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Sample records for calcium 43 target

  1. Proton bombarded reactions of Calcium target nuclei

    Directory of Open Access Journals (Sweden)

    Tel Eyyup

    2017-01-01

    Full Text Available In this study, proton bombarded nuclear reactions calculations of Calcium target nuclei have been investigated in the incident proton energy range of 1–50 MeV. The excitation functions for 40Ca target nuclei reactions have been calculated by using PCROSS nuclear reaction calculation code. Weisskopf-Ewing and the full exciton models were used for equilibrium and for pre-equilibrium calculations, respectively. The excitation functions for 40Ca target nuclei reactions (p,α, (p,n, (p,p have been calculated using the semi-empirical formula Tel et al. [5].

  2. 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...

  3. Specific association of growth-associated protein 43 with calcium release units in skeletal muscles of lower vertebrates

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    G.A. Caprara

    2014-10-01

    Full Text Available Growth-associated protein 43 (GAP43, is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes, and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species.

  4. Targeting connexin 43 in diabetic wound healing: Future perspectives

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    Bajpai S

    2009-01-01

    Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

  5. Heteronemin, a marine sponge terpenoid, targets TDP-43, a key factor in several neurodegenerative disorders.

    Science.gov (United States)

    Cassiano, Chiara; Esposito, Roberta; Tosco, Alessandra; Zampella, Angela; D'Auria, Maria Valeria; Riccio, Raffaele; Casapullo, Agostino; Monti, Maria Chiara

    2014-01-14

    Trans-activation response DNA-binding protein of 43 kDa (TDP-43), a key factor in several neurodegenerative conditions, was discovered as a novel target of heteronemin by chemical proteomics. Combining bio-physical orthogonal approaches with biological analysis, heteronemin was found to influence the binding of TDP-43-cognate nucleic acids and to modulate the TDP-43 aggregation state and its cellular localization.

  6. Low threshold T‐type calcium channels as targets for novel epilepsy treatments

    National Research Council Canada - National Science Library

    Powell, Kim L; Cain, Stuart M; Snutch, Terrance P; O'Brien, Terence J

    2014-01-01

    .... T ‐type calcium channels are expressed widely throughout the brain and peripheral tissues, and thus have been proposed as therapeutic targets for a variety of diseases such as epilepsy, insomnia, pain...

  7. Calcium

    Science.gov (United States)

    ... Turn to calcium-fortified (or "calcium-set") tofu, soy milk, tempeh, soy yogurt, and cooked soybeans (edamame). Calcium-fortified foods. Look for calcium-fortified orange juice, soy or rice milk, breads, and cereal. Beans. You can get decent ...

  8. Natural Abundance 43Ca NMR as a Tool for Exploring Calcium Biomineralization: Renal Stone Formation and Growth

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, Geoffrey M.; Kirkpatrick, Robert J.

    2011-12-07

    Renal stone diseases are a global health issue with little effective therapeutic recourse aside from surgery and shock-wave lithotripsy, primarily because the fundamental chemical mechanisms behind calcium biomineralization are poorly understood. In this work, we show that natural abundance 43Ca NMR at 21.1 T is an effective means to probe the molecular-level Ca2+ structure in oxalate-based kidney stones. We find that the 43Ca NMR resonance of an authentic oxalate-based kidney stone cannot be explained by a single pure phase of any common Ca2+-bearing stone mineral. Combined with XRD results, our findings suggest an altered calcium oxalate monohydrate-like Ca2+ coordination environment for some fraction of Ca2+ in our sample. The evidence is consistent with existing literature hypothesizing that nonoxalate organic material interacts directly with Ca2+ at stone surfaces and is the primary driver of renal stone aggregation and growth. Our findings show that 43Ca NMR spectroscopy may provide unique and crucial insight into the fundamental chemistry of kidney stone formation, growth, and the role organic molecules play in these processes.

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

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    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. ©2015 American Association for Cancer Research.

  10. Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

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    Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

    2016-01-01

    Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Calcium

    Science.gov (United States)

    ... and blood vessels contract and expand, to secrete hormones and enzymes and to send messages through the nervous system. It is important to get plenty of calcium in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with ...

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

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    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.

  13. Low threshold T-type calcium channels as targets for novel epilepsy treatments.

    Science.gov (United States)

    Powell, Kim L; Cain, Stuart M; Snutch, Terrance P; O'Brien, Terence J

    2014-05-01

    Low voltage-activated T-type calcium channels were originally cloned in the 1990s and much research has since focused on identifying the physiological roles of these channels in health and disease states. T-type calcium channels are expressed widely throughout the brain and peripheral tissues, and thus have been proposed as therapeutic targets for a variety of diseases such as epilepsy, insomnia, pain, cancer and hypertension. This review discusses the literature concerning the role of T-type calcium channels in physiological and pathological processes related to epilepsy. T-type calcium channels have been implicated in pathology of both the genetic and acquired epilepsies and several anti-epileptic drugs (AEDs) in clinical use are known to suppress seizures via inhibition of T-type calcium channels. Despite the fact that more than 15 new AEDs have become clinically available over the past 20 years at least 30% of epilepsy patients still fail to achieve seizure control, and many patients experience unwanted side effects. Furthermore there are no treatments that prevent the development of epilepsy or mitigate the epileptic state once established. Therefore there is an urgent need for the development of new AEDs that are effective in patients with drug resistant epilepsy, are anti-epileptogenic and are better tolerated. We also review the mechanisms of action of the current AEDs with known effects on T-type calcium channels and discuss novel compounds that are being investigated as new treatments for epilepsy. © 2013 The British Pharmacological Society.

  14. Calcium

    Science.gov (United States)

    ... from dietary supplements are linked to a greater risk of kidney stones, especially among older adults. But calcium from foods does not appear to cause kidney stones. For most people, other factors (such as not drinking enough fluids) probably have ...

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

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

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    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Target size of calcium pump protein from skeletal muscle sarcoplasmic reticulum.

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    Hymel, L; Maurer, A; Berenski, C; Jung, C Y; Fleischer, S

    1984-04-25

    The oligomeric size of calcium pump protein (CPP) in fast skeletal muscle sarcoplasmic reticulum membrane was determined using target theory analysis of radiation inactivation data. There was a parallel decrease of Ca2+-ATPase and calcium pumping activities with increasing radiation dose. The loss of staining intensity of the CPP band, observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, also correlated directly with the loss of activity. The target size molecular weight of the CPP in the normal sarcoplasmic reticulum membrane ranged between 210,000 and 250,000, which is consistent with a dimeric structure. Essentially the same size is obtained for the non-phosphorylated CPP or for the phosphoenzyme form generated from either ATP (E1 state) or inorganic phosphate (E2 state). Hence, the oligomeric state of the pump does not appear to change during the catalytic cycle. Similar results were obtained with reconstituted sarcoplasmic reticulum membrane vesicles with different lipid to protein ratios. We conclude that the CPP is a dimer in both native and reconstituted sarcoplasmic reticulum membranes. The target size of the calcium-binding protein (calsequestrin) was found to be 50,000 daltons, approximating a monomer.

  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. 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.

  20. Characterization and subcellular targeting of GCaMP-type genetically-encoded calcium indicators.

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    Tianyi Mao

    2008-03-01

    Full Text Available Genetically-encoded calcium indicators (GECIs hold the promise of monitoring [Ca(2+] in selected populations of neurons and in specific cellular compartments. Relating GECI fluorescence to neuronal activity requires quantitative characterization. We have characterized a promising new genetically-encoded calcium indicator-GCaMP2-in mammalian pyramidal neurons. Fluorescence changes in response to single action potentials (17+/-10% DeltaF/F [mean+/-SD] could be detected in some, but not all, neurons. Trains of high-frequency action potentials yielded robust responses (302+/-50% for trains of 40 action potentials at 83 Hz. Responses were similar in acute brain slices from in utero electroporated mice, indicating that long-term expression did not interfere with GCaMP2 function. Membrane-targeted versions of GCaMP2 did not yield larger signals than their non-targeted counterparts. We further targeted GCaMP2 to dendritic spines to monitor Ca(2+ accumulations evoked by activation of synaptic NMDA receptors. We observed robust DeltaF/F responses (range: 37%-264% to single spine uncaging stimuli that were correlated with NMDA receptor currents measured through a somatic patch pipette. One major drawback of GCaMP2 was its low baseline fluorescence. Our results show that GCaMP2 is improved from the previous versions of GCaMP and may be suited to detect bursts of high-frequency action potentials and synaptic currents in vivo.

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

    Science.gov (United States)

    Ojo, Kayode K; Reid, Molly C; Kallur Siddaramaiah, Latha; Müller, Joachim; Winzer, Pablo; Zhang, Zhongsheng; Keyloun, Katelyn R; Vidadala, Rama Subba Rao; Merritt, Ethan A; Hol, Wim G J; Maly, Dustin J; Fan, Erkang; Van Voorhis, Wesley C; Hemphill, Andrew

    2014-01-01

    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 therapy of bovine

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

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

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

  3. 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.

  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. L-type calcium channel targeting and local signalling in cardiac myocytes.

    Science.gov (United States)

    Shaw, Robin M; Colecraft, Henry M

    2013-05-01

    In the heart, Ca(2+) influx via Ca(V)1.2 L-type calcium channels (LTCCs) is a multi-functional signal that triggers muscle contraction, controls action potential duration, and regulates gene expression. The use of LTCC Ca(2+) as a multi-dimensional signalling molecule in the heart is complicated by several aspects of cardiac physiology. Cytosolic Ca(2+) continuously cycles between ~100 nM and ~1 μM with each heartbeat due to Ca(2+) linked signalling from LTCCs to ryanodine receptors. This rapid cycling raises the question as to how cardiac myocytes distinguish the Ca(2+) fluxes originating through L-type channels that are dedicated to contraction from Ca(2+) fluxes originating from other L-type channels that are used for non-contraction-related signalling. In general, disparate Ca(2+) sources in cardiac myocytes such as current through differently localized LTCCs as well as from IP3 receptors can signal selectively to Ca(2+)-dependent effectors in local microdomains that can be impervious to the cytoplasmic Ca(2+) transients that drive contraction. A particular challenge for diversified signalling via cardiac LTCCs is that they are voltage-gated and, therefore, open and presumably flood their microdomains with Ca(2+) with each action potential. Thus spatial localization of Cav1.2 channels to different types of microdomains of the ventricular cardiomyocyte membrane as well as the existence of particular macromolecular complexes in each Cav1.2 microdomain are important to effect different types of Cav1.2 signalling. In this review we examine aspects of Cav1.2 structure, targeting and signalling in two specialized membrane microdomains--transverse tubules and caveolae.

  6. The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design.

    Science.gov (United States)

    Cardew, Emily M; Verlinde, Christophe L M J; Pohl, Ehmke

    2018-02-01

    The apicomplexan protozoan parasites include the causative agents of animal and human diseases ranging from malaria (Plasmodium spp.) to toxoplasmosis (Toxoplasma gondii). The complex life cycle of T. gondii is regulated by a unique family of calcium-dependent protein kinases (CDPKs) that have become the target of intensive efforts to develop new therapeutics. In this review, we will summarize structure-based strategies, recent successes and future directions in the pursuit of specific and selective inhibitors of T. gondii CDPK1.

  7. Contribution of pannexin 1 and connexin 43 hemichannels to extracellular calcium-dependent transport dynamics in human blood-brain barrier endothelial cells.

    Science.gov (United States)

    Kaneko, Yosuke; Tachikawa, Masanori; Akaogi, Ryo; Fujimoto, Kazuhisa; Ishibashi, Megumi; Uchida, Yasuo; Couraud, Pierre-Olivier; Ohtsuki, Sumio; Hosoya, Ken-ichi; Terasaki, Tetsuya

    2015-04-01

    Dysregulation of blood-brain barrier (BBB) transport function is thought to exacerbate neuronal damage in acute ischemic stroke. The purpose of this study was to clarify the characteristics of pannexin (Px) and/or connexin (Cx) hemichannel(s)-mediated transport of organic anions and cations in human BBB endothelial cell line hCMEC/D3 and to identify inhibitors of hemichannel opening in hCMEC/D3 cells in the absence of extracellular Ca(2+), a condition mimicking acute ischemic stroke. In the absence of extracellular Ca(2+), the cells showed increased uptake and efflux transport of organic ionic fluorescent dyes. Classic hemichannel inhibitors markedly inhibited the enhanced uptake and efflux. Quantitative targeted absolute proteomics confirmed Px1 and Cx43 protein expression in plasma membrane of hCMEC/D3 cells. Knockdown of Px1 and Cx43 with the small interfering RNAs significantly inhibited the enhanced uptake and efflux of organic anionic and cationic fluorescent dyes. Clinically used cilnidipine and progesterone, which have neuroprotective effects in animal ischemia models, were identified as inhibitors of hemichannel opening. These findings suggest that altered transport dynamics at the human BBB in the absence of extracellular Ca(2+) is at least partly attributable to opening of Px1 and Cx43 hemichannels. Therefore, we speculate that Px1 and Cx43 may be potential drug targets to ameliorate BBB transport dysregulation during acute ischemia. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors in vitro and in vivo

    Science.gov (United States)

    Eyckmans, J.; Roberts, S.J.; Bolander, J.; Schrooten, J.; Chen, C.S.; Luyten, F.P.

    2014-01-01

    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 hours 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. PMID:23537666

  9. Vasodilation and hypotension of a novel 3-benzylquinazolin- 4(3H)-one derivative via the inhibition of calcium flux.

    Science.gov (United States)

    Sen Li; Zuo, Sai-Jie; Cao, Lei; Liu, Dong-Zheng; Zhang, San-Qi; Cao, Yong-Xiao

    2016-11-15

    A novel 3-benzylquinazolin-4(3H)-one derivative Z32, namely 6,7-dimethoxy-3-(3-chloro-4-(4-fluorobenzyloxy)benzyl)quinazolin-4(3H)-one was synthesized. The vasorelaxant and antihypertensive effects of Z32 and its underlying mechanisms were investigated. The following methods were used. The isometric tension of artery ring segments was recorded using an in vitro myography system. Changes in the calcium influx in mesenteric arteries were surveyed using a real-time confocal microscopy. The arterial pressure of spontaneously hypertensive rats was measured in vivo using a non-invasive tail cuff blood pressure system. The results showed that Z32 can relax rat mesenteric arteries pre-constricted by KCl or phenylephrine in a concentration-dependent manner. The vasorelaxant effects were not affected by the removal of the endothelium, blockade of potassium channels by tetraethylammonium chloride, or inhibition of either guanylate cyclase by ODQ, nitric oxide synthase by l-NAME, or cyclooxygenase by indomethacin. In Ca(2+)-free conditions, Z32 did not affect the constriction evoked by caffeine, however, significantly reduced the constrictions induced (1) by phenylephrine, (2) by CaCl2 in either phenylephrine (in the presence of verapamil) or KCl stimulated arteries, (3) by extracellular Ca(2+) restoration in thapsigargin-treated mesenteric arteries, and (4) by the activator of protein kinase C phorbol-12, 13-dibutyrate, and the inhibitor of protein tyrosine phosphatase sodium orthovanadate. Further, Z32 decreased the systolic and diastolic arterial pressure of spontaneously hypertensive rats in a dose-dependent manner. In conclusion, Z32 lowers the arterial pressure and induces vasorelaxation through the inhibition of calcium flux, probably via a protein tyrosine phosphorylation-dependent way. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Subcellular preconditioning of stem cells: mito-Cx43 gene targeting is cytoprotective via shift of mitochondrial Bak and Bcl-xL balance.

    Science.gov (United States)

    Lu, Gang; Jiang, Shujia; Ashraf, Muhammad; Haider, Khawaja Husnain

    2012-05-01

    To achieve mitochondria-specific expression of connexin-43 (Cx43) transgene for mitochondrial preconditioning in stem cells to improve their survival post-transplantation during heart cell therapy. Cx43- or GFP-encoding adenoviral vectors with a mitochondrial targeting sequence were constructed for transduction of bone marrow Sca-1(+) cells (>90% transduction efficiency). Double-fluorescence immunostaining for cytochrome-c and Cx43 supported by western blotting confirmed mitochondria-specific Cx43 expression in adenoviral-mito-Cx43-transduced cells ((Cx43)Sca-1(+)). (Cx43)Sca-1(+) showed improved survival under lethal oxygen-glucose deprivation culture conditions. (Cx43)Sca-1(+) showed an increased mitochondrial Bcl-xL:Bak ratio and reduced cytochrome-c release into cytosol with concomitantly abolished caspase-3 activity. An in vivo study was performed such that 2 × 10(6) male (Cx43)Sca-1(+) or (GFP)Sca-1(+) cells were injected into a female rat model of acute myocardial infarction. DMEM-injected rats served as controls. On day 7 post-transplantation, 4.3-fold higher survival of (Cx43)Sca-1(+) cells (p targeted Cx43 expression is a novel approach to improve stem cell survival in the infarcted heart.

  11. A FluoPol-ABPP PAD2 high-throughput screen identifies the first calcium site inhibitor targeting the PADs.

    Science.gov (United States)

    Lewallen, Daniel M; Bicker, Kevin L; Madoux, Franck; Chase, Peter; Anguish, Lynne; Coonrod, Scott; Hodder, Peter; Thompson, Paul R

    2014-04-18

    The protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of peptidyl-arginine to form peptidyl-citrulline in a process termed deimination or citrullination. PADs likely play a role in the progression of a range of disease states because dysregulated PAD activity is observed in a host of inflammatory diseases and cancer. For example, recent studies have shown that PAD2 activates ERα target gene expression in breast cancer cells by citrullinating histone H3 at ER target promoters. To date, all known PAD inhibitors bind directly to the enzyme active site. PADs, however, also require calcium ions to drive a conformational change between the inactive apo-state and the fully active calcium bound holoenzyme, suggesting that it would be possible to identify inhibitors that bind the apoenzyme and prevent this conformational change. As such, we set out to develop a screen that can identify PAD2 inhibitors that bind to either the apo or calcium bound form of PAD2. Herein, we provide definitive proof of concept for this approach and report the first PAD inhibitor, ruthenium red (Ki of 17 μM), to preferentially bind the apoenzyme.

  12. 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..

  13. Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer.

    Science.gov (United States)

    Peters, Amelia A; Simpson, Peter T; Bassett, Johnathon J; Lee, Jane M; Da Silva, Leonard; Reid, Lynne E; Song, Sarah; Parat, Marie-Odile; Lakhani, Sunil R; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2012-10-01

    Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression leads to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a subset of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor (ER)-negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared with patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of ER-negative breast cancers.

  14. 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.

  15. 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...

  16. 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.

  17. Contribution of intracellular calcium and pH in ischemic uncoupling of cardiac gap junction channels formed of connexins 43, 40, and 45: a critical function of C-terminal domain.

    Directory of Open Access Journals (Sweden)

    Giriraj Sahu

    Full Text Available Ischemia is known to inhibit gap junction (GJ mediated intercellular communication. However the detail mechanisms of this inhibition are largely unknown. In the present study, we determined the vulnerability of different cardiac GJ channels formed of connexins (Cxs 43, 40, and 45 to simulated ischemia, by creating oxygen glucose deprived (OGD condition. 5 minutes of OGD decreased the junctional conductance (Gj of Cx43, Cx40 and Cx45 by 53±3%, 64±1% and 85±2% respectively. Reduction of Gj was prevented completely by restricting the change of both intracellular calcium ([Ca(2+]i and pH (pHi with potassium phosphate buffer. Clamping of either [Ca(2+]i or pHi, through BAPTA (2 mM or HEPES (80 mM respectively, offered partial resistance to ischemic uncoupling. Anti-calmodulin antibody attenuated the uncoupling of Cx43 and Cx45 significantly but not of Cx40. Furthermore, OGD could reduce only 26±2% of Gj in C-terminus (CT truncated Cx43 (Cx43-Δ257. Tethering CT of Cx43 to the CT-truncated Cx40 (Cx40-Δ249, and Cx45 (Cx45-Δ272 helped to resist OGD mediated uncoupling. Moreover, CT domain played a significant role in determining the junction current density and plaque diameter. Our results suggest; OGD mediated uncoupling of GJ channels is primarily due to elevated [Ca(2+]i and acidic pHi, though the latter contributes more. Among Cx43, Cx40 and Cx45, Cx43 is the most resistant to OGD while Cx45 is the most sensitive one. CT of Cx43 has major necessary elements for OGD induced uncoupling and it can complement CT of Cx40 and Cx45.

  18. 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, 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 such as Cav3.2 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 Cav2.2, 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 Cav2.2 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 Cav2.2 and the developments made to transform them into therapeutics. PMID:22725651

  19. Changes in Intracellular Calcium Concentration and pH of Target Cells During the Cytotoxic Process: A Quantitative Study at the Single Cell Level

    NARCIS (Netherlands)

    de Grooth, B.G.; Radosevic, Katarina; Greve, Jan; Radosevic, K.

    1995-01-01

    This study reports on the changes in intracellular calcium concentration ([Ca2+]in) and intracellular pH ([pH]in) that occur in K562 target cells during interaction with human Natural Killer (NK) cells. The data were obtained using a quantitative fluorescence microscope and fluorescent ratio probes

  20. 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

    IMPORTANCE OF THE FIELD: Cardiovascular risk factors are often associated with endothelial dysfunction, which is also prognostic for occurrence of cardiovascular events. Endothelial dysfunction is reflected by blunted vasodilatation and reduced nitric oxide (NO) bioavailability. Endothelium......-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...... disease. AREAS COVERED IN THIS REVIEW: SK and IK channels are involved in EDHF-type vasodilatation, but recent studies suggest that these channels are also involved in the regulation of NO bioavailability. Here we review how SK and IK channels may regulate NO bioavailability. WHAT THE READER WILL GAIN...

  1. Comparison of Calcium Dynamics and Specific Features for G Protein-Coupled Receptor-Targeting Drugs Using Live Cell Imaging and Automated Analysis.

    Science.gov (United States)

    Gupta, Rishikesh Kumar; Swain, Sarpras; Kankanamge, Dinesh; Priyanka, Pantula Devi; Singh, Ranjana; Mitra, Kishalay; Karunarathne, Ajith; Giri, Lopamudra

    2017-08-01

    G protein-coupled receptors (GPCRs) are targets for designing a large fraction of the drugs in the pharmaceutical industry. For GPCR-targeting drug screening using cell-based assays, measurement of cytosolic calcium has been widely used to obtain dose-response profiles. However, it remains challenging to obtain drug-specific features due to cell-to-cell heterogeneity in drug-cell responses obtained from live cell imaging. Here, we present a framework combining live cell imaging of a cell population and a feature extraction method for classification of responses of drugs targeting GPCRs CXCR4 and α2AR. We measured the calcium dynamics using confocal microscopy and compared the responses for SDF-1α and norepinephrine. The results clearly show that the clustering patterns of responses for the two GPCRs are significantly different. Additionally, we show that different drugs targeting the same GPCR induce different calcium response signatures. We also implemented principal component analysis and k means for feature extraction and used nondominated (ND) sorting for ranking a group of drugs at various doses. The presented approach can be used to model a cell population as a mixture of subpopulations. It also offers specific advantages, such as higher spatial resolution, classification of responses, and ranking of drugs, potentially providing a platform for high-content drug screening.

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

    Directory of Open Access Journals (Sweden)

    Kamran Honarnejad

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

  3. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

    Directory of Open Access Journals (Sweden)

    Linn S Strandberg

    Full Text Available BACKGROUND: Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

  4. 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, a metabolite of ginseng, inhibits colon cancer growth by targeting TRPC channel-mediated calcium influx.

    Science.gov (United States)

    Hwang, Jeong Ah; Hwang, Mun Kyung; Jang, Yongwoo; Lee, Eun Jung; Kim, Jong-Eun; Oh, Mi Hyun; Shin, Dong Joo; Lim, Semi; Ji, Geun og; Oh, Uhtaek; Bode, Ann M; Dong, Zigang; Lee, Ki Won; Lee, Hyong Joo

    2013-06-01

    Abnormal regulation of Ca(2+) mediates tumorigenesis and Ca(2+) channels are reportedly deregulated in cancers, indicating that regulating Ca(2+) signaling in cancer cells is considered as a promising strategy to treat cancer. However, little is known regarding the mechanism by which Ca(2+) affects cancer cell death. Here, we show that 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (20-GPPD), a metabolite of ginseng saponin, causes apoptosis of colon cancer cells through the induction of cytoplasmic Ca(2+). 20-GPPD decreased cell viability, increased annexin V-positive early apoptosis and induced sub-G1 accumulation and nuclear condensation of CT-26 murine colon cancer cells. Although 20-GPPD-induced activation of AMP-activated protein kinase (AMPK) played a key role in the apoptotic death of CT-26 cells, LKB1, a well-known upstream kinase of AMPK, was not involved in this activation. To identify the upstream target of 20-GPPD for activating AMPK, we examined the effect of Ca(2+) on apoptosis of CT-26 cells. A calcium chelator recovered 20-GPPD-induced AMPK phosphorylation and CT-26 cell death. Confocal microscopy showed that 20-GPPD increased Ca(2+) entry into CT-26 cells, whereas a transient receptor potential canonical (TRPC) blocker suppressed Ca(2+) entry. When cells were treated with a TRPC blocker plus an endoplasmic reticulum (ER) calcium blocker, 20-GPPD-induced calcium influx was completely inhibited, suggesting that the ER calcium store, as well as TRPC, was involved. In vivo mouse CT-26 allografts showed that 20-GPPD significantly suppressed tumor growth, volume and weight in a dose-dependent manner. Collectively, 20-GPPD exerts potent anticarcinogenic effects on colon carcinogenesis by increasing Ca(2+) influx, mainly through TRPC channels, and by targeting AMPK. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Calcium - urine

    Science.gov (United States)

    Urinary Ca+2; Kidney stones - calcium in urine; Renal calculi - calcium in your urine; Parathyroid - calcium in urine ... Urine calcium level can help your provider: Decide on the best treatment for the most common type of kidney ...

  6. Insight into the local environment of magnesium and calcium in low-coordination-number organo-complexes using (25)Mg and (43)Ca solid-state NMR: a DFT study.

    Science.gov (United States)

    Gervais, Christel; Jones, Cameron; Bonhomme, Christian; Laurencin, Danielle

    2017-03-01

    With the increasing number of organocalcium and organomagnesium complexes under development, there is a real need to be able to characterize in detail their local environment in order to fully rationalize their reactivity. For crystalline structures, in cases when diffraction techniques are insufficient, additional local spectroscopies like (25)Mg and (43)Ca solid-state NMR may provide valuable information to help fully establish the local environment of the metal ions. In this current work, a prospective DFT investigation on crystalline magnesium and calcium complexes involving low-coordination numbers and N-bearing organic ligands was carried out, in which the (25)Mg and (43)Ca NMR parameters [isotropic chemical shift, chemical shift anisotropy (CSA) and quadrupolar parameters] were calculated for each structure. The analysis of the calculated parameters in relation to the local environment of the metal ions revealed that they are highly sensitive to very small changes in geometry/distances, and hence that they could be used to assist in the refinement of crystal structures. Moreover, such calculations provide a guideline as to how the NMR measurements will need to be performed, revealing that these will be very challenging.

  7. Targeting the tight junction protein, zonula occludens-1, with the connexin43 mimetic peptide, αCT1, reduces VEGF-dependent RPE pathophysiology.

    Science.gov (United States)

    Obert, Elisabeth; Strauss, Randy; Brandon, Carlene; Grek, Christina; Ghatnekar, Gautam; Gourdie, Robert; Rohrer, Bärbel

    2017-05-01

    A critical target tissue in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from attenuation/disruption of intercellular tight junctions. Zonula occludens-1 (ZO-1) is a major structural protein of intercellular junctions. A connexin43-based peptide mimetic, αCT1, was developed to competitively block interactions at the PDZ2 domain of ZO-1, thereby inhibiting ligands that selectively bind to this domain. We hypothesized that targeting ZO-1 signaling using αCT1 would maintain BRB integrity and reduce RPE pathophysiology by stabilizing gap- and/or tight-junctions. RPE-cell barrier dysfunction was generated in mice using laser photocoagulation triggering choroidal neovascularization (CNV) or bright light exposure leading to morphological damage. αCT1 was delivered via eye drops. αCT1 treatment reduced CNV development and fluid leakage as determined by optical coherence tomography, and damage was correlated with disruption in cellular integrity of surrounding RPE cells. Light damage significantly disrupted RPE cell morphology as determined by ZO-1 and occludin staining and tiling pattern analysis, which was prevented by αCT1 pre-treatment. In vitro experiments using RPE and MDCK monolayers indicated that αCT1 stabilizes tight junctions, independent of its effects on Cx43. Taken together, stabilization of intercellular junctions by αCT1 was effective in ameliorating RPE dysfunction in models of AMD-like pathology. The connexin43 mimetic αCT1 accumulates in the mouse retinal pigment epithelium following topical delivery via eye drops. αCT1 eye drops prevented RPE-cell barrier dysfunction in two mouse models. αCT1 stabilizes intercellular tight junctions. Stabilization of cellular junctions via αCT1 may serve as a novel therapeutic approach for both wet and dry age-related macular degeneration.

  8. Fe-bLf nanoformulation targets survivin to kill colon cancer stem cells and maintains absorption of iron, calcium and zinc.

    Science.gov (United States)

    Kanwar, Jagat R; Mahidhara, Ganesh; Roy, Kislay; Sasidharan, Sreenivasan; Krishnakumar, Subramanian; Prasad, Neerati; Sehgal, Rakesh; Kanwar, Rupinder K

    2015-01-01

    To validate the anticancer efficacy of alginate-enclosed, chitosan-conjugated, calcium phosphate, iron-saturated bovine lactoferrin (Fe-bLf) nanocarriers/nanocapsules (NCs) with improved sustained release and ability to induce apoptosis by downregulating survivin, as well as cancer stem cells. The stability, nanotoxicity of the modified nanoformulation was evaluated and their anticancer efficacy was re-examined. Their mechanism of internalization was studied and we identified the role of various miRNAs in absorption of these NCs/iron in various body parts of mice. We determined the effect of these NCs on survivin, stem cell markers, red blood cell count, iron, calcium and zinc concentration in mice, determined the antiangiogenic properties of these NCs and studied their effect on cancer stem-like cells. Spherical NCs (396.1 ± 27.2 nm) exceedingly reduced viability of Caco-2 cells (32 ± 2.83%). The NCs also showed effective internalization and reduction of cancer stem cell markers in triple-positive CD133, survivin and CD44 cancer stem-like cells. Mice treated with the NCs showed no nanotoxicity and did not develop any tumors in xenograft colon cancer models. We found that the serum iron, zinc and calcium absorption were increased. DMT1, LRP, transferrin and lactoferrin receptors were responsible for internalization of the NCs. Different miRNAs were responsible for iron regulation in different organs. Interestingly, NCs inhibited survivin and its different isoforms. Our results confirmed that NCs internalized and changed the expression of selected miRNAs that further enhanced their uptake. The NCs activated both extrinsic, as well as intrinsic apoptotic pathways to induce apoptosis by targeting survivin in cancer cells and cancer stem cells, without inducing any nonspecific nanotoxicity. Apart from inhibiting angiogenesis and stem cell markers, NCs also maintained iron and calcium levels.

  9. Effect of insecticidal fusion proteins containing spider toxins targeting sodium and calcium ion channels on pyrethroid-resistant strains of peach-potato aphid (Myzus persicae).

    Science.gov (United States)

    Yang, Sheng; Fitches, Elaine; Pyati, Prashant; Gatehouse, John A

    2015-07-01

    The recombinant fusion proteins Pl1a/GNA and Hv1a/GNA contain the spider venom peptides δ-amaurobitoxin-PI1a or ω-hexatoxin-Hv1a respectively, linked to snowdrop lectin (GNA). Pl1a targets receptor site 4 of insect voltage-gated sodium channels (NaCh), while Hv1a targets voltage-gated calcium channels. Insecticide-resistant strains of peach-potato aphid (Myzus persicae) contain mutations in NaCh. The pyrethroid-resistant kdr (794J) and super-kdr (UKO) strains contain mutations at residues L1014 and M918 in the channel α-subunit respectively, while the kdr + super-kdr strain (4824J), insensitive to pyrethroids, contains mutations at both L1014 and M918. Pl1a/GNA and Hv1a/GNA fusion proteins have estimated LC50 values of 0.35 and 0.19 mg mL(-1) when fed to wild-type M. persicae. For insecticide-resistant aphids, LC50 for the Pl1a/GNA fusion protein increased by 2-6-fold, correlating with pyrethroid resistance (wild type < kdr < super-kdr < kdr + super-kdr strains). In contrast, LC50 for the Hv1a/GNA fusion protein showed limited correlation with pyrethroid resistance. Mutations in the sodium channel in pyrethroid-resistant aphids also protect against a fusion protein containing a sodium-channel-specific toxin, in spite of differences in ligand-channel interactions, but do not confer resistance to a fusion protein targeting calcium channels. The use of fusion proteins with differing targets could play a role in managing pesticide resistance. © 2014 Society of Chemical Industry.

  10. Synthesis and crystal structure of calcium dizinc iron(III tris(orthophosphate, CaZn2Fe(PO43

    Directory of Open Access Journals (Sweden)

    Jamal Khmiyas

    2016-09-01

    Full Text Available Single crystals of the title compound, CaZn2Fe(PO43, were synthesized by conventional solid-state reaction. In the asymmetric unit, all atoms are located in fully occupied general positions of the P21/c space group. The zinc atoms are located on two crystallographically independent sites with tetrahedral and distorted triangular-based bipyramidal geometries. Two edge-sharing triangular bipyramidal ZnO5 units form a dimer, which is linked to slightly deformed FeO6 octahedra via a common edge. The resulting chains are interconnected through PO4 tetrahedra to form a layer perpendicular to the b axis. Moreover, the remaining PO4 and ZnO4 tetrahedra are linked together through common vertices to form tapes parallel to the c axis and surrounding a chain of Ca2+ cations to build a sheet, also perpendicular to the b axis. The stacking of the two layers along the b axis leads to the resulting three-dimensional framework, which defines channels in which the Ca2+ cations are located, each cation being coordinated by seven oxygen atoms.

  11. Crystal structure of calcium dinickel(II iron(III tris(orthophosphate: CaNi2Fe(PO43

    Directory of Open Access Journals (Sweden)

    Said Ouaatta

    2017-06-01

    Full Text Available The title compound, CaNi2Fe(PO43, was synthesized by solid-state reactions. Its structure is closely related to that of α-CrPO4 in the space group Imma. Except for two O atoms in general positions, all atoms are located in special positions. The three-dimensional framework is built up from two types of sheets extending parallel to (100. The first sheet is made up from two edge-sharing [NiO6] octahedra, leading to the formation of [Ni2O10] double octahedra that are connected to two PO4 tetrahedra through a common edge and corners. The second sheet results from rows of corner-sharing [FeO6] octahedra and PO4 tetrahedra forming an infinite linear chain. These layers are linked together through common corners of PO4 tetrahedra and [FeO6] octahedra, resulting in an open three-dimensional framework that delimits two types of channels parallel to [100] and [010] in which the eightfold-coordinated CaII cations are located.

  12. Crystal structure of calcium dinickel(II) iron(III) tris-(orthophosphate): CaNi2Fe(PO4)3.

    Science.gov (United States)

    Ouaatta, Said; Assani, Abderrazzak; Saadi, Mohamed; El Ammari, Lahcen

    2017-06-01

    The title compound, CaNi2Fe(PO4)3, was synthesized by solid-state reactions. Its structure is closely related to that of α-CrPO4 in the space group Imma. Except for two O atoms in general positions, all atoms are located in special positions. The three-dimensional framework is built up from two types of sheets extending parallel to (100). The first sheet is made up from two edge-sharing [NiO6] octa-hedra, leading to the formation of [Ni2O10] double octa-hedra that are connected to two PO4 tetra-hedra through a common edge and corners. The second sheet results from rows of corner-sharing [FeO6] octa-hedra and PO4 tetra-hedra forming an infinite linear chain. These layers are linked together through common corners of PO4 tetra-hedra and [FeO6] octa-hedra, resulting in an open three-dimensional framework that delimits two types of channels parallel to [100] and [010] in which the eightfold-coordinated Ca(II) cations are located.

