to string theory. I argue for the latter position, because the alternative leaves it unknown what the radius is. Since duals are physically equivalent yet disagree on the radius of target space, it follows that the radius is indeterminate between them. Using an analysis of Brandenberger and Vafa (1989), I explain wh...

  14. Clinical studies of bone metabolism using a simple model of calcium tracer kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Roncari, G.

    1981-08-01

    Bone metabolism studies were performed in 44 subjects with and without bone disease using a calcium tracer kinetics model, the central feature of which is an expanding exchangeable calcium pool. In normal subjects the accretion rate and the exchangeable calcium pool ranged from 1.49 to 8.45 (mean 3.9 +- 2.05) mg.d/sup -1/kg/sup -1/ and from 60 to 131 (mean 81.25 +- 18.11) mg.kg/sup -1/, respectively. The patients with osteogenesis imperfecta, Pierre Marie's disease and one out of two cases of hypoparathyroidism had values which fell within the normal range. Both the accretion rate and the exchangeable calcium pool were significantly elevated in patients with Paget's disease and with hyperparathyroidism. Uremic patients with generalizated bone lesions had accretion rates or both parameters elevated. As far as patients with successful renal transplant are concerned, the results suggest that this method is a very poor means for detecting bone disorders with only focal lesions. In contrast, the method can be very useful when persistent renal osteodystrophy or secondary hyperparathyroidism are suspected.

  15. Nucleation kinetics of the formation of low dimensional calcium sulfate dihydrate crystals in isopropyl alcohol medium

    Energy Technology Data Exchange (ETDEWEB)

    Sandhya, S.; Sureshbabu, S.; Varma, H.K.; Komath, Manoj [Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 012 (India)

    2012-07-15

    Calcium sulfate dihydrate, constituted as uniform crystals of low dimensions, is a potential biomaterial for clinical applications like bone graft substitution and drug delivery. In this work, isopropyl alcohol has been used as a solvent to obtain low dimensional calcium sulfate dihydrate crystals from calcium nitrate - sulfuric acid system. Reactants in 0.5 molar concentration at ambient conditions generated uniform rod-shaped crystals of length 3-5 {mu}m. Analysis using X-ray Diffractometry and Fourier Transform Infrared Spectrometry showed the material to be well crystallized, phase-pure calcium sulfate dihydrate. The nucleation kinetics has been studied by observing the induction time of phase formation in solutions of millimolar concentrations through turbidimetry at 300 K. The data have been analysed using classical nucleation theory to deduce parameters like interfacial tension (or surface free energy), nucleation rate and critical radius. The surface free energy obtained (5.6 mJ/m{sup 2}) is comparatively lower than that reported for aqueous precipitation, which could be attributed to the presence of isopropyl alcohol. On escalating the supersaturation ratio, the nucleation rate drastically increased and the critical radius decreased exponentially. Particles formed at supersaturation 1.39 showed a monomodal distribution centered at 8.2 nm in Dynamic Light Scattering analysis. Comparable particle sizes were obtained in Transmission Electron Microscopy. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. Fast kinetics of calcium signaling and sensor design.

    Science.gov (United States)

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

    2015-08-01

    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.

  17. Relationship of calcium absorption with 25(OH)D and calcium intake in children with rickets.

    Science.gov (United States)

    Thacher, Tom D; Abrams, Steven A

    2010-11-01

    Nutritional rickets has long been considered a disease caused by vitamin D deficiency, but recent data indicate that inadequate dietary calcium intake is an important cause of rickets, particularly in tropical countries. Children with rickets due to calcium deficiency do not have very low 25(OH)D concentrations, and serum 1,25(OH)(2) D values are markedly elevated. Studies of Nigerian children with rickets demonstrated they have high fractional calcium absorption. A high-phytate diet was demonstrated to increase calcium absorption compared with the fasting state, and enzymatic dephytinization did not significantly improve calcium absorption. When given vitamin D, children with rickets have a marked increase in 1,25(OH)(2) D concentrations without any change in fractional calcium absorption. No positive relationship was found between fractional calcium absorption and serum 25(OH)D concentrations in children on low-calcium diets. More research is needed to understand the interaction between calcium and vitamin D and the role of vitamin D in calcium absorption.

  18. Silica-calcium zirconate nanocomposite, studying its thermal and electrical properties

    Indian Academy of Sciences (India)

    Neda Kermani; Maryam Kargar Razi; Seyed Saeed Mirzaee; Reza Tayebee

    2015-06-01

    Silica–calcium zirconate nanocomposite was prepared in a two-step procedure. First, nanocalcium zirconate was synthesized by the modified sol–gel method; then, silica was added to the prepared sol and the resulting product was calcined at 700–1000° C. Dilatometric measurements were performed to determine the coefficient of thermal expansion (). It was concluded that was decreased from 15.96 × 10−6 to 10.26 × 10−6 1° C−1 with the increase in calcium zirconate/silica ratio. Moreover, studies on the dielectric properties and calcination temperature showed that the dielectric constant (r) was increased from 3.9 to 5.7.

  19. Elasticity of calcium and calcium-sodium amphiboles

    Science.gov (United States)

    Brown, J. Michael; Abramson, Evan H.

    2016-12-01

    Measurements of single-crystal elastic moduli under ambient conditions are reported for nine calcium to calcium-sodium amphiboles that lie in the composition range of common crustal constituents. Velocities of body and surface acoustic waves measured by Impulsive Stimulated Light Scattering (ISLS) were inverted to determine the 13 moduli characterizing these monoclinic samples. Moduli show a consistent pattern: C33 > C22 > C11 and C23 > C12 > C13 and C44 > C55 ∼ C66 and for the uniquely monoclinic moduli, |C35| ≫ C46 ∼ |C25| > |C15| ∼ 0. Most of the compositionally-induced variance of moduli is associated with aluminum and iron content. Seven moduli (C11C12C13C22C44C55C66) increase with increasing aluminum while all diagonal moduli decrease with increasing iron. Three moduli (C11, C13 and C44) increase with increasing sodium and potassium occupancy in A-sites. The uniquely monoclinic moduli (C15C25 and C35) have no significant compositional dependence. Moduli associated with the a∗ direction (C11C12C13C55 and C66) are substantially smaller than values associated with structurally and chemically related clinopyroxenes. Other moduli are more similar for both inosilicates. The isotropically averaged adiabatic bulk modulus does not vary with iron content but increases with aluminum content from 85 GPa for tremolite to 99 GPa for pargasite. Increasing iron reduces while increasing aluminum increases the isotropic shear modulus which ranges from 47 GPa for ferro-actinolite to 64 GPa for pargasite. These results exhibit far greater anisotropy and higher velocities than apparent in earlier work. Quasi-longitudinal velocities are as fast as ∼9 km/s and (intermediate between the a∗- and c-axes) are as slow as ∼6 km/s. Voigt-Reuss-Hill averaging based on prior single crystal moduli resulted in calculated rock velocities lower than laboratory measurements, leading to adoption of the (higher velocity) Voigt bound. Thus, former uses of the upper Voigt bound can

  20. Calcium intake and calcium deficiency in toddlers in a slum population of Bhubaneswar

    Directory of Open Access Journals (Sweden)

    Sonali Kar

    2014-12-01

    Full Text Available Introduction: When considering their children's nutrition, parents often think more about fat grams, carbs, and calories, and forget about calcium, a mineral that is important to help build strong and healthy bones and collagen structures like teeth. The RDI recommendation for 1-3 years is minimum 400mg/day. Calcium is selectively present in milk and milk products besides vegetables like spinach and fruits like orange. The current study was undertaken in the urban field practice area of KIMS that caters to a slum population of nearly 20,000. Aims & Objectives: To assess the knowledge of mothers regarding calcium rich foods and its deficiency and their sociodemographic conditions; to assess the average intake of Calcium using the 7 day recall method; to find the prevalence of possible calcium deficiency in the study population ie 1-3 years of age. Methods: All the mothers with children in the age group 1-3 years were recruited in the study after due informed consent, the final sample being nearly 284. The male female child ratio was 56:44. Mostly women i.e. 83% had some formal education and out of the total nearly 65% had heard never heard of calcium and of those who had heard only 30% could say that milk was the best source of calcium. Result: Average daily Calcium intake was poor i.e. 288mg/d which was worse for the female child 233mg/d. Teeth eruption defects or infections and bone deformities were taken as a proxy for calcium deficiency and were detected in 69.2% and 32% respectively. Diarrhea and skin infections were more in those whose calcium intake was less than 220mg/d which was mildly significant. Conclusion: The study suggests more emphasis on dietary calcium intake and probably recommend calcium supplements for the socioeconomically compromised class who probably cannot afford dietary sources of calcium

  1. Effect of calcium intake on urinary oxalate excretion in calcium stone-forming patients

    Directory of Open Access Journals (Sweden)

    Nishiura J.L.

