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Sample records for calcium 44 target

  1. 44gSc from metal calcium targets for PET

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Production of scandium-44 m and scandium-44 g with deuterons on calcium-44: cross section measurements and production yield calculations.

    Science.gov (United States)

    Duchemin, C; Guertin, A; Haddad, F; Michel, N; Métivier, V

    2015-09-01

    HIGHLIGHTS • Production of Sc-44 m, Sc-44 g and contaminants. • Experimental values determined using the stacked-foil technique. • Thick-Target production Yield (TTY) calculations. • Comparison with the TALYS code version 1.6.Among the large number of radionuclides of medical interest, Sc-44 is promising for PET imaging. Either the ground-state Sc-44 g or the metastable-state Sc-44 m can be used for such applications, depending on the molecule used as vector. This study compares the production rates of both Sc-44 states, when protons or deuterons are used as projectiles on an enriched Calcium-44 target. This work presents the first set of data for the deuteron route. The results are compared with the TALYS code. The Thick-Target production Yields of Sc-44 m and Sc-44 g are calculated and compared with those for the proton route for three different scenarios: the production of Sc-44 g for conventional PET imaging, its production for the new 3 γ imaging technique developed at the SUBATECH laboratory and the production of a Sc-44 m/Sc-44 g in vivo generator for antibody labelling. PMID:26301533

  4. Cyclotron production of high purity 44m,44Sc with deuterons from 44CaCO3 targets

    International Nuclear Information System (INIS)

    Introduction: Due to its longer half-life, 44Sc (T1/2 = 3.97 h) as a positron emitter can be an interesting alternative to 68Ga (T1/2 = 67.71 min). It has been already proposed as a PET radionuclide for scouting bone disease and is already available as a 44Ti/44Sc generator. 44Sc has an isomeric state, 44mSc (T1/2 = 58.6 h), which can be co-produced with 44Sc and that has been proved to be considered as an in-vivo PET generator 44mSc/44Sc. This work presents the production route of 44mSc/44Sc generator from 44Ca(d,2n), its extraction/purification process and the evaluation of its performances. Methods: Irradiation was performed in a low activity target station using a deuteron beam of 16 MeV, which favors the number of 44mSc atoms produced simultaneously to 44Sc. Typical irradiation conditions were 60 min at 0.2 μA producing 44 MBq of 44Sc with a 44Sc/44mSc activity ratio of 50 at end of irradiation. Separations of the radionuclides were performed by means of cation exchange chromatography using a DGA® resin (Triskem). Then, the developed process was applied with bigger targets, and could be used for preclinical studies. Results: The extraction/purification process leads to a radionucleidic purity higher than 99.99% (43Sc, 46Sc, 48Sc < DL). 44mSc/44Sc labeling towards DOTA moiety was performed in order to get an evaluation of the specific activities that could be reached with regard to all metallic impurities from the resulting source. Reaction parameters of radiolabeling were optimized, reaching yields over 95%, and leading to a specific activity of about 10–20 MBq/nmol for DOTA. A recycling process for the enriched 44Ca target was developed and optimized. Conclusion: The quality of the final batch with regard to radionucleidic purity, specific activity and metal impurities allowed a right away use for further radiopharmaceutical evaluation. This radionucleidic pair of 44mSc/44Sc offers a quite interesting PET radionuclide for being further evaluated as an in

  5. An attempt of application of short lived 44K activity induced in the 44Ca(n,p)44K reaction using 14 MeV neutrons for total body calcium assessment in human subject

    International Nuclear Information System (INIS)

    The status of in vivo neutron activation analysis techniques for the measurement of total body calcium in human subject is reviewed. Relevant data on the nuclear characteristics of calcium isotopes during interaction with neutrons ranging from slow up to 14 MeV neutrons are presented. Physical aspects of the measurement of in vivo total body calcium (TBCa) using 44K activity induced in the 44Ca(n,p)44K(T1/2=22.3 min) reaction by 14 MeV neutrons are discussed. The measurement of delayed γ-ray emitted during decay of activities induced in enriched 44Ca, natCa, phantom filled with water solution of natural calcium and skeletal arm are considered. Results of measurements on the phantom and skeletal arm indicate a possibility to measure the TBCa using the 44K activity. (author)

  6. Molecular Structure and Target Recognition of Neuronal Calcium Sensor Proteins

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    James Ames

    2012-02-01

    Full Text Available Neuronal calcium sensor (NCS proteins, a sub-branch of the calmodulin superfamily, are expressed in the brain and retina where they transduce calcium signals and are genetically linked to degenerative diseases. The amino acid sequences of NCS proteins are highly conserved but their physiological functions are quite distinct. Retinal recoverin and guanylate cyclase activating proteins (GCAPs both serve as calcium sensors in retinal rod cells, neuronal frequenin (NCS1 modulates synaptic activity and neuronal secretion, K+ channel interacting proteins (KChIPs regulate ion channels to control neuronal excitability, and DREAM (KChIP3 is a transcriptional repressor that regulates neuronal gene expression. Here we review the molecular structures of myristoylated forms of NCS1, recoverin, and GCAP1 that all look very different, suggesting that the sequestered myristoyl group helps to refold these highly homologous proteins into very different structures. The molecular structure of NCS target complexes have been solved for recoverin bound to rhodopsin kinase, NCS-1 bound to phosphatidylinositol 4-kinase, and KChIP1 bound to A-type K+ channels. We propose that N-terminal myristoylation is critical for shaping each NCS family member into a different structure, which upon Ca2+-induced extrusion of the myristoyl group exposes a unique set of previously masked residues that interact with a particular physiological target.

  7. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

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    Chia-Hui Wang

    Full Text Available Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

  8. Molecular Structure and Target Recognition of Neuronal Calcium Sensor Proteins

    OpenAIRE

    James Ames; Mitsuhiko Ikura

    2011-01-01

    Neuronal calcium sensor (NCS) proteins, a sub-branch of the calmodulin superfamily, are expressed in the brain and retina where they transduce calcium signals and are genetically linked to degenerative diseases. The amino acid sequences of NCS proteins are highly conserved but their physiological functions are quite distinct. Retinal recoverin and guanylate cyclase activating proteins (GCAPs) both serve as calcium sensors in retinal rod cells, neuronal frequenin (NCS1) modulates synaptic acti...

  9. Molecular structure and target recognition of neuronal calcium sensor proteins

    OpenAIRE

    Ames, James B.; Lim, Sunghyuk; Ikura, Mitsuhiko

    2012-01-01

    Neuronal calcium sensor (NCS) proteins, a sub-branch of the EF-hand superfamily, are expressed in the brain and retina where they transduce calcium signals and are genetically linked to degenerative diseases. The amino acid sequences of NCS proteins are highly conserved but their physiological functions are quite distinct. Retinal recoverin and guanylate cyclase activating proteins (GCAPs) both serve as calcium sensors in retinal rod cells, neuronal frequenin (NCS1) modulates synaptic activit...

  10. The Role of CD44 in Disease Pathophysiology And Targeted Treatment

    Directory of Open Access Journals (Sweden)

    Andre R. Jordan

    2015-04-01

    Full Text Available The cell-surface glycoprotein CD44 is involved in a multitude of important physiological functions including cell proliferation, adhesion, migration, hematopoiesis, and lymphocyte activation. The diverse physiological activity of CD44 is manifested in the pathology of a number of diseases including cancer, arthritis, bacterial and viral infections, interstitial lung disease, vascular disease and wound healing. This diversity in biological activity is conferred by both a variety of distinct CD44 isoforms generated through complex alternative splicing, posttranslational modifications (e.g., N- and O-glycosylation, interactions with a number of different ligands and the abundance and spatial distribution of CD44 on the cell surface. The extracellular matrix glycosaminoglycan hyaluronan (HA is the principle ligand of CD44. This review focuses both CD44-hyaluronan dependent and independent CD44 signaling and the role of CD44-HA interaction in various pathophysiologies. The review also discusses recent advances in novel treatment strategies that exploit the CD44-HA interaction either for direct targeting or for drug delivery.

  11. Hyaluronic Acid Immobilized Polyacrylamide Nanoparticle Sensors for CD44 Receptor Targeting and pH Measurement in Cells

    DEFF Research Database (Denmark)

    Sun, Honghao; Benjaminsen, Rikke Vicki; Almdal, Kristoffer;

    2012-01-01

    the CD44 receptor, which is overexpressed on the surface of a broad variety of cancer cells, we have synthesized an NP pH sensor system that targets CD44. We used a polyacrylamide nanoparticle matrix bearing hyaluronic acid (HA) on the surface as a CD44 targeting ligand. The HA-coated NPs were...

  12. Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin.

    Science.gov (United States)

    Arabi, Leila; Badiee, Ali; Mosaffa, Fatemeh; Jaafari, Mahmoud Reza

    2015-12-28

    Although liposomes improve the safety and pharmacokinetic properties of free drugs, they have not sufficiently enhanced the therapeutic efficacy compared to them. To address this problem, targeted therapy of tumor cells holds great promise to further enhance therapeutic index and decreases off-target effects compared with non-targeted liposomes. In the context of antibody-mediated targeted cancer therapy, we evaluated the anti-tumor activity and therapeutic efficacy of Doxil, and that of Doxil modified with a monoclonal antibody (mAb) against CD44, which is one of the most well-known surface markers associated with Cancer Stem Cells (CSCs). Flow cytometry analyses and confocal laser scanning microscopy results showed significant enhanced cellular uptake of CD44-targeted Doxil (CD44-Doxil) in CD44-positive C-26 cells compared to Doxil. However, CD44-negative NIH-3T3 cells showed a similar uptake and in vitro cytotoxicity with both CD44-Doxil and non-targeted Doxil. In BALB/c mice bearing C-26 murine carcinoma, CD44-Doxil groups exhibited significantly higher doxorubicin concentration (than Doxil) inside the tumor cells, while their circulation time and distribution profile remained comparable. CD44-Doxil at doses of either 10 or 15 mg/kg resulted in superior tumor growth inhibition and higher inclination to tumor, indicating the potential of anti-CD44 mAb targeting in therapeutic efficacy improvement. This study provides proof-of-principle for actively tumor-targeting concept and merits further investigations. PMID:26518722

  13. Hot fusion-evaporation cross sections of 44Ca-induced reactions with lanthanide targets

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    Werke, T. A.; Mayorov, D. A.; Alfonso, M. C.; Tereshatov, E. E.; Folden, C. M.