  13. Targeting Intracellular Calcium Signaling ([Ca2+]i to Overcome Acquired Multidrug Resistance of Cancer Cells: A Mini-Overview

    Directory of Open Access Journals (Sweden)

    Dietrich Büsselberg

    2017-05-01

    Full Text Available Cancer is a main public health problem all over the world. It affects millions of humans no matter their age, gender, education, or social status. Although chemotherapy is the main strategy for the treatment of cancer, a major problem limiting its success is the intrinsic or acquired drug resistance. Therefore, cancer drug resistance is a major impediment in medical oncology resulting in a failure of a successful cancer treatment. This mini-overview focuses on the interdependent relationship between intracellular calcium ([Ca2+]i signaling and multidrug resistance of cancer cells, acquired upon treatment of tumors with anticancer drugs. We propose that [Ca2+]i signaling modulates gene expression of multidrug resistant (MDR genes which in turn can be modulated by epigenetic factors which in turn leads to modified protein expression in drug resistant tumor cells. A precise knowledge of these mechanisms will help to develop new therapeutic strategies for drug resistant tumors and will improve current chemotherapy.

  14. Calcium Carbonate

    Science.gov (United States)

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

  15. 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 ...

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

    KAUST Repository

    Almadanim, M. Cecília

    2017-01-19

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

  17. A toxin from the spider Phoneutria nigriventer that blocks calcium channels coupled to exocytosis

    Science.gov (United States)

    Guatimosim, C; Romano-Silva, M A; Cruz, J S; Beirão, P S L; Kalapothakis, E; Moraes-Santos, T; Cordeiro, M N; Diniz, C R; Gomez, M V; Prado, M A M

    1997-01-01

    The aim of the present experiments was to investigate the pharmacological action of a toxin from the spider Phoneutria nigriventer, Tx3-3, on the function of calcium channels that control exocytosis of synaptic vesicles. Tx3-3, in confirmation of previous work, diminished the intracellular calcium increase induced by membrane depolarization with KCl (25 mM) in rat cerebrocortical synaptosomes. The toxin was very potent (IC50 0.9 nM) at inhibiting calcium channels that regulate calcium entry in synaptosomes. In addition, Tx3-3 blocked the exocytosis of synaptic vesicles, as measured with the fluorescent dye FM1-43. Using ω-toxins that interact selectively with distinct neuronal calcium channels, we investigated whether the target of Tx3-3 overlaps with known channels that mediate exocytosis. The results indicate that the main population of voltage-sensitive calcium channels altered by Tx3-3 can also be inhibited by ω-agatoxin IVA, an antagonist of P/Q calcium channels. ω-conotoxin GVIA, which inhibits N type calcium channels did not decrease significantly the entry of calcium or exocytosis of synaptic vesicles in depolarized synaptosomes. It is concluded that Tx3-3 potently inhibits ω-agatoxin IVA-sensitive calcium channels, which are involved in controlling exocytosis in rat brain cortical synaptosomes. PMID:9351520

  18. 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.

  19. Cosmic ray source abundance of calcium

    CERN Document Server

    Perron, C

    1978-01-01

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

  20. Vinculin but not alpha-actinin is a target of PKC phosphorylation during junctional assembly induced by calcium

    DEFF Research Database (Denmark)

    Perez-Moreno, M; Avila, A; Islas, S

    1998-01-01

    proteins ZO1, ZO2 and ZO3, in a previous work we specifically explored these molecules but found no alteration in their phosphorylation pattern. To continue the search for the target of protein kinase C, in the present work we have studied the subcellular distribution and phosphorylation of vinculin...

  1. Bcl-2 regulation of the inositol 1,4,5-trisphosphate receptor and calcium signaling in normal and malignant lymphocytes: potential new target for cancer treatment.

    Science.gov (United States)

    Greenberg, Edward F; Lavik, Andrew R; Distelhorst, Clark W

    2014-10-01

    The anti-apoptotic protein Bcl-2 is a versatile regulator of cell survival. Its interactions with its own pro-apoptotic family members are widely recognized for their role in promoting the survival of cancer cells. These interactions are thus being targeted for cancer treatment. Less widely recognized is the interaction of Bcl-2 with the inositol 1,4,5-trisphosphate receptor (InsP3R), an InsP3-gated Ca(2+) channel located on the endoplasmic reticulum. The nature of this interaction, the mechanism by which it controls Ca(2+) release from the ER, its role in T-cell development and survival, and the possibility of targeting it as a novel cancer treatment strategy are summarized in this review. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Cyclotron production of {sup 43}Sc for PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Walczak, Rafał [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Krajewski, Seweryn [Synektik S.A., Research and Development Center, Warsaw (Poland); Szkliniarz, Katarzyna [Department of Nuclear Physics, University of Silesia, Katowice (Poland); Sitarz, Mateusz [Heavy Ion Laboratory, University of Warsaw, Warsaw (Poland); Abbas, Kamel [Nuclear Security Unit, Joint Research Centre, Institute for Transuranium Elements, European Commission, Ispra (Italy); Choiński, Jarosław; Jakubowski, Andrzej; Jastrzębski, Jerzy [Heavy Ion Laboratory, University of Warsaw, Warsaw (Poland); Majkowska, Agnieszka [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Simonelli, Federica [Nuclear Decommissioning Unit, Joint Research Centre, Ispra Site Management Directorate, European Commission, Ispra (Italy); Stolarz, Anna; Trzcińska, Agnieszka [Heavy Ion Laboratory, University of Warsaw, Warsaw (Poland); Zipper, Wiktor [Department of Nuclear Physics, University of Silesia, Katowice (Poland); Bilewicz, Aleksander [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)

    2015-12-04

    Recently, significant interest in {sup 44}Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by {sup 44}Sc of high-energy γ rays (E{sub γ} = 1157, 1499 keV) causes a dangerous increase of the radiation dose to the patients and clinical staff. However, it is possible to produce another radionuclide of scandium—{sup 43}Sc—having properties similar to {sup 44}Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of {sup 43}Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate. Natural CaCO{sub 3} and enriched [{sup 40}Ca]CaCO{sub 3} were irradiated with alpha particles for 1 h in an energy range of 14.8–30 MeV at a beam current of 0.5 or 0.25 μA. In order to find the optimum method for the separation of {sup 43}Sc from irradiated calcium targets, three processes previously developed for {sup 44}Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained {sup 43}Sc-DOTATATE was tested in human serum. Studies of {sup nat}CaCO{sub 3} target irradiation by alpha particles show that the optimum alpha particle energies are in the range of 24–27 MeV, giving 102 MBq/μA/h of {sup 43}Sc radioactivity which creates the opportunity to produce several GBq of {sup 43}Sc. The separation experiments performed indicate that, as with {sup 44}Sc, due to the simplicity of the operations and because of the chemical purity of the {sup 43}Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained {sup 43}Sc with a yield >98 % at elevated temperature. Tens of GBq activities of {sup 43}Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam.

  3. SW43-DOX ± loading onto drug-eluting bead, a potential new targeted drug delivery platform for systemic and locoregional cancer treatment - An in vitro evaluation.

    Science.gov (United States)

    Ludwig, Johannes M; Gai, Yongkang; Sun, Lingyi; Xiang, Guangya; Zeng, Dexing; Kim, Hyun S

    2016-08-01

    Treatment of unresectable primary cancer and their distant metastases, with the liver representing one of the most frequent location, is still plagued by insufficient treatment success and poor survival rates. The Sigma-2 receptor is preferentially expressed on many tumor cells making it an appealing target for therapy. Thus, we developed a potential targeted drug conjugate consisting of the Sigma-2 receptor ligand SW43 and Doxorubicin (SW43-DOX) for systemic cancer therapy and for locoregional treatment of primary and secondary liver malignancies when loaded onto drug-eluting bead (DEB) which was compared in vitro to the treatment with Doxorubicin alone. SW43-DOX binds specifically to the Sigma-2 receptor expressed on hepatocellular (Hep G2, Hep 3B), pancreatic (Panc-1) and colorectal (HT-29) carcinoma cell lines with high affinity and subsequent early specific internalization. Free SW43-DOX showed superior concentration and time depended cancer toxicity than treatment with Doxorubicin alone. Action mechanisms analysis revealed an apoptotic cell death with increased caspase 3/7 activation and reactive oxygen species (ROS) production. Only ROS scavenging with α-Tocopherol, but not the caspase inhibition (Z-VAD-FMK), partly reverted the effect. SW43-DOX could successfully be loaded onto DEB and showed prolonged eluting kinetics compared to Doxorubicin. SW43-DOX loaded DEB vs. Doxorubicin loaded DEB showed a significantly greater time dependent toxicity in all cell lines. In conclusion, the novel conjugate SW43-DOX ± loading onto DEB is a promising drug delivery platform for targeted systemic and locoregional cancer therapy. Copyright © 2016. Published by Elsevier B.V.

  4. Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Xiu-Lan

    2010-02-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the most common cancers in the world which is highly chemoresistant to currently available chemotherapeutic agents. Thus, novel therapeutic targets are needed to be sought for the successful treatment of HCC. Peptaibols, a family of peptides synthesized non-ribosomally by the Trichoderma species and other fungi, exhibit antibiotic activities against bacteria and fungi. Few studies recently showed that peptaibols exerted cytotoxicity toward human lung epithelial and breast carcinoma cells. However, the mechanism involved in peptaibol-induced cell death remains poorly understood. Results Here, we showed that Trichokonin VI (TK VI, a peptaibol from Trichoderma pseudokoningii SMF2, induced growth inhibition of HCC cells in a dose-dependent manner. It did not obviously impair the viability of normal liver cells at lower concentration. Moreover, the suppression of cell viability resulted from the programmed cell death (PCD with characteristics of apoptosis and autophagy. An influx of Ca2+ triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and subsequent promotion of apoptosis. On the other hand, typically morphological characteristics consistent with autophagy were also observed by punctate distribution of MDC staining and the induction of LC3-II, including extensive autophagic vacuolization and enclosure of cell organelles by these autophagosomes. More significantly, specific depletion of Bak expression by small RNA interfering (siRNA could partly attenuate TK VI-induced autophagy. However, siRNA against Bax led to increased autophagy. Conclusion Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells.

  5. Gene-Targeted Mice with the Human Troponin T R141W Mutation Develop Dilated Cardiomyopathy with Calcium Desensitization.

    Directory of Open Access Journals (Sweden)

    Mohun Ramratnam

    Full Text Available Most studies of the mechanisms leading to hereditary dilated cardiomyopathy (DCM have been performed in reconstituted in vitro systems. Genetically engineered murine models offer the opportunity to dissect these mechanisms in vivo. We generated a gene-targeted knock-in murine model of the autosomal dominant Arg141Trp (R141W mutation in Tnnt2, which was first described in a human family with DCM. Mice heterozygous for the mutation (Tnnt2R141W/+ recapitulated the human phenotype, developing left ventricular dilation and reduced contractility. There was a gene dosage effect, so that the phenotype in Tnnt2R141W/+mice was attenuated by transgenic overexpression of wildtype Tnnt2 mRNA transcript. Male mice exhibited poorer survival than females. Biomechanical studies on skinned fibers from Tnnt2R141W/+ hearts showed a significant decrease in pCa50 (-log[Ca2+] required for generation of 50% of maximal force relative to wildtype hearts, indicating Ca2+ desensitization. Optical mapping studies of Langendorff-perfused Tnnt2R141W/+ hearts showed marked increases in diastolic and peak systolic intracellular Ca2+ ([Ca2+]i, and prolonged systolic rise and diastolic fall of [Ca2+]i. Perfused Tnnt2R141W/+ hearts had slower intrinsic rates in sinus rhythm and reduced peak heart rates in response to isoproterenol. Tnnt2R141W/+ hearts exhibited a reduction in phosphorylated phospholamban relative to wildtype mice. However, crossing Tnnt2R141W/+ mice with phospholamban knockout (Pln-/- mice, which exhibit increased Ca2+ transients and contractility, had no effect on the DCM phenotype. We conclude that the Tnnt2 R141W mutation causes a Ca2+ desensitization and mice adapt by increasing Ca2+-transient amplitudes, which impairs Ca2+ handling dynamics, metabolism and responses to β-adrenergic activation.

  6. Cyclotron Produced 44gSc from Natural Calcium

    Science.gov (United States)

    Severin, G.W.; Engle, J.W.; Valdovinos, H.F.; Barnhart, T.E.; Nickles, R.J.

    2012-01-01

    44gSc was produced by 16 MeV proton irradiation of unenriched calcium metal with radionuclidic purity greater than 95%. The thick target yield at saturation for 44gSc was 213 MBq/μA, dwarfing the yields of contaminants 43Sc,44mSc, 47Sc and 48Sc for practical bombardment times of 1–2 h. Scandium was isolated from the dissolved calcium target by filtration, and reconstituted in small volumes of dilute HCl. Reactions with the chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) indicated a reactivity of 54±14 Gbq/μmol at end-of-bombardment. PMID:22728844

  7. Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123)

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Stahlhut, Martin; Mohammed, Shabaz

    2006-01-01

    and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass...

  8. 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...

  9. Gualou Guizhi decoction reverses brain damage with cerebral ischemic stroke, multi-component directed multi-target to screen calcium-overload inhibitors using combination of molecular docking and protein-protein docking.

    Science.gov (United States)

    Hu, Juan; Pang, Wen-Sheng; Han, Jing; Zhang, Kuan; Zhang, Ji-Zhou; Chen, Li-Dian

    2018-12-01

    Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats. GLGZD contains Trichosanthin and various small molecular that they are the potential active ingredients directed against NR2A, NR2B, FKBP12 and Calnodulin target proteins/enzyme have been screened by computer simulation. "Multicomponent systems" is capable to create pharmacological superposition effects. The Chinese medicine compound prescriptions could be considered as promising sources of candidates for discovery new agents.

  10. 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

  11. Paclitaxel induces apoptosis in breast cancer cells through different calcium--regulating mechanisms depending on external calcium conditions.

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-02-17

    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.

  12. Expression changes of microRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats

    NARCIS (Netherlands)

    Neumann, Elena; Hermanns, Henning; Barthel, Franziska; Werdehausen, Robert; Brandenburger, Timo

    2015-01-01

    MicroRNAs (miRNAs) are involved in the neuroplastic changes which induce and maintain neuropathic pain. However, it is unknown whether nerve injury leads to altered miRNA expression and modulation of pain relevant target gene expression within peripheral nerves. In the present study, expression

  13. Get Enough Calcium

    Science.gov (United States)

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

  14. Calcium 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 ...

  15. 43 CFR 423.43 - Alcoholic beverages.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Alcoholic beverages. 423.43 Section 423.43 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE....43 Alcoholic beverages. You must not possess or consume alcoholic beverages in violation of Federal...

  16. 43 CFR 43.670 - Suspension.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Suspension. 43.670 Section 43.670 Public... WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.670 Suspension. Suspension means an action taken by a..., subpart 9.4) and 2 CFR part 180. Suspension of a recipient is a distinct and separate action from...

  17. 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,

  18. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting...... in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal......43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium....

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

    Science.gov (United States)

    Almadanim, M Cecília; Alexandre, Bruno M; Rosa, Margarida T G; Sapeta, Helena; Leitão, António E; Ramalho, José C; Lam, TuKiet T; Negrão, Sónia; Abreu, Isabel A; Oliveira, M Margarida

    2017-07-01

    Calcium-dependent protein kinases (CDPKs) are involved in plant tolerance mechanisms to abiotic stresses. Although CDPKs are recognized as key messengers in signal transduction, the specific role of most members of this family remains unknown. Here, we test the hypothesis that OsCPK17 plays a role in rice cold stress response by analysing OsCPK17 knockout, silencing and overexpressing rice lines under low temperature. Altered OsCPK17 gene expression compromises cold tolerance performance, without affecting the expression of key cold stress-inducible genes. A comparative phosphoproteomic approach led to the identification of six potential in vivo OsCPK17 targets, which are associated with sugar and nitrogen metabolism, and with osmotic regulation. To test direct interaction, in vitro kinase assays were performed, showing that the sucrose-phosphate synthase OsSPS4 and the aquaporin OsPIP2;1/OsPIP2;6 are phosphorylated by OsCPK17 in a calcium-dependent manner. Altogether, our data indicates that OsCPK17 is required for a proper cold stress response in rice, likely affecting the activity of membrane channels and sugar metabolism. © 2017 John Wiley & Sons Ltd.

  20. Separation of no-carrier-added {sup 203}Pb, a surrogate radioisotope, from proton irradiated {sup nat}Tl{sub 2}CO{sub 3} target using calcium alginate hydrogel beads

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Kangkana; Sen, Kamalika [Univ. of Calcutta, Kolkata (India). Dept. of Chemistry; Lahiri, Susanta [Saha Institute of Nuclear Physics, Kolkata (India)

    2016-07-01

    {sup 203}Pb is a promising radioisotope in the field of medical science as an imaging surrogate of {sup 212}Pb. In the present investigation {sup 203}Pb was produced by proton irradiation of natural Tl{sub 2}CO{sub 3} target and was separated from the bulk Tl target using calcium alginate (CA) hydrogel beads with a high separation factor (3.8 x 10{sup 4} at 10{sup -3} M HNO{sub 3}). During the separation process {sup 203}Pb was encapsulated in CA beads and desorption of the radioisotope could only be achieved in 1M HNO{sub 3}. Possibility of Tl uptake was also checked in Fe doped CA (Fe-CA) beads after oxidation of Tl(I) to Tl(III) by sodium bismuthate. No significant uptake of Tl(III) was noticed in the Fe-CA beads. The matrix is therefore suitable for isolation of {sup 203}Pb from the target as well as its storage in the bead for therapeutic as well as diagnostic purpose.

  1. Intercomparison 9711. pH, conductivity, alkalinity, nitrate + nitrite, chloride, sulfate, calcium, magnesium, sodium, potassium, total aluminium, reactive and non-labile aluminium, dissolved organic carbon, and chemical oxygen demand (ICP Waters report)

    OpenAIRE

    Hovind, H.

    1997-01-01

    47 laboratories in 22 countries participated in intercomparison 9711. One sample set for the determination of major ions, organic matter and aluminium fractions, were used. Based on the general target accuracy of + 20%, 78% of the results were acceptable. More than 80% of the result pairs were acceptable for chloride, sulfate, calcium, mangnesium, sodium, dissolved organic carbon and chemical oxygen demand. For pH only 43% of the result pairs were acceptable in relation to the extended target...

  2. Temperature-Sensitive Cav1.2 Calcium Channels Support Intrinsic Firing of Pyramidal Neurons and Provide a Target for the Treatment of Febrile Seizures

    Science.gov (United States)

    Radzicki, Daniel; Yau, Hau-Jie; Pollema-Mays, Sarah L.; Mlsna, Lauren; Cho, Kangho; Koh, Sookyong

    2013-01-01

    Febrile seizures are associated with increased brain temperature and are often resistant to treatments with antiepileptic drugs, such as carbamazepine and phenytoin, which are sodium channel blockers. Although they are clearly correlated with the hyperthermic condition, the precise cellular mechanisms of febrile seizures remain unclear. We performed patch-clamp recordings from pyramidal cells in acute rat brain slices at temperatures up to 40°C and found that, at ≥37°C, L-type calcium channels are active at unexpectedly hyperpolarized potentials and drive intrinsic firing, which is also supported by a temperature-dependent, gadolinium-sensitive sodium conductance. Pharmacological data, RT-PCR, and the current persistence in Cav1.3 knock-out mice suggested a critical contribution of Cav1.2 subunits to the temperature-dependent intrinsic firing, which was blocked by nimodipine. Because intrinsic firing may play a critical role in febrile seizures, we tested the effect of nimodipine in an in vivo model of febrile seizures and found that this drug dramatically reduces both the incidence and duration of febrile seizures in rat pups, suggesting new possibilities of intervention for this important pathological condition. PMID:23761887

  3. Coronary Calcium Scan

    Science.gov (United States)

    ... Back To Health Topics / Coronary Calcium Scan Coronary Calcium Scan Also known as Calcium Scan Test A coronary calcium scan is a CT scan of your heart that detects and measures the amount of calcium in the walls of your coronary arteries. Overview ...

  4. 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 ...

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. Calcium blood test

    Science.gov (United States)

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

  9. Enhanced expression of a calcium-dependent protein kinase from ...

    Indian Academy of Sciences (India)

    Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an interesting class of kinases which are activated by calcium binding. They have been implicated in a diverse array of responses to hormonal and environmental stimuli. In order to dissect the role of CDPKs in the moss ...

  10. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. 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

    Directory of Open Access Journals (Sweden)

    Eriko Maeda

    2016-01-01

    Full Text Available 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 set at 75%. In Group CS (n = 41, CS was obtained at 75% and the diagnostic phase showing minimal artifacts was applied as the center of the CCTA acquisition window. Image quality was evaluated using a four-point scale (4-excellent and the mean scores were compared between groups. Results. The CCTA scan diagnostic phase occurred significantly earlier in CS (75.7 ± 3.2% vs. 73.6 ± 4.5% for Groups 75% and CS, resp., p = 0.013. The mean Group CS image quality score (3.58 ± 0.63 was also higher than that for Group 75% (3.19 ± 0.66, p < 0.0001. Conclusions. The image quality of CCTA in Target CTA mode was significantly better when the center of acquisition window is adjusted using CS.

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

    Directory of Open Access Journals (Sweden)

    Honorio-França AC

    2016-02-01

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

  13. Targeting of CaV3.2 T-type calcium channels in peripheral sensory neurons for the treatment of painful diabetic neuropathy.

    Science.gov (United States)

    Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2014-04-01

    Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglion (DRG) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of insufficient knowledge about the mechanisms for this hypersensitization, current treatment for painful PDN has been limited to somewhat nonspecific systemic drugs having significant side effects or potential for abuse. Recent studies have established that the CaV3.2 isoform of T-channels makes a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of type 1 and type 2 PDN. Furthermore, it has been reported that the glycosylation inhibitor neuraminidase can inhibit the native and recombinant CaV3.2 T-currents in vitro and completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of posttranslational regulation of nociceptive channel activity via glycosylation may facilitate development of novel therapies for treatment of painful PDN. Pharmacological targeting the specific pathogenic mechanism rather than the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes.

  14. Plant Calcium Content: Ready to Remodel

    Directory of Open Access Journals (Sweden)

    Mary Lou Guerinot

    2012-08-01

    Full Text Available By identifying the relationship between calcium location in the plant cell and nutrient bioavailability, the plant characteristics leading to maximal calcium absorption by humans can be identified. Knowledge of plant cellular and molecular targets controlling calcium location in plants is emerging. These insights should allow for better strategies for increasing the nutritional content of foods. In particular, the use of preparation-free elemental imaging technologies such as synchrotron X-ray fluorescence (SXRF microscopy in plant biology may allow researchers to understand the relationship between subcellular location and nutrient bioavailability. These approaches may lead to better strategies for altering the location of calcium within the plant to maximize its absorption from fruits and vegetables. These modified foods could be part of a diet for children and adults identified as at-risk for low calcium intake or absorption with the ultimate goal of decreasing the incidence and severity of inadequate bone mineralization.

  15. Plant Calcium Content: Ready to Remodel

    Science.gov (United States)

    Yang, Jian; Punshon, Tracy; Guerinot, Mary Lou; Hirschi, Kendal D.

    2012-01-01

    By identifying the relationship between calcium location in the plant cell and nutrient bioavailability, the plant characteristics leading to maximal calcium absorption by humans can be identified. Knowledge of plant cellular and molecular targets controlling calcium location in plants is emerging. These insights should allow for better strategies for increasing the nutritional content of foods. In particular, the use of preparation-free elemental imaging technologies such as synchrotron X-ray fluorescence (SXRF) microscopy in plant biology may allow researchers to understand the relationship between subcellular location and nutrient bioavailability. These approaches may lead to better strategies for altering the location of calcium within the plant to maximize its absorption from fruits and vegetables. These modified foods could be part of a diet for children and adults identified as at-risk for low calcium intake or absorption with the ultimate goal of decreasing the incidence and severity of inadequate bone mineralization. PMID:23016135

  16. Substitutions in Calcium Aluminates and Calcium Aluminoferrites.

    Science.gov (United States)

    ALUMINUM COMPOUNDS, *CEMENTS, * CALCIUM COMPOUNDS, * FERRITES , *SCIENTIFIC RESEARCH, INFRARED SPECTROSCOPY, X RAY DIFFRACTION, CHEMICAL COMPOSITION, SUBSTITUTES, CHEMICAL ANALYSIS, ALKALI METAL COMPOUNDS.

  17. Calcium channel blocker overdose

    Science.gov (United States)

    ... 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 to ...

  18. 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 ...

  19. 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.

  20. 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

  1. 43 CFR 12.43 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... payments. Accrued income means the sum of: (1) Earnings during a given period from services performed by... to State and Local Governments General § 12.43 Definitions. As used in this part: Accrued... payments made to contractors and subgrantees. For reports prepared on an accrued expenditure basis, outlays...

  2. Calcium-induced calcium release supports recruitment of synaptic vesicles in auditory hair cells.

    Science.gov (United States)

    Castellano-Muñoz, Manuel; Schnee, Michael E; Ricci, Anthony J

    2016-01-01

    Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of calcium-induced calcium release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for calcium and potassium channels. However, these drugs exerted a reduction in vesicle release measured by dual-sine capacitance methods. In addition, calcium substitution by barium reduced release efficacy by delaying release onset and diminishing vesicle recruitment. Together these results demonstrate a role for calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that calcium entry via calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic calcium signal to modulate vesicle trafficking. Copyright © 2016 the American Physiological Society.

  3. The pathological phenotypes of human TDP-43 transgenic mouse models are independent of downregulation of mouse Tdp-43.

    Directory of Open Access Journals (Sweden)

    Ya-Fei Xu

    Full Text Available Tar DNA binding protein 43 (TDP-43 is the major component of pathological deposits in frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP and in amyotrophic lateral sclerosis (ALS. It has been reported that TDP-43 transgenic mouse models expressing human TDP-43 wild-type or ALS-associated mutations recapitulate certain ALS and FTLD pathological phenotypes. Of note, expression of human TDP-43 (hTDP-43 reduces the levels of mouse Tdp-43 (mTdp-43. However, it remained unclear whether the mechanisms through which TDP-43 induces ALS or FTLD-like pathologies resulted from a reduction in mTdp-43, an increase in hTDP-43, or a combination of both. In elucidating the role of mTdp-43 and hTDP-43 in hTDP-43 transgenic mice, we observed that reduction of mTdp-43 in non-transgenic mice by intraventricular brain injection of AAV1-shTardbp leads to a dramatic increase in the levels of splicing variants of mouse sortilin 1 and translin. However, the levels of these two abnormal splicing variants are not increased in hTDP-43 transgenic mice despite significant downregulation of mTdp-43 in these mice. Moreover, further downregulation of mTdp-43 in hTDP-43 hemizygous mice, which are asymptomatic, to the levels equivalent to that of mTdp-43 in hTDP-43 homozygous mice does not induce the pathological phenotypes observed in the homozygous mice. Lastly, the number of dendritic spines and the RNA levels of TDP-43 RNA targets critical for synapse formation and function are significantly decreased in symptomatic homozygous mice. Together, our findings indicate that mTdp-43 downregulation does not lead to a loss of function mechanism or account for the pathological phenotypes observed in hTDP-43 homozygous mice because hTDP-43 compensates for the reduction, and associated functions of mTdp-43. Rather, expression of hTDP-43 beyond a certain threshold leads to abnormal metabolism of TDP-43 RNA targets critical for neuronal structure and function, which might

  4. The pathological phenotypes of human TDP-43 transgenic mouse models are independent of downregulation of mouse Tdp-43.

    Science.gov (United States)

    Xu, Ya-Fei; Prudencio, Mercedes; Hubbard, Jaime M; Tong, Jimei; Whitelaw, Ena C; Jansen-West, Karen; Stetler, Caroline; Cao, Xiangkun; Song, John; Zhang, Yong-Jie

    2013-01-01

    Tar DNA binding protein 43 (TDP-43) is the major component of pathological deposits in frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and in amyotrophic lateral sclerosis (ALS). It has been reported that TDP-43 transgenic mouse models expressing human TDP-43 wild-type or ALS-associated mutations recapitulate certain ALS and FTLD pathological phenotypes. Of note, expression of human TDP-43 (hTDP-43) reduces the levels of mouse Tdp-43 (mTdp-43). However, it remained unclear whether the mechanisms through which TDP-43 induces ALS or FTLD-like pathologies resulted from a reduction in mTdp-43, an increase in hTDP-43, or a combination of both. In elucidating the role of mTdp-43 and hTDP-43 in hTDP-43 transgenic mice, we observed that reduction of mTdp-43 in non-transgenic mice by intraventricular brain injection of AAV1-shTardbp leads to a dramatic increase in the levels of splicing variants of mouse sortilin 1 and translin. However, the levels of these two abnormal splicing variants are not increased in hTDP-43 transgenic mice despite significant downregulation of mTdp-43 in these mice. Moreover, further downregulation of mTdp-43 in hTDP-43 hemizygous mice, which are asymptomatic, to the levels equivalent to that of mTdp-43 in hTDP-43 homozygous mice does not induce the pathological phenotypes observed in the homozygous mice. Lastly, the number of dendritic spines and the RNA levels of TDP-43 RNA targets critical for synapse formation and function are significantly decreased in symptomatic homozygous mice. Together, our findings indicate that mTdp-43 downregulation does not lead to a loss of function mechanism or account for the pathological phenotypes observed in hTDP-43 homozygous mice because hTDP-43 compensates for the reduction, and associated functions of mTdp-43. Rather, expression of hTDP-43 beyond a certain threshold leads to abnormal metabolism of TDP-43 RNA targets critical for neuronal structure and function, which might be responsible

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

    Directory of Open Access Journals (Sweden)

    Yajin Liao

    2017-02-01

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

  6. Safety Instruction No 43

    CERN Document Server

    2004-01-01

    Please note that the Safety Instruction No 43 (IS 43) entitled "ASBESTOS - DANGERS AND PRECAUTIONS" is available on the web at the following URL: https://edms.cern.ch/document/335809/LAST_RELEASED/ Paper copies can also be obtained from the SC secretariat, e-mail: tis.secretariat@cern.ch. SC Secretariat

  7. Transgenic plants with increased calcium stores

    Science.gov (United States)

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

    2004-01-01

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

  8. 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.

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

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

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

  10. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

    Science.gov (United States)

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

    2015-01-01

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

  11. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

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

    African Journals Online (AJOL)

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

  13. 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.

  14. 76 FR 71459 - Prohexadione Calcium; Pesticide Tolerances

    Science.gov (United States)

    2011-11-18

    ... requested that 40 CFR 180.547 be amended by establishing tolerances for residues of the plant growth... subgroups of consumers, including infants and children. Prohexadione calcium is not acutely toxic by the..., and kidneys were the target organ for toxicity in the dogs. Following repeated dermal exposures for 28...

  15. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. The relation of carotid calcium volume with carotid artery stenosis in symptomatic patients

    NARCIS (Netherlands)

    Marquering, H. A.; Majoie, C. B. L. M.; Smagge, L.; Kurvers, A. G.; Gratama van Andel, H. A.; van den Berg, R.; Nederkoorn, P. J.

    2011-01-01

    Recent research showed a strong correlation of calcium volume scores with degree of stenosis, suggesting that calcium volume could be used in the diagnosis of carotid artery stenosis. We investigated the accuracy of the use of calcium volume scores to diagnose carotid artery stenosis in our target

  17. Calcium and bones

    Science.gov (United States)

    ... eat in their diet. Vitamin D is the hormone that helps the gut absorb more calcium. Many older adults have common risks that make bone health worse. Calcium intake in the diet (milk, cheese, yogurt) is low. Vitamin D levels are ...

  18. 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...

  19. Extracellular Calcium and Magnesium

    African Journals Online (AJOL)

    ABSTRACT. The cause of preeclampsia remains unknown and calcium and magnesium supplement are being suggested as means of prevention. The objective of this study was to assess magnesium and calcium in the plasma and cerebrospinal fluid of Nigerian women with preedamp sia and eclampsia. Setting was ...

  20. 43 CFR 418.12 - Project efficiency.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Project efficiency. 418.12 Section 418.12... Delivery § 418.12 Project efficiency. (a) The principal feature of this part is to obtain a reasonable level of efficiency in supplying water to the headgate by the District. The efficiency targets...

  1. 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...

  2. 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

  3. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.

    Science.gov (United States)

    Arnold, Eveline S; Ling, Shuo-Chien; Huelga, Stephanie C; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B; McAlonis-Downes, Melissa; Platoshyn, Oleksandr; Parone, Philippe A; Da Cruz, Sandrine; Clutario, Kevin M; Swing, Debbie; Tessarollo, Lino; Marsala, Martin; Shaw, Christopher E; Yeo, Gene W; Cleveland, Don W

    2013-02-19

    Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43-dependent alternative splicing events conferred by both human wild-type and mutant TDP-43(Q331K), but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43(Q331K) enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage.

  4. Imidazopyridazine inhibitors of Plasmodium falciparum calcium dependent protein kinase 1 also target cGMP-dependent protein kinase and heat shock protein 90 to kill the parasite at different stages of intracellular development.

    OpenAIRE

    Green, JL; Moon, RW; Whalley, D; Bowyer, PW; Wallace, C.; Rochani, A; Nageshan, RK; Howell, SA; Grainger, M.; Jones, HM; Ansell, KH; Chapman, TM; Taylor, DL; Osborne, SA; Baker, DA

    2015-01-01

    : Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in...

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

    Directory of Open Access Journals (Sweden)

    Mitsuru Nakazawa

    2011-01-01

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

  6. Calcium sensing in exocytosis

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Wu, Bingbing; Han, Weiping

    2012-01-01

    Neurotransmitters, neuropeptides and hormones are released through regulated exocytosis of synaptic vesicles and large dense core vesicles. This complex and highly regulated process is orchestrated by SNAREs and their associated proteins. The triggering signal for regulated exocytosis is usually...... an increase in intracellular calcium levels. Besides the triggering role, calcium signaling modulates the precise amount and kinetics of vesicle release. Thus, it is a central question to understand the molecular machineries responsible for calcium sensing in exocytosis. Here we provide an overview of our...

  7. Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium.

    Science.gov (United States)

    Hämäläinen, M M

    1994-06-01

    The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts.

  8. Calcium – how and why?

    Indian Academy of Sciences (India)

    Unknown

    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 ...

  9. Calcium and Your Child

    Science.gov (United States)

    ... Milk Allergy Figuring Out Food Labels What's a Vegetarian? Osteoporosis Minerals Your Bones Mineral Chart Vitamin D ... Need to Drink Milk? Lactose Intolerance Becoming a Vegetarian Soy Foods and Health Calcium Bones, Muscles, and ...

  10. Stoichiometry of Calcium Medicines

    Science.gov (United States)

    Pinto, Gabriel

    2005-01-01

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

  11. Magnesium, calcium and cancer

    National Research Council Canada - National Science Library

    Anghileri, Leopoldo J

    2009-01-01

    Magnesium ion (Mg(2+)) and calcium ion (Ca(2+)) control a diverse and important range of cellular processes, such as gene transcription, cell proliferation, neoplastic transformation, immune response and therapeutic treatment...

  12. Optimisation and validation of a high throughput screening compatible assay to identify inhibitors of the plasma membrane calcium ATPase pump--a novel therapeutic target for contraception and malaria.

