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Sample records for calcium 41 target

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

    Science.gov (United States)

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    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.

  2. Regulation of gamma T-cell antigen receptor expression by intracellular calcium in acute lymphoblastic leukemia cell line DND41.

    Science.gov (United States)

    Peralta-Zaragoza, O; Martínez-Valdez, H; Madrid-Marina, V

    1996-01-01

    The calcium ionophore, ionomycin, promotes an increase of intracellular calcium and regulates mRNA expression of gamma/delta-TcR gene in human T lymphocytes. The mechanism of this regulation is not yet clear. Thus, the regulation by intracellular calcium requires elucidation. We studied the gamma-TcR gene expression in acute lymphoblastic leukemia cell line DND41 (CD4- CD8-) by Northern blot and flow cytometric analysis. The mRNA levels of gamma-TcR increased by ionomycin, anti-CD3, and with TPA. TPA had an antagonistic effect to both ionomycin and anti-CD3. Also, TPA inhibits the increased intracellular calcium promoted by ionomycin but not the increase promoted by anti-CD3 and ionomycin. Our results suggest that intracellular calcium induces mRNA and protein expression of gamma-TcR chain. This effect is antagonized by protein kinase C-activation. Thus, we conclude that the target cells of the differential regulation on gamma-TcR mRNA expression by intracellular calcium modulators are the CD4- CD8- cells, and this is due to cytosolic calcium mobilization. PMID:8854386

  3. Calcium-41 as a long-term biological tracer for bone resorption

    Science.gov (United States)

    Elmore, David; Bhattacharyya, Maryka H.; Sacco-Gibson, Nancy; Peterson, David P.

    1990-12-01

    The use of 41Ca (half-life 1 × 10 5 yr) as a tracer for studying calcium metabolism in living systems is compared to the shorter-lived radionuclides 45Ca (165 d) and 47Ca (45 d) and the stable isotopes 42Ca and 44Ca. The feasibility of using accelerator mass spectrometry (AMS) measurements of 41Ca for studying multi-year calcium resorption in humans was tested as part of a companion study that used 45Ca to measure the effects of dietary cadmium on calcium metabolism in dogs. It was shown that Ca resorbed from prelabeled bones correlates well with 45Ca for a period of 28 weeks. The advantage of 41Ca is that, even with a negligible radiation dose, it can be measured by AMS long after the 45Ca becomes unmeasurable.

  4. 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...

  5. 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 Institute...

  6. Tannin inhibits HIV-1 entry by targeting gp41

    Institute of Scientific and Technical Information of China (English)

    Lin L(U); Shu-wen LIU; Shi-bo JIANG; Shu-guang WU

    2004-01-01

    AIM: To investigate the mechanism by which tannin inhibits HIV-1 entry into target cells. METHODS: The inhibitory activity of tannin on HIV-1 replication and entry was detected by p24 production and HIV-1-mediated cell fusion, respectively. The inhibitory activity on the gp41 six-helix bundle formation was determined by an improved sandwich ELISA. RESULTS: Tannins from different sources showed potent inhibitory activity on HIV-1 replication,HIV-1-mediated cell fusion, and the gp4 six-helix bundle formation. CONCLUSION: Tannin inhibits HIV-1 entry into target cells by interfering with the gp41 six-helix bundle formation, thus blocking HIV-1 fusion with the target cell.

  7. Human calcium metabolism including bone resorption measured with {sup 41}Ca tracer

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.P.H.T. [Lawrence Livermore National Lab., CA (United States); King, J.C. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Vieira, N.E. [National Inst. of Child Health and Human Development, Bethesda, MD (United States); Woodhouse, L.R. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Yergey, A.L. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)

    1996-08-01

    Accelerator mass spectrometry is so sensitive to small quantities of {sup 41}Ca that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, {sup 41}Ca tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state. Resorbing bone may thus be directly measured. We have tested such a protocol against a conventional stable isotope experiment with good agreement.

  8. Computer-Aided Approaches for Targeting HIVgp41

    Directory of Open Access Journals (Sweden)

    William J. Allen

    2012-08-01

    Full Text Available Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41 which advances through four distinct conformational states: (i native, (ii pre-hairpin intermediate, (iii fusion active (fusogenic, and (iv post-fusion. The pre-hairpin intermediate is a particularly attractive step for therapeutic intervention given that gp41 N-terminal heptad repeat (NHR and C‑terminal heptad repeat (CHR domains are transiently exposed prior to the formation of a six-helix bundle required for fusion. Most peptide-based inhibitors, including the FDA‑approved drug T20, target the intermediate and there are significant efforts to develop small molecule alternatives. Here, we review current approaches to studying interactions of inhibitors with gp41 with an emphasis on atomic-level computer modeling methods including molecular dynamics, free energy analysis, and docking. Atomistic modeling yields a unique level of structural and energetic detail, complementary to experimental approaches, which will be important for the design of improved next generation anti-HIV drugs.

  9. Calcium Isolation from Large-Volume Human Urine Samples for 41Ca Analysis by Accelerator Mass Spectrometry

    Science.gov (United States)

    Miller, James J; Hui, Susanta K; Jackson, George S; Clark, Sara P; Einstein, Jane; Weaver, Connie M; Bhattacharyya, Maryka H

    2013-01-01

    Calcium oxalate precipitation is the first step in preparation of biological samples for 41Ca analysis by accelerator mass spectrometry. A simplified protocol for large-volume human urine samples was characterized, with statistically significant increases in ion current and decreases in interference. This large-volume assay minimizes cost and effort and maximizes time after 41Ca administration during which human samples, collected over a lifetime, provide 41Ca:Ca ratios that are significantly above background. PMID:23672965

  10. 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.

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

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    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.

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

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    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.

  13. 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.

  14. Subcellular targeting of nine calcium-dependent protein kinase isoforms from Arabidopsis

    Science.gov (United States)

    Dammann, Christian; Ichida, Audrey; Hong, Bimei; Romanowsky, Shawn M.; Hrabak, Estelle M.; Harmon, Alice C.; Pickard, Barbara G.; Harper, Jeffrey F.; Evans, M. L. (Principal Investigator)

    2003-01-01

    Calcium-dependent protein kinases (CDPKs) are specific to plants and some protists. Their activation by calcium makes them important switches for the transduction of intracellular calcium signals. Here, we identify the subcellular targeting potentials for nine CDPK isoforms from Arabidopsis, as determined by expression of green fluorescent protein (GFP) fusions in transgenic plants. Subcellular locations were determined by fluorescence microscopy in cells near the root tip. Isoforms AtCPK3-GFP and AtCPK4-GFP showed a nuclear and cytosolic distribution similar to that of free GFP. Membrane fractionation experiments confirmed that these isoforms were primarily soluble. A membrane association was observed for AtCPKs 1, 7, 8, 9, 16, 21, and 28, based on imaging and membrane fractionation experiments. This correlates with the presence of potential N-terminal acylation sites, consistent with acylation as an important factor in membrane association. All but one of the membrane-associated isoforms targeted exclusively to the plasma membrane. The exception was AtCPK1-GFP, which targeted to peroxisomes, as determined by covisualization with a peroxisome marker. Peroxisome targeting of AtCPK1-GFP was disrupted by a deletion of two potential N-terminal acylation sites. The observation of a peroxisome-located CDPK suggests a mechanism for calcium regulation of peroxisomal functions involved in oxidative stress and lipid metabolism.

  15. 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.

  16. Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket

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    Asim K. Debnath

    2013-01-01

    Full Text Available The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon, was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD, it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.

  17. 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.

  18. 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.

  19. Study on Different Forms of Calcium Metabolic Behavior in Normal and Osteoporosis Rats by ~(41)Ca Tracing

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Because of calcium deficiency,there were about 90 million Chinese people suffering from osteoporosis which caused a great calcium supplement boom in 2009. However, recent studies have shown that excess calcium supplement may cause some other diseases

  20. Assessing potential targets of calcium action in light-modulated gravitropism

    Science.gov (United States)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

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

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    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

  2. Why Basic Calcium Phosphate Crystals Should Be Targeted In the Treatment of Osteoarthritis

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    Claire-Louise Murphy

    2014-07-01

    Full Text Available Osteoarthritis (OA is the most common form of arthritis and results in significant social, psychological, and economic costs. It is characterised by progressive cartilage loss, bone remodelling, osteophyte formation, and synovial inflammation with resultant joint pain and disability. Since OA affects the entire joint, it is not surprising that there has been difficulty developing an effective targeted treatment. Treatments available for structural disease modification are limited. Current options appear to mostly reduce symptoms. Basic calcium phosphate (BCP crystals represent a potential therapeutic target in OA; they have been found in 100% of knee and hip cartilages removed at joint replacement. Intra-articular BCP crystals are associated with large joint effusions and dissolution of intra-articular structures, synovial proliferation, and marked degeneration as assessed by diagnostic imaging. While BCP deposition has been considered by many to be simply a consequence of advanced OA, there is substantial evidence to support BCP crystal deposition as an active pathogenic mediator of OA. BCP crystals exhibit a multiplicity of biologic effects in vitro including the ability to stimulate mitogenesis and prostaglandin, cytokine, and matrix metalloproteinase (MMP synthesis in a number of cell types including macrophages, synovial fibroblasts, and chondrocytes. BCP crystals also contribute to inflammation in OA through direct interaction with the innate immune system. Intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation in mice in vivo . Although intra-articular BCP crystals are difficult to detect at the bedside, advances in modern technology should allow improved identification and quantitation of BCP crystals. Our article focuses on why basic calcium crystals are important in the pathogenesis of OA. There is ample evidence that BCP crystals should be explored as a therapeutic target in OA.

  3. Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

    International Nuclear Information System (INIS)

    The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar

  4. Calcium channels in the brain as targets for the calcium-channel modulators used in the treatment of neurological disorders

    NARCIS (Netherlands)

    Peters, Thies; WILFFERT, B; VANHOUTTE, PM; VANZWIETEN, PA

    1991-01-01

    Recent investigations of calcium channels in brain cells by voltage-clamp techniques have revealed that, in spite of electrophysiological similarities, the pharmacological properties of these channels differ considerably from channels in peripheral tissues, e.g., heart and smooth muscle. Therefore,

  5. Calcium-activated potassium channels in insect pacemaker neurons as unexpected target site for the novel fumigant dimethyl disulfide.

    Science.gov (United States)

    Gautier, Hélène; Auger, Jacques; Legros, Christian; Lapied, Bruno

    2008-01-01

    Dimethyl disulfide (DMDS), a plant-derived insecticide, is a promising fumigant as a substitute for methyl bromide. To further understand the mode of action of DMDS, we examined its effect on cockroach octopaminergic neurosecretory cells, called dorsal unpaired median (DUM) neurons, using whole-cell patch-clamp technique, calcium imaging and antisense oligonucleotide strategy. At low concentration (1 microM), DMDS modified spontaneous regular spike discharge into clear bursting activity associated with a decrease of the amplitude of the afterhyperpolarization. This effect led us to suspect alterations of calcium-activated potassium currents (IKCa) and [Ca(2+)](i) changes. We showed that DMDS reduced amplitudes of both peak transient and sustained components of the total potassium current. IKCa was confirmed as a target of DMDS by using iberiotoxin, cadmium chloride, and pSlo antisense oligonucleotide. In addition, we showed that DMDS induced [Ca(2+)](i) rise in Fura-2-loaded DUM neurons. Using calcium-free solution, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxy-phenyl)ethyl]-acetamide (LOE 908) [an inhibitor of transient receptor potential (TRP)gamma], we demonstrated that TRPgamma initiated calcium influx. By contrast, omega-conotoxin GVIA (an inhibitor of N-type high-voltage-activated calcium channels), did not affect the DMDS-induced [Ca(2+)](i) rise. Finally, the participation of the calcium-induced calcium release mechanism was investigated using thapsigargin, caffeine, and ryanodine. Our study revealed that DMDS-induced elevation in [Ca(2+)](i) modulated IKCa in an unexpected bell-shaped manner via intracellular calcium. In conclusion, DMDS affects multiple targets, which could be an effective way to improve pest control efficacy of fumigation. PMID:17942746

  6. 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.

  7. Calcium/calmodulin-dependent protein kinase IV: A multifunctional enzyme and potential therapeutic target.

    Science.gov (United States)

    Naz, Huma; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-05-01

    The calcium/calmodulin-dependent protein kinase IV (CAMKIV) belongs to the serine/threonine protein kinase family, and is primarily involved in transcriptional regulation in lymphocytes, neurons and male germ cells. CAMKIV operates the signaling cascade and regulates activity of several transcription activators by phosphorylation, which in turn plays pivotal roles in immune response, inflammation and memory consolidation. In this review, we tried to focus on different aspects of CAMKIV to understand the significance of this protein in the biological system. This enzyme is associated with varieties of disorders such as cerebral hypoxia, azoospermia, endometrial and ovarian cancer, systemic lupus, etc., and hence it is considered as a potential therapeutic target. Structure of CAMKIV is comprised of five distinct domains in which kinase domain is responsible for enzyme activity. CAMKIV is involved in varieties of cellular functions such as regulation of gene expression, T-cell maturation, regulation of survival phase of dendritic cells, bone growth and metabolism, memory consolidation, sperm motility, regulation of microtubule dynamics, cell-cycle progression and apoptosis. In this review, we performed an extensive analysis on structure, function and regulation of CAMKIV and associated diseases. PMID:26773169

  8. Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain

    OpenAIRE

    Vink, S.; Alewood, PF

    2012-01-01

    Chronic pain affects approximately 20% of people worldwide and places a large economic and social burden on society. Despite the availability of a range of analgesics, this condition is inadequately treated, with complete alleviation of symptoms rarely occurring. In the past 30 years, the voltage-gated calcium channels (VGCCs) have been recognized as potential targets for analgesic development. Although the majority of the research has been focused on Cav2.2 in particular, other VGCC subtypes...

  9. An amplified promoter system for targeted expression of calcium indicator proteins in the cerebellar cortex

    Directory of Open Access Journals (Sweden)

    Bernd eKuhn

    2012-07-01

    Full Text Available Recording of identified neuronal network activity using genetically encoded calcium indicators (GECIs requires labeling that is cell type-specific and bright enough for the detection of functional signals. However, specificity and strong expression are often not achievable using the same promoter. Here we present a combinatorial approach for targeted expression and single-cell-level quantification in which a weak promoter is used to drive trans-amplification under a strong general promoter. We demonstrated this approach using recombinant adeno-associated viruses (rAAVs to deliver the sequence of the GECI D3cpv in the mouse cerebellar cortex. Direct expression under the human synapsin promoter (hSYN led to high levels of expression (50-100 µM in five interneuron types of the cerebellar cortex but not in Purkinje cells (PCs (≤10 μM, yielding sufficient contrast to allow functional signals to be recorded from somata and processes in awake animals using two-photon microscopy. When the hSYN promoter was used to drive expression of the tetracycline transactivator (tTA, a second rAAV containing the bidirectional TET promoter (Ptetbi could drive strong D3cpv expression in PCs (10-300 µM, enough to allow reliable complex spike detection in the dendritic arbor. An amplified approach should be of use in monitoring neural processing in selected cell types and boosting expression of optogenetic probes. Additionally, we overcome cell toxicity associated with rAAV injection and/or local GECI overexpression by combining the virus injection with systemic pre-injection of hyperosmotic D-mannitol, and by this double the time window for functional imaging.

  10. 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.

  11. 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..

  12. Proteomic analysis of imatinib-resistant CML-T1 cells reveals calcium homeostasis as a potential therapeutic target

    Science.gov (United States)

    Toman, O.; Kabickova, T.; Vit, O.; Fiser, R.; Polakova, K. Machova; Zach, J.; Linhartova, J.; Vyoral, D.; Petrak, J.

    2016-01-01

    Chronic myeloid leukemia (CML) therapy has markedly improved patient prognosis after introduction of imatinib mesylate for clinical use. However, a subset of patients develops resistance to imatinib and other tyrosine kinase inhibitors (TKIs), mainly due to point mutations in the region encoding the kinase domain of the fused BCR-ABL oncogene. To identify potential therapeutic targets in imatinib-resistant CML cells, we derived imatinib-resistant CML-T1 human cell line clone (CML-T1/IR) by prolonged exposure to imatinib in growth media. Mutational analysis revealed that the Y235H mutation in BCR-ABL is probably the main cause of CML-T1/IR resistance to imatinib. To identify alternative therapeutic targets for selective elimination of imatinib-resistant cells, we compared the proteome profiles of CML-T1 and CML-T1/IR cells using 2-DE-MS. We identified eight differentially expressed proteins, with strongly upregulated Na+/H+ exchanger regulatory factor 1 (NHERF1) in the resistant cells, suggesting that this protein may influence cytosolic pH, Ca2+ concentration or signaling pathways such as Wnt in CML-T1/IR cells. We tested several compounds including drugs in clinical use that interfere with the aforementioned processes and tested their relative toxicity to CML-T1 and CML-T1/IR cells. Calcium channel blockers, calcium signaling antagonists and modulators of calcium homeostasis, namely thapsigargin, ionomycin, verapamil, carboxyamidotriazole and immunosuppressive drugs cyclosporine A and tacrolimus (FK-506) were selectively toxic to CML-T1/IR cells. The putative cellular targets of these compounds in CML-T1/IR cells are postulated in this study. We propose that Ca2+ homeostasis can be a potential therapeutic target in CML cells resistant to TKIs. We demonstrate that a proteomic approach may be used to characterize a TKI-resistant population of CML cells enabling future individualized treatment options for patients. PMID:27430982

  13. 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

  14. 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.

  15. Proteomic analysis of imatinib-resistant CML-T1 cells reveals calcium homeostasis as a potential therapeutic target.

    Science.gov (United States)

    Toman, O; Kabickova, T; Vit, O; Fiser, R; Polakova, K Machova; Zach, J; Linhartova, J; Vyoral, D; Petrak, J

    2016-09-01

    Chronic myeloid leukemia (CML) therapy has markedly improved patient prognosis after introduction of imatinib mesylate for clinical use. However, a subset of patients develops resistance to imatinib and other tyrosine kinase inhibitors (TKIs), mainly due to point mutations in the region encoding the kinase domain of the fused BCR-ABL oncogene. To identify potential therapeutic targets in imatinib‑resistant CML cells, we derived imatinib-resistant CML-T1 human cell line clone (CML-T1/IR) by prolonged exposure to imatinib in growth media. Mutational analysis revealed that the Y235H mutation in BCR-ABL is probably the main cause of CML-T1/IR resistance to imatinib. To identify alternative therapeutic targets for selective elimination of imatinib-resistant cells, we compared the proteome profiles of CML-T1 and CML-T1/IR cells using 2-DE-MS. We identified eight differentially expressed proteins, with strongly upregulated Na+/H+ exchanger regulatory factor 1 (NHERF1) in the resistant cells, suggesting that this protein may influence cytosolic pH, Ca2+ concentration or signaling pathways such as Wnt in CML-T1/IR cells. We tested several compounds including drugs in clinical use that interfere with the aforementioned processes and tested their relative toxicity to CML-T1 and CML-T1/IR cells. Calcium channel blockers, calcium signaling antagonists and modulators of calcium homeostasis, namely thapsigargin, ionomycin, verapamil, carboxyamidotriazole and immunosuppressive drugs cyclosporine A and tacrolimus (FK-506) were selectively toxic to CML-T1/IR cells. The putative cellular targets of these compounds in CML-T1/IR cells are postulated in this study. We propose that Ca2+ homeostasis can be a potential therapeutic target in CML cells resistant to TKIs. We demonstrate that a proteomic approach may be used to characterize a TKI-resistant population of CML cells enabling future individualized treatment options for patients. PMID:27430982

  16. New Conotoxin SO-3 Targeting N-type Voltage-Sensitive Calcium Channels

    Directory of Open Access Journals (Sweden)

    Lei Wen

    2006-04-01

    Full Text Available Selective blockers of the N-type voltage-sensitive calcium (CaV channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to ω-conotoxin MVIIA (MVIIA, a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.

  17. 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.

  18. Mitochondria and calcium flux as targets of neuroprotection caused by minocycline in cerebellar granule cells

    OpenAIRE

    Garcia-Martinez, Eva Maria; Sanz-Blasco, Sara; Karachitos, Andonis; Bandez, Miguel J.; Fernandez-Gomez, Francisco J.; Perez-Alvarez, Sergio; Mera, Raquel Maria Melero Fernandez De; Jordan, Maria J.; Aguirre, Norberto; Galindo, Maria F.; Villalobos, Carlos; Navarro, Ana; Kmita, Hanna; Jordán, Joaquín

    2009-01-01

    Abstract Minocycline, an antibiotic of the tetracycline family, has attracted considerable interest for its theoretical therapeutic applications in neurodegenerative diseases. However, the mechanism of action underlying its effect remains elusive. Here we have studied the effect of minocycline under excitotoxic conditions. Fluorescence and bioluminescence imaging studies in rat cerebellar granular neuron cultures using fura-2/AM and mitochondria-targeted aequorin revealed that mino...

  19. Efficiency of calcium phosphate composite nanoparticles in targeting Ehrlich carcinoma cells transplanted in mice

    Directory of Open Access Journals (Sweden)

    Eman I. Abdel-Gawad

    2016-01-01

    Full Text Available The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Groups 1 and 2 were allocated as the EAC control. Groups 3 and 4 were injected once intratumorally (IT by nano-calcium phosphate (nano-CaP. Groups 5 and 6 received once intraperitoneal injection (IP of nano-CaP. Groups 7, 8, and 9 received nano-CaP (IP weekly. Blood samples and thigh skeletal muscle were collected after three weeks from groups 1, 3, 5, and 7 and after four weeks from groups 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT, and gamma-aminobutyric acid (GABA were measured. In serum, 8-Hydroxy-deoxyguanosine (8-OHDG, adenosine triphosphate (ATP, and vascular endothelial growth factor (VEGF were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA. Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months.

  20. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  1. Stable Extended Human Immunodeficiency Virus Type 1 gp41 Coiled Coil as an Effective Target in an Assay for High-Affinity Fusion Inhibitors▿

    OpenAIRE

    Cai, Lifeng; Balogh, Edina; Gochin, Miriam

    2009-01-01

    The human immunodeficiency virus type 1 (HIV-1) gp41 coiled-coil domain is an important target for fusion inhibitors, including the peptide T20, which has been approved as a drug against HIV-1. Research into nonpeptide fusion inhibitors has focused primarily on a hydrophobic pocket located within the coiled coil and has so far yielded compounds with relatively weak fusion inhibitory activity. Here, we describe metal ion-assisted stabilization of an extended 39-residue construct of gp41, which...

  2. Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain.

    Science.gov (United States)

    Vink, S; Alewood, P F

    2012-11-01

    Chronic pain affects approximately 20% of people worldwide and places a large economic and social burden on society. Despite the availability of a range of analgesics, this condition is inadequately treated, with complete alleviation of symptoms rarely occurring. In the past 30 years, the voltage-gated calcium channels (VGCCs) have been recognized as potential targets for analgesic development. Although the majority of the research has been focused on Ca(v) 2.2 in particular, other VGCC subtypes such as Ca(v) 3.2 have recently come to the forefront of analgesic research. Venom peptides from marine cone snails have been proven to be a valuable tool in neuroscience, playing a major role in the identification and characterization of VGCC subtypes and producing the first conotoxin-based drug on the market, the ω-conotoxin, ziconotide. This peptide potently and selectively inhibits Ca(v) 2.2, resulting in analgesia in chronic pain states. However, this drug is only available via intrathecal administration, and adverse effects and a narrow therapeutic window have limited its use in the clinic. Other Ca(v) 2.2 inhibitors are currently in development and offer the promise of an improved route of administration and safety profile. This review assesses the potential of targeting VGCCs for analgesic development, with a main focus on conotoxins that block Ca(v) 2.2 and the developments made to transform them into therapeutics. PMID:22725651

  3. Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Simonsen, Ulf

    2010-01-01

    : Opening of SK and IK channels is associated with EDHF-type vasodilatation, but, through increased endothelial cell Ca(2+) influx, L-arginine uptake, and decreased ROS production, it may also lead to increased NO bioavailability and endothelium-dependent vasodilatation. TAKE HOME MESSAGE: Opening of SK and...... IK channels can increase both EDHF and NO-mediated vasodilatation. Therefore, openers of SK and IK channels may have the potential of improving endothelial cell function in cardiovascular disease.......-dependent vasodilatation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarising factor (EDHF), and involves small (SK) and intermediate (IK) conductance Ca(2+)-activated K(+) channels. Therefore, SK and IK channels may be drug targets for the treatment of endothelial dysfunction in cardiovascular...

  4. The juvenile myoclonic epilepsy mutant of the calcium channel β(4) subunit displays normal nuclear targeting in nerve and muscle cells.

    Science.gov (United States)

    Etemad, Solmaz; Campiglio, Marta; Obermair, Gerald J; Flucher, Bernhard E

    2014-01-01

    Voltage-gated calcium channels regulate gene expression by controlling calcium entry through the plasma membrane and by direct interactions of channel fragments and auxiliary β subunits with promoters and the epigenetic machinery in the nucleus. Mutations of the calcium channel β(4) subunit gene (CACNB4) cause juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice. Recently a model has been proposed according to which failed nuclear translocation of the truncated β(4) subunit R482X mutation resulted in altered transcriptional regulation and consequently in neurological disease. Here we examined the nuclear targeting properties of the truncated β(4b(1–481)) subunit in tsA-201 cells, skeletal myotubes, and in hippocampal neurons. Contrary to expectation, nuclear targeting of β(4b(1–481)) was not reduced compared with full-length β(4b) in any one of the three cell systems. These findings oppose an essential role of the β(4) distal C-terminus in nuclear targeting and challenge the idea that the nuclear function of calcium channel β(4) subunits is critically involved in the etiology of epilepsy and ataxia in patients and mouse models with mutations in the CACNB4 gene. PMID:24875574

  5. The juvenile myoclonic epilepsy mutant of the calcium channel β4 subunit displays normal nuclear targeting in nerve and muscle cells

    Science.gov (United States)

    Etemad, Solmaz; Campiglio, Marta; Obermair, Gerald J; Flucher, Bernhard E

    2014-01-01

    Voltage-gated calcium channels regulate gene expression by controlling calcium entry through the plasma membrane and by direct interactions of channel fragments and auxiliary β subunits with promoters and the epigenetic machinery in the nucleus. Mutations of the calcium channel β4 subunit gene (CACNB4) cause juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice. Recently a model has been proposed according to which failed nuclear translocation of the truncated β4 subunit R482X mutation resulted in altered transcriptional regulation and consequently in neurological disease. Here we examined the nuclear targeting properties of the truncated β4b(1–481) subunit in tsA-201 cells, skeletal myotubes, and in hippocampal neurons. Contrary to expectation, nuclear targeting of β4b(1–481) was not reduced compared with full-length β4b in any one of the three cell systems. These findings oppose an essential role of the β4 distal C-terminus in nuclear targeting and challenge the idea that the nuclear function of calcium channel β4 subunits is critically involved in the etiology of epilepsy and ataxia in patients and mouse models with mutations in the CACNB4 gene. PMID:24875574

  6. Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy.

    Science.gov (United States)

    Schrand, Brett; Berezhnoy, Alexey; Brenneman, Randall; Williams, Anthony; Levay, Agata; Kong, Ling-Yuan; Rao, Ganesh; Zhou, Shouhao; Heimberger, Amy B; Gilboa, Eli

    2014-09-01

    Despite the recent successes of using immune modulatory Abs in patients with cancer, autoimmune pathologies resulting from the activation of self-reactive T cells preclude the dose escalations necessary to fully exploit their therapeutic potential. To reduce the observed and expected toxicities associated with immune modulation, here we describe a clinically feasible and broadly applicable approach to limit immune costimulation to the disseminated tumor lesions of the patient, whereby an agonistic 4-1BB oligonucleotide aptamer is targeted to the tumor stroma by conjugation to an aptamer that binds to a broadly expressed stromal product, VEGF. This approach was predicated on the premise that by targeting the costimulatory ligands to products secreted into the tumor stroma, the T cells will be costimulated before their engagement of the MHC-peptide complex on the tumor cell, thereby obviating the need to target the costimulatory ligands to noninternalizing cell surface products expressed on the tumor cells. Underscoring the potency of stroma-targeted costimulation and the broad spectrum of tumors secreting VEGF, in preclinical murine tumor models, systemic administration of the VEGF-targeted 4-1BB aptamer conjugates engendered potent antitumor immunity against multiple unrelated tumors in subcutaneous, postsurgical lung metastasis, methylcholantrene-induced fibrosarcoma, and oncogene-induced autochthonous glioma models, and exhibited a superior therapeutic index compared with nontargeted administration of an agonistic 4-1BB Ab or 4-1BB aptamer.

  7. Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Anti-scuticociliate Chemotherapy.

    Science.gov (United States)

    Mallo, Natalia; Lamas, Jesús; DeFelipe, Ana-Paula; Sueiro, Rosa-Ana; Fontenla, Francisco; Leiro, José-Manuel

    2016-07-01

    Inorganic pyrophosphate (PPi) is a key metabolite in cellular bioenergetics under chronic stress conditions in prokaryotes, protists and plants. Inorganic pyrophosphatases (PPases) are essential enzymes controlling the cellular concentration of PPi and mediating intracellular pH and Ca(2+) homeostasis. We report the effects of the antimalarial drugs chloroquine (CQ) and artemisinin (ART) on the in vitro growth of Philasterides dicentrarchi, a scuticociliate parasite of turbot; we also evaluated the action of these drugs on soluble (sPPases) and vacuolar H+-PPases (H+-PPases). CQ and ART inhibited the in vitro growth of ciliates with IC50 values of respectively 74 ± 9 μM and 80 ± 8 μM. CQ inhibits the H+ translocation (with an IC50 of 13.4 ± 0.2 μM), while ART increased translocation of H+ and acidification. However, both drugs caused a decrease in gene expression of H+-PPases. CQ significantly inhibited the enzymatic activity of sPPases, decreasing the consumption of intracellular PPi. ART inhibited intracellular accumulation of Ca(2+) induced by ATP, indicating an effect on the Ca(2+) -ATPase. The results suggest that CQ and ART deregulate enzymes associated with PPi and Ca(2+) metabolism, altering the intracellular pH homeostasis vital for parasite survival and providing a target for the development of new drugs against scuticociliatosis. PMID:26751587

  8. 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

  9. Nef decreases HIV-1 sensitivity to neutralizing antibodies that target the membrane-proximal external region of TMgp41.