    2015-11-01

    Background: Previously reported cross sections of 45Sc-induced reactions with lanthanide targets are much smaller than 48Ca-induced reactions on the same targets. 44Ca is one proton removed from 45Sc and could be used to produce nuclei with a relative neutron content between those produced in the 45Sc- and 48Ca-induced reactions. Purpose: As part of a systematic investigation of fusion-evaporation reactions, cross sections of 44Ca-induced reactions on lanthanide targets were measured. These results are compared to available data for 48Ca- and 45Sc-induced fusion-evaporation cross sections on the same lanthanide targets. Collectively, these data provide insight into the importance of the survival against fission of excited compound nuclei produced near spherical shell closures. Methods: A beam of 6+Ca at an energy of ≈5 MeV /u was delivered by the K500 superconducting cyclotron at the Cyclotron Institute at Texas A&M University. The desired evaporation residues were selected by the Momentum Achromat Recoil Spectrometer and identified via their characteristic α -decay energies. Excitation functions for the 44Ca+158Gd ,159Tb, and 162Dy reactions were measured at five or more energies each. A theoretical model was employed to study the fusion-evaporation process. Results: The 44Ca-induced reactions have x n cross sections that are two orders of magnitude larger than 45Sc-induced reactions but two orders of magnitude smaller than 48Ca-induced reactions on the same targets. Proton emission competes effectively with neutron emission for the 44Ca+159Tb and 162Dy reactions. The maximum 4 n cross sections in the 44Ca+158Gd ,159Tb, and 162Dy reactions were 2100 ± 230 ,230 ± 20 , and 130 ±20 μ b , respectively. The 44Ca+158Gd and 159Tb cross sections are in good agreement with the respective cross bombardments of 48Ca+154Gd and 45Sc+158Gd once differences in capture cross sections and compound nucleus formation probabilities are corrected for. Conclusions: Excitation

  14. Production of a 44 Ti target and its cross section of thermal neutron capture

    International Nuclear Information System (INIS)

    A study of the production of a 44 Ti target was carried out aiming the determination of its thermal neutron capture cross-section. With this purpose, the cross-section of the reaction 45 Sc(p,2 n) 44 Ti was determined in the energies 16-, 18-, 20-22- and 45 MeV. The cross-section of the reactions (p,n) 45 Ti, (p,pn) 44m Sc, (p,pn) 44g Sc and (p,p2n)43 Sc were also measured. The results in the low energy region are in good agreement with a previous work by McGee et al. On the other hand, the cross-section at 45 MeV is different from McGee's result and indicates the existence of an abnormal behavior of the excitation function at higher energies. Furthermore, a radiochemical separation method was developed in order to eliminate Sc from the 44 Ti target which was irradiated with neutrons. It was possible to determine an upper limit for the cross-section of the reaction 44 Ti (n, γ) of 4 x 103 b. At last, it is presented a discussion of the results obtained and their possible astrophysical implications. (author)

  15. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    Science.gov (United States)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  16. Functionalizing Liposomes with anti-CD44 Aptamer for Selective Targeting of Cancer Cells.

    Science.gov (United States)

    Alshaer, Walhan; Hillaireau, Hervé; Vergnaud, Juliette; Ismail, Said; Fattal, Elias

    2015-07-15

    CD44 receptor protein is found to be overexpressed by many tumors and is identified as one of the most common cancer stem cell surface markers including tumors affecting colon, breast, pancreas, and head and neck, making this an attractive receptor for therapeutic targeting. In this study, 2'-F-pyrimidine-containing RNA aptamer (Apt1), previously selected against CD44, was successfully conjugated to the surface of PEGylated liposomes using the thiol-maleimide click reaction. The conjugation of Apt1 to the surface of liposomes was confirmed by the change in size and zeta potential and by migration on agarose gel electrophoresis. The binding affinity of Apt1 was improved after conjugation compared to free-Apt1. The cellular uptake for Apt1-Lip was tested by flow cytometry and confocal imaging using the two CD44(+) cell lines, human lung cancer cells (A549) and human breast cancer cells (MDA-MB-231), and the CD44(-) cell line, mouse embryonic fibroblast cells (NIH/3T3). The results showed higher sensitivity and selectivity for Apt1-Lip compared to the blank liposomes (Mal-Lip). In conclusion, we demonstrate a successful conjugation of anti-CD44 aptamer to the surface of liposome and binding preference of Apt1-Lip to CD44-expressing cancer cells and conclude to a promising potency of Apt1-Lip as a specific drug delivery system. PMID:25343502

  17. Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells

    Directory of Open Access Journals (Sweden)

    Embi Abraham

    2012-12-01

    , and extracellular calcium chelation stores of the Astrocytes (which has been shown to slow neural conduction. Implications of the Hypothesis The life expectancy in patients with metastasized malignant melanoma brain tumors could be significantly prolonged if the chemotherapeutic issue of brain metastasis is overcome. Other cancerous tumors can also be treated by this Targeted Chelation Approach. Ionic calcium sequestration using naturally occurring calcium chelators, viz., oxalates, could accomplish this desired outcome.

  18. Ion microscopic imaging of calcium transport in the intestinal tissue of vitamin D-deficient and vitamin D-replete chickens: A 44Ca stable isotope study

    International Nuclear Information System (INIS)

    The intestinal absorption of calcium includes at least three definable steps; transfer across the microvillar membrane, movement through the cytosolic compartment, and energy-dependent extrusion into the lamina propria, Tracing the movement of calcium through the epithelium has been hampered by lack of suitable techniques and, in this study, advantage was taken of ion microscopy in conjunction with cryosectioning and use of the stable isotope 44Ca to visualize calcium in transit during the absorptive process. The effect of vitamin D, required for optimal calcium absorption, was investigated. Twenty millimolar 44Ca was injected into the duodenal lumen in situ of vitamin D-deficient and vitamin D-replete chickens. At 2.5, 5.0, and 20.0 min after injection, duodenal tissue was obtained and processed for ion microscopic imaging. At 2.5 min. 44Ca was seen to be concentrated in the region subjacent to the microvillar membrane in tissue from both groups. At 5.0 and 20.0 min, a similar pattern of localization was evident in D-deficient tissues. In D-replete tissues, the distribution of 44Ca became more homogenous, indicating that vitamin D increased the rate of transfer of Ca2+ from the apical to the basolateral membrane, a function previously ascribed to the vitamin D-induced calcium-binding protein (28-kDa calbindin-D). Quantitative aspects of the calcium absorptive process were determined in parallel experiments with the radionuclide 47Ca. Complementary information on the localization of the naturally occurring isotopes of calcium (40Ca) and potassium (39K) is also described

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

    Science.gov (United States)

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

    2016-06-01

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

  20. Application of Collagen-Model Triple-Helical Peptide-Amphiphiles for CD44-Targeted Drug Delivery Systems

    OpenAIRE

    Ndinguri, Margaret W.; Alexander Zheleznyak; Lauer, Janelle L.; Anderson, Carolyn J.; Fields, Gregg B.

    2012-01-01

    Cancer treatment by chemotherapy is typically accompanied by deleterious side effects, attributed to the toxic action of chemotherapeutics on proliferating cells from nontumor tissues. The cell surface proteoglycan CD44 has been recognized as a cancer stem cell marker. The present study has examined CD44 targeting as a way to selectively deliver therapeutic agents encapsulated inside colloidal delivery systems. CD44/chondroitin sulfate proteoglycan binds to a triple-helical sequence derived f...

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

    Science.gov (United States)

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

    2003-01-01

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

  2. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    Science.gov (United States)

    Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

    2012-12-01

    In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

  3. miR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Henry, Jon C. [Department of Surgery, Ohio State University Medical Center, Columbus, OH (United States); Park, Jong-Kook; Jiang, Jinmai; Kim, Ji Hye [College of Pharmacy, Ohio State University, Columbus, OH (United States); Nagorney, David M.; Roberts, Lewis R. [Divisions of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN (United States); Banerjee, Soma [Center for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata (India); Schmittgen, Thomas D., E-mail: Schmittgen.2@osu.edu [College of Pharmacy, Ohio State University, Columbus, OH (United States)

    2010-12-03

    Research highlights: {yields} miR-199a-3p targets CD44 in HCC. {yields} Proliferation and invasion are reduced by miR-199a-3p in CD44+ HCC. {yields} miR-199a-3p is reduced and CD44 protein is increased in HCC tissues. {yields} The duplex form of miR-199a-3p mimetic is required for activity. -- Abstract: Previous work by us and others reported decreased expression of miR-199a-3p in hepatocellular carcinoma (HCC) tissues compared to adjacent benign tissue. We report here a significant reduction of miR-199a-3p expression in 7 HCC cell lines. To determine if miR-199a-3p has a tumor suppressive role, pre-miR-199a-3p oligonucleotides were transfected into the HCC cell lines. Pre-miR-199a-3p oligonucleotide reduced cell proliferation by approximately 60% compared to control oligonucleotide in only two cell lines (SNU449 and SNU423); the proliferation of the other 5 treated cell lines was similar to control oligonucleotide. A pre-miR-199a-3p oligonucleotide formulated with chemical modifications to enhance stability while preserving processing, reduced cell proliferation in SNU449 and SNU423 to the same extent as the commercially available pre-miR-199a-3p oligonucleotide. Furthermore, only the duplex miR-199a-3p oligonucleotide, and not the guide strand alone, was effective at reducing cell viability. Since a CD44 variant was essential for c-Met signaling [V. Orian-Rousseau, L. Chen, J.P. Sleeman, P. Herrlich, H. Ponta, CD44 is required for two consecutive steps in HGF/c-Met signaling, Genes Dev. 16 (2002) 3074-3086] and c-Met is a known miR-199a-3p target, we hypothesized that miR-199a-3p may also target CD44. Immunoblotting confirmed that only the two HCC lines that were sensitive to the effects of pre-miR-199a-3p were CD44+. Direct targeting of CD44 by miR-199a-3p was confirmed using luciferase reporter assays and immunoblotting. Transfection of miR-199a-3p into SNU449 cells reduced in vitro invasion and sensitized the cells to doxorubicin; both effects were enhanced

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-11

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

  5. Effects of shRNA Targeting Survivin on Apoptosis of Human Retinoblastoma Cell Line Hxo-rb44 in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Guojun; HU Yanhua; LI Pengcheng

    2006-01-01

    In order to construct a recombinant plasmid containing short hairpin RNA (shRNA) targeting survivin and to investigate its effect on survivin expression and cell apoptosis of human retinoblastoma cell line Hxo-rb44 in vitro, RNA interference plasmid pSIRENS that can express shRNA of survivin was designed, constructed, and transfected into human retinoblastoma cell line Hxo-rb44.Survivin and c-Myc expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Apoptosis of Hxo-rb44 cells was assayed by Honchest33258 staining and cell growth curve was drawn. The results showed that the oligonucleotide targeting survivin was identified in pSIRENS plasmid. After pSIRENS plasmid transfected, survivin and c-Myc expression in Hxo-rb44 cells was decreased significantly. Apoptotic rate of cells was up-regulated from (3.5±1.29) % to (36.1±19.66) %. The proliferation ability of Hxo-rb44 cells was inhibited. No significant effects on survivin expression and apoptosis of the cells were found when negative control plasmid was transfected. In conclusion, the plasmid containing shRNA targeting survivin was constructed successfully. It could inhibit efficiently the expression of survivin and c-Myc in human retinoblastoma cell Hxo-rb44 in vitro. The inhibition of the expression of c-Myc might be involved in the apoptosis of Hxo-rb44 cells.