    Science.gov (United States)

    Mohamed, Tamer M A; Zakeri, Simon A; Baudoin, Florence; Wolf, Markus; Oceandy, Delvac; Cartwright, Elizabeth J; Gul, Sheraz; Neyses, Ludwig

    2013-01-01

    ATPases, which constitute a major category of ion transporters in the human body, have a variety of significant biological and pathological roles. However, the lack of high throughput assays for ATPases has significantly limited drug discovery in this area. We have recently found that the genetic deletion of the ATP dependent calcium pump PMCA4 (plasma membrane calcium/calmodulin dependent ATPase, isoform 4) results in infertility in male mice due to a selective defect in sperm motility. In addition, recent discoveries in humans have indicated that a single nucleotide polymorphism (SNP) in the PMCA4 gene determines the susceptibility towards malaria plasmodium infection. Therefore, there is an urgent need to develop specific PMCA4 inhibitors. In the current study, we aim to optimise and validate a high throughput screening compatible assay using recombinantly expressed PMCA4 and the HTRF® Transcreener® ADP (TR-FRET) assay to screen a drug library. PMCA4 membrane microsomes were prepared from HEK293 cells overexpressing PMCA4. Western blot quantification revealed nearly nine-fold increased expression of PMCA4 compared to LacZ (control virus)-infected cells. Maximal PMCA4 microsomal activity was achieved in the TR-FRET assay with 15ng/μl microsomal concentration, 30-minute pre-incubation with compounds at 37°C, and calcium buffering with 1mM EGTA providing 1μM free-calcium. Finally a dose-response curve for carboxyeosin (a non-specific PMCA inhibitor) under optimised conditions showed significant PMCA4 inhibition. Upon confirmation that the assay was suitable for high-throughput screening, we have screened the ChemBioNet small molecule library (~21,000 compounds) against the PMCA4 assay to identify those that are its apparent inhibitors. This screening yielded 1,494 primary hits. We have optimised the HTRF® Transcreener® ADP assay for high-throughput screening to identify PMCA4 inhibitors. The output of the screening campaign has provided preliminary chemical

  13. Voltage-Gated Calcium Channels in Nociception

    Science.gov (United States)

    Yasuda, Takahiro; Adams, David J.

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

  14. [Calcium 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

  15. Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Salomonsson, Max; Braunstein, Thomas Hartig

    2008-01-01

    in transmission of conducted vasoconstrictor signals in the preglomerular arterioles is unknown. Connexin mimetic peptides were previously reported to target and inhibit specific connexins. We, therefore, investigated whether conducted vasoconstriction in isolated renal arterioles could be blocked by the use...... of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response...... was measured 500 mum from the site of stimulation. Application of connexin mimetic peptides directed against Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit the propagated response, whereas the nonselective gap junction uncoupler carbenoxolone completely abolished the propagated...

  16. 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

  17. High speed two-photon imaging of calcium dynamics in dendritic spines: consequences for spine calcium kinetics and buffer capacity.

    Directory of Open Access Journals (Sweden)

    L Niels Cornelisse

    Full Text Available Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR, we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity.

  18. High speed two-photon imaging of calcium dynamics in dendritic spines: consequences for spine calcium kinetics and buffer capacity.

    Science.gov (United States)

    Cornelisse, L Niels; van Elburg, Ronald A J; Meredith, Rhiannon M; Yuste, Rafael; Mansvelder, Huibert D

    2007-10-24

    Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP) are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR), we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity.

  19. [Microbial geochemical calcium cycle].

    Science.gov (United States)

    Zavarzin, G A

    2002-01-01

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

  20. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jorgensen, N R; Geist, S T; Civitelli, R

    1997-01-01

    stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied...... mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein...... connexin43 (Cx43), are well dye coupled, and lack P2U receptors, transmitted slow gap junction-dependent calcium waves that did not require release of intracellular calcium stores. UMR 106-01 cells predominantly express the gap junction protein connexin 45 (Cx45), are poorly dye coupled, and express P2U...

  1. Calcium orthophosphates in dentistry.

    Science.gov (United States)

    Dorozhkin, Sergey V

    2013-06-01

    Dental caries, also known as tooth decay or a cavity, remains a major public health problem in the most communities even though the prevalence of disease has decreased since the introduction of fluorides for dental care. Therefore, biomaterials to fill dental defects appear to be necessary to fulfill customers' needs regarding the properties and the processing of the products. Bioceramics and glass-ceramics are widely used for these purposes, as dental inlays, onlays, veneers, crowns or bridges. Calcium orthophosphates belong to bioceramics but they have some specific advantages over other types of bioceramics due to a chemical similarity to the inorganic part of both human and mammalian bones and teeth. Therefore, calcium orthophosphates (both alone and as components of various formulations) are used in dentistry as both dental fillers and implantable scaffolds. This review provides brief information on calcium orthophosphates and describes in details current state-of-the-art on their applications in dentistry and dentistry-related fields. Among the recognized dental specialties, calcium orthophosphates are most frequently used in periodontics; however, the majority of the publications on calcium orthophosphates in dentistry are devoted to unspecified "dental" fields.

  2. Calcium Signalling: Fishing Out Molecules of Mitochondrial Calcium Transport

    OpenAIRE

    Hajnóczky, György; Csordás, György

    2010-01-01

    Cellular energy metabolism, survival and death are controlled by mitochondrial calcium signals originating in the cytoplasm. Now, RNAi studies link three proteins — MICU1, NCLX and LETM1 — to the previously unknown molecular mechanism of mitochondrial calcium transport.

  3. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    Science.gov (United States)

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

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

  4. Calcium pathway machinery at fertilization in echinoderms.

    Science.gov (United States)

    Ramos, Isabela; Wessel, Gary M

    2013-01-01

    Calcium signaling in cells directs diverse physiological processes. The calcium waves triggered by fertilization is a highly conserved calcium signaling event essential for egg activation, and has been documented in every egg tested. This activity is one of the few highly conserved events of egg activation through the course of evolution. Echinoderm eggs, as well as many other cell types, have three main intracellular Ca(2+) mobilizing messengers - IP3, cADPR and NAADP. Both cADPR and NAADP were identified as Ca(2+) mobilizing messengers using the sea urchin egg homogenate, and this experimental system, along with the intact urchin and starfish oocyte/egg, continues to be a vital tool for investigating the mechanism of action of calcium signals. While many of the major regulatory steps of the IP3 pathway are well resolved, both cADPR and NAADP remain understudied in terms of our understanding of the fundamental process of egg activation at fertilization. Recently, NAADP has been shown to trigger Ca(2+) release from acidic vesicles, separately from the ER, and a new class of calcium channels, the two-pore channels (TPCs), was identified as the likely targets for this messenger. Moreover, it was found that both cADPR and NAADP can be synthesized by the same family of enzymes, the ADP-rybosyl cyclases (ARCs). In this context of increasing amount of information, the potential coupling and functional roles of different messengers, intracellular stores and channels in the formation of the fertilization calcium wave in echinoderms will be critically evaluated. Copyright © 2012. Published by Elsevier India Pvt Ltd.

  5. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

    Full Text Available In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan and Heibrunn (USA experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are

  6. Children's Bone Health and Calcium

    Science.gov (United States)

    ... Email Share Dialog × Print Children's Bone Health and Calcium: Condition Information What is bone health and how ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  7. Stable prenucleation calcium carbonate clusters

    OpenAIRE

    Gebauer, Denis; Völkel, Antje; Cölfen, Helmut

    2008-01-01

    Calcium carbonate forms scales, geological deposits, biominerals, and ocean sediments. Huge amounts of carbon dioxide are retained as carbonate ions, and calcium ions represent a major contribution to water hardness. Despite its relevance, little is known about the precipitation mechanism of calcium carbonate, and specified complex crystal structures challenge the classical view on nucleation considering the formation of metastable ion clusters. We demonstrate that dissolved calcium carbonate...

  8. Assay for calcium channels

    Energy Technology Data Exchange (ETDEWEB)

    Glossmann, H.; Ferry, D.R.

    1985-01-01

    This chapter focuses on biochemical assays for Ca/sup 2 +/-selective channels in electrically excitable membranes which are blocked in electrophysiological and pharmacological experiments by verapamil, 1,4-dihydropyridines, diltiazen (and various other drugs), as well as inorganic di- or trivalent cations. The strategy employed is to use radiolabeled 1,4-dihydropyridine derivatives which block calcium channels with ED/sub 50/ values in the nanomolar range. Although tritiated d-cis-diltiazem and verapamil can be used to label calcium channels, the 1,4-dihydropyridines offer numerous advantages. The various sections cover tissue specificity of channel labeling, the complex interactions of divalent cations with the (/sup 3/H)nimodipine-labeled calcium channels, and the allosteric regulation of (/sup 3/H)nimodipine binding by the optically pure enantiomers of phenylalkylamine and benzothiazepine calcium channel blockers. A comparison of the properties of different tritiated 1,4-dihydropyridine radioligands and the iodinated channel probe (/sup 125/I)iodipine is given.

  9. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

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

  10. The Plasma Membrane Calcium Pump

    Science.gov (United States)

    Rasmussen, H.

    1983-01-01

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

  11. 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...

  12. Impregnating Coal With Calcium Carbonate

    Science.gov (United States)

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

    1991-01-01

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

  13. Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric OxideSummary

    Directory of Open Access Journals (Sweden)

    Isola A.M. Brown

    2016-01-01

    Full Text Available Background & Aims: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R; triggering adenosine triphosphate (ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca2+]i in surrounding enteric glia. We tested the hypothesis that the activation of enteric glia contributes to neuron death during inflammation. Methods: We studied neuroinflammation in vivo using the 2,4-dinitrobenzene sulfonic acid model of colitis and in situ using whole-mount preparations of human and mouse intestine. Transgenic mice with a targeted deletion of glial connexin-43 (Cx43 [GFAP::CreERT2+/−/Cx43f/f] were used to specifically disrupt glial signaling pathways. Mice deficient in inducible nitric oxide (NO synthase (iNOS−/− were used to study NO production. Protein expression and oxidative stress were measured using immunohistochemistry and in situ Ca2+ and NO imaging were used to monitor glial [Ca2+]i and [NO]i. Results: Purinergic activation of enteric glia drove [Ca2+]i responses and enteric neuron death through a Cx43-dependent mechanism. Neurotoxic Cx43 activity, driven by NO production from glial iNOS, was required for neuron death. Glial Cx43 opening liberated ATP and Cx43-dependent ATP release was potentiated by NO. Conclusions: Our results show that the activation of glial cells in the context of neuroinflammation kills enteric neurons. Mediators of inflammation that include ATP and NO activate neurotoxic pathways that converge on glial Cx43 hemichannels. The glial response to inflammatory mediators might contribute to the development of motility disorders. Keywords: Enteric Nervous System, Hemichannels

  14. 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.

  15. Crystal structure of metagenomic β-xylosidase/ α-l-arabinofuranosidase activated by calcium.

    Science.gov (United States)

    Matsuzawa, Tomohiko; Kaneko, Satoshi; Kishine, Naomi; Fujimoto, Zui; Yaoi, Katsuro

    2017-09-01

    The crystal structure of metagenomic β-xylosidase/α-l-arabinofuranosidase CoXyl43, activated by calcium ions, was determined in its apo and complexed forms with xylotriose or l-arabinose in the presence and absence of calcium. The presence of calcium ions dramatically increases the kcat of CoXyl43 for p-nitrophenyl β-d-xylopyranoside and reduces the Michaelis constant for p-nitrophenyl α-l-arabinofuranoside. CoXyl43 consists of a single catalytic domain comprised of a five-bladed β-propeller. In the presence of calcium, a single calcium ion was observed at the centre of this catalytic domain, behind the catalytic pocket. In the absence of calcium, the calcium ion was replaced with one sodium ion and one water molecule, and the positions of these cations were shifted by 1.3 Å. The histidine-319 side chain, which coordinates to the 2-hydroxyl oxygen atom of the bound xylose molecule in the catalytic pocket, also coordinates to the calcium ion, but not to the sodium ion. The calcium-dependent increase in activity appears to be caused by the structural change in the catalytic pocket induced by the tightly bound calcium ion and coordinating water molecules, and by the protonation state of glutamic acid-268, the catalytic acid of the enzyme. Our findings further elucidate the complex relationship between metal ions and glycosidases. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  16. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. 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.

  18. 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

  19. The increasing of enamel calcium level after casein phosphopeptideamorphous calcium phosphate covering

    Directory of Open Access Journals (Sweden)

    Widyasri Prananingrum

    2012-06-01

    Full Text Available Background: Caries process is characterized by the presence of demineralization. Demineralization is caused by organic acids as a result of carbohydrate substrate fermentation. Remineralization is a natural repair process for non-cavitated lesions. Remineralization occurs if there are Ca2+ and PO43- ions in sufficient quantities. Casein-amorphous calcium phosphate phosphopeptide (CPP-ACP is a paste material containing milk protein (casein, that actually contains minerals, such as calcium and phosphate. The casein ability to stabilize calcium phosphate and enhance mineral solubility and bioavailability confers upon CPP potential to be biological delivery vehicles for calcium and phosphate. Purpose: The aim of this study was to determine the calcium levels in tooth enamel after being covered with CPP-ACP 2 times a day for 3, 14 and 28 days. Methods: Sample were bovine incisors of 3 year old cows divided into 4 groups, namely group I as control group, group II, III and IV as treatment groups covered with CPP-ACP 2 times a day. All of those teeth were then immersed in artificial saliva. Group II was immersed for 3 days, while group III was immersed for 14 days, and group IV was immersed for 28 days. One drop of CPP-ACP was used to cover the entire labial surface of teeth. The measurement of the calcium levels was then conducted by using titration method. All data were analyzed by One- Way ANOVA test with 5% degree of confidence. Results: The results showed significant difference of the calcium levels in tooth enamel of those groups after covered with CPP-ACP 2 times a day for 3, 14 and 28 days (p = 0.001. There is also significant difference of the calcium levels in tooth enamel of those treatment groups and the control group (p = 0.001. Conclusion: The calcium levels of tooth enamel are increased after covered with CPP-ACP 2 times a day for 3, 14 and 28 days.Latar belakang: Proses terjadinya karies gigi ditandai oleh adanya demineralisasi

  20. 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.

  1. Calcium metabolism and cardiovascular function after spaceflight

    Science.gov (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P platelet free calcium (intracellular calcium concentration) were also reduced (P metabolism (P metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  2. Diagnosis of alterations of serum calcium metabolism.

    Science.gov (United States)

    Lumachi, Franco; Cappelletti, Piero; Tozzoli, Renato; Basso, Stafano M M; Luisetto, Giovanni; Camozzi, Valentina

    2012-07-01

    Calcium is essential to homeostasis and functioning of multiple organ systems. Its circulating concentration is maintained within a very tight physiologic range: 2.25 and 2.50 mmol/L. Under physiological conditions, the ionized calcium concentration is regulated by the parathyroid hormone (PTH), and 1,25(OH)(2) vitamin D through interactions on target organs such as kidney, bone and intestine. In mild, moderate, and severe hypercalcemia, laboratory findings are essential in assessing and monitoring disease course and therapy. The main tools are specific standard biochemical tests able to assess calcium balance and renal function, and some specific biochemical tests, such as PTH, 25(OH) vitamin D, and genetic sequencing, used to clarify the cause of hypercalcemia and, subsequently, to determine appropriate therapy. Once hypercalcemia is confirmed by ionized calcium measurement, the intact PTH assay plays a crucial role to differentiate PTH-mediated from non-PTH-mediated hypercalcemia. Mild hypercalcemia is also present in up to 10-20% of patients treated with lithium for bipolar disorders, in 7-8% of those treated with thiazide diuretics, and in patients with prolonged immobilization, while very high (>3.5 mmol/L) serum calcium levels, together with low PTH, and a rapid increase of hypercalcemia, usually suggest a malignancy-associated hypercalcemic syndrome. The measurement of PTH-related protein, a tumor product that mimics certain action of PTH, is useful only in selected cases. The role of biochemical markers of bone turnover for predicting metastatic bone disease, and monitoring bone metabolic changes, and their usefulness as a predictive mean of the likelihood of bone loss or fractures risk is still unclear.

  3. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

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

  4. 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.

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

    Science.gov (United States)

    Wilson, Rosamund J; Copley, J Brian

    2017-01-01

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

  6. Transposable elements in TDP-43-mediated neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Wanhe Li

    Full Text Available Elevated expression of specific transposable elements (TEs has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

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

    OpenAIRE

    Bizzozero, Julien; Scrivener, Karen

    2015-01-01

    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 ...

  8. Mixed calcium-magnesium pre-nucleation clusters enrich calcium

    OpenAIRE

    Verch, Andreas; Antonietti, Markus; Cölfen, Helmut

    2012-01-01

    It is demonstrated that magnesium and carbonate ions can form pre-nucleation clusters in analogy to calcium carbonate. If a mixed calcium and magnesium solution is brought in contact with carbonate ions, mixed pre-nucleation clusters form. The equilibrium constants for their formation are reported revealing that over the entire range of possible cation mixing ratios, calcium gets enriched over magnesium in the pre-nucleation clusters. This can explain high magnesium contents in amorphous calc...

  9. Biological Reactions to Calcium Phosphate-coated Calcium Carbonate Particles

    National Research Council Canada - National Science Library

    Tetsunari NISHIKAWA; Kazuya MASUNO; Tomoharu OKAMURA; Kazuya TOMINAGA; Masahiro WATO; Mayu KOKUBU; Koichi IMAI; Shoji TAKEDA; Yoichro TAGUCHI; Masatoshi UEDA; Akio TANAKA

    2010-01-01

    [SYNOPSIS][Objectives]: In order to histopathologically investigate biological reactions to materials used for scaffolds, we examined the cytotoxicity to calcium particles in vitro and bioabsorption in vivo...

  10. Osteoporosis, calcium and physical activity.

    OpenAIRE

    Martin, A. D.; Houston, C S

    1987-01-01

    Sales of calcium supplements have increased dramatically since 1983, as middle-aged women seek to prevent or treat bone loss due to osteoporosis. However, epidemiologic studies have failed to support the hypothesis that larger amounts of calcium are associated with increased bone density or a decreased incidence of fractures. The authors examine the evidence from controlled trials on the effects of calcium supplementation and physical activity on bone loss and find that weight-bearing activit...

  11. Estimation of calcium and magnesium in serum and urine by atomic absorption spectrophotometry

    Science.gov (United States)

    Thin, Christian G.; Thomson, Patricia A.

    1967-01-01

    A method has been described for the estimation of calcium and magnesium in serum and urine using atomic absorption spectrophotometry. The precision and accuracy of the techniques have been determined and were found to be acceptable. The range of values for calcium and magnesium in the sera of normal adults was found to be: serum calcium (corrected to a specific gravity of 1·026) 8·38-10·08 mg. per 100 ml.; serum magnesium 1·83-2·43 mg. per 100 ml. PMID:5602562

  12. Novel Pharmacophores of Connexin43 Based on the “RXP” Series of Cx43-binding Peptides

    Science.gov (United States)

    Verma, Vandana; Larsen, Bjarne Due; Coombs, Wanda; Lin, Xianming; Spagnol, Gaelle; Sorgen, Paul L; Taffet, Steven M; Delmar, Mario

    2009-01-01

    Gap junction pharmacology is a nascent field. Previous studies have identified molecules that enhance intercellular communication, and may offer potential for innovative antiarrhythmic therapy. However, their specific molecular target(s) and mechanism(s) of action remain unknown. Previously, we identified a 34-amino acid peptide (RXP-E) that binds the carboxyl terminal domain of Cx43 (Cx43CT) and prevents cardiac gap junction closure and action potential propagation block. These results supported the feasibility of a peptide-based pharmacology to Cx43, but the structure of the core active element in RXP-E, an essential step for pharmacological development, remained undefined. Here, we used a combination of molecular modeling, surface plasmon resonance, nuclear magnetic resonance and patch clamp strategies to define, for the first time, a unique ensemble of pharmacophores that bind Cx43CT and prevent closure of Cx43 channels. Two particular molecules are best representatives of this family: a cyclized heptapeptide (called CyRP-71), and a linear octapeptide of sequence RRNYRRNY. These two small compounds offer the first structural platform for the design of Cx43-interacting gap junction openers. Moreover, the structure of these compounds offers an imprint of a region of Cx43CT that is fundamental to gap junction channel function. PMID:19556520

  13. 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.

  14. Laser Sintered Calcium Phosphate Bone

    National Research Council Canada - National Science Library

    Vail, Neil

    1999-01-01

    ...) technology selective laser sintering (SLS). BME has successfully implemented a pilot facility to fabricate calcium phosphate implants using anatomical data coupled with the selective laser sintering process...

  15. 21 CFR 73.1070 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... precipitated calcium carbonate (CaCO3). (2) Color additive mixtures for drug use made with calcium carbonate... precipitated calcium carbonate in the United States Pharmacopeia XX (1980). (c) Uses and restrictions. Calcium... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Calcium carbonate. 73.1070 Section 73.1070 Food...

  16. 21 CFR 184.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium carbonate. 184.1191 Section 184.1191 Food... Specific Substances Affirmed as GRAS § 184.1191 Calcium carbonate. (a) Calcium carbonate (CaCO3, CAS Reg... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation...

  17. Calcium Signaling and Cardiac Arrhythmias.

    Science.gov (United States)

    Landstrom, Andrew P; Dobrev, Dobromir; Wehrens, Xander H T

    2017-06-09

    There has been a significant progress in our understanding of the molecular mechanisms by which calcium (Ca2+) ions mediate various types of cardiac arrhythmias. A growing list of inherited gene defects can cause potentially lethal cardiac arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia, congenital long QT syndrome, and hypertrophic cardiomyopathy. In addition, acquired deficits of multiple Ca2+-handling proteins can contribute to the pathogenesis of arrhythmias in patients with various types of heart disease. In this review article, we will first review the key role of Ca2+ in normal cardiac function-in particular, excitation-contraction coupling and normal electric rhythms. The functional involvement of Ca2+ in distinct arrhythmia mechanisms will be discussed, followed by various inherited arrhythmia syndromes caused by mutations in Ca2+-handling proteins. Finally, we will discuss how changes in the expression of regulation of Ca2+ channels and transporters can cause acquired arrhythmias, and how these mechanisms might be targeted for therapeutic purposes. © 2017 American Heart Association, Inc.

  18. Calcium signalling: fishing out molecules of mitochondrial calcium transport.

    Science.gov (United States)

    Hajnóczky, György; Csordás, György

    2010-10-26

    Cellular energy metabolism, survival and death are controlled by mitochondrial calcium signals originating in the cytoplasm. Now, RNAi studies link three proteins - MICU1, NCLX and LETM1 - to the previously unknown molecular mechanism of mitochondrial calcium transport. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Calcium nutrition and extracellular calcium sensing: relevance for the pathogenesis of osteoporosis, cancer and cardiovascular diseases.

    Science.gov (United States)

    Peterlik, Meinrad; Kállay, Enikoe; Cross, Heide S

    2013-01-22

    Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR). This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca2+ to function as a "first messenger" for various intracellular signaling cascades. Evidence demonstrates that Ca2+/CaSR signaling in functional linkage with vitamin D receptor (VDR)-activated pathways (i) promotes osteoblast differentiation and formation of mineralized bone; (ii) targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; (iii) evokes Ca2+ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca2+/CaSR signaling opens Ca2+-sensitive K+ conductance channels in vascular endothelial cells, and also participates in IP(3)-dependent regulation of cytoplasmic Ca2+, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca2+/CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease.

  20. 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 off...

  1. Hybrid Calcium Phosphate Coatings for Titanium Implants

    Science.gov (United States)

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

    2017-01-01

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

  2. ISS Expedition 43 Press Kit

    Data.gov (United States)

    National Aeronautics and Space Administration — Press kit for ISS mission Expedition 43 from 11/2014-06/2015. Press kits contain information about each mission overview, crew, mission timeline, benefits, and media...

  3. Individual and family correlates of calcium-rich food intake among parents of early adolescent children.

    Science.gov (United States)

    Reicks, Marla; Ballejos, Miriam Edlefsen; Goodell, L Suzanne; Gunther, Carolyn; Richards, Rickelle; Wong, Siew Sun; Auld, Garry; Boushey, Carol J; Bruhn, Christine; Cluskey, Mary; Misner, Scottie; Olson, Beth; Zaghloul, Sahar

    2011-03-01

    Most adults do not meet calcium intake recommendations. Little is known about how individual and family factors, including parenting practices that influence early adolescents' intake of calcium-rich foods, affect calcium intake of parents. This information could inform the development of effective nutrition education programs. To identify individual and family factors associated with intake of calcium-rich foods among parents of early adolescents (aged 10 to 13 years). A cross-sectional survey was used with 14 scales to assess attitudes/preferences and parenting practices regarding calcium-rich foods and a calcium-specific food frequency questionnaire (2006-2007). A convenience sample of self-reporting non-Hispanic white, Hispanic, and Asian (n=661) parents was recruited in nine states. Parents were the primary meal planner/preparer and completed questionnaires in homes or community settings. Predictors of calcium intake from three food groupings-all food sources, dairy foods, and milk. Multivariate regression analyses identified demographic, attitude/preference, and behavioral factors associated with calcium intake. Most respondents were women (∼90%) and 38% had a college degree. Education was positively associated with calcium intake from all three food groupings, whereas having an Asian spouse compared to a non-Hispanic white spouse was negatively associated with calcium intake only from all food sources and from dairy foods. Expectations for and encouragement of healthy beverage intake for early adolescents were positively associated with calcium intake from dairy foods and milk, respectively. Parental concern regarding adequacy of intake was negatively associated, whereas perception of health benefits from calcium-rich foods was positively associated with calcium intake from all food sources and from dairy foods. Between 20% and 32% of the variance in calcium intake from all food groupings was explained in these models. Individual factors and positive

  4. Calcium-Sensitive MRI Contrast Agents Based on Superparamagnetic Iron Oxide Nanoparticles and Calmodulin

    National Research Council Canada - National Science Library

    Tatjana Atanasijevic; Maxim Shusteff; Peter Fam; Alan Jasanoff

    2006-01-01

    We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calciumsensing protein calmodulin and its targets...

  5. 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.

  6. 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 ...

  7. Calcium Supplements: Do Men Need Them Too?

    Science.gov (United States)

    ... Lifestyle Nutrition and healthy eating Should men take calcium supplements? Answers from Katherine Zeratsky, R.D., L. ... Most healthy men don't need to take calcium supplements. Calcium is important for men for optimal ...

  8. Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer.

    Science.gov (United States)

    Rinella, Erica S; Bankaitis, Eric D; Threadgill, David W

    2012-02-01

    The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and Apc (Min/+) and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of dietary calcium supplementation and EGFR inhibitors also resulted in elevated toxicity suggesting that careful consideration be given when combining dietary supplements with prescribed cancer therapies.

  9. Stable prenucleation calcium carbonate clusters.

    Science.gov (United States)

    Gebauer, Denis; Völkel, Antje; Cölfen, Helmut

    2008-12-19

    Calcium carbonate forms scales, geological deposits, biominerals, and ocean sediments. Huge amounts of carbon dioxide are retained as carbonate ions, and calcium ions represent a major contribution to water hardness. Despite its relevance, little is known about the precipitation mechanism of calcium carbonate, and specified complex crystal structures challenge the classical view on nucleation considering the formation of metastable ion clusters. We demonstrate that dissolved calcium carbonate in fact contains stable prenucleation ion clusters forming even in undersaturated solution. The cluster formation can be characterized by means of equilibrium thermodynamics, applying a multiple-binding model, which allows for structural preformation. Stable clusters are the relevant species in calcium carbonate nucleation. Such mechanisms may also be important for the crystallization of other minerals.

  10. Calcium metabolism & hypercalcemia in adults.

    Science.gov (United States)

    Lumachi, F; Motta, R; Cecchin, D; Ave, S; Camozzi, V; Basso, S M M; Luisetto, G

    2011-01-01

    Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.

  11. Calcium Aluminate Cement Hydration Model

    Directory of Open Access Journals (Sweden)

    Matusinović, T.

    2011-01-01

    Full Text Available Calcium aluminate cement (AC is a very versatile special cement used for specific applications. As the hydration of AC is highly temperature dependent, yielding structurally different hydration products that continuously alter material properties, a good knowledge of thermal properties at early stages of hydration is essential. The kinetics of AC hydration is a complex process and the use of single mechanisms models cannot describe the rate of hydration during the whole stage.This paper examines the influence of temperature (ϑ=5–20 °C and water-to-cement mass ratio (mH /mAC = 0.4; 0.5 and 1.0 on hydration of commercial iron-rich AC ISTRA 40 (producer: Istra Cement, Pula, Croatia, which is a part of CALUCEM group, Figs 1–3. The flow rate of heat generation of cement pastes as a result of the hydration reactions was measured with differential microcalorimeter. Chemically bonded water in the hydrated cement samples was determined by thermo-gravimetry.Far less heat is liberated when cement and water come in contact for the first time, Fig. 1, than in the case for portland cement (PC. Higher water-to-cement ratio increases the heat evolved at later ages (Fig. 3 due to higher quantity of water available for hydration. A significant effect of the water-to-cement ratio on the hydration rate and hydration degree showed the importance of water as being the limiting reactant that slows down the reaction early. A simplified stoichiometric model of early age AC hydration (eq. (8 based on reaction schemes of principal minerals, nominally CA, C12A7 and C4AF (Table 1, was employed. Hydration kinetics after the induction period (ϑ < 20 °C had been successfully described (Fig. 4 and Table 2 by a proposed model (eq. (23 which simultaneously comprised three main mechanisms: nucleation and growth, interaction at phase boundary, and mass transfer. In the proposed kinetic model the nucleation and growth is proportional to the amount of reacted minerals (eq

  12. Calcium and Calcium Supplements: Achieving the Right Balance

    Science.gov (United States)

    ... Duyff RL. American Dietetic Association Complete Food and Nutrition Guide. 4th ed. Hoboken, N.J.: John Wiley & Sons; 2012:140. Rosen HN. Calcium and vitamin D supplementation in osteoporosis. http://www.uptodate.com/home/index. ...

  13. Calcium carbonate and calcium sulfate in Martian meteorite EETA79001

    Science.gov (United States)

    Gooding, J. L.; Wentworth, S. J.

    1987-01-01

    Chips of glassy Lithology C of EETA79001 were studied by scanning electron microscopy and energy dispersive X-ray spectroscopy to determine the mineralogy and petrogenesis of the glass that was shown by others to contain trapped Mars-like gases. Calcium carbonite was identified as massive to acicular crystals for which Ca, C, and O were the major elements. Calcium sulfate was identified as prismatic-acicular crystals with Ca and S as the major elements.

  14. 21 CFR 184.1187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

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

  15. Extracellular and Intracellular Regulation of Calcium Homeostasis

    Directory of Open Access Journals (Sweden)

    Felix Bronner

    2001-01-01

    Full Text Available An organism with an internal skeleton must accumulate calcium while maintaining body fluids at a well-regulated, constant calcium concentration. Neither calcium absorption nor excretion plays a significant regulatory role. Instead, isoionic calcium uptake and release by bone surfaces causes plasma calcium to be well regulated. Very rapid shape changes of osteoblasts and osteoclasts, in response to hormonal signals, modulate the available bone surfaces so that plasma calcium can increase when more low-affinity bone calcium binding sites are made available and can decrease when more high-affinity binding sites are exposed. The intracellular free calcium concentration of body cells is also regulated, but because cells are bathed by fluids with vastly higher calcium concentration, their major regulatory mechanism is severe entry restriction. All cells have a calcium-sensing receptor that modulates cell function via its response to extracellular calcium. In duodenal cells, the apical calcium entry structure functions as both transporter and a vitamin D–responsive channel. The channel upregulates calcium entry, with intracellular transport mediated by the mobile, vitamin D–dependent buffer, calbindin D9K, which binds and transports more than 90% of the transcellular calcium flux. Fixed intracellular calcium binding sites can, like the body's skeleton, take up and release calcium that has entered the cell, but the principal regulatory tool of the cell is restricted entry.

  16. Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice

    Directory of Open Access Journals (Sweden)

    Dickson Dennis W

    2011-10-01

    model remain unknown. However, our results suggest that overexpression of the hTDP-43M337V can cause neuronal dysfunction due to its effect on a number of cell organelles and proteins, such as mitochondria and TDP-43, that are critical for neuronal activity. The mutant model will serve as a valuable tool in the development of future studies designed to uncover pathways associated with TDP-43 neurotoxicity and the precise roles TDP-43 RNA targets play in neurodegeneration.

  17. Calcium phosphates for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Canillas, M.; Pena, P.; Aza, A.H. de; Rodriguez, M.A.

    2017-07-01

    The history of calcium phosphates in the medicine field starts in 1769 when the first evidence of its existence in the bone tissue is discovered. Since then, the interest for calcium phosphates has increased among the scientific community. Their study has been developed in parallel with new advances in materials sciences, medicine or tissue engineering areas. Bone tissue engineering is the field where calcium phosphates have had a great importance. While the first bioceramics are selected according to bioinert, biocompatibility and mechanical properties with the aim to replace bone tissue damaged, calcium phosphates open the way to the bone tissue regeneration challenge. Nowadays, they are present in the majority of commercial products directed to repair or regenerate damaged bone tissue. Finally, in the last few decades, they have been suggested and studied as drug delivering devices and as vehicles of DNA and RNA for the future generation therapies. (Author)

  18. Polysulfide calcium as multyfunctional product

    Directory of Open Access Journals (Sweden)

    G. Abramova

    2012-12-01

    Full Text Available A modified method of producing of polysulfide calcium, the influence of various factors on the degree of polysulfide of product, as well as possible directions for its use as a multifunctional compound were considered.

  19. [Calcium metabolism after the menopause].

    Science.gov (United States)

    Kanovitch, D; Klotz, H P

    1976-02-16

    The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix.

  20. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

  2. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pantothenate, calcium chloride double salt. 172.330 Section 172.330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may...

  3. 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.

  4. The SCFA receptor GPR43 and energy metabolism

    Directory of Open Access Journals (Sweden)

    Ikuo eKimura

    2014-06-01

    Full Text Available Free fatty acids (FFAs are essential nutrients and act as signaling molecules in various cellular processes via binding with FFA receptors. Of these receptors, GPR43 is activated by short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate. During feeding, SCFAs are produced by microbial fermentation of dietary fiber in the gut, and these SCFAs become important energy sources for the host. The gut microbiota affects nutrient acquisition and energy regulation of the host and can influence the development of obesity, insulin resistance, and diabetes. Recently, GPR43 has been reported to regulate host energy homeostasis in the gastrointestinal tract and adipose tissues. Hence, GPR43 is also thought to be a potential drug target for metabolic disorders, such as obesity and diabetes. In this review, we summarize the identification, structure, and activities of GPR43, with a focus on host energy regulation, and present an essential overview of our current understanding of its physiological roles in host energy regulation that is mediated by gut microbiota. We also discuss the potential for GPR43 as a therapeutic target.

  5. Calcium affects on vascular endpoints

    Directory of Open Access Journals (Sweden)

    Patel Vaishali B

    2012-03-01

    Full Text Available Abstract Calcium is one of the most abundant minerals in the body and its metabolism is one of the basic biologic processes in humans. Although historically linked primarily to bone structural development and maintenance, calcium is now recognized as a key component of many physiologic pathways necessary for optimum health including cardiovascular, neurological, endocrine, renal, and gastrointestinal systems. A recent meta-analysis published in August 2011 showed a potential increase in cardiovascular events related to calcium supplementation. The possible mechanism of action of this correlation has not been well elucidated. This topic has generated intense interest due to the widespread use of calcium supplements, particularly among the middle aged and elderly who are at the most risk from cardiac events. Prior studies did not control for potential confounding factors such as the use of statins, aspirin or other medications. These controversial results warrant additional well-designed studies to investigate the relationship between calcium supplementation and cardiovascular outcomes. The purpose of this review is to highlight the current literature in regards to calcium supplementation and cardiovascular health; and to identify areas of future research.

  6. Screening, identification, and characterization of a GH43 family β-xylosidase/α-arabinofuranosidase from a compost microbial metagenome.