    2002-01-01

    Full Text Available Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption of dietary oxalate that is bound by intestinal calcium. The aim of the present study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic patients under different calcium intake. Fifty patients (26 females and 24 males, 41 ± 10 years old, whose 4-day dietary records revealed a regular low calcium intake (<=500 mg/day, received an oral calcium load (1 g/day for 7 days. A 24-h urine was obtained before and after load and according to the calciuria under both diets, patients were considered as normocalciuric (NC, N = 15, diet-dependent hypercalciuric (DDHC, N = 9 or diet-independent hypercalciuric (DIHC, N = 26. On regular diet, mean oxaluria was 30 ± 14 mg/24 h for all patients. The 7-day calcium load induced a significant decrease in mean oxaluria compared to the regular diet in NC and DIHC (20 ± 12 vs 26 ± 7 and 27 ± 18 vs 32 ± 15 mg/24 h, respectively, P<0.05 but not in DDHC patients (22 ± 10 vs 23 ± 5 mg/24 h. The lack of an oxalate decrease among DDHC patients after the calcium load might have been due to higher calcium absorption under higher calcium supply, with a consequent lower amount of calcium left in the intestine to bind with oxalate. These data suggest that a long-lasting regular calcium consumption <500 mg was not associated with high oxaluria and that a subpopulation of hypercalciuric patients who presented a higher intestinal calcium absorption (DDHC tended to hyperabsorb oxalate as well, so that oxaluria did not change under different calcium intake.

  2. Vitamin D, calcium homeostasis and aging

    Science.gov (United States)

    Veldurthy, Vaishali; Wei, Ran; Oz, Leyla; Dhawan, Puneet; Jeon, Yong Heui; Christakos, Sylvia

    2016-01-01

    Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25(OH)2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis (which remains controversial) are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance. PMID:27790378

  3. Lead removal in rats using calcium alginate.

    Science.gov (United States)

    Savchenko, Olga V; Sgrebneva, Marina N; Kiselev, Vladimir I; Khotimchenko, Yuri S

    2015-01-01

    Lead (Pb) exposure, even at low levels, causes a variety of health problems. The aims of this study were to investigate the tissue distribution of lead in the bodies of rats, to evaluate lead removal from the internal organs and bones using calcium alginate in doses of 500, 200 and 100 mg/kg per day for 28 days and to assess the impact of calcium alginate on the level of essential elements. Lead (Pb), calcium (Ca), manganese (Mn), iron (Fe), copper (Cu) and zinc (Zn) levels in the blood, hearts, kidneys, livers and femurs of the experimental animals were measured using mass spectrometry with inductively coupled plasma. The results revealed that lead acetate exposure increased the levels of Pb in the blood and organs of the animals and significantly reduced contents of Ca, Mn, Fe, Cu and Zn. Treatment with calcium alginate in dose 500 mg/kg contributed to significant decreases in the amount of lead in the kidney, heart and bones of animals and a slight increase in the content of essential elements in the liver, kidneys and heart, although these changes were not significant. Decreasing of lead was not significant in the internal organs, bones and blood of animals treated with calcium alginate 200 and 100 mg/kg. Consequently, calcium alginate dose of 500 mg/kg more efficiently removes lead accumulated in the body. Calcium alginate does not have negative effect on level of essential elements quite the contrary; reducing the levels of lead, calcium alginate helps normalize imbalances of Ca, Mn, Fe, Cu and Zn. The results of this study suggest that calcium alginate may potentially be useful for the treatment and prevention of heavy metal intoxications.

  4. Dysbalance of astrocyte calcium under hyperammonemic conditions.

    Directory of Open Access Journals (Sweden)

    Nicole Haack

    Full Text Available Increased brain ammonium (NH4(+/NH3 plays a central role in the manifestation of hepatic encephalopathy (HE, a complex syndrome associated with neurological and psychiatric alterations, which is primarily a disorder of astrocytes. Here, we analysed the influence of NH4(+/NH3 on the calcium concentration of astrocytes in situ and studied the underlying mechanisms of NH4(+/NH3-evoked calcium changes, employing fluorescence imaging with Fura-2 in acute tissue slices derived from different regions of the mouse brain. In the hippocampal stratum radiatum, perfusion with 5 mM NH4(+/NH3 for 30 minutes caused a transient calcium increase in about 40% of astrocytes lasting about 10 minutes. Furthermore, the vast majority of astrocytes (∼ 90% experienced a persistent calcium increase by ∼ 50 nM. This persistent increase was already evoked at concentrations of 1-2 mM NH4(+/NH3, developed within 10-20 minutes and was maintained as long as the NH4(+/NH3 was present. Qualitatively similar changes were observed in astrocytes of different neocortical regions as well as in cerebellar Bergmann glia. Inhibition of glutamine synthetase resulted in significantly larger calcium increases in response to NH4(+/NH3, indicating that glutamine accumulation was not a primary cause. Calcium increases were not mimicked by changes in intracellular pH. Pharmacological inhibition of voltage-gated sodium channels, sodium-potassium-chloride-cotransporters (NKCC, the reverse mode of sodium/calcium exchange (NCX, AMPA- or mGluR5-receptors did not dampen NH4(+/NH3-induced calcium increases. They were, however, significantly reduced by inhibition of NMDA receptors and depletion of intracellular calcium stores. Taken together, our measurements show that sustained exposure to NH4(+/NH3 causes a sustained increase in intracellular calcium in astrocytes in situ, which is partly dependent on NMDA receptor activation and on release of calcium from intracellular stores. Our study

  5. Calcium Signaling Is Required for Erythroid Enucleation.

    Science.gov (United States)

    Wölwer, Christina B; Pase, Luke B; Russell, Sarah M; Humbert, Patrick O

    2016-01-01

    Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  6. Calcium Signaling Is Required for Erythroid Enucleation.

    Directory of Open Access Journals (Sweden)

    Christina B Wölwer

    Full Text Available Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  7. Calcium signaling in physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    He-ping CHENG; Sheng WEI; Li-ping WEI; Alexei VERKHRATSKY

    2006-01-01

    Calcium ions are the most ubiquitous and pluripotent cellular signaling molecules that control a wide variety of cellular processes.The calcium signaling system is represented by a relatively limited number of highly conserved transporters and channels,which execute Ca2+ movements across biological membranes and by many thousands of Ca2+-sensitive effectors.Molecular cascades,responsible for the generation of calcium signals,are tightly controlled by Ca2+ ions themselves and by genetic factors,which tune the expression of different Ca2+-handling molecules according to adaptational requirements.Ca2+ ions determine normal physiological reactions and the development of many pathological processes.