  6. 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.

  7. 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.

  8. CD44 Antibody Inhibition of Macrophage Phagocytosis Targets Fcγ Receptor- and Complement Receptor 3-Dependent Mechanisms.

    Science.gov (United States)

    Amash, Alaa; Wang, Lin; Wang, Yawen; Bhakta, Varsha; Fairn, Gregory D; Hou, Ming; Peng, Jun; Sheffield, William P; Lazarus, Alan H

    2016-04-15

    Targeting CD44, a major leukocyte adhesion molecule, using specific Abs has been shown beneficial in several models of autoimmune and inflammatory diseases. The mechanisms contributing to the anti-inflammatory effects of CD44 Abs, however, remain poorly understood. Phagocytosis is a key component of immune system function and can play a pivotal role in autoimmune states where CD44 Abs have shown to be effective. In this study, we show that the well-known anti-inflammatory CD44 Ab IM7 can inhibit murine macrophage phagocytosis of RBCs. We assessed three selected macrophage phagocytic receptor systems: Fcγ receptors (FcγRs), complement receptor 3 (CR3), and dectin-1. Treatment of macrophages with IM7 resulted in significant inhibition of FcγR-mediated phagocytosis of IgG-opsonized RBCs. The inhibition of FcγR-mediated phagocytosis was at an early stage in the phagocytic process involving both inhibition of the binding of the target RBC to the macrophages and postbinding events. This CD44 Ab also inhibited CR3-mediated phagocytosis of C3bi-opsonized RBCs, but it did not affect the phagocytosis of zymosan particles, known to be mediated by the C-type lectin dectin-1. Other CD44 Abs known to have less broad anti-inflammatory activity, including KM114, KM81, and KM201, did not inhibit FcγR-mediated phagocytosis of RBCs. Taken together, these findings demonstrate selective inhibition of FcγR and CR3-mediated phagocytosis by IM7 and suggest that this broadly anti-inflammatory CD44 Ab inhibits these selected macrophage phagocytic pathways. The understanding of the immune-regulatory effects of CD44 Abs is important in the development and optimization of therapeutic strategies for the potential treatment of autoimmune conditions. PMID:26944929

  9. Calcium-sensing receptor: A new target for therapy of diarrhea.

    Science.gov (United States)

    Cheng, Sam Xianjun

    2016-03-01

    Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxin-mediated excessive secretion, reduced absorption and compromised barrier function - the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calcium-sensing receptor (CaSR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears "all-inclusive": it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating CaSR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of CaSR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed. PMID:26973410

  10. Ligand binding to anti-cancer target CD44 investigated by molecular simulations.

    Science.gov (United States)

    Nguyen, Tin Trung; Tran, Duy Phuoc; Pham Dinh Quoc Huy; Hoang, Zung; Carloni, Paolo; Van Pham, Phuc; Nguyen, Chuong; Li, Mai Suan

    2016-07-01

    CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated the mechanism and energetics of F-19848A binding to CD44 using molecular simulation. Using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method, we obtained the binding free energy and inhibition constant of the complex. The van der Waals (vdW) interaction and the extended portion of F-19848A play key roles in the binding affinity. We screened natural products from a traditional Chinese medicine database to search for CD44 inhibitors. From combining pharmaceutical requirements with docking and molecular dynamics simulations, we found ten compounds that are potentially better or equal to the F-19848A ligand at binding to CD44 receptor. Therefore, we have identified new candidates of CD44 inhibitors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer. PMID:27342250

  11. Application of Collagen-Model Triple-Helical Peptide-Amphiphiles for CD44-Targeted Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Margaret W. Ndinguri

    2012-01-01

    Full Text Available Cancer treatment by chemotherapy is typically accompanied by deleterious side effects, attributed to the toxic action of chemotherapeutics on proliferating cells from nontumor tissues. The cell surface proteoglycan CD44 has been recognized as a cancer stem cell marker. The present study has examined CD44 targeting as a way to selectively deliver therapeutic agents encapsulated inside colloidal delivery systems. CD44/chondroitin sulfate proteoglycan binds to a triple-helical sequence derived from type IV collagen, α1(IV1263–1277. We have assembled a peptide-amphiphile (PA in which α1(IV1263–1277 was sandwiched between 4 repeats of Gly-Pro-4-hydroxyproline and conjugated to palmitic acid. The PA was incorporated into liposomes composed of DSPG, DSPC, cholesterol, and DSPE-PEG-2000 (1 : 4 : 5 : 0.5. Doxorubicin-(DOX-loaded liposomes with and without 10% α1(IV1263–1277 PA were found to exhibit similar stability profiles. Incubation of DOX-loaded targeted liposomes with metastatic melanoma M14#5 and M15#11 cells and BJ fibroblasts resulted in IC50 values of 9.8, 9.3, and >100 μM, respectively. Nontargeted liposomes were considerably less efficacious for M14#5 cells. In the CD44+ B16F10 mouse melanoma model, CD44-targeted liposomes reduced the tumor size to 60% of that of the untreated control, whereas nontargeted liposomes were ineffective. These results suggest that PA targeted liposomes may represent a new class of nanotechnology-based drug delivery systems.

  12. The Role of CD44 in Disease Pathophysiology and Targeted Treatment

    OpenAIRE

    Jordan, Andre R.; Racine, Ronny R.; Hennig, Martin J. P.; Lokeshwar, Vinata B.

    2015-01-01

    The cell-surface glycoprotein CD44 is involved in a multitude of important physiological functions including cell proliferation, adhesion, migration, hematopoiesis, and lymphocyte activation. The diverse physiological activity of CD44 is manifested in the pathology of a number of diseases including cancer, arthritis, bacterial and viral infections, interstitial lung disease, vascular disease, and wound healing. This diversity in biological activity is conferred by both a variety of distinct C...

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Dual-stimuli responsive hyaluronic acid-conjugated mesoporous silica for targeted delivery to CD44-overexpressing cancer cells.

    Science.gov (United States)

    Zhao, Qinfu; Liu, Jia; Zhu, Wenquan; Sun, Changshan; Di, Donghua; Zhang, Ying; Wang, Pu; Wang, Zhanyou; Wang, Siling

    2015-09-01

    In this paper, a redox and enzyme dual-stimuli responsive delivery system (MSN-SS-HA) based on mesoporous silica nanoparticles (MSN) for targeted drug delivery has been developed, in which hyaluronic acid (HA) was conjugated on the surface of silica by cleavable disulfide (SS) bonds. HA possesses many attractive features, including acting as a targeting ligand and simultaneously a capping agent to achieve targeted and controlled drug release, prolonging the blood circulation time, and increasing the physiological stability and biocompatibility of MSN. The anticancer drug doxorubicin (DOX) was chosen as a model drug. In vitro drug release profiles showed that the release of DOX was markedly restricted in pH 7.4 and pH 5.0 phosphate buffer solution (PBS), while it was significantly accelerated upon the addition of glutathione (GSH)/hyaluronidases (HAase). In addition, the release was further accelerated in the presence of both GSH and HAase. Confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) showed that MSN-SS-HA exhibited a higher cellular uptake via cluster of differentiation antigen-44 (CD44) receptor-mediated endocytosis compared with thiol (SH)-functionalized MSN (MSN-SH) in CD44 receptor over-expressed in human HCT-116 cells. The DOX-loaded MSN-SS-HA was more cytotoxic against HCT-116 cells than NIH-3T3 (CD44 receptor-negative) cells due to the enhanced cellular uptake of MSN-SS-HA. This paper describes the development of an effective method for using a single substance as multi-functional material for MSN to simultaneously regulate drug release and achieve targeted delivery. PMID:25985912

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

    International Nuclear Information System (INIS)

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

  16. Cyclotron production of {sup 44}Sc for clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Krajewski, S.; Bilewicz, A. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); Cydzik, I. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); European Commission Joint Research Center, Ispra (Italy). Inst. for Health and Consumer Protection; Warsaw Univ. (Poland). Heavy Ion Lab.; Abbas, K. [European Commission Joint Research Center, Ispra (Italy). Institute for Transuranium Elements; Bulgheroni, A.; Simonelli, F.; Holzwarth, U. [European Commission Joint Research Center, Ispra (Italy). Inst. for Health and Consumer Protection

    2013-08-01

    {sup 44} is a promising {beta}{sup +}-emitter for molecular imaging with intermediate half-life of 4 h. Due to the chemical similarity of Sc{sup 3+} to the Lu{sup 3+} and Y{sup 3+} cations, {sup 44}Sc-DOTA bioconjugates are expected to demonstrate similar properties in vivo as the {sup 177}Lu- and {sup 90}Y-bioconjugates, what is important in planning the radionuclide therapy. {sup 44}Sc can be obtained from the {sup 44}Ti/{sup 44}Sc generator. An alternative method for {sup 44}Sc production can be the irradiation of {sup 44}Ca target at small cyclotrons. The aim of our work was to optimize the parameters of {sup 44}CaCO{sub 3} irradiation and to develop a simple procedure for {sup 44}Sc separation from the calcium target. For optimization study, {sup 44}CaCO{sub 3} targets were irradiated by protons in the energy range of 5.6-17.5 MeV with 9 MeV being found to be the best energy for {sup 44}Ca irradiations. A simple and fast separation procedure of {sup 44}Sc from calcium target was developed using chelating resin Chelex 100. DOTATATE conjugate was successfully radiolabelled with high yield at elevated temperature using the produced {sup 44}Sc. While {sup 44}CaCO{sub 3} is relatively expensive, the cost of {sup 44}Sc-DOTATATE production can be reduced by target recovery. Due to low proton energy required to produce GBq activity level of {sup 44}Sc, the availability of {sup 44}Sc radioisotope could be enhanced to open new opportunities for applications in medical imaging. (orig.)