    Science.gov (United States)

    Matsuzawa, Tomohiko; Kaneko, Satoshi; Yaoi, Katsuro

    2015-11-01

    A putative glycoside hydrolase family 43 β-xylosidase/α-arabinofuranosidase (CoXyl43) that promotes plant biomass saccharification was isolated via functional screening of a compost microbial metagenomic library and characterized. CoXyl43 promoted the saccharification of plant biomasses, including xylans (xylan and arabinoxylan), rice straw, and Erianthus, by degrading xylooligosaccharide residues to monosaccharide residues. The recombinant CoXyl43 protein exhibited both β-xylosidase and α-arabinofuranosidase activities for chromogenic substrates, with optimal activity at pH 7.5 and 55 °C. Both of these activities were inactivated by ethanol, dimethylsulfoxide, and zinc and copper ions but were activated by manganese ions. Only the β-xylosidase activity of recombinant CoXyl43 was enhanced in the presence of calcium ions. These results indicate that CoXyl43 exhibits unique enzymatic properties useful for biomass saccharification.

  7. 26 CFR 1.43-3 - Certification

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Certification 1.43-3 Section 1.43-3 Internal... § 1.43-3 Certification (a) Petroleum engineer's certification of a project—(1) In general. A petroleum... requirements of section 43(c)(2)(A). A petroleum engineer's certification must be submitted for each project...

  8. 26 CFR 43.0-1 - Introduction.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 43.0-1 Section 43.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX ON TRANSPORTATION BY WATER § 43.0-1 Introduction. The regulations in this part 43 are designated...

  9. ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

    Science.gov (United States)

    Kaus, Anjoscha; Sareen, Dhruv

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

  10. Target Laboratory

    Data.gov (United States)

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

  11. Inverse-kinematics proton scattering from 43P

    Science.gov (United States)

    Skiles, L. M.; Gregory, S. D.; Haldeman, E. B.; Klybor, B. R.; Riley, L. A.; Cottle, P. D.; Kemper, K. W.; Bazin, D.; Belarge, J.; Bender, P. C.; Elman, B.; Gade, A.; Lipschutz, S.; Longfellow, B.; Lunderberg, E.; Mijatovic, T.; Pereira, J.; Titus, R.; Weisshaar, D.; Zamora, J. C.; Zegers, R. G. T.

    2017-09-01

    Following an experiment at the National Superconducting Cyclotron Laboratory at Michigan State University (NSCL) in October 2016, we study the excited states of the neutron-rich N = 28 isotope 43P via inverse-kinematic proton scattering with the GRETINA gamma-ray tracking array and the NSCL/Ursinus College liquid hydrogen target. We discuss preliminary analysis and results, including measured cross sections for populating excited states of 43P. This work was supported by the National Science Foundation under Grant Nos. PHY-1617250, PHY-1303480 and PHY-1102511 and by the US Department of Energy under Grant No. DE-AC02-05CH11231.

  12. Calcium: the molecular basis of calcium action in biology and medicine

    National Research Council Canada - National Science Library

    Pochet, Roland; Donato, Rosario

    2000-01-01

    ... of Calcium Calcium Signalling in Excitable Cells Ca2+ Release in Muscle Cells by N. Macrez and J. Mironneau Calcium Signalling in Neurons Exemplified by Rat Sympathetic Ganglion Cells by S.J. M...

  13. Oryza sativa Chloroplast Signal Recognition Particle 43 (OscpSRP43) Is Required for Chloroplast Development and Photosynthesis.

    Science.gov (United States)

    Lv, Xiang-guang; Shi, Yong-feng; Xu, Xia; Wei, Yan-lin; Wang, Hui-mei; Zhang, Xiao-bo; Wu, Jian-li

    2015-01-01

    A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS)-induced IR64 (Oryza sativa L. ssp. indica) mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43) with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43) was required for the normal development of chloroplasts and photosynthesis in rice.

  14. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

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

    2010-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX....... Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon...... 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 1 s...

  15. XPS and GDOES Characterization of Porous Coating Enriched with Copper and Calcium Obtained on Tantalum via Plasma Electrolytic Oxidation

    Directory of Open Access Journals (Sweden)

    Krzysztof Rokosz

    2016-01-01

    Full Text Available XPS and GDOES characterizations of porous coatings on tantalum after Plasma Electrolytic Oxidation (PEO at 450 V for 3 minutes in electrolyte containing concentrated (85% phosphoric acid with calcium nitrate and copper (II nitrate are described. Based on the obtained data, it may be concluded that the PEO coating consists of tantalum (Ta5+, calcium (Ca2+, copper (Cu2+  and Cu+, and phosphates (PO43-. It has to be pointed out that copper and calcium are distributed throughout the volume. The authors also propose a new model of PEO, based on the derivative of GDOES signals with sputtering time.

  16. Topical Administration of a Connexin43-based peptide Augments Healing of Chronic Neuropathic Diabetic Foot Ulcers: A Multicenter, Randomized Trial

    OpenAIRE

    Grek, Christina L.; Prasad, G.M.; Viswanathan, Vijay; Armstrong, David G.; Gourdie, Robert G.; Ghatnekar, Gautam S.

    2015-01-01

    Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap-junctional protein connexin43 (Cx43) has roles in dermal wound healing and targeting Cx43 signaling accelerates wound reepithelialization. In a prospective, randomized, multi-center clinical trial we evaluated the efficacy and safety of a peptide mimetic of the C-terminus of Cx43, ACT1, in accelerating the healing of chronic diabetic foot ulcers (DFUs) when incorporated into standard of care ...

  17. Inflammation Induces TDP-43 Mislocalization and Aggregation.

    Directory of Open Access Journals (Sweden)

    Ana Sofia Correia

    Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

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

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

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

  19. Calcium metabolism and cardiovascular function after spaceflight

    Science.gov (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P parathyroid hormone levels (P animals (P = 0.057). However, mean arterial pressure was elevated (P animals fed low- compared with high-calcium diets (P parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  20. [Regulatory mechanism of calcium metabolism.

    Science.gov (United States)

    Ozono, Keiichi

    It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney. Then, 1,25(OH)2D binds to vitamin D receptor(VDR), which works as a ligand-dependent transcription factor. Hypocalcemia and hypercalcemia are caused by various disorders including abnormal regulation of PTH and vitamin D production and their signal transduction.

  1. Calcium signaling and cell proliferation.

    Science.gov (United States)

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

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Calcium regulation of muscle contraction.

    Science.gov (United States)

    Szent-Györgyi, A G

    1975-07-01

    Calcium triggers contraction by reaction with regulatory proteins that in the absence of calcium prevent interaction of actin and myosin. Two different regulatory systems are found in different muscles. In actin-linked regulation troponin and tropomyosin regulate actin by blocking sites on actin required for complex formation with myosin; in myosin-linked regulation sites on myosin are blocked in the absence of calcium. The major features of actin control are as follows: there is a requirement for tropomyosin and for a troponin complex having three different subunits with different functions; the actin displays a cooperative behavior; and a movement of tropomyosin occurs controlled by the calcium binding on troponin. Myosin regulation is controlled by a regulatory subunit that can be dissociated in scallop myosin reversibly by removing divalent cations with EDTA. Myosin control can function with pure actin in the absence of tropomyosin. Calcium binding and regulation of molluscan myosins depend on the presence of regulatory light chains. It is proposed that the light chains function by sterically blocking myosin sites in the absence of calcium, and that the "off" state of myosin requires cooperation between the two myosin heads. Both myosin control and actin control are widely distributed in different organisms. Many invertebrates have muscles with both types of regulation. Actin control is absent in the muscles of molluscs and in several minor phyla that lack troponin. Myosin control is not found in striated vertebrate muscles and in the fast muscles of crustacean decapods, although regulatory light chains are present. While in vivo myosin control may not be excluded from vertebrate striated muscles, myosin control may be absent as a result of mutations of the myosin heavy chain.

  3. Nuclear Calcium Signaling Induces Expression of the Synaptic Organizers Lrrtm1 and Lrrtm2*

    Science.gov (United States)

    Hayer, Stefanie N.; Bading, Hilmar

    2015-01-01

    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 Ca2+/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. PMID:25527504

  4. 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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Can total cardiac calcium predict the coronary calcium score?

    Science.gov (United States)

    Pressman, Gregg S; Crudu, Vitalie; Parameswaran-Chandrika, Anoop; Romero-Corral, Abel; Purushottam, Bhaskar; Figueredo, Vincent M

    2011-01-21

    Mitral annular calcification (MAC) shares the same risk factors as atherosclerosis and is associated with coronary artery disease as well as cardiovascular events. However, sensitivity and positive predictive value are low. We hypothesized that a global echocardiographic calcium score would better predict coronary atherosclerotic burden, as assessed by coronary artery calcium score (CAC), than MAC alone. An echocardiographic score was devised to measure global cardiac calcification in a semi-quantitative manner; this included calcification in the aortic valve and root, the mitral valve and annulus, and the sub-mitral apparatus. This score, and a simplified version, were compared with a similar calcification score by CT scan, as well as the CAC. There was a good correlation between the two global calcification scores; the echocardiographic score also correlated with CAC. Using CAC >400 as a measure of severe coronary atherosclerosis, an echocardiographic score ≥5 had a positive predictive value of 60%. Importantly, the simplified score performed equally well (≥3 had a positive predictive value of 62%). Global cardiac calcification, assessed by CT scan or echocardiography, correlates with the extent of coronary calcium. A semi-quantitative calcium score can be easily applied during routine echocardiographic interpretation and can alert the reader to the possibility of severe coronary atherosclerosis. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  6. Calcium ferrite formation from the thermolysis of calcium tris (maleato)

    Indian Academy of Sciences (India)

    stoichiometric quantities of aqueous solutions of calcium maleate, iron(III) maleate and maleic acid. The reaction mixture was concentrated on a water bath until a brown coloured product formed after the addition of excess of acetone. The complex was vacuum dried and its identity was established by chemical analysis.

  7. Calcium ferrite formation from the thermolysis of calcium tris ...

    Indian Academy of Sciences (India)

    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 ...

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

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

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

  9. Calcium fertilization increases the concentration of calcium in sapwood and calcium oxalate in foliage of red spruce

    Science.gov (United States)

    Kevin T. Smith; Walter C. Shortle; Jon H. Connolly; Rakesh Minocha; Jody Jellison

    2009-01-01

    Calcium cycling plays a key role in the health and productivity of red spruce forests in the northeastern US. A portion of the flowpath of calcium within forests includes translocation as Ca2+ in sapwood and accumulation as crystals of calcium oxalate in foliage. Concentrations of Ca in these tree tissues have been used as markers of...

  10. Calcium release from experimental dental materials.

    Science.gov (United States)

    Okulus, Zuzanna; Buchwald, Tomasz; Voelkel, Adam

    2016-11-01

    The calcium release from calcium phosphate-containing experimental dental restorative materials was examined. The possible correlation of ion release with initial calcium content, solubility and degree of curing (degree of conversion) of examined materials was also investigated. Calcium release was measured with the use of an ion-selective electrode in an aqueous solution. Solubility was established by the weighing method. Raman spectroscopy was applied for the determination of the degree of conversion, while initial calcium content was examined with the use of energy-dispersive spectroscopy. For examined materials, the amount of calcium released was found to be positively correlated with solubility and initial calcium content. It was also found that the degree of conversion does not affect the ability of these experimental composites to release calcium ions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 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...

  12. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... Bone Health Featured Resource Find an Endocrinologist Search Vitamin D, Calcium, and Bone Health March 2012 Download ... also helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin ...

  13. Safety of calcium dobesilate in chronic venous disease, diabetic retinopathy and haemorrhoids.

    Science.gov (United States)

    Allain, Hervé; Ramelet, Albert A; Polard, Elisabeth; Bentué-Ferrer, Danièle

    2004-01-01

    The aim of the present review is to consider the adverse effects and the safety profile of calcium dobesilate. Calcium dobesilate (Doxium) is a veno-tonic drug, which is widely prescribed in more than 60 countries from Europe, Latin America, Asia and the Middle East for three main indications: chronic venous disease, diabetic retinopathy and the symptoms of haemorrhoidal attack. Data sources used for this review comprise the international literature (1970-2003), a postmarketing surveillance (PMS) report for calcium dobesilate from OM Pharma (Geneva, Switzerland) covering the period 1974-1998, and periodic safety update reports (PSUR) covering the period 1995-2003 from the French Regulatory authorities pharmacovigilance database and OM Pharma. Data from the PMS report for 1974-1998 indicated that adverse events with calcium dobesilate did not occur very frequently and had the following distribution in terms of frequency: fever (26%), gastrointestinal disorders (12.5%), skin reactions (8.2%), arthralgia (4.3%), and agranulocytosis (4.3%). No deaths were attributed to calcium dobesilate in the PMS report. Using data on product use in the Swiss Compendium we estimated the prevalence of agranulocytosis to be 0.32 cases/million treated patients, i.e. ten times less than the calculated prevalence of agranulocytosis in the general population. Most adverse events are type B, i.e. rare and unrelated to the pharmacological properties of calcium dobesilate. This review concludes that the risk of an adverse effect with calcium dobesilate 500-1500 mg/day is low and constant over time. The recently raised problem of agranulocytosis (a total of 13 known cases drawn from all data sources) appears to be related to methodological bias. Such a review reinforces the need for a strong international pharmacovigilance organisation using similar methods to detect and analyse the adverse effects of drugs.

  14. 21 CFR 184.1229 - Calcium stearate.

    Science.gov (United States)

    2010-04-01

    ... Specific Substances Affirmed as GRAS § 184.1229 Calcium stearate. (a) Calcium stearate (Ca(C17H35COO)2, CAS Reg. No. 1529-23-0) is the calcium salt of stearic acid derived from edible sources. It is prepared as... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium stearate. 184.1229 Section 184.1229 Food...

  15. Bioactive and Hemocompatible Calcium Sulphoaluminate Cement

    OpenAIRE

    Acuña-Gutiérrez, Iván Omar; Escobedo-Bocardo, José Concepción; Almanza-Robles, José Manuel; Cortés-Hernández, Dora Alicia; Saldívar-Ramírez, Mirna María Guadalupe; Reséndiz-Hernández, Perla Janet; Zugasti-Cruz, Alejandro

    2015-01-01

    Calcium sulphoaluminate cement (CSAC) is an attractive candidate for biomedical applications due to its appropriate mechanical properties and high calcium content. In vitro bioactivity and hemocompatibility of calcium sulphoaluminate cement were assessed. The cement was prepared from a mixture of calcium sulphoaluminate (CSA) clinker, gypsum and water. Cement samples were immersed in a simulated body fluid (SBF) at 37 °C for different periods of time (7, 14 and 21 days). The analyses of these...

  16. Calcium Balance in Chronic Kidney Disease

    OpenAIRE

    Hill Gallant, Kathleen M.; Spiegel, David M.

    2017-01-01

    Purpose of Review The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balan...

  17. Calcium Balance in Chronic Kidney Disease.

    Science.gov (United States)

    Hill Gallant, Kathleen M; Spiegel, David M

    2017-06-01

    The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

  18. 22 CFR 204.43 - Governing law.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 204.43 Section 204.43 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Administration § 204.43 Governing law. This Guaranty shall be governed by and construed in accordance with the laws of...

  19. 22 CFR 221.43 - Governing law.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 221.43 Section 221.43 Foreign... Administration § 221.43 Governing law. This Guarantee shall be governed by and construed in accordance with the laws of the United States of America governing contracts and commercial transactions of the United...

  20. 28 CFR 550.43 - Drug counseling.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Drug counseling. 550.43 Section 550.43... Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.43 Drug counseling. (a) Drug counseling shall be provided to sentenced inmates in contract community treatment...

  1. 40 CFR 75.43 - Accessibility criteria.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Accessibility criteria. 75.43 Section 75.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Alternative Monitoring Systems § 75.43 Accessibility criteria. To demonstrate...

  2. 15 CFR 990.43 - Data collection.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Data collection. 990.43 Section 990.43... DAMAGE ASSESSMENTS Preassessment Phase § 990.43 Data collection. Trustees may conduct data collection and analyses that are reasonably related to Preassessment Phase activities. Data collection and analysis during...

  3. 46 CFR 167.43-10 - Use.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Use. 167.43-10 Section 167.43-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Work Vests § 167.43-10 Use. (a) Approved buoyant work vests are considered to be items of safety apparel and may be...

  4. 10 CFR 436.43 - Procurement planning.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Procurement planning. 436.43 Section 436.43 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Agency Procurement of Energy Efficient Products § 436.43 Procurement planning. (a) Agencies should consider the...

  5. 19 CFR 201.43 - Program.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Program. 201.43 Section 201.43 Customs Duties... Information § 201.43 Program. The Director of Administration is designated as the official of the Commission who is responsible for implementation and oversight of information security programs and procedures...

  6. 14 CFR 33.43 - Vibration test.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Vibration test. 33.43 Section 33.43... STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.43 Vibration test. (a) Each engine must undergo a vibration survey to establish the torsional and bending vibration characteristics...

  7. 14 CFR 47.43 - Invalid registration.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Invalid registration. 47.43 Section 47.43... REGISTRATION Certificates of Aircraft Registration § 47.43 Invalid registration. (a) The registration of an...) compliance with 49 U.S.C. 44101-44104. (b) If the registration of an aircraft is invalid under paragraph (a...

  8. 16 CFR 4.3 - Time.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Time. 4.3 Section 4.3 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE MISCELLANEOUS RULES § 4.3 Time. (a) Computation. Computation of any period of time prescribed or allowed by the rules in this chapter, by order of...

  9. 32 CFR 2700.43 - Reproduction controls.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Reproduction controls. 2700.43 Section 2700.43... SECURITY INFORMATION REGULATIONS Safeguarding § 2700.43 Reproduction controls. OMSN and SLNO shall maintain records to show the number and distribution of all OMSN originated classified documents. Reproduction of...

  10. 7 CFR 956.43 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 956.43 Section 956.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... VALLEY OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Expenses and Assessments § 956.43 Accounting. (a) All...

  11. 7 CFR 955.43 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 955.43 Section 955.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Expenses and Assessments § 955.43 Accounting. (a) All funds received by the committee pursuant to the...

  12. 7 CFR 959.43 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 959.43 Section 959.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Expenses and Assessments § 959.43 Accounting. (a) Assessments collected in excess of...

  13. 7 CFR 945.43 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 945.43 Section 945.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Assessments § 945.43 Accounting. (a) All funds received by the committee pursuant to the provisions of this...

  14. 7 CFR 966.43 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 966.43 Section 966.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Expenses and Assessments § 966.43 Accounting. (a) All funds received by the committee...

  15. 37 CFR 2.43 - Service mark.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Service mark. 2.43 Section 2.43 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES The Written Application § 2.43 Service mark. In an...

  16. 28 CFR 544.43 - Incentives.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Incentives. 544.43 Section 544.43... Mandatory English-as-a-Second Language Program (ESL) § 544.43 Incentives. The Warden or designee shall establish a system of incentives to encourage an inmate to meet the mandatory ESL program requirements. ...

  17. 19 CFR 146.43 - Domestic status.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Domestic status. 146.43 Section 146.43 Customs... (CONTINUED) FOREIGN TRADE ZONES Status of Merchandise in a Zone § 146.43 Domestic status. (a) General. Domestic status may be granted to merchandise: (1) The growth, product, or manufacture of the U.S. on which...

  18. 21 CFR 20.43 - Multitrack processing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Multitrack processing. 20.43 Section 20.43 Food... INFORMATION Procedures and Fees § 20.43 Multitrack processing. (a) Each Food and Drug Administration component... maintained by that component. A multitrack system provides two or more tracks for processing requests, based...

  19. 12 CFR 303.43 - Processing.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Processing. 303.43 Section 303.43 Banks and... Establishment and Relocation of Domestic Branches and Offices § 303.43 Processing. (a) Expedited processing for... processing, unless the applicant is notified in writing to the contrary and provided with the basis for that...

  20. 25 CFR 43.3 - Student rights.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Student rights. 43.3 Section 43.3 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MAINTENANCE AND CONTROL OF STUDENT RECORDS IN BUREAU SCHOOLS § 43.3 Student rights. The regulations in this part do not prevent educational institutions from...

  1. Electrochemical Induced Calcium Phosphate Precipitation

    NARCIS (Netherlands)

    Lei, Yang; Song, Bingnan; Weijden, van der Renata D.; Saakes, M.; Buisman, Cees J.N.

    2017-01-01

    Phosphorus (P) is an essential nutrient for living organisms and cannot be replaced or substituted. In this paper, we present a simple yet efficient membrane free electrochemical system for P removal and recovery as calcium phosphate (CaP). This method relies on in situ formation of hydroxide

  2. 21 CFR 582.7187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

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

  3. Abnormalities of serum calcium and magnesium

    Science.gov (United States)

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

  4. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    When there is an extracellular change, cells get the message either by introduction of calcium ions into ... as it precipitates phosphate, the established energy currency of cells. Prolonged high intracellular calcium ... trigger proteins upon binding with free calcium ion(s) change their confirmation to modulate enzymes and ion ...

  5. 21 CFR 582.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... Additives § 582.1191 Calcium carbonate. (a) Product. Calcium carbonate. (b) Conditions of use. This... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium carbonate. 582.1191 Section 582.1191 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  6. 21 CFR 582.5191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... Supplements 1 § 582.5191 Calcium carbonate. (a) Product. Calcium carbonate. (b) Conditions of use. This... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium carbonate. 582.5191 Section 582.5191 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  7. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

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

  8. Mitochondrial Calcium Sparkles Light Up Astrocytes.

    Science.gov (United States)

    MacVicar, Brian A; Ko, Rebecca W Y

    2017-02-27

    Discrete calcium signals in the fine processes of astrocytes are a recent discovery and a new mystery. In a recent issue of Neuron, Agarwal et al. (2017) report that calcium efflux from mitochondria during brief openings of the mitochondrial permeability transition pore (mPTP) contribute to calcium microdomains. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  9. 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). (b...

  10. 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). (b...

  11. ORIGINAL ARTICLES Calcium supplementation to prevent pre ...

    African Journals Online (AJOL)

    ORIGINAL ARTICLES. Calcium supplementation to prevent pre-eclampsia - a systematic review. G J Hofmeyr, A Roodt, A N Atallah, L Duley. Background. Calcium supplementation during pregnancy may prevent high blood pressure and preterm labour. Objective. To assess the effects of calcium supplementation.

  12. Calcium Orthophosphate-Based Bioceramics

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2013-09-01

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

  13. Calcium antagonists: a ready prescription for treating infectious diseases?

    Science.gov (United States)

    Clark, Kevin B; Eisenstein, Edward M; Krahl, Scott E

    2013-01-01

    Emergence of new and medically resistant pathogenic microbes continues to escalate toward worldwide public health, wild habitat, and commercial crop and livestock catastrophes. Attempts at solving this problem with sophisticated modern biotechnologies, such as smart vaccines and microbicidal and microbistatic drugs that precisely target parasitic bacteria, fungi, and protozoa, remain promising without major clinical and industrial successes. However, discovery of a more immediate, broad spectrum prophylaxis beyond conventional epidemiological approaches might take no longer than the time required to fill a prescription at your neighborhood pharmacy. Findings from a growing body of research suggest calcium antagonists, long approved and marketed for various human cardiovascular and neurological indications, may produce safe, efficacious antimicrobial effects. As a general category of drugs, calcium antagonists include compounds that disrupt passage of Ca(2+) molecules across cell membranes and walls, sequestration and mobilization of free intracellular Ca(2+), and downstream binding proteins and sensors of Ca(2+)-dependent regulatory pathways important for proper cell function. Administration of calcium antagonists alone at current therapeutically relevant doses and schedules, or with synergistic compounds and additional antimicrobial medications, figures to enhance host immunoprotection by directly altering pathogen infection sequences, life cycles, homeostasis, antibiotic tolerances, and numerous other infective, survival, and reproductive processes. Short of being miracle drugs, calcium antagonists are welcome old drugs with new tricks capable of controlling some of the most virulent and pervasive global infectious diseases of plants, animals, and humans, including Chagas' disease, malaria, and tuberculosis.

  14. Calcium sensing receptor signalling in physiology and cancer.

    Science.gov (United States)

    Brennan, Sarah C; Thiem, Ursula; Roth, Susanne; Aggarwal, Abhishek; Fetahu, Irfete Sh; Tennakoon, Samawansha; Gomes, Ana Rita; Brandi, Maria Luisa; Bruggeman, Frank; Mentaverri, Romuald; Riccardi, Daniela; Kallay, Enikö

    2013-07-01

    The calcium sensing receptor (CaSR) is a class C G-protein-coupled receptor that is crucial for the feedback regulation of extracellular free ionised calcium homeostasis. While extracellular calcium (Ca(2+)o) is considered the primary physiological ligand, the CaSR is activated physiologically by a plethora of molecules including polyamines and l-amino acids. Activation of the CaSR by different ligands has the ability to stabilise unique conformations of the receptor, which may lead to preferential coupling of different G proteins; a phenomenon termed 'ligand-biased signalling'. While mutations of the CaSR are currently not linked with any malignancies, altered CaSR expression and function are associated with cancer progression. Interestingly, the CaSR appears to act both as a tumour suppressor and an oncogene, depending on the pathophysiology involved. Reduced expression of the CaSR occurs in both parathyroid and colon cancers, leading to loss of the growth suppressing effect of high Ca(2+)o. On the other hand, activation of the CaSR might facilitate metastasis to bone in breast and prostate cancer. A deeper understanding of the mechanisms driving CaSR signalling in different tissues, aided by a systems biology approach, will be instrumental in developing novel drugs that target the CaSR or its ligands in cancer. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 43rd Aerospace Mechanisms Symposium

    Science.gov (United States)

    Boesiger, Edward A.

    2016-01-01

    The Aerospace Mechanisms Symposium (AMS) provides a unique forum for those active in the design, production and use of aerospace mechanisms. A major focus is the reporting of problems and solutions associated with the development and flight certification of new mechanisms. Sponsored and organized by the Mechanisms Education Association, responsibility for hosting the AMS is shared by the National Aeronautics and Space Administration and Lockheed Martin Space Systems Company (LMSSC). Now in its 43rd symposium, the AMS continues to be well attended, attracting participants from both the U.S. and abroad. The 43rd AMS was held in Santa Clara, California on May 4, 5 and 6, 2016. During these three days, 42 papers were presented. Topics included payload and positioning mechanisms, components such as hinges and motors, CubeSats, tribology, and mechanism testing. Hardware displays during the supplier exhibit gave attendees an opportunity to meet with developers of current and future mechanism components. The high quality of this symposium is a result of the work of many people, and their efforts are gratefully acknowledged. This extends to the voluntary members of the symposium organizing committee representing the eight NASA field centers, LMSSC, and the European Space Agency. Appreciation is also extended to the session chairs, the authors, and particularly the personnel at ARC responsible for the symposium arrangements and the publication of these proceedings. A sincere thank you also goes to the symposium executive committee who is responsible for the year-to-year management of the AMS, including paper processing and preparation of the program. The use of trade names of manufacturers in this publication does not constitute an official endorsement of such products or manufacturers, either expressed or implied, by the National Aeronautics and Space Administration.

  16. Calcium and phosphorus supplementation of human milk for preterm infants.

    Science.gov (United States)

    Harding, Jane E; Wilson, Jess; Brown, Julie

    2017-02-26

    data from a single small trial). We found no evidence of a difference between calcium and phosphorus supplementation versus no supplementation for neonatal growth outcomes (weight, length, head circumference) at any time point reported (two, four or six weeks postnatal age). At six weeks postnatal age, supplementation with calcium/phosphorus was associated with a decrease in serum alkaline phosphatase concentration (MD -56.85 IU/L, 95% CI -101.27 to -12.43; one randomised controlled trial (RCT); n = 40 infants). Investigators provided no data on growth at 12 to 18 months, neonatal fractures, feed intolerance, breastfeeding or any of the prespecified childhood outcomes for this review (fractures, growth, neurodevelopmental outcomes). We identified one small trial including only 40 infants that compared supplementation of human milk with calcium and phosphorus versus no supplementation in hospitalised preterm infants. We judged the evidence to be of low quality and found no evidence of differences between groups for clinically important outcomes including growth and fractures. Although serum alkaline phosphatase concentration was reduced in the group receiving supplementation at six weeks postnatal age, this difference is unlikely to be of clinical significance. We conclude that evidence is insufficient to determine whether benefit or harm ensues when human milk is supplemented with calcium and/or phosphorus for the hospitalised preterm infant. We see no advantage of conducting further trials of this intervention because with the advent of multi-component human milk fortifier, supplementation of human milk with calcium and/or phosphorus alone is no longer common practice. Future trials should consider assessing effects of multi-component fortifiers with different mineral compositions on clinically important outcomes during the neonatal period and in later childhood.

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

    OpenAIRE

    Huaigang Cheng; Xiaoxi Zhang; Huiping Song

    2014-01-01

    Ultrafine calcium carbonate is a widely used cheap additive. The research is conducted in low degree supersaturation solution in order to study the polymorphic phases’ change and its factors of the calcium carbonate precipitate in the ammonification-carbonization process of the solution with calcium. Fine particles of calcium carbonate are made in the solution containing 0.015 mol/L of Ca2+. Over 98% of the calcium carbonate precipitate without ammonification resembles the morphology of calci...

  18. Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Richard Francis

    Full Text Available Knockout mice deficient in the gap junction gene connexin43 exhibit developmental anomalies associated with abnormal neural crest, primordial germ cell, and proepicardial cell migration. These migration defects are due to a loss of directional cell movement, and are associated with abnormal actin stress fiber organization and a loss of polarized cell morphology. To elucidate the mechanism by which Cx43 regulates cell polarity, we used a wound closure assays with mouse embryonic fibroblasts (MEFs to examine polarized cell morphology and directional cell movement. Studies using embryonic fibroblasts from Cx43 knockout (Cx43KO mice showed Cx43 deficiency caused cell polarity defects as characterized by a failure of the Golgi apparatus and the microtubule organizing center to reorient with the direction of wound closure. Actin stress fibers at the wound edge also failed to appropriately align, and stabilized microtubule (Glu-tubulin levels were markedly reduced. Forced expression of Cx43 with deletion of its tubulin-binding domain (Cx43dT in both wildtype MEFs and neural crest cell explants recapitulated the cell migration defects seen in Cx43KO cells. However, forced expression of Cx43 with point mutation causing gap junction channel closure had no effect on cell motility. TIRF imaging revealed increased microtubule instability in Cx43KO cells, and microtubule targeting of membrane localized Cx43 was reduced with expression of Cx43dT construct in wildtype cells. Together, these findings suggest the essential role of Cx43 gap junctions in development is mediated by regulation of the tubulin cytoskeleton and cell polarity by Cx43 via a nonchannel function.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-08-22

    Crystallization from amorphous phases is an emerging pathway for making advanced materials. Biology has made use of amorphous precursor phases for eons and used them to produce structures with remarkable properties. Herein, we show how the design of the amorphous phase greatly influences the nanocrystals formed therefrom. We investigate the transformation of mixed amorphous calcium phosphate/amorphous calcium carbonate phases into bone-like nanocrystalline apatite using in situ synchrotron X-ray diffraction and IR spectroscopy. The speciation of phosphate was controlled by pH to favor HPO4 (2-) . In a carbonate free system, the reaction produces anisotropic apatite crystallites with large aspect ratios. The first formed crystallites are highly calcium deficient and hydrogen phosphate rich, consistent with thin octacalcium phosphate (OCP)-like needles. During growth, the crystallites become increasingly stoichiometric, which indicates that the crystallites grow through addition of near-stoichiometric apatite to the OCP-like initial crystals through a process that involves either crystallite fusion/aggregation or Ostwald ripening. The mixed amorphous phases were found to be more stable against phase transformations, hence, the crystallization was inhibited. The resulting crystallites were smaller and less anisotropic. This is rationalized by the idea that a local phosphate-depletion zone formed around the growing crystal until it was surrounded by amorphous calcium carbonate, which stopped the crystallization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    DEFF Research Database (Denmark)

    Tetens, Inge

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

  2. 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

    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 CaV1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (CaV3) 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 (CaV2.2) 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., CaV1.2 and CaV1.3 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 CaV1.3 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, and

  3. Calcium homeostasis is altered in skeletal muscle of spontaneously hypertensive rats: cytofluorimetric and gene expression analysis.

    Science.gov (United States)

    Liantonio, Antonella; Camerino, Giulia M; Scaramuzzi, Antonia; Cannone, Maria; Pierno, Sabata; De Bellis, Michela; Conte, Elena; Fraysse, Bodvael; Tricarico, Domenico; Conte Camerino, Diana

    2014-10-01

    Hypertension is often associated with skeletal muscle pathological conditions related to function and metabolism. The mechanisms underlying the development of these pathological conditions remain undefined. Because calcium homeostasis is a biomarker of muscle function, we assessed whether it is altered in hypertensive muscles. We measured resting intracellular calcium and store-operated calcium entry (SOCE) in fast- and slow-twitch muscle fibers from normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) by cytofluorimetric technique and determined the expression of SOCE gene machinery by real-time PCR. Hypertension caused a phenotype-dependent dysregulation of calcium homeostasis; the resting intracellular calcium of extensor digitorum longus and soleus muscles of SHRs were differently altered with respect to the related muscle of normotensive animals. In addition, soleus muscles of SHR showed reduced activity of the sarcoplasmic reticulum and decreased sarcolemmal calcium permeability at rest and after SOCE activation. Accordingly, we found an alteration of the expression levels of some SOCE components, such as stromal interaction molecule 1, calcium release-activated calcium modulator 1, and transient receptor potential canonical 1. The hypertension-induced alterations of calcium homeostasis in the soleus muscle of SHRs occurred with changes of some functional outcomes as excitability and resting chloride conductance. We provide suitable targets for therapeutic interventions aimed at counterbalancing muscle performance decline in hypertension, and propose the reported calcium-dependent parameters as indexes to predict how the antihypertensive drugs could influence muscle function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. The Calcium Wave of Vegetable Cells

    Directory of Open Access Journals (Sweden)

    TD. Geydan

    2007-08-01

    Full Text Available Calcium is an essential nutrient for plants; it is involved in developmental processes and in responses to biotic and abiotic factors. Several signals that modify the calcium concentration in the cytoplasm, endoplasmic reticulum, nucleus and/or plastids have been observed. These changes in the calcium concentration in the cell interior are rapidly returned to basal levels, in the meantime, innumerable and complex signaling cascades. This note exposes the mechanisms of calcium transport through the cell membranes of the entrance of calcium in the plant cells.

  6. Calcium intake in the United States from dietary and supplemental sources across adult age groups: new estimates from the National Health and Nutrition Examination Survey 2003-2006.

    Science.gov (United States)

    Mangano, Kelsey M; Walsh, Stephen J; Insogna, Karl L; Kenny, Anne M; Kerstetter, Jane E

    2011-05-01

    Adequate lifelong calcium intake is essential in optimizing bone health. Recent National Health and Nutrition Examination Survey data were used to quantify variation in calcium intake across adult age groups and to relate age-associated changes in calcium intake with energy intake. Additional goals were to assess differences in dietary calcium intake between supplemental calcium users and nonusers and to evaluate associations between age and calcium density in the diet. This cross-sectional analysis determined calcium and energy intake for National Health and Nutrition Examination Survey respondents during 2003-2006. Diet was assessed with 24-hour recall and supplement use via questionnaire. Trends in median intakes for dietary calcium, total calcium, and energy across age categories were assessed using survey analysis methods. Nutrient density was represented using calcium to energy intake ratios. The analyses included data from 9,475 adults. When compared to the 19- to 30-year age group, median dietary calcium intake was lower in the ≥81-year age group by 23% in men (Pcalcium supplement use increased (Pcalcium intake was greater than in nonusers (P=0.02). Calcium density in the diet significantly increased relative to age in men and women (Pcalcium to energy ratios were insufficient to meet target ratios inferred by adequate intake standards after age 50 years. Although supplemental calcium use and calcium density were highest in older age groups, they were not sufficient in meeting recommended levels. New approaches to increasing the frequency and level of calcium supplement use to enhance calcium density in diets may be necessary to reduce osteoporosis risk among older Americans. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  7. 43 CFR 43.105 - Does this part apply to me?