    Directory of Open Access Journals (Sweden)

    Rachel P J Lai

    2011-12-01

    Full Text Available Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs that target the membrane proximal external region (MPER of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly

  10. Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.

    Science.gov (United States)

    Etemad, Solmaz; Obermair, Gerald J; Bindreither, Daniel; Benedetti, Ariane; Stanika, Ruslan; Di Biase, Valentina; Burtscher, Verena; Koschak, Alexandra; Kofler, Reinhard; Geley, Stephan; Wille, Alexandra; Lusser, Alexandra; Flockerzi, Veit; Flucher, Bernhard E

    2014-01-22

    The β subunits of voltage-gated calcium channels regulate surface expression and gating of CaV1 and CaV2 α1 subunits and thus contribute to neuronal excitability, neurotransmitter release, and calcium-induced gene regulation. In addition, certain β subunits are targeted into the nucleus, where they interact directly with the epigenetic machinery. Whereas their involvement in this multitude of functions is reflected by a great molecular heterogeneity of β isoforms derived from four genes and abundant alternative splicing, little is known about the roles of individual β variants in specific neuronal functions. In the present study, an alternatively spliced β4 subunit lacking the variable N terminus (β4e) is identified. It is highly expressed in mouse cerebellum and cultured cerebellar granule cells (CGCs) and modulates P/Q-type calcium currents in tsA201 cells and CaV2.1 surface expression in neurons. Compared with the other two known full-length β4 variants (β4a and β4b), β4e is most abundantly expressed in the distal axon, but lacks nuclear-targeting properties. To determine the importance of nuclear targeting of β4 subunits for transcriptional regulation, we performed whole-genome expression profiling of CGCs from lethargic (β4-null) mice individually reconstituted with β4a, β4b, and β4e. Notably, the number of genes regulated by each β4 splice variant correlated with the rank order of their nuclear-targeting properties (β4b > β4a > β4e). Together, these findings support isoform-specific functions of β4 splice variants in neurons, with β4b playing a dual role in channel modulation and gene regulation, whereas the newly detected β4e variant serves exclusively in calcium-channel-dependent functions. PMID:24453333

  11. Structure and selectivity of novel ω-conotoxins and conus catus that target neuronal calcium channel subtypes

    International Nuclear Information System (INIS)

    Full text: ω-Conotoxins selective for N-type voltage-sensitive calcium channels have promising therapeutic applications in conditions such as pain and neurodegeneration following cerebral ischaemia. Here we report the discovery of novel conotoxins from the piscivorous snail Conus carus using 125I-GVIA binding to rat brain membrane to guide fractionation of crude venom, and cloning to identify the expressed gene products from the venom duct tissue. Four peptides were isolated and named ω-conotoxins CVIA-D (CVIA-D) on the basis of their pharmacology and structure. CVIA-D had varying extents of homology to other ω-conotoxins, with loop 4 of CVID showing significant sequence divergence. From binding studies in rat brain, the rank order of potency to displace 125I-GVIA from N-type calcium channel (CVID = GVIA=MVIIA > CVIA > CVIC = CVIB > MVIIC) was reversed at the P/Q-type calcium channel (defined by 125I-MVIIC). CVID was most selective for N-type vs P/Q-type calcium channels, being 1.5 to 2-orders of magnitude more selective than GVIA and MVIIA, respectively. CVIA-D each inhibited neurally-evoked contractions in rat vas deferens in a reversible manner, with potencies that correlated with their ability to inhibit 125I-GVIA binding. Compared with GVIA, CVID was a more potent inhibitor of central N-type calcium channels (α1,B-dexpressed in Xenopus oocytes) than of peripheral N-type calcium channels (rat vas deferens). 1H NMR studies revealed that CVID adopts a similar 3D fold to other ω-conotoxins. However, in contrast to GVIA, MVIIA or MVIIC, CVID has two hydrogen bonds that hold loops 2 and 4 proximal, a factor that may contribute to the enhanced ability of CVID to discriminate among neuronal calcium channels

  12. 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.

  13. 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.

  14. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.

    Directory of Open Access Journals (Sweden)

    Maria Consolata Miletta

    Full Text Available Butyrate is a short-chain fatty acid (SCFA closely related to the ketone body ß-hydroxybutyrate (BHB, which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR, GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

  15. 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.

  16. Calcium - urine

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003603.htm Calcium - urine To use the sharing features on this ... enable JavaScript. This test measures the amount of calcium in urine. All cells need calcium in order ...

  17. Calcium supplements

    Science.gov (United States)

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

  18. 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.

  19. 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.

  20. Measurement of proton induced thick target γ-ray yields on B, N, Na, Al and Si from 2.5 to 4.1 MeV

    Science.gov (United States)

    Chiari, M.; Ferraccioli, G.; Melon, B.; Nannini, A.; Perego, A.; Salvestrini, L.; Lagoyannis, A.; Preketes-Sigalas, K.

    2016-01-01

    Thick target yields for proton induced γ-ray emission (PIGE) on low-Z nuclei, namely B, N, Na, Al and Si, were measured for proton energies from 2.5 to 4.1 MeV and emission angles of 0°, 45° and 90°, at the 3 MV Tandetron laboratory of INFN-LABEC in Florence. The studied reactions were: 10B(p,α‧γ)7Be (Eγ = 429 keV), 10B(p,p‧γ)10B (Eγ = 718 keV) and 11B(p,p‧γ)11B (Eγ = 2125 keV) for boron; 14N(p,p‧γ)14N (Eγ = 2313 keV) for nitrogen; 23Na(p,p‧γ)23Na (Eγ = 441 and 1636 keV) and 23Na(p,α‧γ)20Ne (Eγ = 1634 keV) for sodium; 27Al(p,p‧γ)27Al (Eγ = 844 and 1014 keV) and 27Al(p,α‧γ)24Mg (Eγ = 1369 keV) for aluminum; 28Si(p,p‧γ)28Si (Eγ = 1779 keV) and 29Si(p,p‧γ)29Si (Eγ = 1273 keV) for silicon. The PIGE thick target yields have been measured with an overall uncertainty typically better than 10%. The use of the measured thick target yield to benchmark and validate experimental cross sections available in the literature is demonstrated.

  1. Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.

    Science.gov (United States)

    Di Scala, Coralie; Yahi, Nouara; Flores, Alessandra; Boutemeur, Sonia; Kourdougli, Nazim; Chahinian, Henri; Fantini, Jacques

    2016-02-01

    Growing evidence supports a role for brain gangliosides in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's. Recently we deciphered the ganglioside-recognition code controlling specific ganglioside binding to Alzheimer's β-amyloid (Aβ1-42) peptide and Parkinson's disease-associated protein α-synuclein. Cracking this code allowed us to engineer a short chimeric Aβ/α-synuclein peptide that recognizes all brain gangliosides. Here we show that ganglioside-deprived neural cells do no longer sustain the formation of zinc-sensitive amyloid pore channels induced by either Aβ1-42 or α-synuclein, as assessed by single-cell Ca(2+) fluorescence microscopy. Thus, amyloid channel formation, now considered a key step in neurodegeneration, is a ganglioside-dependent process. Nanomolar concentrations of chimeric peptide competitively inhibited amyloid pore formation induced by Aβ1-42 or α-synuclein in cultured neural cells. Moreover, this peptide abrogated the intracellular calcium increases induced by Parkinson's-associated mutant forms of α-synuclein (A30P, E46K and A53T). The chimeric peptide also prevented the deleterious effects of Aβ1-42 on synaptic vesicle trafficking and decreased the Aβ1-42-induced impairment of spontaneous activity in rat hippocampal slices. Taken together, these data show that the chimeric peptide has broad anti-amyloid pore activity, suggesting that a common therapeutic strategy based on the prevention of amyloid-ganglioside interactions is a reachable goal for both Alzheimer's and Parkinson's diseases. PMID:26655601

  2. 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.

  3. Calcium Influx of Mast Cells Is Inhibited by Aptamers Targeting the First Extracellular Domain of Orai1

    Science.gov (United States)

    Sun, Renshan; Yang, Yongqiang; Ran, Xinze; Yang, Tao

    2016-01-01

    Using the systematic evolution of ligands by exponential enrichment (SELEX) method, we identified oligonucleotides that bind to the first extracellular domain of the Orai1 protein with high affinities and high specificities. These ligands were isolated from a random single-strand DNA (ssDNA) library with 40 randomized sequence positions, using synthesized peptides with amino acid sequences identical to the first extracellular domain of the Orai1 protein as the targets for SELEX selection. Seven aptamers were obtained after 12 rounds of SELEX. An enzyme-linked oligonucleotide assay (ELONA) was performed to determine the affinities of the aptamers. Aptamer Y1 had the highest affinity (Kd = 1.72×10−8 mol/L) and was selected for functional experiments in mast cells. Using LAD2 cells with the human high-affinity IgE receptor and Ca2+ release activation channel (CRAC), we demonstrated that Aptamer Y1 blocked IgE-mediated β-hexosaminidase release from cells triggered by biotin-IgE and streptavidin. A specific binding assay showed that Aptamer Y1 not only bound the Orai1 peptide specifically but also that the Orai1 peptide did not bind significantly to other random oligonucleotide molecules. Furthermore, Aptamer Y1 regulation of intracellular Ca2+ mobilization was investigated by probing intracellular Ca2+ with a Fluo-4-AM fluorescent probe. We found that Aptamer Y1 inhibits Ca2+ influx into antigen-activated mast cells. These results indicate that the target of Aptamer Y1 in the degranulation pathway is upstream of Ca2+ influx. Therefore, these oligonucleotide agents represent a novel class of CRAC inhibitors that may be useful in the fight against allergic diseases. PMID:27390850

  4. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    Directory of Open Access Journals (Sweden)

    Trond eUlven

    2012-10-01

    Full Text Available The deorphanization of the free fatty acid (FFA receptors FFA1 (GPR40, FFA2 (GPR43, FFA3 (GPR41, GPR84 and GPR120 made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane receptors free fatty acid receptor 2 (FFA2 and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD. Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and regulation of appetite. More research is however required to clarify potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that the situation may soon improve, and that proper tool compounds will enable studies critical to validate the receptors as new drug targets.

  5. Diagnostic Phase of Calcium Scoring Scan Applied as the Center of Acquisition Window of Coronary Computed Tomography Angiography Improves Image Quality in Minimal Acquisition Window Scan (Target CTA Mode) Using the Second Generation 320-Row CT

    OpenAIRE

    Eriko Maeda; Kodai Yamamoto; Shigeaki Kanno; Kenji Ino; Nobuo Tomizawa; Masaaki Akahane; Rumiko Torigoe; Kuni Ohtomo

    2016-01-01

    Objective. To compare the image quality of coronary computed tomography angiography (CCTA) acquired under two conditions: 75% fixed as the acquisition window center (Group 75%) and the diagnostic phase for calcium scoring scan as the center (CS; Group CS). Methods. 320-row cardiac CT with a minimal acquisition window (scanned using “Target CTA” mode) was performed on 81 patients. In Group 75% (n = 40), CS was obtained and reconstructed at 75% and the center of the CCTA acquisition window was ...

  6. 4-(1-Ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide – A new pleiotropic HDAC inhibitor targeting cancer cell signalling and cytoskeletal organisation

    Energy Technology Data Exchange (ETDEWEB)

    Mahal, Katharina, E-mail: katharina.mahal@uni-bayreuth.de [Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany); Kahlen, Philip, E-mail: philip.kahlen@uni-bayreuth.de [Department of Genetics, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany); Biersack, Bernhard, E-mail: bernhard.biersack@yahoo.com [Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany); Schobert, Rainer, E-mail: rainer.schobert@uni-bayreuth.de [Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany)

    2015-08-15

    Histone deacetylases (HDAC) which play a crucial role in cancer cell proliferation are promising drug targets. However, HDAC inhibitors (HDACi) modelled on natural hydroxamic acids such as trichostatin A frequently lead to resistance or even an increased agressiveness of tumours. As a workaround we developed 4-(1-ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide (etacrox), a hydroxamic acid that combines HDAC inhibition with synergistic effects of the 4,5-diarylimidazole residue. Etacrox proved highly cytotoxic against a panel of metastatic and resistant cancer cell lines while showing greater specificity for cancer over non-malignant cells when compared to the approved HDACi vorinostat. Like the latter, etacrox and the closely related imidazoles bimacroxam and animacroxam acted as pan-HDACi yet showed some specificity for HDAC6. Akt signalling and interference with nuclear beta-catenin localisation were elicited by etacrox at lower concentrations when compared to vorinostat. Moreover, etacrox disrupted the microtubule and focal adhesion dynamics of cancer cells and inhibited the proteolytic activity of prometastatic and proangiogenic matrix metalloproteinases. As a consequence, etacrox acted strongly antimigratory and antiinvasive against various cancer cell lines in three-dimensional transwell invasion assays and also antiangiogenic in vivo with respect to blood vessel formation in the chorioallantoic membrane assay. These pleiotropic effects and its water-solubility and tolerance by mice render etacrox a promising new HDACi candidate. - Graphical abstract: A novel histone deacetylase inhibitor with pleiotropic anticancer effects. - Highlights: • Etacrox is a new HDACi with cytotoxic, antiangiogenic and antiinvasive activity. • Etacrox causes aberrant cancer cell signalling and cytoskeletal reorganisation. • Pro-metastatic and angiogenic matrix metalloproteinases are inhibited by etacrox. • Etacrox impairs blood vessel maturation in vivo and cancer cell

  7. Calcium Carbonate

    Science.gov (United States)

    ... before being swallowed; do not swallow them whole. Drink a full glass of water after taking either the regular or chewable tablets or capsules. Some liquid forms of calcium carbonate must be shaken well before use.Do not ...

  8. Calcium Calculator

    Science.gov (United States)

    ... Latvia - Lebanon - Libya - Lithuania - Luxembourg - Macedonia, Republic of - Malaysia - Malta - Mexico - Moldova - Morocco - Netherlands - New Zealand - Nigeria - ... and Statistics Popular content Calcium content of common foods What is Osteoporosis? The Board Introduction to Bone ...

  9. 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

  10. 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. PMID:26478017

  11. Design, synthesis and activity assessment of aryl-substituent benzyl acid targeting HIV gp41%以艾滋病病毒gp41为靶点的芳基苯甲酸类化合物的设计、合成及活性评价

    Institute of Scientific and Technical Information of China (English)

    王海波; 陈之朋; 裘佳寅; 余小玲; 谢扬; 刘叔文

    2013-01-01

    目的 以艾滋病病毒(HIV)gp41为作用靶点,设计合成了12个含芳基取代的苯甲酸类化合物,并对其进行抗HIV活性测试.方法 以卤代苯甲酸或间羧基苯硼酸为原料,通过Suzuki-Miyaura偶连反应及Knoevenagel缩合反应,引入含取代基的芳环及芳杂环.ELISA法检测其抑制HIV gp41六螺旋束形成的活性.荧光素酶法检测化合物抗HIV活性.结果 化合物结构经NMR、MS得到确认,其中5个化合物(7b、7c、7d、7e、7g)具有抑制HIV gp41六螺旋束形成的活性,其中7d活性最强.该化合物能抑制HIV-1 SF33病毒株的复制,其IC50为20 μmol/L.结论 合成的芳基苯甲酸类化合物7d能通过抑制HIV gp41六螺旋束结构的形成来抑制HIV的复制.%Objective To synthesize novel aryl-substituent benzyl acid compounds targeting HIV gp41 and characterize their anti-HIV activities. Methods Twelve analogues of aryl-substituent benzyl acid were designed and synthesized by Suzuki-Miyaura cross-coupling and Knoevenagel condensation reactions using halo-benzyl acid or 3-carboxybenzeneboronic acid as the raw material. The inhibitory activities of these compounds on gp41 six-helix bundle formation were tested by ELISA, and their anti-HIV activities were determined using a luciferase assay. Results The structures of the compounds were characterized by nuclear magnetic resonance and mass spectrography. Among the 12 compounds, 5 (7b, 7c, 7d, 7e, and 7g) could inhibit the gp41 six-helix bundle formation, and 7d showed the most potent effect, and could also inhibit the replication of HIV-1 SF33 strain with an IC50 of 20 μmol/L. Conclusion The synthesized aryl-substituent benzyl acid compound 7d could inhibit HIV replication by blocking the gp41 six-helix bundle formation.

  12. Effect of a Chinese herbal prescription on femur calcium deposition in rats under simulated weightlessness: by using 41 Ca tracing-accelerator mass spectrometry analysis%中药干预模拟失重大鼠股骨外源钙沉积研究

    Institute of Scientific and Technical Information of China (English)

    胡素敏; 周鹏; 姜山; 何明; 傅骞; 杨佳佳; 高学敏

    2009-01-01

    To study the effect of a Chinese herbal prescription on external calcium deposition to weight-bearing bone in simula-ted weightlessness rats. Method:Twenty-one male Wistar rats were divided into 3 groups: control group, tail suspension group, tail suspension with Chinese medicine group which takes a Chinese herbal prescription extract ( containing Radix Rehmanniae Preparata,Radix Acanthopanacis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by intragastric administration. After 1 week adaption, there start off 3 weeks simulated weightlessness by tail suspension. At the eleventh day of simu-lated weightlessness , every rat was given one equal dose of ~(41)Ca tracer by intragnstric administration. Right femurs were separated as experiment over, and the ratio of ~(41)Ca to ~(40) Ca ( ~(41) Ca / ~(40) Ca) was measured by accelerator mass spectrometry ( AMS ) , while total femur calcium was measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Femur ~(41) Ca deposition amount (DA) and femur ~(41) Ca deposition ratio (DR) were calculated. Result:The results showed that compared with control group, ~(41) Ca / ~(40) Ca de-creased significantly (P <0.001 ) in tail suspension group, while in tail suspension with Chinese medicine group, it significantly in-creased ( P < 0.05 ). DA and DR were both decreased significantly ( P < 0.001 ) in tail suspension group, but no significant change in tail suspension with Chinese medicine group as compared with control group. Compared with tail suspension group, DA and DR in-creased significantly (P < 0. 001 ) in tail suspension with Chinese medicine group. Conclusion:Simulated weightlessness by tail sus-pension can cause decreased deposition of external calcium to weight-bearing bone, and the Chinese herbal prescription in this trial is effective to prevent the decrease. Moreover, multiple mechanisms may contribute to weightlessness induced osteoporosis, besides

  13. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    OpenAIRE

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors...

  14. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    OpenAIRE

    Trond eUlven

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84 and GPR120 made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane receptors free fatty...

  15. Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats.

    Science.gov (United States)

    Shevtsov, M A; Parr, M A; Ryzhov, V A; Zemtsova, E G; Arbenin, A Yu; Ponomareva, A N; Smirnov, V M; Multhoff, G

    2016-01-01

    Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues. PMID:27386761

  16. 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. ...

  17. Calcium carbonate overdose

    Science.gov (United States)

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

  18. Get Enough Calcium

    Science.gov (United States)

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

  19. Human cytomegalovirus microRNA miR-US4-1 inhibits CD8+ T cell response by targeting the aminopeptidase ERAP1

    OpenAIRE

    Kim, Sungchul; Lee, Sanghyun; Shin, Jinwook; Kim, Youngkyun; Evnouchidou, Irini; Kim, Donghyun; Kim, Young-Kook; Kim, Young-Eui; Ahn, Jin-Hyun; Riddell, Stanley R; Stratikos, Efstratios; Kim, V. Narry; Ahn, Kwangseog

    2011-01-01

    The major histocompatibility complex (MHC) class I molecules present peptides on the cell surface by CD8+ T cells, which is critical for killing of virally infected or transformed cells. Precursors of MHC class I-presented peptides are trimmed to mature epitopes by endoplasmic reticulum aminopeptidase 1 (ERAP1). The US2-US11 genomic region of human cytomegalovirus (HCMV) is dispensable for viral replication and harbors 3 microRNAs (miRNAs). We show here the HCMV miR-US4-1 specifically down-re...

  20. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    DEFF Research Database (Denmark)

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber...... produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence...

  1. Protein phosphatase 2A is regulated by PKCα-dependent phosphorylation of its targeting subunit B56α at Ser41

    DEFF Research Database (Denmark)

    Kirchhefer, Uwe; Heinick, Alexander; König, Simone;

    2014-01-01

    Protein phosphatase 2A (PP2A) is a family of multifunctional serine/threonine phosphatases consisting of a catalytic C, a structural A, and a regulatory B subunit. The substrate and therefore the functional specificity of PP2A are determined by the assembly of the enzyme complex with the appropri......Protein phosphatase 2A (PP2A) is a family of multifunctional serine/threonine phosphatases consisting of a catalytic C, a structural A, and a regulatory B subunit. The substrate and therefore the functional specificity of PP2A are determined by the assembly of the enzyme complex...... with the appropriate regulatory B subunit families, namely B55, B56, PR72 or PR93/PR110. It has been suggested that additional levels of regulating PP2A function may result from the phosphorylation of B56 isoforms. In this study, we identified a novel phosphorylation site at Ser41 of B56α. This phosphoamino acid...... inhibition was markedly increased by PKCα phosphorylation. PP2A activity was also reduced in HEK293 cells transfected with a B56α mutant, where serine-41 was replaced by aspartic acid, which mimics phosphorylation. More evidence for a functional role of PKCα-dependent phosphorylation of B56α was derived from...

  2. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

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

    1984-01-01

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

  3. 37 CFR 41.41 - Reply brief.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Reply brief. 41.41 Section 41... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Ex Parte Appeals § 41.41 Reply brief... file a reply brief to an examiner's answer within two months from the date of the examiner's answer....

  4. 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.

  5. 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. PMID:27472825

  6. 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...

  7. Study of events in absence of target/projectile fragments in interactions of nuclei with emulsion at 4.5 and 4.1 AGeV/c

    Energy Technology Data Exchange (ETDEWEB)

    Rahim, Magda A., E-mail: dr.magda2006@hotmail.co [Physics Department, Faculty of Science, Sana' s University (Yemen); Fakhraddin, S., E-mail: sakinafa1@hotmail.co [Physics Department, Faculty of Science, Sana' s University (Yemen)

    2009-12-01

    This work is devoted to study two types of events. Type (a): events with no target fragments, the incident nucleus is dissociated in emulsion accompanied with the pions. Type (b): events with no projectile fragments, total break-up of the two colliding nuclei into relatively small fragments. Case of central collisions. The main characteristics of these reactions, that is multiplicity distributions of projectile and target fragments have been studied and compared for interactions of {sup 4}He, {sup 12}C, {sup 16}O, {sup 22}Ne and {sup 28}Si nuclei with emulsion at almost same momentum. The dependence of the mean multiplicity of different PFs on the projectile mass is investigated. Also the percentage of occurrence of these two events for different projectiles are analyzed.

  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 source (image)

    Science.gov (United States)

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

  10. Calcium hydroxide poisoning

    Science.gov (United States)

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

  11. Calcium and bones (image)

    Science.gov (United States)

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

  12. Coronary Calcium Scan

    Science.gov (United States)

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

  13. Calcium Pyrophosphate Deposition (CPPD)

    Science.gov (United States)

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

  14. 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.

  15. 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.

  16. 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.

  17. Calcium and Vitamin D

    Science.gov (United States)

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

  18. Calcium channel blocker overdose

    Science.gov (United States)

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

  19. Fenoprofen calcium overdose

    Science.gov (United States)

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

  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 en cardioplegie

    NARCIS (Netherlands)

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

    1985-01-01

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

  2. Calcium-Dependent Physiologic and Pathologic Stimulus-Metabolic Response Coupling in Hepatocytes

    OpenAIRE

    Gaspers, Lawrence D.; Mémin, Elisabeth; Thomas, Andrew P.

    2012-01-01

    A recurrent paradigm in calcium signaling is the coordination of the target response of the calcium signal with activation of metabolic energy production to support that response. This occurs in many tissues, including cardiac and skeletal muscle where contractile activity and ATP production are coordinately regulated by the frequency and amplitude of calcium transients, endocrine and exocrine cells that use calcium to drive the secretory process, and hepatocytes where the downstream targets ...

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

    Directory of Open Access Journals (Sweden)

    Zhi Pan

    2014-02-01

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

  5. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

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

  6. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  7. Revised Safety Instruction 41 (IS41 REV.)

    CERN Document Server

    SC Secretariat

    2005-01-01

    Please note that the Revised Safety Instruction No. 41 (IS41 REV.), entitled 'The use of plastic and other non-metallic materials at CERN with respect to fire safety and radiation resistance' is available on the web at the following url: https://edms.cern.ch/document/335806/LAST_RELEASED Paper copies can also be obtained from the SC Unit Secretariat, e-mail: sc.secretariat@cern.ch SC Secretariat

  8. Measurements of intracellular calcium

    International Nuclear Information System (INIS)

    Intracellular calcium concentration ([Ca2+]i) has been measured in cultured cells by using Fura-2 load cells and a computer-controlled Perkin Elmer LS-5B spectrofluorometer. Increased [Ca2+]i in cells exposed to extracellular bilirubin was observed both with and without extracellular calcium. However, the increase was considerable larger with extracellular calcium. The enhancement of [Ca2+]i became smaller with decreasing bilirubin/BSA (bovine serum albumine) ratio. 5 refs., 5 figs

  9. Development and validation of fluorescence-based and automated patch clamp-based functional assays for the inward rectifier potassium channel Kir4.1.

    Science.gov (United States)

    Raphemot, Rene; Kadakia, Rishin J; Olsen, Michelle L; Banerjee, Sreedatta; Days, Emily; Smith, Stephen S; Weaver, C David; Denton, Jerod S

    2013-01-01

    The inward rectifier potassium (Kir) channel Kir4.1 plays essential roles in modulation of neurotransmission and renal sodium transport and may represent a novel drug target for temporal lobe epilepsy and hypertension. The molecular pharmacology of Kir4.1 is limited to neurological drugs, such as fluoxetine (Prozac(©)), exhibiting weak and nonspecific activity toward the channel. The development of potent and selective small-molecule probes would provide critically needed tools for exploring the integrative physiology and therapeutic potential of Kir4.1. A fluorescence-based thallium (Tl(+)) flux assay that utilizes a tetracycline-inducible T-Rex-HEK293-Kir4.1 cell line to enable high-throughput screening (HTS) of small-molecule libraries was developed. The assay is dimethyl sulfoxide tolerant and exhibits robust screening statistics (Z'=0.75±0.06). A pilot screen of 3,655 small molecules and lipids revealed 16 Kir4.1 inhibitors (0.4% hit rate). 3,3-Diphenyl-N-(1-phenylethyl)propan-1-amine, termed VU717, inhibits Kir4.1-mediated thallium flux with an IC50 of ∼6 μM. An automated patch clamp assay using the IonFlux HT workbench was developed to facilitate compound characterization. Leak-subtracted ensemble "loose patch" recordings revealed robust tetracycline-inducible and Kir4.1 currents that were inhibited by fluoxetine (IC50=10 μM), VU717 (IC50=6 μM), and structurally related calcium channel blocker prenylamine (IC50=6 μM). Finally, we demonstrate that VU717 inhibits Kir4.1 channel activity in cultured rat astrocytes, providing proof-of-concept that the Tl(+) flux and IonFlux HT assays can enable the discovery of antagonists that are active against native Kir4.1 channels. PMID:24266659

  10. 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

  11. 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.

  12. 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.

  13. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

    2016-01-01

    Molar conductivity of saturated aqueous solutions of calcium d-saccharate, used as a stabilizer of beverages fortified with calcium d-gluconate, increases strongly upon dilution, indicating complex formation between calcium and d-saccharate ions, for which, at 25 °C, Kassoc = 1032 ± 80, ΔHassoc......° = -34 ± 6 kJ mol-1, and ΔSassoc° = -55 ± 9 J mol-1 K-1, were determined electrochemically. Calcium d-saccharate is sparingly soluble, with a solubility product, Ksp, of (6.17 ± 0.32) × 10-7 at 25 °C, only moderately increasing with the temperature: ΔHsol° = 48 ± 2 kJ mol-1, and ΔSassoc° = 42 ± 7 J mol-1...... K-1. Equilibria in supersaturated solutions of calcium d-saccharate seem only to adjust slowly, as seen from calcium activity measurements in calcium d-saccharate solutions made supersaturated by cooling. Solutions formed by isothermal dissolution of calcium d-gluconate in aqueous potassium d...

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

    OpenAIRE

    Zhi Pan; Andrew Avila; Lauren Gollahon

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and...

  15. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free calciu

  16. THE GENERATION,EVOLUTION AND PHYSIOLOGICAL RESPONSES OF INTRACELLUAR CALCIUM OSCILLATIONS AND WAVES

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-min

    2004-01-01

    The Atri intracellular calcium oscillations model was extended, and two new models were established. Furthermore, a unified model of the protein phosphorylation driven by cytosolic calcium oscillations was constructed. The numerical results obtained verified related experimental conclusions. And the analytical expressions of intracellular calcium spiral and target waves in the Xenopus laevis oocyte were obtained, resulting in velocity and waveform of calcium solitary pulse wave were found.

  17. Should we prescribe calcium supplements for osteoporosis prevention?

    Science.gov (United States)

    Reid, Ian R

    2014-02-01

    Advocacy for the use of calcium supplements arose at a time when there were no other effective interventions for the prevention of osteoporosis. Their promotion was based on the belief that increasing calcium intake would increase bone formation. Our current understandings of the biology of bone suggest that this does not occur, though calcium does act as a weak antiresorptive. Thus, it slows postmenopausal bone loss but, despite this, recent meta-analyses suggest no significant prevention of fractures. In sum, there is little substantive evidence of benefit to bone health from the use of calcium supplements. Against this needs to be balanced the likelihood that calcium supplement use increases cardiovascular events, kidney stones, gastrointestinal symptoms, and admissions to hospital with acute gastrointestinal problems. Thus, the balance of risk and benefit seems to be consistently negative. As a result, current recommendations are to obtain calcium from the diet in preference to supplements. Dietary calcium intake has not been associated with the adverse effects associated with supplements, probably because calcium is provided in smaller boluses, which are absorbed more slowly since they come together with quantities of protein and fat, resulting in a slower gastric transit time. These findings suggest that calcium supplements have little role to play in the modern therapeutics of osteoporosis, which is based around the targeting of safe and effective anti-resorptive drugs to individuals demonstrated to be at increased risk of future fractures. PMID:24707464

  18. Calcium intake and prostate cancer among African Americans: effect modification by vitamin D receptor calcium absorption genotype.