  17. Cyclotron production of 44Sc for clinical application

    International Nuclear Information System (INIS)

    44 is a promising β+-emitter for molecular imaging with intermediate half-life of 4 h. Due to the chemical similarity of Sc3+ to the Lu3+ and Y3+ cations, 44Sc-DOTA bioconjugates are expected to demonstrate similar properties in vivo as the 177Lu- and 90Y-bioconjugates, what is important in planning the radionuclide therapy. 44Sc can be obtained from the 44Ti/44Sc generator. An alternative method for 44Sc production can be the irradiation of 44Ca target at small cyclotrons. The aim of our work was to optimize the parameters of 44CaCO3 irradiation and to develop a simple procedure for 44Sc separation from the calcium target. For optimization study, 44CaCO3 targets were irradiated by protons in the energy range of 5.6-17.5 MeV with 9 MeV being found to be the best energy for 44Ca irradiations. A simple and fast separation procedure of 44Sc from calcium target was developed using chelating resin Chelex 100. DOTATATE conjugate was successfully radiolabelled with high yield at elevated temperature using the produced 44Sc. While 44CaCO3 is relatively expensive, the cost of 44Sc-DOTATATE production can be reduced by target recovery. Due to low proton energy required to produce GBq activity level of 44Sc, the availability of 44Sc radioisotope could be enhanced to open new opportunities for applications in medical imaging. (orig.)

  18. Synergistic active targeting of dually integrin αvβ3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies.

    Science.gov (United States)

    Shi, Sanjun; Zhou, Min; Li, Xin; Hu, Min; Li, Chenwen; Li, Min; Sheng, Fangfang; Li, Zhuoheng; Wu, Guolin; Luo, Minghe; Cui, Huanhuan; Li, Ziwei; Fu, Ruoqiu; Xiang, Mingfeng; Xu, Jing; Zhang, Qian; Lu, Laichun

    2016-08-10

    Conventional enhanced permeation and retention (EPR) mediates the effects of many drugs, including the accumulation of nanocarriers at tumor sites, but its efficiency remains low. In this study, this limitation was overcome by developing a dual-targeting delivery system based on hyaluronan (HA, a major ligand of CD44) and tetraiodothyroacetic acid (tetrac, a specific ligand of αvβ3), which was exploited to carry docetaxel (DTX) for the synergistic active targeting to tumors. First, a tetrac-HA (TeHA) conjugate was synthesized and grafted onto the surfaces of solid lipid nanoparticles (SLNs) (TeHA-SLNs/DTX), with a high encapsulation efficiency of >91.6%. The resulting SLNs exhibited an approximately toroid morphology revealed using TEM. The cellular uptake and cytotoxicity of various formulations on CD44/αvβ3-enriched B16F10 cells were then assessed, and both results confirmed the selective uptake and high cytotoxicity of the TeHA-SLNs/DTX in a TeHA-dependent manner. In vivo imaging and vessel distribution tests revealed the efficiency of synergistic active targeting was higher than that of EPR-mediated passive targeting by the TeHA-SLNs to αvβ3-expressing tumor blood vessels and CD44-expressing tumor cells via selective targeting. Finally, in both xenograft tumor mice and in situ lung metastasis tumor mice, tumor growth was significantly inhibited by TeHA-SLNs/DTX. Therefore, TeHA-SLNs are an efficient system for the dual-targeted delivery of drugs to treat cancer in vivo. PMID:27235150

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

    Science.gov (United States)

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

    2008-01-01

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

  20. An Induction Linac Driver For A 0.44 MJ Heavy-Ion Direct Drive Target

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, P.A.; Lee, E.P.; Bangerter, R.O.; Faltens, A.

    2010-02-08

    The conceptual design of a heavy ion fusion driver system is described, including all major components. Particular issues emerging from this exercise are identified and discussed. The most important conclusion of our study is that due to stringent requirements on ion pulse phase space, we are unable to find a credible accelerator design that meets the requirements of the example target. Either the target design must be modified to accept larger ion ranges and larger focal spot sizes, or we must consider other target options.

  1. An Induction Linac Driver For A 0.44 MJ Heavy-Ion Direct Drive Target

    International Nuclear Information System (INIS)

    The conceptual design of a heavy ion fusion driver system is described, including all major components. Particular issues emerging from this exercise are identified and discussed. The most important conclusion of our study is that due to stringent requirements on ion pulse phase space, we are unable to find a credible accelerator design that meets the requirements of the example target. Either the target design must be modified to accept larger ion ranges and larger focal spot sizes, or we must consider other target options.

  2. Multifragmentation in Collisions of 4.4gev-Deuterons with Gold Target

    CERN Document Server

    Avdeyev, S P; Oeschler, H; Kirakosyan, V V; Rukoyatkin, P A; Budzanowski, A; Karcz, W; Norbeck, E; Botvina, A S

    2010-01-01

    The relative velocity correlation function of pairs of intermediate mass fragments has been studied for d+Au collitions at 4.4 GeV. Experimental correlation functions are compared to that obtained by multibody Coulomb trajectory calculations under the assumption of various decay timees of the fragmenting system. The combined approach with the empirically modified intranuclear cascade code followed by the statistical multifragmentation model was used to generate the starting conditions for these calculations. The fragment emossion time is found to be less than 40 fm/c.

  3. Hyaluronan-decorated polymer nanoparticles targeting the CD44 receptor for the combined photo/chemo-therapy of cancer

    Science.gov (United States)

    Maiolino, Sara; Moret, Francesca; Conte, Claudia; Fraix, Aurore; Tirino, Pasquale; Ungaro, Francesca; Sortino, Salvatore; Reddi, Elena; Quaglia, Fabiana

    2015-03-01

    In the attempt to develop novel concepts in designing targeted nanoparticles for combination therapy of cancer, we propose here CD44-targeted hyaluronan-decorated double-coated nanoparticles (dcNPs) delivering the lipophilic chemotherapeutic docetaxel (DTX) and an anionic porphyrin (TPPS4). dcNPs are based on electrostatic interactions between a negative DTX-loaded nanoscaffold of poly(lactide-co-glycolide), a polycationic shell of polyethyleneimine entangling negatively-charged TPPS4 and finally decorated with hyaluronan (HA) to promote internalization through CD44 receptor-mediated endocytosis. DTX/TPPS4-dcNPs, prepared through layer-by-layer deposition, showed a hydrodynamic diameter of around 180 nm, negative zeta potential and efficient loading of both DTX and TPPS4. DTX/TPPS4-dcNPs were freeze-dried with trehalose giving a powder that could be easily dispersed in different media. Excellent stability of dcNPs in specific salt- and protein-containing media was found. Spectroscopic behavior of DTX/TPPS4-dcNPs demonstrated a face-to-face arrangement of the TPPS4 units in non-photoresponsive H-type aggregates accounting for an extensive aggregation of the porphyrin embedded in the shell. Experiments in MDA-MB-231 cells overexpressing the CD44 receptor demonstrated a 9.4-fold increase in the intracellular level of TPPS4 delivered from dcNPs as compared to free TPPS4. Light-induced death increased tremendously in cells that had been treated with a combination of TPPS4 and DTX delivered through dcNPs as compared with free drugs, presumably due to efficient uptake and co-localization inside the cells. In perspective, the strategy proposed here to target synergistic drug combinations through HA-decorated nanoparticles seems very attractive to improve the specificity and efficacy of cancer treatment.In the attempt to develop novel concepts in designing targeted nanoparticles for combination therapy of cancer, we propose here CD44-targeted hyaluronan-decorated double

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

    Science.gov (United States)

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

    2016-05-01

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

  5. CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells

    OpenAIRE

    Liang, Shujing; Li, Chao; Zhang, Chunlei; Chen, Yunsheng; Xu, Liang; Bao, Chenchen; Wang, Xiaoyong; Liu, Gang; ZHANG, FENGCHUN; Cui, Daxiang

    2015-01-01

    Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upo...

  6. Production of a {sup 44} Ti target and its cross section of thermal neutron capture; Producao de um alvo de {sup 44} Ti e sua secao de choque para captura de neutrons termicos

    Energy Technology Data Exchange (ETDEWEB)

    Ejnisman, R

    1993-12-31

    A study of the production of a {sup 44} Ti target was carried out aiming the determination of its thermal neutron capture cross-section. With this purpose, the cross-section of the reaction {sup 45} Sc(p,2 n) {sup 44} Ti was determined in the energies 16-, 18-, 20-22- and 45 MeV. The cross-section of the reactions (p,n) {sup 45} Ti, (p,pn) {sup 44m} Sc, (p,pn) {sup 44g} Sc and (p,p2n){sup 43} Sc were also measured. The results in the low energy region are in good agreement with a previous work by McGee et al. On the other hand, the cross-section at 45 MeV is different from McGee`s result and indicates the existence of an abnormal behavior of the excitation function at higher energies. Furthermore, a radiochemical separation method was developed in order to eliminate Sc from the {sup 44} Ti target which was irradiated with neutrons. It was possible to determine an upper limit for the cross-section of the reaction {sup 44} Ti (n, {gamma}) of 4 x 10{sup 3} b. At last, it is presented a discussion of the results obtained and their possible astrophysical implications. (author) 94 refs.

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

    OpenAIRE

    Vink, S.; Alewood, PF

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bernd eKuhn

    2012-07-01

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

  9. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer

    Science.gov (United States)

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor

  10. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer.