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Does this part apply to me? 43.105 Section 43.105 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Purpose and Coverage § 43.105 Does this part apply to me? (a...

  8. TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury.

    Science.gov (United States)

    Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K; Cario, Elke

    2009-08-14

    Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1alpha-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.

  9. Calcium Intake in the Moroccan Elderly

    Directory of Open Access Journals (Sweden)

    Sebbar El-houcine

    2017-08-01

    Full Text Available Introduction: Calcium intakes of elderly people are often below the recommendations which are 1200 mg/day. The advancing age may be accompanied by a loss of capacity to absorb additional calcium in case of deficiency. The aim of our work is to evaluate the calcium intake in the Moroccan elderly. Methods: The version translated into Arabic dialect Fardellone questionnaire is tested on a sample of 159 subjects aged over 60 years. Results: The study population includes 87 women (55%, 72 men (45%. The mean calcium intake was respectively 3078 mg by week (that means 440 mg/day. The assessment of calcium intake showed a deficiency and the average consumption of calcium per day is significantly lower than the recommended daily amount for this population. The comparison of both gender found a deficit higher among women than among men. Conclusion: Evaluation of the calcium intake is an essential tool for better management of metabolic bone diseases.

  10. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

    Calcium is one of the several elements that can be found in milk distributed between the micellar and the serum milk phase. Calcium is important from a nutritional point of view, but its contribution to the functional and structural properties of dairy products has only recently been...... acknowledgement. The presence of calcium in a dynamic equilibrium between the serum and the micellar milk phase make the distribution susceptible to certain physicochemical conditions and to technological treatments of milk resulting in fluctuations in pH and temperature and also sensitive to addition of calcium...... 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...

  11. 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.

  12. Exopolysaccharides regulate calcium flow in cariogenic biofilms.

    Science.gov (United States)

    Astasov-Frauenhoffer, Monika; Varenganayil, Muth M; Decho, Alan W; Waltimo, Tuomas; Braissant, Olivier

    2017-01-01

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

  13. Exopolysaccharides regulate calcium flow in cariogenic biofilms.

    Directory of Open Access Journals (Sweden)

    Monika Astasov-Frauenhoffer

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

  14. Calcium precipitate induced aerobic granulation.

    Science.gov (United States)

    Wan, Chunli; Lee, Duu-Jong; Yang, Xue; Wang, Yayi; Wang, Xingzu; Liu, Xiang

    2015-01-01

    Aerobic granulation is a novel biotechnology for wastewater treatment. This study refined existing aerobic granulation mechanisms as a sequencing process including formation of calcium precipitate under alkaline pH to form inorganic cores, followed by bacterial attachment and growth on these cores to form the exopolysaccharide matrix. Mature granules comprised an inner core and a matrix layer and a rim layer with enriched microbial strains. The inorganic core was a mix of different crystals of calcium and phosphates. Functional strains including Sphingomonas sp., Paracoccus sp. Sinorhizobium americanum strain and Flavobacterium sp. attached onto the cores. These functional strains promote c-di-GMP production and the expression by Psl and Alg genes for exopolysaccharide production to enhance formation of mature granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Connexin 43 impacts on mitochondrial potassium uptake

    Directory of Open Access Journals (Sweden)

    Kerstin eBoengler

    2013-06-01

    Full Text Available In cardiomyocytes, connexin 43 (Cx43 forms gap junctions and unopposed hemichannels at the plasma membrane, but the protein is also present at the inner membrane of subsarcolemmal mitochondria. Both inhibition and genetic ablation of Cx43 reduce ADP-stimulated complex 1 respiration. Since mitochondrial potassium influx impacts on oxygen consumption, we investigated whether or not inhibition or ablation of mitochondrial Cx43 alters mitochondrial potassium uptake.Subsarcolemmal mitochondria were isolated from rat left ventricular (LV myocardium and loaded with the potassium-sensitive dye PBFI. Intramitochondrial potassium was replaced by TEA (tetraethylammonium. Mitochondria were incubated under control conditions or treated with 250 µM Gap19, a peptide that specifically inhibits Cx43-dependent hemichannels at plasma membranes. Subsequently, 140 mM KCl was added and the slope of the increase in PBFI fluorescence over time was calculated. The slope of the PBFI fluorescence of the control mitochondria was set to 100%. In the presence of Gap19, the mitochondrial potassium influx was reduced from 100±11.6 % in control mitochondria to 65.5±10.7 % (n=6, p<0.05. In addition to the pharmacological inhibition of Cx43, potassium influx was studied in mitochondria isolated from conditional Cx43 knockout mice. Here, the ablation of Cx43 was achieved by the injection of 4-hydroxytamoxifen (Cx43Cre-ER(T/fl + 4-OHT. The mitochondria of the Cx43Cre-ER(T/fl + 4-OHT mice contained 3±1% Cx43 (n=6 of that in control mitochondria (100±11%, n=8, p<0.05. The ablation of Cx43 (n=5 reduced the velocity of the potassium influx from 100±11.2 % in control mitochondria (n=9 to 66.6±5.5 % (p<0.05.Taken together, our data indicate that both pharmacological inhibition and genetic ablation of Cx43 reduce mitochondrial potassium influx.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-04-17

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

  18. 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...... higher urinary calcium excretion than female mice and their renal calcium transporters were expressed at a lower level. We also found that orchidectomized mice excreted less calcium in their urine than sham-operated control mice and that the hypocalciuria was normalized after testosterone replacement...... calcium transport. Thus, our study shows that gender differences in renal calcium handling are, in part, mediated by the inhibitory actions of androgens on TRPV5-mediated active renal calcium transport....

  19. A Closer look at calcium absorption and the benefits and risks of dietary versus supplemental calcium.

    Science.gov (United States)

    Booth, Anna; Camacho, Pauline

    2013-11-01

    To perform a thorough search of the literature on calcium research and specifically address the topic of calcium absorption. PubMed and Ovid were the main engines used for primary literature searches; textbooks, review articles, and book chapters are examples of the other sources used for supplemental information. Regarding calcium absorption, it seems apparent that the absorption efficiency of all calcium salts, regardless of solubility, is fairly equivalent and not significantly less than the absorption efficiency of dietary calcium. However, dietary calcium has been shown to have greater impact in bone building than supplemental calcium. This is likely due to improved absorption with meals and the tendency of people to intake smaller amounts more frequently, which is more ideal for the body's method of absorption. In addition, the cardiovascular risks of excessive calcium intake appear to be more closely related to calcium supplements than dietary calcium; this relationship continues to be controversial in the literature. We conclude that further studies are needed for direct comparison of supplemental and dietary calcium to fully establish if one is superior to the other with regard to improving bone density. We also propose further studies on the cardiovascular risk of long-term increased calcium intake and on physician estimates of patients' daily calcium intake to better pinpoint those patients who require calcium supplementation.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

  2. Presenilin-mediated modulation of capacitative calcium entry.

    Science.gov (United States)

    Yoo, A S; Cheng, I; Chung, S; Grenfell, T Z; Lee, H; Pack-Chung, E; Handler, M; Shen, J; Xia, W; Tesco, G; Saunders, A J; Ding, K; Frosch, M P; Tanzi, R E; Kim, T W

    2000-09-01

    We studied a novel function of the presenilins (PS1 and PS2) in governing capacitative calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores. Abrogation of functional PS1, by either knocking out PS1 or expressing inactive PS1, markedly potentiated CCE, suggesting a role for PS1 in the modulation of CCE. In contrast, familial Alzheimer's disease (FAD)-linked mutant PS1 or PS2 significantly attenuated CCE and store depletion-activated currents. While inhibition of CCE selectively increased the amyloidogenic amyloid beta peptide (Abeta42), increased accumulation of the peptide had no effect on CCE. Thus, reduced CCE is most likely an early cellular event leading to increased Abeta42 generation associated with FAD mutant presenilins. Our data indicate that the CCE pathway is a novel therapeutic target for Alzheimer's disease.

  3. Increased Calcium Supplementation Postpartum Is Associated with Breastfeeding among Chinese Mothers: Finding from Two Prospective Cohort Studies.

    Science.gov (United States)

    Zhao, Jian; Zhao, Yun; Binns, Colin W; Lee, Andy H

    2016-10-09

    The calcium supplementation status during the postpartum period among Chinese lactating women is still unclear. The objective of this study is to utilize data from two population-based prospective cohort studies to examine the calcium supplementation status and to identify whether breastfeeding is associated with increased calcium supplementation among Chinese mothers after child birth. Information from 1540 mothers on breastfeeding and calcium supplementation measured at discharge, 1, 3, and 6 months postpartum were extracted to evaluate the association between breastfeeding and calcium supplementation postpartum. A generalized linear mixed model was applied to each study initially to account for the inherent correlation among repeated measurements, adjusting for socio-demographic, obstetric factors and calcium supplementation during pregnancy. In addition, breastfeeding status measured at different follow-up time points was treated as a time dependent variable in the longitudinal analysis. Furthermore, the effect sizes of the two cohort studies were pooled using fixed effect model. Based on the two cohort studies, the pooled likelihood of taking calcium supplementation postpartum among breastfeeding mothers was 4.02 times (95% confidence interval (2.30, 7.03)) higher than that of their non-breastfeeding counterparts. Dietary supplementation intervention programs targeting different subgroups should be promoted in Chinese women, given currently a wide shortage of dietary calcium intake and calcium supplementation postpartum.

  4. Cross-talk between ROS and calcium in regulation of nuclear activities.

    Science.gov (United States)

    Mazars, Christian; Thuleau, Patrice; Lamotte, Olivier; Bourque, Stéphane

    2010-07-01

    Calcium and Reactive Oxygen Species (ROS) are acknowledged as crucial second messengers involved in the response to various biotic and abiotic stresses. However, it is still not clear how these two compounds can play a role in different signaling pathways leading the plant to a variety of processes such as root development or defense against pathogens. Recently, it has been shown that the concept of calcium and ROS signatures, initially discovered in the cytoplasm, can also be extended to the nucleus of plant cells. In addition, it has been clearly proved that both ROS and calcium signals are intimately interconnected. How this cross-talk can finally modulate the translocation and/or the activity of nuclear proteins leading to the control of specific genes expression is the main focus of this review. We will especially focus on how calcium and ROS interact at the molecular level to modify their targets.

  5. Alternative Splicing at C Terminus of CaV1.4 Calcium Channel Modulates Calcium-dependent Inactivation, Activation Potential, and Current Density

    Science.gov (United States)

    Tan, Gregory Ming Yeong; Yu, Dejie; Wang, Juejin; Soong, Tuck Wah

    2012-01-01

    The CaV1.4 voltage-gated calcium channel is predominantly expressed in the retina, and mutations to this channel have been associated with human congenital stationary night blindness type-2. The L-type CaV1.4 channel displays distinct properties such as absence of calcium-dependent inactivation (CDI) and slow voltage-dependent inactivation (VDI) due to the presence of an autoinhibitory domain (inhibitor of CDI) in the distal C terminus. We hypothesized that native CaV1.4 is subjected to extensive alternative splicing, much like the other voltage-gated calcium channels, and employed the transcript scanning method to identify alternatively spliced exons within the CaV1.4 transcripts isolated from the human retina. In total, we identified 19 alternative splice variations, of which 16 variations have not been previously reported. Characterization of the C terminus alternatively spliced exons using whole-cell patch clamp electrophysiology revealed a splice variant that exhibits robust CDI. This splice variant arose from the splicing of a novel alternate exon (43*) that can be found in 13.6% of the full-length transcripts screened. Inclusion of exon 43* inserts a stop codon that truncates half the C terminus. The CaV1.4 43* channel exhibited robust CDI, a larger current density, a hyperpolarized shift in activation potential by ∼10 mV, and a slower VDI. Through deletional experiments, we showed that the inhibitor of CDI was responsible for modulating channel activation and VDI, in addition to CDI. Calcium currents in the photoreceptors were observed to exhibit CDI and are more negatively activated as compared with currents elicited from heterologously expressed full-length CaV1.4. Naturally occurring alternative splice variants may in part contribute to the properties of the native CaV1.4 channels. PMID:22069316

  6. Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin.

    Science.gov (United States)

    Bahls, F H; Ozuna, J; Ritchie, D E

    1991-05-01

    We describe a retrospective analysis of the frequency of adverse interactions between calcium channel blockers and anticonvulsant drugs (phenytoin and carbamazepine) in a series of 43 patients. Ten patients receiving carbamazepine and three patients receiving phenytoin exhibited symptoms or signs of toxicity. Toxicity occurred with both diltiazem and verapamil, but not with nifedipine. These results emphasize the need for careful clinical and laboratory monitoring of patients receiving both classes of medication.

  7. 26 CFR 43.4472-1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Definitions. 43.4472-1 Section 43.4472-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX ON TRANSPORTATION BY WATER § 43.4472-1 Definitions. (a) In general. For definitions of the terms “covered voyage” and “passenger vessel,...

  8. The Role of Calcium in Osteoporosis

    Science.gov (United States)

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

    1991-01-01

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

  9. Assessment of calcium intake by adolescents

    Directory of Open Access Journals (Sweden)

    Cristiane Franco de Oliveira

    2014-06-01

    Full Text Available OBJECTIVE: To evaluate the daily calcium intake of adolescents in schools from Chapecó, Santa Catarina, Southern Brazil, to check if calcium intake is in accordance with the Dietary Reference Intakes (DRI, and to investigate variables associated with daily calcium intake.METHODS: Cross-sectional study approved by the Institutional Review Board and developed in 2010. Students of the 8th grade completed questionnaires with personal data and questions about the calcium-rich foods intake frequency. In order to compare students with adequate (1300mg or inadequate intake of calcium/day (<1300mg, parametric and nonparametric tests were used.RESULTS: A total of 214 students with a mean age of 14.3±1.0 years were enrolled. The median daily calcium intake was 540mg (interquartile range - IQ: 312-829mg and only 25 students (11.7% had calcium intake within the recommendations of the DRI for age. Soft drink consumption ≥3 times/week was associated with a lower intake of calcium.CONCLUSIONS: Few students ingested adequate levels of calcium for the age group. It is necessary to develop a program to encourage a greater intake of calcium-rich foods in adolescence.

  10. The Risks and Benefits of Calcium Supplementation

    Directory of Open Access Journals (Sweden)

    Chan Soo Shin

    2015-03-01

    Full Text Available The association between calcium supplementation and adverse cardiovascular events has recently become a topic of debate due to the publication of two epidemiological studies and one meta-analysis of randomized controlled clinical trials. The reports indicate that there is a significant increase in adverse cardiovascular events following supplementation with calcium; however, a number of experts have raised several issues with these reports such as inconsistencies in attempts to reproduce the findings in other populations and questions concerning the validity of the data due to low compliance, biases in case ascertainment, and/or a lack of adjustment. Additionally, the Auckland Calcium Study, the Women's Health Initiative, and many other studies included in the meta-analysis obtained data from calcium-replete subjects and it is not clear whether the same risk profile would be observed in populations with low calcium intakes. Dietary calcium intake varies widely throughout the world and it is especially low in East Asia, although the risk of cardiovascular events is less prominent in this region. Therefore, clarification is necessary regarding the occurrence of adverse cardiovascular events following calcium supplementation and whether this relationship can be generalized to populations with low calcium intakes. Additionally, the skeletal benefits from calcium supplementation are greater in subjects with low calcium intakes and, therefore, the risk-benefit ratio of calcium supplementation is likely to differ based on the dietary calcium intake and risks of osteoporosis and cardiovascular diseases of various populations. Further studies investigating the risk-benefit profiles of calcium supplementation in various populations are required to develop population-specific guidelines for individuals of different genders, ages, ethnicities, and risk profiles around the world.

  11. TDP-43 protein variants as biomarkers in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Williams, Stephanie M; Khan, Galam; Harris, Brent T; Ravits, John; Sierks, Michael R

    2017-01-25

    TDP-43 aggregates accumulate in individuals affected by amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, representing potential diagnostic and therapeutic targets. Using an atomic force microscopy based biopanning protocol developed in our lab, we previously isolated 23 TDP-43 reactive antibody fragments with preference for human ALS brain tissue relative to frontotemporal dementia, a related neurodegeneration, and healthy samples from phage-displayed single chain antibody fragment (scFv) libraries. Here we further characterize the binding specificity of these different scFvs and identify which ones have promise for detecting ALS biomarkers in human brain tissue and plasma samples. We developed a sensitive capture ELISA for detection of different disease related TDP-43 variants using the scFvs identified from the ALS biopanning. We show that a wide variety of disease selective TDP-43 variants are present in ALS as the scFvs show different reactivity profiles amongst the ALS cases. When assaying individual human brain tissue cases, three scFvs (ALS-TDP6, ALS-TDP10 and ALS-TDP14) reacted with all the ALS cases and 12 others reacted with the majority of the ALS cases, and none of the scFvs reacted with any control samples. When assaying individual human plasma samples, 9 different scFvs reacted with all the sporadic ALS samples and again none of them reacted with any control samples. These 9 different scFvs had different patterns of reactivity with plasma samples obtained from chromosome 9 open reading frame 72 (c9orf72) cases indicating that these familial ALS genetic variants may display different TDP-43 pathology than sporadic ALS cases. These results indicated that a range of disease specific TDP-43 variants are generated in ALS patients with different variants being generated in sporadic and familial cases. We show that a small panel of scFvs recognizing different TDP-43 variants can generate a neuropathological and plasma biomarker

  12. Effects on anionic salts in a pre-partum dairy ration on calcium metabolism

    Directory of Open Access Journals (Sweden)

    C.J. Van Dijk

    2001-07-01

    Full Text Available The effects of anionic salts in the transition diet on serum and urine calcium at calving and on peripartal health, subsequent milk production and fertility performance were studied in a well-managed, high-producing Friesland dairy herd. Over a period of a year, approximately 21 days before the expected date of calving, 28 pre-partum heifers and 44 multiparous dry cows were randomly allocated within parity to 1 of 2 transition diets, designated control and experimental anionic diets. The anionic diet contained the same quantities of the basic transition ration fed to the control group as well as a standard anionic salt mixture containing 118 g NH4Cl, 36 g (NH42SO4 and 68 g MgSO4 (total 222 g per animal per day. This reduced the DCAD to -11.68 mEq/100 g dietary dry matter compared to +13.57 for the control diet. Blood and urine were randomly sampled from 7 to 8 animals within each category within 3 hours post-partum. Serum calcium (total and ionised and creatinine, urine calcium and creatinine and the fractional clearance of calcium were assessed. Relevant clinical, milk production, and fertility data were collected. The total serum calcium (2.07 versus 1.60 mmol/ , serum ionised calcium (1.12 vs 1.02 mmol/ , urine calcium (0.92 vs 0.10 mmol/ and the fractional clearance of calcium (1.88 vs 0.09 % were significantly higher (P <0.01 at calving for multiparous cows fed the anionic diet compared to those fed the control diet. In the primiparous cows there were no significant differences in serumcalcium levels. However, the urine calcium (1.07 vs 0.43 mmol/ and the fractional clearance of calcium was higher (1.75 vs 0.45 % in cows fed the anionic diet (P <0.05 and 0.01 respectively. These results illustrated that there were benefits, although no differences were demonstrated with respect to health, milk production or fertility. The supplementation of diets with anionic salts in the last 2-3 weeks before calving has the potential to significantly

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

    OpenAIRE

    Eder, Anja; Bading, Hilmar

    2007-01-01

    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 nuc...

  14. 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...

  15. Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

    Science.gov (United States)

    Krause, M; Keller, J; Beil, B; van Driel, I; Zustin, J; Barvencik, F; Schinke, T; Amling, M

    2015-03-01

    We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution

  16. Influence of calcium sources on microbially induced calcium carbonate precipitation by Bacillus sp. CR2.

    Science.gov (United States)

    Achal, Varenyam; Pan, Xiangliang

    2014-05-01

    Stimulation of microbially induced calcium carbonate precipitation (MICCP) is likely to be influenced by calcium sources. In order to study such influences, we performed MICCP using Bacillus sp. CR2 in nutrient broth containing urea, supplemented with different calcium sources (calcium chloride, calcium oxide, calcium acetate and calcium nitrate). The experiment lasted 7 days, during which bacterial growth, urease activity, calcite production and pH were measured. Our results showed that calcium chloride is the better calcium source for MICCP process, since it provides higher urease activity and more calcite production. The influences of calcium sources on MICCP were further studied using Fourier transform-infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses. These analyses confirmed that the precipitate formed was CaCO3 and composed of predominantly calcite crystals with a little amount of aragonite and vaterite crystals. The maximum yield of calcite precipitation was achievable with calcium chloride followed by calcium nitrate as a calcium source. The results of present study may be applicable to media preparation during efficient MICCP process.

  17. 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.

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

    Science.gov (United States)

    Eder, Anja; Bading, Hilmar

    2007-01-01

    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. PMID:17663775

  19. Impact of calcium sulphate and calcium carbide on nitrogen use efficiency of wheat in normal and saline sodic soils

    Directory of Open Access Journals (Sweden)

    I.A. Mahmood

    2009-05-01

    Full Text Available pot experiment was conducted to study the effect of calcium as CaSO4 or CaC2 (20 mg Ca kg-1 of soil from each source on N use efficiency of wheat (Triticum aestivum L. var. Inqlab-91 under normal (ECe=0.7 dS m-1, SAR=4.37 and pH=8.1 and saline-sodic soils (ECe=8.7 dS m-1, SAR=21.43 and pH=9.2 in glass house at National Agricultural Research Centre, Islamabad during Kharif season 2007-08. The crop was grown to maturity and data on tillering, plant height, panicle length, grains spike-1, straw and grain yields were recorded at the time of crop harvest. A considerable reduction in plant height (38% and grain yield (44% was observed when grown in saline-sodic soil (ECe=8.7 dS m-1 as compared to normal soil (ECe=0.7 dS m-1 while N application significantly improved plant growth and yield in both conditions. Among the treatments, N application even at lower rate supplemented with calcium as CaSO4, CaC2 or their mixture (1:1 showed better performance than that of straight N application in both soils. A 41 to 53% increase in plant growth and 36 to 44% in grain yield over control (without N were observed through N fertilization at 25 and 50 mg kg-1 of soil supplemented with calcium as CaC2 in salinesodic soil. Similarly, calcium as CaSO4 application also caused a considerable improvement in plant growth (34 to 52% and grain yield (25 to 43%. However, the effect of mixture application of CaSO4 and CaC2 (1:1 on plant growth and yield was comparatively more pronounced for both the soils. Interestingly, lower dose ofN (25 mg kg-1 with calcium as CaC2 alone or in combination with CaSO4 (1:1 supplementation showed statistically equal performance to that of higher dose (N=50 mg kg-1 alone. Tissue Na+ significantly decreased while K+ and Ca2+ concentrations were elevated due to N application along with calcium nutrition. Maximum N uptake and apparent N recovery were revealed from treatments where N was applied @ 50 mg kg-1 soil supplemented with calcium as CaC2

  20. Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis

    Science.gov (United States)

    Khaing, Win; Vallibhakara, Sakda Arj-Ong; Tantrakul, Visasiri; Vallibhakara, Orawin; Rattanasiri, Sasivimol; McEvoy, Mark; Attia, John; Thakkinstian, Ammarin

    2017-01-01

    Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings. PMID:29057843

  1. Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Win Khaing

    2017-10-01

    Full Text Available Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo. Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs of 0.54 (0.41, 0.70, 0.47 (0.24, 0.89 and 0.50 (0.32, 0.78, respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69, 0.43 (0.17, 1.11, and 0.57 (0.30, 1.10, respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%, calcium (31.6% and calcium plus vitamin D (19.6%, respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings.

  2. Induced calcium carbonate precipitation using Bacillus species.

    Science.gov (United States)

    Seifan, Mostafa; Samani, Ali Khajeh; Berenjian, Aydin

    2016-12-01

    Microbially induced calcium carbonate precipitation is an emerging process for the production of self-healing concrete. This study was aimed to investigate the effects and optimum conditions on calcium carbonate biosynthesis. Bacillus licheniformis, Bacillus sphaericus, yeast extract, urea, calcium chloride and aeration were found to be the most significant factors affecting the biomineralization of calcium carbonate. It was noticed that the morphology of microbial calcium carbonate was mainly affected by the genera of bacteria (cell surface properties), the viscosity of the media and the type of electron acceptors (Ca2+). The maximum calcium carbonate concentration of 33.78 g/L was achieved at the optimum conditions This value is the highest concentration reported in the literature.

  3. Calcium excretion in feces of ungulates.

    Science.gov (United States)

    Schryver, H F; Foose, T J; Williams, J; Hintz, H F

    1983-01-01

    1. Fecal excretion of calcium was examined in 122 individual ungulates representing 7 species of Equidae, 3 species of Tapiridae, 3 species of Rhinocerotidae, 2 species of Elephantidae, 2 species of Hippopotamidae, 12 species of Bovidae, 2 species of Cervidae, 3 species of Camellidae and 1 species of Giraffidae. 2. Animals were fed timothy hay, a low calcium diet or alfalfa hay, a high calcium diet. 3. In a few cases oat straw or prairie hay was used instead of timothy hay. 4. Samples of feces were obtained from individuals daily for 4 days following a 20 day dietary equilibration period. 5. Feces of equids, tapirs, rhinoceros and elephants had a lower calcium concentration and a lower Ca/P ratio than feces of ruminants when the animals were fed diets of equivalent calcium content. 6. The findings suggest that the non-ruminant ungulate equids, tapirs, rhinoceros and elephants absorb a larger proportion of dietary calcium than ruminants do.

  4. 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.

  5. WAYS TO CORRECT CALCIUM DEFFICIT AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    N.I. Taibulatov

    2007-01-01

    Full Text Available The article is dedicated to the urgent issue of the pediatrics — calcium deficit among children. The authors provide modern data on the scheme of the normal calcium exchange in the human body. They also review the main diseases related to the disorders of the pho sphorocalcic metabolism, requiring prompt prevention and treatment by calcium based medications. The researchers stress the diseases of the musculoskeletal system, as insufficient calcium, phosphorus and vitamins supply of the child's body chiefly effects the state of the skeletal and muscular tissue. They give recommendations how to use the vitamin and mineral complex to correct calcium deficit.Key words: calcium deficit, diseases of the musculoskeletal system, vitamin and mineral complex, children.

  6. Divergent Phenotypes in Mutant TDP-43 Transgenic Mice Highlight Potential Confounds in TDP-43 Transgenic Modeling

    Science.gov (United States)

    D’Alton, Simon; Altshuler, Marcelle; Cannon, Ashley; Dickson, Dennis W.; Petrucelli, Leonard; Lewis, Jada

    2014-01-01

    The majority of cases of frontotemporal lobar degeneration and amyotrophic lateral sclerosis are pathologically defined by the cleavage, cytoplasmic redistribution and aggregation of TAR DNA binding protein of 43 kDa (TDP-43). To examine the contribution of these potentially toxic mechanisms in vivo, we generated transgenic mice expressing human TDP-43 containing the familial amyotrophic lateral sclerosis-linked M337V mutation and identified two lines that developed neurological phenotypes of differing severity and progression. The first developed a rapid cortical neurodegenerative phenotype in the early postnatal period, characterized by fragmentation of TDP-43 and loss of endogenous murine Tdp-43, but entirely lacking aggregates of ubiquitin or TDP-43. A second, low expressing line was aged to 25 months without a severe neurodegenerative phenotype, despite a 30% loss of mouse Tdp-43 and accumulation of lower molecular weight TDP-43 species. Furthermore, TDP-43 fragments generated during neurodegeneration were not C-terminal, but rather were derived from a central portion of human TDP-43. Thus we find that aggregation is not required for cell loss, loss of murine Tdp-43 is not necessarily sufficient in order to develop a severe neurodegenerative phenotype and lower molecular weight TDP-43 positive species in mouse models should not be inherently assumed to be representative of human disease. Our findings are significant for the interpretation of other transgenic studies of TDP-43 proteinopathy. PMID:24466128

  7. Divergent phenotypes in mutant TDP-43 transgenic mice highlight potential confounds in TDP-43 transgenic modeling.

    Directory of Open Access Journals (Sweden)

    Simon D'Alton

    Full Text Available The majority of cases of frontotemporal lobar degeneration and amyotrophic lateral sclerosis are pathologically defined by the cleavage, cytoplasmic redistribution and aggregation of TAR DNA binding protein of 43 kDa (TDP-43. To examine the contribution of these potentially toxic mechanisms in vivo, we generated transgenic mice expressing human TDP-43 containing the familial amyotrophic lateral sclerosis-linked M337V mutation and identified two lines that developed neurological phenotypes of differing severity and progression. The first developed a rapid cortical neurodegenerative phenotype in the early postnatal period, characterized by fragmentation of TDP-43 and loss of endogenous murine Tdp-43, but entirely lacking aggregates of ubiquitin or TDP-43. A second, low expressing line was aged to 25 months without a severe neurodegenerative phenotype, despite a 30% loss of mouse Tdp-43 and accumulation of lower molecular weight TDP-43 species. Furthermore, TDP-43 fragments generated during neurodegeneration were not C-terminal, but rather were derived from a central portion of human TDP-43. Thus we find that aggregation is not required for cell loss, loss of murine Tdp-43 is not necessarily sufficient in order to develop a severe neurodegenerative phenotype and lower molecular weight TDP-43 positive species in mouse models should not be inherently assumed to be representative of human disease. Our findings are significant for the interpretation of other transgenic studies of TDP-43 proteinopathy.

  8. Calcium dobesilate: pharmacology and future approaches.

    Science.gov (United States)

    Tejerina, T; Ruiz, E

    1998-09-01

    1. Calcium dobesilate (2,5-dihydroxybenzene sulfonate) is a drug commonly used in the treatment of diabetic retinopathy and chronic venous insufficiency. 2. The pharmacology of calcium dobesilate reveals its ability to decrease capillary permeability, as well as platelet aggregation and blood viscosity. 3. Furthermore, recent data show that calcium dobesilate increases endothelium-dependent relaxation owing to an increase in nitric oxide synthesis.

  9. Presynaptic calcium dynamics of learning neurons

    OpenAIRE

    Meyer-Hermann, Michael; Erler, Frido; Soff, Gerhard

    2002-01-01

    We present a new model for the dynamics of the presynaptic intracellular calcium concentration in neurons evoked by various stimulation protocols. The aim of the model is twofold: We want to discuss the calcium transients during and after specific stimulation protocols as they are used to induce long-term-depression and long-term-potentiation. In addition we would like to provide a general tool which allows the comparison of different calcium experiments. This may help to draw conclusions on ...

  10. Protein-Mediated Precipitation of Calcium Carbonate

    OpenAIRE

    Izabela Polowczyk; Anna Bastrzyk; Marta Fiedot

    2016-01-01

    Calcium carbonate is an important component in exoskeletons of many organisms. The synthesis of calcium carbonate was performed by mixing dimethyl carbonate and an aqueous solution of calcium chloride dihydrate. The precipitation product was characterized by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) measurements. In addition, the turbidity of the reaction solution was acquire...

  11. Mechanical Properties of a Calcium Dietary Supplement, Calcium Fumarate Trihydrate.

    Science.gov (United States)

    Sun, Shijing; Henke, Sebastian; Wharmby, Michael T; Yeung, Hamish H-M; Li, Wei; Cheetham, Anthony K

    2015-12-07

    The mechanical properties of calcium fumarate trihydrate, a 1D coordination polymer considered for use as a calcium source for food and beverage enrichment, have been determined via nanoindentation and high-pressure X-ray diffraction with single crystals. The nanoindentation studies reveal that the elastic modulus (16.7-33.4 GPa, depending on crystallographic orientation), hardness (1.05-1.36 GPa), yield stress (0.70-0.90 GPa), and creep behavior (0.8-5.8 nm/s) can be rationalized in view of the anisotropic crystal structure; factors include the directionality of the inorganic Ca-O-Ca chain and hydrogen bonding, as well as the orientation of the fumarate ligands. High-pressure single-crystal X-ray diffraction studies show a bulk modulus of ∼ 20 GPa, which is indicative of elastic recovery intermediate between small molecule drug crystals and inorganic pharmaceutical ingredients. The combined use of nanoindentation and high-pressure X-ray diffraction techniques provides a complementary experimental approach for probing the critical mechanical properties related to tableting of these dietary supplements.

  12. Calcium influx affects intracellular transport and membrane repair following nanosecond pulsed electric field exposure.

    Science.gov (United States)

    Thompson, Gary Lee; Roth, Caleb C; Dalzell, Danielle R; Kuipers, Marjorie; Ibey, Bennett L

    2014-05-01

    The cellular response to subtle membrane damage following exposure to nanosecond pulsed electric fields (nsPEF) is not well understood. Recent work has shown that when cells are exposed to nsPEF, ion permeable nanopores (2  nm) created by longer micro- and millisecond duration pulses. Nanoporation of the plasma membrane by nsPEF has been shown to cause a transient increase in intracellular calcium concentration within milliseconds after exposure. Our research objective is to determine the impact of nsPEF on calcium-dependent structural and repair systems in mammalian cells. Chinese hamster ovary (CHO-K1) cells were exposed in the presence and absence of calcium ions in the outside buffer to either 1 or 20, 600-ns duration electrical pulses at 16.2  kV/cm, and pore size was determined using propidium iodide and calcium green. Membrane organization was observed with morphological changes and increases in FM1-43 fluorescence. Migration of lysosomes, implicated in membrane repair, was followed using confocal microscopy of red fluorescent protein-tagged LAMP1. Microtubule structure was imaged using mEmerald-tubulin. We found that at high 600-ns PEF dosage, calcium-induced membrane restructuring and microtubule depolymerization coincide with interruption of membrane repair via lysosomal exocytosis.

  13. Parathyroid hormone, calcium, and sodium bridging between osteoporosis and hypertension in postmenopausal Korean women.

    Science.gov (United States)

    Park, Jee Soo; Choi, Soo Beom; Rhee, Yumie; Chung, Jai Won; Choi, Eui-Young; Kim, Deok Won

    2015-05-01

    The coexistence of osteoporosis and hypertension, which are considered distinct diseases, has been widely reported. In addition, daily intake of calcium and sodium, as well as parathyroid hormone levels (PTH), is known to be associated with osteoporosis and hypertension. This study aimed to determine the association of low calcium intake, high sodium intake, and PTH levels with osteoporosis and hypertension in postmenopausal Korean women. Data for postmenopausal Korean women aged 50 years or older were obtained from the Korea National Health and Nutrition Examination Survey 2008-2011. Osteoporosis was diagnosed using dual energy X-ray absorptiometry, while hypertension was diagnosed using blood pressure data. The odds ratios for osteoporosis and hypertension were calculated using logistic regression analysis for quartiles of the daily calcium intake, daily sodium intake, and PTH levels. Women with hypertension had a high coexistence of osteoporosis (43.6 vs. 36.5 %; P = 0.022), and vice versa (21.1 vs. 16.6 %; P = 0.022). PTH was significantly associated with osteoporosis and hypertension, and a high intake of calcium was strongly correlated with a low incidence of osteoporosis. This is the first study to report the characteristics of postmenopausal Korean women who have high dietary sodium intake and low dietary calcium intake, in association with the incidence of osteoporosis and hypertension. Osteoporosis and hypertension were strongly associated with each other, and PTH appears to be a key mediator of both diseases, suggesting a possible pathogenic link.

  14. 44 CFR 208.43 - Rehabilitation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Rehabilitation. 208.43... Agreements § 208.43 Rehabilitation. DHS will reimburse costs incurred to return System equipment and... Activation. (3) Personnel costs associated with equipment cache rehabilitation. DHS will reimburse costs...

  15. 18 CFR 420.43 - Exempt use.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Exempt use. 420.43... MANUAL BASIN REGULATIONS-WATER SUPPLY CHARGES Charges; Exemptions § 420.43 Exempt use. The following uses shall be exempt from charge: (a) Non-consumptive uses of less than 1,000 gallons during any day, and...