  8. STIM and calcium channel complexes in cancer.

    Science.gov (United States)

    Jardin, Isaac; Rosado, Juan A

    2016-06-01

    The ion Ca(2+) is a ubiquitous second messenger that mediates a variety of cellular functions. Dysfunction of the mechanisms involved in Ca(2+) homeostasis underlies a number of pathological processes, including cancer. Store-operated Ca(2+) entry (SOCE) is a major mechanism for Ca(2+) entry modulated by the intracellular Ca(2+) stores. The Ca(2+)-selective store-operated current (ICRAC) is mediated by the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the store-operated Ca(2+) (SOC) channel Orai1, while other non-selective cation currents (ISOC) involves the participation of members of the canonical transient receptor potential (TRPC) channel family, including TRPC1. Distinct isoforms of the key components of SOCE have been described in mammalian cells, STIM1 and 2, Orai1-3 and TRPC1-7. In cancer cells, SOCE has been reported to play an important role in cell cycle progression and proliferation, migration, metastasis and evasion of apoptosis. Changes in the expression of the key elements of SOCE and Ca(2+) homeostasis remodeling have been account to play important roles in the phenotypic changes observed in transformed cells. Despite there are differences in the expression level of the molecular components of SOCE, as well as in the relevance of the STIM, Orai and TRPC isoforms in SOCE and tumorigenesis among cancer cell types, there is a body of evidence supporting an important role for SOCE underlying the phenotypic modifications of cancer cells that propose STIM and the SOC channels as suitable candidate targets for future prognostic or therapeutic strategies. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.

  9. Convergent landscape. 39 and a half as (multi promotional intertext

    Directory of Open Access Journals (Sweden)

    Katarzyna Kopecka- Piech

    2010-12-01

    Full Text Available The purpose of this article is to provide a broader characterisation of the media convergence strategy applied by producers of the Polish commercial television station (TVN series 39 and a half (39 i pół. In order to examine the convergence strategies of production, distribution, promotion and media usage, this paper analyzes metaphors of landscape, terrain, map and simulacrum. Moreover the concept of convergent (intertext is proposed. In the case study of 39 and a half the author examines three main strategies implemented by the creators: the promotional virtualisation of reality, making virtual reality more real, and multiplied fiction. Transmedial and synergetic brands illustrate the hybridisation of the convergent and integrated media landscape.

  10. Thermochemistry of calcium oxide and calcium hydroxide in fluoride slags

    Science.gov (United States)

    Chattopadhyay, S.; Mitchell, A.

    1990-08-01

    Calcium oxide activity in binary CaF2-CaO and ternary CaF2-CaO-Al2O3 and CaF2-CaO-SiO2 slags has been determined by CO2-slag equilibrium experiments at 1400 °C. The carbonate ca-pacity of these slags has also been computed and compared with sulfide capacity data available in the literature. The similarity in trends suggests the possibility of characterizing carbonate capacity as an alternative basicity index for fluoride-base slags. Slag-D2O equilibrium experi-ments are performed at 1400°C with different fluoride-base slags to determine water solubility at two different partial pressures of D2O, employing a new slag sampling technique. A novel isotope tracer detection technique is employed to analyze water in the slags. The water solubility data found show higher values than the previous literature data by an order of magnitude but show a linear relationship with the square root of water vapor partial pressure. The activity of hydroxide computed from the data is shown to be helpful in estimating water solubility in in-dustrial electroslag remelting (ESR) slags.

  11. In vitro Study of a Novel Stent Coating Using Modified CD39 Messenger RNA to Potentially Reduce Stent Angioplasty-Associated Complications.

    Directory of Open Access Journals (Sweden)

    Meike-Kristin Abraham

    Full Text Available Stent angioplasty provides a minimally invasive treatment for atherosclerotic vessels. However, no treatment option for atherosclerosis-associated endothelial dysfunction, which is accompanied by a loss of CD39, is available, and hence, adverse effects like thromboembolism and restenosis may occur. Messenger RNA (mRNA-based therapy represents a novel strategy, whereby de novo synthesis of a desired protein is achieved after delivery of a modified mRNA to the target cells.Our study aimed to develop an innovative bioactive stent coating that induces overexpression of CD39 in the atherosclerotic vessel. Therefore, a modified CD39-encoding mRNA was produced by in vitro transcription. Different endothelial cells (ECs were transfected with the mRNA, and CD39 expression and functionality were analyzed using various assays. Furthermore, CD39 mRNA was immobilized using poly(lactic-co-glycolic-acid (PLGA, and the transfection efficiency in ECs was analyzed. Our data show that ECs successfully translate in vitro-generated CD39 mRNA after transfection. The overexpressed CD39 protein is highly functional in hydrolyzing ADP and in preventing platelet activation. Furthermore, PLGA-immobilized CD39 mRNA can be delivered to ECs without losing its functionality.In summary, we present a novel and promising concept for a stent coating for the treatment of atherosclerotic blood vessels, whereby patients could be protected against angioplasty-associated complications.

  12. In vivo two-photon calcium imaging in the visual system.

    Science.gov (United States)

    Ohki, Kenichi; Reid, R Clay

    2014-04-01

    Two-photon imaging of calcium-sensitive dyes in vivo has become a common tool used by neuroscientists, largely because of the development of bolus loading techniques, which can label every neuron in a local circuit with calcium-sensitive dye. Like multielectrode recordings, two-photon imaging paired with bolus loading provides a method for monitoring many neurons at once, but, in addition, it provides a means for determining the precise location of every neuron. Thus, it is an ideal method for studying the fine-scale functional architecture of the cortex and guiding the experimenter to individual neurons that can be targeted for further anatomical study. Two-photon calcium imaging enables study of the fine structure of functional maps in the visual cortex in cats and rodents. In mice, it can allow the characterization of specific cell types when paired with transgenic or retrograde labeling.

  13. 41 CFR 101-39.104 - Notice of establishment of a fleet management system.

    Science.gov (United States)

    2010-07-01

    ... of a fleet management system. 101-39.104 Section 101-39.104 Public Contracts and Property Management..., TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management Systems § 101-39.104 Notice of establishment of a fleet...

  14. 41 CFR 101-39.104-1 - Consolidations into a fleet management system.

    Science.gov (United States)

    2010-07-01

    ... fleet management system. 101-39.104-1 Section 101-39.104-1 Public Contracts and Property Management..., TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management Systems § 101-39.104-1 Consolidations into a fleet...

  15. 41 CFR 101-39.105-1 - Transfers from discontinued or curtailed fleet management systems.

    Science.gov (United States)

    2010-07-01

    ... discontinued or curtailed fleet management systems. 101-39.105-1 Section 101-39.105-1 Public Contracts and... AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management Systems § 101-39.105-1 Transfers...

  16. A Low Affinity GCaMP3 Variant (GCaMPer) for Imaging the Endoplasmic Reticulum Calcium Store.

    Science.gov (United States)

    Henderson, Mark J; Baldwin, Heather A; Werley, Christopher A; Boccardo, Stefano; Whitaker, Leslie R; Yan, Xiaokang; Holt, Graham T; Schreiter, Eric R; Looger, Loren L; Cohen, Adam E; Kim, Douglas S; Harvey, Brandon K

    2015-01-01

    Endoplasmic reticulum calcium homeostasis is critical for cellular functions and is disrupted in diverse pathologies including neurodegeneration and cardiovascular disease. Owing to the high concentration of calcium within the ER, studying this subcellular compartment requires tools that are optimized for these conditions. To develop a single-fluorophore genetically encoded calcium indicator for this organelle, we targeted a low affinity variant of GCaMP3 to the ER lumen (GCaMPer (10.19)). A set of viral vectors was constructed to express GCaMPer in human neuroblastoma cells, rat primary cortical neurons, and human induced pluripotent stem cell-derived cardiomyocytes. We observed dynamic changes in GCaMPer (10.19) fluorescence in response to pharmacologic manipulations of the ER calcium store. Additionally, periodic calcium efflux from the ER was observed during spontaneous beating of cardiomyocytes. GCaMPer (10.19) has utility in imaging ER calcium in living cells and providing insight into luminal calcium dynamics under physiologic and pathologic states.