    Science.gov (United States)

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44. PMID:27203688

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-31

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

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Separation of no-carrier-added 62Zn from 7Li irradiated cobalt target using calcium alginate beads

    International Nuclear Information System (INIS)

    A 59Co target was irradiated with 47 MeV 7Li, which produced NCA 62Zn in the target matrix. NCA 62Zn was separated from the target matrix by adsorption on calcium alginate beads kept in HNO3 solutions of different pH values (1-6). The optimum separation condition was achieved at pH 5, where ∼83% NCA 62Zn was adsorbed on the alginate beads along with some contamination from the bulk Co. The complete separation of 62Zn from the bulk was achieved on desorbing Co from the beads with 0.1 M NaNO2. The remaining 62Zn was separated on re-adsorption under the same condition. (author)

  14. CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells

    Science.gov (United States)

    Liang, Shujing; Li, Chao; Zhang, Chunlei; Chen, Yunsheng; Xu, Liang; Bao, Chenchen; Wang, Xiaoyong; liu, Gang; zhang, Fengchun; Cui, Daxiang

    2015-01-01

    Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm2, 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future. PMID:26155313

  15. CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

    Science.gov (United States)

    Liang, Shujing; Li, Chao; Zhang, Chunlei; Chen, Yunsheng; Xu, Liang; Bao, Chenchen; Wang, Xiaoyong; Liu, Gang; Zhang, Fengchun; Cui, Daxiang

    2015-01-01

    Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future. PMID:26155313

  16. Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals

    Science.gov (United States)

    Lee, Taeksu; Lim, Eun-Kyung; Lee, Jaemin; Kang, Byunghoon; Choi, Jihye; Park, Hyo Seon; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

    2013-04-01

    Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.

  17. Targeting CD44 by Hyaluronic Acid-Based Nano Drug Delivery Systems May Eradicate Cancer Stem Cells in Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Rassoul Dinarvand

    2011-01-01

    Full Text Available Despite the significant progress in cancer diagnosis and therapy, still invasion and metastasis of cancer cells, development of drug resistance and cancer recurrence are the main causes of mortality in cancer patients. Recent researches on cancer stem cells (CSCs along with the role of CD44 marker in drug resistance and as the main marker of breast CSCs, highlight the importance of CD44 in cancer targeted therapy. Additionally, co-localization of MDR1 and CD44 in cancer cell population showed that one protein directly influences the expression of the other and disruption of interaction has significant effects on drug resistance, cell migration and in vitro invasion. Based on the above information, using nanotechnology-derived CD44 targeted drug delivery systems will be able to address recurrence of the disease and other major obstacles in cancer chemotherapy. Therefore, we hypotheses that using combination of cytotoxic agents and CSC specific agents anchored in hyaluronic acid (as the endogenous substrate of CD44, have the potential to develop novel drug delivery systems to eradicate breast cancer.

  18. Target β-catenin/CD44/Nanog axis in colon cancer cells by certain N'-(2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazides.

    Science.gov (United States)

    Radwan, Awwad A; Al-Mohanna, F; Alanazi, Fares K; Manogaran, P S; Al-Dhfyan, Abdullah

    2016-04-01

    Cell surface molecule CD44 plays a major role in regulation of cancer stem cells CSCs on both phenotypic and functional level, however chemical inhibition approach of CD44 to targets CSCs is poorly studied. Herein, we report the discovery of certain N'-(2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazides as a novel inhibitor of CD44. Molecular docking study showed interference of the scaffold of these compounds with β-catenin/TCF-4 complex, building a direct relationship between CD44 inhibition and observed well-fitted binding domain. Compound 11a, most potent member elicits inhibition effect on TCF/LEF reporter activity conformed the involvement of Wnt pathway inhibition as a mechanism of action. Furthermore, the treatment by the mentioned compound leads to inhibition of embryonic transcriptional factor Nanog but not Sox2 or Oct-4 suggested specific targeted effect. Moreover, the cytotoxicity and cell cycle effect of this series seems to be dependent on CD44 expression. PMID:26944615

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

    Science.gov (United States)

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

    2016-09-01

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

  20. CD44-Targeted Hyaluronic Acid-Coated Redox-Responsive Hyperbranched Poly(amido amine)/Plasmid DNA Ternary Nanoassemblies for Efficient Gene Delivery.

    Science.gov (United States)

    Gu, Jijin; Chen, Xinyi; Ren, Xiaoqing; Zhang, Xiulei; Fang, Xiaoling; Sha, Xianyi

    2016-07-20

    Hyaluronic acid (HA), which can specifically bind to CD44 receptor, is a specific ligand for targeting to CD44-overexpressing cancer cells. The current study aimed to develop ternary nanoassemblies based on HA-coating for targeted gene delivery to CD44-positive tumors. A novel reducible hyperbranched poly(amido amine) (RHB) was assembled with plasmid DNA (pDNA) to form RHB/pDNA nanoassemblies. HA/RHB/pDNA nanoassemblies were fabricated by coating HA on the surface of the RHB/pDNA nanoassembly core through electrostatic interaction. After optimization, HA/RHB/pDNA nanoassemblies were spherical, core-shell nanoparticles with nanosize (187.6 ± 11.4 nm) and negative charge (-9.1 ± 0.3 mV). The ternary nanoassemblies could efficiently protect the condensed pDNA from enzymatic degradation by DNase I, and HA could significantly improve the stability of nanoassemblies in the sodium heparin solution or serum in vitro. As expected, HA significantly decreased the cytotoxicity of RHB/pDNA nanoassemblies due to the negative surface charges. Moreover, it revealed that HA/RHB/pDNA nanoassemblies showed higher transfection activity than RHB/pDNA nanoassemblies in B16F10 cells, especially in the presence of serum in vitro. Because of the active recognition between HA and CD44 receptor, there was significantly different transfection efficiency between B16F10 (CD44+) and NIH3T3 (CD44-) cells after treatment with HA/RHB/pDNA nanoassemblies. In addition, the cellular targeting and transfection activity of HA/RHB/pDNA nanoassemblies were further evaluated in vivo. The results indicated that the interaction between HA and CD44 receptor dramatically improved the accumulation of HA/RHB/pDNA nanoassemblies in CD44-positive tumor, leading to higher gene expression than RHB/pDNA nanoassemblies. Therefore, HA/RHB/pDNA ternary nanoassemblies may be a potential gene vector for delivery of therapeutic genes to treat CD44-overexpressing tumors in vivo. PMID:27311558

  1. CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel.

    Science.gov (United States)

    Muntimadugu, Eameema; Kumar, Rajendra; Saladi, Shantikumar; Rafeeqi, Towseef Amin; Khan, Wahid

    2016-07-01

    This combinational therapy is mainly aimed for complete eradication of tumor by killing both cancer cells and cancer stem cells. Salinomycin (SLM) was targeted towards cancer stem cells whereas paclitaxel (PTX) was used to kill cancer cells. Drug loaded poly (lactic-co-glycolic acid) nanoparticles were prepared by emulsion solvent diffusion method using cationic stabilizer. Size of the nanoparticles (below 150nm) was determined by dynamic light scattering technique and transmission electron microscopy. In vitro release study confirmed the sustained release pattern of SLM and PTX from nanoparticles more than a month. Cytotoxicity studies on MCF-7 cells revealed the toxicity potential of nanoparticles over drug solutions. Hyaluronic acid (HA) was coated onto the surface of SLM nanoparticles for targeting CD44 receptors over expressed on cancer stem cells and they showed the highest cytotoxicity with minimum IC50 on breast cancer cells. Synergistic cytotoxic effect was also observed with combination of nanoparticles. Cell uptake studies were carried out using FITC loaded nanoparticles. These particles showed improved cellular uptake over FITC solution and HA coating further enhanced the effect by 1.5 folds. CD44 binding efficiency of nanoparticles was studied by staining MDA-MB-231 cells with anti CD44 human antibody and CD44(+) cells were enumerated using flow cytometry. CD44(+) cell count was drastically decreased when treated with HA coated SLM nanoparticles indicating their efficiency towards cancer stem cells. Combination of HA coated SLM nanoparticles and PTX nanoparticles showed the highest cytotoxicity against CD44(+) cells. Hence combinational therapy using conventional chemotherapeutic drug and cancer stem cell inhibitor could be a promising approach in overcoming cancer recurrence due to resistant cell population. PMID:27045981

  2. In vivo evaluation of novel ketal-based oligosaccharides of hyaluronan micelles as multifunctional CD44 receptor-targeting and tumor pH-responsive carriers.

    Science.gov (United States)

    Chen, Daquan; Sun, Jingfang; Sun, Kaoxiang; Liu, Wanhui; Wu, Zimei

    2016-05-01

    In this report, the oligosaccharides of hyaluronan (oHA)-histidine-menthone 1,2-glycerol ketal (MGK) (oHM) carried pH-sensitive MGK as hydrophobic moieties and oHA as the target of the CD44 receptor. The oHM could self-assemble, with a diameter of 65 nm. The cellular uptake, indicated by the fluorescent signals, was higher at 4 h. The ex vivo imaging indicated that micelles have a longer blood circulation, beyond 5 h. The fluorescence intensity of the micelles in the liver and spleen was much higher from 5 to 24 h. The CD44 receptor-targeting, indicated by the fluorescence signals of A549 and MDA-MB-231 group, were higher than those of the HepG2 and the control. PMID:25613026

  3. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    Science.gov (United States)

    Yang, Xiaoqian; Lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-02-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer.

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

    Directory of Open Access Journals (Sweden)

    Zhiling Zhang

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

  5. 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.

  6. 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...

  7. 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.

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

    Science.gov (United States)

    Vink, S; Alewood, P F

    2012-11-01

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

  9. LNA aptamer based multi-modal, Fe3O4-saturated lactoferrin (Fe3O4-bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumor targeting and NIR, MRI and CT imaging.