  16. 38 CFR 43.25 - Program income.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Program income. 43.25... Requirements Financial Administration § 43.25 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from fees for services performed, from the...

  17. 45 CFR 74.43 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Competition. 74.43 Section 74.43 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR AWARDS AND SUBAWARDS TO INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, OTHER NONPROFIT ORGANIZATIONS, AND COMMERCIAL ORGANIZATIONS Post-Award...

  18. 7 CFR 915.43 - Contributions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Contributions. 915.43 Section 915.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE AVOCADOS GROWN IN SOUTH FLORIDA Order...

  19. 50 CFR 622.43 - Closures.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Closures. 622.43 Section 622.43 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... hind, rock hind, yellowmouth grouper, tiger grouper, yellowfin grouper, graysby, and coney. (6...

  20. 38 CFR 43.32 - Equipment.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Equipment. 43.32 Section... Requirements Changes, Property, and Subawards § 43.32 Equipment. (a) Title. Subject to the obligations and conditions set forth in this section, title to equipment acquired under a grant or subgrant will vest upon...

  1. 7 CFR 958.43 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 958.43 Section 958.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Accounting. (a) All funds received by the committee pursuant to the provisions of this part shall be used...

  2. 40 CFR 30.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competition. 30.43 Section 30.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM.... In order to ensure objective contractor performance and eliminate unfair competitive advantage...

  3. 38 CFR 4.43 - Osteomyelitis.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Osteomyelitis. 4.43... DISABILITIES Disability Ratings The Musculoskeletal System § 4.43 Osteomyelitis. Chronic, or recurring, suppurative osteomyelitis, once clinically identified, including chronic inflammation of bone marrow, cortex...

  4. 27 CFR 555.43 - Permit fees.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Permit fees. 555.43 Section 555.43 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND.... (a) Each applicant must pay a fee for obtaining a permit as follows: (1) User—$100 for a three-year...

  5. 24 CFR 84.43 - Competition.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Competition. 84.43 Section 84.43 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development UNIFORM... free competition. The recipient shall be alert to organizational conflicts of interest as well as...

  6. 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... Post-Award Requirements Reports, Records, Retention, and Enforcement § 43.41 Financial reporting. (a... may from time to time be authorized by OMB, for: (i) Submitting financial reports to Federal agencies...

  7. 7 CFR 983.43 - Procedure.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Procedure. 983.43 Section 983.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... through the use of a conference telephone or similar communication equipment, as long as all members...

  8. 29 CFR 1956.43 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Developmental schedule. 1956.43 Section 1956.43 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) STATE PLANS FOR THE DEVELOPMENT AND ENFORCEMENT OF STATE STANDARDS APPLICABLE TO STATE AND LOCAL...

  9. Calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum in skeletal muscle fibers.

    Science.gov (United States)

    Simon, B J; Klein, M G; Schneider, M F

    1991-03-01

    The steady-state calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum was studied in voltage-clamped, cut segments of frog skeletal muscle fibers containing two calcium indicators, fura-2 and anti-pyrylazo III (AP III). Fura-2 fluorescence was used to monitor resting calcium and relatively small calcium transients during small depolarizations. AP III absorbance signals were used to monitor larger calcium transients during larger depolarizations. The rate of release (Rrel) of calcium from the sarcoplasmic reticulum was calculated from the calcium transients. The equilibrium calcium dependence of inactivation of calcium release was determined using 200-ms prepulses of various amplitudes to elevate [Ca2+] to various steady levels. Each prepulse was followed by a constant test pulse. The suppression of peak Rrel during the test pulse provided a measure of the extent of inactivation of release at the end of the prepulse. The [Ca2+] dependence of inactivation indicated that binding of more than one calcium ion was required to inactivate each release channel. Half-maximal inactivation was produced at a [Ca2+] of approximately 0.3 microM. Variation of the prepulse duration and amplitude showed that the suppression of peak release was consistent with calcium-dependent inactivation of calcium release but not with calcium depletion. The same calcium dependence of inactivation was obtained using different amplitude test pulses to determine the degree of inactivation. Prepulses that produced near maximal inactivation of release during the following test pulse produced no suppression of intramembrane charge movement during the test pulse, indicating that inactivation occurred at a step beyond the voltage sensor for calcium release. Three alternative set of properties that were assumed for the rapidly equilibrating calcium-binding sites intrinsic to the fibers gave somewhat different Rrel records, but gave very similar calcium dependence of

  10. Protein-Mediated Precipitation of Calcium Carbonate.

    Science.gov (United States)

    Polowczyk, Izabela; Bastrzyk, Anna; Fiedot, Marta

    2016-11-22

    Calcium carbonate is an important component in exoskeletons of many organisms. The synthesis of calcium carbonate was performed by mixing dimethyl carbonate and an aqueous solution of calcium chloride dihydrate. The precipitation product was characterized by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) measurements. In addition, the turbidity of the reaction solution was acquired to monitor the kinetics of the calcium carbonate structure's growth in the investigated system. In this study, samples of CaCO₃ particles obtained with individual proteins, such as ovalbumin, lysozyme, and a mixture of the proteins, were characterized and compared with a control sample, i.e., synthesized without proteins. The obtained data indicated that the addition of ovalbumin to the reaction changed the morphology of crystals from rhombohedral to 'stack-like' structures. Lysozyme, however, did not affect the morphology of calcium carbonate, yet the presence of the protein mixture led to the creation of more complex composites in which the calcium carbonate crystals were constructed in protein matrices formed by the ovalbumin-lysozyme interaction. It was also observed that in the protein mixture, ovalbumin has a major influence on the CaCO₃ formation through a strong interaction with calcium ions, which leads to the coalescence and creation of a steric barrier reducing particle growth. The authors proposed a mechanism of calcium carbonate grain growth in the presence of both proteins, taking into account the interaction of calcium ions with the protein.

  11. Diuretics and disorders of calcium homeostasis.

    Science.gov (United States)

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. [ZINK IS ACTIVATOR OF ENTERAL CALCIUM METABOLISM].

    Science.gov (United States)

    Polyakova, E P; Ksenofontov, D A; Revyakin, A O; Ivanov, A A

    2015-01-01

    Experiments on goats and rabbits showed that zinc supplement to the diet leads to calcium concentration rise in muscle, bone and blood of animals. However, this rise was not adequate to increase in.zinc consumption. The bulk of alimentary zinc stayed in soluble fraction, dense endogen fraction and infusoria fraction of digesta and stimulated calcium release from food particles, it's accumulation in digesta fractions and calcium utilization on the whole. Authors estimate animal digesta as homeostatic, spatial organized, endogenic formation in which zinc and calcium are functionally dependent through enteral mucosa.

  13. The Electronic Structure of Calcium

    DEFF Research Database (Denmark)

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

    1981-01-01

    .149 Ryd, respectively, relative to the s band, give the best possible agreement. Under increasing pressure the s and p electrons are found to transfer into the d band, and Ca undergoes metal-semimetal-metal electronic transitions. Calculations of the bandstructure and the electronic pressure, including......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. Distinct Calcium Sources Support Multiple Modes of Synaptic Release from Cranial Sensory Afferents.

    Science.gov (United States)

    Fawley, Jessica A; Hofmann, Mackenzie E; Andresen, Michael C

    2016-08-24

    sources: CaVs and TRPV1. We demonstrate that calcium segregation distinguishes three vesicle release mechanisms. Most surprisingly, asynchronous release is associated with CaV and not TRPV1 calcium entry. This reveals that asynchronous release is an additional and separate phenotypic marker of unmyelinated afferents rather than operated by TRPV1. The functional independence of the two calcium sources expands the regulatory repertoire of transmission and imbues these inputs with additional modulation targets for synaptic release not present at conventional CaV synapses. Peptides and lipid mediators may target one or both of these calcium sources at afferent terminals within the solitary tract nucleus to independently modify release from distinct, functionally segregated vesicle pools. Copyright © 2016 the authors 0270-6474/16/368957-10$15.00/0.

  15. Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial.

    Science.gov (United States)

    Thacher, Tom D; Fischer, Philip R; Pettifor, John M

    2014-09-01

    To determine whether children with calcium-deficiency rickets have a better response to treatment with vitamin D and calcium than with calcium alone. Randomised controlled trial. Jos University Teaching Hospital, Jos, Nigeria. Nigerian children with active rickets treated with calcium carbonate as limestone (approximately 938 mg elemental calcium twice daily) were, in addition, randomised to receive either oral vitamin D2 50,000 IU (Ca+D, n=44) or placebo (Ca, n=28) monthly for 24 weeks. Achievement of a 10-point radiographic severity score ≤1.5 and serum alkaline phosphatase ≤350 U/L. The median (range) age of enrolled children was 46 (15-102) months, and baseline characteristics were similar in the two groups. Mean (±SD) 25-hydroxyvitamin D (25(OH)D) was 30.2±13.2 nmol/L at baseline, and 29 (43%) had values children (94% of original cohort) who completed 24 weeks of treatment, 29 (67%) in the Ca+D group and 11 (44%) in the Ca group achieved the primary outcome (p=0.06). Baseline 25(OH)D did not alter treatment group effects (p=0.99 for interaction). At the end of 24 weeks, 25(OH)D values were 55.4±17.0 nmol/L and 37.9±20.0 nmol/L in the Ca+D and Ca groups, respectively, (pchildren with calcium-deficiency rickets, there is a trend for vitamin D to improve the response to treatment with calcium carbonate as limestone, independent of baseline 25(OH)D concentrations. ClinicalTrials.gov NCT00949832. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Short communication: Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis

    NARCIS (Netherlands)

    Dijcker, J.C.; Kummeling, A.; Hagen-Plantinga, E.A.; Hendriks, W.H.

    2012-01-01

    Introduction Urine concentrations of oxalate and calcium play an important role in calcium oxalate (CaOx) urolith formation in dogs and cats, with high excretions of both substances increasing the chance of CaOx urolithiasis. In 17 CaOx-forming dogs, urine calcium:creatinine ratio (Ca:Cr) was found

  17. Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats

    NARCIS (Netherlands)

    Jongwattanapisan, P.; Suntornsaratoon, P.; Wongdee, K.; Dorkkam, N.; Krishnamra, N.; Charoenphandhu, N.

    2012-01-01

    An earlier study reported that cecal calcium absorption contributes less than 10% of total calcium absorbed by the intestine, although the cecum has the highest calcium transport rate compared with other intestinal segments. Thus, the physiological significance of the cecum pertaining to body

  18. Pharmacological modulation of mitochondrial calcium homeostasis.

    Science.gov (United States)

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca2+ homeostasis have been linked to a variety of pathological conditions and are critical in the etiology of several human diseases. Efforts have been taken to harness mitochondrial Ca2+ transport mechanisms for therapeutic intervention but pharmacological compounds that direct and selectively modulate mitochondrial Ca2+ homeostasis are currently lacking. New avenues have however emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progresses towards a systems-level pharmacological targeting of mitochondrial Ca2+ homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Plasma membrane calcium pump and sodium-calcium exchanger in maintenance and control of calcium concentrations in platelets.

    Science.gov (United States)

    Juska, Alfonsas

    2010-01-29

    The purpose of this research was to elucidate the activity of the mechanisms responsible for control of cytosolic calcium concentration in platelets by modeling the time-course of the concentration changing in response to discharge of the intracellular stores or store-operated calcium entry (SOCE). The parameters estimated as a result of model fitting to experimental data are related to physiological or pathological state of the cells. It has been shown that: (a) the time-course is determined by the passive calcium fluxes and activities of the corresponding mechanisms; (b) the decline in the concentration (after its rise) develops due to activity of plasma membrane calcium ATPase (PMCA) both in the case of discharge of the stores of platelets contained in calcium-free medium and in the case of SOCE; (c) impulsive extrusion of calcium in response to its sudden influx, presumably, is the main function of PMCA; (d) the function of sodium-calcium exchanger (NCX) is to extrude calcium excess by permanent counteracting its influx. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  20. Pulsar Science with the Green Bank 43m Telescope

    OpenAIRE

    Mickaliger, M. B.; McLaughlin, M. A.; Lorimer, D. R.; Langston, G. I.; Bilous, A. V.; Kondratiev, V. I.; Ransom, S. M.; Crawford, F.

    2011-01-01

    The 43m telescope at the NRAO site in Green Bank, WV has recently been outfitted with a clone of the Green Bank Ultimate Pulsar Processing Instrument (GUPPI \\cite{Ransom:2009}) backend, making it very useful for a number of pulsar related studies in frequency ranges 800-1600 MHz and 220-440 MHz. Some of the recent science being done with it include: monitoring of the Crab pulsar, a blind search for transient sources, pulsar searches of targets of opportunity, and an all-sky mapping project. F...

  1. Calcium dobesilate in the treatment of diabetic retinopathy.

    Science.gov (United States)

    Garay, Ricardo P; Hannaert, Patrick; Chiavaroli, Carlo

    2005-01-01

    The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.e. aldose reductase inhibitors and protein kinase C-beta inhibitors) have failed to demonstrate significant efficacy in the treatment of diabetic retinopathy in clinical trials. In contrast, calcium dobesilate (2,5-dihydroxybenzenesulfonate), which was discovered more than 40 years ago and is registered for the treatment of diabetic retinopathy in more than 20 countries remains, to our knowledge, the only angioprotective agent that reduces the progression of this disease. An overall review of published studies involving calcium dobesilate (CLS 2210) depicts a rather 'non-specific' compound acting moderately, but significantly, on the various and complex disorders that contribute to diabetic retinopathy. Recent studies have shown that calcium dobesilate is a potent antioxidant, particularly against the highly damaging hydroxyl radical. In addition, it improves diabetic endothelial dysfunction, reduces apoptosis, and slows vascular cell proliferation.

  2. Pseudogout and Calcium Pyrophosphate Disease

    Directory of Open Access Journals (Sweden)

    Andrew Williamson

    2017-01-01

    Full Text Available History of present illness: A 53-year-old male presented with worsening right knee pain and swelling over the past 48 hours. He denied recent trauma to the knee, history of IV drug use, and recent illness. He had no history of diabetes, immunodeficiency, chronic steroids, rheumatologic disease, or knee replacement. He described the pain as sharp, non-radiating, and worse with movement. He was unable to walk due to pain. Significant findings: Radiographs of the knee showed multiple radio-dense lines paralleling the articular surface (see red arrows consistent with calcium pyrophosphate crystal deposition within the joint often seen in calcium pyrophosphate disease (CPPD also known as pseudogout. Discussion: Patients commonly present to the emergency department with non-traumatic joint pain. Arthrocentesis is an important diagnostic tool to evaluate for septic arthritis, gout, or pseudogout. Arthrocentesis can demonstrate crystals or abnormal cell count, gram stain, and culture.[1] In the evaluation of joint pain, plain films are usually obtained to evaluate for fracture, dislocation, effusion, or secondary signs of infection. In this case the classic x-ray supported the diagnosis of CPPD.2 The patient was found to have positively birefringent rhomboid shaped crystals consistent with pseudogout on arthrocentesis. Gram stain and culture were both negative. The patient was discharged with NSAIDs and had significant improvement in symptoms upon follow up with primary care physician in 3 days.

  3. Spatiotemporal intracellular calcium dynamics during cardiac alternans

    Science.gov (United States)

    Restrepo, Juan G.; Karma, Alain

    2009-09-01

    Cellular calcium transient alternans are beat-to-beat alternations in the peak cytosolic calcium concentration exhibited by cardiac cells during rapid electrical stimulation or under pathological conditions. Calcium transient alternans promote action potential duration alternans, which have been linked to the onset of life-threatening ventricular arrhythmias. Here we use a recently developed physiologically detailed mathematical model of ventricular myocytes to investigate both stochastic and deterministic aspects of intracellular calcium dynamics during alternans. The model combines a spatially distributed description of intracellular calcium cycling, where a large number of calcium release units are spatially distributed throughout the cell, with a full set of ionic membrane currents. The results demonstrate that ion channel stochasticity at the level of single calcium release units can influence the whole-cell alternans dynamics by causing phase reversals over many beats during fixed frequency pacing close to the alternans bifurcation. They also demonstrate the existence of a wide range of dynamical states. Depending on the sign and magnitude of calcium-voltage coupling, calcium alternans can be spatially synchronized or desynchronized, in or out of phase with action potential duration alternans, and the node separating out-of-phase regions of calcium alternans can be expelled from or trapped inside the cell. This range of states is found to be larger than previously anticipated by including a robust global attractor where calcium alternans can be spatially synchronized but out of phase with action potential duration alternans. The results are explained by a combined theoretical analysis of alternans stability and node motion using general iterative maps of the beat-to-beat dynamics and amplitude equations.

  4. Microwave-assisted biomimetic synthesis of hydroxyapatite using different sources of calcium.

    Science.gov (United States)

    Türk, S; Altınsoy, I; ÇelebiEfe, G; Ipek, M; Özacar, M; Bindal, C

    2017-07-01

    In this study, some properties of biomimetic synthesized hydroxyapatite by using different sources of calcium were investigated. Biomimetic synthesis of hydroxyapatite was carried out in microwave oven using 1.5 simulated body fluid (SBF) solution having different calcium sources with 800W power for 15min. As phosphorus source di-ammonium hydrogen phosphate ((NH4)2HPO4) while for each sample as a calcium sources calcium chloride (CaCl2), calcium nitrate tetra hydrate (Ca(NO3)2·4H2O) and calcium hydroxide (Ca(OH)2) were utilized, respectively. For comparison, precipitation process was also performed in only 1.5 SBF solution without calcium and phosphorus sources. The presence of phases in synthesized hydroxyapatite was confirmed by XRD. The crystallinity and crystalline size of the phases in as synthesized powders were also calculated by using XRD data. It was found that the unique phase is hydroxyapatite (HAp, Ca5(PO4)3(OH)) by using the calcium nitrate tetra hydrate and calcium hydroxide sources, while the dominant phases are tri-calcium phosphates (TCP) and HAp for CaCl2 source and 1.5SBF which does not contain any additional Ca source. SEM studies revealed that nano-hexagonal rods and nano-spherical hydroxyapatites could be synthesized by using this process. Energy-dispersive X-ray spectroscopy (EDS) analysis revealed that the Ca/P ratio near to be as 1.5 which is the value for HAp in bone. Raman and Fourier transform-infrared spectroscopy (FT-IR) results combined with the X-ray diffraction (XRD) indicates that dominantly the present of single phase is HAp. The crystal size and fraction crystallinity of as synthesized HAp powders were changed between 29.5 and 45.4nm and 0.53-2.37, respectively. Results showed that microwave assisted biomimetic synthesis is a promising method for obtaining HAp powders in shorter process time. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. When Neurons Encounter Nanoobjects: Spotlight on Calcium Signalling

    Directory of Open Access Journals (Sweden)

    Davide Lovisolo

    2014-09-01

    Full Text Available Nanosized objects are increasingly present in everyday life and in specialized technological applications. In recent years, as a consequence of concern about their potential adverse effects, intense research effort has led to a better understanding of the physicochemical properties that underlie their biocompatibility or potential toxicity, setting the basis for a rational approach to their use in the different fields of application. Among the functional parameters that can be perturbed by interaction between nanoparticles (NPs and living structures, calcium homeostasis is one of the key players and has been actively investigated. One of the most relevant biological targets is represented by the nervous system (NS, since it has been shown that these objects can access the NS through several pathways; moreover, engineered nanoparticles are increasingly developed to be used for imaging and drug delivery in the NS. In neurons, calcium homeostasis is tightly regulated through a complex set of mechanisms controlling both calcium increases and recovery to the basal levels, and even minor perturbations can have severe consequences on neuronal viability and function, such as excitability and synaptic transmission. In this review, we will focus on the available knowledge about the effects of NPs on the mechanisms controlling calcium signalling and homeostasis in neurons. We have taken into account the data related to environmental NPs, and, in more detail, studies employing engineered NPs, since their more strictly controlled chemical and physical properties allow a better understanding of the relevant parameters that determine the biological responses they elicit. The literature on this specific subject is all quite recent, and we have based the review on the data present in papers dealing strictly with nanoparticles and calcium signals in neuronal cells; while they presently amount to about 20 papers, and no related review is available, the field is

  6. 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

  7. Modification of nanostructured calcium carbonate for efficient gene delivery.

    Science.gov (United States)

    Zhao, Dong; Wang, Chao-Qun; Zhuo, Ren-Xi; Cheng, Si-Xue

    2014-06-01

    In this study, a facile method to modify nanostructured calcium carbonate (CaCO3) gene delivery systems by adding calcium phosphate (CaP) component was developed. CaCO3/CaP/DNA nanoparticles were prepared by the co-precipitation of Ca(2+) ions with plasmid DNA in the presence of carbonate and phosphate ions. For comparison, CaCO3/DNA nanoparticles and CaP/DNA co-precipitates were also prepared. The effects of carbonate ion/phosphate ion (CO3(2-)/PO4(3-)) ratio on the particle size and gene delivery efficiency were investigated. With an appropriate CO3(2-)/PO4(3-) ratio, the co-existence of carbonate and phosphate ions could control the size of co-precipitates effectively, and CaCO3/CaP/DNA nanoparticles with a decreased size and improved stability could be obtained. The in vitro gene transfections mediated by different nanoparticles in 293T cells and HeLa cells were carried out, using pGL3-Luc as a reporter plasmid. The gene transfection efficiency of CaCO3/CaP/DNA nanoparticles could be significantly improved as compared with CaCO3/DNA nanoparticles and CaP/DNA co-precipitates. The confocal microscopy study indicated that the cellular uptake and nuclear localization of CaCO3/CaP/DNA nanoparticles were significantly enhanced as compared with unmodified CaCO3/DNA nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Erika Guimarães

    Full Text Available Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10. In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.

  9. Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Arunakar Kuchipudi

    2016-05-01

    Full Text Available Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Our recent work has demonstrated the natural occurrence and autonomous synthesis of an exclusive lipid phosphatidylthreonine in T. gondii. Targeted gene disruption of phosphatidylthreonine synthase impairs the parasite virulence due to unforeseen attenuation of the consecutive events of motility, egress and invasion. However, the underlying basis of such an intriguing phenotype in the parasite mutant remains unknown. Using an optogenetic sensor (gene-encoded calcium indicator, GCaMP6s, we show that loss of phosphatidylthreonine depletes calcium stores in intracellular tachyzoites, which leads to dysregulation of calcium release into the cytosol during the egress phase of the mutant. Consistently, the parasite motility and egress phenotypes in the mutant can be entirely restored by ionophore-induced mobilization of calcium. Collectively, our results suggest a novel regulatory function of phosphatidylthreonine in calcium signaling of a prevalent parasitic protist. Moreover, our application of an optogenetic sensor to monitor subcellular calcium in a model intracellular pathogen exemplifies its wider utility to other entwined systems.

  10. Calcium homeostasis and signaling in fungi and their relevance for pathogenicity of yeasts and filamentous fungi

    Directory of Open Access Journals (Sweden)

    Renata Tisi

    2016-09-01

    Full Text Available Though fungi show peculiarities in the purposes and specific traits of calcium signaling pathways, the general scheme and the most important players are well conserved if compared to higher eukaryotes. This provides a powerful opportunity either to investigate shared features using yeast as a model or to exploit fungal specificities as potential targets for antifungal therapies. The sequenced genomes from yeast Saccharomyces cerevisiae, Schizosaccharomyces pombe and the filamentous fungus Neurospora crassa were already published more than ten years ago. More recently the genome sequences of filamentous fungi of Aspergillus genus, some of which threatening pathogens, and dimorphic fungi Ustilago maydis were published, giving the chance to identify several proteins involved in calcium signaling based on their homology to yeast or mammalian counterparts. Nonetheless, unidentified calcium transporters are still present in these organisms which await to be molecularly characterized. Despite the relative simplicity in yeast calcium machinery and the availability of sophisticated molecular tools, in the last years, a number of new actors have been identified, albeit not yet fully characterized. This review will try to describe the state of the art in calcium channels and calcium signaling knowledge in yeast, with particular attention to the relevance of this knowledge with respect to pathological fungi.

  11. Calcium intake and colorectal cancer risk: Results from the nurses' health study and health professionals follow-up study.

    Science.gov (United States)

    Zhang, Xuehong; Keum, NaNa; Wu, Kana; Smith-Warner, Stephanie A; Ogino, Shuji; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L

    2016-11-15

    The relationship between calcium intake and colorectal cancer (CRC) risk remains inconclusive. We conducted this study to evaluate whether the association between calcium intake and CRC risk differs by anatomic subsite and determine the dose-response relationship for this association, as well as assess when in carcinogenesis calcium may play a role. We assessed calcium intake every 4 years and followed 88,509 women (1980-2012) in the Nurses' Health Study and 47,740 men (1986-2012) in the Health Professionals Follow-Up Study. We documented 3,078 incident CRC cases. Total calcium intake (≥1,400 vs. cancer (multivariable relative risk: 0.78, 95%CI: 0.65-0.95). Similar results were observed by different sources of calcium (from all foods or dairy products only). The inverse association was linear and suggestively stronger for distal colon cancer (0.65, 0.43-0.99) than for proximal colon cancer (0.94, 0.72-1.22, p-common effects  = 0.14). Additionally, when comparing different latencies, the overall pattern suggested that the inverse association appeared to be stronger with increasing latency and was strongest for intakes 12-16 years before diagnosis. Comparing total calcium intakes of ≥1,400 vs. calcium intake was associated with a lower risk of developing colon cancer, especially for distal colon cancer. Overall inverse association was linear and did not differ by intake source. Additionally, calcium intake approximately 10 years before diagnosis appeared to be associated with a lower risk of CRC. © 2016 UICC.

  12. Calcium Blood Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... this page: https://medlineplus.gov/labtests/calciumbloodtest.html Calcium Blood Test To use the sharing features on this page, please enable JavaScript. What is a Calcium Blood Test? A calcium blood test measures the ...

  13. Calcium channel regulator Mid1 links TORC2-mediated changes in mitochondrial respiration to autophagy

    OpenAIRE

    Vlahakis, Ariadne; Lopez Muniozguren, Nerea; Powers, Ted

    2016-01-01

    Autophagy is a catabolic process that recycles cytoplasmic contents and is crucial for cell survival during stress. The target of rapamycin (TOR) kinase regulates autophagy as part of two distinct protein complexes, TORC1 and TORC2. TORC1 negatively regulates autophagy according to nitrogen availability. In contrast, TORC2 functions as a positive regulator of autophagy during amino acid starvation, via its target kinase Ypk1, by repressing the activity of the calcium-dependent phosphatase cal...

  14. D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

    Science.gov (United States)

    Kisilevsky, Alexandra E; Mulligan, Sean J; Altier, Christophe; Iftinca, Mircea C; Varela, Diego; Tai, Chao; Chen, Lina; Hameed, Shahid; Hamid, Jawed; Macvicar, Brian A; Zamponi, Gerald W

    2008-05-22

    Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

  15. Actein induces calcium release in human breast cancer cells.

    Science.gov (United States)

    Einbond, Linda Saxe; Mighty, Jason; Redenti, Stephen; Wu, Hsan-au

    2013-12-01

    The triterpene glycoside actein from the herb black cohosh preferentially inhibits the growth of breast cancer cells and activates the ER stress response. The ER IP3 receptor and Na,K-ATPase form a signaling microdomain. Since actein is lipophilic, its action may be limited by bioavailability. To develop actein to prevent and treat cancer, we examined the primary targets and combinations with chemotherapy agents, as well as the ability of nanoparticles to enhance the activity. To reveal signaling pathways, we treated human breast and colon cancer, as well as 293T and 293T (NF-κB), cells with actein, and measured effects using the MTT, luciferase promoter, Western blot and histology assays. To assess effects on calcium release, we preloaded cells with the calcium sensitive dye Fura-2. To enhance bioavailability, we conjugated actein to nanoparticle liposomes. Actein strongly inhibited the growth of human breast cancer cells and induced a dose dependent release of calcium into the cytoplasm. The ER IP3 receptor antagonist heparin blocked this release, indicating that the receptor is required for activity. Heparin partially blocked the growth inhibitory effect, while the MEK inhibitor U0126 enhanced it. Consistent with this, actein synergized with the ER mobilizer thapsigargin. Further, actein preferentially inhibited the growth of 293T (NF-κB) cells. Nanoparticle liposomes increased the growth inhibitory activity of actein. Actein alters the activity of the ER IP3 receptor and Na,K-ATPase, induces calcium release and modulates the NF-κB and MEK pathways and may be worthwhile to explore to prevent and treat breast cancer. © 2013.

  16. Rates of calcium carbonate removal from soils.

    NARCIS (Netherlands)

    Breemen, van N.; Protz, R.

    1988-01-01

    Mean annual rates of calcium carbonate removal from soils in a subarctic climate estimated from data on two chronosequences of calcareous storm ridges, appeared to be relatively constant through time. Concentrations of dissolved calcium carbonate in the soil solution in the study sites calculated

  17. Calcium and M'yocardial Infarction

    African Journals Online (AJOL)

    1974-03-16

    Mar 16, 1974 ... Urinary excretion of calcium tended to be even lower in these .... 16 March 1974. S.A. MEDICAL JOURNAL. 525. 150. 50. Fig. 5. Urine calcium in myocardial infarction (means and standard error relative to age). AGE OF PATIENT .... Plasma proteins and blood urea were also measured in. 10 consecutive ...

  18. 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.

  19. 21 CFR 182.8223 - Calcium pyrophosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium...

  20. 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 HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8217 Calcium...

  1. 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.

  2. Role of calcium in selenium cataract.

    Science.gov (United States)

    Shearer, T R; David, L L

    The purpose of this research was to test the role of certain minerals in the formation of cataract caused by an overdose of selenium. Several pieces of information indicated that lenticular calcium may play an important role in selenite cataractogenesis: 1) Lens calcium concentrations in selenite treated rats were increased more than 5-fold, and the increase in lens calcium was localized in the nucleus. 2) Lens calcium concentrations were elevated at least one full day before actual formation of nuclear cataract, but serum calcium levels were not changed. 3) In older rats not susceptible to selenite cataract, lens calcium was not significantly increased. 4) No evidence was found for a generalized disruption in lens permeability, since no major changes in lens water, sodium, and potassium levels were observed, and 5) when levels of calcium observed in selenite cataract were added to solutions of soluble proteins from rat lenses, light scattering was increased. Selenium-overdose cataracts may provide an important model for studies on the role of calcium in cataractogenesis.

  3. Adding calcium improves lithium ferrite core

    Science.gov (United States)

    Lessoff, H.

    1969-01-01

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

  4. 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...

  5. Comparison of Serum Calcium and Magnesium Between ...

    African Journals Online (AJOL)

    The present study compared serum calcium and magnesium in forty preeclamptic (cases) and forty normotensive (control) pregnant women matched for age, parity, and socioeconomic status. Serum calcium and magnesium levels were measured using atomic absorption spectrophotometer. Statistical analysis was done ...

  6. Dairy Dilemma: Are You Getting Enough Calcium?

    Science.gov (United States)

    ... body also needs vitamin D to absorb calcium. Nutrition surveys have shown that most people in the U.S. aren’t getting the calcium they need. If you’re avoiding milk and dairy ... taking nutritional supplements and choosing reduced-lactose or non-dairy ...

  7. 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

  8. 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......, a sudden solubilization of micellar calcium was observed at 50 oC and 60 oC, which revealed an interesting role of calcium during acidification at elevated temperatures. After enrichment of milk with calcium D-lactobionate, the added calcium was distributed between the micellar and serum milk phase at pH 6...

  9. Bespuiten met calcium kan neusrot voorkomen

    NARCIS (Netherlands)

    Blom-Zandstra, Greet; Marcelis, L.F.M.

    2000-01-01

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

  10. Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics.

    Directory of Open Access Journals (Sweden)

    An-a Kazuno

    2006-08-01

    Full Text Available Mitochondrial DNA (mtDNA is highly polymorphic, and its variations in humans may contribute to individual differences in function as well as susceptibility to various diseases such as Parkinson disease, Alzheimer disease, bipolar disorder, and cancer. However, it is unclear whether and how mtDNA polymorphisms affect intracellular function, such as calcium signaling or pH regulation. Here we searched for mtDNA polymorphisms that have intracellular functional significance using transmitochondrial hybrid cells (cybrids carrying ratiometric Pericam (RP, a fluorescent calcium indicator, targeted to the mitochondria and nucleus. By analyzing the entire mtDNA sequence in 35 cybrid lines, we found that two closely linked nonsynonymous polymorphisms, 8701A and 10398A, increased the basal fluorescence ratio of mitochondria-targeted RP. Mitochondrial matrix pH was lower in the cybrids with 8701A/10398A than it was in those with 8701G/10398G, suggesting that the difference observed by RP was mainly caused by alterations in mitochondrial calcium levels. Cytosolic calcium response to histamine also tended to be higher in the cybrids with 8701A/10398A. It has previously been reported that 10398A is associated with an increased risk of Parkinson disease, Alzheimer disease, bipolar disorder, and cancer, whereas 10398G associates with longevity. Our findings suggest that these mtDNA polymorphisms may play a role in the pathophysiology of these complex diseases by affecting mitochondrial matrix pH and intracellular calcium dynamics.

  11. Calcium overload injury of rats' enterocyte IEC-6 by heat stress in vitro

    Directory of Open Access Journals (Sweden)

    Yan GENG

    2013-07-01

    Full Text Available Objective To investigate the effect of gradient heat stress on calcium overload of rats' enterocyte IEC-6 and calcium overload-related cell injury in vitro. Methods Thermal gradient was set in culturing IEC-6 cells in vitro. After thermal stimulation, Fluo-3Am probe with fluorescence microscope or flow cytometry was used to detect the change in intracellular Ca2+ concentration of IEC-6 cells. Phase contrast microscope was used to observe the morphological change in IEC-6. Coomassie blue dying method was employed to test the change in IEC-6 cytoskeleton. CCK-8 assay was used to assess cellular viability. Adhesion assay was applied to test the change in basilar membrane adhesiveness of IEC-6 cells. Results Compared with normal control group, cells of heat stress groups showed a thermal-dependent increase in intracellular Ca2+ concentration (P<0.01. Cells of heat stress groups were rounded in shape, the pseudopod was shorter, and cell space was enlarged. These phenomena were more obvious in 45℃ culture than in that of 43℃. Coomassie blue dying showed that the cytoskeleton of cells in heat stress groups became thickened and disordered, and stress fibers appeared. These phenomena were also more obvious in 45℃ culture than in that of 43℃. A thermal-dependant decline of cell viability in heat stress groups was observed via CCK-8 assay (P<0.01, and a thermal-dependant decline of basilar membrane adhesiveness in heat stress groups was observed via adhesion assay (P<0.01. Conclusion Heat stress may cause calcium overload of IEC-6 cells, and thus resulting in a series of calcium overload-related cell injury. Further investigation of the effect and mechanism of heat stress on calcium overload of intestinal mucosa endothelial cells may help further understand the mechanism of the pathogenesis of heat stroke.

  12. Reciprocal Interaction of Dendrite Geometry and Nuclear Calcium-VEGFD Signaling Gates Memory Consolidation and Extinction.