    Science.gov (United States)

    Rowland, Glovioell W; Schwartz, Gary G; John, Esther M; Ingles, Sue Ann

    2012-01-01

    High dietary intake of calcium has been classified as a probable cause of prostate cancer, although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African-American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African-American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene interactions by conditional logistic regression. Compared with men in the lowest quartile of calcium intake, men in the highest quartile had an approximately twofold increased risk of localized and advanced prostate cancer (odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.40, 3.46), with a significant dose-response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR = 0.41, 95% CI = 0.19, 0.90). The gene-calcium interaction was statistically significant (p = 0.03). Among men with calcium intake below the median (680 mg/day), carriers of the G allele had an approximately 50% decreased risk compared with men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium.

  19. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  20. 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 inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport...

  1. The Effect of Calcium on the Binding of Calmodulin to Calcium/Calmodulin Protein Kinase II.

    Science.gov (United States)

    Porta, Angela R.

    2000-01-01

    Introduces a follow-up laboratory experiment demonstrating the formation change when calcium binds to calmodulin. This conformation change allows this complex to bind to a target protein. Presents the necessary information to conduct the experiment and discusses the results. (YDS)

  2. Strength of the $E_{\\text{p}}$=1.842 MeV resonance in the $^{40}$Ca(p,$\\gamma$)$^{41}$Sc reaction revisited

    CERN Document Server

    Schmidt, Konrad; Anders, Michael; Bemmerer, Daniel; Caciolli, Antonio; Dietz, Mirco; Elekes, Zoltán; Junghans, Arnd R; Menzel, Marie-Luise; Schwengner, Ronald; Wagner, Andreas; Zuber, Kai

    2014-01-01

    The strength of the $E_{\\rm p} = 1.842$ MeV resonance in the $^{40}$Ca(p,$\\gamma$)$^{41}$Sc reaction is determined with two different methods: First, by an absolute strength measurement using calcium hydroxide targets, and second, relative to the well-determined strength of the resonance triplet at $E_\\alpha$ = 4.5 MeV in the $^{40}$Ca($\\alpha$,$\\gamma$)$^{44}$Ti reaction. The present new value of $\\omega\\gamma=(0.192\\pm0.017)$ eV is 37% (equivalent to $3.5\\sigma$) higher than the evaluated literature value. In addition, the ratio of the strengths of the 1.842 MeV $^{40}$Ca(p,$\\gamma$)$^{41}$Sc and 4.5 MeV $^{40}$Ca($\\alpha$,$\\gamma$)$^{44}$Ti resonances has been determined to be $0.0229\\pm0.0018$. The newly corrected strength of the 1.842-MeV resonance can be used in the future as a normalization point for experiments with calcium targets.

  3. [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

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

    Science.gov (United States)

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

  5. A sensor for calcium uptake

    OpenAIRE

    Collins, Sean; Meyer, Tobias

    2010-01-01

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

  6. Children's Bone Health and Calcium

    Science.gov (United States)

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

  7. 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

  8. 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...

  9. 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

  10. 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.

  11. Concurrent Imaging of Synaptic Vesicle Recycling and Calcium Dynamics

    Science.gov (United States)

    Li, Haiyan; Foss, Sarah M.; Dobryy, Yuriy L.; Park, C. Kevin; Hires, Samuel Andrew; Shaner, Nathan C.; Tsien, Roger Y.; Osborne, Leslie C.; Voglmaier, Susan M.

    2011-01-01

    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. Reacidification 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. PMID:22065946

  12. Interaction of H2S with Calcium Permeable Channels and Transporters

    Directory of Open Access Journals (Sweden)

    Weihua Zhang

    2015-01-01

    Full Text Available A growing amount of evidence has suggested that hydrogen sulfide (H2S, as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC, T-type calcium channels (TTCC, sodium/calcium exchangers (NCX, transient receptor potential (TRP channels, β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.

  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. Expert review on coronary calcium

    Directory of Open Access Journals (Sweden)

    Matthew J Budoff

    2008-04-01

    Full Text Available Matthew J Budoff, Khawar M GulDivision of Cardiology, Saint John’s Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California, USAAbstract: While there is no doubt that high risk patients (those with >20% ten year risk of future cardiovascular event need more aggressive preventive therapy, a majority of cardiovascular events occur in individuals at intermediate risk (10%–20% ten year risk. Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. It has been suggested that traditional risk assessment may be refined with the selective use of coronary artery calcium (CAC or other methods of subclinical atherosclerosis measurement. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CAC for the presence of coronary artery disease but a lower specificity for obstructive CAD depending on the magnitude of the CAC. Several large clinical trials found clear, incremental predictive value of CAC over the Framingham risk score when used in asymptomatic patients. Based on multiple observational studies, patients with increased plaque burdens (increased CAC are approximately ten times more likely to suffer a cardiac event over the next 3–5 years. Coronary calcium scores have outperformed conventional risk factors, highly sensitive C-reactive protein (CRP and carotid intima media thickness (IMT as a predictor of cardiovascular events. The relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of atherosclerotic vascular disease. Current data suggests intermediate risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is

  15. 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

  16. 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.

  17. The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

    OpenAIRE

    Gerald W Zamponi; Striessnig, Joerg; Koschak, Alexandra; Dolphin, Annette C.

    2015-01-01

    Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type ...

  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. 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...

  20. 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...

  1. 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.

  2. Calcium Messenger Heterogeneity: A Possible Signal for Spike-Timing-Dependent Plasticity

    Directory of Open Access Journals (Sweden)

    Stefan Mihalas

    2011-01-01

    Full Text Available Calcium concentrations as well as time courses have been used to model the signaling cascades leading to changes in the strength of synaptic connections. Previous models consider the dendritic spines as uniform compartments regarding calcium signaling. However calcium concentrations can vary drastically on distances much smaller than typical spine sizes, and often downstream targets of calcium signals are often found exactly in these calcium nanodomains. Even though most downstream targets are activated by calcium via calmodulin, which is a diffusive molecule, the capacity of calmodulin to bind to its targets even when it is not fully loaded with calcium, allows its downstream cascade to be highly local. In this study, a model is proposed which uses the heterogeneity of calcium concentrations as a signal for spike-timing-dependent plasticity. The model is minimalistic and includes three sources of calcium in spines: NMDA receptors (NMDARs and voltage gated calcium channels (VGCCs and IP3 receptors (IP3Rs. It is based on the biochemical cascades and assumption of spatial locations of four calcium-dependent enzymes: calcium/calmodulin-dependent protein kinase II (CaMKII located near NMDARs, calcineurin (CaN located near VGCCs, cyclic nucleotide phosphodiesterase (PDE located near IP3Rs or NMDARs and adenylyl cyclase (AC, located between VDCCs and NMDARs. To quantify the changes in synaptic weights the model also includes a simple description of AMPA receptors insertion in the membrane and docking to the postsynaptic density (PSD. Two parameters of the model are tuned such that weight changes produced by either pre or postsynaptic firing alone are minimal. The model reproduces the typical shape of spike timing dependent plasticity (STDP for spike doublets. If PDE is located near IP3Rs, the behavior for spike triplets is consistent with that observed in hippocampal cell culture; if near NMDAR, the behavior is similar to that observed in cortical L2

  3. Calcium-dependent activation of Pyk2 by hypoxia.

    Science.gov (United States)

    Beitner-Johnson, Dana; Ferguson, Tsuneo; Rust, Randy T; Kobayashi, Shuichi; Millhorn, David E

    2002-02-01

    The Pyk2 tyrosine kinase can be activated by both calcium-dependent and calcium-independent mechanisms. Exposure to moderate hypoxia (5% O(2)) induced a rapid and persistent tyrosine phosphorylation of Pyk2 in pheochromocytoma (PC12) cells. Hypoxia and KCl-depolarization increased the phosphotyrosine content of Pyk2 by twofold and fourfold, respectively. Both of these effects were abolished in the absence of extracellular calcium. There was a modest activation of MAPK in parallel with the onset of Pyk2 phosphorylation. However, there was no detectable activation of either JNK or c-src, two other known downstream targets of Pyk2. Thus, exposure to hypoxia may selectively target specific subsets of Pyk2 signalling pathways. PMID:11781137

  4. 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.

  5. 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.

  6. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid

    2013-07-01

    Full Text Available Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%–31% increase in risk of myocardial infarction, and a 12%–20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.

  7. 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......

  8. 21 CFR 573.240 - Calcium periodate.

    Science.gov (United States)

    2010-04-01

    ... with calcium hydroxide or calcium oxide to form a substance consisting of not less than 60 percent by... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium periodate. 573.240 Section 573.240 Food... Additive Listing § 573.240 Calcium periodate. The food additive calcium periodate may be safely used...

  9. 21 CFR 573.260 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium silicate. 573.260 Section 573.260 Food and... Listing § 573.260 Calcium silicate. Calcium silicate, including synthetic calcium silicate, may be safely used as an anticaking agent in animal feed, provided that the amount of calcium silicate does...

  10. Calcium isotope analysis by mass spectrometry.

    Science.gov (United States)

    Boulyga, Sergei F

    2010-01-01

    The variations in the isotopic composition of calcium caused by fractionation in heterogeneous systems and by nuclear reactions can provide insight into numerous biological, geological, and cosmic processes, and therefore isotopic analysis finds a wide spectrum of applications in cosmo- and geochemistry, paleoclimatic, nutritional, and biomedical studies. The measurement of calcium isotopic abundances in natural samples has challenged the analysts for more than three decades. Practically all Ca isotopes suffer from significant isobaric interferences, whereas low-abundant isotopes can be particularly affected by neighboring major isotopes. The extent of natural variations of stable isotopes appears to be relatively limited, and highly precise techniques are required to resolve isotopic effects. Isotope fractionation during sample preparation and measurements and instrumental mass bias can significantly exceed small isotope abundance variations in samples, which have to be investigated. Not surprisingly, a TIMS procedure developed by Russell et al. (Russell et al., 1978. Geochim Cosmochim Acta 42: 1075-1090) for Ca isotope measurements was considered as revolutionary for isotopic measurements in general, and that approach is used nowadays (with small modifications) for practically all isotopic systems and with different mass spectrometric techniques. Nevertheless, despite several decades of calcium research and corresponding development of mass spectrometers, the available precision and accuracy is still not always sufficient to achieve the challenging goals. The present article discusses figures of merits of presently used analytical methods and instrumentation, and attempts to critically assess their limitations. In Sections 2 and 3, mass spectrometric methods applied to precise stable isotope analysis and to the determination of (41)Ca are described. Section 4 contains a short summary of selected applications, and includes tracer experiments and the potential use

  11. A Convenient Approach to Heterocyclic Building Blocks: Synthesis of Novel Ring Systems Containing a [5,6]Pyrano[2,3-c]pyrazol-4(1H-one Moiety

    Directory of Open Access Journals (Sweden)

    Wolfgang Holzer

    2007-01-01

    Full Text Available Starting from commercially available educts, a straightforward synthetic route to new heterocyclic building blocks is exemplified with the one- or two-step synthesis of tri-, tetra-, or pentacyclic ring systems. Representatives of the following novel ring systems are prepared from 3-methyl-1-phenyl-2-pyrazolin-5-one and the corresponding o-halo-arenecarbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane: pyrimidino[4',5':5,6]pyrano[2,3-c]pyrazol-4(1H-one, thieno[3',2':5,6]pyrano[2,3c]pyrazol- 4-(1H-one, thieno[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H-one, thieno[3'',2'':4',5']thieno[2',3':5,6]-pyrano[2,3-c]pyrazol-4(1H-one, [1,3]dioxolo[5',6'][1]benzothieno[2',3':5,6]pyrano-[2,3-c]- pyrazol-4(1H-one, pyridazino[4',3':5,6]pyrano[2,3-c]pyrazol-4(1H-one and pyrazolo-[4'',3'':5',6']pyrido[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H-one. While the latter two ring systems are directly obtained due to a spontaneous intramolecular substitution reaction, in the other reactions uncyclised 4-aroylpyrazol-5-ols are produced, which are cyclised into the target heterocycles in a subsequent synthetic step (i.e. treatment with NaH in DMF. Detailed NMR spectroscopic investigations (1H-, 13C-, 15N- with the obtained compounds were undertaken to unambiguously prove the new structures.

  12. Documentation of spectrom-41

    International Nuclear Information System (INIS)

    SPECTROM-41 is a finite element heat transfer computer program developed to analyze thermal problems related to nuclear waste disposal. The code is part of the SPECTROM (Special Purpose Engineering Codes for Thermal/ROck Mechanics) series of special purpose finite element programs that are continually being developed by RE/SPEC Inc. (RSI) to address the many unique formations. This document presents the theoretical basis for the mathematical model, the finite element formulation of the program, and a description of the input data for the program, along with details about program support and continuing documentation. The documentation is intended to satisfy the requirements and guidelines outlined in NUREG-0856. The principal component model used in the programs based on Fourier's law of conductance. Numerous program options provide the capability of considering various boundary conditions, material stratification and anisotropy, and time-dependent heat generation that are characteristic of problems involving the disposal of nuclear waste in geologic formation. Numerous verification problems are included in the documentation in addition to highlights of past and ongoing verification and validation efforts. A typical repository problem is solving using SPECTROM-41 to demonstrate the use of the program in addressing problems related to the disposal of nuclear waste

  13. PYRETHROID INDUCED ALTERATIONS IN TRANSCRIPTION OF CALCIUM RESPONSIVE AND IMMEDIATE EARLY GENES IN VIVO.

    Science.gov (United States)

    Multiple molecular targets for pyrethroid insecticides have been evaluated in in vitro preparations, including but not limited to voltage-sensitive sodium channels (VSSCs), voltage-sensitive calcium channels (VSCCs), GABAergic receptors, ATPases and mitochondrial respiratory chai...

  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. 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.

  16. 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

  17. Melittin binding causes a large calcium-dependent conformational change in calmodulin.

    OpenAIRE

    Kataoka, M.(LAPP, CNRS/IN2P3 and Université de Savoie, Annecy-le-Vieux, France); Head, J F; Seaton, B A; Engelman, D M

    1989-01-01

    The interaction between calmodulin and its target protein is a key step in many calcium-regulated cellular functions. Melittin binds tightly to calmodulin in the presence of calcium and is a competitive inhibitor of calmodulin function. Using melittin as a model for the target peptide of calmodulin, we have found a large Ca2+-dependent conformational change of calmodulin in solution induced by peptide binding. Mg2+ does not substitute for Ca2+ in producing the conformation change. Small-angle...

  18. 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 ...

  19. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

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

  20. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    OpenAIRE

    Choksi Krishna; Shenoy Ashoka M; A. R. Shabharaya; Lala Minaxi

    2011-01-01

    The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg) and calcium gluconate (5 mg/kg) were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg) to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate cou...

  1. 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...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...... in the char conversion process. Comprehensive global equilibrium calculations predicted important characteristics of the inorganic ash residue. Equilibrium calculations predict the formation of liquid salt if sufficient amounts of Ca are added and according to experiments as well as calculations calcium binds...

  2. 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.

  3. Sensitivity to calcium intake in calcium stone forming patients.

    Science.gov (United States)

    Heilberg, I P; Martini, L A; Draibe, S A; Ajzen, H; Ramos, O L; Schor, N

    1996-01-01

    The absorptive or renal origin of hypercalciuria can be discriminated using an acute oral calcium load test (ACLT). Of 86 patients with calcium oxalate kidney stones, 28 (23%) were found to be hypercalciuric (HCa) and 58 (67%) normocalciuric (NCa) on their customary free diet, containing 542 +/- 29 mg/day (mean +/- SE) of calcium. Since the apparently normal 24-hour calcium excretion of many calcium stone formers (CSF) may be due to a combination of high calcium absorption with moderately low calcium intake, all patients were investigated by ACLT. Of 28 HCa patients, 13 (46%) were classified as absorptive (AH) and 15 (54%) as renal hypercalciuria (RH). Of the 58 NCa patients, 38 (65%) presented features of intestinal hyperabsorption and were therefore designated as AH-like, and 20 (35%) as RH-like. To further elucidate the role of dietary calcium in these CSF, a chronic calcium load test (CCLT), consisting of 1 g/day of oral Ca for 7 days, was designed. A positive response to the CCLT was considered to occur when urinary calcium (uCa) was > or = 4 mg/ kg/24 h on the 7th day. Among NCa patients, 29% of AH-like subjects responded to the CCLT and 71% did not; 50% of RH-like subjects also responded and 50% did not. In HCa patients, 85% of AH and 67% of RH subjects maintained uCa > or = 4 mg/kg/24 h after the CCLT and 15% of AH and 23% of RH subjects did not. However, a significant additional increase in mean uCa was not observed among HCa patients. All patients were submitted to a second evaluation of fasting calciuria (Ca/Cr). A modification of this parameter was noticed in 89% of RH-like and 78% of RH patients. In conclusion, these data suggest the presence of subpopulations of patients sensitive or not to calcium intake, regardless of whether the acute response to a calcium overload test suggested AH or RH. The CCLT disclosed dietary hypercalciuria in 21/58 (36%) of previously NCa patients. In these NCa patients, the ACLT may be replaced by the CCLT. The distinction

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

    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.

  5. 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.

  6. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    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. PMID:7488645

  7. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    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.

  8. Calcium channel blocking activity of fruits of callistemon citrinus

    International Nuclear Information System (INIS)

    Callistemon citrinus is a plant of family myrtaceae that has a great medicinal importance. Traditional uses of the aerial parts of Callistemon citrinus in ethnic tribal communities are in practice, and very little are known about its importance on scientific grounds. Therefore, the crude methanolic extract of fruits of Callistemon citrinus (C.c) was screened for possible spasmolytic activity on isolated rabbit's jejunum preparations. The extract produced a relaxing effect on spontaneous contraction of rabbit's jejunum. Explaining the mode of action, the extract produced a dose dependent relaxant effect and shifted the calcium response curves to the rightward (EC50 +- SEM = -2.05 +- 0.05 vs. control EC50 +- SEM = -2.5 +- 0.05). The effect of extract was comparable with the effect of verapamil, a standard calcium channel blocker and therefore, the plant specie could be a potential target for isolation of calcium antagonist(s). (author)

  9. Biodegradable magnetic calcium phosphate nanoformulation for cancer therapy.

    Science.gov (United States)

    Tang, Zhaomin; Zhou, Yangbo; Sun, Huili; Li, Dan; Zhou, Shaobing

    2014-05-01

    We fabricated a magnetic calcium phosphate nanoformulation by the biomineralization of calcium phosphate on the surface of magnetic nanoparticles with abundant amino groups, and thus the inorganic layer of calcium phosphate can improve the biocompatibility and simultaneously the magnetic iron oxide can maintain the magnetic targeting function. Two types of anticancer drug models, doxorubicin hydrochloride and DNA, were entrapped in these nanocarriers, respectively. This delivery system displayed high pH sensitivity in drug-controlled release profile as the dissolution of CaP under acid pH condition. Magnetofection was performed to investigate the intracellular uptake and the anti-proliferative effect of tumor cells in the presence of an external magnet. The transfection of the DNA-loaded magnetic system in A549 and HepG2 tumor cells demonstrated that the magnetic nanoformulation could enhance the transfection efficiency to 30% with an applied external magnetic field. PMID:24462792

  10. Variability of calcium absorption

    International Nuclear Information System (INIS)

    Variability in calcium absorption was estimated in three groups of normal subjects in whom Ca absorption was measured by standard isotopic-tracer methods at interstudy intervals ranging from 1 to 4 mo. Fifty absorption tests were performed in 22 subjects. Each was done in the morning after an overnight fast with an identical standard breakfast containing a Ca load of approximately 250 mg. Individual fractional absorption values were normalized to permit pooling of the data. The coefficient of variation (CVs) for absorption for the three groups ranged from 10.57 to 12.79% with the size of the CV increasing with interstudy duration. One other published study presenting replicate absorption values was analyzed in a similar fashion and was found to have a CV of absorption of 9.78%. From these data we estimate that when the standard double-isotope method is used to measure Ca absorption there is approximately 10% variability around any given absorption value within an individual human subject and that roughly two-thirds of this represents real biological variability in absorption

  11. Urine risk factors in children with calcium kidney stones and their siblings.

    Science.gov (United States)

    Bergsland, Kristin J; Coe, Fredric L; White, Mark D; Erhard, Michael J; DeFoor, William R; Mahan, John D; Schwaderer, Andrew L; Asplin, John R

    2012-06-01

    Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones. PMID:22358148

  12. Serum Calcium Concentration Is Inversely Associated With Radiographic Knee Osteoarthritis

    OpenAIRE

    Li, Hui; ZENG, CHAO; Wei, Jie; Yang, Tuo; GAO, SHU-GUANG; Li, Yu-Sheng; Luo, Wei; Xiao, Wen-feng; Xiong, Yi-lin; LEI, GUANG-HUA

    2016-01-01

    Abstract To examine the relationship between serum calcium (Ca) concentration and radiographic knee osteoarthritis (OA). This study covered a total of 2855 subjects. The serum Ca concentration was detected by the Arsenazo III method. The radiographic OA of the knee was defined as changes equivalent to Kellgren–Lawrence grade 2 on 1 side at least. The serum Ca concentration was categorized into 4 quartiles, which are ≤2.27, 2.28–2.34, 2.35–2.41, and ≥2.42 mmol/L, respectively. The relationship...

  13. Meals and dephytinization affect calcium and zinc absorption in Nigerian children with rickets.

    Science.gov (United States)

    Thacher, Tom D; Aliu, Oluseyi; Griffin, Ian J; Pam, Sunday D; O'Brien, Kimberly O; Imade, Godwin E; Abrams, Steven A

    2009-05-01

    Nutritional rickets resulting from calcium insufficiency is common in Nigeria and high dietary phytate is thought to inhibit calcium and zinc absorption. We compared the effects of a high-phytate meal and enzymatic dephytinization on calcium and zinc absorption in Nigerian children with and without rickets. Nineteen children with rickets and 15 age-matched control children, aged 2-10 y, were given calcium (600 mg/d) and ergocalciferol (1250 microg/wk). After 6 wk, calcium and zinc absorption were measured in both groups with and without maize porridge using stable isotopes. One week later, absorption measurements were repeated to assess the effects of enzymatic dephytinization and fermentation of the maize porridge. The phytate concentration of maize porridge (3.87 +/- 0.38 g/kg wet weight) was reduced by enzymatic dephytinization (2.83 +/- 0.41 g/kg; P porridge. Calcium absorption was greater with a meal (61.3 +/- 25.1%) than without (27.8 +/- 14.6%; P porridge, but zinc absorption was reduced. Enzymatic dephytinization increased zinc absorption. Multiple strategies may be required to optimize calcium and zinc absorption in deficient populations.

  14. Redox control of calcium channels: from mechanisms to therapeutic opportunities.

    Science.gov (United States)

    Hool, Livia C; Corry, Ben

    2007-04-01

    Calcium plays an integral role in cellular function. It is a well-recognized second messenger necessary for signaling cellular responses, but in excessive amounts can be deleterious to function, causing cell death. The main route by which calcium enters the cytoplasm is either from the extracellular compartment or internal addistores via calcium channels. There is good evidence that calcium channels can respond to pharmacological compounds that reduce or oxidize thiol groups on the channel protein. In addition, reactive oxygen species such as hydrogen peroxide and superoxide that can mediate oxidative pathology also mediate changes in channel function via alterations of thiol groups. This review looks at the structure and function of calcium channels, the evidence that changes in cellular redox state mediate changes in channel function, and the role of redox modification of channels in disease processes. Understanding how redox modification of the channel protein alters channel structure and function is providing leads for the design of therapeutic interventions that target oxidative stress responses.

  15. 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.

  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. 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.

  18. 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.

  19. Chronic neuropathic pain: mechanisms, drug targets and measurement

    DEFF Research Database (Denmark)

    Finnerup, Nanna B; Sindrup, Søren H; Jensen, Troels S

    2007-01-01

    . Preclinical research provides several promising targets for treatment such as sodium and calcium channels, glutamate receptors, monoamines and neurotrophic factors; however, treatment is often insufficient. A mechanism-based treatment approach is suggested to improve treatment. Valid and reliable tools...

  20. Seafloor Surficial Sediments (Deck 41)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The National Geophysical Data Center (NGDC) "Deck41" database contains surficial sediment descriptions for over 36,000 seafloor samples worldwide. The file was...

  1. 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.

  2. Particle physics using nuclear targets

    International Nuclear Information System (INIS)

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references

  3. Particle physics using nuclear targets

    Energy Technology Data Exchange (ETDEWEB)

    Ferbel, T.

    1978-01-01

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references.

  4. Aging and calcium as an environmental factor.

    Science.gov (United States)

    Fujita, T

    1985-12-01

    Calcium deficiency is a constant menace to land-abiding animals, including mammals. Humans enjoying exceptional longevity on earth are especially susceptible to calcium deficiency in old age. Low calcium and vitamin D intake, short solar exposure, decreased intestinal absorption, and falling renal function with insufficient 1,25(OH)2 vitamin D biosynthesis all contribute to calcium deficiency, secondary hyperparathyroidism, bone loss and possibly calcium shift from the bone to soft tissue, and from the extracellular to the intracellular compartment, blunting the sharp concentration gap between these compartments. The consequences of calcium deficiency might thus include not only osteoporosis, but also arteriosclerosis and hypertension due to the increase of calcium in the vascular wall, amyotrophic lateral sclerosis and senile dementia due to calcium deposition in the central nervous system, and a decrease in cellular function, because of blunting of the difference in extracellular-intracellular calcium, leading to diabetes mellitus, immune deficiency and others (Fig. 6). PMID:2943880

  5. Optimizing calcium selective fluorimetric nanospheres.

    Science.gov (United States)

    Kisiel, Anna; Kłucińska, Katarzyna; Gniadek, Marianna; Maksymiuk, Krzysztof; Michalska, Agata

    2015-11-01

    Recently it was shown that optical nanosensors based on alternating polymers e.g. poly(maleic anhydride-alt-1-octadecene) were characterized by a linear dependence of emission intensity on logarithm of concentration over a few of orders of magnitude range. In this work we focus on the material used to prepare calcium selective nanosensors. It is shown that alternating polymer nanosensors offer competitive performance in the absence of calcium ionophore, due to interaction of the nanospheres building blocks with analyte ions. The emission increase corresponds to increase of calcium ions contents in the sample within the range from 10(-4) to 10(-1) M. Further improvement in sensitivity (from 10(-6) to 10(-1) M) and selectivity can be achieved by incorporating calcium ionophore in the nanospheres. The optimal results were obtained for core-shell nanospheres, where the core was prepared from poly(styrene-co-maleic anhydride) and the outer layer from poly(maleic anhydride-alt-1-octadecene). Thus obtained chemosensors were showing linear dependence of emission on logarithm of calcium ions concentration within the range from 10(-7) to 10(-1) M. PMID:26452839

  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

    -type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article......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. Search for an exosphere in sodium and calcium in the transmission spectrum of exoplanet 55 Cancri e

    Science.gov (United States)

    Ridden-Harper, A. R.; Snellen, I. A. G.; Keller, C. U.; de Kok, R. J.; Di Gloria, E.; Hoeijmakers, H. J.; Brogi, M.; Fridlund, M.; Vermeersen, B. L. A.; van Westrenen, W.

    2016-10-01

    Context. The atmospheric and surface characterization of rocky planets is a key goal of exoplanet science. Unfortunately, the measurements required for this are generally out of reach of present-day instrumentation. However, the planet Mercury in our own solar system exhibits a large exosphere composed of atomic species that have been ejected from the planetary surface by the process of sputtering. Since the hottest rocky exoplanets known so far are more than an order of magnitude closer to their parent star than Mercury is to the Sun, the sputtering process and the resulting exospheres could be orders of magnitude larger and potentially detectable using transmission spectroscopy, indirectly probing their surface compositions. Aims: The aim of this work is to search for an absorption signal from exospheric sodium (Na) and singly ionized calcium (Ca+) in the optical transmission spectrum of the hot rocky super-Earth 55 Cancri e. Although the current best-fitting models to the planet mass and radius require a possible atmospheric component, uncertainties in the radius exist, making it possible that 55 Cancri e could be a hot rocky planet without an atmosphere. Methods: High resolution (R ~ 110 000) time-series spectra of five transits of 55 Cancri e, obtained with three different telescopes (UVES/VLT, HARPS/ESO 3.6 m and HARPS-N/TNG) were analysed. Targeting the sodium D lines and the calcium H and K lines, the potential planet exospheric signal was filtered out from the much stronger stellar and telluric signals, making use of the change of the radial component of the orbital velocity of the planet over the transit from -57 to +57 km s-1. Results: Combining all five transit data sets, we detect a signal potentially associated with sodium in the planet exosphere at a statistical significance level of 3σ. Combining the four HARPS transits that cover the calcium H and K lines, we also find a potential signal from ionized calcium (4.1σ). Interestingly, this latter

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Virus and calcium : an unexpected tandem to optimize insecticide efficacy

    OpenAIRE

    Apaire-Marchais, V; Ogliastro, M.; Chandre, Fabrice; Pennetier, Cédric; Raymond, V; Lapied, B

    2016-01-01

    The effective control of insect pests is based on the rational use of the most efficient and safe insecticide treatments. To increase the effects of classical insecticides and to avoid the ability of certain pest insects to develop resistance, it is essential to propose novel strategies. Previous studies have shown that calcium-dependent phosphorylation/dephosphorylation is now considered as a new cellular mechanism for increasing the target sensitivity to insecticides. Because it is known th...

  13. 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.

  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. Calcium and lithium ion production for laser ion source

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, M., E-mail: okamura@bnl.gov [Collider-Accelerator Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Nishina Center for Accelerator-Based Science, RIKEN, Saitama (Japan); Palm, K. [Department of Physics, Cornell University, Ithaca, New York 14853-2501 (United States); Stifler, C. [Engineering Physics Systems Department, Providence College, Providence, Rhode Island 02918 (United States); Steski, D.; Kanesue, T. [Collider-Accelerator Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Ikeda, S. [Nishina Center for Accelerator-Based Science, RIKEN, Saitama (Japan); Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Kanagawa (Japan); Kumaki, M. [Nishina Center for Accelerator-Based Science, RIKEN, Saitama (Japan); Research Institute for Science and Engineering, Waseda University, Tokyo (Japan)

    2016-02-15

    Calcium and lithium ion beams are required by NASA Space Radiation Laboratory at Brookhaven National Laboratory to simulate the effects of cosmic radiation. To identify the difficulties in providing such highly reactive materials as laser targets, both species were experimentally tested. Plate shaped lithium and calcium targets were fabricated to create ablation plasmas with a 6 ns 1064 nm neodymium-doped yttrium aluminum garnet 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 used to create 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 of oxide 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 10 s, 30 s, 60 s, and 120 s interval lengths, showing a linear relation between the interval time and the amount of oxygen in the beam.