    Science.gov (United States)

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

    2015-12-01

    This is the first ever attempt to combine anti-cancer therapeutic effects of emerging anticancer biodrug bovine lactoferrin (bLf), and multimodal imaging efficacy of Fe3O4 nanoparticles (NPs) together, as a saturated Fe3O4-bLf. For cancer stem cell specific uptake of nanocapsules/nanocarriers (NCs), Fe3O4-bLf was encapsulated in alginate enclosed chitosan coated calcium phosphate (AEC-CP) NCs targeted (Tar) with locked nucleic acid (LNA) modified aptamers against epithelial cell adhesion molecule (EpCAM) and nucleolin markers. The nanoformulation was fed orally to mice injected with triple positive (EpCAM, CD133, CD44) sorted colon cancer stem cells in the xenograft cancer stem cell mice model. The complete regression of tumor was observed in 70% of mice fed on non-targeted (NT) NCs, with 30% mice showing tumor recurrence after 30 days, while only 10% mice fed with Tar NCs showed tumor recurrence indicating a significantly higher survival rate. From tumor tissue analyses of 35 apoptotic markers, 55 angiogenesis markers, 40 cytokines, 15 stem cell markers and gene expression studies of important signaling molecules, it was revealed that the anti-cancer mechanism of Fe3O4-bLf was intervened through TRAIL, Fas, Fas-associated protein with death domain (FADD) mediated phosphorylation of p53, to induce activation of second mitochondria-derived activator of caspases (SMAC)/DIABLO (inhibiting survivin) and mitochondrial depolarization leading to release of cytochrome C. Induction of apoptosis was observed by inhibition of the Akt pathway and activation of cytokines released from monocytes/macrophages and dendritic cells (interleukin (IL) 27, keratinocyte chemoattractant (KC)). On the other hand, the recurrence of tumor in AEC-CP-Fe3O4-bLf NCs fed mice mainly occurred due to activation of alternative pathways such as mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK) and Wnt signaling leading to an increase in expression of survivin

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

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Simonsen, Ulf

    2010-01-01

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

  11. Combination wt-p53 and MicroRNA-125b Transfection in a Genetically Engineered Lung Cancer Model Using Dual CD44/EGFR-targeting Nanoparticles.

    Science.gov (United States)

    Talekar, Meghna; Trivedi, Malav; Shah, Parin; Ouyang, Qijun; Oka, Adwait; Gandham, Srujan; Amiji, Mansoor M

    2016-04-01

    Mutations in KRAS and p53 signaling pathways contribute to loss of responsiveness to current therapies and a decreased survival in lung cancer. In this study, we have investigated the delivery and transfection of wild-type (wt-) p53 and microRNA-125b (miR-125b) expressing plasmid DNA, in SK-LU-1 human lung adenocarcinoma cells as well as in Kras(G12D)/p53(fl/fl) (KP) genetically engineered mouse model of lung cancer. Systemic plasmid DNA delivery with dual CD44/EGFR-targeted hyaluronic acid (HA)-based nanoparticles (NPs) resulted in a 2- to 20-fold increase in wt-p53 and miR-125b gene expression in SK-LU-1 cells. This resulted in enhanced apoptotic activity as seen with increased APAF-1 and caspase-3 gene expression. Similarly, in vivo evaluations in KP mouse model indicated successful CD44/EGFR-targeted delivery. Tumor growth inhibition and apoptotic induction were also observed with (wt-p53+miR125b) combination therapy in KP tumor model. Lastly, J774.A1 murine macrophages co-cultured with transfected SK-LU-1 cells showed a 14- to 35-fold increase in the iNOS-Arg-1 ratio, supportive of previous results demonstrating a role of miR-125b in macrophage repolarization. Overall, these results show tremendous promise of wt-p53 and miR-125b gene therapy using dual CD44/EGFR-targeting HA NP vector for effective treatment of lung cancer. PMID:26686386

  12. Calcium pectinate gel beads obtained from callus cultures pectins as promising systems for colon-targeted drug delivery.

    Science.gov (United States)

    Günter, Elena A; Popeyko, Oxana V

    2016-08-20

    Low methyl-esterified pectins obtained from the cell walls of the campion (SV, SV>300), tansy (TV, TV>300) and duckweed (LM, LM>300) callus cultures and apple pectin (AP, Classic AU 701) were used as the carriers for colon delivery of prednisolone. The pectins with molecular weight more than 300kDa (SV>300, TV>300, LM>300) formed gels which exhibited the higher gel strength. The higher gel strength of these gels appeared to be related to the higher Mw and the lower degree of methylesterification (DE) of these pectins. Release aspects of prednisolone in the simulated gastric (pH 1.25), intestinal (pH 7.0) and colonic (pH 7.0+pectinase) media were investigated. The LM-5%, AP-3% and AP-5% beads destroyed in simulated intestinal medium probably due to the higher DE of the LM and AP pectins. The SV>300-3% and TV>300-3% prednisolone loaded bead systems showed a high stability at pH 1.25 and pH 7.0. Prednisolone release occurred in a larger extent in colonic medium due to the enzymatic erosion of the beads. The SV>300-3% and TV>300-3% particles showed a more controlled release that appeared to be related to the lower DE, rhamnogalacturonan content, rhamnogalacturonan I branching and the higher linearity and Mw of the TV>300 and SV>300 pectins, as well as to the higher gel strength. This in vitro study suggests that calcium pectinate gel beads obtained from callus cultures pectins can be proposed as potential systems for colon-targeted drug delivery. PMID:27178956

  13. Cyclotron production of 44Sc: From bench to bedside

    International Nuclear Information System (INIS)

    Introduction: 44Sc, a PET radionuclide, has promising decay characteristics (T1/2 = 3.97 h, Eβ+av = 632 keV) for nuclear imaging and is an attractive alternative to the short-lived 68Ga (T1/2 = 68 min, Eβ+av = 830 keV). The aim of this study was the optimization of the 44Sc production process at an accelerator, allowing its use for preclinical and clinical PET imaging. Methods: 44CaCO3 targets were prepared and irradiated with protons (~ 11 MeV) at a beam current of 50 μA for 90 min. 44Sc was separated from its target material using DGA extraction resin and concentrated using SCX cation exchange resin. Radiolabeling experiments at activities up to 500 MBq and stability tests were performed with DOTANOC by investigating different scavengers, including gentisic acid. Dynamic PET of an AR42J tumor-bearing mouse was performed after injection of 44Sc-DOTANOC. Results: The optimized chemical separation method yielded up to 2 GBq 44Sc of high radionuclidic purity. In the presence of gentisic acid, radiolabeling of 44Sc with DOTANOC was achieved with a radiochemical yield of ~ 99% at high specific activity (10 MBq/nmol) and quantities which would allow clinical application. The dynamic PET images visualized increasing uptake of 44Sc-DOTANOC into AR42J tumors and excretion of radioactivity through the kidneys of the investigated mouse. Conclusions: The concept “from-bench-to-bedside” was clearly demonstrated in this extended study using cyclotron-produced 44Sc. Sufficiently high activities of 44Sc of excellent radionuclidic purity are obtainable for clinical application, by irradiation of enriched calcium at a cyclotron. This work demonstrates a promising basis for introducing 44Sc to clinical routine of nuclear imaging using PET

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

    International Nuclear Information System (INIS)

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

  15. Choice of labeling and cell line influences interactions between the Fab fragment AbD15179 and its target antigen CD44v6

    International Nuclear Information System (INIS)

    Medical imaging by use of immunotargeting generally relies on a labeled molecule binding to a specific target on the cell surface. It is important to utilize both cell-based and time-resolved binding assays in order to understand the properties of such molecular interactions in a relevant setting. In this report we describe the detailed characterization of the interaction properties for AbD15179, a promising CD44v6-targeting antibody fragment for radio-immunotargeting. Influence of labeling and cell-line model on the protein interaction kinetics was assessed using three different labeling approaches (111In, 125I and FITC) on three different squamous carcinoma cell lines. Interactions were measured using time-resolved assays on living cells, and further analyzed with Interaction Map®. Results demonstrated a general biphasic appearance of a high- and a low-affinity binding event in all cases. The relative contribution from these two interactions differed between conjugates. For 125I-Fab, the population of low-affinity binders could be significantly increased by extending the chloramine T exposure during labeling, whereas the 111In-labeling predominantly resulted in a high-affinity interaction. Interactions were also shown to be cell line dependent, with e.g. SCC-25 cells generally mediating a faster dissociation of conjugates compared to the other cell lines. In conclusion, we report both cell line dependent and labeling associated variations in interaction kinetics for AbD15179 binding to CD44v6. This has implications for cell-based kinetic assays and applications based on labeled conjugates in general, as well as in a clinical setting, where each individual tumor may create different kinetic profiles for the same conjugate

  16. Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Daquan, E-mail: cdq1981@126.com [Peking University, School of Pharmaceutical Sciences, Health Science Center (China); Wang, Guohua [China Academy of Chinese Medical Sciences, Institute of Chinese Materia Madica (China); Song, Weiguo [Shouguang Fukang Pharmceutial Co., Ltd. (China); Zhang, Qiang, E-mail: zqdodo@bjmu.edu.cn [Peking University, School of Pharmaceutical Sciences, Health Science Center (China)

    2015-10-15

    Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug

  17. Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

    International Nuclear Information System (INIS)

    Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug

  18. In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study

    OpenAIRE

    Haylock, Anna-Karin; Spiegelberg, Diana; Nilvebrant, Johan; Sandström, Karl; Nestor, Marika

    2014-01-01

    Background Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent...

  19. Calcium - urine

    Science.gov (United States)

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

  20. 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 ...

  1. Calcium Oscillations

    OpenAIRE

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

    2011-01-01

    Calcium signaling results from a complex interplay between activation and inactivation of intracellular and extracellular calcium permeable channels. This complexity is obvious from the pattern of calcium signals observed with modest, physiological concentrations of calcium-mobilizing agonists, which typically present as sequential regenerative discharges of stored calcium, a process referred to as calcium oscillations. In this review, we discuss recent advances in understanding the underlyin...

  2. MicroRNA-223 Induced Repolarization of Peritoneal Macrophages Using CD44 Targeting Hyaluronic Acid Nanoparticles for Anti-Inflammatory Effects

    Science.gov (United States)

    Tran, Thanh-Huyen; Krishnan, Swathi; Amiji, Mansoor M.