  17. A Low Affinity GCaMP3 Variant (GCaMPer for Imaging the Endoplasmic Reticulum Calcium Store.

    Directory of Open Access Journals (Sweden)

    Mark J Henderson

    Full Text Available Endoplasmic reticulum calcium homeostasis is critical for cellular functions and is disrupted in diverse pathologies including neurodegeneration and cardiovascular disease. Owing to the high concentration of calcium within the ER, studying this subcellular compartment requires tools that are optimized for these conditions. To develop a single-fluorophore genetically encoded calcium indicator for this organelle, we targeted a low affinity variant of GCaMP3 to the ER lumen (GCaMPer (10.19. A set of viral vectors was constructed to express GCaMPer in human neuroblastoma cells, rat primary cortical neurons, and human induced pluripotent stem cell-derived cardiomyocytes. We observed dynamic changes in GCaMPer (10.19 fluorescence in response to pharmacologic manipulations of the ER calcium store. Additionally, periodic calcium efflux from the ER was observed during spontaneous beating of cardiomyocytes. GCaMPer (10.19 has utility in imaging ER calcium in living cells and providing insight into luminal calcium dynamics under physiologic and pathologic states.

  18. Hydrolytic conversion of amorphous calcium phosphate into apatite accompanied by sustained calcium and orthophosphate ions release.

    Science.gov (United States)

    Niu, Xufeng; Chen, Siqian; Tian, Feng; Wang, Lizhen; Feng, Qingling; Fan, Yubo

    2017-01-01

    The aim of this study is to investigate the calcium and orthophosphate ions release during the transformation of amorphous calcium phosphate (ACP) to hydroxyapatite (HA) in aqueous solution. The ACP is prepared by a wet chemical method and further immersed in the distilled water for various time points till 14d. The release of calcium and orthophosphate ions is measured with calcium and phosphate colorimetric assay kits, respectively. The transition of ACP towards HA is detected by x-ray diffraction (XRD), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR). The results indicate that the morphological conversion of ACP to HA occurs within the first 9h, whereas the calcium and orthophosphate ions releases last for over 7d. Such sustained calcium and orthophosphate ions release is very useful for ACP as a candidate material for hard tissue regeneration.

  19. Calcium acetate versus calcium carbonate as phosphorus binders in patients on chronic haemodialysis: a controlled study.

    Science.gov (United States)

    Ring, T; Nielsen, C; Andersen, S P; Behrens, J K; Sodemann, B; Kornerup, H J

    1993-01-01

    The first reported double-blind cross-over comparison between the phosphorus binders calcium carbonate and calcium acetate was undertaken in 15 stable patients on chronic maintenance haemodialysis. Detailed registration of diet and analysis of the protein catabolic rate suggested an unchanged phosphorus intake during the study. It was found that predialytic serum phosphate concentration was significantly decreased by 0.11 mmol/l (0.34 mg/dl) (P = 0.021, 95% confidence limits 0.02-0.21 mmol/l; 0.06-0.65 mg/dl) during calcium acetate treatment. The calcium phosphate product was insignificantly decreased during treatment with calcium acetate whereas we could not exclude the possibility that calcium concentration had increased.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-09-21

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

  1. Alternative positron-target design for electron-positron colliders

    Energy Technology Data Exchange (ETDEWEB)

    Donahue, R.J. (Lawrence Berkeley Lab., CA (United States)); Nelson, W.R. (Stanford Linear Accelerator Center, Menlo Park, CA (United States))

    1991-04-01

    Current electron-positron linear colliders are limited in luminosity by the number of positrons which can be generated from targets presently used. This paper examines the possibility of using an alternate wire-target geometry for the production of positrons via an electron-induced electromagnetic cascade shower. 39 refs., 38 figs., 5 tabs.

  2. Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells.

    Science.gov (United States)

    Stern, Michael D; Maltseva, Larissa A; Juhaszova, Magdalena; Sollott, Steven J; Lakatta, Edward G; Maltsev, Victor A

    2014-05-01

    The sinoatrial node, whose cells (sinoatrial node cells [SANCs]) generate rhythmic action potentials, is the primary pacemaker of the heart. During diastole, calcium released from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) interacts with membrane currents to control the rate of the heartbeat. This "calcium clock" takes the form of stochastic, partially periodic, localized calcium release (LCR) events that propagate, wave-like, for limited distances. The detailed mechanisms controlling the calcium clock are not understood. We constructed a computational model of SANCs, including three-dimensional diffusion and buffering of calcium in the cytosol and SR; explicit, stochastic gating of individual RyRs and L-type calcium channels; and a full complement of voltage- and calcium-dependent membrane currents. We did not include an anatomical submembrane space or inactivation of RyRs, the two heuristic components that have been used in prior models but are not observed experimentally. When RyRs were distributed in discrete clusters separated by >1 µm, only isolated sparks were produced in this model and LCR events did not form. However, immunofluorescent staining of SANCs for RyR revealed the presence of bridging RyR groups between large clusters, forming an irregular network. Incorporation of this architecture into the model led to the generation of propagating LCR events. Partial periodicity emerged from the interaction of LCR events, as observed experimentally. This calcium clock becomes entrained with membrane currents to accelerate the beating rate, which therefore was controlled by the activity of the SERCA pump, RyR sensitivity, and L-type current amplitude, all of which are targets of β-adrenergic-mediated phosphorylation. Unexpectedly, simulations revealed the existence of a pathological mode at high RyR sensitivity to calcium, in which the calcium clock loses synchronization with the membrane, resulting in a paradoxical decrease in beating

  3. Astrocyte calcium signaling: the third wave.

    Science.gov (United States)

    Bazargani, Narges; Attwell, David

    2016-02-01

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

  4. Synthesis of calcium hydroxyapatite from calcium carbonate and different orthophosphate sources: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Pham Minh, Doan, E-mail: doan.phamminh@mines-albi.fr [Universite de Toulouse, Mines Albi, CNRS, Centre RAPSODEE, Campus Jarlard, F-81013 Albi cedex 09 (France); Lyczko, Nathalie; Sebei, Haroun; Nzihou, Ange [Universite de Toulouse, Mines Albi, CNRS, Centre RAPSODEE, Campus Jarlard, F-81013 Albi cedex 09 (France); Sharrock, Patrick [Universite de Toulouse, SIMAD, IUT Paul Sabatier, Avenue Georges Pompidou, 81104 Castres (France)

    2012-08-01

    Highlights: Black-Right-Pointing-Pointer Calcium hydroxyapatite was synthesized from CaCO{sub 3} and four orthophosphates. Black-Right-Pointing-Pointer Only H{sub 3}PO{sub 4} led to the complete precipitation of orthophosphate species. Black-Right-Pointing-Pointer H{sub 3}PO{sub 4} was also the most efficient for calcium dissolution. Black-Right-Pointing-Pointer Reaction pathway was dissolution-precipitation accompanied by agglomeration step. - Abstract: The synthesis of calcium hydroxyapatite (Ca-HA) starting from calcium carbonate and different orthophosphate sources, including orthophosphoric acid, potassium, sodium and ammonium dihydrogen orthophosphates, was investigated under ambient conditions. The reaction started with calcium carbonate dissolution in an acid medium, followed by rapid precipitation of calcium cations with orthophosphate species to form calcium phosphate based particles which were in the size range of 0.4-1 {mu}m. These particles then agglomerated into much larger ones, up to 350 {mu}m in diameter (aggregates). These aggregates possessed an unstable porous structure which was responsible for the porosity of the final products. The highest specific surface area and pore volume were obtained with potassium dihydrogen orthophosphate. On the other hand, orthophosphoric acid led to the highest dissolution of calcium carbonate and the complete precipitation of orthophosphate species. Under ambient conditions, calcium phosphate based solid products of low crystallinity were formed. Different intermediates were identified and a reaction pathway proposed.