  16. Structure elucidation of alkaline earth impregnated MCM-41 type mesoporous materials obtained by direct synthesis: An experimental and theoretical study

    Science.gov (United States)

    Paz, Gizeuda L.; Silva, Francisco das Chagas M.; Araújo, Maciel M.; Lima, Francisco das Chagas A.; Luz, Geraldo E.

    2014-06-01

    In this work, MCM-41 were synthesized hydrothermally and functionalized with calcium and strontium salts by direct method, using the Si/M = 50 molar ratio, in order to elucidate the way as the alkaline earth is incorporated on MCM-41 molecular sieve. The materials were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, nitrogen adsorption-desorption and theoretical calculations by DFT method. Experimental results and computer simulations showed that the alkaline earths were incorporated on MCM-41 through a complex structure, which negatively influences on basic sites formation.

  17. Calcium release-activated calcium current in rat mast cells.

    Science.gov (United States)

    Hoth, M; Penner, R

    1993-06-01

    1. Whole-cell patch clamp recordings of membrane currents and fura-2 measurements of free intracellular calcium concentration ([Ca2+]i) were used to study the biophysical properties of a calcium current activated by depletion of intracellular calcium stores in rat peritoneal mast cells. 2. Calcium influx through an inward calcium release-activated calcium current (ICRAC) was induced by three independent mechanisms that result in store depletion: intracellular infusion of inositol 1,4,5-trisphosphate (InsP3) or extracellular application of ionomycin (active depletion), and intracellular infusion of calcium chelators (ethylene glycol bis-N,N,N',N'-tetraacetic acid (EGTA) or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)) to prevent reuptake of leaked-out calcium into the stores (passive depletion). 3. The activation of ICRAC induced by active store depletion has a short delay (4-14 s) following intracellular infusion of InsP3 or extracellular application of ionomycin. It has a monoexponential time course with a time constant of 20-30 s and, depending on the complementary Ca2+ buffer, a mean normalized amplitude (at 0 mV) of 0.6 pA pF-1 (with EGTA) and 1.1 pA pF-1 (with BAPTA). 4. After full activation of ICRAC by InsP3 in the presence of EGTA (10 mM), hyperpolarizing pulses to -100 mV induced an instantaneous inward current that decayed by 64% within 50 ms. This inactivation is probably mediated by [Ca2+]i, since the decrease of inward current in the presence of the fast Ca2+ buffer BAPTA (10 mM) was only 30%. 5. The amplitude of ICRAC was dependent on the extracellular Ca2+ concentration with an apparent dissociation constant (KD) of 3.3 mM. Inward currents were nonsaturating up to -200 mV. 6. The selectivity of ICRAC for Ca2+ was assessed by using fura-2 as the dominant intracellular buffer (at a concentration of 2 mM) and relating the absolute changes in the calcium-sensitive fluorescence (390 nm excitation) with the calcium current integral

  18. 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.

  19. 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.

  20. 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.

  1. Preparation of calcium carbonate particles coated with titanium dioxide

    Institute of Scientific and Technical Information of China (English)

    Hai Lin; Ying-bo Dong; Le-yong Jiang

    2009-01-01

    The preparation of a new mineral composite material, calcium carbonate particles coated with titanium dioxide, was stud-ied. The mechanism of the preparation process was proposed. The new mineral composite material was made by the mechanochemi-eal method under the optimum condition that the mass ratio of calcium carbonate particles to titanium dioxide was 6.5:3.5. The mass ratios of two different types of titanium dioxide (anatase to rutile) and grinding media to grinded materials were 8:2 and 4:1 respec-tively, and the modified density was 60%. Under this condition, the new material was capable of forming after 120-min modification.The hiding power and oil absorption of this new material were 29.12 g/m~2 and 23.30%, respectively. The results show that the modi-fication is based on surface hydroxylation. After coating with titanium dioxide, the hiding power of calcium carbonate can be im-proved greatly. The new mineral composite materials can be used as the substitute for titanium dioxide.

  2. 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.

  3. 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.

  4. 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...

  5. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... can break easily, even without an obvious injury. Vitamin D helps your body absorb calcium. Eat foods that provide the right amounts of calcium, vitamin D, and protein. This kind of diet will give ...

  6. Dairy Dilemma: Are You Getting Enough Calcium?

    Science.gov (United States)

    ... Dairy Dilemma Dairy Dilemma Are You Getting Enough Calcium? You may be avoiding dairy products because of ... But dairy products are a major source of calcium, vitamin D and other nutrients that are important ...

  7. 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.

  8. CERN: Fixed target targets

    International Nuclear Information System (INIS)

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become

  9. 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.

  10. 21 CFR 184.1210 - Calcium oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium oxide. 184.1210 Section 184.1210 Food and... Substances Affirmed as GRAS § 184.1210 Calcium oxide. (a) Calcium oxide (CaO, CAS Reg. No. 1305-78-8) is also known as lime, quick lime, burnt lime, or calx. It is produced from calcium carbonate, limestone,...

  11. 21 CFR 184.1185 - Calcium acetate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium acetate. 184.1185 Section 184.1185 Food and... Substances Affirmed as GRAS § 184.1185 Calcium acetate. (a) Calcium acetate (Ca (C2H3O2)2, CAS Reg. No. 62-54-4), also known as acetate of lime or vinegar salts, is the calcium salt of acetic acid. It may...

  12. 4 CFR 4.1 - Training.

    Science.gov (United States)

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Training. 4.1 Section 4.1 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM EMPLOYEE PERFORMANCE AND UTILIZATION § 4.1 Training. The provisions of chapter 41, of title 5, United States Code, and Office of Personnel Management implementing...

  13. 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...

  14. 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…

  15. Virus and calcium: an unexpected tandem to optimize insecticide efficacy.

    Science.gov (United States)

    Apaire-Marchais, Véronique; Ogliastro, Mylène; Chandre, Fabrice; Pennetier, Cédric; Raymond, Valérie; Lapied, Bruno

    2016-04-01

    The effective control of insect pests is based on the rational use of the most efficient and safe insecticide treatments. To increase the effects of classical insecticides and to avoid the ability of certain pest insects to develop resistance, it is essential to propose novel strategies. Previous studies have shown that calcium-dependent phosphorylation/dephosphorylation is now considered as a new cellular mechanism for increasing the target sensitivity to insecticides. Because it is known that virus entry is correlated with intracellular calcium concentration rise, this report attempts to present the most important data relevant to the feasibility of combining an insect virus such as baculovirus or densovirus with an insecticide. In this case, the insect virus is not used as a bioinsecticide but acts as a synergistic agent able to trigger calcium rise and to activate calcium-dependent intracellular signalling pathways involved in the increase of the membrane receptors and/or ion channels sensitivity to insecticides. This virus-insecticide mixture represents a promising alternative to optimize the efficacy of insecticides against insect pests while reducing the doses. PMID:26743399

  16. 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. PMID:26944102

  17. 21 CFR 582.1205 - Calcium hydroxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium hydroxide. 582.1205 Section 582.1205 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1205 Calcium hydroxide. (a) Product. Calcium hydroxide. (b) Conditions of use....

  18. 21 CFR 182.2227 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium silicate. 182.2227 Section 182.2227 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Anticaking Agents § 182.2227 Calcium silicate. (a) Product. Calcium silicate....

  19. 21 CFR 582.2227 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium silicate. 582.2227 Section 582.2227 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium silicate. (a) Product. Calcium silicate. (b) Tolerance. 2 percent and 5 percent. (c)...

  20. 21 CFR 582.5210 - Calcium oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium oxide. 582.5210 Section 582.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance...

  1. Lactulose stimulates calcium absorption in postmenopausal women

    NARCIS (Netherlands)

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

    1999-01-01

    Animal studies have indicated that calcium absorption is increased by lactulose, a synthetic disaccharide. Therefore, the influence of lactulose on calcium absorption was measured in postmenopausal women who may benefit from the possible enhancing effect of lactulose on calcium absorption. Twelve po

  2. 21 CFR 582.1210 - Calcium oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium oxide. 582.1210 Section 582.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance is...

  3. 21 CFR 582.6185 - Calcium acetate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium acetate. 582.6185 Section 582.6185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium acetate. (a) Product. Calcium acetate. (b) Conditions of use. This substance is...

  4. 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)....

  5. 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)....

  6. 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)....

  7. Sputter target

    Science.gov (United States)

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  8. The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.

    Science.gov (United States)

    Zamponi, Gerald W; Striessnig, Joerg; Koschak, Alexandra; Dolphin, Annette C

    2015-10-01

    Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type Ca(V)1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca(V)3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (Ca(V)2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., Ca(V)1.2 and Ca(V)1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective Ca(V)1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson's disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep

  9. Production Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Olivas, Eric Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  10. 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

    BACKGROUND: Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation...... offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium...... 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...

  11. Calcium signals and calcium channels in osteoblastic cells

    Science.gov (United States)

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

    1998-01-01

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

  12. Computational study of a calcium release-activated calcium channel

    Science.gov (United States)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  13. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Directory of Open Access Journals (Sweden)

    Nawal Zabouri

    Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  14. 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.

  15. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    Directory of Open Access Journals (Sweden)

    Choksi Krishna

    2011-03-01

    Full Text Available The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg and calcium gluconate (5 mg/kg were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate could not show significant anti-inflammatory activity on their own in acute as well as subacute inflammation models. Aspirin at sub-anti-inflammatory dose (50mg/Kg when co-administered along with calcium salts produced the significant anti-inflammatory response which was comparable to anti-inflammatory response of aspirin at therapeutic dose (200mg/Kg. Also co-adminostration minimized the gastro-toxicity of aspirin.

  16. Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium Channels

    OpenAIRE

    Autoosa Salari; Benjamin S. Vega; Milescu, Lorin S.; Mirela Milescu

    2016-01-01

    Few gating-modifier toxins have been reported to target low-voltage-activated (LVA) calcium channels, and the structural basis of toxin sensitivity remains incompletely understood. Studies of voltage-gated potassium (Kv) channels have identified the S3b–S4 “paddle motif,” which moves at the protein-lipid interface to drive channel opening, as the target for these amphipathic neurotoxins. Voltage-gated calcium (Cav) channels contain four homologous voltage sensor domains, suggesting multiple t...

  17. 41Ca ultratrace determination with isotopic selectivity > 10(12) by diode-laser-based RIMS.

    Science.gov (United States)

    Müller, P; Bushaw, B A; Blaum, K; Diel, S; Geppert, C; Nähler, A; Trautmann, N; Nörtershäuser, W; Wendt, K

    2001-07-01

    41Ca ultratrace determination by diode-laser-based resonance ionization mass spectrometry with extremely high isotopic selectivity is presented. Application to environmental dosimetry of nuclear reactor components, to cosmochemical investigations of production cross sections, and biomedical isotope-tracer studies of human calcium kinetics are discussed. Future investigations are possible use in 41Ca-radiodating. Depending on the application, 41Ca isotopic abundances in the range of 10(-9) to 10(-15) relative to the dominant stable isotope 40Ca must be determined. Either double- or triple-resonance optical excitation with narrow-band extended cavity diode lasers and subsequent non-resonant photoionization of calcium in a collimated atomic beam were used. The resulting photoions are detected with a quadrupole mass spectrometer optimized for background reduction and neighboring mass suppression. Applying the full triple-resonance scheme provides a selectivity of approximately 5 x 10(12) in the suppression of neighboring isotopes and > 10(8) for isobars, together with an overall detection efficiency of approximately 5 x 10(-5). Measurements on a variety of sample types are discussed; the accuracy and reproducibility of the resulting 41Ca/40Ca isotope ratios was better than 5%.

  18. Calcium sensitizers: What have we learned over the last 25 years?

    Science.gov (United States)

    Pollesello, P; Papp, Z; Papp, J Gy

    2016-01-15

    The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. Drugs such as cardiac glycosides, cathecolamines, phosphodiestherase inhibitors, and calcium sensitizers have been in turn proposed. However, the number of new chemical entities in this therapeutic field has been surprisingly low, and the current selection of drugs is limited. One of the paradigm shifts in the discovery for new inotropes was to focus on 'calcium sensitizers' instead of 'calcium mobilizers'. This was designed to lead to the development of safer inotropes, devoid of the complications that arise due to increased intracellular calcium levels. However, only three such calcium sensitizers have been fully developed over the latest 30 years. Moreover, two of these, levosimendan and pimobendan, have multiple molecular targets and other pharmacologic effects in addition to inotropy, such as peripheral vasodilation. More recently, omecamtiv mecarbil was described, which is believed to have a pure inotropy action that is devoid of pleiotropic effects. When the clinical data of these three calcium sensitizers are compared, it appears that the less pure inotropes have the cutting edge over the purer inotrope, due to additional effects during the treatment of a complex syndrome such as acute congested heart failure. This review aims to answer the question whether calcium sensitization per se is a sufficient strategy for bringing required clinical benefits to patients with heart failure. This review is dedicated to the memory of Heimo Haikala, a true and passionate innovator in this challenging field. PMID:26580334

  19. [Calcium pyrophosphate dihydrate deposition disease].

    Science.gov (United States)

    Koitschev, C; Kaiserling, E; Koitschev, A

    2003-08-01

    Calcium pyrophosphate dihydrate deposition disease (CPPD) of the temporomandibular joint is rare. The disorder is characterized by the presence of crystal deposits within the affected joint. The deposition of crystals in adjacent soft tissue may lead to the formation of pseudotumors. This form of the disease is called tophaceous pseudogout and typically affects the temporomandibular joint. It is difficult to differentiate the disease, particularly from malignant tumors, on the clinical and radiographic findings alone. The diagnosis is based on histological identification of the calcium pyrophosphate crystals. We present an unusually advanced case of tophaceous pseudogout of the temporomandibular joint. The etiology, clinical and diagnostic criteria as well as treatment options are discussed on the basis of our own experience and a review of the literature. PMID:12942180

  20. Serum calcium in pulmonary tuberculosis

    OpenAIRE

    Subhash C. Sharma

    1981-01-01

    Serum calcium was studied serially in 94 patients with active pulmonary tuberculosis. An equal number of age- and sex-matched patients with chronic obstructive pulmonary disease were controls. Seventy patients in the study group were normocalcaemic and 10 were hypercalcaemic. These 10 were on a higher supplement of vitamin D than the 70 normocalcaemic patients. There was a positive correlation between the daily vitamin intake and the degree and duration of hypercalcaemia. None of the controls...

  1. Influence of calcium oxalate crystal accumulation on the calcium content of seeds from Medicago truncatula.

    Science.gov (United States)

    Nakata, Paul A

    2012-04-01

    Crystals of calcium oxalate often form in cells adjacent to the vascular bundles in the tissues along the xylem stream. This spatial crystal pattern suggests a role for calcium oxalate formation in regulating calcium transport and partitioning to edible organs such as seeds. To investigate this potential role, microscopic and biochemical comparisons were conducted on the different tissues of Medicago truncatula wild-type and the calcium oxalate defective (cod) 5 which lacks the ability to accumulate prismatic crystals in the cells adjacent to the vascular bundles. Calcium measurements showed that cod5 seeds had more calcium and cod5 pods contained less calcium than the corresponding wild-type tissues. Roots, stems, and leaves from cod5 and wild-type had similar calcium content. Although cod5 was devoid of prismatic crystals, cod5 pods were observed to form druse crystals of calcium oxalate not found in wild-type pods. Taken together these findings suggest a functional role for calcium oxalate formation in regulating calcium transport to the seeds. Regulating calcium uptake at the roots also appeared to be another point of control in determining seed calcium content. Overall, regulating the long distance transport and partitioning of calcium to the seeds appears to be a complex process with multiple points of control. PMID:22325887

  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. Calmodulin-binding domains in Alzheimer's disease proteins: extending the calcium hypothesis.

    Science.gov (United States)

    O'Day, Danton H; Myre, Michael A

    2004-08-01

    The calcium hypothesis of Alzheimer's disease (AD) invokes the disruption of calcium signaling as the underlying cause of neuronal dysfunction and ultimately apoptosis. As a primary calcium signal transducer, calmodulin (CaM) responds to cytosolic calcium fluxes by binding to and regulating the activity of target CaM-binding proteins (CaMBPs). Ca(2+)-dependent CaMBPs primarily contain domains (CaMBDs) that can be classified into motifs based upon variations on the basic amphiphilic alpha-helix domain involving conserved hydrophobic residues at positions 1-10, 1-14 or 1-16. In contrast, an IQ or IQ-like domain often mediates Ca(2+)-independent CaM-binding. Based on these attributes, a search for CaMBDs reveals that many of the proteins intimately linked to AD may be calmodulin-binding proteins, opening new avenues for research on this devastating disease. PMID:15249195

  4. [Progress in calcium regulation in myocardial and vascular ischemia-reperfusion injury].

    Science.gov (United States)

    He, Xi; Bi, Xue-Yuan; Wang, Hao; Yu, Xiao-Jiang; Zang, Wei-Jin

    2012-06-25

    Ischemia-reperfusion injury (IRI) has been recognized as a serious problem for therapy of cardiovascular diseases. Calcium regulation appears to be an important issue in the study of IRI. This article reviews calcium regulation in myocardial and vascular IRI, including the calcium overload and calcium sensitivity in IRI. This review is focused on the key players in Ca(2+) handling in IRI, including membrane damage resulting in increase in Ca(2+) influx, reverse-mode of Na(+)-Ca(2+) exchangers leading to increased Ca(2+) entry, the decreased activity of sarcoplasmic reticulum (SR) Ca(2+)-ATPase causing SR Ca(2+) uptake dysfunction, and increased activity of Rho kinase. These key players in Ca(2+) homeostasis will provide promising strategies and potential targets for therapy of cardiovascular IRI. PMID:22717637

  5. Serotonin and calcium homeostasis during the transition period.

    Science.gov (United States)

    Weaver, S R; Laporta, J; Moore, S A E; Hernandez, L L

    2016-07-01

    The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently

  6. Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients

    Science.gov (United States)

    López, Esther; Berna-Erro, Alejandro; Bermejo, Nuria; Brull, José María; Martinez, Rocío; Garcia Pino, Guadalupe; Alvarado, Raul; Salido, Ginés María; Rosado, Juan Antonio; Cubero, Juan José; Redondo, Pedro Cosme

    2013-01-01

    The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long-term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura-2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time-dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long-term administration of rapamycin to kidney transplant patients evokes alteration in platelet function. PMID:23577651

  7. A study on hormonal control of calcium homeostasis in egyptian women

    International Nuclear Information System (INIS)

    This investigation was conducted to study the possible role of circulating hormones that regulate the calcium flux, in addition to serum levels of the inorganic mineral contents, calcium and phosphorus, on the pathogenesis of post-menopausal osteoporosis in egyptian women. The investigation studied also the response of these variables to both of estradiol withdrawal and age progress. Five groups of 11 postmenopausal osteoporotic (mean age 73 -+ 2.3 years), 26 postmenopausal women (mean age 56.2 -+ 2.4 years), 17 premenopausal women (mean age 48.8 -+ 0.7 years), 26 premenopausal women (mean age 41.5 -+ o.7 years) and 11 young adult premenopausal women(mean age 27.3 -+ 0.9 years) were recruited for this study. The post-peri- and pre- groups were further classified into subgroups according to their chronological age. Serum was assayed for parathyroid hormone (PTH), 25-hydroxyvitamin D, (25-OHD3), calcitonin (CT) total calcium (Ca), and inorganic phosphorus (ph), concentrations of estradiol (E2) in all subjects were also assayed for further correlation. The obtained data showed that the levels of hormones were not significantly changed among the different groups and subgroups leading to normal calcium homeostasis. PTH and total calcium were significantly correlated with both estrodial levels and chronological age

  8. Effect of calcium triphosphate cement on proximal humeral fracture osteosynthesis: a finite element analysis.

    Science.gov (United States)

    Kennedy, Jim; Feerick, Emer; McGarry, Patrick; FitzPatrick, David; Mullett, Hannan

    2013-08-01

    PURPOSE. To measure the effect of void-filling calcium triphosphate cement on the loads at the implant-bone interface of a proximal humeral fracture osteosynthesis using a finite element analysis. METHODS. Finite element models of a 3-part proximal humeral fracture fixed with a plate with and without calcium triphosphate cement augmentation were generated from a quantitative computed tomography dataset of an intact proximal humerus. Material properties were assigned to bone fragments using published expressions relating Young's modulus to local Hounsfield number. Boundary conditions were then applied to the model to replicate the physiological loads. The effect of void-filling calcium triphosphate cement was analysed. RESULTS. When the void was filled with calcium triphosphate cement, the pressure gradient of the bone surrounding the screws in the medial fracture fragment decreased 97% from up to 21.41 to 0.66 MPa. Peak pressure of the fracture planes decreased 95% from 6.10 to 0.30 MPa and occurred along the medial aspect. The mean stress in the screw locking mechanisms decreased 78% from 71.23 to 15.92 MPa. The angled proximal metaphyseal screw had the highest stress. CONCLUSION. Augmentation with calcium triphosphate cement improves initial stability and reduces stress on the implant-bone interface. PMID:24014777

  9. Sources of calcium in agonist-induced contraction of rat distal colon smooth muscle in vitro

    Institute of Scientific and Technical Information of China (English)

    Hua Zhou; De-Hu Kong; QunWan Pan; HaiHua Wang

    2008-01-01

    AIM:To study the origin of calcium necessary foragonist-induced contraction of the distal colon in rats.METHODS:The change in intracellular calcium concentration ([Ca2+]i)evoked by elevating external Ca2+was detected by fura 2/AM fluorescence.Contractile activity was measured with a force displacement transducer.Tension was continuously monitored and recorded using a Powerlab 4/25T data acquisition system with an ML110 bridge bioelectric physiographic amplifier.RESULTS:Store depletion induced Ca2+ influx had an effect on [Ca2+]i.In nominally Ca2+-free medium,the sarco-endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (1 μmol/L) increased [Ca2+]i from 68 to 241 nmol/L,and to 458 (P<0.01) and 1006 nmol/L (P<0.01),respectively,when 1.5 mmol/L and 3.0 mmol/L extracellular Ca2+ was reintroduced.Furthermore,the change in [Ca2+]1.was observed with verapamil (5 μmol/L),La3+(1 mmol/L) or KCI (40 mmol/L) in the bathing solution.These channels were sensitive to La3+(P<0.01),insensitive to verapamil,and voltage independent.In isolated distal colons we found that in normal Krebs solution,contraction induced by acetylcholine (ACh) was partially inhibited by verapamil,and the inhibitory rate was 41% (P<0.05).On the other hand,in Ca2+-free Krebs solution,ACh induced transient contraction due to Ca2+ release from the inLracellular stores.The transient contraction lasted until the Ca2+ store was depleted.Restoration of extracellular Ca2+ in the presence of atropine produced contraction,mainly due to Ca2+ influx.Such contraction was not inhibited by verapamil,but was decreased by La3+ (50 μmol/L) from 0.96 to 0.72 g (P<0.01).CONCLUSION:The predominant source of activator Ca2+ for the contractile response to agonist is extracellular Ca2+,and intracellular Caz+ has little role to play in mediating excitation-contraction coupling by agonists in rat distal colon smooth muscle in vitro.The influx of extracellular Ca2+ is mainly mediated through voltage-,receptor- and

  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. Binding of calcium and carbonate to polyacrylates.

    Science.gov (United States)

    Tribello, Gareth A; Liew, CheeChin; Parrinello, Michele

    2009-05-21

    Polyacrylate molecules can be used to slow the growth of calcium carbonate. However, little is known about the mechanism by which the molecules impede the growth rate. A recent computational study (Bulo et al. Macromolecules 2007, 40, 3437) used metadynamics to investigate the binding of calcium to polyacrylate chains and has thrown some light on the coiling and precipitation of these polymers. We extend these simulations to examine the binding of calcium and carbonate to polyacrylate chains. We show that calcium complexed with both carbonate and polyacrylate is a very stable species. The free energies of calcium-carbonate-polyacrylate complexes, with different polymer configurations, are calculated, and differences in the free energy of the binding of carbonate are shown to be due to differences in the amount of steric hindrance about the calcium, which prevents the approach of the carbonate ion. PMID:19400592

  12. 28 CFR 2.41 - Travel approval.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Travel approval. 2.41 Section 2.41..., YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.41 Travel approval. (a) The probation officer may approve travel outside the district without approval of...

  13. 22 CFR 51.41 - Documentary evidence.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Documentary evidence. 51.41 Section 51.41 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Evidence of U.S. Citizenship or Nationality § 51.41 Documentary evidence. The applicant must provide documentary evidence that he or she is...

  14. 27 CFR 41.112 - Tax return.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Tax return. 41.112 Section 41.112 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF... States Deferred Payment of Tax in Puerto Rico on Tobacco Products § 41.112 Tax return. The...

  15. 45 CFR 400.41 - Definitions

    Science.gov (United States)

    2010-10-01

    ... Identification of Refugees § 400.41 Definitions For purposes of this subpart— Applicant for asylum means an... 45 Public Welfare 2 2010-10-01 2010-10-01 false Definitions 400.41 Section 400.41 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN...

  16. 46 CFR 356.41 - Management agreements.

    Science.gov (United States)

    2010-10-01

    ... which the management company provides marketing services, consulting services or other services that are... 46 Shipping 8 2010-10-01 2010-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner...

  17. 43 CFR 41.405 - Housing.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Housing. 41.405 Section 41.405 Public... in Education Programs or Activities Prohibited § 41.405 Housing. (a) Generally. A recipient shall not... offer different services or benefits related to housing, except as provided in this section...

  18. 7 CFR 1215.41 - Contracts.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Contracts. 1215.41 Section 1215.41 Agriculture..., Consumer Information, and Industry Information § 1215.41 Contracts. The Board shall not contract with any... and approved by the Secretary. Any contract or agreement shall provide that: (a) The contractor...

  19. 22 CFR 41.12 - Classification symbols.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Classification symbols. 41.12 Section 41.12... AND NATIONALITY ACT, AS AMENDED Classification of Nonimmigrants § 41.12 Classification symbols. A visa... appropriate visa symbol to show the classification of the alien. The symbol shall be inserted in the...

  20. 43 CFR 41.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.310 Section 41.310 Public... in Admission and Recruitment Prohibited § 41.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  1. 43 CFR 41.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.510 Section 41.510 Public... in Employment in Education Programs or Activities Prohibited § 41.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  2. 43 CFR 41.540 - Advertising.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Advertising. 41.540 Section 41.540 Public... in Employment in Education Programs or Activities Prohibited § 41.540 Advertising. A recipient shall not in any advertising related to employment indicate preference, limitation, specification,...

  3. 29 CFR 1917.41 - House falls.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false House falls. 1917.41 Section 1917.41 Labor Regulations...) MARINE TERMINALS Cargo Handling Gear and Equipment § 1917.41 House falls. (a) Span beams shall be secured... working with house fall blocks. (c) Designated employees shall inspect chains, links, shackles,...

  4. 14 CFR 431.41 - Communications plan.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Communications plan. 431.41 Section 431.41... Launch and Reentry of a Reusable Launch Vehicle § 431.41 Communications plan. (a) An applicant shall submit a plan providing vehicle safety operations personnel communications procedures during the...

  5. 15 CFR 265.41 - Gambling.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Gambling. 265.41 Section 265.41..., GAITHERSBURG, MARYLAND, AND BOULDER AND FORT COLLINS, COLORADO Buildings and Grounds § 265.41 Gambling. No... gambling devices, the conduct of lotteries or pools, or in the selling or purchasing of numbers tickets,...

  6. 22 CFR 41.71 - Transit aliens.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Transit aliens. 41.71 Section 41.71 Foreign... NATIONALITY ACT, AS AMENDED Transit Aliens § 41.71 Transit aliens. (a) Transit aliens—general. An alien is classifiable as a nonimmigrant transit alien under INA 101(a) (15) (C) if the consular officer is...

  7. 22 CFR 204.41 - Arbitration.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Arbitration. 204.41 Section 204.41 Foreign... § 204.41 Arbitration. Any controversy or claim between A.I.D. and the Lender or any Assignee arising out of this Guaranty shall be settled by arbitration to be held in Washington, DC in accordance with...

  8. 22 CFR 221.41 - Arbitration.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Arbitration. 221.41 Section 221.41 Foreign... Administration § 221.41 Arbitration. Any controversy or claim between A.I.D. and any noteholder arising out of this Guarantee shall be settled by arbitration to be held in Washington, DC in accordance with the...

  9. 40 CFR 230.41 - Wetlands.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Wetlands. 230.41 Section 230.41... Aquatic Sites § 230.41 Wetlands. (a)(1) Wetlands consist of areas that are inundated or saturated by...) Where wetlands are adjacent to open water, they generally constitute the transition to upland....

  10. 50 CFR 85.41 - Allowable costs.

    Science.gov (United States)

    2010-10-01

    ... applicable Federal cost principles in 43 CFR 12.60(b). Purchase of informational signs, program signs, and... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Allowable costs. 85.41 Section 85.41... Use/Acceptance of Funds § 85.41 Allowable costs. (a) Allowable grant costs are limited to those...

  11. 8 CFR 1240.41 - Immigration judges.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judges. 1240.41 Section 1240.41 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION..., 1997) § 1240.41 Immigration judges. (a) Authority. In any proceeding conducted under this part...

  12. 40 CFR 406.41 - Specialized definitions.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Specialized definitions. 406.41 Section 406.41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Bulgur Wheat Flour Milling Subcategory § 406.41...

  13. 29 CFR 97.41 - Financial reporting.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Financial reporting. 97.41 Section 97.41 Labor Office of the... LOCAL GOVERNMENTS Post-Award Requirements Reports, Records Retention, and Enforcement § 97.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a)(2) and (5) of this section, grantees...

  14. 45 CFR 602.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Financial reporting. 602.41 Section 602.41 Public... Requirements § 602.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when...

  15. 45 CFR 1157.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Financial reporting. 1157.41 Section 1157.41... Enforcement § 1157.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when...

  16. 49 CFR 18.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Financial reporting. 18.41 Section 18.41... Enforcement § 18.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when...

  17. 22 CFR 135.41 - Financial reporting.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Financial reporting. 135.41 Section 135.41... Enforcement § 135.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when...