    2016-01-01

    The aim of this study was to evaluate macrophages repolarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype upon transfection with microRNA-223 (miR-223) duplexes and miR-223 expressing plasmid DNA encapsulated in CD44-targeting hyaluronic acid-poly(ethyleneimine) (HA-PEI) nanoparticles (NPs). The HA-PEI/miR-223 NPs with spherical shape and an average diameter of 200 nm were efficiently internalized by J774A.1 alveolar and primary peritoneal macrophages and non-cytotoxic at HA-PEI concentration less than 200 μg/mL. Transfection of HA-PEI/miR-223 NPs in J774A.1 macrophages showed significantly higher miR-223 expression than that with HA-PEI/plasmid DNA expressing miR-223 (pDNA-miR-223). HA-PEI/miR-223 NPs mediated transfection increased miR-223 expression to 90 fold in primary peritoneal macrophages compared to untreated cells. The overexpression of miR-223 in both J774A.1 and peritoneal macrophages induced a phenotypic change from M1 to M2 state as indicated by a decrease in iNOS-2 (M1 marker) and an increase in Arg-1 (M2 marker) levels compared to those in lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-stimulated macrophages (M1). The change in macrophage phenotype by HA-PEI/miR-223 NPs could suppress the inflammation in peritoneal macrophages induced by LPS as evidenced by a significant decrease in pro-inflammatory cytokine levels TNF-α, IL-1β and IL-6, compared to LPS-stimulated peritoneal macrophages without treatment. The results demonstrated that miR-223-encapsulated HA-PEI NPs modulated macrophage polarity toward an anti-inflammatory M2 phenotype, which has potential for the treatment of inflammatory diseases. PMID:27148749

  3. Modulation of Macrophage Functional Polarity towards Anti-Inflammatory Phenotype with Plasmid DNA Delivery in CD44 Targeting Hyaluronic Acid Nanoparticles.

    Science.gov (United States)

    Tran, Thanh-Huyen; Rastogi, Ruchir; Shelke, Juili; Amiji, Mansoor M

    2015-01-01

    The purpose of this study was to modulate macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype using plasmid DNA (pDNA) expressing interleukin-4 (IL4) or interleukin-10 (IL10)-encapsulated in hyaluronic acid-poly(ethyleneimine) (HA-PEI) nanoparticles (NPs). The HA-PEI/pDNA NPs with spherical shape, average size of 186 nm were efficiently internalized by J774A.1 macrophages. Transfection of HA-PEI/pDNA-IL4 and HA-PEI/pDNA-IL10 NPs increased IL4 and IL10 gene expression in J774 macrophages which could re-program the macrophages from M1 to M2 phenotype as evidenced by a significant increase in the Arg/iNOS level, and upregulation of CD206 and CD163 compared to untreated macrophages. Following intraperitoneal (IP) injection to C57BL/6 mice, HA-PEI NPs effectively targeted peritoneal macrophages over-expressing CD44 receptor. In an in vivo model of stimulated peritoneal macrophages, IP administration of HA-PEI/pDNA-IL4 and HA-PEI/pDNA-IL10 to C57BL/6 mice significantly increased the Arg/iNOS ratio and CD163 expression in the cells. Furthermore, HA-PEI/pDNA-IL10 NPs significantly increased peritoneal and serum IL10 levels which effectively suppressed LPS-induced inflammation by reducing level of TNF-α and IL-1β in peritoneal macrophages and in the peritoneal fluid. The results demonstrated that pDNA-IL10-encapsulate HA-PEI NPs skewed macrophage functional polarity from M1 toward an anti-inflammatory M2 phenotype which may be a promising platform for the treatment of inflammatory diseases. PMID:26577684

  4. Calcium hydroxide isotope effect in calcium isotope enrichment by ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Jepson, B.E.; Shockey, G.C.

    1984-01-01

    The enrichment of calcium isotopes has been observed in ion-exchange chromatography with an aqueous phase of calcium hydroxide and a solid phase of sulfonic acid resin. The band front was exceedingly sharp as a result of the acid-base reaction occuring at the front of the band. Single-stage separation coefficients were found to be epsilon(/sup 44/Ca//sup 40/Ca) = 11 x 10 /sup -4/ and epsilon(/sup 48/Ca//sup 40/Ca) = 18 x 10/sup -4/. The maximum column separation factors achieved were 1.05 for calcium-44 and 1.09 for calcium-48 with the heavy isotopes enriching in the fluid phase. The calcium isotope effect between fully hydrated aqueous calcium ions and undissociated aqueous calcium hydroxide was estimated. For the calcium-44/40 isotope pair the separation coefficient was 13 x 10/sup -4/. 20 references, 2 figures.

  5. Analysis of Noncanonical Calcium-Dependent Protein Kinases in Toxoplasma gondii by Targeted Gene Deletion Using CRISPR/Cas9.

    Science.gov (United States)

    Long, Shaojun; Wang, Qiuling; Sibley, L David

    2016-05-01

    Calcium-dependent protein kinases (CDPKs) are expanded in apicomplexan parasites, especially in Toxoplasma gondii where 14 separate genes encoding these enzymes are found. Although previous studies have shown that several CDPKs play a role in controlling invasion, egress, and cell division in T. gondii, the roles of most of these genes are unexplored. Here we developed a more efficient method for gene disruption using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) that was modified to completely delete large, multiexonic genes from the genome and to allow serial replacement by recycling of the selectable marker using Cre-loxP. Using this system, we generated a total of 24 mutants in type 1 and 2 genetic backgrounds to ascertain the functions of noncanonical CDPKs. Remarkably, although we were able to confirm the essentiality of CDPK1 and CDPK7, the majority of CDPKs had no discernible phenotype for growth in vitro or infection in the mouse model. The exception to this was CDPK6, loss of which leads to reduced plaquing, fitness defect in a competition assay, and reduced tissue cyst formation in chronically infected mice. Our findings highlight the utility of CRISPR/Cas9 for rapid serial gene deletion and also suggest that additional models are needed to reveal the functions of many genes in T. gondii. PMID:26755159

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

    Science.gov (United States)

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

    2016-02-01

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

  7. The small conductance calcium-activated potassium channel 3 (SK3) is a molecular target for Edelfosine to reduce the invasive potential of urothelial carcinoma cells.

    Science.gov (United States)

    Steinestel, Konrad; Eder, Stefan; Ehinger, Konstantin; Schneider, Juliane; Genze, Felicitas; Winkler, Eva; Wardelmann, Eva; Schrader, Andres J; Steinestel, Julie

    2016-05-01

    Metastasis is the survival-determining factor in urothelial carcinoma (UC) of the urinary bladder. The small conductance calcium-activated potassium channel 3 (SK3) enhances tumor cell invasion in breast cancer and malignant melanoma. Since Edelfosine, a glycerophospholipid with antitumoral properties, effectively inhibits SK3 channel activity, our goal was to evaluate SK3 as a potential molecular target to inhibit the gain of an invasive phenotype in UC. SK3 protein expression was analyzed in 208 tissue samples and UC cell lines. Effects of Edelfosine on SK3 expression and intracellular calcium levels as well as on cell morphology, cell survival and proliferation were assessed using immunoblotting, potentiometric fluorescence microscopy, and clonogenic/cell survival assay; furthermore, we analyzed the effect of Edelfosine and SK3 RNAi knockdown on tumor cell migration and invasion in vitro and in vivo. We found that SK3 is strongly expressed in muscle-invasive UC and in the RT112 cellular tumor model. Higher concentrations of Edelfosine have a strong antitumoral effect on UC cells, while 1 μM effectively inhibits migration/invasion of UC cells in vitro and in vivo comparable to the SK3 knockdown phenotype. Taken together, our results show strong expression of SK3 in muscle-invasive UC, consistent with the postulated role of the protein in tumor cell invasion. Edelfosine is able to effectively inhibit migration and invasion of UC cells in vitro and in vivo in an SK3-dependent way, pointing towards a possible role for Edelfosine as an antiinvasive drug to effectively inhibit UC cell invasion and metastasis. PMID:26619845

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

    Science.gov (United States)

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

    2016-01-01

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

  9. SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

    Energy Technology Data Exchange (ETDEWEB)

    Li, S; Charpentier, P; Sayler, E; Micaily, B; Miyamoto, C [Temple University Hospital, Phila., PA (United States); Geng, J [Xigen LLC, Gaithersburg, MD (United States)

    2015-06-15

    Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection and principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large deformable

  10. SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

    International Nuclear Information System (INIS)

    Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection and principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large deformable

  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

    OpenAIRE

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

    2016-01-01

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

  12. Effects of new targets of CDK2 RNA interference on proliferation of SHG44 cells%新靶点CDK2干扰RNA对人脑胶质瘤增殖影响

    Institute of Scientific and Technical Information of China (English)

    呼格吉乐; 张军力; 段美庆; 王俊瑞; 高乃康

    2013-01-01

    Objective To construct four new eukaryotic expression vectors of RNA interference specific for cyclindependent kinase-2 (CDK2) and transfect the vectors into SHG44 cells for the detection of vectors with strong interferential effect.Methods Four new eukaryotic expression vectors of RNA interference specific for CDK2 were constructed.The human glioma SHG44 cell line was transfected with the four new vectors.The mRNA contents of CDK2 were detected using reverse transcriptase-PCR (RT-PCR).The change in proliferation of SHG44 cells was assayed.Results The new vectors ith new targets of eukaryotic expression of RNA interference specific for CDK2 were constructed (PCDK2-1,PCDK2-2,PCDK2-3,PCDK2-4).CDK2 small interfering RNA (siRNA) could suppress expression of mRNA and pCDK2-1.siRNA could inhibit the proliferation of SHG44 cell line.Conclusion The proliferation of human SHG44 cell line could be significantly inhibited after the transfection with new eukaryotic expression vectors of CDK2 siRNA.%目的 构建4个新靶点的人细胞周期蛋白依赖性激酶2(CDK2)干扰RNA真核表达载体,转染人脑胶质瘤细胞后,检测出干扰效果最好的载体及细胞增殖能力的变化.方法 构建4个新靶点CDK2干扰RNA真核表达载体并用双酶切和测序鉴定;分别转染上述4个载体到人脑胶质瘤细胞株SHG44;通过逆转录聚合酶链反应(RT-PCR)比较转染后CDK2 mRNA的表达量,选出干扰效果最好的一个,检测细胞增殖能力的变化.结果 成功构建4个新靶点的CDK2干扰RNA真核表达载体PCDK2-1、PCDK2-2、PCDK2-3、PCDK2-4;CDK2 mRNA表达和细胞增殖明显受到抑制,PCDK2-1的干扰效果为56%;PCDK2-1-SHG44细胞与对照组相比增殖能力减弱.结论 成功构建并筛选出效果最好的新靶点CDK2干扰RNA真核表达载体,并使SHG44细胞的增殖水平降低.