  5. Morphological Investigation of Calcium Carbonate during Ammonification-Carbonization Process of Low Concentration Calcium Solution

    Directory of Open Access Journals (Sweden)

    Huaigang Cheng

    2014-01-01

    Full Text Available Ultrafine calcium carbonate is a widely used cheap additive. The research is conducted in low degree supersaturation solution in order to study the polymorphic phases’ change and its factors of the calcium carbonate precipitate in the ammonification-carbonization process of the solution with calcium. Fine particles of calcium carbonate are made in the solution containing 0.015 mol/L of Ca2+. Over 98% of the calcium carbonate precipitate without ammonification resembles the morphology of calcite, while the introduction of ammonia can benefit the formation of vaterite. It was inferred that the main cause should be serious partial oversaturation or steric effects. Ammonia also helps to form the twin spherical calcium carbonate. However, particles formed in the process of ammonification-carbonization in solution with low concentration degree of calcium are not even with a scale of the particle diameter from 5 to 12 μm. Inorganic salts, alcohol, or organic acid salts have significant controlling effect on the particle diameter of calcium carbonate and can help to decrease the particle diameter to about 3 μm. Anionic surfactants can prevent the conglobation of calcium carbonate particles and shrink its diameter to 500 nm–1 μm.

  6. Diagnosis and clinical manifestations of calcium pyrophosphate and basic calcium phosphate crystal deposition diseases.

    Science.gov (United States)

    Ea, Hang-Korng; Lioté, Frédéric

    2014-05-01

    Basic calcium phosphate and pyrophosphate calcium crystals are the 2 main calcium-containing crystals that can deposit in all skeletal tissues. These calcium crystals give rise to numerous manifestations, including acute inflammatory attacks that can mimic alarming and threatening differential diagnoses, osteoarthritis-like lesions, destructive arthropathies, and calcific tendinitis. Awareness of uncommon localizations and manifestations such as intraspinal deposition (eg, crowned dens syndrome, tendinitis of longus colli muscle, massive cervical myelopathy compression) prevents inappropriate procedures and cares. Coupling plain radiography, ultrasonography, computed tomography, and synovial fluid analysis allow accurate diagnosis by directly or indirectly identifying the GRAAL of microcrystal-related symptoms.

  7. Transport of calcium in seedlings and cuttings of mung bean

    Energy Technology Data Exchange (ETDEWEB)

    Broadbent, W.

    1984-01-01

    At germination, a very small proportion of stored calcium is mobilized to the axis in the absence of exogenous supplies of calcium. There is no evidence for transport in phloem since exported calcium does not enter the seedling root. /sup 45/Calcium is not redistributed when applied to cotyledons at germination of leaves of seedlings. A subsequent large addition of unlabelled calcium promotes a small redistribution from leaves. Triiodobenzoic acid (TIBA), applied to leaves, leads to a small reduction in calcium accumulation but does not effect redistribution. Auxin is without effect and auxin plus TIBA promotes accumulation. These results are discussed in relation to possible extracellular binding sites for calcium.

  8. ERp57 modulates mitochondrial calcium uptake through the MCU.

    Science.gov (United States)

    He, Jingquan; Shi, Weikang; Guo, Yu; Chai, Zhen

    2014-06-01

    ERp57 participates in the regulation of calcium homeostasis. Although ERp57 modulates calcium flux across the plasma membrane and the endoplasmic reticulum membrane, its functions on mitochondria are largely unknown. Here, we found that ERp57 can regulate the expression of the mitochondrial calcium uniporter (MCU) and modulate mitochondrial calcium uptake. In ERp57-silenced HeLa cells, MCU was downregulated, and the mitochondrial calcium uptake was inhibited, consistent with the effect of MCU knockdown. When MCU was re-expressed in the ERp57 knockdown cells, mitochondrial calcium uptake was restored. Thus, ERp57 is a potent regulator of mitochondrial calcium homeostasis.

  9. Calcium signaling in neocortical development.

    Science.gov (United States)

    Uhlén, Per; Fritz, Nicolas; Smedler, Erik; Malmersjö, Seth; Kanatani, Shigeaki

    2015-04-01

    The calcium ion (Ca(2+) ) is an essential second messenger that plays a pivotal role in neurogenesis. In the ventricular zone (VZ) of the neocortex, neural stem cells linger to produce progenitor cells and subsequently neurons and glial cells, which together build up the entire adult brain. The radial glial cells, with their characteristic radial fibers that stretch from the inner ventricular wall to the outer cortex, are known to be the neural stem cells of the neocortex. Migrating neurons use these radial fibers to climb from the proliferative VZ in the inner part of the brain to the outer layers of the cortex, where differentiation processes continue. To establish the complex structures that constitute the adult cerebral cortex, proliferation, migration, and differentiation must be tightly controlled by various signaling events, including cytosolic Ca(2+) signaling. During development, cells regularly exhibit spontaneous Ca(2+) activity that stimulates downstream effectors, which can elicit these fundamental cell processes. Spontaneous Ca(2+) activity during early neocortical development depends heavily on gap junctions and voltage dependent Ca(2+) channels, whereas later in development neurotransmitters and synapses exert an influence. Here, we provide an overview of the literature on Ca(2+) signaling and its impact on cell proliferation, migration, and differentiation in the neocortex. We point out important historical studies and review recent progress in determining the role of Ca(2+) signaling in neocortical development.

  10. Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter.

    Science.gov (United States)

    Lee, Youngjin; Min, Choon Kee; Kim, Tae Gyun; Song, Hong Ki; Lim, Yunki; Kim, Dongwook; Shin, Kahee; Kang, Moonkyung; Kang, Jung Youn; Youn, Hyung-Seop; Lee, Jung-Gyu; An, Jun Yop; Park, Kyoung Ryoung; Lim, Jia Jia; Kim, Ji Hun; Kim, Ji Hye; Park, Zee Yong; Kim, Yeon-Soo; Wang, Jimin; Kim, Do Han; Eom, Soo Hyun

    2015-10-01

    The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti-/pro-apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N-terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake-1 and mitochondrial calcium uptake-2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca(2+) uptake in a stable MCU knockdown HeLa cell line and exerted dominant-negative effects in the wild-type MCU-expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.

  11. Coupling calcium dynamics and mitochondrial bioenergetic: an in silico study to simulate cardiomyocyte dysfunction.

    Science.gov (United States)

    Das, Phonindra Nath; Pedruzzi, Gabriele; Bairagi, Nandadulal; Chatterjee, Samrat

    2016-03-01

    The coupling of intracellular Ca(2+) dynamics with mitochondrial bioenergetic is crucial for the functioning of cardiomyocytes both in healthy and disease conditions. The pathophysiological signature of the Cardiomyocyte Dysfunction (CD) is commonly related to decreased ATP production due to mitochondrial functional impairment and to an increased mitochondrial calcium content ([Ca(2+)]m). These features advanced the therapeutic approaches which aim to reduce [Ca(2+)]m. But whether [Ca(2+)]m overload is the pathological trigger for CD or a physiological consequence, remained controversial. We addressed this issue in silico and showed that [Ca(2+)]m might not directly cause CD. Through model parameter recalibration, we demonstrated how mitochondria cope up with functionally impaired processes and consequently accumulate calcium. A strong coupling of the [Ca(2+)]m oscillations with the ATP synthesis rate ensures robust calcium cycling and avoids CD. We suggested a cardioprotective role of the mitochondrial calcium uniporter and predicted that a mitochondrial sodium calcium exchanger could be a potential therapeutic target to restore the normal functioning of the cardiomyocyte.

  12. Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology.