  18. 29 CFR 1470.41 - Financial reporting.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Financial reporting. 1470.41 Section 1470.41 Labor... Reports, Records Retention, and Enforcement § 1470.41 Financial reporting. (a) General. (1) Except as... authorized by OMB, for: (i) Submitting financial reports to Federal agencies, or (ii) Requesting advances...

  19. 45 CFR 1174.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Financial reporting. 1174.41 Section 1174.41... Enforcement § 1174.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when...

  20. 45 CFR 1183.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Financial reporting. 1183.41 Section 1183.41... Enforcement § 1183.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a)(2) and (5) of...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when...

  1. 19 CFR 12.41 - Prohibited films.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Prohibited films. 12.41 Section 12.41 Customs... SPECIAL CLASSES OF MERCHANDISE Immoral Articles § 12.41 Prohibited films. (a) Importers of films, shall certify on Customs Form 3291 that the imported films contain no obscene or immoral matter, nor any...

  2. 27 CFR 4.1 - General.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false General. 4.1 Section 4.1 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.1 General. The regulations in this part...

  3. 12 CFR 560.41 - Leasing.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Leasing. 560.41 Section 560.41 Banks and... Investment Powers for Federal Savings Associations § 560.41 Leasing. (a) Permissible activities. Subject to the limitations of this section, a Federal savings association may engage in leasing activities....

  4. 43 CFR 41.525 - Fringe benefits.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Fringe benefits. 41.525 Section 41.525... in Employment in Education Programs or Activities Prohibited § 41.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical,...

  5. 9 CFR 146.41 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Definitions. 146.41 Section 146.41 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...-Type Turkey Slaughter Plants § 146.41 Definitions. Meat-type turkey. A domesticated turkey grown...

  6. 43 CFR 41.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Compensation. 41.515 Section 41.515 Public... in Employment in Education Programs or Activities Prohibited § 41.515 Compensation. A recipient shall... of pay or other compensation; (b) Results in the payment of wages to employees of one sex at a...

  7. 30 CFR 36.41 - Testing methods.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Testing methods. 36.41 Section 36.41 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF... Requirements § 36.41 Testing methods. Mobile diesel-powered transportation equipment submitted...

  8. 29 CFR 1912.41 - Legal services.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Legal services. 1912.41 Section 1912.41 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) ADVISORY COMMITTEES ON STANDARDS Miscellaneous § 1912.41 Legal services. The Solicitor of Labor...

  9. 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...

  10. 28 CFR 527.41 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Definitions. 527.41 Section 527.41 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INMATE ADMISSION, CLASSIFICATION, AND TRANSFER TRANSFERS Transfer of Offenders To or From Foreign Countries § 527.41 Definitions. For the purpose of this rule the following definitions...

  11. 7 CFR 2902.41 - Metalworking fluids.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Metalworking fluids. 2902.41 Section 2902.41... Items § 2902.41 Metalworking fluids. (a) Definition. (1) Fluids that are designed to provide cooling, lubrication, corrosion prevention, and reduced wear on the contact parts of machinery used for...

  12. 7 CFR 993.41 - Marketing policy.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing policy. 993.41 Section 993.41 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Marketing Policy § 993.41 Marketing policy. (a) On or before the first...

  13. 24 CFR 206.41 - Counseling.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Counseling. 206.41 Section 206.41... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgagors § 206.41 Counseling. (a) List... receive counseling. (b) Information to be provided. A counselor must discuss with the mortgagor: (1)...

  14. Regulation of the Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells.

    Science.gov (United States)

    Asanoma, Kazuo; Liu, Ge; Yamane, Takako; Miyanari, Yoko; Takao, Tomoka; Yagi, Hiroshi; Ohgami, Tatsuhiro; Ichinoe, Akimasa; Sonoda, Kenzo; Wake, Norio; Kato, Kiyoko

    2015-12-01

    BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors that play key roles in multiple cell behaviors. BHLHE40/41 were recently shown to be involved in an epithelial-to-mesenchymal transition (EMT). However, the precise mechanism of EMT control by BHLHE40/41 remains unclear. In the present study, we demonstrated that BHLHE40/41 expression was controlled in a pathological stage-dependent manner in human endometrial cancer (HEC). Our in vitro assays showed that BHLHE40/41 suppressed tumor cell invasion. BHLHE40/41 also suppressed the transcription of the EMT effectors SNAI1, SNAI2, and TWIST1. We identified the critical promoter regions of TWIST1 for its basal transcriptional activity. We elucidated that the transcription factor SP1 was involved in the basal transcriptional activity of TWIST1 and that BHLHE40/41 competed with SP1 for DNA binding to regulate gene transcription. This study is the first to report the detailed functions of BHLHE40 and BHLHE41 in the suppression of EMT effectors in vitro. Our results suggest that BHLHE40/41 suppress tumor cell invasion by inhibiting EMT in tumor cells. We propose that BHLHE40/41 are promising markers to predict the aggressiveness of each HEC case and that molecular targeting strategies involving BHLHE40/41 and SP1 may effectively regulate HEC progression.

  15. 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...

  16. Biphasic calcium phosphate in periapical surgery

    OpenAIRE

    Suneelkumar, Chinni; Datta, Krithika; Manali R Srinivasan; Kumar, Sampath T

    2008-01-01

    Calcium phosphate ceramics like hydroxyapatite and β -tricalcium phosphate (β -TCP) possess mineral composition that closely resembles that of the bone. They can be good bone substitutes due to their excellent biocompatibility. Biphasic calcium phosphate is a bone substitute which is a mixture of hydroxyapatite and β -tricalcium phosphate in fixed ratios. Studies have demonstrated the osteoconductive potential of this composition. This paper highlights the clinical use of biphasic calcium pho...

  17. 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.

  18. [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.

  19. 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.

  20. 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. PMID:23212081

  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. Calcium supplements: do they help or harm?

    Science.gov (United States)

    Manson, Joann E; Bassuk, Shari S

    2014-01-01

    Current recommendations for calcium intake call for 1,000 mg per day for women ages 19-50 and 1,200 mg per day for women over age 50 to ensure bone health. Given recent concerns that calcium supplements may raise risk for cardiovascular disease and kidney stones, women should aim to meet this recommendation primarily by eating a calcium-rich diet and taking calcium supplements only if needed to reach the RDA goal (often only approximately 500 mg per day in supplements is required). PMID:23880796

  3. Peroxisome is a reservoir of intracellular calcium.

    Science.gov (United States)

    Raychaudhury, Bikramjit; Gupta, Shreedhara; Banerjee, Shouvik; Datta, Salil C

    2006-07-01

    We have examined fura 2-loaded purified peroxisomes under confocal microscope to prove that this mammalian organelle is a store of intracellular calcium pool. Presence of calcium channel and vanadate sensitive Ca(2+)-ATPase in the purified peroxisomal membrane has been demonstrated. We have further observed that machineries to maintain calcium pool in this mammalian organelle are impaired during infection caused by Leishmania donovani. Results reveal that peroxisomes have a merit to play a significant role in the metabolism of intracellular calcium. PMID:16713100

  4. Calcium Imaging Perspectives in Plants

    Directory of Open Access Journals (Sweden)

    Chidananda Nagamangala Kanchiswamy

    2014-03-01

    Full Text Available 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.

  5. Calcium Absorption from Fortified Ice Cream Formulations Compared with Calcium Absorption from Milk

    OpenAIRE

    van der Hee, Regine M.; Miret, Silvia; Slettenaar, Marieke; Duchateau, Guus S.M.J.E.; Rietveld, Anton G.; Wilkinson, Joy E.; Quail, Patricia J.; Berry, Mark J.; Dainty, Jack R.; Teucher, Birgit; Fairweather-Tait, Susan J

    2009-01-01

    Objective Optimal bone mass in early adulthood is achieved through appropriate diet and lifestyle, thereby protecting against osteoporosis and risk of bone fracture in later life. Calcium and vitamin D are essential to build adequate bones, but calcium intakes of many population groups do not meet dietary reference values. In addition, changes in dietary patterns are exacerbating the problem, thereby emphasizing the important role of calcium-rich food products. We have designed a calcium-fort...

  6. Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

    OpenAIRE

    A Rathod; Bonny, O; Guessous, I; Suter, P M; Conen, D; Erne, P; Binet, I; Gabutti, L; Gallino, A; Muggli, F; Hayoz, D; Pechere-Bertschi, A; Paccaud, F.; Burnier, M.; Bochud, M

    2015-01-01

    BACKGROUND AND OBJECTIVES: Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dep...

  7. The Kinetics of Calcination of High Calcium Limestone

    Directory of Open Access Journals (Sweden)

    P. C. Okonkwo

    2012-02-01

    Full Text Available The kinetics of calcination of a high calcium type of limestone was studied. Ukpilla limestone found in the central region of Nigeria was studied. The limestone composition shows that the limestone has 51.29% calcium oxide and 41.53% loss on ignition and magnesium oxide content of 2.23%. The following parameters were determined; diffusion coefficient of lime layer, and mass transfer coefficient, conductivity of lime layer and beat transfer coefficient, convective parameter and diffusive parameter for temperatures 9000C, 10000C, 10600C and 10800C. The reaction was found to be limited by mass and heat transfers across the tune layer of the calcining article, theoptimal temperature of calcination was found to be 10600C. Diffusivity and mass transfer coefficient decreases with increase in calcination temperature. The thermal conductivity increases with increase in temperature. The diffusive and convective parameter decreases with increase in temperature. The reactivity of lime calcined at different temperatures were determined. The reactivity of the lime increases with decrease in calcination temperature.

  8. Calcium

    Science.gov (United States)

    ... for lunch; and beans, salsa, taco sauce, and cheese for dinner. Create mini-pizzas by topping whole-wheat English muffins or bagels with pizza sauce and low-fat mozzarella or soy cheese. Try whole-grain crackers with low-fat cheese ...

  9. 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 ...

  10. 41 CFR 102-41.235 - May we sell forfeited drug paraphernalia?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false May we sell forfeited drug paraphernalia? 102-41.235 Section 102-41.235 Public Contracts and Property Management Federal... Requiring Special Handling Drug Paraphernalia § 102-41.235 May we sell forfeited drug paraphernalia? No,...

  11. 41 CFR 102-41.175 - May we sell unclaimed personal property?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false May we sell unclaimed personal property? 102-41.175 Section 102-41.175 Public Contracts and Property Management Federal Property... § 102-41.175 May we sell unclaimed personal property? Yes, you may sell unclaimed personal...

  12. 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.

  13. 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...

  14. 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...

  15. 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.

  16. 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. PMID:25078809

  17. The Calcium Triplet metallicity calibration for galactic bulge stars

    CERN Document Server

    Vasquez, S; Hill, V; Gonzalez, O A; Saviane, I; Rejkuba, M; Battaglia, G

    2015-01-01

    We present a new calibration of the Calcium II Triplet equivalent widths versus [Fe/H], constructed upon K giant stars in the Galactic bulge. This calibration will be used to derive iron abundances for the targets of the GIBS survey, and in general it is especially suited for solar and supersolar metallicity giants, typical of external massive galaxies. About 150 bulge K giants were observed with the GIRAFFE spectrograph at VLT, both at resolution R~20,000 and at R~6,000. In the first case, the spectra allowed us to perform direct determination of Fe abundances from several unblended Fe lines, deriving what we call here high resolution [Fe/H] measurements. The low resolution spectra allowed us to measure equivalent widths of the two strongest lines of the near infrared Calcium II triplet at 8542 and 8662 A. By comparing the two measurements we derived a relation between Calcium equivalent widths and [Fe/H] that is linear over the metallicity range probed here, -1<[Fe/H]<+0.7. By adding a small second or...

  18. A new organic reference material, L-glutamic acid, USGS41a, for δ13C and δ15N measurements − a replacement for USGS41

    Science.gov (United States)

    Qi, Haiping; Coplen, Tyler B.; Mroczkowski, Stanley J.; Brand, Willi A.; Brandes, Lauren; Geilmann, Heike; Schimmelmann, Arndt

    2016-01-01

    RationaleThe widely used l-glutamic acid isotopic reference material USGS41, enriched in both 13C and 15N, is nearly exhausted. A new material, USGS41a, has been prepared as a replacement for USGS41.MethodsUSGS41a was prepared by dissolving analytical grade l-glutamic acid enriched in 13C and 15N together with l-glutamic acid of normal isotopic composition. The δ13C and δ15N values of USGS41a were directly or indirectly normalized with the international reference materials NBS 19 calcium carbonate (δ13CVPDB = +1.95 mUr, where milliurey = 0.001 = 1 ‰), LSVEC lithium carbonate (δ13CVPDB = −46.6 mUr), and IAEA-N-1 ammonium sulfate (δ15NAir = +0.43 mUr) and USGS32 potassium nitrate (δ15N = +180 mUr exactly) by on-line combustion, continuous-flow isotope-ratio mass spectrometry, and off-line dual-inlet isotope-ratio mass spectrometry.ResultsUSGS41a is isotopically homogeneous; the reproducibility of δ13C and δ15N is better than 0.07 mUr and 0.09 mUr, respectively, in 200-μg amounts. It has a δ13C value of +36.55 mUr relative to VPDB and a δ15N value of +47.55 mUr relative to N2 in air. USGS41 was found to be hydroscopic, probably due to the presence of pyroglutamic acid. Experimental results indicate that the chemical purity of USGS41a is substantially better than that of USGS41.ConclusionsThe new isotopic reference material USGS41a can be used with USGS40 (having a δ13CVPDB value of −26.39 mUr and a δ15NAir value of −4.52 mUr) for (i) analyzing local laboratory isotopic reference materials, and (ii) quantifying drift with time, mass-dependent isotopic fractionation, and isotope-ratio-scale contraction for isotopic analysis of biological and organic materials. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

  19. Translocation and bonding of calcium (45Ca) in two-year-old seedlings of spruce (Picea abies[L.] Karst.) and pine (Pinus sylvestris L.)

    International Nuclear Information System (INIS)

    Within the framework of the project ''Effect of liming and magnesium fertilization on the uptake, transport, and chemical bonding form of calcium and magnesium in conifers'', experiments regarding the calcium budget of two-year-old spruce and pine seedlings under conditions of controlled nutrition in a gravel culture were carried out. Two variants of calcium nutrition demonstrated which of the mechanisms in the calcium metabolism of trees are dependent on changes in element availability. Root labelling using the radioactive tracer 45Ca permitted aimed investigation of the uptake and translocation of calcium during shoot formation in May. The functional importance of the investigated nutritive element was characterized by breaking up the total calcium contents (45Ca) into the three essential chemical bonding forms (water-soluble Ca, Ca-pectate, Ca-oxalate) for the different tree fractions.- The culture experiments led to the conclusion that the root tips are most important as sites of calcium uptake. Translocation within the roots to the shoot took place via diffusion and exchange displacement as a function of calcium supply in the nutritive solution. There is no clue to support the assumption of a regulation of calcium uptake in spruces; in pines, by contrast, it cannot be excluded.- From a nutrition-physiological viewpoint, a total calcium content of 2 mg per gramme of dry mass is to be considered as sufficient. As this target is always attained, even where calcium supply is scarce, it is not appropriate to equate increased calcium availability with enhanced nutrient supply. Rather, the results discussed seem to support the theory that the trees now need to detoxicate excessively high calcium concentrations, which are liable to endanger the physiological cell metabolism, by a reaction with oxalic acid resulting in the formation of calcium oxalate. (orig.)

  20. 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.

  1. Presynaptic calcium signalling in cerebellar mossy fibres

    Directory of Open Access Journals (Sweden)

    Louiza B Thomsen

    2010-02-01

    Full Text Available 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 TTX-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. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none tetrodotoxin (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 appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than one second affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

  2. Elevated Intracellular Calcium Increases Ferritin H Expression Through an NFAT-Independent Posttranscriptional Mechanism Involving mRNA Stabilization

    OpenAIRE

    MacKenzie, Elizabeth L.; Tsuji, Yoshiaki

    2008-01-01

    An increase in intracellular Ca2+ is one of the initiating events in T cell activation. A calcium-mediated signaling cascade in T cells involves activation of calcineurin and the dephosphorylation and translocation of Nuclear Factor of Activated T-cells (NFAT), resulting in the transcriptional activation of target genes such as IL-2. In the present study, we found that increased intracellular calcium leads to induction of the antioxidant protein ferritin H. We previously reported that the fer...

  3. 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.

  4. 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.

  5. Calcium and Vitamin D: Important at Every Age

    Science.gov (United States)

    ... supported by your browser. Home Bone Basics Nutrition Calcium and Vitamin D: Important at Every Age Publication ... Osteoporosis Program For Your Information The Role of Calcium Calcium is needed for our heart, muscles, and ...

  6. Bone Up on the Need for Calcium.

    Science.gov (United States)

    Mann, Peggy

    1987-01-01

    Most grade-schoolers drink milk at each meal, but teens, especially girls, often switch to carbonated soda at mealtime just as they should be building up their bone bank of calcium. Why calcium is important and how to get enough of it are covered. (MT)

  7. Stochastic models of intracellular calcium signals

    International Nuclear Information System (INIS)

    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

  8. Stochastic Kinetics of Intracellular Calcium Oscillations

    Institute of Scientific and Technical Information of China (English)

    陈昌胜; 曾仁端

    2003-01-01

    A stochastic model of intracellular calcium oscillations is put forward by taking into account the random opening-closing of Ca2+ channels in endoplasmic reticulum (ER) membrane. The numerical results of the stochastic model show simple and complex calcium oscillations, which accord with the experiment results.

  9. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

    salts. The perturbation of calcium equilibria by these factors will affect the final properties of acid, calcium and rennet milk gels. By decreasing the pH from 6.0 to 5.2 (acid gels), the calcium equilibrium was significantly affected by temperature (4, 20, 30, 40 oC), and different combinations...... of temperature and pH may result in different final structure properties in dairy products such as cheese. A significant amount of calcium remained in the micelles between pH 4.8 and 4.6, this can contribute to the final strength of acid milk gels, such as in yogurt or in cream cheeses. After the gelation point...... enriched dairy products. Calcium gels can be produced by addition of a calcium salt and heat treatment at temperatures higher than 70 oC for several minutes. The combination of heat treatment and calcium addition to milk with pH values between 6.6 and 5.6, will produce calcium milk gels with unique...

  10. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

    WELBERG, JWM; KLEIBEUKER, JH; VANDERMEER, R; MULDER, NH; DEVRIES, EGE

    1991-01-01

    Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal epithel

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. Optogenetic Control of Calcium Oscillation Waveform Defines NFAT as an Integrator of Calcium Load.

    Science.gov (United States)

    Hannanta-Anan, Pimkhuan; Chow, Brian Y

    2016-04-27

    It is known that the calcium-dependent transcription factor NFAT initiates transcription in response to pulsatile loads of calcium signal. However, the relative contributions of calcium oscillation frequency, amplitude, and duty cycle to transcriptional activity remain unclear. Here, we engineer HeLa cells to permit optogenetic control of intracellular calcium concentration using programmable LED arrays. This approach allows us to generate calcium oscillations of constant peak amplitude, in which frequency is varied while holding duty cycle constant, or vice versa. Using this setup and mathematical modeling, we show that NFAT transcriptional activity depends more on duty cycle, defined as the proportion of the integrated calcium concentration over the oscillation period, than on frequency alone. This demonstrates that NFAT acts primarily as a signal integrator of cumulative load rather than a frequency-selective decoder. This approach resolves a fundamental question in calcium encoding and demonstrates the value of optogenetics for isolating individual dynamical components of larger signaling behaviors. PMID:27135540

  18. 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.

  19. Effects of Nickel on Calcium Phosphate Formation

    Science.gov (United States)

    Guerra-López, J.; González, R.; Gómez, A.; Pomés, R.; Punte, G.; Della Védova, C. O.

    2000-05-01

    We have investigated the effect of nickel on calcium phosphate formation from aqueous solutions. The calcium phosphates prepared under different reaction conditions (pH, temperature, and nickel concentration) were characterized by X-ray diffraction, FTIR spectroscopy, and chemical analysis. The apatite compounds were also studied thermogravimetrically. From the combined results of the techniques employed we have determined that nickel favors the formation of brushite and amorphous calcium phosphate. We have found, as well, that the presence of nickel in the solution inhibits calcium hydroxyapatite (CaHAP) and octacalcium phosphate formation. However in the synthesis performed at basic pH and 95°C the apatitic phase (HAP) could be obtained. The present results suggest that the presence of nickel may modify the precipitation of oral calcium phosphate.

  20. 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.

  1. 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

  2. Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41.

    Science.gov (United States)

    Basiorka, Ashley A; McGraw, Kathy L; De Ceuninck, Leentje; Griner, Lori N; Zhang, Ling; Clark, Justine A; Caceres, Gisela; Sokol, Lubomir; Komrokji, Rami S; Reuther, Gary W; Wei, Sheng; Tavernier, Jan; List, Alan F

    2016-06-15

    In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-Rα receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. Cancer Res; 76(12); 3531-40. ©2016 AACR. PMID:27197154

  3. 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...

  4. Tyroserleutide tripeptide affects calcium homeostasis of human hepatocarcinoma BEL-7402 cells

    Institute of Scientific and Technical Information of China (English)

    FU Zheng; LU Rong; LI Guoli; ZHAO Lan; GAO Weizhen; CHE Xuchun; JIAN Xu; ZHOU Chunlei; YAO Zhi

    2005-01-01

    This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg·kg-1·d-1, 160μg·kg-1·d-1 and 320μg·kg-1·d-1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium overload. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p<0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.

  5. Calcium: a code coupling tool

    International Nuclear Information System (INIS)

    Today, the calculation performances of computers allow the precise and global simulation of complex industrial processes such as the functioning of a nuclear reactor core. One can question the need for the elaboration of new global numerical models in order to make use of the overall capability of computers. Another less time consuming solution consist in the coupling of existing well validated numerical models in order to make them working together. This paper presents the basic principles of the coupling of numerical codes, the tools required, the Calcium tool for codes coupling and an example of application of this tool in the coupling of the THYC (EdF), COCCINELLE (EdF) and CATHARE (CEA-EdF-Framatome) codes for the modeling of the thermal-hydraulic and neutronic behaviour of a reactor core during accidental situation. (J.S.)

  6. 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...

  7. Molecular aspects of intestinal calcium absorption.

    Science.gov (United States)

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  8. 48 CFR 2131.205-41 - Taxes.

    Science.gov (United States)

    2010-10-01

    ....S.C. 8714(c) or other Federal law prohibits the imposition of taxes, fees, or other monetary... preempted tax is an unallowable expense under FAR 31.205-41(b)(3). (c) Paragraph (b)(1) of FAR 31.205-41 is...) Notwithstanding any other provision in FAR 31.205-41, an amount equal to the “DAC Tax” is an allowable tax...

  9. Measurements of natural 41Ca concentrations

    International Nuclear Information System (INIS)

    Atomic mass spectroscopic examinations on 41Ca were carried out in the UNILAC accelerator. A sensitivity of about 10-15 was achieved. This would allow the measurement of present natural 41Ca concentrations as soon as the problem of the transmission determination is solved. In this respect suggestions were worked out and their feasibility discussed. The detection of 41Ca-ions is especially free of background when high UNILAC-energies are applied. An estimation showed a background level corresponding with a 41Ca concentration of less then 10-17 referred to 40Ca. Besides an independent concept for the electromagnetic concentration of 41Ca with variable concentration factors was developed. After being concentrated up to 50 respectively 25 times the initial concentration in the GSI mass separator, the 41Ca concentration of three recent deer bones found in the Odenwald was measured by atomic mass spectroscopy in the 14UD-Pelletron Tandem in Rehovot (Israel). The measured 41Ca concentrations ranged between 10-14 to 10-13 with consideration of the concentration factor. A theoretical study of the 41Ca production in the earth's surface based on cosmic radiation illustrates the influence of trace elements on the neutron flux and thus on the 41Ca production. This influence might be a possible explanation for the observed amplitude of variation of the 41Ca concentration in recent bones which are of decisive importance for the feasibility of 41Ca-related dating. In this work a method is suggested that does not depend on the amplitude of variation mentioned above and which would allow the determination of the erosion rate of rocks by its 41Ca concentrations. (orig./HP)

  10. Effects of inositol trisphosphate on calcium mobilization in high-voltage and saponin-permeabilized platelets

    International Nuclear Information System (INIS)

    Interest in phosphatidylinositol metabolism has been greatly stimulated by the findings that diglyceride and inositol phosphates may serve as second messengers in modulating cellular function. Formation of 1,4,5-inositol trisphosphate (IP3), in particular, has been linked to mobilization of intracellular calcium in a number of cell types. The authors have examined the ability of IP3 to mobilize calcium in human platelets permeabilized by either saponin or high-voltage discharge. Saponin at 15 μg/ml effectively permeabilized platelets to exogenous inositol 1,4,5-trisphosphate which released bound [45Ca] within 1 min and with a Ka of 7.4 +/- 4.1 μM. A small (25%) azide-sensitive pool was also responsive to inositol trisphosphate. The calcium pools were completely discharged by A-23187 and the ATP-dependent uptake was prevented by dinitrophenol. In contrast to the result with saponin, platelets accessed by high-voltage discharge were insensitive to challenge by inositol 1,4,5-trisphosphate. The data suggest that while inositol 1,4,5-trisphosphate can rapidly mobilize platelet calcium, the ability to demonstrate this depends on the method of permeabilization

  11. 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.

  12. 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.

  13. Requirement of the isocitrate lyase gene ICL1 for VPS41-mediated starvation response in Cryptococcus neoformans.

    Science.gov (United States)

    Xu, Zhe; Zhi, Yafei; Dong, Jianzhang; Lin, Benfeng; Ye, Di; Liu, Xiaoguang

    2016-07-01

    Cryptococcus neoformans is a major cause of fungal meningitis in individuals with impaired immunity. Our previous studies have shown that the VPS41 gene plays a critical role in the survival of Cryptococcus neoformans under nitrogen starvation; however, the molecular mechanisms underlying VPS41-mediated starvation response remain to be elucidated. In the present study, we show that, under nitrogen starvation, VPS41 strongly enhanced ICL1 expression in C. neoformans and that overexpression of ICL1 in the vps41 mutant dramatically suppressed its defects in starvation response due to the loss of VPS41 function. Moreover, targeted deletion of ICL1 resulted in a dramatic decline in viability of C. neoformans cells under nitrogen deprivation. Taken together, our data suggest a model in which VPS41 up-regulates ICL1 expression, directly or indirectly, to promote survival of C. neoformans under nitrogen starvation. PMID:27350614

  14. 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.

  15. 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.

  16. 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.

  17. Calcium Signaling Is Required for Erythroid Enucleation

    Science.gov (United States)

    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. PMID:26731108

  18. 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

  19. 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.

  20. Modulation of Intracellular Calcium Levels by Calcium Lactate Affects Colon Cancer Cell Motility through Calcium-Dependent Calpain

    OpenAIRE

    Pasupathi Sundaramoorthy; Jae Jun Sim; Yeong-Su Jang; Siddhartha Kumar Mishra; Keun-Yeong Jeong; Poonam Mander; Oh Byung Chul; Won-Sik Shim; Seung Hyun Oh; Ky-Youb Nam; Hwan Mook Kim

    2015-01-01

    Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstrea...

  1. 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.

  2. 43 CFR 423.41 - Aircraft.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Aircraft. 423.41 Section 423.41 Public... Aircraft. (a) You must comply with any applicable Federal, State, and local laws, and with any additional... this part 423, with respect to aircraft landings, takeoffs, and operation on or in the proximity...

  3. 43 CFR 41.505 - Employment criteria.

    Science.gov (United States)

    2010-10-01

    ... EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 41.505 Employment criteria. A... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Employment criteria. 41.505 Section...

  4. 43 CFR 41.500 - Employment.

    Science.gov (United States)

    2010-10-01

    ... subjected to discrimination in employment, or recruitment, consideration, or selection therefor, whether... §§ 41.500 through 41.550 apply to: (1) Recruitment, advertising, and the process of application for..., layoff, termination, application of nepotism policies, right of return from layoff, and rehiring;...

  5. 22 CFR 40.41 - Public charge.

    Science.gov (United States)

    2010-04-01

    ... Consular Services (22 CFR 22.1). (c) Joint Sponsors. Submission of one or more additional affidavits of... subscribed to before a notary public by the employer or an authorized employee or agent of the employer. The... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Public charge. 40.41 Section 40.41...

  6. 6 CFR 37.41 - Security plan.

    Science.gov (United States)

    2010-01-01

    ... Information (SSI) and must be handled and protected in accordance with 49 CFR Part 1520. ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Security plan. 37.41 Section 37.41 Domestic... Security plan. (a) In General. States must have a security plan that addresses the provisions in...

  7. 12 CFR 41.3 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Definitions. 41.3 Section 41.3 Banks and..., limited liability company, business trust, general or limited partnership, association, or similar..., directly or indirectly, a controlling influence over the management or policies of a company, as the...

  8. 40 CFR 142.41 - Variance request.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Variance request. 142.41 Section 142...) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the Administrator Under Section 1415(a) of the Act § 142.41 Variance request. A supplier of water may request the granting of...

  9. 7 CFR 6.41 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... price-undercutting is occurring. (b) Country of origin means the country, as defined in 19 CFR 134.1(b... 7 Agriculture 1 2010-01-01 2010-01-01 false Definitions. 6.41 Section 6.41 Agriculture Office of the Secretary of Agriculture IMPORT QUOTAS AND FEES Price-Undercutting of Domestic Cheese by...

  10. 37 CFR 41.126 - Arbitration.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Arbitration. 41.126 Section... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.126 Arbitration. (a) Parties to a contested case may resort to binding arbitration to determine any issue in...

  11. 34 CFR 675.41 - Special definitions.

    Science.gov (United States)

    2010-07-01

    ... following definitions apply to this subpart: (a) Work-college: An eligible institution that— (1) Is a public... institution's educational philosophy and program; (2) Requires participation of all resident students for... 34 Education 3 2010-07-01 2010-07-01 false Special definitions. 675.41 Section 675.41...

  12. 37 CFR 41.67 - Appellant's brief.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Appellant's brief. 41.67... Appellant's brief. (a)(1) Appellant(s) may once, within time limits for filing set forth in § 41.66, file a... title. (2) The brief must be signed by the appellant, or the appellant's duly authorized attorney...

  13. 9 CFR 3.41 - Handling.