    Science.gov (United States)

    Hemstedt, Thekla J; Bengtson, C Peter; Ramírez, Omar; Oliveira, Ana M M; Bading, Hilmar

    2017-07-19

    Nuclear calcium is an important signaling end point in synaptic excitation-transcription coupling that is critical for long-term neuroadaptations. Here, we show that nuclear calcium acting via a target gene, VEGFD, is required for hippocampus-dependent fear memory consolidation and extinction in mice. Nuclear calcium-VEGFD signaling upholds the structural integrity and complexity of the dendritic arbor of CA1 neurons that renders those cells permissive for the efficient generation of synaptic input-evoked nuclear calcium transients driving the expression of plasticity-related genes. Therefore, the gating of memory functions rests on the reciprocally reinforcing maintenance of an intact dendrite geometry and a functional synapse-to-nucleus communication axis. In psychiatric and neurodegenerative disorders, therapeutic application of VEGFD may help to stabilize dendritic structures and network connectivity, which may prevent cognitive decline and could boost the efficacy of extinction-based exposure therapies. SIGNIFICANCE STATEMENT This study uncovers a reciprocal relationship between dendrite geometry, the ability to generate nuclear calcium transients in response to synaptic inputs, and the subsequent induction of expression of plasticity-related and dendritic structure-preserving genes. Insufficient nuclear calcium signaling in CA1 hippocampal neurons and, consequently, reduced expression of the nuclear calcium target gene VEGFD, a dendrite maintenance factor, leads to reduced-complexity basal dendrites of CA1 neurons, which severely compromises the animals' consolidation of both memory and extinction memory. The structure-protective function of VEGFD may prove beneficial in psychiatric disorders as well as neurodegenerative and aging-related conditions that are associated with loss of neuronal structures, dysfunctional excitation-transcription coupling, and cognitive decline. Copyright © 2017 the authors 0270-6474/17/376946-10$15.00/0.

  13. 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.

  14. Store-operated calcium entry is essential for glial calcium signalling in CNS white matter.

    Science.gov (United States)

    Papanikolaou, M; Lewis, A; Butt, A M

    2017-02-28

    'Calcium signalling' is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca(2+) stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them. Using quantitative RT-PCR, we identified Orai1 channels, both Stim1 and Stim2, and the transient receptor potential M3 channel (TRPM3) as the primary channels for SOCE in the optic nerve, and their expression in both astrocytes and oligodendrocytes was demonstrated by immunolabelling of optic nerve sections and cultures. The functional importance of SOCE was demonstrated by fluo-4 calcium imaging on isolated intact optic nerves and optic nerve cultures. Removal of extracellular calcium ([Ca(2+)]o) resulted in a marked depletion of glial cytosolic calcium ([Ca(2+)]i), which recovered rapidly on restoration of [Ca(2+)]o via SOCE. 2-aminoethoxydiphenylborane (2APB) significantly decreased SOCE and severely attenuated ATP-mediated calcium signalling. The results provide evidence that Orai/Stim and TRPM3 are important components of the 'calcium toolkit' that underpins SOCE and the sustainability of calcium signalling in white matter glia.

  15. The energy transfer from Eu2+ to Tb3+ in calcium chlorapatite phosphor and its potential application in LEDs

    Science.gov (United States)

    Zhang, Z.; Wang, J.; Zhang, M.; Zhang, Q.; Su, Q.

    2008-06-01

    Energy transfer from Eu2+ to Tb3+ was observed by investigating the optical properties from photoluminescence spectra and decay time curves in Tb3+ singly doped and Eu2+ Tb3+ co-doped calcium chlorapatite, Ca5(PO4)3Cl (CPCl). It is dominated by the cooperation of a phonon-assisted energy transfer process and a non-radiative resonant energy transfer process caused by the exchange interaction. Eu2+ Tb3+ co-doped calcium chlorapatite phosphors in which Tb3+ can be efficiently excited by 400 nm are potential candidates for phosphor-converted LED.

  16. Endoplasmic reticulum calcium stores in dendritic spines.

    Science.gov (United States)

    Segal, Menahem; Korkotian, Eduard

    2014-01-01

    Despite decades of research, the role of calcium stores in dendritic spines structure, function and plasticity is still debated. The reasons for this may have to do with the multitude of overlapping calcium handling machineries in the neuron, including stores, voltage and ligand gated channels, pumps and transporters. Also, different cells in the brain are endowed with calcium stores that are activated by different receptor types, and their differential compartmentalization in dendrites, spines and presynaptic terminals complicates their analysis. In the present review we address several key issues, including the role of calcium stores in synaptic plasticity, their role during development, in stress and in neurodegenerative diseases. Apparently, there is increasing evidence for a crucial role of calcium stores, especially of the ryanodine species, in synaptic plasticity and neuronal survival.

  17. 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.

  18. Calcium phosphate: a substitute for aluminum adjuvants?

    Science.gov (United States)

    Masson, Jean-Daniel; Thibaudon, Michel; Bélec, Laurent; Crépeaux, Guillemette

    2017-03-01

    Calcium phosphate was used as an adjuvant in France in diphtheria, tetanus, pertussis and poliomyelitis vaccines. It was later completely substituted by alum salts in the late 80's, but it still remains as an approved adjuvant for the World Health Organization for human vaccination. Area covered: Thus, calcium phosphate is now considered as one of the substances that could replace alum salts in vaccines. The aim of this paper is to draw a review of existing data on calcium phosphate as an adjuvant in order to bring out the strengths and weaknesses for its use on a large scale. Expert commentary: Calcium phosphate is a compound naturally present in the organism, safe and already used in human vaccination. Beyond comparisons with the other adjuvants, calcium phosphate represents a good candidate to replace or to complete alum salts as a vaccine adjuvant.

  19. The calcium and vitamin D controversy

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2017-01-01

    or subanalyses while maintaining balancing. Though large clinical RCTs currently evaluate the effects of higher vitamin D doses (equivalent to 50–83 μg/d) there is no current research effort regarding the calcium controversy. In the absence of such studies it is not possible to provide clinicians with evidence......Areas of the world where vitamin D levels are low for months of the year and intakes of calcium are high have a high prevalence of osteoporosis and cardiovascular disease. This suggests a public health message of avoiding calcium supplements and increasing vitamin D intake. No message could be more...... welcome as vitamin D can be given as a bolus while calcium must be taken daily and may be poorly tolerated. This approach is based on no evidence from intervention studies. Randomized controlled trials (RCTs) suggest that vitamin D given with calcium elicits a small reduction in fracture risk and deaths...

  20. 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.

  1. Strontium Substitution for Calcium in Lithogenesis

    Science.gov (United States)

    Blaschko, Sarah D.; Chi, Thomas; Miller, Joe; Flechner, Lawrence; Fakra, Sirine; Kapahi, Pankaj; Kahn, Arnold; Stoller, Marshall L.

    2013-01-01

    Purpose Strontium has chemical similarity to calcium, which enables the replacement of calcium by strontium in biomineralization processes. Incorporating strontium into human bone and teeth has been studied extensively but little research has been performed of the incorporation of strontium into urinary calculi. We used synchrotron based x-ray fluorescence and x-ray absorption techniques to examine the presence of strontium in different types of human kidney stones. Materials and Methods Multiple unique human stone samples were obtained via consecutive percutaneous nephrolithotomies/ureteroscopies. A portion of each stone was sent for standard laboratory analysis and a portion was retained for x-ray fluorescence and x-ray absorption measurements. X-ray fluorescence and x-ray absorption measurements determined the presence, spatial distribution and speciation of strontium in each stone sample. Results Traditional kidney stone analyses identified calcium oxalate, calcium phosphate, uric acid and cystine stones. X-ray fluorescence measurements identified strontium in all stone types except pure cystine. X-ray fluorescence elemental mapping of the samples revealed co-localization of calcium and strontium. X-ray absorption measurements of the calcium phosphate stone showed strontium predominately present as strontium apatite. Conclusions Advanced x-ray fluorescence imaging identified strontium in all calcium based stones, present as strontium apatite. This finding may be critical since apatite is thought to be the initial nidus for calcium stone formation. Strontium is not identified by standard laboratory stone analyses. Its substitution for calcium can be reliably identified in stones from multiple calcium based stone formers, which may offer opportunities to gain insight into early events in lithogenesis. PMID:23260568

  2. A comparison of total calcium, corrected calcium, and ionized calcium concentrations as indicators of calcium homeostasis among hypoalbuminemic dogs requiring intensive care.

    Science.gov (United States)

    Sharp, Claire R; Kerl, Marie E; Mann, F A

    2009-12-01

    (1) To evaluate whether total calcium (tCa) correlates with ionized calcium (iCa) in hypoalbuminemic dogs; (2) to evaluate whether calcium adjusted for albumin (Alb), or total protein (TP), or both accurately predict iCa concentrations and hence can be used to monitor calcium homeostasis in critically ill hypoalbuminemic dogs; and (3) to evaluate factors associated with any potential discrepancy in calcium classification between corrected total and ionized values. Prospective observational clinical study. Small animal intensive care unit in a veterinary medical teaching hospital. Twenty-eight client-owned dogs with hypoalbuminemia. None. iCa was determined using ion-specific electrode methodology, on heparinized plasma. The tCa concentration was adjusted for Alb and TP using published equations. In total 29% (8/28) of the hypoalbuminemic, critically ill dogs in this study were hypocalcemic at intensive care unit admission, as determined by iCa measurement. Corrected calcium values failed to accurately classify calcium status in 67.9% and 64.3% of cases, according to whether the Alb-adjusted or TP-adjusted values, respectively, were used. The sensitivity and specificity of the tCa to evaluate hypocalcemia was 100% and 47%, respectively. The sensitivity and specificity of the correction formulae were 37.5% and 79% for the Alb-adjusted values and 37.5% and 74% for TP-adjusted values. tCa overestimated the presence of hypocalcemia and underestimated the presence of normocalcemia, while corrected calcium values overestimated the presence of normocalcemia and underestimated the presence of hypocalcemia. Calcium homeostasis in hypoalbuminemic critically ill dogs should be evaluated by iCa concentrations rather than tCa or calcium adjusted for Alb or TP. Given that tCa has 100% sensitivity for detecting hypocalcemia in this population it is recommended that all hypoalbuminemic and critically ill patients with low tCa should be evaluated with an iCa measurement.

  3. Tuning local calcium availability: cell-type-specific immobile calcium buffer capacity in hippocampal neurons.

    Science.gov (United States)

    Matthews, Elizabeth A; Schoch, Susanne; Dietrich, Dirk

    2013-09-04

    It has remained difficult to ascribe a specific functional role to immobile or fixed intracellular calcium buffers in central neurons because the amount of these buffers is unknown. Here, we explicitly isolated the fixed buffer fraction by prolonged whole-cell patch-clamp dialysis and quantified its buffering capacity in murine hippocampal slices using confocal calcium imaging and the "added-buffer" approach. In dentate granule cells, the calcium binding ratio (κ) after complete washout of calbindin D28k (Cb), κfixed, displayed a substantial value of ∼100. In contrast, in CA1 oriens lacunosum moleculare (OLM) interneurons, which do not contain any known calcium-binding protein(s), κfixed amounted to only ∼30. Based on these values, a theoretical analysis of dendritic spread of calcium after local entry showed that fixed buffers, in the absence of mobile species, decrease intracellular calcium mobility 100- and 30-fold in granule cells and OLM cells, respectively, and thereby strongly slow calcium signals. Although the large κfixed alone strongly delays the spread of calcium in granule cells, this value optimizes the benefits of additionally expressing the mobile calcium binding protein Cb. With such high κfixed, Cb effectively increases the propagation velocity to levels seen in OLM cells and, contrary to expectation, does not affect the peak calcium concentration close to the source but sharpens the spatial and temporal calcium gradients. The data suggest that the amount of fixed buffers determines the temporal availability of calcium for calcium-binding partners and plays a pivotal role in setting the repertoire of cellular calcium signaling regimens.

  4. 25 CFR 43.20 - Directory information.

    Science.gov (United States)

    2010-04-01

    ... BUREAU SCHOOLS § 43.20 Directory information. (a) Any educational institution making public directory... recognized activities and sports, weight and height of members of athletic teams, dates of attendance...

  5. Molecular Neuropathology of TDP-43 Proteinopathies

    Directory of Open Access Journals (Sweden)

    Manuela Neumann

    2009-01-01

    Full Text Available The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U and amyotrophic lateral sclerosis (ALS resolved a long-standing enigma concerning the nature of the ubiquitinated disease protein under these conditions. Anti-TDP-43 immunohistochemistry and the recent development of novel tools, such as phosphorylation-specific TDP-43 antibodies, have increased our knowledge about the spectrum of pathological changes associated with FTLD-U and ALS and moreover, facilitated the neuropathological routine diagnosis of these conditions. This review summarizes the recent advances in our understanding on the molecular neuropathology and pathobiology of TDP-43 in FTLD and ALS.

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

    Science.gov (United States)

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

    2012-05-15

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

  7. Non-calcium desulphurisation technologies

    Energy Technology Data Exchange (ETDEWEB)

    Qian Zhu [IEA Clean Coal Centre, London (United Kingdom)

    2010-06-15

    Flue gas desulphurisation (FGD) is traditionally based on limestone/lime sorbent. The majority of the installed FGD systems worldwide use limestone or lime as sorbent. However, technologies are rapidly evolving that allow desulphurisation in regions where there are limited resources of lime or limestone. These technologies provide alternatives to limestone/lime scrubbers for efficient and cost effective control of SO{sub 2} emissions from coal combustion. This report reviews the existing and emerging non-calcium based FGD processes as well as FGD technologies currently under development that apply new concepts and different approaches. It looks at the fundamentals and features of these processes, the recent technical advances and their applications in coal-fired power plants. The capital and operating costs of the processes are evaluated where information available. 66 refs., 15 figs., 10 tabs.

  8. 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...

  9. Internal translation of the connexin 43 transcript.

    Science.gov (United States)

    Salat-Canela, Clàudia; Sesé, Marta; Peula, Cristina; Ramón y Cajal, Santiago; Aasen, Trond

    2014-05-08

    Connexin 43 (Cx43), the most widely expressed gap junction protein, is associated with a number of physiological and pathological conditions. Many functions of Cx43 have been shown to be independent of gap junction formation and only require the expression of Cx43 C-terminal fragments. Recent evidence demonstrated that naturally occurring C-terminal isoforms can be generated via internal translation. Here, we confirm that C-terminal domains of Cx43, particularly the major 20-kDa isoform, can be independently generated and regulated by internal translation of the same single GJA1 gene transcript that encodes full-length Cx43. Through direct RNA transfection experiments, we provide evidence that internal translation is not due to a bona fide cap-independent IRES-mediated mechanism, as upstream ribosomal scanning or translation is required. In addition to the mTOR pathway, we show for the first time, using both inhibitors and cells from knockout mice, that the Mnk1/2 pathway regulates the translation of the main 20-kDa isoform. Internal translation of the Cx43 transcript occurs but is not cap-independent and requires translation upstream of the internal start codon. In addition to the PI3K/AKT/mTOR pathway, the major 20-kDa isoform is regulated by the Mnk1/2 pathway. Our results have major implications for past and future studies describing gap junction-independent functions of Cx43 in cancer and other pathological conditions. This study provides further clues to the signalling pathways that regulate internal mRNA translation, an emerging mechanism that allows for increased protein diversity and functional complexity from a single mRNA transcript.

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

    Directory of Open Access Journals (Sweden)

    Lu Ake Tzu-Hui

    2012-12-01

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

  11. Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells.

    Science.gov (United States)

    Ming, Jia; Zhou, Yan; Du, Junze; Fan, Shenghao; Pan, Beibei; Wang, Yinhuan; Fan, Lingjun; Jiang, Jun

    2015-08-17

    Both miRNAs (miRs) and connexin 43 (Cx43) were important regulators of the metastasis of breast cancer, whereas the miRs regulating Cx43 expression in breast cancer cells were still obscure. In the present study, we scanned and found miR-1, miR-206, miR-200a, miR-381, miR-23a/b and miR-186 were functional suppressors of human Cx43 mRNA and protein expression. Specially, we demonstrated that only miR-200a could directly target the 3'-untranslated region (3'-UTR) of human Cx43 gene. Functionally, overexpression of Cx43 in MCF cells potentiated the migration activity, whereas additional miR-200a treatment notably prevented this effect. Finally, we demonstrated that decreased levels of miR-200a and elevated expression of Cx43 in the metastatic breast cancer tissues compared with the primary ones. Thus, we are the first to identify miR-200a as a novel and direct suppressor of human Cx43, indicating that miR200a/Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer. © 2015 Authors.

  12. Dietary habits in women with recurrent idiopathic calcium nephrolithiasis.

    Science.gov (United States)

    Meschi, Tiziana; Nouvenne, Antonio; Ticinesi, Andrea; Prati, Beatrice; Guerra, Angela; Allegri, Franca; Pigna, Federica; Soldati, Laura; Vezzoli, Giuseppe; Gambaro, Giovanni; Lauretani, Fulvio; Maggio, Marcello; Borghi, Loris

    2012-03-28

    Nutrition has been widely recognized to influence the risk of kidney stone formation. Therefore the aim of our study was to assess: a) whether usual diet of women with idiopathic calcium nephrolithiasis (ICN) living in Parma (Northern-Italy) is different compared to healthy controls, b) how their diet differs from Italian National guidelines and c) whether it is related to nephrolithiasis clinical course. 143 women with recurrent ICN (mean age 43 ± 13 ys) and 170 healthy women (mean age 42 ± 11 ys) were enrolled. All women completed a food frequency questionnaire for the last 60-days and a 3-day dietary diary analysed with a dedicated software. Stone formers showed a higher consumption of sausages, ham, meat and sweets than healthy controls (43.1% vs 11.1%, 29.4% vs 13.9%, 21.6% vs 4.2%, 66.7% vs 18.1%, p 40 years), the differences described above were amplified in the class ≤30 years, where nephrolithiasis presented a more serious course (shorter recurrence interval, greater stone-rate). In this age group the intake of fruit and vegetables was notably lower than guideline recommendations. We conclude that the usual diet of women with recurrent ICN is different from controls and characterized by low intake of fruits and vegetables and higher consumption of simple sugars and foods with high protein and salt content. This dietary imbalance could play a role in the ICN pathogenesis, especially in younger women.

  13. 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. © 2010 International Life Sciences Institute.

  14. Calcium phosphate scaffold from biogenic calcium carbonate by fast ambient condition reactions

    Science.gov (United States)

    Dutta, Abhishek; Fermani, Simona; Arjun Tekalur, Srinivasan; Vanderberg, Abigail; Falini, Giuseppe

    2011-12-01

    Calcium phosphate biogenic materials are biocompatible and promote bioactivity and osteoconductivity, which implies their natural affinity and tendency to bond directly to bones subsequently replacing the host bone after implantation owing to its biodegradability. Calcium hydrogen phosphate dihydrate, CaHPO 4·2H 2O, is known to be a nucleation precursor, in aqueous solutions, for apatitic calcium phosphates and, hence, a potential starting material for bone substitutes. Numerous approaches, via hydrothermal and ambient synthetic routes, have been used to produce calcium phosphate from biogenic calcium carbonate, taking advantage of the peculiar architecture and composition of the latter. In this article, the lamellar region of the cuttlefish bone ( Sepia officinalis) was used as a framework for the organized deposition of calcium phosphate crystals, at ambient conditions via a fast procedure involving an amorphous calcium carbonate intermediate, and ending with a conversion to calcium phosphate and a fixation procedure, thereby resulting in direct conversion of biogenic calcium carbonate into calcium phosphates at ambient conditions from the scale of months to hours.

  15. In vitro antioxidant properties of calcium dobesilate.

    Science.gov (United States)

    Brunet, J; Farine, J C; Garay, R P; Hannaert, P

    1998-01-01

    Calcium dobesilate, a vascular protective agent, was tested in vitro for its scavenging action against oxygen free radicals. Calcium dobesilate was as potent as rutin to scavenge hydroxyl radicals (IC50 = 1.1 vs 0.7 microM, respectively). It was also able to scavenge superoxide radicals, but with 23 times less potency than rutin (IC50 = 682 vs 30 microM, respectively). Calcium dobesilate significantly reduced platelet activating factor (PAF)-induced chemiluminescence in human PMN cells and lipid peroxidation by oxygen free radicals in human erythrocyte membranes, although these actions required calcium dobesilate concentrations > or = 50 microM. Finally, in cultured bovine aortic endothelial cells, magnesium dobesilate reduced the increase in cytosolic free calcium induced by hydrogen peroxide and inhibited phenazine methosulfate-induced cell potassium loss. In conclusion, calcium dobesilate was effective in scavenging hydroxyl radicals in vitro, at therapeutically relevant concentrations. Conversely, higher concentrations of the compound were required to scavenge superoxide radicals or to protect the cells against the deleterious effects of intracellular reactive oxygen species. Further studies in vivo are required to determine if these antioxidant properties of calcium dobesilate can play a role in its vascular protective mechanisms.

  16. Intracellular sphingosine releases calcium from lysosomes

    Science.gov (United States)

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

    2015-01-01

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. DOI: http://dx.doi.org/10.7554/eLife.10616.001 PMID:26613410

  17. Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones.

    Science.gov (United States)

    Yu, Ji-Kuen; Pan, Huichin; Huang, Shing-Moo; Huang, Nan-Lan; Yao, Chung-Chin; Hsiao, Kuang-Ming; Wu, Chew-Wun

    2013-01-01

    Our aim was to investigate the calcium content of different gallstone compositions and the pathogenic mechanisms of calcium carbonate gallstones. Between August 2001 and July 2007, gallstones from 481 patients, including 68 calcium carbonate gallstones, were analyzed for total calcium content. Gallbladder bile samples from 33 cases and six controls were analyzed for pH, carbonate anion level, free-ionized calcium concentration and saturation index for calcium carbonate. Total calcium content averaged 75.6 %, 11.8 %, and 4.2 % for calcium carbonate, calcium bilirubinate and cholesterol gallstones. In 29.4 % of patients, chronic and/or intermittent cystic duct obstructions were caused by polypoid lesions in the neck region and 70.6 % were caused by stones. A total of 82 % of patients had chronic low-grade inflammation of the gallbladder wall and 18.0 % had acute inflammatory exacerbations. In the bile, we found the mean pH, mean carbonate anion, free-ionized calcium concentrations, and mean saturation index for calcium carbonate to be elevated in comparison to controls. From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO(3) from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate. Copyright © 2012. Published by Elsevier B.V.

  18. 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.

  19. Peptides of Matrix Gla protein inhibit nucleation and growth of hydroxyapatite and calcium oxalate monohydrate crystals.

    Directory of Open Access Journals (Sweden)

    Maria Goiko

    Full Text Available Matrix Gla protein (MGP is a phosphorylated and γ-carboxylated protein that has been shown to prevent the deposition of hydroxyapatite crystals in the walls of blood vessels. MGP is also expressed in kidney and may inhibit the formation of kidney stones, which mainly consist of another crystalline phase, calcium oxalate monohydrate. To determine the mechanism by which MGP prevents soft-tissue calcification, we have synthesized peptides corresponding to the phosphorylated and γ-carboxylated sequences of human MGP in both post-translationally modified and non-modified forms. The effects of these peptides on hydroxyapatite formation and calcium oxalate crystallization were quantified using dynamic light scattering and scanning electron microscopy, respectively. Peptides YGlapS (MGP1-14: YγEpSHEpSMEpSYELNP, YEpS (YEpSHEpSMEpSYELNP, YGlaS (YγESHESMESYELNP and SK-Gla (MGP43-56: SKPVHγELNRγEACDD inhibited formation of hydroxyapatite in order of potency YGlapS > YEpS > YGlaS > SK-Gla. The effects of YGlapS, YEpS and YGlaS on hydroxyapatite formation were on both crystal nucleation and growth; the effect of SK-Gla was on nucleation. YGlapS and YEpS significantly inhibited the growth of calcium oxalate monohydrate crystals, while simultaneously promoting the formation of calcium oxalate dihydrate. The effects of these phosphopeptides on calcium oxalate monohydrate formation were on growth of crystals rather than nucleation. We have shown that the use of dynamic light scattering allows inhibitors of hydroxyapatite nucleation and growth to be distinguished. We have also demonstrated for the first time that MGP peptides inhibit the formation of calcium oxalate monohydrate. Based on the latter finding, we propose that MGP function not only to prevent blood-vessel calcification but also to inhibit stone formation in kidney.

  20. Protein-Mediated Precipitation of Calcium Carbonate

    Directory of Open Access Journals (Sweden)

    Izabela Polowczyk

    2016-11-01

    Full Text Available Calcium carbonate is an important component in exoskeletons of many organisms. The synthesis of calcium carbonate was performed by mixing dimethyl carbonate and an aqueous solution of calcium chloride dihydrate. The precipitation product was characterized by means of scanning electron microscopy (SEM, transmission electron microscopy (TEM, X-ray diffraction (XRD, and Fourier transform infrared spectroscopy (FTIR measurements. In addition, the turbidity of the reaction solution was acquired to monitor the kinetics of the calcium carbonate structure’s growth in the investigated system. In this study, samples of CaCO3 particles obtained with individual proteins, such as ovalbumin, lysozyme, and a mixture of the proteins, were characterized and compared with a control sample, i.e., synthesized without proteins. The obtained data indicated that the addition of ovalbumin to the reaction changed the morphology of crystals from rhombohedral to ‘stack-like’ structures. Lysozyme, however, did not affect the morphology of calcium carbonate, yet the presence of the protein mixture led to the creation of more complex composites in which the calcium carbonate crystals were constructed in protein matrices formed by the ovalbumin-lysozyme interaction. It was also observed that in the protein mixture, ovalbumin has a major influence on the CaCO3 formation through a strong interaction with calcium ions, which leads to the coalescence and creation of a steric barrier reducing particle growth. The authors proposed a mechanism of calcium carbonate grain growth in the presence of both proteins, taking into account the interaction of calcium ions with the protein.

  1. Protein-Mediated Precipitation of Calcium Carbonate

    Science.gov (United States)

    Polowczyk, Izabela; Bastrzyk, Anna; Fiedot, Marta

    2016-01-01

    Calcium carbonate is an important component in exoskeletons of many organisms. The synthesis of calcium carbonate was performed by mixing dimethyl carbonate and an aqueous solution of calcium chloride dihydrate. The precipitation product was characterized by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) measurements. In addition, the turbidity of the reaction solution was acquired to monitor the kinetics of the calcium carbonate structure’s growth in the investigated system. In this study, samples of CaCO3 particles obtained with individual proteins, such as ovalbumin, lysozyme, and a mixture of the proteins, were characterized and compared with a control sample, i.e., synthesized without proteins. The obtained data indicated that the addition of ovalbumin to the reaction changed the morphology of crystals from rhombohedral to ‘stack-like’ structures. Lysozyme, however, did not affect the morphology of calcium carbonate, yet the presence of the protein mixture led to the creation of more complex composites in which the calcium carbonate crystals were constructed in protein matrices formed by the ovalbumin-lysozyme interaction. It was also observed that in the protein mixture, ovalbumin has a major influence on the CaCO3 formation through a strong interaction with calcium ions, which leads to the coalescence and creation of a steric barrier reducing particle growth. The authors proposed a mechanism of calcium carbonate grain growth in the presence of both proteins, taking into account the interaction of calcium ions with the protein. PMID:28774065

  2. 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.

  3. Coronary artery calcium score: current status

    Science.gov (United States)

    Neves, Priscilla Ornellas; Andrade, Joalbo; Monção, Henry

    2017-01-01

    The coronary artery calcium score plays an Important role In cardiovascular risk stratification, showing a significant association with the medium- or long-term occurrence of major cardiovascular events. Here, we discuss the following: protocols for the acquisition and quantification of the coronary artery calcium score by multidetector computed tomography; the role of the coronary artery calcium score in coronary risk stratification and its comparison with other clinical scores; its indications, interpretation, and prognosis in asymptomatic patients; and its use in patients who are symptomatic or have diabetes. PMID:28670030

  4. FM dyes enter via a store-operated calcium channel and modify calcium signaling of cultured astrocytes

    Science.gov (United States)

    Li, Dongdong; Hérault, Karine; Oheim, Martin; Ropert, Nicole

    2009-01-01

    The amphiphilic fluorescent styryl pyridinium dyes FM1-43 and FM4-64 are used to probe activity-dependent synaptic vesicle cycling in neurons. Cultured astrocytes can internalize FM1-43 and FM4-64 inside vesicles but their uptake is insensitive to the elevation of cytosolic calcium (Ca2+) concentration and the underlying mechanism remains unclear. Here we used total internal reflection fluorescence microscopy and pharmacological tools to study the mechanisms of FM4-64 uptake into cultured astrocytes from mouse neocortex. Our data show that: (i) endocytosis is not a major route for FM4-64 uptake into astrocytes; (ii) FM4-64 enters astrocytes through an aqueous pore and strongly affects Ca2+ homeostasis; (iii) partitioning of FM4-64 into the outer leaflet of the plasma membrane results in a facilitation of store-operated Ca2+ entry (SOCE) channel gating; (iv) FM4-64 permeates and competes with Ca2+ for entry through a SOCE channel; (v) intracellular FM4-64 mobilizes Ca2+ from the endoplasmic reticulum stores, conveying a positive feedback to activate SOCE and to sustain dye uptake into astrocytes. Our study demonstrates that FM dyes are not markers of cycling vesicles in astrocytes and calls for a careful interpretation of FM fluorescence. PMID:20007370

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    . The use of coronary calcium image subtraction improved the reader confidence in 66% of these segments. In target segments, specificity (86% vs 65%; P positive predictive value (71% vs 51%, P = .03) were improved using CCTAsub compared to CCTAconv without loss in negative predictive value....... We defined target segments on CCTAconv as motion-free coronary segments with calcification or stent and low reader confidence. The effect of CCTAsub was assessed. No approval from the ethics committee was required according to Danish law. RESULTS: A total of 76 target segments were identified...... severity leading to false-positive results. In a pilot study, we tested the feasibility of a new coronary calcium image subtraction algorithm in relation to reader confidence and diagnostic accuracy. METHODS: Forty-three patients underwent clinically indicated ICA and CCTA using a 320-detector row CT...

  6. Fractional Absorption of Active Absorbable Algal Calcium (AAACa and Calcium Carbonate Measured by a Dual Stable-Isotope Method

    Directory of Open Access Journals (Sweden)

    Steven A. Abrams

    2010-07-01

    Full Text Available With the use of stable isotopes, this study aimed to compare the bioavailability of active absorbable algal calcium (AAACa, obtained from oyster shell powder heated to a high temperature, with an additional heated seaweed component (Heated Algal Ingredient, HAI, with that of calcium carbonate. In 10 postmenopausal women volunteers aged 59 to 77 years (mean ± S.D., 67 ± 5.3, the fractional calcium absorption of AAACa and CaCO3 was measured by a dual stable isotope method. 44Ca-enriched CaCO3 and AAACa were administered in all subjects one month apart. After a fixed-menu breakfast and pre-test urine collection (Urine 0, 42Ca-enriched CaCl2 was intravenously injected, followed by oral administration of 44Ca-enriched CaCO3 without carrier 15 minutes later, and complete urine collection for the next 24 hours (Urine 24. The fractional calcium absorption was calculated as the ratio of Augmentation of 44Ca from Urine 0 to Urine 24/ augmentation of 42Ca from Urine 0 to Urine 24. Differences and changes of 44Ca and 42Ca were corrected by comparing each with 43Ca. Fractional absorption of AAACa (mean ± S.D., 23.1 ± 6.4, was distinctly and significantly higher than that of CaCO3 (14.7 ± 6.4; p = 0.0060 by paired t-test. The mean fractional absorption was approximately 1.57-times higher for AAACa than for CaCO3. The serum 25(OH vitamin D level was low (mean ± S.D., 14.2 ± 4.95 ng/ml, as is common in this age group in Japan. Among the parameters of the bone and mineral metabolism measured, none displayed a significant correlation with the fractional absorption of CaCO3 and AAACa. Higher fractional absorption of AAACa compared with CaCO3 supports previous reports on the more beneficial effect of AAACa than CaCO3 for osteoporosis.

  7. STIM and calcium channel complexes in cancer.

    Science.gov (United States)

    Jardin, Isaac; Rosado, Juan A

    2016-06-01

    The ion Ca(2+) is a ubiquitous second messenger that mediates a variety of cellular functions. Dysfunction of the mechanisms involved in Ca(2+) homeostasis underlies a number of pathological processes, including cancer. Store-operated Ca(2+) entry (SOCE) is a major mechanism for Ca(2+) entry modulated by the intracellular Ca(2+) stores. The Ca(2+)-selective store-operated current (ICRAC) is mediated by the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the store-operated Ca(2+) (SOC) channel Orai1, while other non-selective cation currents (ISOC) involves the participation of members of the canonical transient receptor potential (TRPC) channel family, including TRPC1. Distinct isoforms of the key components of SOCE have been described in mammalian cells, STIM1 and 2, Orai1-3 and TRPC1-7. In cancer cells, SOCE has been reported to play an important role in cell cycle progression and proliferation, migration, metastasis and evasion of apoptosis. Changes in the expression of the key elements of SOCE and Ca(2+) homeostasis remodeling have been account to play important roles in the phenotypic changes observed in transformed cells. Despite there are differences in the expression level of the molecular components of SOCE, as well as in the relevance of the STIM, Orai and TRPC isoforms in SOCE and tumorigenesis among cancer cell types, there is a body of evidence supporting an important role for SOCE underlying the phenotypic modifications of cancer cells that propose STIM and the SOC channels as suitable candidate targets for future prognostic or therapeutic strategies. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Calcium wave signaling in cancer cells

    Science.gov (United States)

    PARKASH, JAI; ASOTRA, KAMLESH

    2010-01-01

    Ca2+ functions as an important signaling messenger right from beginning of the life to final moment of the end of the life. Ca2+ is needed at several steps of the cell cycle such as early G1, at the G1/S, and G2/M transitions. The Ca2+ signals in the form of time-dependent changes in intracellular Ca2+ concentrations, [Ca2+]i, are presented as brief spikes organized into regenerative Ca2+ waves. Ca2+-mediated signaling pathways have also been shown to play important roles in carcinogenesis such as transformation of normal cells to cancerous cells, tumor formation and growth, invasion, angiogenesis and metastasis. Since the global Ca2+ oscillations arise from Ca2+ waves initiated locally, it results in stochastic oscillations because although each cell has many IP3Rs and Ca2+ ions, the law of large numbers does not apply to the initiating event which is restricted to very few IP3Rs due to steep Ca2+ concentration gradients. The specific Ca2+ signaling information is likely to be encoded in a calcium code as the amplitude, duration, frequency, waveform or timing of Ca2+ oscillations and decoded again at a later stage. Since Ca2+ channels or pumps involved in regulating Ca2+ signaling pathways show altered expression in cancer, one can target these Ca2+ channels and pumps as therapeutic options to decrease proliferation of cancer cells and to promote their apoptosis. These studies can provide novel insights into alterations in Ca2+ wave patterns in carcinogenesis and lead to development of newer technologies based on Ca2+ waves for the diagnosis and therapy of cancer. PMID:20875431

  9. A hybrid composite system of biphasic calcium phosphate granules loaded with hyaluronic acid-gelatin hydrogel for bone regeneration.

    Science.gov (United States)

    Faruq, Omar; Kim, Boram; Padalhin, Andrew R; Lee, Gun Hee; Lee, Byong-Taek

    2017-10-01

    An ideal bone substitute should be made of biocompatible materials that mimic the structure, characteristics, and functions of natural bone. Many researchers have worked on the fabrication of different bone scaffold systems including ceramic-polymer hybrid system. In the present study, we incorporated hyaluronic acid-gelatin hydrogel to micro-channeled biphasic calcium phosphate granules as a carrier to improve cell attachment and proliferation through highly interconnected porous structure. This hybrid system is composed of ceramic biphasic calcium phosphate granules measuring 1 mm in diameter with seven holes and hyaluronic acid-gelatin hydrogel. This combination of biphasic calcium phosphate and hyaluronic acid-gelatin retained suitable characteristics for bone regeneration. The resulting scaffold had a porosity of 56% with a suitable pore sizes. The mechanical strength of biphasic calcium phosphate granule increased after loading hyaluronic acid-gelatin from 4.26 ± 0.43 to 6.57 ± 0.25 MPa, which is highly recommended for cancellous bone substitution. Swelling and degradation rates decreased in the hybrid scaffold compared to hydrogel due to the presence of granules in hybrid scaffold. In vitro cytocompatibility studies were observed by preosteoblasts (MC3T3-E1) cell line and the result revealed that biphasic calcium phosphate/hyaluronic acid-gelatin significantly increased cell growth and proliferation compared to biphasic calcium phosphate granules. Analysis of micro-computed tomography data and stained tissue sections from the implanted samples showed that the hybrid scaffold had good osseointegration and better bone formation in the scaffold one and two months postimplantation. Histological section confirmed the formation of dense collagenous tissue and new bone in biphasic calcium phosphate/hyaluronic acid-gelatin scaffolds at two months. Our study demonstrated that such hybrid biphasic calcium phosphate/hyaluronic acid-gelatin scaffold is a

  10. GPR41 and GPR43¬ in obesity and inflammation – protective or causative?

    Directory of Open Access Journals (Sweden)

    Zhiwei eAng

    2016-02-01

    Full Text Available 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.