    Science.gov (United States)

    Dolphin, Annette C

    2016-10-01

    Voltage-gated calcium channels are essential players in many physiological processes in excitable cells. There are three main subdivisions of calcium channel, defined by the pore-forming α1 subunit, the CaV 1, CaV 2 and CaV 3 channels. For all the subtypes of voltage-gated calcium channel, their gating properties are key for the precise control of neurotransmitter release, muscle contraction and cell excitability, among many other processes. For the CaV 1 and CaV 2 channels, their ability to reach their required destinations in the cell membrane, their activation and the fine tuning of their biophysical properties are all dramatically influenced by the auxiliary subunits that associate with them. Furthermore, there are many diseases, both genetic and acquired, involving voltage-gated calcium channels. This review will provide a general introduction and then concentrate particularly on the role of auxiliary α2 δ subunits in both physiological and pathological processes involving calcium channels, and as a therapeutic target.

  13. Rickets induced by calcium or phosphate depletion.

    OpenAIRE

    Abugassa, S.; Svensson, O.

    1990-01-01

    We studied the effects of calciopenia and phosphopenia on longitudinal growth, skeletal mineralization, and development of rickets in young Sprague-Dawley rats. At an age of 21 days, two experimental groups were given diets containing 0.02% calcium or 0.02% phosphorus; otherwise the diets were nutritionally adequate. After 7, 14, and 21 days, five animals from each group were randomly chosen. The animals were anaesthetized and blood samples were drawn for analysis of calcium, phosphorus, and ...

  14. Fractal aspects of calcium binding protein structures

    Energy Technology Data Exchange (ETDEWEB)

    Isvoran, Adriana [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania)], E-mail: aisvoran@cbg.uvt.ro; Pitulice, Laura [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania); Craescu, Constantin T. [INSERM U759/Institute Curie-Recherche, Centre Universitaire Paris-Sud, Batiment 112, 91405 Orsay (France); Chiriac, Adrian [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania)

    2008-03-15

    The structures of EF-hand calcium binding proteins may be classified into two distinct groups: extended and compact structures. In this paper we studied 20 different structures of calcium binding proteins using the fractal analysis. Nine structures show extended shapes, one is semi-compact and the other 10 have compact shapes. Our study reveals different fractal characteristics for protein backbones belonging to different structural classes and these observations may be correlated to the physicochemical forces governing the protein folding.

  15. Physical Properties of Acidic Calcium Phosphate Cements

    OpenAIRE

    2014-01-01

    The gold standard for bone replacement today, autologous bone, suffers from several disadvantages, such as the increased risk of infection due to the need for two surgeries. Degradable synthetic materials with properties similar to bone, such as calcium phosphate cements, are a promising alternative. Calcium phosphate cements are suited for a limited amount of applications and improving their physical properties could extend their use into areas previously not considered possible. For example...

  16. Evaluation of quick disintegrating calcium carbonate tablets

    OpenAIRE

    Fausett, Hector; Gayser, Charles; Dash, Alekha K.

    2000-01-01

    The purpose of this investigation was to develop a rapidly disintegrating calcium carbonate (CC) tablet by direct compression and compare it with commercially available calcium tablets. CC tablets were formulated on a Carver press using 3 different forms of CC direct compressed granules (Cal-Carb 4450®, Cal-Carb 4457®, and Cal-Carb 4462®). The breaking strength was measured using a Stokes-Monsanto hardness tester. The disintegration and dissolution properties of the tablets were studied using...

  17. Calcium Imaging of Sonoporation of Mammalian Cells

    Science.gov (United States)

    Sabens, David; Aehle, Matthew; Steyer, Grant; Kourennyi, Dmitri; Deng, Cheri X.

    2006-05-01

    Ultrasound mediated delivery of compounds is a relatively recent development in drug delivery and gene transfection techniques. Due to the lack of methods for real-time monitoring of sonoporation at the cellular level, the efficiency of drug/gene delivery and sonoporation associated side effects, such as the loss of cell viability and enhanced apoptosis, have been studied only through post US exposure analyses, requiring days for cell incubation. Furthermore, because microporation appears to be transient in nature, it was not possible to correlate transfection with microporation on an individual cellular basis. By studying the role of calcium in the cell and using fluorescent calcium imaging to study sonoporation it is possible to quantify both cell porosity and sonoporation side effects. Since both post sonoporation cell survival and delivery efficiency are related to the dynamic process of the cell membrane poration, calcium imaging of sonoporation will provide important knowledge to obtain improved understanding of sonoporation mechanism. Our experimental results demonstrated the feasibility of calcium imaging of sonoporation in Chinese Hamster Ovary (CHO) cells. We have measured the changes in the intracellular calcium concentration using Fura-2, a fluorescent probe, which indicate influx or flow of Calcium across the cell membrane. Analysis of data identified key aspects in the dynamic sonoporation process including the formation of pores in the cell membrane, and the relative temporal duration of the pores and their resealing. These observations are obtained through the analysis of the rate the calcium concentration changes within the cells, making it possible to visualize membrane opening and repair in real-time through such changes in the intracellular calcium concentration.

  18. Is Excess Calcium Harmful to Health?

    OpenAIRE

    Daly, Robin M.; Ebeling, Peter R.

    2010-01-01

    Most current guidelines recommend that older adults and the elderly strive for a total calcium intake (diet and supplements) of 1,000 to 1,300 mg/day to prevent osteoporosis and fractures. Traditionally, calcium supplements have been considered safe, effective and well tolerated, but their safety has recently been questioned due to potential adverse effects on vascular disease which may increase mortality. For example, the findings from a meta-analysis of randomized controlled trials (current...

  19. Understanding calcium dynamics experiments and theory

    CERN Document Server

    Malchow, Dieter

    2003-01-01

    Intracellular Calcium is an important messenger in living cells. Calcium dynamics display complex temporal and spatial structures created by the concentration patterns which are characteristic for a nonlinear system operating far from thermodynamic equilibrium. Written as a set of tutorial reviews on both experimental facts and theoretical modelling, this volume is intended as an introduction and modern reference in the field for graduate students and researchers in biophysics, biochemistry and applied mathematics.

  20. Gel time of calcium acrylate grouting material

    Institute of Scientific and Technical Information of China (English)

    韩同春

    2004-01-01

    Calcium acrylate is a polymerized grout, and can polymerize in an aqueous solution. The polymerization reaction utilizes ammonium persulfate as a catalyst and sodium thiosulfate as the activator. Based on the theory of reaction kinetics, this study on the relation between gel time and concentration of activator and catalyst showed that gel time of calcium acrylate is inversely proportional to activator and catalyst concentration. A formula of gel time is proposed, and an example is provided to verify the proposed formula.

  1. [Bone and Nutrition. Vitamin D independent calcium absorption].

    Science.gov (United States)

    Masuyama, Ritsuko

    2015-07-01

    Vitamin D endocrine system is required for normal calcium and bone homeostasis. Trans-epithelial calcium absorption is initiated with calcium entry into the intestinal epithelial cells from luminal fluid through calcium permeable channels, and those expressions are strongly supported by vitamin D action. On the other hands, dietary treatment, mineral supplementation or restriction, successfully improves intestinal calcium absorption in global vitamin D receptor knock-out (VDR KO) mice, though vitamin D dependent active transport pathway is lacking. Dietary rescue of intestinal calcium absorption provided a positive calcium balance in this mouse model, and suggested that the major role of vitamin D function on calcium homeostasis was considered to be intestinal active absorption. To elucidate the entire process of intestinal calcium absorption, vitamin D independent calcium transport system was characterized into either trans-cellular or para-cellular process.