    Science.gov (United States)

    2010-01-01

    ... person subject to the Animal Welfare Act and holding any live guinea pig or hamster in an animal holding... Welfare regulations and who moves live guinea pigs or hamsters from an animal holding area of a terminal... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Handling. 3.41 Section 3.41...

  14. 44 CFR 5.41 - FEMA publications.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false FEMA publications. 5.41 Section 5.41 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... obtain FEMA publications without charge from the FEMA Headquarters, Regional Offices, the FEMA Library...

  15. 27 CFR 41.60 - Assessment.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Assessment. 41.60 Section... PROCESSED TOBACCO Taxes Assessment of Taxes § 41.60 Assessment. Whenever any person required by law to pay... amount is nominal or the result of an evident mathematical error, no such assessment shall be made...

  16. 7 CFR 3016.41 - Financial reporting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Financial reporting. 3016.41 Section 3016.41 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER... Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of this...

  17. 13 CFR 143.41 - Financial reporting.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Financial reporting. 143.41... Reports, Records, Retention, and Enforcement § 143.41 Financial reporting. (a) General. (1) Except as... authorized by OMB, for: (i) Submitting financial reports to Federal agencies, or (ii) Requesting advances...

  18. 24 CFR 85.41 - Financial reporting.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Financial reporting. 85.41 Section... § 85.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of this... financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when letters of...

  19. 15 CFR 24.41 - Financial reporting.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Financial reporting. 24.41 Section 24..., Records, Retention, and Enforcement § 24.41 Financial reporting. (a) General. (1) Except as provided in... by OMB, for: (i) Submitting financial reports to Federal agencies, or (ii) Requesting advances...

  20. 36 CFR 1207.41 - Financial reporting.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Financial reporting. 1207.41... GOVERNMENTS Post-Award Requirements Reports, Records, Retention, and Enforcement § 1207.41 Financial reporting... forms as may from time to time be authorized by OMB, for: (i) Submitting financial reports to...

  1. 38 CFR 41.230 - Audit costs.

    Science.gov (United States)

    2010-07-01

    ..., the Federal Acquisition Regulation (FAR) (48 CFR parts 30 and 31), or other applicable cost principles... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Audit costs. 41.230 Section 41.230 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED)...

  2. 28 CFR 550.41 - Urine surveillance.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Urine surveillance. 550.41 Section 550.41 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS... aftercare as a condition of release; (2) Who have a known history of drug abuse; or (3) Who are suspected...

  3. 28 CFR 541.41 - Institutional referral.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Institutional referral. 541.41 Section 541.41 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT... alone or together with an inmate's prior history, may warrant consideration for a control unit...

  4. 40 CFR 63.41 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... steam generating unit means any fossil fuel fired combustion unit of more than 25 megawatts that serves... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Definitions. 63.41 Section 63.41... Definitions. Terms used in this subpart that are not defined in this section have the meaning given to them...

  5. 36 CFR 1150.41 - Informal resolution.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Informal resolution. 1150.41... Motions § 1150.41 Informal resolution. (a) The A&TBCB immediately shall send copies of complaints to all... within the ten (10) day period after termination of the one hundred eighty (180) day informal...

  6. 16 CFR 1203.41 - Recordkeeping requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Recordkeeping requirements. 1203.41 Section 1203.41 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS... helmet positioning index (HPI) used to define the proper position of the helmet on the headform; (6)...

  7. 27 CFR 41.34 - Cigarette papers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette papers. 41.34... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.34 Cigarette papers. Cigarette papers are taxed at the...

  8. 31 CFR 8.41 - Solicitation.

    Science.gov (United States)

    2010-07-01

    ... in approved law lists and reputable professional journals and directories, as well as professional... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Solicitation. 8.41 Section 8.41 Money and Finance: Treasury Office of the Secretary of the Treasury PRACTICE BEFORE THE BUREAU OF...

  9. 38 CFR 43.41 - Financial reporting.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Financial reporting. 43.41 Section 43.41 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... required on an annual basis, they will be due 90 days after the grant year. Final reports will be due...

  10. 38 CFR 41.400 - Responsibilities.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Responsibilities. 41.400 Section 41.400 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AUDITS... for providing annual updates of the compliance supplement to OMB. (d) Pass-through...

  11. 38 CFR 41.505 - Audit reporting.

    Science.gov (United States)

    2010-07-01

    ... differently from the manner presented in this section. The auditor's report(s) shall state that the audit was... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Audit reporting. 41.505... OF STATES, LOCAL GOVERNMENTS, AND NON-PROFIT ORGANIZATIONS Auditors § 41.505 Audit reporting....

  12. 44 CFR 295.41 - Administrative appeal.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Administrative appeal. 295.41 Section 295.41 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... supplement the statement of reasons and provide any additional documentary evidence supporting the...

  13. 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.

  14. In vivo Calcium Imaging of Evoked Calcium Waves in the Embryonic Cortex

    OpenAIRE

    Yuryev, Mikhail; Pellegrino, Christophe; Jokinen, Ville; Andriichuk, Liliia; Khirug, Stanislav; Khiroug, Leonard; Rivera, Claudio

    2016-01-01

    The dynamics of intracellular calcium fluxes are instrumental in the proliferation, differentiation, and migration of neuronal cells. Knowledge thus far of the relationship between these calcium changes and physiological processes in the developing brain has derived principally from ex vivo and in vitro experiments. Here, we present a new method to image intracellular calcium flux in the cerebral cortex of live rodent embryos, whilst attached to the dam through the umbilical cord. Using this ...

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

    OpenAIRE

    Sandra Tavares da Silva; Neuza Maria Brunoro Costa; Frederico Souzalima Caldoncelli Franco; Antônio José Natali

    2013-01-01

    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 a...

  16. Technology obtaining of nitrogen fertilizer from the calcium is containing waste of production of calcium saltpetre

    OpenAIRE

    Власян, Світлана Варужанівна; Шестозуб, Анатолій Борисович; Волошин, Микола Дмитрович

    2013-01-01

    The new technology of obtaining nitrogen fertilizer from calcium-containing sludge of calcium saltpeter production is considered in the paper. The main objective of the research is the development of processing technology of sludge of calcium saltpeter production into alkaline nitrogen fertilizer, analysis of the composition of initial material and finished product, testing of fertilizer by means of vegeta­tive studies and determination of expenditure of drying agent that is exhaust gases of ...

  17. {sup 3}H-tetracycline as a proxy for {sup 41}Ca for measuring dietary perturbations of bone resorption

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Connie [Department of Foods and Nutrition, Purdue University, 700 W. State Street, West Lafayette, IN 47906-2059 (United States)]. E-mail: weavercm@purdue.edu; Cheong, Jennifer [Department of Foods and Nutrition, Purdue University, 700 W. State Street, West Lafayette, IN 47906-2059 (United States); Jackson, George [PRIME Lab, Purdue University, West Lafayette, IN (United States); Elmore, David [PRIME Lab, Purdue University, West Lafayette, IN (United States); McCabe, George [Statistics, Purdue University, West Lafayette, IN (United States); Martin, Berdine [Department of Foods and Nutrition, Purdue University, 700 W. State Street, West Lafayette, IN 47906-2059 (United States)

    2007-06-15

    Our group is interested in evaluating early effects of dietary interventions on bone loss. Postmenopausal women lose bone following reduction in estrogen which leads to increased risk of fracture. Traditional means of monitoring bone loss and effectiveness of treatments include changes in bone density, which takes 6 months to years to observe effects, and changes in biochemical markers of bone turnover, which are highly variable and lack specificity. Prelabeling bone with {sup 41}Ca and measuring urinary {sup 41}Ca excretion with accelerator mass spectrometry provides a sensitive, specific, and rapid approach to evaluating effectiveness of treatment. To better understand {sup 41}Ca technology as a tool for measuring effective treatments on reducing bone resorption, we perturbed bone resorption by manipulating dietary calcium in rats. We used {sup 3}H-tetracycline ({sup 3}H-TC) as a proxy for {sup 41}Ca and found that a single dose is feasible to study bone resorption. Suppression of bone resorption, as measured by urinary {sup 3}H-TC, by dietary calcium was observed in rats stabilized after ovariectomy, but not in recently ovariectomized rats.

  18. 3H-tetracycline as a proxy for 41Ca for measuring dietary perturbations of bone resorption

    Science.gov (United States)

    Weaver, Connie; Cheong, Jennifer; Jackson, George; Elmore, David; McCabe, George; Martin, Berdine

    2007-06-01

    Our group is interested in evaluating early effects of dietary interventions on bone loss. Postmenopausal women lose bone following reduction in estrogen which leads to increased risk of fracture. Traditional means of monitoring bone loss and effectiveness of treatments include changes in bone density, which takes 6 months to years to observe effects, and changes in biochemical markers of bone turnover, which are highly variable and lack specificity. Prelabeling bone with 41Ca and measuring urinary 41Ca excretion with accelerator mass spectrometry provides a sensitive, specific, and rapid approach to evaluating effectiveness of treatment. To better understand 41Ca technology as a tool for measuring effective treatments on reducing bone resorption, we perturbed bone resorption by manipulating dietary calcium in rats. We used 3H-tetracycline (3H-TC) as a proxy for 41Ca and found that a single dose is feasible to study bone resorption. Suppression of bone resorption, as measured by urinary 3H-TC, by dietary calcium was observed in rats stabilized after ovariectomy, but not in recently ovariectomized rats.

  19. 3H-tetracycline as a proxy for 41Ca for measuring dietary perturbations of bone resorption

    International Nuclear Information System (INIS)

    Our group is interested in evaluating early effects of dietary interventions on bone loss. Postmenopausal women lose bone following reduction in estrogen which leads to increased risk of fracture. Traditional means of monitoring bone loss and effectiveness of treatments include changes in bone density, which takes 6 months to years to observe effects, and changes in biochemical markers of bone turnover, which are highly variable and lack specificity. Prelabeling bone with 41Ca and measuring urinary 41Ca excretion with accelerator mass spectrometry provides a sensitive, specific, and rapid approach to evaluating effectiveness of treatment. To better understand 41Ca technology as a tool for measuring effective treatments on reducing bone resorption, we perturbed bone resorption by manipulating dietary calcium in rats. We used 3H-tetracycline (3H-TC) as a proxy for 41Ca and found that a single dose is feasible to study bone resorption. Suppression of bone resorption, as measured by urinary 3H-TC, by dietary calcium was observed in rats stabilized after ovariectomy, but not in recently ovariectomized rats

  20. Calcium and Cancer Prevention: Strengths and Limits of the Evidence

    Science.gov (United States)

    ... calcium carbonate has about 40 percent elemental calcium, meaning that 500 mg of calcium carbonate actually contains ... in this trial also contained vitamin D (400 international units [ IU ]). During ... and calcium in relation to prostate cancer risk among more than 142, ...

  1. 21 CFR 172.120 - Calcium disodium EDTA.

    Science.gov (United States)

    2010-04-01

    ... Food Preservatives § 172.120 Calcium disodium EDTA. The food additive calcium disodium EDTA (calcium... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium disodium EDTA. 172.120 Section 172.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  2. 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.

  3. Discrete stochastic modeling of calcium channel dynamics

    CERN Document Server

    Baer, M E; Levine, H; Tsimring, L S; Baer, Markus; Falcke, Martin; Levine, Herbert; Tsimring, Lev S.

    1999-01-01

    We propose a simple discrete stochastic model for calcium dynamics in living cells. Specifically, the calcium concentration distribution is assumed to give rise to a set of probabilities for the opening/closing of channels which release calcium thereby changing those probabilities. We study this model in one dimension, analytically in the mean-field limit of large number of channels per site N, and numerically for small N. As the number of channels per site is increased, the transition from a non-propagating region of activity to a propagating one changes in nature from one described by directed percolation to that of deterministic depinning in a spatially discrete system. Also, for a small number of channels a propagating calcium wave can leave behind a novel fluctuation-driven state, in a parameter range where the limiting deterministic model exhibits only single pulse propagation.

  4. Discrete Stochastic Modeling of Calcium Channel Dynamics

    International Nuclear Information System (INIS)

    We propose a discrete stochastic model for calcium dynamics in living cells. A set of probabilities for the opening/closing of calcium channels is assumed to depend on the calcium concentration. We study this model in one dimension, analytically in the limit of a large number of channels per site N , and numerically for small N . As the number of channels per site is increased, the transition from a nonpropagating region of activity to a propagating one changes from one described by directed percolation to that of deterministic depinning in a spatially discrete system. Also, for a small number of channels a propagating calcium wave can leave behind a novel fluctuation-driven state. (c) 2000 The American Physical Society

  5. 21 CFR 184.1195 - Calcium citrate.

    Science.gov (United States)

    2010-04-01

    ... with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the National Academy Press, 2101... four moles of water per mole of calcium citrate. (b) The ingredient meets the specifications of...

  6. 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.

  7. Effect of albumin and free calcium concentrations on calcium binding in vitro.

    OpenAIRE

    Besarab, A; DeGuzman, A; Swanson, J W

    1981-01-01

    In vivo equilibrium dialysis studies were performed to define further the characteristics of calcium binding to bovine albumin. The concentration range for albumin (1 to 9 g/dl) as well as ultrafilterable calcium (0.5 to 2.5 mM) studied encompassed those that might be ordinarily encountered in most clinical situations. Major differences in the regressions of total calcium on ultrafilterable calcium occurred at albumin concentrations of 1, 2, and 9 g/dl but only small differences at albumin co...

  8. Characterization of Calcium Compounds in Opuntia ficus indica as a Source of Calcium for Human Diet

    OpenAIRE

    Isela Rojas-Molina; Elsa Gutiérrez-Cortez; Moustapha Bah; Alejandra Rojas-Molina; César Ibarra-Alvarado; Eric Rivera-Muñoz; Alicia del Real; Ma. de los Angeles Aguilera-Barreiro

    2015-01-01

    Analyses of calcium compounds in cladodes, soluble dietary fiber (SDF), and insoluble dietary fiber (IDF) of Opuntia ficus indica are reported. The characterization of calcium compounds was performed by using Scanning Electron Microscopy, Energy Dispersive Spectrometry, X-ray diffraction, and infrared spectroscopy. Atomic Absorption Spectroscopy and titrimetric methods were used for quantification of total calcium and calcium compounds. Whewellite (CaC2O4·H2O), weddellite (CaC2O4·(H2O)2.375),...

  9. Relating a calcium indicator signal to the unperturbed calcium concentration time-course

    Directory of Open Access Journals (Sweden)

    Abarbanel Henry DI

    2007-02-01

    Full Text Available Abstract Background Optical indicators of cytosolic calcium levels have become important experimental tools in systems and cellular neuroscience. Indicators are known to interfere with intracellular calcium levels by acting as additional buffers, and this may strongly alter the time-course of various dynamical variables to be measured. Results By investigating the underlying reaction kinetics, we show that in some ranges of kinetic parameters one can explicitly link the time dependent indicator signal to the time-course of the calcium influx, and thus, to the unperturbed calcium level had there been no indicator in the cell.

  10. 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.

  11. Effect of Calcium on the Vanadium Extraction from High Calcium Type Stone Coal

    Institute of Scientific and Technical Information of China (English)

    BAO Shenxu; LIANG Liang; ZHANG Yimin; HAN Shihua; HU Yangjia

    2015-01-01

    The high calcium type stone coal from Hubei province was leached by water and dilute acid separately after being roasted with different dosage of NaCl. The water leaching rate of vanadium (WLRV) was low and only 26.8%of vanadium can be leached by water when 4%NaCl was added, but the acid leaching rate of vanadium (ALRV) was relatively high. Calcium in the high calcium type stone coal is greatly superfluous relative to vanadium, hence, the calcium reacts with vanadium to form Ca(VO3)2, Ca2V2O7 and Ca3(VO4)2 orderly during the stone coal roasting process and high temperature is beneficial to the reactions between calcium and vanadium, which was validated by simulated reactions between pure calcium carbonate and vanadium pentoxide. These calcium vanadates are all water insoluble but acid soluble and this causes the low WLRV and relatively high ALRV. After calcium removal by HCl, the WLRV is highly enhanced and reaches about 50%when only 2%NaCl was added. If the HCl content is too high, the stone coal is easily sintered and the formed glass structure can enwrap vanadium, which leads the WLRV to decline. Single water leaching process is not appropriate to extract vanadium from high calcium type stone coal.

  12. Study of calcium chloride and calcium nitrate purification on inorganic sorbents

    International Nuclear Information System (INIS)

    Purification of calcium chloride and calcium nitrate from iron, chromium, manganese and cobalt impurities by sorption on some inorganic collectors are considered in this article. Study was conducted by means of radioactive-tracer technique at concurrent use of several γ-radioactive isotopes. As a collectors were used hydrated aluminium and zirconium oxides. Dependence of effectiveness of precipitation by collectors on ph-value of medium, quantity of collector, nature and concentration of components is studied. Optimal parameters of purification of calcium chloride and calcium nitrate are defined.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Moritz Treeck

    2014-06-01

    Full Text Available 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-labeling with amino acids in cell culture (SILAC. This revealed known and novel phosphorylation events on proteins predicted to play a role in host-cell egress, but also a novel function of TgCDPK3 as an upstream regulator of other calcium-dependent signaling pathways, as we also identified proteins that are differentially phosphorylated prior to egress, including proteins important for ion-homeostasis and metabolism. This observation is supported by the observation that basal calcium levels are increased in parasites where TgCDPK3 has been inactivated. Most of the differential phosphorylation observed in CDPK3 mutants is rescued by complementation of the mutants with a wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed hyperphosphorylation of two targets of a related calcium-dependent kinase (TgCDPK1, as well as TgCDPK1 itself, indicating that this latter kinase appears to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1 partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this conclusion. These results show that TgCDPK3 plays a pivotal role in regulating tachyzoite functions including, but not limited to, egress.

  15. 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.

  16. DETERMINATION OF CALCIUM CONTENT IN DIETARY SUPPLEMENTS

    OpenAIRE

    Marjanović-Balaban, Željka R.; Antunović, Vesna R.; Jelić, Dijana R.; Živković, Tanja M.

    2015-01-01

    Calcium is a macro element that is very important for the human body: its content and circulation in the body is large, it serves as the electrolyte, it has a building role and participates in the process of metabolism. The European Union, the World Health Organization (WHO) and the Ministry of Food and Drug (Food and Drug Administration, FDA) gave the RDA (Recommended Dietary Allowances,) for this macro element. The absorption and bioavailability of the calcium may vary depending on a number...

  17. Gel time of calcium acrylate grouting material.

    Science.gov (United States)

    Han, Tong-Chun

    2004-08-01

    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. PMID:15236477

  18. Dietary habits of calcium stone formers.

    Science.gov (United States)

    Martini, L A; Heilberg, I P; Cuppari, L; Medeiros, F A; Draibe, S A; Ajzen, H; Schor, N

    1993-08-01

    1. Since dietary factors are known to be related to nephrolithiasis, calcium stone-forming (CSF) patients were evaluated in terms of calcium, total protein of both animal and plant origin, carbohydrate and energy intakes, on the basis of 72-h dietary records during the week plus 24-h dietary records during the week-end. 2. The data for 77 calcium stone formers (57 with absorptive hypercalciuria and 20 with renal hypercalciuria) were compared to those for 29 age-matched healthy subjects. The body mass index of the CSF group was higher than that of healthy subjects (P < 0.05). Consumption of all nutrients was similar for both groups during the week but week-end dietary records for CSF showed higher calcium intake (586 +/- 38 vs 438 +/- 82 mg/day, P < 0.05), protein to body weight ratio (1.2 +/- 0.1 vs 1.0 +/- 0.5 g kg-1 day-1, P < 0.05) and animal protein (56 +/- 3 vs 40 +/- 3 g/day, P < 0.05) when compared with healthy subjects. 3. Comparison of hypercalciuria subtypes (renal hypercalciuria and absorptive hypercalciuria) did not indicate any difference in calcium or energy intake between groups, either during the week or during the week-end. However, the absorptive hypercalciuric group presented higher protein and animal protein consumption during the week-end. 4. These data suggest a low calcium intake in this population, even by stone formers. The higher animal protein consumption by our calcium stone formers observed during week-ends seems to be more important than calcium intake for stone formation. PMID:8298515

  19. 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.

  20. 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 ...

  1. Tx1, from Phoneutria nigriventer spider venom, interacts with dihydropyridine sensitive-calcium channels in GH3 cells

    International Nuclear Information System (INIS)

    The aim of this work was to use the binding assay of tritiated-dihydropyridine and radioiodinated Tx1, isolated from the Phoneutria nigriventer venom, in order to show the presence of Cav1 calcium channels on pituitary tumour cell (GH3). We showed that GH3 cells have specific sites for 125I-Tx1, which are sensitive to nifedipine (∼20%). Reverse competition assay with 3H-PN200-110 (40% inhibition) and electrophysiological data (50% inhibition) suggest that Cav1 calcium channels are target sites for this toxin. To summarize, Tx1 binds to specific sites on GH3 cells and this interaction results in Cav1 calcium channel blockade. 3H-PN200-110 and 125I-Tx1 binding assays proved to be useful tools to show the presence of calcium channels on GH3 cells. (author)

  2. Modulation of the dimer interface at ionotropic glutamate-like receptor d2 by D-serine and extracellular calcium

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Naur, Peter; Kurtkaya, Natalie L;

    2009-01-01

    that calcium binding stabilizes the dimer interface formed between two agonist-binding domains and increases GluRdelta2(Lc) currents. The data further suggest that d-serine binding induces rearrangements at the dimer interface to diminish GluRdelta2(Lc) currents by a mechanism that resembles desensitization...... at AMPA and kainate receptors. Thus, we propose that calcium and d-serine binding have opposing effects on the stability of the dimer interface. Furthermore, the effects of calcium are observed at concentrations that are within the physiological range, suggesting that the ability of native GluRdelta2...... to respond to ligand binding may be modulated by extracellular calcium. These findings place GluRdelta2 among AMPA and kainate receptors, where the dimer interface is not only a biologically important site for functional regulation, but also an important target for exogenous and endogenous ligands...

  3. A calcium-induced calcium release mechanism mediated by calsequestrin.

    Science.gov (United States)

    Lee, Young-Seon; Keener, James P

    2008-08-21

    Calcium (Ca(2+))-induced Ca(2+) release (CICR) is widely accepted as the principal mechanism linking electrical excitation and mechanical contraction in cardiac cells. The CICR mechanism has been understood mainly based on binding of cytosolic Ca(2+) with ryanodine receptors (RyRs) and inducing Ca(2+) release from the sarcoplasmic reticulum (SR). However, recent experiments suggest that SR lumenal Ca(2+) may also participate in regulating RyR gating through calsequestrin (CSQ), the SR lumenal Ca(2+) buffer. We investigate how SR Ca(2+) release via RyR is regulated by Ca(2+) and calsequestrin (CSQ). First, a mathematical model of RyR kinetics is derived based on experimental evidence. We assume that the RyR has three binding sites, two cytosolic sites for Ca(2+) activation and inactivation, and one SR lumenal site for CSQ binding. The open probability (P(o)) of the RyR is found by simulation under controlled cytosolic and SR lumenal Ca(2+). Both peak and steady-state P(o) effectively increase as SR lumenal Ca(2+) increases. Second, we incorporate the RyR model into a CICR model that has both a diadic space and the junctional SR (jSR). At low jSR Ca(2+) loads, CSQs are more likely to bind with the RyR and act to inhibit jSR Ca(2+) release, while at high SR loads CSQs are more likely to detach from the RyR, thereby increasing jSR Ca(2+) release. Furthermore, this CICR model produces a nonlinear relationship between fractional jSR Ca(2+) release and jSR load. These findings agree with experimental observations in lipid bilayers and cardiac myocytes. PMID:18538346

  4. Analytical models of calcium binding in a calcium channel

    International Nuclear Information System (INIS)

    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+ and Ca2+ for [CaCl2] ranging from 10−8 to 10−2 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

  5. Contribution of calcium oxalate to soil-exchangeable calcium

    Science.gov (United States)

    Dauer, Jenny M.; Perakis, Steven S.

    2013-01-01

    Acid deposition and repeated biomass harvest have decreased soil calcium (Ca) availability in many temperate forests worldwide, yet existing methods for assessing available soil Ca do not fully characterize soil Ca forms. To account for discrepancies in ecosystem Ca budgets, it has been hypothesized that the highly insoluble biomineral Ca oxalate might represent an additional soil Ca pool that is not detected in standard measures of soil-exchangeable Ca. We asked whether several standard method extractants for soil-exchangeable Ca could also access Ca held in Ca oxalate crystals using spike recovery tests in both pure solutions and soil extractions. In solutions of the extractants ammonium chloride, ammonium acetate, and barium chloride, we observed 2% to 104% dissolution of Ca oxalate crystals, with dissolution increasing with both solution molarity and ionic potential of cation extractant. In spike recovery tests using a low-Ca soil, we estimate that 1 M ammonium acetate extraction dissolved sufficient Ca oxalate to contribute an additional 52% to standard measurements of soil-exchangeable Ca. However, in a high-Ca soil, the amount of Ca oxalate spike that would dissolve in 1 M ammonium acetate extraction was difficult to detect against the large pool of exchangeable Ca. We conclude that Ca oxalate can contribute substantially to standard estimates of soil-exchangeable Ca in acid forest soils with low soil-exchangeable Ca. Consequently, measures of exchangeable Ca are unlikely to fully resolve discrepancies in ecosystem Ca mass balance unless the contribution of Ca oxalate to exchangeable Ca is also assessed.

  6. GPR41 and GPR43 in Obesity and Inflammation - Protective or Causative?

    Science.gov (United States)

    Ang, Zhiwei; Ding, Jeak Ling

    2016-01-01

    GPR41 and GPR43 are a pair of mammalian G protein-coupled receptors (GPCRs) expressed in human adipocytes, colon epithelial cells, and peripheral blood mononuclear cells. These receptors are activated by short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate - which are produced during dietary fiber fermentation by resident gut bacteria. This unique ligand specificity suggests that GPR41 and GPR43 may mediate the interaction between the human host and the gut microbiome. Indeed, studies on knockout mice implicate GPR41 and GPR43 in chronic inflammatory disorders such as obesity, colitis, asthma and arthritis. However, whether GPR41 and GPR43 are protective or causative is inconsistent between studies. This discrepancy may be due to differences in the disease models used, the inbred mouse strains, or non-specific knockout effects. Here, we review the latest findings on GPR41 and GPR43, highlighting contradictory observations. With GPR41 and GPR43 being considered as drug targets, it is pertinent that their role is fully elucidated. We propose that future studies on human tissues, ex vivo, may allow us to confirm the role of GPR41 and GPR43 in humans, be it protective or causative. PMID:26870043

  7. A study of the 40Ar(p,γ)41K reaction

    International Nuclear Information System (INIS)

    This experiment has been undertaken to gain information on 40Ar(p,γ)41K resonances and the 41K nucleus. The targets were prepared by implanting high purity argon gas into tantalum backings. Proton beams were produced by the 2,6 MeV Van de Graaff accelerator at the Potchefstroom University for CHE. The spread in beam energy was 1 keV at 1 MeV. The excitation curve for the 40Ar(p,γ)41K reaction has been measured in the energy range 0,9 MeV 40Ar(p,γ)41K resonances. The gamma decay of these resonances have been studied utilizing a large Ge(Li) detector. The uncertain 4.03→2.32 and 4.75→1.70 keV transitions are confirmed. 9 figs., 30 refs., 5 tabs

  8. A theory of Plasma Membrane Calcium Pump stimulation and activity

    CERN Document Server

    Graupner, M; Meyer-Hermann, M; Erler, Frido; Graupner, Michael; Meyer-Hermann, Michael

    2003-01-01

    The ATP-driven Plasma Membrane Calcium (PMCA) pump is characterized by a high affinity to calcium and a low transport rate compared to other transmembrane calcium transport proteins. It plays a crucial role for calcium extrusion from cells. Calmodulin is an intracellular calcium buffering protein which is capable in its Calcium-liganded form to stimulate the PMCA pump by increasing both, the affinity to calcium and the maximum calcium transport rate. We introduce a new model of this stimulation process and deduce analytical expressions for experimental observables in order to determine the model parameter on the basis of specific experiments. Furthermore a model for the pumping activity is developed. In contrast to the biological process we have to describe the pumping rate behavior by assuming a ATP:Calcium stoichiometry of 2 in order to reproduce experimental data. The conjunction of the description of calcium pumping and the stimulation model fully and correctly simulates PMCA pump function. Therewith the ...

  9. 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.

  10. 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.

  11. Oyster shell calcium induced parotid swelling

    Directory of Open Access Journals (Sweden)

    Muthiah Palaniappan

    2014-01-01

    Full Text Available A 59 year old female consumer was started on therapy with oyster shell calcium in combination with vitamin D3 and she presented with swelling below the ear, after two doses. She stopped the drug by herself and the swelling disappeared in one day. She started the drug one day after recovery and again she developed the swelling. She was advised to stop the drug with a suggestion to take lemon to enhance parotid secretion and the swelling subsided. Calcium plays major role in salivary secretion and studies have shown reduced parotid secretion in rats, deficient of vitamin D. But in humans involvement of calcium and vitamin D3 in parotid secretion is unknown. However, the patient had no history of reaction though she had previously taken vitamin D3 with calcium carbonate which was not from oyster shell. Hence, we ruled out vitamin D3 in this reaction and suspecting oyster shell calcium as a culprit. This adverse drug reaction (ADR was assessed using World Health Organization (WHO causality assessment, Naranjo′s and Hartwig severity scales. As per WHO causality assessment scale, the ADR was classified as "certain". This reaction was analyzed as per Naranjo′s algorithm and was classified as probable. According to Hartwig′s severity scale the reaction was rated as mild. Our case is an example of a mild but rare adverse effect of oyster shell calcium carbonate which is widely used.