  11. 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.

  12. The effect of calcium supplementation on blood lead levels in Nigerian children.

    Science.gov (United States)

    Keating, Elizabeth M; Fischer, Philip R; Pettifor, John M; Pfitzner, Mark; Isichei, Christian O; Thacher, Tom D

    2011-11-01

    To determine whether calcium supplementation alters the risk of lead toxicity. Children aged 12-18 months from 3 communities in Nigeria were assigned to receive daily calcium supplementation, as either calcium carbonate (400 mg) or ground dried fish (529 ± 109 mg), or placebo. All children received 2500 IU of vitamin A. Levels of blood lead, calcium, and vitamin D metabolites were measured at baseline and after 12-18 months (n = 358). The mean (± SD) baseline lead level was 11.1 ± 7.8 μg/dL (range, 1-43 μg/dL; median, 9 μg/dL); 44.7% of subjects had a lead level >10 μg/dL. After 12-18 months, the mean lead level was 8.1 ± 6.3 μg/dL (range, 1-48 μg/dL; median, 6 μg/dL), with 22.6% with a level >10 μg/dL. Lead levels at baseline varied among communities (P = .01) and were higher in children who used eye cosmetics or lived near a lead-acid battery melter (both P affect blood lead levels. Copyright © 2011 Mosby, Inc. All rights reserved.

  13. Calcium absorption from fortified ice cream formulations compared with calcium absorption from milk.

    Science.gov (United States)

    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

    2009-05-01

    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-fortified ice cream formulation that is lower in fat than regular ice cream and could provide a useful source of additional dietary calcium. Calcium absorption from two different ice cream formulations was determined in young adults and compared with milk. Sixteen healthy volunteers (25 to 45 years of age), recruited from the general public of The Netherlands, participated in a randomized, reference-controlled, double-blind cross-over study in which two test products and milk were consumed with a light standard breakfast on three separate occasions: a standard portion of ice cream (60 g) fortified with milk minerals and containing a low level (3%) of butter fat, ice cream (60 g) fortified with milk minerals and containing a typical level (9%) of coconut oil, and reduced-fat milk (1.7% milk fat) (200 mL). Calcium absorption was measured by the dual-label stable isotope technique. Effects on calcium absorption were evaluated by analysis of variance. Fractional absorption of calcium from the 3% butterfat ice cream, 9% coconut oil ice cream, and milk was 26%+/-8%, 28%+/-5%, and 31%+/-9%, respectively, and did not differ significantly (P=0.159). Results indicate that calcium bioavailability in the two calcium-fortified ice cream formulations used in this study is as high as milk, indicating that ice cream may be a good vehicle for delivery of calcium.

  14. Effects of Adding Chymosin to Milk on Calcium Homeostasis

    DEFF Research Database (Denmark)

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

    2014-01-01

    either chymosin or similar placebo was added. Compared with placebo, chymosin did not affect 24-h urinary calcium, calcium/creatinine ratio, plasma parathyroid hormone, calcitonin or ionized calcium levels. However, during the first 4 h after intake of milk with chymosin, urinary calcium-creatinine ratio...

  15. Does calcium constrain reproductive activity in insectivorous bats ...

    African Journals Online (AJOL)

    Insects are a poor source of dietary calcium and since they are seasonally abundant, it has been suggested that calcium availability may play a significant role in controlling the timing of reproduction in insectivorous bats. To assess the possible role of dietary calcium, we have measured bone calcium concentrations in ...

  16. Model of intracellular calcium cycling in ventricular myocytes.

    Science.gov (United States)

    Shiferaw, Y; Watanabe, M A; Garfinkel, A; Weiss, J N; Karma, A

    2003-12-01

    We present a mathematical model of calcium cycling that takes into account the spatially localized nature of release events that correspond to experimentally observed calcium sparks. This model naturally incorporates graded release by making the rate at which calcium sparks are recruited proportional to the whole cell L-type calcium current, with the total release of calcium from the sarcoplasmic reticulum (SR) being just the sum of local releases. The dynamics of calcium cycling is studied by pacing the model with a clamped action potential waveform. Experimentally observed calcium alternans are obtained at high pacing rates. The results show that the underlying mechanism for this phenomenon is a steep nonlinear dependence of the calcium released from the SR on the diastolic SR calcium concentration (SR load) and/or the diastolic calcium level in the cytosol, where the dependence on diastolic calcium is due to calcium-induced inactivation of the L-type calcium current. In addition, the results reveal that the calcium dynamics can become chaotic even though the voltage pacing is periodic. We reduce the equations of the model to a two-dimensional discrete map that relates the SR and cytosolic concentrations at one beat and the previous beat. From this map, we obtain a condition for the onset of calcium alternans in terms of the slopes of the release-versus-SR load and release-versus-diastolic-calcium curves. From an analysis of this map, we also obtain an understanding of the origin of chaotic dynamics.

  17. Vitamin D with calcium reduces mortality

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Avenell, Alison; Masud, Tahir

    2012-01-01

    Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either...... calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06).Conclusion:Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone....... vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight...

  18. 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.

  19. Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage

    National Research Council Canada - National Science Library

    Cencic, Regina; Miura, Hisashi; Malina, Abba; Robert, Francis; Ethier, Sylvain; Schmeing, T Martin; Dostie, Josée; Pelletier, Jerry

    2014-01-01

    ...') protospacer adjacent motifs (PAM). Yet among 43 ChIP-seq sites harboring seed regions analyzed for mutational status, we find editing only at the intended on-target locus and one off-target site...

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

    Directory of Open Access Journals (Sweden)

    Huaigang Cheng

    2014-01-01

    Full Text Available Ultrafine calcium carbonate is a widely used cheap additive. The research is conducted in low degree supersaturation solution in order to study the polymorphic phases’ change and its factors of the calcium carbonate precipitate in the ammonification-carbonization process of the solution with calcium. Fine particles of calcium carbonate are made in the solution containing 0.015 mol/L of Ca2+. Over 98% of the calcium carbonate precipitate without ammonification resembles the morphology of calcite, while the introduction of ammonia can benefit the formation of vaterite. It was inferred that the main cause should be serious partial oversaturation or steric effects. Ammonia also helps to form the twin spherical calcium carbonate. However, particles formed in the process of ammonification-carbonization in solution with low concentration degree of calcium are not even with a scale of the particle diameter from 5 to 12 μm. Inorganic salts, alcohol, or organic acid salts have significant controlling effect on the particle diameter of calcium carbonate and can help to decrease the particle diameter to about 3 μm. Anionic surfactants can prevent the conglobation of calcium carbonate particles and shrink its diameter to 500 nm–1 μm.

  1. Fractal aspects of calcium binding protein structures

    Energy Technology Data Exchange (ETDEWEB)

    Isvoran, Adriana [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania)], E-mail: aisvoran@cbg.uvt.ro; Pitulice, Laura [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania); Craescu, Constantin T. [INSERM U759/Institute Curie-Recherche, Centre Universitaire Paris-Sud, Batiment 112, 91405 Orsay (France); Chiriac, Adrian [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania)

    2008-03-15

    The structures of EF-hand calcium binding proteins may be classified into two distinct groups: extended and compact structures. In this paper we studied 20 different structures of calcium binding proteins using the fractal analysis. Nine structures show extended shapes, one is semi-compact and the other 10 have compact shapes. Our study reveals different fractal characteristics for protein backbones belonging to different structural classes and these observations may be correlated to the physicochemical forces governing the protein folding.

  2. 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.

  3. Analytical models of calcium binding in a calcium channel

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jinn-Liang [Department of Applied Mathematics, National Hsinchu University of Education, Hsinchu 300, Taiwan (China); Eisenberg, Bob [Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois 60612 (United States)

    2014-08-21

    The anomalous mole fraction effect of L-type calcium channels is analyzed using a Fermi like distribution with the experimental data of Almers and McCleskey [J. Physiol. 353, 585 (1984)] and the atomic resolution model of Lipkind and Fozzard [Biochemistry 40, 6786 (2001)] of the selectivity filter of the channel. Much of the analysis is algebraic, independent of differential equations. The Fermi distribution is derived from the configuration entropy of ions and water molecules with different sizes, different valences, and interstitial voids between particles. It allows us to calculate potentials and distances (between the binding ion and the oxygen ions of the glutamate side chains) directly from the experimental data using algebraic formulas. The spatial resolution of these results is comparable with those of molecular models, but of course the accuracy is no better than that implied by the experimental data. The glutamate side chains in our model are flexible enough to accommodate different types of binding ions in different bath conditions. The binding curves of Na{sup +} and Ca{sup 2+} for [CaCl{sub 2}] ranging from 10{sup −8} to 10{sup −2} M with a fixed 32 mM background [NaCl] are shown to agree with published Monte Carlo simulations. The Poisson-Fermi differential equation—that includes both steric and correlation effects—is then used to obtain the spatial profiles of energy, concentration, and dielectric coefficient from the solvent region to the filter. The energy profiles of ions are shown to depend sensitively on the steric energy that is not taken into account in the classical rate theory. We improve the rate theory by introducing a steric energy that lumps the effects of excluded volumes of all ions and water molecules and empty spaces between particles created by Lennard-Jones type and electrostatic forces. We show that the energy landscape varies significantly with bath concentrations. The energy landscape is not constant.

  4. 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.

  5. Conceptual Design Plan SM-43 Replacement Project

    Energy Technology Data Exchange (ETDEWEB)

    University of California, Los Alamos National Laboratory, SCC Project Office

    2000-11-01

    The Los Alamos National Laboratory Conceptual Design Plan for the SM-43 Replacement Project outlines plans for replacing the SM-43 Administration Building. Topics include the reasons that replacement is considered a necessity; the roles of the various project sponsors; and descriptions of the proposed site and facilities. Also covered in this proposal is preliminary information on the project schedule, cost estimates, acquisition strategy, risk assessment, NEPA strategy, safety strategy, and safeguards and security. Spreadsheets provide further detail on space requirements, project schedules, and cost estimates.

  6. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease.

    Science.gov (United States)

    Fanelli, F; Cannavale, A; Gazzetti, M; Lucatelli, P; Wlderk, A; Cirelli, C; d'Adamo, A; Salvatori, F M

    2014-08-01

    This study was designed to assess the effect of calcium on the efficacy of DEB during revascularization of steno-obstructive SFA lesions. Sixty patients with de novo lesions of the superficial femoral artery underwent endovascular treatment with drug eluting balloons (DEB). DEB was selected according to vessel reference diameter (1:1). In case of residual stenosis > 50 % or flow-limiting dissection, postdilatation with conventional balloon or provisional stenting was done. Patients were classified into eight groups according to circumferential distribution of calcium on CT-angiography axial images (from 0° to 360°) and to its length (length  3 cm) evaluated with digital-subtraction-angiography. Ankle-brachial index (ABI), late lumen loss (LLL), target lesion revascularization (TLR), primary (PP) and secondary (SP) patency, major adverse events (MAE), and Rutherford shift were evaluated at 1-year follow-up and correlated with the amount of calcium. Revascularization was successful in all cases. Flow-limiting dissection occurred in five cases (8.3 %) with a higher circumferential degree of calcium and solved in three cases with postdilatation and in the other two with provisional stenting. DEB effect was lower in patients with higher degree of calcium (>270° vs. <90°): ABI 0.71 ± 0.07 versus 0.92 ± 0.07; LLL 0.75 ± 0.21 versus 0.45 ± 0.1; PP 50 versus 100 %; SP 50 versus 100 %; TLR 25 versus 0 %; MAE 25 versus 0 %. Calcium represents a barrier to optimal drug absorption. Circumferential distribution seems to be the most influencing factor with the worst effect noticed in 360° calcium presence.

  7. Calcium intake and colorectal cancer risk: dose-response meta-analysis of prospective observational studies.

    Science.gov (United States)

    Keum, NaNa; Aune, Dagfinn; Greenwood, Darren C; Ju, Woong; Giovannucci, Edward L

    2014-10-15

    Mechanistic and epidemiologic studies provide considerable evidence for a protective association between calcium intake and incident colorectal cancer (CRC). While the relationship has not been substantiated by short-duration randomized controlled trials (RCTs) of CRC, trials do show a benefit on adenomas, a precursor to CRC. To address some of this inconsistency, we conducted dose-response meta-analyses by sources of calcium intake, based on prospective observational studies published up to December 2013 identified from PubMed, Embase, and BIOSIS. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. For total calcium intake, each 300 mg/day increase was associated with an approximately 8% reduced risk of CRC (summary RR = 0.92, 95% CI = 0.89-0.95, I(2)  = 47%, 15 studies with 12,305 cases, intake = 250-1,900 mg/day, follow-up = 3.3-16 years). While the risk decreased less steeply in higher range of total calcium intake (P(non-linearity)  = 0.04), the degree of curvature was mild and statistical significance of non-linearity was sensitive to one study. For supplementary calcium, each 300 mg/day increase was associated with an approximately 9% reduced risk of CRC (summary RR = 0.91, 95% CI = 0.86-0.98, I(2)  = 67%, six studies with 8,839 cases, intake = 0-1,150 mg/day, follow-up = 5-10 years). The test for non-linearity was not statistically significant (P(non-linearity)  = 0.11). In conclusion, both dietary and supplementary calcium intake may continue to decrease CRC risk beyond 1,000 mg/day. Calcium supplements and non-dairy products fortified with calcium may serve as additional targets in the prevention of CRC. RCTs of calcium supplements with at least 10 years of follow-up are warranted to confirm a benefit of calcium supplements on CRC risk. © 2014 UICC.

  8. Self-Setting Calcium Orthophosphate Formulations

    Science.gov (United States)

    Dorozhkin, Sergey V.

    2013-01-01

    In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are bioactive and biodegradable grafting bioceramics in the form of a powder and a liquid. After mixing, both phases form pastes, which set and harden forming either a non-stoichiometric calcium deficient hydroxyapatite or brushite. Since both of them are remarkably biocompartible, bioresorbable and osteoconductive, self-setting calcium orthophosphate formulations appear to be promising bioceramics for bone grafting. Furthermore, such formulations possess excellent molding capabilities, easy manipulation and nearly perfect adaptation to the complex shapes of bone defects, followed by gradual bioresorption and new bone formation. In addition, reinforced formulations have been introduced, which might be described as calcium orthophosphate concretes. The discovery of self-setting properties opened up a new era in the medical application of calcium orthophosphates and many commercial trademarks have been introduced as a result. Currently such formulations are widely used as synthetic bone grafts, with several advantages, such as pourability and injectability. Moreover, their low-temperature setting reactions and intrinsic porosity allow loading by drugs, biomolecules and even cells for tissue engineering purposes. In this review, an insight into the self-setting calcium orthophosphate formulations, as excellent bioceramics suitable for both dental and bone grafting applications, has been provided. PMID:24956191

  9. Calcium signaling in human pluripotent stem cells.

    Science.gov (United States)

    Apáti, Ágota; Berecz, Tünde; Sarkadi, Balázs

    2016-03-01

    Human pluripotent stem cells provide new tools for developmental and pharmacological studies as well as for regenerative medicine applications. Calcium homeostasis and ligand-dependent calcium signaling are key components of major cellular responses, including cell proliferation, differentiation or apoptosis. Interestingly, these phenomena have not been characterized in detail as yet in pluripotent human cell sates. Here we review the methods applicable for studying both short- and long-term calcium responses, focusing on the expression of fluorescent calcium indicator proteins and imaging methods as applied in pluripotent human stem cells. We discuss the potential regulatory pathways involving calcium responses in hPS cells and compare these to the implicated pathways in mouse PS cells. A recent development in the stem cell field is the recognition of so called "naïve" states, resembling the earliest potential forms of stem cells during development, as well as the "fuzzy" stem cells, which may be alternative forms of pluripotent cell types, therefore we also discuss the potential role of calcium homeostasis in these PS cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. High speed two-photon imaging of calcium dynamics in dendritic spines: consequences for spine calcium kinetics and buffer capacity

    NARCIS (Netherlands)

    Cornelisse, L.N.; van Elburg, R.A.J.; Meredith, R.M.; Yuste, R.; Mansvelder, H.D.

    2007-01-01

    Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action

  11. High Speed Two-Photon Imaging of Calcium Dynamics in Dendritic Spines: : Consequences for Spine Calcium Kinetics and Buffer Capacity

    NARCIS (Netherlands)

    van Elburg, R.A.J.; Cornelisse, L.N; Meredith, R.M; Yuste, R; Mansvelder, H.D

    2007-01-01

    Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action

  12. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease.

    Science.gov (United States)

    Hill, Kathleen M; Martin, Berdine R; Wastney, Meryl E; McCabe, George P; Moe, Sharon M; Weaver, Connie M; Peacock, Munro

    2013-05-01

    Patients with chronic kidney disease (CKD) are given calcium carbonate to bind dietary phosphorus, reduce phosphorus retention, and prevent negative calcium balance; however, data are limited on calcium and phosphorus balance during CKD to support this. Here, we studied eight patients with stage 3 or 4 CKD (mean estimated glomerular filtration rate 36 ml/min) who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo-controlled cross-over design. All feces and urine were collected during weeks 2 and 3 of each balance period and fasting blood, and urine was collected at baseline and at the end of each week. Calcium kinetics were determined using oral and intravenous (45)calcium. Patients were found to be in neutral calcium and phosphorus balance while on the placebo. Calcium carbonate supplementation produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance, suggesting soft-tissue deposition. Fasting blood and urine biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. Thus, the positive calcium balance produced by calcium carbonate treatment within 3 weeks cautions against its use as a phosphate binder in patients with stage 3 or 4 CKD, if these findings can be extrapolated to long-term therapy.

  13. Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells

    Science.gov (United States)

    LANGE, INGO; MOSCHNY, JULIA; TAMANYAN, KAMILLA; KHUTSISHVILI, MANANA; ATHA, DANIEL; BORRIS, ROBERT P.; KOOMOA, DANA-LYNN

    2016-01-01

    Effective neuroblastoma (NB) treatments are still limited despite treatment options available today. Therefore, this study attempted to identify novel plant extracts that have anticancer effects. Cytotoxicity and increased intracellular calcium levels were determined using the Sulforhodamine B (SRB) assay and Fluo4-AM (acetoxymethyl) staining and fluorescence microscopy in NB cells in order to screen a library of plant extracts. The current study examined the anticancer effects of a dichloromethane extract from Scrophularia orientalis L. (Scrophulariaceae), a plant that has been used in Traditional Chinese Medicine. This extract contained highly potent agents that significantly reduced cell survival and increased calcium levels in NB cells. Further analysis revealed that cell death induced by this extract was associated with intracellular calcium release, opening of the MPTP, caspase 3- and PARP-cleavage suggesting that this extract induced aberrant calcium signaling that resulted in apoptosis via the mitochondrial pathway. Therefore, agents from Scrophularia orientalis may have the potential to lead to new chemo therapeutic anticancer drugs. Furthermore, targeting intracellular calcium signaling may be a novel strategy to develop more effective treatments for NB. PMID:26848085

  14. The influence of environmental calcium concentrations on calcium flux, compensatory drinking and epithelial calcium channel expression in a freshwater cartilaginous fish.

    Science.gov (United States)

    Allen, Peter J; Weihrauch, Dirk; Grandmaison, Vanessa; Dasiewicz, Patricia; Peake, Stephan J; Anderson, W Gary

    2011-03-15

    Calcium metabolism and mRNA levels of the epithelial calcium channel (ECaC) were examined in a freshwater cartilaginous fish, the lake sturgeon Acipenser fulvescens. Lake sturgeon were acclimated for ≥2 weeks to 0.1 (low), 0.4 (normal) or 3.3 (high) mmol l(-1) environmental calcium. Whole-body calcium flux was examined using (45)Ca as a radioactive marker. Net calcium flux was inward in all treatment groups; however, calcium influx was greatest in the low calcium environment and lowest in the high calcium environment, whereas efflux had the opposite relationship. A significant difference in the concentration of (45)Ca in the gastrointestinal tract (GIT) of fish in the low calcium environment led to the examination of drinking rate and calcium flux across the anterior-middle (mid) intestine. Drinking rate was not different between treatments; however, calcium influx across the mid-intestine in the low calcium treatment was significantly greater than that in both the normal and high calcium treatments. The lake sturgeon ECaC was 2831 bp in length, with a predicted protein sequence of 683 amino acids that shared a 66% identity with the closest sequenced ECaCs from the vertebrate phyla. ECaC mRNA levels were examined in the gills, kidney, pyloric caeca, mid-intestine and spiral intestine. Expression levels were highest in the gills, then the kidneys, and were orders of magnitude lower in the GIT. Contrary to existing models for calcium uptake in the teleost gill, ECaC expression was greatest in high calcium conditions and kidney ECaC expression was lowest in low calcium conditions, suggesting that cellular transport mechanisms for calcium may be distinctly different in these freshwater cartilaginous fishes.

  15. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

    Science.gov (United States)

    Karp, Heini J; Ketola, Maarit E; Lamberg-Allardt, Christel J E

    2009-11-01

    Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

  16. 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.

  17. [Results of an intervention to reduce potentially inappropriate prescriptions of beta blockers and calcium channel blockers].

    Science.gov (United States)

    Machado-Alba, J E; Giraldo-Giraldo, C; Aguirre Novoa, A

    2016-01-01

    To determine the frequency of simultaneous prescription of β-blockers and calcium channel blockers, notify the cardiovascular risk of these patients to the health care professionals in charge of them, and achieve a reduction in the number of those who use them. Quasi-experimental, prospective study by developing an intervention on medical prescriptions of patients older than 65 years treated between January 1 and July 30, 2014, affiliated to the Health System in 101 cities in Colombia. A total of 43,180 patients received a β-blocker each month, and 14,560 receiving a calcium channel blocker were identified. Educational interventions were performed and an evaluation was made, using sociodemographic and pharmacological variables, on the number of patients that stopped taking any of the two drugs in the following three months. A total of 535 patients, with a mean age 75.8±6.7 years received concomitant β-blockers plus calcium channel blockers. Modification of therapy was achieved in 235 patients (43.9% of users) after 66 educational interventions. In 209 cases (88.9%) one of the two drugs was suspended, and 11.1% changed to other antihypertensive drugs. The variable of being more than 85 years old (OR: 1.93; 95% CI: 1.07-3.50), and receiving concomitant medication with inhibitors of the renin-angiotensin system (OR: 2.16; 95% CI: 1.28-3.65) were associated with increased risk of their doctor changing or stopping the prescription. An improved adherence to recommendations for appropriate use of β-blockers and calcium channel blockers by health service providers was achieved. Intervention programs that reduce potentially inappropriate prescriptions for patients treated for cardiovascular disease should be used more frequently. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  18. Dairy foods are an important source of calcium and vitamin D among Canadian-born and Asian-born Chinese in Edmonton, Alberta.

    Science.gov (United States)

    Yu, Yan Han; Farmer, Anna; Mager, Diana R; Willows, Noreen D

    2012-03-01

    Low intakes of calcium and vitamin D increase the risk for osteoporosis, bone fracture, and other health problems. This study aimed to examine the calcium and vitamin D intakes of Canadian-born Chinese (CBC) and Asian-born Chinese (ABC) in Edmonton, Canada, and to identify usual food sources of these nutrients. We hypothesized that CBC would have higher intakes of calcium and vitamin D than ABC and that the food sources of these nutrients would differ by region of birth (Canada vs Asia). Two in-person multipass 24-hour dietary recalls were administered for 1 weekday and weekend day for 81 healthy ethnically Chinese aged 18 to 58 years. The risks for calcium and vitamin D inadequacy were calculated as were the contributions of specific foods to calcium and vitamin D intakes. Calcium intake was 781 ± 337 mg/d for CBC and 809 ± 369 mg/d for ABC (P = .737). Vitamin D intake was 3.8 ± 3.4 μg/d for CBC and 5.0 ± 3.9 μg/d for ABC (P = .158). Respective risks for calcium and vitamin D inadequacy were 36% and 98% for men and 78% and 100% for women. Dairy contributed most to the calcium (43%) and vitamin D (52%) intake of participants. For ABC, soybean products contributed to 8.1% of calcium, whereas fatty fish contributed to 16.7% of vitamin D. For CBC, red meats contributed to 11.1% of vitamin D. Dietary intakes of calcium and vitamin D need to be increased in Chinese Canadians through the promotion of dairy and culturally relevant sources of these nutrients. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. 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....

  20. 43 CFR 418.29 - Project management.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Project management. 418.29 Section 418.29....29 Project management. In addition to the provisions of § 418.28, if the District is found to be... management of the diversion and outlet works (Derby Dam and Lahontan Dam/Reservoir) or any or all of the...

  1. 43 CFR 29.11 - Investment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Investment. 29.11 Section 29.11 Public... Investment. (a) The monies accumulated in the Fund shall be prudently invested in the following types of... investment advisor or custodian to the Fund, or their affiliates may be purchased or held by the Fund. (3...

  2. Water SA - Vol 43, No 2 (2017)

    African Journals Online (AJOL)

    Calibration and testing of AquaCrop for selected sorghum genotypes · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Sandile T. Hadebe, Albert T. Modi, Tafadzwanashe Mabhaudhi, 209-221. http://dx.doi.org/10.4314/wsa.v43i2.05 ...

  3. 43 CFR 426.22 - Public participation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Public participation. 426.22 Section 426... THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.22 Public participation. (a) Notification... participation. (1) Reclamation can provide, as appropriate: meetings, workshops, or hearings to provide local...

  4. 38 CFR 43.30 - Changes

    Science.gov (United States)

    2010-07-01

    ... awarding agency. (b) Relation to cost principles. The applicable cost principles (see § 43.22) contain... the awarding agency. (4) Under nonconstruction projects, contracting out, subgranting (if authorized by law) or otherwise obtaining the services of a third party to perform activities which are central...

  5. 43 CFR 23.9 - Performance bond.

    Science.gov (United States)

    2010-10-01

    ... cash or negotiable bonds of the U.S. Government. The cash deposit or the market value of such... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Performance bond. 23.9 Section 23.9 Public... LANDS § 23.9 Performance bond. (a)(1) Upon approval of an exploration plan or mining plan, the operator...

  6. 43 CFR 15.8 - Skin diving.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Skin diving. 15.8 Section 15.8 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.8 Skin diving. Diving with camera, or diving for observation and pleasure is permitted and encouraged within the...

  7. 43 CFR 12.932 - Real property.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Real property. 12.932 Section 12.932... Requirements § 12.932 Real property. Each Federal awarding agency shall prescribe requirements for recipients concerning the use and disposition of real property acquired in whole or in part under awards. Unless...

  8. 43 CFR 12.71 - Real property.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Real property. 12.71 Section 12.71 Public... to State and Local Governments Changes, Property, and Subawards § 12.71 Real property. (a) Title. Subject to the obligations and conditions set forth in this section, title to real property acquired under...

  9. 43 CFR 12.936 - Intangible property.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Intangible property. 12.936 Section 12.936... Requirements § 12.936 Intangible property. (a) The recipient may copyright any work that is subject to... intangible property and debt instruments acquired under an award or subaward vests upon acquisition in the...

  10. 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 of...

  11. 43 CFR 3.16 - Seizure.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Seizure. 3.16 Section 3.16 Public Lands: Interior Office of the Secretary of the Interior PRESERVATION OF AMERICAN ANTIQUITIES § 3.16 Seizure. Any object of antiquity taken, or collection made, on lands owned or controlled by the United States, without...

  12. 43 CFR 4.1105 - Parties.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Parties. 4.1105 Section 4.1105 Public... Special Rules Applicable to Surface Coal Mining Hearings and Appeals General Provisions § 4.1105 Parties. (a) All persons indicated in the act as parties to administrative review proceedings under the act...

  13. 43 CFR 423.37 - Winter activities.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Winter activities. 423.37 Section 423.37 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE....37 Winter activities. (a) You must not tow persons on skis, sleds, or other sliding devices with a...

  14. 43 CFR 2812.1-2 - Contents.

    Science.gov (United States)

    2006-10-01

    ... 43 Public Lands: Interior 2 2006-10-01 2006-10-01 false Contents. 2812.1-2 Section 2812.1-2 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT... Bay Revested Lands § 2812.1-2 Contents. (a) An individual applicant and each member of any...

  15. 43 CFR 10010.18 - Content.

    Science.gov (United States)

    2006-10-01

    ... 43 Public Lands: Interior 2 2006-10-01 2006-10-01 false Content. 10010.18 Section 10010.18 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.18 Content. (a) At a minimum, an EA will include brief discussions of the need...

  16. 43 CFR § 10010.18 - Content.

    Science.gov (United States)

    2015-10-01

    ... 43 Public Lands: Interior 2 2015-10-01 2015-10-01 false Content. § 10010.18 Section § 10010.18 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.18 Content. (a) At a minimum, an EA will include brief discussions of the need...

  17. 43 CFR 1862.1 - Contents.

    Science.gov (United States)

    1997-10-01

    ... 43 Public Lands: Interior 2 1997-10-01 1997-10-01 false Contents. 1862.1 Section 1862.1 GENERAL MANAGEMENT (1000) CONVEYANCES, DISCLAIMERS AND CORRECTION DOCUMENTS Patent Preparation and Issuance § 1862.1 Contents. (a) Patents for lands entered or located under general laws can be issued only in the name of the...

  18. 34 CFR 200.43 - Restructuring.

    Science.gov (United States)

    2010-07-01

    ... Programs Operated by Local Educational Agencies Lea and School Improvement § 200.43 Restructuring. (a... supplemental educational services in accordance with § 200.45. (3) Prepare a plan to carry out one of the... plan; and (B) Participate in the development of any restructuring plan. (5) Continue to comply with...

  19. 43 CFR 15.7 - Fishing.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Fishing. 15.7 Section 15.7 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.7 Fishing. (a) Spear fishing within the boundaries or confines of this Preserve is prohibited. (b) The use of poisons, electric...

  20. 43 CFR 17.232 - Postsecondary education.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Postsecondary education. 17.232 Section 17... Postsecondary education. This section applies to postsecondary education and activities, including postsecondary vocational education programs or activities, that receive Federal financial assistance and to recipients that...

  1. 43 CFR 423.35 - Animals.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Animals. 423.35 Section 423.35 Public... Animals. (a) You must not bring pets or other animals into public buildings, public transportation vehicles, or sanitary facilities. This provision does not apply to properly trained animals assisting...

  2. 43 CFR 4.336 - Docketing.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Docketing. 4.336 Section 4.336 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Rules... Relating to Probate Proceedings § 4.336 Docketing. An appeal shall be assigned a docket number by the Board...

  3. 43 CFR 4.1606 - Department representation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Department representation. 4.1606 Section 4.1606 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND...-76 § 4.1606 Department representation. (a) Upon receipt of the docketing notice, the Solicitor shall...

  4. 27 CFR 30.43 - Packaged spirits.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Packaged spirits. 30.43... Packaged spirits. When the quantity of spirits (including denatured spirits when gauged by weight) in... by weighing each package on an accurate weighing beam or platform scale having a beam or dial showing...

  5. 43 CFR 414.5 - Water quality.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Water quality. 414.5 Section 414.5 Public... APPORTIONMENT IN THE LOWER DIVISION STATES Water Quality and Environmental Compliance § 414.5 Water quality. (a) Water Quality is not guaranteed. The Secretary does not warrant the quality of water released or...

  6. 43 CFR 4.1110 - Intervention.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Intervention. 4.1110 Section 4.1110 Public... Intervention. (a) Any person, including a State, or OSM may petition for leave to intervene at any stage of a... or may be adversely affected. (c) The administrative law judge or the Board shall grant intervention...

  7. 43 CFR 6.53 - Unpatented inventions.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Unpatented inventions. 6.53 Section 6.53... Unpatented inventions. The Secretary of the Interior may also have transferable interests in inventions which... benefit of the public, a license may be granted with respect to such an invention only if (a) a patent...

  8. 43 CFR 26.4 - Legislation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Legislation. 26.4 Section 26.4 Public Lands: Interior Office of the Secretary of the Interior GRANTS TO STATES FOR ESTABLISHING YOUTH CONSERVATION CORPS PROGRAMS § 26.4 Legislation. State programs must meet all of the requirements of section 4...

  9. 43 CFR 7.19 - Report.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Report. 7.19 Section 7.19 Public Lands... § 7.19 Report. (a) Each Federal land manager, when requested by the Secretary of the Interior, will... comprehensively report on activities carried out under provisions of the Act. (b) The Secretary of the Interior...

  10. 43 CFR 15.5 - Wrecks.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Wrecks. 15.5 Section 15.5 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.5 Wrecks. No person shall willfully destroy molest, remove, deface, displace, or tamper with any wrecks, parts of wrecks or...

  11. 43 CFR 2.53 - Government contracts.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Government contracts. 2.53 Section 2.53 Public Lands: Interior Office of the Secretary of the Interior RECORDS AND TESTIMONY; FREEDOM OF INFORMATION ACT Privacy Act § 2.53 Government contracts. (a) Required contract provisions. When a contract...

  12. 43 CFR 4.451 - Government contests.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Government contests. 4.451 Section 4.451 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES... Fact § 4.451 Government contests. ...

  13. 49 CFR 230.43 - Gauge siphon.

    Science.gov (United States)

    2010-10-01

    ... TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Steam Gauges § 230.43 Gauge siphon. The steam gauge supply pipe shall have a siphon on it of ample capacity to prevent steam from entering the gauge. The supply pipe shall directly enter the boiler and be maintained steam...

  14. 22 CFR 201.43 - Diversion clause.

    Science.gov (United States)

    2010-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES AND PROCEDURES APPLICABLE TO COMMODITY TRANSACTIONS FINANCED BY USAID General Provisions Relating to USAID Financing of Commodities and Commodity-Related Services § 201.43 Diversion clause. USAID may require that charter parties, bills of lading, or other ocean...

  15. 43 CFR 402.10 - Patent.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Patent. 402.10 Section 402.10 Public Lands... LANDS IN FEDERAL RECLAMATION PROJECTS Public Lands § 402.10 Patent. When a purchaser has complied fully... and patent and shall state the statutory authority for such liens. The receipt shall be submitted to...

  16. 43 CFR 12.65 - Program income.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Program income. 12.65 Section 12.65 Public... to State and Local Governments Post-Award Requirements § 12.65 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from fees for...

  17. 43 CFR 12.924 - Program income.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Program income. 12.924 Section 12.924... Requirements § 12.924 Program income. (a) Federal awarding agencies shall apply the standards set forth in this section in requiring recipient organizations to account for program income related to projects financed in...

  18. 43 CFR 10.6 - Custody.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Custody. 10.6 Section 10.6 Public Lands... Tribal Lands § 10.6 Custody. (a) Priority of custody. This section carries out section 3 (a) of the Act, subject to the limitations of § 10.15, regarding the custody of human remains, funerary objects, sacred...

  19. 43 CFR 36.3 - Preapplication.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Preapplication. 36.3 Section 36.3 Public..., AND ACCESS INTO, CONSERVATION SYSTEM UNITS IN ALASKA § 36.3 Preapplication. (a) Anyone interested in... necessary to obtain information for filing the SF 299, that the activities would not cause significant or...

  20. 43 CFR 36.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Definitions. 36.2 Section 36.2 Public..., AND ACCESS INTO, CONSERVATION SYSTEM UNITS IN ALASKA § 36.2 Definitions. As used in this part, the... Federal Lands” (SF 299). (n) Right-of-way permit means a right-of-way permit, lease, license, certificate...