  2. Biocalcite, a multifunctional inorganic polymer: Building block for calcareous sponge spicules and bioseed for the synthesis of calcium phosphate-based bone

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    2014-05-01

    Full Text Available Calcium carbonate is the material that builds up the spicules of the calcareous sponges. Recent results revealed that the calcium carbonate/biocalcite-based spicular skeleton of these animals is formed through an enzymatic mechanism, such as the skeleton of the siliceous sponges, evolutionarily the oldest animals that consist of biosilica. The enzyme that mediates the calcium carbonate deposition has been identified as a carbonic anhydrase (CA and has been cloned from the calcareous sponge species Sycon raphanus. Calcium carbonate deposits are also found in vertebrate bones besides the main constituent, calcium phosphate/hydroxyapatite (HA. Evidence has been presented that during the initial phase of HA synthesis poorly crystalline carbonated apatite is deposited. Recent data summarized here indicate that during early bone formation calcium carbonate deposits enzymatically formed by CA, act as potential bioseeds for the precipitation of calcium phosphate mineral onto bone-forming osteoblasts. Two different calcium carbonate phases have been found during CA-driven enzymatic calcium carbonate deposition in in vitro assays: calcite crystals and round-shaped vaterite deposits. The CA provides a new target of potential anabolic agents for treatment of bone diseases; a first CA activator stimulating the CA-driven calcium carbonate deposition has been identified. In addition, the CA-driven calcium carbonate crystal formation can be frozen at the vaterite state in the presence of silintaphin-2, an aspartic acid/glutamic acid-rich sponge-specific protein. The discovery that calcium carbonate crystals act as bioseeds in human bone formation may allow the development of novel biomimetic scaffolds for bone tissue engineering. Na-alginate hydrogels, enriched with biosilica, have recently been demonstrated as a suitable matrix to embed bone forming cells for rapid prototyping bioprinting/3D cell printing applications.

  3. Analytical models of calcium binding in a calcium channel

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jinn-Liang [Department of Applied Mathematics, National Hsinchu University of Education, Hsinchu 300, Taiwan (China); Eisenberg, Bob [Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois 60612 (United States)

    2014-08-21

    The anomalous mole fraction effect of L-type calcium channels is analyzed using a Fermi like distribution with the experimental data of Almers and McCleskey [J. Physiol. 353, 585 (1984)] and the atomic resolution model of Lipkind and Fozzard [Biochemistry 40, 6786 (2001)] of the selectivity filter of the channel. Much of the analysis is algebraic, independent of differential equations. The Fermi distribution is derived from the configuration entropy of ions and water molecules with different sizes, different valences, and interstitial voids between particles. It allows us to calculate potentials and distances (between the binding ion and the oxygen ions of the glutamate side chains) directly from the experimental data using algebraic formulas. The spatial resolution of these results is comparable with those of molecular models, but of course the accuracy is no better than that implied by the experimental data. The glutamate side chains in our model are flexible enough to accommodate different types of binding ions in different bath conditions. The binding curves of Na{sup +} and Ca{sup 2+} for [CaCl{sub 2}] ranging from 10{sup −8} to 10{sup −2} M with a fixed 32 mM background [NaCl] are shown to agree with published Monte Carlo simulations. The Poisson-Fermi differential equation—that includes both steric and correlation effects—is then used to obtain the spatial profiles of energy, concentration, and dielectric coefficient from the solvent region to the filter. The energy profiles of ions are shown to depend sensitively on the steric energy that is not taken into account in the classical rate theory. We improve the rate theory by introducing a steric energy that lumps the effects of excluded volumes of all ions and water molecules and empty spaces between particles created by Lennard-Jones type and electrostatic forces. We show that the energy landscape varies significantly with bath concentrations. The energy landscape is not constant.

  4. Effect of Calcium Oxide Microstructure on the Diffusion of Isotopes

    CERN Document Server

    Fernandes Ramos, João Pedro; Stora, T

    2012-01-01

    Calcium oxide (CaO) powder targets have been successfully used at CERN-ISOLDE to produce neutron deficient exotic argon and carbon isotopes under proton irradiation at high temperatures (>1000°C). These targets outperform the other related targets for the production of the same beams. However, they presented either slow release rates (yields) from the beginning or a rapid decrease over time. This problem was believed to come from the target microstructure degradation, justifying the material investigation. In order to do so, the synthesis, reactivity in ambient air and sintering kinetics of CaO were studied, through surface area determination by N2 adsorption, X-ray diffraction for crystalline phase identification and crystallite size determination, and scanning and transmission electron microscopy to investigate the microstructure. The synthesis studies revealed that a nanometric material is obtained from the decarbonation of CaCO3 in vacuum at temperatures higher than 550°C, which is very reactive in air....

  5. 48 CFR 39.104 - Information technology services.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Information technology... SPECIAL CATEGORIES OF CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 39.104 Information technology services. When acquiring information technology services, solicitations must not describe...

  6. 39 CFR 501.16 - PC postage payment methodology.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false PC postage payment methodology. 501.16 Section 501.16 Postal Service UNITED STATES POSTAL SERVICE POSTAGE PROGRAMS AUTHORIZATION TO MANUFACTURE AND DISTRIBUTE POSTAGE EVIDENCING SYSTEMS § 501.16 PC postage payment methodology. (a) The PC Postage customer...

  7. 40Ar/39Ar age calibration against counted annuallayers

    DEFF Research Database (Denmark)

    Storey, Michael; Stecher, Ole

    2008-01-01

    worth exploring for an improved absolute age basis for the 40Ar/39Ar system is through cross-calibration with counted annual layers (e.g. tree rings, varves and ice cores). North Atlantic Ash Zone (NAAZ) II is found within the dated part of the annual Greenland ice core record. NAAZ II has been...

  8. 14 CFR 142.39 - Training program curriculum requirements.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Training program curriculum requirements... TRANSPORTATION (CONTINUED) SCHOOLS AND OTHER CERTIFICATED AGENCIES TRAINING CENTERS Aircrew Curriculum and Syllabus Requirements § 142.39 Training program curriculum requirements. Each training program...

  9. Atom trap trace analysis of {sup 39}Ar

    Energy Technology Data Exchange (ETDEWEB)

    Welte, Joachim

    2011-12-14

    Detection of {sup 39}Ar in natural water samples can be employed for radiometric dating on a timescale of 50 to 1000 years before present. This experimental work comprises the setup of an atomic beam and trap apparatus that captures and detects {sup 39}Ar atoms by the laser-cooling technique ''Atom Trap Trace Analysis''. With this approach, the limitations of low-level counting, regarding sample size and measurement time, could be overcome. In the course of this work, the hyperfine structure spectrum of the cooling transition 1s{sub 5}-2p{sub 9} has been experimentally determined. A high intensity, optically collimated beam of slow metastable argon atoms has been set up and fluorescence detection of individual {sup 39}Ar atoms in a magneto-optical trap is realized. {sup 39}Ar count rates of 1 atom in about 4 hours have been achieved for atmospheric argon. Recent improvements further suggest that even higher count rates of 1 atom/hour are within reach.

  10. Searchlights Illuminate Apollo 8 on Pad 39-A

    Science.gov (United States)

    1968-01-01

    Searchlights penetrate the darkness surrounding Apollo 8 on Pad 39-A at Kennedy Space Center. This mission was the first manned flight using the Saturn V. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

  11. 39 CFR 3050.27 - Workers' Compensation Report.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Workers' Compensation Report. 3050.27 Section 3050.27 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL PERIODIC REPORTING § 3050.27 Workers' Compensation Report. The Workers' Compensation Report, including summary workpapers, shall be provided by...

  12. 39 CFR 601.107 - Initial disagreement resolution.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Initial disagreement resolution. 601.107 Section... disagreement resolution. (a) Definitions. (1) Days. Calendar days; however, any time period will run until a... officer or the Supplier Disagreement Resolution Official, as appropriate. (5) SDR Official. The...

  13. 39 CFR 601.108 - SDR Official disagreement resolution.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false SDR Official disagreement resolution. 601.108... disagreement resolution. (a) General. If a disagreement under § 601.107 is not resolved within 10 days after it... supplier is not satisfied with the contracting officer's resolution of the disagreement, or if the...

  14. 41 CFR 109-39.301 - Utilization guidelines.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Utilization guidelines... Management System Vehicles § 109-39.301 Utilization guidelines. DOE activities utilizing GSA IFMS motor... meeting DOE utilization guidelines or established local use objectives, as appropriate. Those vehicles...