  12. Membrane associated complexes in calcium dynamics modelling

    International Nuclear Information System (INIS)

    Mitochondria not only govern energy production, but are also involved in crucial cellular signalling processes. They are one of the most important organelles determining the Ca2+ regulatory pathway in the cell. Several mathematical models explaining these mechanisms were constructed, but only few of them describe interplay between calcium concentrations in endoplasmic reticulum (ER), cytoplasm and mitochondria. Experiments measuring calcium concentrations in mitochondria and ER suggested the existence of cytosolic microdomains with locally elevated calcium concentration in the nearest vicinity of the outer mitochondrial membrane. These intermediate physical connections between ER and mitochondria are called MAM (mitochondria-associated ER membrane) complexes. We propose a model with a direct calcium flow from ER to mitochondria, which may be justified by the existence of MAMs, and perform detailed numerical analysis of the effect of this flow on the type and shape of calcium oscillations. The model is partially based on the Marhl et al model. We have numerically found that the stable oscillations exist for a considerable set of parameter values. However, for some parameter sets the oscillations disappear and the trajectories of the model tend to a steady state with very high calcium level in mitochondria. This can be interpreted as an early step in an apoptotic pathway. (paper)

  13. Study on bone resorption behavior of osteoclast under drug effect using {sup 41}Ca tracing

    Energy Technology Data Exchange (ETDEWEB)

    Dong Kejun [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); Lu Liyan [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); CNNC Third Qinshan Nuclear Power Co. Ltd., Haiyan 314300 (China); He Ming; Ouyang Yinggen; Xue Yan; Li Chaoli; Wu Shaoyong [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); Wang Xianggao [College of Physics Science and Technology, Guangxi University, Nanning 530004 (China); Shen Hongtao [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); Gao Jianjun [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Wang Wei [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); China National Nuclear Corporation, Beijing 100822 (China); Chen Dafu; Xing Yonggang [Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035 (China); Jian, Yuan [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); Jiang Shan, E-mail: jiangs@ciae.ac.cn [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China)

    2013-01-15

    The mechanisms governing calcium fluxes during bone remodeling processes in Osteoporosis (OP) patients are poorly known. Understanding the changes of Osteoclasts (OC) during this dynamic transition is important to prevent and cure OP. The exploration of long-lived {sup 41}Ca (T{sub 1/2} = 1.04 Multiplication-Sign 10{sup 5} years) tracer combined with AMS measurements leads to the possibility of monitoring the bone resorption behavior of OC in OP patients. In this work, the behavior of OC with the administration of Strontium Ranelate (SR), a drug for OP, was studied by using {sup 41}Ca labeled hydroxyapatite (HAP) to simulate the bone. AMS on the HI-13 tandem accelerator at CIAE was used to determine trace amounts of {sup 41}Ca. The results show that the technique of {sup 41}Ca tracing with AMS can be used to quantitatively monitor the behavior of OC in bone resorption under the effects of drugs. Experimental details and preliminary results will be presented.

  14. 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.

  15. Increased absolute calcium binding to albumin in hypoalbuminaemia.

    OpenAIRE

    Besarab, A; Caro, J F

    1981-01-01

    The amount of calcium bound to protein was measured in 30 patients with differing diseases and varying degrees of hypoalbuminaemia. Total serum calcium increased directly with both serum albumin and ultrafilterable calcium concentrations. The estimated amount of calcium bound per gram of albumin varied inversely with the albumin concentration, decreasing from 2.1 to 1.0 mg calcium/g albumin as albumin concentration increased from 1.7 to 3.1 g/dl. Circulating parathyroid hormone (PTH) concentr...

  16. The effect of dimethylsulfoxide on the calcium paradox.

    OpenAIRE

    Ruigrok, T. J.; Moes, D.; Slade, A.M.; Nayler, W. G.

    1981-01-01

    Reperfusion of isolated rat hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). Experiments were undertaken to study the effect of dimethylsulfoxide (DMSO) on the occurrence of the calcium paradox in rat heart muscle. DMSO (1.4 mol/l) was added to the calcium-free or the reperfusion medium. Cell damage was quantitated in terms of creatine kinase (CK) release, cardiac electrogram (CEG) changes, and ultras...

  17. Factors to consider in the selection of a calcium supplement.

    OpenAIRE

    Shangraw, R F

    1989-01-01

    Calcium supplements are widely used, yet many questions remain as to the absorption of various calcium salts. Because the solubility of many calcium salts is dependent upon pH, the type of salt used, the condition of the patient, and the time of administration should be considered. Studies show that many calcium supplements on the market today do not meet standards of quality established in the "U.S. Pharmacopeia" (USP). Consumers must be discerning about the products they purchase. Calcium s...

  18. 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....

  19. Hydrogen sulfide inhibits L-type calcium currents depending upon the protein sulfhydryl state in rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Rongyuan Zhang

    Full Text Available Hydrogen sulfide (H(2S is a novel gasotransmitter that inhibits L-type calcium currents (I (Ca, L. However, the underlying molecular mechanisms are unclear. In particular, the targeting site in the L-type calcium channel where H(2S functions remains unknown. The study was designed to investigate if the sulfhydryl group could be the possible targeting site in the L-type calcium channel in rat cardiomyocytes. Cardiac function was measured in isolated perfused rat hearts. The L-type calcium currents were recorded by using a whole cell voltage clamp technique on the isolated cardiomyocytes. The L-type calcium channel containing free sulfhydryl groups in H9C2 cells were measured by using Western blot. The results showed that sodium hydrosulfide (NaHS, an H(2S donor produced a negative inotropic effect on cardiac function, which could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM. H(2S donor inhibited the peak amplitude of I( Ca, L in a concentration-dependent manner. However, dithiothreitol (DTT, a reducing sulfhydryl modifier markedly reversed the H(2S donor-induced inhibition of I (Ca, L in cardiomyocytes. In contrast, in the presence of DM, H(2S donor could not alter cardiac function and L type calcium currents. After the isolated rat heart or the cardiomyocytes were treated with DTT, NaHS could markedly alter cardiac function and L-type calcium currents in cardiomyocytes. Furthermore, NaHS could decrease the functional free sulfhydryl group in the L-type Ca(2+ channel, which could be reversed by thiol reductant, either DTT or reduced glutathione. Therefore, our results suggest that H(2S might inhibit L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes.

  20. The formation of calcium phosphate coatings by pulse laser deposition on the surface of polymeric ferroelectric

    Energy Technology Data Exchange (ETDEWEB)

    Bolbasov, E.N. [Tomsk Polytechnic University, 30 Lenin Avenue, Tomsk 634050 (Russian Federation); Lapin, I.N.; Svetlichnyi, V.A. [Tomsk State University, 36 Lenin Avenue, Tomsk 634050 (Russian Federation); Lenivtseva, Y.D. [Tomsk Polytechnic University, 30 Lenin Avenue, Tomsk 634050 (Russian Federation); Malashicheva, A. [Federal Almazov Medical Research Centre, 2 Akkuratova St., St. Petersburg 197341 (Russian Federation); St. Petersburg State University, 7/9 Universitetskaya nab., St. Petersburg 199034 (Russian Federation); ITMO University, Institute of translational Medicine, St. Petersburg (Russian Federation); Malashichev, Y. [St. Petersburg State University, 7/9 Universitetskaya nab., St. Petersburg 199034 (Russian Federation); Golovkin, A.S. [Federal Almazov Medical Research Centre, 2 Akkuratova St., St. Petersburg 197341 (Russian Federation); Anissimov, Y.G. [Griffith University, School of Natural Sciences, Engineering Dr., Southport, QLD 4222 (Australia); Tverdokhlebov, S.I., E-mail: tverd@tpu.ru [Tomsk Polytechnic University, 30 Lenin Avenue, Tomsk 634050 (Russian Federation)

    2015-09-15

    Graphical abstract: - Highlights: • Calcium phosphate coatings were obtained on ferroelectric polymer materials surface by using PLD method. • Obtained coatings have well-developed surface. • Depending on sputtering target composition it is possible to obtain crystalline or amorphous coating. • Formation of coating does not change the crystal structure of the ferroelectric polymer material. - Abstract: This work analyses the properties of calcium phosphate coatings obtained by pulsed laser deposition on the surface of the ferroelectric polymer material. Atomic force and scanning electron microscopy studies demonstrate that, regardless of the type of sputtering target, the calcium phosphate coatings have a multiscale rough surface that is potentially capable of promoting the attachment and proliferation of osteoblasts. This developed surface of the coatings is due to its formation mainly from a liquid phase. The chemical and crystalline composition of the coatings depends on the type of sputtering target used. It was shown that, regardless of the type of sputtering target, the crystalline structure of the ferroelectric polymer material does not change. Cell viability and adhesion studies of mesenchymal stromal cells on the coatings were conducted using flow cytometry and fluorescent microscopy. These studies indicated that the produced coatings are non-toxic.

  1. The formation of calcium phosphate coatings by pulse laser deposition on the surface of polymeric ferroelectric

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Calcium phosphate coatings were obtained on ferroelectric polymer materials surface by using PLD method. • Obtained coatings have well-developed surface. • Depending on sputtering target composition it is possible to obtain crystalline or amorphous coating. • Formation of coating does not change the crystal structure of the ferroelectric polymer material. - Abstract: This work analyses the properties of calcium phosphate coatings obtained by pulsed laser deposition on the surface of the ferroelectric polymer material. Atomic force and scanning electron microscopy studies demonstrate that, regardless of the type of sputtering target, the calcium phosphate coatings have a multiscale rough surface that is potentially capable of promoting the attachment and proliferation of osteoblasts. This developed surface of the coatings is due to its formation mainly from a liquid phase. The chemical and crystalline composition of the coatings depends on the type of sputtering target used. It was shown that, regardless of the type of sputtering target, the crystalline structure of the ferroelectric polymer material does not change. Cell viability and adhesion studies of mesenchymal stromal cells on the coatings were conducted using flow cytometry and fluorescent microscopy. These studies indicated that the produced coatings are non-toxic

  2. Effect of combining different calcium concentration dialysate on calcium balance in peritoneal dialysis patients

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hui-ping; WU Bei; LU Li-xia; QIAO Jie; WU Xiang-lan; WANG Mei

    2012-01-01

    Background Calcium and phosphorus metabolic disturbance are common in dialysis patients and associated with increased morbidity and mortality.Therefore,maintaining the balance of calcium and phosphate metabolism and suitable intact parathyroid hormone(iPTH)level has become the focus of attention.We investigated the effects of different peritoneal dialysate calcium concentrations on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal dialysis(CAPD)patients.Methods Forty stable CAPD patients with normal serum calcium were followed for six months of treatment with 1.25 mmol/L calcium dialysate(DCa1.25,PD4,22 patients)or a combination of 1.75 mmol/L calcium dialysate(DCa1.75,PD2)and PD4(18 patients)twice a day respectively.Total serum calcium(after albumin correction),serum phosphorus,iPTH,alkaline phosphatase(ALP)and blood pressure were recorded before and 1,3 and 6 months after treatment commenced.Results No significant difference was found in baseline serum calcium,phosphorus between the two patient groups,but the levels of iPTH were significantly different.No significant changes were found in the dosage of calcium carbonate and active vitamin D during 6 months.In the PD4 group,serum calcium level at the 1st,3rd,6th months were significantly lower than the baseline(P<0.05).There was no significant difference in serum phosphorus after 6 months treatment.iPTH was significantly higher(P<0.001)at the 1st,3rd,and 6th months compared with the baseline.No differences were seen in ALP and blood pressure.In the PD4+PD2 group,no significant changes in serum calcium,phosphorus,iPTH,ALP and BP during the 6-month follow-up period.Conclusions Treatment with 1.25 mmol/L calcium dialysate for six months can decrease serum calcium,increase iPTH,without change in serum phosphorus,ALP,and BP.The combining of PD4 and PD2 can stabilize the serum calcium and avoid fluctuations in iPTH levels.

  3. Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.

    Directory of Open Access Journals (Sweden)

    Stefanie Ryglewski

    2007-04-01

    Full Text Available Neuronal calcium acts as a charge carrier during information processing and as a ubiquitous intracellular messenger. Calcium signals are fundamental to numerous aspects of neuronal development and plasticity. Specific and independent regulation of these vital cellular processes is achieved by a rich bouquet of different calcium signaling mechanisms within the neuron, which either can operate independently or may act in concert. This study demonstrates the existence of a novel calcium signaling mechanism by simultaneous patch clamping and calcium imaging from acutely isolated central neurons. These neurons possess a membrane voltage sensor that, independent of calcium influx, causes G-protein activation, which subsequently leads to calcium release from intracellular stores via phospholipase C and inositol 1,4,5-trisphosphate receptor activation. This allows neurons to monitor activity by intracellular calcium release without relying on calcium as the input signal and opens up new insights into intracellular signaling, developmental regulation, and information processing in neuronal compartments lacking calcium channels.

  4. Calcium homeostasis in barley aleurone

    Energy Technology Data Exchange (ETDEWEB)

    Jones, R.L.

    1990-02-21

    Under the auspices of the Department of Energy we investigated calcium homeostasis in aleurone cells of barley. This investigation was initiated to explore the role played by extracellular Ca{sup 2+} in gibberellic acid (GA)-induced synthesis and secretion of hydrolases in the aleurone layer. We have focused our attention on four topics that relate to the role of Ca{sup 2+} in regulating the synthesis of {alpha}-amylase. First, we determined the stoichiometry of Ca{sup 2+} binding to the two principal classes of barley {alpha}-amylase and examined some of the biochemical and physical properties of the native and Ca{sup 2+}-depleted forms of the enzyme. Second, since {alpha}-amylase is a Ca{sup 2+} containing metalloenzyme that binds one atom of Ca{sup 2+} per molecule, we developed methods to determine the concentration of Ca{sup 2+} in the cytosol of the aleurone cell. We developed a technique for introducing Ca{sup 2+}-sensitive dyes into aleurone protoplasts that allows the measurement of Ca{sup 2+} in both cytosol and endoplasmic reticulum (ER). Third, because the results of our Ca{sup 2+} measurements showed higher levels of Ca{sup 2+} in the ER than in the cytosol, we examined Ca{sup 2+} transport into the ER of control and GA-treated aleurone tissue. And fourth, we applied the technique of patch-clamping to the barley aleurone protoplast to examine ion transport at the plasma membrane. Our results with the patch-clamp technique established the presence of K{sup +} channels in the plasma membrane of the aleurone protoplast, and they showed that this cell is ideally suited for the application of this methodology for studying ion transport. 34 refs.

  5. Update on calcium pyrophosphate deposition.

    Science.gov (United States)

    Abhishek, Abhishek; Doherty, Michael

    2016-01-01

    Calcium pyrophosphate crystal deposition (CPPD) associates with ageing, osteoarthritis (OA), uncommon metabolic diseases, mutations and polymorphisms in the ankylosis human gene (ANKH). CPPD is frequently polyarticular, occurs due to a generalised articular predisposition, and the association between CPPD and OA is joint specific, for example CPPD associates with knee OA, but not with hip OA. Other recently identified associations include knee malalignment (knee CC), low cortical BMD and soft-tissue calcification. CPPD is generally asymptomatic. A recent study reported that knees with OA plus CC at the index joint, or at distant joints (in absence of index joint CC), were more likely to have attrition. CPPD can cause acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and is frequently present in joints with OA. Joint aspiration remains the gold standard for diagnosing CPPD, although other promising techniques are emerging. Patients with polyarticular or young onset CPPD should be screened for underlying metabolic abnormalities, however, such testing can be unrewarding. The treatment of CPPD is symptomatic. Acute CPP crystal arthritis is treated with rest, local application of ice-packs, joint aspiration, colchicine and/or intra-articular corticosteroid injection (once infection is excluded). Colchicine, low-dose corticosteroids, hydroxychloroquine and radiosynovectomy are recommended for the treatment of chronic or recurrent acute CPP crystal arthritis. Recent RCTs did not confirm any benefit from methotrexate, and although there is increasing interest in the use of anti-IL1 agents for acute or chronic CPP crystal arthritis, their efficacy has not been formally examined. Unlike gout, currently there are no treatments to eliminate CPP crystal deposits. PMID:27586801

  6. Period derivative of the Soft Gamma-ray Repeater SGR 1627-41

    NARCIS (Netherlands)

    P. Esposito; A. Tiengo; S. Mereghetti; A. De Luca; G.L. Israel; D. Gotz; N. Rea; R. Turolla; S. Zane; P. Romano; M. Burgay; A. Possenti

    2009-01-01

    After nearly a decade of quiescence, the soft gamma-ray repeater SGR 1627-41 reactivated on 2008 May 28 with a bursting episode (Esposito et al. 2008, MNRAS, 390, L34). On 2008 September 27-28 we performed an XMM-Newton target of opportunity observation of the source and discovered its long-sought s

  7. Alteração do teor de cálcio no banho de DP para 2,5 mEq/L é eficaz no reestabelecimento dos valores preconizados por diretrizes atuais em pacientes com PTH < 150 pg/dL Low-calcium peritoneal dialysis solution is effective in bringing PTH levels to the range recommended by current guidelines in patients with PTH levels < 150 pg/dL

    Directory of Open Access Journals (Sweden)

    Thyago Proença de Moraes

    2010-09-01

    followed by nephrosclerosis (25% and glomerulonephritis (14%. Converted group presented a greater increase in PTH levels when compared with the control group (Δ194 pg/dL versus Δ 92/dL; p < 0,05. Among patients switched to low calcium solution, 41% reached the target values (PTH 150300 pg/mL compared to 14% whose remain with normal calcium solutions (p < 0.05. There were no differences between groups regarding calcium, phosphorus and alkaline phosphatase. CONCLUSION: In patients with PTH < 150 pg/mL conversion to low calcium solutions (2.5 mEq/L appears to be a simple and effective strategy to bring PTH levels to the range determined by current guidelines when compared with 3.5mEq/L calcium PD solutions.

  8. Eggshell powder, a comparable or better source of calcium than purified calcium carbonate: Piglet studies

    NARCIS (Netherlands)

    Schaafsma, A.; Beelen, G.M.

    1999-01-01

    Powdered chicken eggshells might be an interesting and widely available source of calcium. In two studies using piglets we determined the digestibility of calcium from different diets. The first study compared casein-based diets with CaCO3 (CasCC) or eggshell powder (CasES). The second study compare

  9. Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

    The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate......+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle....

  10. Discovery of novel tetrahydroisoquinoline derivatives as orally active N-type calcium channel blockers with high selectivity for hERG potassium channels.

    Science.gov (United States)

    Ogiyama, Takashi; Inoue, Makoto; Honda, Shugo; Yamada, Hiroyoshi; Watanabe, Toshihiro; Gotoh, Takayasu; Kiso, Tetsuo; Koakutsu, Akiko; Kakimoto, Shuichiro; Shishikura, Jun-ichi

    2014-12-15

    N-type calcium channels represent a promising target for the treatment of neuropathic pain. The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration. We identified tetrahydroisoquinoline derivative 1a as a novel potent N-type calcium channel blocker. However, this compound also exhibited potent inhibitory activity against hERG channels. Structural optimizations led to identification of (1S)-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-{[(1-hydroxycyclohexyl)methyl]amino}ethanone ((S)-1h), which exhibited high selectivity for hERG channels while retaining potency for N-type calcium channel inhibition. (S)-1h went on to demonstrate in vivo efficacy as an orally available N-type calcium channel blocker in a rat spinal nerve ligation model of neuropathic pain. PMID:25456079

  11. Characterization of dihydropyridine-sensitive calcium channels

    International Nuclear Information System (INIS)

    The structural and regulatory properties of the dihydropyridine-sensitive calcium channel were studied by isolating protein components of the channel complex from both cardiac and skeletal muscle. Hydrodynamic characterization of the (+)-(3H)PN200-110-labeled cardiac calcium channel revealed that the protein components of the complex had a total molecular mass of 370,000 daltons, a Stokes radius of 86 angstrom, and a frictional ratio of 1.3. A technique is described for the rapid incorporation of the CHAPS solubilized skeletal muscle calcium channel complex into phospholipid vesicles. 45Ca2+ uptake into phospholipid vesicles containing calcium channels was inhibited by phenylalkalamine calcium antagonists. Wheat germ lectin followed by DEAE chromatography of the CHAPS solubilized complex resulted in the dissociation of regulatory components of the complex from channel components. The DEAE preparation gave rise to 45Ca2+ uptake that was not inhibited by verapamil but was inhibited by GTPgS activated G0. The inhibition of 45Ca2+ uptake by verapamil was restored by co-reconstitution of wash fractions from wheat germ lectin chromatography. Phosphorylation of polypeptides in this fraction by polypeptide-dependent protein kinase prevented the restoration of verapamil sensitivity. The partial purification of an endogenous skeletal muscle ADP-ribosyltransferase is also described. ADP-ribosylation of the α2 subunit of the calcium channel complex is enhanced by polylysine and inhibited by GTPγS, suggesting that regulation of this enzyme is under the control of GTP binding proteins. These results suggest a complex model, involving a number of different protein components, for calcium channel regulation in skeletal muscle

  12. Calcium-ATPases: Gene disorders and dysregulation in cancer.

    Science.gov (United States)

    Dang, Donna; Rao, Rajini

    2016-06-01

    Ca(2+)-ATPases belonging to the superfamily of P-type pumps play an important role in maintaining low, nanomolar cytoplasmic Ca(2+) levels at rest and priming organellar stores, including the endoplasmic reticulum, Golgi, and secretory vesicles with high levels of Ca(2+) for a wide range of signaling functions. In this review, we introduce the distinct subtypes of Ca(2+)-ATPases and their isoforms and splice variants and provide an overview of their specific cellular roles as they relate to genetic disorders and cancer, with a particular emphasis on recent findings on the secretory pathway Ca(2+)-ATPases (SPCA). Mutations in human ATP2A2, ATP2C1 genes, encoding housekeeping isoforms of the endoplasmic reticulum (SERCA2) and secretory pathway (SPCA1) pumps, respectively, confer autosomal dominant disorders of the skin, whereas mutations in other isoforms underlie various muscular, neurological, or developmental disorders. Emerging evidence points to an important function of dysregulated Ca(2+)-ATPase expression in cancers of the colon, lung, and breast where they may serve as markers of differentiation or novel targets for therapeutic intervention. We review the mechanisms underlying the link between calcium homeostasis and cancer and discuss the potential clinical relevance of these observations. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26608610

  13. Drugs Used in Paediatric Bone and Calcium Disorders.

    Science.gov (United States)

    Cheung, Moira S

    2015-01-01

    Calcium and bone disorders in children and adolescents are treated with a wide variety of drugs. Several of these drugs have been used for many years on the basis of accepted practice, without being subjected to rigorous trials. Bisphosphonates are the mainstay treatment for children with osteoporosis, but newer, more potent compounds such as zoledronate and risedronate have begun to replace the older-generation bisphosphonates. Hypocalcaemia is managed with calcium and vitamin D and its metabolites. In difficult cases that are secondary to hypoparathyroidism, subcutaneous injections or infusions of parathyroid hormone have been used. Multiple daily phosphate supplements and calcitriol are the standard treatment for hypophosphataemic rickets, but trials of an anti-fibroblast growth factor 23 antibody appear promising, and the results are eagerly awaited. Many new medications are undergoing clinical trials and are starting to emerge as viable treatment options for children. Some of these drugs target specific diseases, such as recombinant alkaline phosphatase for hypophosphatasia and a C-type natriuretic peptide analogue for achondroplasia. Other drugs, such as denosumab and odanacatib, have been used successfully in the adult population, and the appropriate use of these drugs in children is now being evaluated. PMID:26138848

  14. Calcium ferrite formation from the thermolysis of calcium tris (maleato) ferrate(III)

    Indian Academy of Sciences (India)

    B S Randhawa; Kamaljeet Sweety

    2000-08-01

    For preparing calcium ferrite, calcium tris (maleato) ferrate(III) precursor was prepared by mixing aqueous solutions of iron(III) maleate, calcium maleate and maleic acid. Various physico-chemical techniques i.e. TG, DTG, DTA, Mössbauer, XRD, IR etc have been used to study the decomposition behaviour from ambient to 900°C and ferrite formation. Three consecutive decomposition steps leading to the formation of -Fe2O3 and calcium carbonate have been observed at various stages of thermolysis. In the final stage the ferrite, Ca2Fe2O5, is obtained as a result of solid state reaction between -Fe2O3 and calcium carbonate at 788°C, a temperature much lower than for ceramic method. The results have been compared with those of the oxalate precursor.

  15. The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter.

    Science.gov (United States)

    Pan, Xin; Liu, Jie; Nguyen, Tiffany; Liu, Chengyu; Sun, Junhui; Teng, Yanjie; Fergusson, Maria M; Rovira, Ilsa I; Allen, Michele; Springer, Danielle A; Aponte, Angel M; Gucek, Marjan; Balaban, Robert S; Murphy, Elizabeth; Finkel, Toren

    2013-12-01

    Mitochondrial calcium has been postulated to regulate a wide range of processes from bioenergetics to cell death. Here, we characterize a mouse model that lacks expression of the recently discovered mitochondrial calcium uniporter (MCU). Mitochondria derived from MCU(-/-) mice have no apparent capacity to rapidly uptake calcium. Whereas basal metabolism seems unaffected, the skeletal muscle of MCU(-/-) mice exhibited alterations in the phosphorylation and activity of pyruvate dehydrogenase. In addition, MCU(-/-) mice exhibited marked impairment in their ability to perform strenuous work. We further show that mitochondria from MCU(-/-) mice lacked evidence for calcium-induced permeability transition pore (PTP) opening. The lack of PTP opening does not seem to protect MCU(-/-) cells and tissues from cell death, although MCU(-/-) hearts fail to respond to the PTP inhibitor cyclosporin A. Taken together, these results clarify how acute alterations in mitochondrial matrix calcium can regulate mammalian physiology.

  16. Effect of dietary calcium and phosphorus on intestinal calcium absorption and vitamin D metabolism

    International Nuclear Information System (INIS)

    To understand better dietary regulation of intestinal calcium absorption, a quantitative assessment of the metabolites in plasma and duodenum of rats given daily doses of radioactive vitamin D3 and diets differing in calcium and phosphorus content was made. All known vitamin D metabolites were ultimately identified by high-pressure liquid chromatography. In addition to the known metabolites (25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3, 25,26-dihydroxyvitamin D3, and 1,24,25-trihydroxyvitamin D3), several new and unidentified metabolites were found. In addition to 1,25-dihydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3, the levels of some of the unknown metabolites could be correlated with intestinal calcium transport. However, whether or not any of these metabolites plays a role in the stimulation of intestinal calcium absorption by low dietary calcium or low dietary phosphorus remains unknown

  17. Single dendrite-targeting interneurons generate branch-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Caleb eStokes

    2014-11-01

    Full Text Available Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence pyramidal cells in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

  18. Helix A Stabilization Precedes Amino-terminal Lobe Activation upon Calcium Binding to Calmodulin

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Baowei [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lowry, David [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mayer, M. Uljana [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Squier, Thomas C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2008-08-09

    The structural coupling between opposing domains of CaM was investigated using the conformationally sensitive biarsenical probe 4,5-bis(1,3,2-dithioarsolan-2-yl)-resorufin (ReAsH), which upon binding to an engineered tetracysteine binding motif near the end of helix A (Thr-5 to Phe-19) becomes highly fluorescent. Changes in conformation and dynamics are reflective of the native CaM structure, as there is no change in the 1H-15N HSQC NMR spectrum in comparison to wild-type CaM. We find evidence of a conformational intermediate associated with CaM activation, where calcium occupancy of sites in the amino-terminal and carboxyl-terminal lobes of CaM differentially affect the fluorescence intensity of bound ReAsH. Insight into the structure of the conformational intermediate is possible from a consideration of calcium-dependent changes in rates of ReAsH binding and helix A mobility, which respectively distinguish secondary structural changes associated with helix A stabilization from the tertiary structural reorganization of the amino-terminal lobe of CaM necessary for high-affinity binding to target proteins. Helix A stabilization is associated with calcium occupancy of sites in the carboxyl-terminal lobe (Kd = 0.36 ± 0.04 μM), which results in a reduction in the rate of ReAsH binding from 4900 M-1 sec-1 to 370 M-1 sec-1. In comparison, tertiary structural changes involving helix A and other structural elements in the amino-terminal lobe requires calcium-occupancy of amino-terminal sites (Kd = 18 ± 3 μM). Observed secondary and tertiary structural changes involving helix A in response to the sequential calcium occupancy of carboxyl- and amino-terminal lobe calcium binding sites suggest an important involvement of helix A in mediating the structural coupling between the opposing domains of CaM. These results are discussed in terms of a model in which carboxyl-terminal lobe calcium activation induces

  19. 40 CFR 98.41 - Reporting threshold.

    Science.gov (United States)

    2010-07-01

    ...) MANDATORY GREENHOUSE GAS REPORTING Electricity Generation § 98.41 Reporting threshold. You must report GHG emissions under this subpart if your facility contains one or more electricity generating units and...

  20. 14 CFR 33.41 - Applicability.

    Science.gov (United States)

    2010-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.41 Applicability. This subpart prescribes the block tests and inspections for reciprocating aircraft engines....

  1. 17 CFR 41.48 - Undermargined accounts.

    Science.gov (United States)

    2010-04-01

    ... PRODUCTS Customer Accounts and Margin Requirements § 41.48 Undermargined accounts. (a) Failure to satisfy....44(a)(1) of this subpart, § 220.4(d) of Regulation T (12 CFR 220.4(d)) respecting liquidation...

  2. Deck41 Surficial Seafloor Sediment Description Database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Deck41 is a digital summary of surficial sediment composition for 36,401 seafloor samples worldwide. Data include collecting source, ship, cruise, sample id,...

  3. Effects of Adding Chymosin to Milk on Calcium Homeostasis

    DEFF Research Database (Denmark)

    Møller, Ulla Kristine; Jensen, Lars Thorbjørn; Mosekilde, Leif;

    2014-01-01

    Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome...... of the study was 24-h renal calcium excretion that is considered a proxy measure of the amount of calcium absorbed from the intestine. We studied 125 healthy men and women, aged 34 (25-45) years on two separate days. On each day, a light breakfast was served together with 500 ml of semi-skimmed milk to which...... not depend on plasma 25-hydroxyvitamin D levels. Chymosin added to milk increases renal calcium excretion in the hours following intake without affecting plasma levels of calcium or calciotropic hormones. The effect most likely represents enhanced intestinal calcium absorption shortly after intake. Further...

  4. Role of mitochondria and network connectivity in intercellular calcium oscillations

    CERN Document Server

    Dokukina, I V; Grachev, E A; Gunton, J D; Dokukina, Irina V.; Gracheva, Maria E.; Grachev, Eugene A.; Gunton, James D.

    2005-01-01

    Mitochondria are large-scale regulators of cytosolic calcium under normal cellular conditions. In this paper we model the complex behavior of mitochondrial calcium during the action of inositol 1,4,5-trisphosphate on a single cell and find results that are in good agreement with recent experimental studies. We also study the influence of the cellular network connectivity on intercellular signalling via gap junction diffusion. We include in our model the dependence of the junctional conductivity on the cytosolic calcium concentrations in adjacent cells. We consider three different mechanisms of calcium wave propagation through gap junctions: via calcium diffusion, inositol 1,4,5-trisphosphate diffusion, and both calcium and inositol 1,4,5-trisphosphate diffusion. We show that inositol 1,4,5-trisphosphate diffusion is the mechanism of calcium wave propagation and that calcium diffusion is the mechanism of synchronization of cytosolic calcium oscillations in adjacent cells. We also study the role of different to...