  15. 41 CFR 101-39.301 - Utilization guidelines.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Utilization guidelines... § 101-39.301 Utilization guidelines. An agency must be able to justify a full-time vehicle assignment. The following guidelines may be employed by an agency requesting GSA Interagency Fleet...

  16. 39 CFR 775.8 - Environmental evaluation guidelines.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Environmental evaluation guidelines. 775.8 Section 775.8 Postal Service UNITED STATES POSTAL SERVICE ENVIRONMENTAL REGULATIONS NATIONAL ENVIRONMENTAL POLICY ACT PROCEDURES § 775.8 Environmental evaluation guidelines. (a) Approach. When dealing...

  17. 39 CFR 3001.115 - Participant statement or brief.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Participant statement or brief. 3001.115 Section... Participant statement or brief. (a) Participant statement. Upon the filing of the petition for review of a... or she may file a brief as described in paragraph (b) of this section presenting the arguments,...

  18. 39 CFR 959.3 - Office, business hours.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Office, business hours. 959.3 Section 959.3 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO THE PRIVATE EXPRESS STATUTES § 959.3 Office, business hours. The offices of the officials mentioned in these rules...

  19. 39 CFR 952.4 - Office business hours.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Office business hours. 952.4 Section 952.4 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO FALSE REPRESENTATION AND LOTTERY ORDERS § 952.4 Office business hours. The offices of the officials mentioned in...

  20. 39 CFR 954.4 - Office business hours.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Office business hours. 954.4 Section 954.4 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO THE DENIAL, SUSPENSION, OR REVOCATION OF PERIODICALS MAIL PRIVILEGES § 954.4 Office business hours. The offices of...

  1. 39 CFR 267.5 - National Security Information.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false National Security Information. 267.5 Section 267.5 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION PROTECTION OF INFORMATION § 267.5 National Security Information. (a) Purpose and scope. The purpose of this section is to provide regulations implementing Executive...

  2. 39 CFR 267.4 - Information security standards.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Information security standards. 267.4 Section 267.4 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION PROTECTION OF INFORMATION § 267.4 Information security standards. (a) The Postal Service will operate under a uniform set of information security standards which...

  3. 39 CFR 3002.14 - Office of the Consumer Advocate.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Office of the Consumer Advocate. 3002.14 Section... Consumer Advocate. (a) The Office of the Consumer Advocate provides representation for the interests of the... pendency of a proceeding, personnel serving in the Office of the Consumer Advocate are prohibited...

  4. 39 CFR 761.6 - Delivery of Postal Service securities.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Delivery of Postal Service securities. 761.6... POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.6 Delivery of Postal Service securities. A Reserve Bank... obligations under this part by the delivery of Postal Service securities in definitive form to its...

  5. 39 CFR 3002.10 - The Commission and its offices.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false The Commission and its offices. 3002.10 Section... its offices. (a) The Commissioners. The Postal Regulatory Commission is an independent establishment... accessible through the Internet, on its website at www.prc.gov....

  6. 19 CFR 111.39 - Advice to client.

    Science.gov (United States)

    2010-04-01

    ... CUSTOMS BROKERS Duties and Responsibilities of Customs Brokers § 111.39 Advice to client. (a) Withheld or false information. A broker must not withhold information relative to any customs business from a client... false information relative to any customs business. (b) Error or omission by client. If a broker...

  7. 39 CFR 10.4 - Financial disclosure reports.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Financial disclosure reports. 10.4 Section 10.4... CONDUCT FOR POSTAL SERVICE GOVERNORS (ARTICLE X) § 10.4 Financial disclosure reports. (a) Requirement of submission of reports. At the time of their nomination, Governors complete a financial disclosure...

  8. 39 CFR 775.7 - Planning and early coordination.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Planning and early coordination. 775.7 Section 775.7 Postal Service UNITED STATES POSTAL SERVICE ENVIRONMENTAL REGULATIONS NATIONAL ENVIRONMENTAL POLICY ACT PROCEDURES § 775.7 Planning and early coordination. Early planning and coordination...

  9. 39 CFR 761.2 - Authority of Reserve Banks.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Authority of Reserve Banks. 761.2 Section 761.2 Postal Service UNITED STATES POSTAL SERVICE POSTAL SERVICE DEBT OBLIGATIONS; DISBURSEMENT POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.2 Authority of Reserve Banks. Each Reserve Bank is hereby...

  10. 39 CFR 122.2 - Stand-alone special services.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Stand-alone special services. 122.2 Section 122.2 Postal Service UNITED STATES POSTAL SERVICE POST OFFICE SERVICES SERVICE STANDARDS FOR MARKET-DOMINANT SPECIAL SERVICES PRODUCTS § 122.2 Stand-alone special services. (a) The service standard for P. O....

  11. 39 CFR 3050.40 - Additional financial reporting.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Additional financial reporting. 3050.40 Section... financial reporting. (a) In general. The Postal Service shall file with the Commission: (1) Within 40 days...), beginning with the annual report for fiscal year 2010. (c) Financial reporting. The reports required...

  12. 14 CFR 399.39 - Equipment purchase deposits.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Equipment purchase deposits. 399.39 Section... Equipment purchase deposits. Equipment purchase deposits are advance payments made by air carriers to manufacturers for the purchase of equipment to be delivered in the future, or funds segregated by air...

  13. 18 CFR 39.3 - Electric Reliability Organization certification.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Electric Reliability... CERTIFICATION OF THE ELECTRIC RELIABILITY ORGANIZATION; AND PROCEDURES FOR THE ESTABLISHMENT, APPROVAL, AND ENFORCEMENT OF ELECTRIC RELIABILITY STANDARDS § 39.3 Electric Reliability Organization certification. (a)...

  14. Phenotype abnormality: 39 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available 39 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u545i abnormal for trait of behavioral quality... in organ named flower during process named organ development ... flower ... abnormal ... organ development ... behavioral quality

  15. 14 CFR 136.39 - Air tour management plans (ATMP).

    Science.gov (United States)

    2010-01-01

    ... curfews) for the adoption of quiet technology aircraft by commercial air tour operators conducting... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Air tour management plans (ATMP). 136.39... (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS COMMERCIAL...

  16. 39 CFR 6.4 - Attendance by conference telephone call.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Attendance by conference telephone call. 6.4 Section 6.4 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE MEETINGS (ARTICLE VI) § 6.4 Attendance by conference telephone call. For regularly scheduled meetings...

  17. 39 CFR 601.104 - Postal purchasing authority.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Postal purchasing authority. 601.104 Section 601...: INTELLECTUAL PROPERTY RIGHTS OTHER THAN PATENTS PURCHASING OF PROPERTY AND SERVICES § 601.104 Postal purchasing..., or terminating any contract regarding the acquisition of property, services, and related...

  18. 39 CFR 955.31 - Dismissal without prejudice.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Dismissal without prejudice. 955.31 Section 955.31... OF CONTRACT APPEALS § 955.31 Dismissal without prejudice. In certain cases, appeals docketed before... discretion, dismiss such appeals from its docket without prejudice to their restoration when the cause...

  19. 39 CFR 265.5 - Public reading rooms.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Public reading rooms. 265.5 Section 265.5 Postal... reading rooms. The Library of the Postal Service Headquarters, 475 L'Enfant Plaza SW, Washington, DC 20260-1641, serves as public reading room for the materials which are listed in paragraphs (a)(2), (3),...

  20. 9 CFR 113.39 - Cat safety tests.

    Science.gov (United States)

    2010-01-01

    ... on susceptible cell cultures for the presence of the virus. Blood samples shall also be drawn and... paragraphs (a)(1)(i) and (ii) of this section, a method acceptable to Animal and Plant Health Inspection... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cat safety tests. 113.39 Section...