  5. THERMAL DEGRADATION AND FLAME RETARDANCY OF CALCIUM ALGINATE FIBERS

    Institute of Scientific and Technical Information of China (English)

    Qing-shan Kong; Bing-bing Wang; Quan Ji; Yan-zhi Xia; Zhao-xia Guo; Jian Yu

    2009-01-01

    Calcium alginate fibers were prepared by wet spinning of sodium alginate into a coagulating bath containing calcium chloride. The thermal degradation and flame retardancy of calcium alginate fibers were investigated with thermal gravimetry (TG), X-ray diffraction (XRD), limiting oxygen index (LOI) and cone calorimeter (CONE). The results show that calcium alginate fibers are inherently flame retardant with a LOI value of 34, and the heat release rate (HRR), total heat release (THR), CO and CO_2 concentrations during combustion are much lower compared with those of viscose fibers. Calcium carbonate and calcium oxide were formed during thermal degradation of calcium alginate fibers at different temperatures. The shape of calcium alginate fibers is well kept after LOI test. The rigid combustion residue char acts as an effective barrier to the outward diffusion of flame and heat. The combustion process and flame retardant mechanism of calcium alginate fibers are also discussed.

  6. Role of calcium in gravity perception of plant roots

    Science.gov (United States)

    Evans, Michael L.

    1986-01-01

    Calcium ions may play a key role in linking graviperception by the root cap to the asymmetric growth which occurs in the elongation zone of gravistimulated roots. Application of calcium-chelating agents to the root cap inhibits gravitropic curvature without affecting growth. Asymmetric application of calcium to one side of the root cap induces curvature toward the calcium source, and gravistimulation induces polar movement of applied (Ca-45)(2+) across the root cap toward the lower side. The action of calcium may be linked to auxin movement in roots since: (1) auxin transport inhibitors interfere both with gravitropic curvature and graviinduced polar calcium movement and (2) asymmetric application of calcium enhances auxin movement across the elongation zone of gravistimulated roots. Indirect evidence indicates that the calcium-modulated regulator protein, calmodulin, may be involved in either the transport or action of calcium in the gravitropic response mechanism of roots.

  7. Role of calcium in gravity perception of plant roots

    Science.gov (United States)

    Evans, Michael L.

    Calcium ions may play a key role in linking graviperception by the root cap to the asymmetric growth which occurs in the elongation zone of gravistimulated roots. Application of calcium-chelating agents to the root cap inhibits gravitropic curvature without affecting growth. Asymmetric application of calcium to one side of the root cap induces curvature toward the calcium source, and gravistimulation induces polar movement of applied 45Ca2+ across the root cap toward the lower side. The action of calcium may be linked to auxin movement in roots since 1) auxin transport inhibitors interfere both with gravitropic curvature and gravi-induced polar calcium movement and 2) asymmetric application of calcium enhances auxin movement across the elongation zone of gravistimulated roots. Indirect evidence indicates that the calcium-modulated regulator protein, calmodulin, may be involved in either the transport or action of calcium in the gravitropic response mechanism of roots.

  8. Effects of calcium gluconate on the utilization of magnesium and the nephrocalcinosis in rats fed excess dietary phosphorus and calcium.

    Science.gov (United States)

    Chonan, O; Takahashi, R; Kado, S; Nagata, Y; Kimura, H; Uchida, K; Watanuki, M

    1996-08-01

    The effects of calcium gluconate on the utilization of magnesium and nephrocalcinosis in male Wistar rats made magnesium-deficient by adding excess dietary phosphorus (1.195 g of phosphorus/100 g of diet) and calcium (1.04 g of calcium/100 g of diet) were compared with the effects of calcium carbonate. The effects of dietary magnesium concentration on the magnesium status and nephrocalcinosis were also examined. Adding excess dietary phosphorus and calcium decreased the apparent magnesium absorption ratios and the concentrations of magnesium in the serum and femur and increased the deposition of calcium in the kidney, and the low magnesium condition (0.024 g of magnesium/100 g of diet) aggravated the deposition of calcium and the low magnesium status. The apparent magnesium absorption ratios and femur magnesium concentration in the rats fed a calcium gluconate diet (an equimolar mixture of calcium gluconate and calcium carbonate was used as a source of calcium) were significantly higher than in the rats fed a calcium carbonate diet (only calcium carbonate was used as a source of calcium), irrespective of dietary magnesium concentration. Dietary calcium gluconate lessened the accumulation of calcium in the kidney and increased the serum magnesium concentration compared with dietary calcium carbonate, when the rats were fed the normal magnesium diet (0.049 g of magnesium/100 g of diet) but not the low magnesium diet. We speculate that the increased utilization of magnesium by feeding the calcium gluconate diet to a limited extent prevented the low magnesium status and the severity of nephrocalcinosis caused by adding excess dietary phosphorus and calcium.

  9. Mesenteric lymph return is an important contributor to vascular hyporeactivity and calcium desensitization after hemorrhagic shock.

    Science.gov (United States)

    Zhao, Zi-Gang; Niu, Chun-Yu; Wei, Yan-Ling; Zhang, Yu-Ping; Si, Yong-Hua; Zhang, Jing

    2012-08-01

    . Even more importantly, mesenteric lymph 1 h after shock was an important contributor to vascular hyporeactivity, and its mechanism of action was related to calcium desensitization. Targeting lymph may therefore have therapeutic potential in the treatment of severe shock-induced hypotension.

  10. Information flow through calcium binding proteins

    Science.gov (United States)

    Bak, Ji Hyun; Bialek, William

    2013-03-01

    Calcium signaling is a ubiquitous mode of biological communication, which regulates a great variety of vital processes in living systems. Such a signal typically begins with an elementary event, in which calcium ions bind to a protein, inducing a change in the protein's structure. Information can only be lost, from what was conveyed through this initial event, as the signal is further transduced through the downstream networks. In the present work we analyze and optimize the information flow in the calcium binding process. We explicitly calculate the mutual information between the calcium concentration and the states of the protein, using a simple model for allosteric regulation in a dimeric protein. The optimal solution depends on the dynamic range of the input as well as on the timescale of signal integration. According to our result, the optimizing strategy involves allowing the calcium-binding protein to be ``activated'' by a partial occupation of its sites, and tuning independently the strengths of cooperative interactions in the binding and unbinding processes.

  11. Calcium's Role in Mechanotransduction during Muscle Development

    Directory of Open Access Journals (Sweden)

    Tatiana Benavides Damm

    2014-01-01

    Full Text Available Mechanotransduction is a process where cells sense their surroundings and convert the physical forces in their environment into an appropriate response. Calcium plays a crucial role in the translation of such forces to biochemical signals that control various biological processes fundamental in muscle development. The mechanical stimulation of muscle cells may for example result from stretch, electric and magnetic stimulation, shear stress, and altered gravity exposure. The response, mainly involving changes in intracellular calcium concentration then leads to a cascade of events by the activation of downstream signaling pathways. The key calcium-dependent pathways described here include the nuclear factor of activated T cells (NFAT and mitogen-activated protein kinase (MAPK activation. The subsequent effects in cellular homeostasis consist of cytoskeletal remodeling, cell cycle progression, growth, differentiation, and apoptosis, all necessary for healthy muscle development, repair, and regeneration. A deregulation from the normal process due to disuse, trauma, or disease can result in a clinical condition such as muscle atrophy, which entails a significant loss of muscle mass. In order to develop therapies against such diseased states, we need to better understand the relevance of calcium signaling and the downstream responses to mechanical forces in skeletal muscle. The purpose of this review is to discuss in detail how diverse mechanical stimuli cause changes in calcium homeostasis by affecting membrane channels and the intracellular stores, which in turn regulate multiple pathways that impart these effects and control the fate of muscle tissue.

  12. Calcium and bone disorders in pregnancy

    Directory of Open Access Journals (Sweden)

    Shriraam Mahadevan

    2012-01-01

    Full Text Available Significant transplacental calcium transfer occurs during pregnancy, especially during the last trimester, to meet the demands of the rapidly mineralizing fetal skeleton. Similarly, there is an obligate loss of calcium in the breast milk during lactation. Both these result in considerable stress on the bone mineral homeostasis in the mother. The maternal adaptive mechanisms to conserve calcium are different in pregnancy and lactation. During pregnancy, increased intestinal absorption of calcium from the gut mainly due to higher generation of calcitriol (1,25 dihydroxy vitamin D helps in maintaining maternal calcium levels. On the other hand, during lactation, the main compensatory mechanism is skeletal resorption due to increased generation of parathormone related peptide (PTHrP from the breast. Previous studies suggest that in spite of considerable changes in bone mineral metabolism during pregnancy, parity and lactation are not significantly associated with future risk for osteoporosis. However, in India, the situation may not be the same as a significant proportion of pregnancies occur in the early twenties when peak bone mass is not yet achieved. Further, malnutrition, anemia and vitamin D deficiency are commonly encountered in this age group. This may have an impact on future bone health of the mother. It may also probably provide an opportunity for health care providers for prevention. Other metabolic bone diseases like hypoparathyroidism, hyperparathyroidism and pseudohypoparathyroidism are rarely encountered in pregnancy. Their clinical implications and management are also discussed.

  13. 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.

  14. 36 CFR 228.41 - Scope.

    Science.gov (United States)

    2010-07-01

    ... vegetative materials used as or for: Soil conditioners or amendments applied to physically alter soil... soil amendment because of a constituent element other than calcium or magnesium carbonate that... Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal...

  15. Oxidative Stress and Maxi Calcium-Activated Potassium (BK Channels

    Directory of Open Access Journals (Sweden)

    Anton Hermann

    2015-08-01

    Full Text Available All cells contain ion channels in their outer (plasma and inner (organelle membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells, alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle. In this chapter we summarize effects of oxidative stress and redox mechanisms on some ion channels, in particular on maxi calcium-activated potassium (BK channels which play an outstanding role in a plethora of physiological and pathophysiological functions in almost all cells and tissues. We first elaborate on some general features of ion channel structure and function and then summarize effects of oxidative alterations of ion channels and their functional consequences.

  16. Calcium Phosphate Nanocomposite Particles for In Vitro Imaging and Encapsulated Chemotherapeutic Drug Delivery to Cancer Cells

    OpenAIRE

    Kester, Mark; Heakal, Y.; Sharma, A.; Robertson, Gavin P.; Morgan, Thomas T.; İ Altinoğlu, Erhan; Tabaković, Amra; Parette, Mylisa R.; Rouse, Sarah; Ruiz-Velasco, Victor; Adair, James H.

    2008-01-01

    Paradigm-shifting modalities to more efficiently deliver drugs to cancerous lesions require the following attributes: nanoscale-size, targetability and stability under physiological conditions. Often, these nanoscale drug delivery vehicles are limited due to agglomeration, poor solubility or cytotoxicity. Thus, we have designed a methodology to encapsulate hydrophobic antineoplastic chemotherapeutics within a 20-30 nm diameter, pH-responsive, non-agglomerating, non-toxic calcium phosphate nan...

  17. Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

    Science.gov (United States)

    Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M.; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred

    2015-01-01

    Background and objectives Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Design, settings, participants, & measurements Multivariable linear regression was used to explore factors associated with square root–transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. Results In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15–95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein–corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, −0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, −0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. Conclusions There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. PMID:25518946

  18. KIR4.1: K+ Channel Illusion or Reality in the Autoimmune Pathogenesis of Multiple Sclerosis

    Science.gov (United States)

    Gu, Chen

    2016-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Many believe autoimmune pathogenesis plays a key role in MS, but its target(s) remains elusive. A recent study detected autoantibodies against KIR4.1, an ATP-sensitive, inward rectifier potassium channel, in nearly half of the MS patients examined. KIR4.1 channels are expressed in astrocytes. Together with aquaporin 4 (AQP4) water channels, they regulate astrocytic functions vital for myelination. Autoantibodies against AQP4 have been established as a key biomarker for neuromyelitis optica (NMO) and contributed to diagnostic and treatment strategy adjustments. Similarly, identification of KIR4.1 autoantibodies could have high therapeutic values in treating MS. Consistent with its potential role in MS, KIR4.1 dysfunction is implicated in several neurological disorders. However, the enrichment of KIR4.1 autoantibodies in MS patients is questioned by follow-up studies. Further, investigations are needed to clarify this controversy and unravel the underlying mechanisms of MS pathogenesis. PMID:27729847

  19. OSTEOPOROSIS IN CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

    Directory of Open Access Journals (Sweden)

    S A Vladimirov

    2013-01-01

    Full Text Available Objective: to study the incidence of osteoporosis (OP in patients with calcium pyrophosphate crystal deposition disease (CPCDD. Subjects and methods. Eighty patients with CPCDD were examined. Bone mineral density (BMD of the forearm, lumbar spine, and femoral neck was determined by dual-energy X-ray absorptiometry. Laboratory diagnosis involved determination of the blood levels of C-reactive protein, parathyroid hormone, calcium, magnesium, and phosphorus and the daily urinary excretion of calcium and phosphates. Results. The patients with OP were significantly older than those with normal BMD and osteopenia. Forearm bones were the most common isolated location of OP and osteopenia. Injuries in the history, traumatic fractures, and the intake of diuretics were somewhat more common in the patients diagnosed with OP. The incidence of hyperparathyroidism did not differ significantly in the groups.

  20. Glial calcium signaling in physiology and pathophysioilogy

    Institute of Scientific and Technical Information of China (English)

    Alexei VERKHRASKY

    2006-01-01

    Neuronal-glial circuits underlie integrative processes in the nervous system.Function of glial syncytium is,to a very large extent,regulated by the intracellular calcium signaling system.Glial calcium signals are triggered by activation of multiple receptors,expressed in glial membrane,which regulate both Ca2+ entry and Ca2+ release from the endoplasmic reticulum.The endoplasmic reticulum also endows glial cells with intracellular excitable media,which is able to produce and maintain long-ranging signaling in a form of propagating Ca2+ waves.In pathological conditions,calcium signals regulate glial response to injury,which might have both protective and detrimental effects on the nervous tissue.

  1. Calcium carbide poisoning via food in childhood.

    Science.gov (United States)

    Per, Hüseyin; Kurtoğlu, Selim; Yağmur, Fatih; Gümüş, Hakan; Kumandaş, Sefer; Poyrazoğlu, M Hakan

    2007-02-01

    The fast ripening of fruits means they may contain various harmful properties. A commonly used agent in the ripening process is calcium carbide, a material most commonly used for welding purposes. Calcium carbide treatment of food is extremely hazardous because it contains traces of arsenic and phosphorous. Once dissolved in water, the carbide produces acetylene gas. Acetylene gas may affect the neurological system by inducing prolonged hypoxia. The findings are headache, dizziness, mood disturbances, sleepiness, mental confusion, memory loss, cerebral edema and seizures. We report the case of a previously healthy 5 year-old girl with no chronic disease history who was transferred to our Emergency Department with an 8-h history of coma and delirium. A careful history from her father revealed that the patient ate unripe dates treated with calcium carbide.

  2. The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane

    DEFF Research Database (Denmark)

    Draeby, Ingrid; Woods, Yvonne L; la Cour, Jonas Marstrand;

    2007-01-01

    ALG-2 (apoptosis linked gene 2 product) is a calcium binding protein for which no clear cellular function has been established. In this study we identified Scotin as a novel ALG-2 target protein containing 6 PXY and 4 PYP repeats, earlier identified in the ALG-2 binding regions of AIP1/ALIX and T...... cells. Overexpression of ALG-2 led to accumulation of Scotin in MCF7 and H1299 cells. In vitro and in vivo binding of ALG-2 to Scotin was demonstrated to be strictly calcium dependent indicating a role of this interaction in calcium signaling pathways....

  3. Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

    Science.gov (United States)

    Laporta, Jimena; Moore, Spencer A E; Weaver, Samantha R; Cronick, Callyssa M; Olsen, Megan; Prichard, Austin P; Schnell, Brian P; Crenshaw, Thomas D; Peñagaricano, Francisco; Bruckmaier, Rupert M; Hernandez, Laura L

    2015-07-01

    A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism. PMID:26099356

  4. Impairment of ciprofloxacin absorption by calcium polycarbophil.

    Science.gov (United States)

    Kato, Ryuji; Ueno, Kazuyuki; Imano, Hideki; Kawai, Masayuki; Kuwahara, Shiro; Tsuchishita, Yoshimasa; Yonezawa, Emi; Tanaka, Kazuhiko

    2002-07-01

    The effect of calcium polycarbophil on the absorption of ciprofloxacin, a broad-spectrum antibacterial agent, was evaluated in an in vitro and in vivo study. In the in vitro study, the release of ciprofloxacin from the cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, male ST Wistar rats and male volunteers were employed. First, 20 mg/kg of ciprofloxacin alone (Rat Study 1) or 20 mg/kg of ciprofloxacin in combination with 64 mg/kg of calcium chloride (Rat Study 2) was administered orally to 3 rats. Second, a volunteer study was employed and a randomized crossover design with twophases was used. In onephase, volunteers received 400 mg of ciprofloxacin alone (Study 1); in the other phase, they received 400 mg of ciprofloxacin and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The plasma and serum concentrations of ciprofloxacin were measured by high-performance liquid chromatography. The release of ciprofloxacin from the cellulose membrane in the presence of aluminum, calcium, or iron ions was slower than that in the absence of these metal ions. The AUC0-4 and Cmax in Rat Study 2 were lower than those respective values in Rat Study 1. AUC0-4 was approximately 60% lower in Rat Study 2 than Rat Study 1. In the volunteer study, the AUC0-12 and Cmax in Study 2 were lower than those respective values in Study 1. In particular, AUC0-12 was approximately 50% lowerin Study 2 than in Study 1. These findings suggest that when ciprofloxacin and calcium polycarbophil were coadministered concomitantly, a decrease of ciprofloxacin absorption was observed, and this action was caused by the formation of chelate complexes. Therefore, it seems clear that we should avoid the concomitant administration of ciprofloxacin and calcium polycarbophil.

  5. Characterization of Calcium Compounds in Opuntia ficus indica as a Source of Calcium for Human Diet

    Directory of Open Access Journals (Sweden)

    Isela Rojas-Molina

    2015-01-01

    Full Text Available Analyses of calcium compounds in cladodes, soluble dietary fiber (SDF, and insoluble dietary fiber (IDF of Opuntia ficus indica are reported. The characterization of calcium compounds was performed by using Scanning Electron Microscopy, Energy Dispersive Spectrometry, X-ray diffraction, and infrared spectroscopy. Atomic Absorption Spectroscopy and titrimetric methods were used for quantification of total calcium and calcium compounds. Whewellite (CaC2O4·H2O, weddellite (CaC2O4·(H2O2.375, and calcite (CaCO3 were identified in all samples. Significant differences (P≤0.05 in the total calcium contents were detected between samples. CaC2O4·H2O content in cladodes and IDF was significantly higher (P≤0.05 in comparison to that observed in SDF, whereas minimum concentration of CaCO3 was detected in IDF with regard to CaCO3 contents observed in cladodes and SDF. Additionally, molar ratio oxalate : Ca2+ in all samples changed in a range from 0.03 to 0.23. These results support that calcium bioavailability in O. ficus indica modifies according to calcium compounds distribution.

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

    Science.gov (United States)

    Komar, Nemanja; Zeebe, Richard

    2016-04-01

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

  7. 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...... discusses the current knowledge on the structure and potential function of this protein. Several putative binding partners of ALG-2 have been identified hinting to functions of ALG-2 in apoptosis and possibly also in proliferation, endocytosis and transcriptional regulation during development. Gene deletion...

  8. NMR study of hydrated calcium silicates

    International Nuclear Information System (INIS)

    Radioactive wastes storage methods are developed by the CEA. As cements are important materials as well for hours living radioisotopes than for years living radioisotopes, a better knowledge of this material will allow to anticipate its behaviour and to obtain safer storage methods. The structure of calcium silicates (C-S-H) (main constituent of cements) have then been determined in this thesis by nuclear magnetic resonance. This method has allow to explain in structural terms, the different calcium rates that can be measured in the C-S-H too. (O.M.)

  9. Calcium and weight control-Publications summaries

    Directory of Open Access Journals (Sweden)

    Feride Çelebi

    2011-08-01

    Full Text Available Obesity is a public health problem. And it is known that both energy balance and nutritional factors are effective on it. The effects of dietary calcium on bone health are known however with recent studies, it has become a food item that focused on the effect on body weight control. Most epidemiyolojik studies claim that there is a relationship between long-term consumption of diary milk and milk products and the decrease of body weight and fat mass. In this article, there are different studies that support or do not support this idea. However the effect mechanism of calcium on weight control is tried to be explained.

  10. The effects of UV light on calcium metabolism in ball pythons (Python regius).

    Science.gov (United States)

    Hedley, J; Eatwell, K

    2013-10-12

    Despite the popularity of keeping snakes in captivity, there has been limited investigation into the effects of UV radiation on vitamin D levels in snakes. The aim of this study was to investigate the effects of UV-b radiation on plasma 25-hydroxyvitamin D3 levels and ionised calcium concentrations in ball pythons (Python regius). Blood samples were taken from 14 ball pythons, which had never been exposed to UV-b light, to obtain baseline 25-hydroxyvitamin D3 levels and ionised calcium concentrations. Blood samples were then taken again from the same snakes 70 days later after one group (Group 1, n=6 females) were exposed to UV-b radiation daily, and the other group (Group 2, n=5 males and 3 females) were exposed to no UV-b radiation. Mean±sd 25-hydroxyvitamin D3 levels on day 0 in Group 1 were 197±35 nmol/l, and on day 70 were 203.5±13.8 nmol/l. Mean±sd 25-hydroxyvitamin D3 levels in Group 2 on day 0 were 77.7±41.5 nmol/l, and on day 70 were 83.0±41.9 nmol/l. Mean±sd ionised calcium levels at day 0 were 1.84±0.05 mmol/l for Group 1, and on day 70 were 1.78±0.07 mmol/l. Mean±sd ionised calcium levels at day 0 were 1.79±0.07 mmol/l for Group 2, and on day 70 were 1.81±0.05 mmol/l. No association was demonstrated between exposure to UV-b radiation and plasma 25-hydroxyvitamin D3 and ionised calcium concentrations. These results may provide baseline parameters for future studies in this and other snake species to determine ability to utilise UV-b light for vitamin D production.

  11. Avian eggshell formation in calcium-rich and calcium-poor habitats: Importance of snail shells and anthropogenic calcium sources

    NARCIS (Netherlands)

    Graveland, J.

    1996-01-01

    Most passerines depend on the intake of calcium-rich material in addition to their normal food for proper eggshell formation and skeletal growth. A large proportion of Great Tits (Pants major) in forests on nutrient-poor soils in the Netherlands produce eggs with defective shells as a result of calc

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

    DEFF Research Database (Denmark)

    Hsu, Yu-Juei; Dimke, Henrik Anthony; Schoeber, Joost P H;

    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....... Androgen deficiency increased the abundance of the renal mRNA and protein of both the luminal transient receptor potential vanilloid-subtype 5 (TRPV5) and intracellular calbindin-D(28K) transporters, which in turn were suppressed by testosterone treatment. There were no significant differences in serum...

  13. Calcium Supplements Might Raise Older Women's Dementia Risk

    Science.gov (United States)

    ... nutrient," she said. "For example, calcium, phosphorus and magnesium all are typically looked at for their effects ... which was not originally designed to assess calcium intake," MacKay noted. "Further, the new analysis included only ...

  14. Intolerance to oral and intravenous calcium supplements in atopic eczema.

    OpenAIRE

    Devlin, J; David, T J

    1990-01-01

    Children treated with dietary restriction for food intolerance may require calcium supplementation, particularly if cows' milk and milk substitutes are not tolerated. We report two children with atopic eczema who reacted adversely to a number of calcium supplement formulations.

  15. Inulin and fructooligosaccharide affect in vitro calcium uptake and absorption from calcium-enriched gluten-free bread.

    Science.gov (United States)

    Krupa-Kozak, U; Swiątecka, D; Bączek, N; Brzóska, M M

    2016-04-01

    Compromised intestinal calcium absorption affecting a deterioration of bone state is a sign of coeliac disease. Experimental calcium-fortified gluten-free bread (GFB) of improved calcium bioavailability could increase calcium content in the diets of coeliac disease patients, allowing them to obtain the amount of calcium they need for therapeutic use. Prebiotics, including inulin-type fructans (IFs) have a beneficial effect on calcium bioavailability. In the present study, the in vitro model composed of the intestinal-like Caco-2 cells and the human intestinal bacteria (Lactobacillus, Enterococcus and Enterobacteriaceae) were used to analyse the effect of inulin and fructooligosaccharide (FOS) of different chain lengths, on calcium uptake and absorption from experimental GFB. Analysed IFs, especially short-chain FOS, significantly (p < 0.05) increased cellular calcium uptake from GFB digest and stimulated the intestinal bacteria applied in the cultures to the intensive synthesis of organic acids. In particular, the concentration of butyric, valeric and lactic acids increased significantly. Similarly, in the calcium absorption experiment, IFs increased the cellular calcium retention but concomitantly reduced its content in basolateral filtrates. The results obtained suggest that the applied IFs affected differentially calcium uptake and absorption from the experimental calcium-enriched GFB, therefore a further study is needed to assess whether these observations made in vitro contribute to IF effects on calcium absorption from experimental GFB in vivo.

  16. Inulin and fructooligosaccharide affect in vitro calcium uptake and absorption from calcium-enriched gluten-free bread.

    Science.gov (United States)

    Krupa-Kozak, U; Swiątecka, D; Bączek, N; Brzóska, M M

    2016-04-20

    Compromised intestinal calcium absorption affecting a deterioration of bone state is a sign of coeliac disease. Experimental calcium-fortified gluten-free bread (GFB) of improved calcium bioavailability could increase calcium content in the diets of coeliac disease patients, allowing them to obtain the amount of calcium they need for therapeutic use. Prebiotics, including inulin-type fructans (IFs) have a beneficial effect on calcium bioavailability. In the present study, the in vitro model composed of the intestinal-like Caco-2 cells and the human intestinal bacteria (Lactobacillus, Enterococcus and Enterobacteriaceae) were used to analyse the effect of inulin and fructooligosaccharide (FOS) of different chain lengths, on calcium uptake and absorption from experimental GFB. Analysed IFs, especially short-chain FOS, significantly (p < 0.05) increased cellular calcium uptake from GFB digest and stimulated the intestinal bacteria applied in the cultures to the intensive synthesis of organic acids. In particular, the concentration of butyric, valeric and lactic acids increased significantly. Similarly, in the calcium absorption experiment, IFs increased the cellular calcium retention but concomitantly reduced its content in basolateral filtrates. The results obtained suggest that the applied IFs affected differentially calcium uptake and absorption from the experimental calcium-enriched GFB, therefore a further study is needed to assess whether these observations made in vitro contribute to IF effects on calcium absorption from experimental GFB in vivo. PMID:26965706

  17. 41 CFR 60-1.41 - Solicitations or advertisements for employees.

    Science.gov (United States)

    2010-07-01

    ... advertisements for employees. 60-1.41 Section 60-1.41 Public Contracts and Property Management Other Provisions... or advertisements for employees. In solicitations or advertisements for employees placed by or on... U.S.C. 701; (c) Uses a single advertisement, and the advertisement is grouped with...

  18. Calcium Intake in Elderly Australian Women Is Inadequate

    Directory of Open Access Journals (Sweden)

    Colin W. Binns

    2010-09-01

    Full Text Available The role of calcium in the prevention of bone loss in later life has been well established but little data exist on the adequacy of calcium intakes in elderly Australian women. The aim of this study was to compare the dietary intake including calcium of elderly Australian women with the Australian dietary recommendation, and to investigate the prevalence of calcium supplement use in this population. Community-dwelling women aged 70–80 years were randomly recruited using the Electoral Roll for a 2-year protein intervention study in Western Australia. Dietary intake was assessed at baseline by a 3-day weighed food record and analysed for energy, calcium and other nutrients. A total of 218 women were included in the analysis. Mean energy intake was 7,140 ± 1,518 kJ/day and protein provided 19 ± 4% of energy. Mean dietary calcium intake was 852 ± 298 mg/day, which is below Australian recommendations. Less than one quarter of women reported taking calcium supplements and only 3% reported taking vitamin D supplements. Calcium supplements by average provided calcium 122 ± 427 mg/day and when this was taken into account, total calcium intake increased to 955 ± 504 mg/day, which remained 13% lower than the Estimated Average Requirement (EAR, 1,100 mg/day for women of this age group. The women taking calcium supplements had a higher calcium intake (1501 ± 573 mg compared with the women on diet alone (813 ± 347 mg. The results of this study indicate that the majority of elderly women were not meeting their calcium requirements from diet alone. In order to achieve the recommended dietary calcium intake, better strategies for promoting increased calcium, from both diet and calcium supplements appears to be needed.

  19. Calcium phosphate mineralization is widely applied in crustacean mandibles

    OpenAIRE

    Shmuel Bentov; Aflalo, Eliahu D.; Jenny Tynyakov; Lilah Glazer; Amir Sagi

    2016-01-01

    Crustaceans, like most mineralized invertebrates, adopted calcium carbonate mineralization for bulk skeleton reinforcement. Here, we show that a major part of the crustacean class Malacostraca (which includes lobsters, crayfishes, prawns and shrimps) shifted toward the formation of calcium phosphate as the main mineral at specified locations of the mandibular teeth. In these structures, calcium phosphate is not merely co-precipitated with the bulk calcium carbonate but rather creates speciali...

  20. The stability mechanisms of an injectable calcium phosphate ceramic suspension.

    OpenAIRE

    Fatimi, Ahmed; Tassin, Jean-François; Axelos, Monique,; Weiss, Pierre

    2010-01-01

    International audience Calcium phosphate ceramics are widely used as bone substitutes in dentistry and orthopedic applications. For minimally invasive surgery an injectable calcium phosphate ceramic suspension (ICPCS) was developed. It consists in a biopolymer (hydroxypropylmethylcellulose: HPMC) as matrix and bioactive calcium phosphate ceramics (biphasic calcium phosphate: BCP) as fillers. The stability of the suspension is essential to this generation of "ready to use" injectable biomat...