  13. Calcium Carbonate

    Science.gov (United States)

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

  14. 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<0.0001) or...

  15. Calcium Calculator

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2015-12-28

    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. PMID:26478017

  17. Calcium pyrophosphate arthritis

    Science.gov (United States)

    Calcium pyrophosphate dihydrate deposition disease; CPPD disease; Acute CPPD arthritis; Pseudogout ... Calcium pyrophosphate arthritis is caused by the collection of salt called calcium pyrophosphate dihydrate (CPPD). The buildup ...

  18. Calcium and bones

    Science.gov (United States)

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

  19. Get Enough Calcium

    Science.gov (United States)

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

  20. 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 ...

  1. Calcium absorption from corn tortilla is relatively high and is dependent upon calcium content and liming in Mexican women.

    Science.gov (United States)

    Rosado, Jorge L; Díaz, Margarita; Rosas, Angélica; Griffit, Ian; García, Olga P

    2005-11-01

    Corn tortillas are the staple food of Mexico. During their preparation, calcium is added to the tortillas; therefore, tortillas are the main source of calcium for a large proportion of the population. The bioavailability of calcium from lime-treated tortillas in humans is not known. The objectives of the present study were to determine calcium absorption from corn tortilla, to determine the effect of lime treatment on calcium absorption from corn tortilla, and to compare calcium absorption from tortilla prepared with a commercial corn flour and tortillas prepared with the traditional lime treatment at home. Nonpregnant, nonlactating women (n = 9) were administered 3 different treatments: 1) 180 g of corn tortilla prepared from corn flour with no lime treatment (CF), 2) 180 g of corn tortilla prepared from lime-treated commercial corn flour (LTCCF), or 3) 180 g of corn tortillas prepared from lime-treated home-prepared corn flour (LTHCF). Calcium absorption was measured using an established dual-tracer stable isotope technique. Calcium absorption of CF, LTCCF, and LTHCF was (mean +/- SD): 44 +/- 3.2, 32 +/- 4.4, and 30 +/- 2.4%, respectively; the fractional calcium absorption from CF differed from that of either LTCCF or LTHCF (P tortillas is high and dependent on calcium concentration. The addition of calcium during lime treatment increases calcium concentration and total calcium absorption. PMID:16251614

  2. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

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

    1984-01-01

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

  3. Thin-target excitation functions, cross-sections and optimised thick-target yields for natMo(p,xn)94g,95m,95g,96(m+g)Tc nuclear reactions induced by protons from threshold up to 44 MeV. No Carrier Added radiochemical separation and quality control

    International Nuclear Information System (INIS)

    This work describes the method adopted in our laboratories, to produce 94gTc, 95gTc, 95mTc and 96gTc radionuclides via proton-cyclotron irradiation on molybdenum targets of natural isotopic composition. A new set of experimental thin-target excitation functions and 'effective' cross-sections for direct natMo(p,xn)ATc [with A=94, 95, 95, 96] nuclear reactions, with incident proton energy in the range from threshold up to 44 MeV is presented. Some definitions of the equations used and nuclear data traceability are reported. Thick-target yield values were calculated and optimised, by numerical fitting and integration of the measured excitation functions. These values allow optimisation of production yield of one radionuclide, minimising at the same time the yield of the others. Radiochemical separation on NCA technetium radionuclides from both molybdenum target and niobium, zirconium and yttrium radioactive by-products is reported. Quality control tests of the radiotracers were developed for the applications envisaged in environmental metallo-biochemical toxicology

  4. Calcium isotope ratios in animal and human bone

    Science.gov (United States)

    Reynard, L. M.; Henderson, G. M.; Hedges, R. E. M.

    2010-07-01

    Calcium isotopes in tissues are thought to be influenced by an individual's diet, reflecting parameters such as trophic level and dairy consumption, but this has not been carefully assessed. We report the calcium isotope ratios (δ 44/42Ca) of modern and archaeological animal and human bone ( n = 216). Modern sheep raised at the same location show 0.14 ± 0.08‰ higher δ 44/42Ca in females than in males, which we attribute to lactation by the ewes. In the archaeological bone samples the calcium isotope ratios of the herbivorous fauna vary by location. At a single site, the archaeological fauna do not show a trophic level effect. Humans have lower δ 44/42Ca than the mean site fauna by 0.22 ± 0.22‰, and the humans have a greater δ 44/42Ca range than the animals. No effect of sex or age on the calcium isotope ratios was found, and intra-individual skeletal δ 44/42Ca variability is negligible. We rule out dairy consumption as the main cause of the lower human δ 44/42Ca, based on results from sites pre-dating animal domestication and dairy availability, and suggest instead that individual physiology and calcium intake may be important in determining bone calcium isotope ratios.

  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. Coronary Calcium Scan

    Science.gov (United States)

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

  7. 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 ...

  8. 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 ...

  9. Calcium in diet

    Science.gov (United States)

    Diet - calcium ... Calcium is one of the most important minerals for the human body. It helps form and maintain healthy teeth and bones. A proper level of calcium in the body over a lifetime can help ...

  10. 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 ...

  11. Expression and Function of CD44 in Epithelial Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Joelle D. Sacks

    2015-11-01

    Full Text Available CD44, a cell surface glycoprotein, has been increasingly implicated in the pathogenesis and progression of epithelial ovarian cancer, the deadliest gynecologic malignancy in women. Here, we review recent reports on the expression and function of CD44 in epithelial ovarian carcinoma. Further functional data for CD44 in peritoneal adhesion and metastatic progression and its association with stem cells is highlighted. Recent studies utilizing CD44 for therapeutic targeting are also discussed.

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

    Science.gov (United States)

    Honorio-França, Adenilda Cristina; Nunes, Gabriel Triches; Fagundes, Danny Laura Gomes; de Marchi, Patrícia Gelli Feres; Fernandes, Rubian Trindade da Silva; França, Juliana Luzia; França-Botelho, Aline do Carmo; Moraes, Lucélia Campelo Albuquerque; Varotti, Fernando de Pilla; França, Eduardo Luzía

    2016-01-01

    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 percentage of apoptotic cells was observed. The highest apoptosis index was observed when the cells were treated with PEG microspheres with adsorbed SIgA. Conclusion These data suggest that colostral SIgA adsorbed to PEG microspheres has antitumor effects on human MCF-7 breast cancer cells and that the presence of large amounts of this protein in secreted breast milk may provide protection against breast tumors in women who breastfed. PMID:26893571

  13. Calcium and Vitamin D

    Science.gov (United States)

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

  14. 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

  15. Importance of Calcium

    OpenAIRE

    TANDOĞAN, Berivan; ULUSU, N. Nuray

    2005-01-01

    Calcium is the most abundant mineral in the body. Calcium regulates many cellular processes and has important structural roles in living organisms. Skeletal muscle structure and function, polymerisation of fibrin and the conduction of impulses in the nervous system are regulated by calcium. Calcium is an important intracellular messenger in protozoa, plants, and animals. Calcium-transporting systems which are located in the plasma membrane and in the organelles, regulate the ionic concentrati...

  16. Calcium in diet

    Science.gov (United States)

    ... best source. Milk and dairy products such as yogurt, cheeses, and buttermilk contain a form of calcium ... the amount of calcium in a dairy product. Yogurt, most cheeses, and buttermilk are excellent sources of ...

  17. Fenoprofen calcium overdose

    Science.gov (United States)

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

  18. Calcium channel blocker overdose

    Science.gov (United States)

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

  19. Fenoprofen calcium overdose

    Science.gov (United States)

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

  20. Calcium and magnesium disorders.

    Science.gov (United States)

    Goff, Jesse P

    2014-07-01

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

  1. 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.

  2. Calcium en cardioplegie

    NARCIS (Netherlands)

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

    1985-01-01

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

  3. Expression of CD44 in pancreatic cancer and its significance

    OpenAIRE

    Li, Xiao-Ping; Zhang, Xiao-Wei; Zheng, Lei-Zhen; Guo, Wei-Jian

    2015-01-01

    Background: CD44 is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 has been reported to correlate with poor prognosis of pancreatic cancer in most literatures. The purpose of this study is to investigate the roles of CD44 in pancreatic caner, and their correlation with the prognosis of pancreatic cancer patients. Methods: 67 pancreatic cancer samples were collected in Xinhua hospital affiliated to Shanghai Jiaotong University da...

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

    Science.gov (United States)

    Komar, N.; Zeebe, R. E.

    2016-01-01

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

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

    Science.gov (United States)

    Komar, Nemanja; Zeebe, Richard

    2016-04-01

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

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

    OpenAIRE

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

    2012-01-01

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

  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. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

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

    2001-01-01

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

  9. 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.

  10. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

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

  11. EXERCISE ENHANCING CALCIUM ABSORPTION MECHANISM

    OpenAIRE

    Muliani

    2013-01-01

    Calcium has important role in many biological processes therefore calcium homeostasis should be maintained. Imbalance in calcium homeostasis would affects the bone metabolism, neuromuscular function, blood coagulation, cell proliferation and signal transduction. Homeostasis of calcium is maintained by three major organs: gastrointestinal tract, bone and kidney. Intestinal calcium absorption is the sole mechanism to supply calcium to the body. Calcium absorption controlled by calcitropic hormo...

  12. CD44: A key player in breast cancer

    Directory of Open Access Journals (Sweden)

    M T Anand

    2014-01-01

    Full Text Available CD44 is a principal transmembrane hyluronate receptor, which acts as a hook between Extracellular Matrix and the cytoskeleton. CD44 is up regulated in breast cancer, which in turn helps in tumor progression and metastasis. There has been a lot of attention given to CD44 in recent years because of the discovery, CD44+/CD24- lineage marks breast cancer stem cells. Recent clinical and experimental findings show that CD44 is involved in the tumor associated proliferation, invasion, migration, and in many pathways involved in maintaining cancer cells which inturn are correlated with patient′s survival. All these findings make CD44 as a potential target for breast cancer treatment. The methods of literature search for this article include Pubmed, BMC cancer and other printed journal article.

  13. Dengue and Calcium

    OpenAIRE

    Shivanthan, Mitrakrishnan C; Rajapakse, Senaka

    2014-01-01

    Dengue is potentially fatal unless managed appropriately. No specific treatment is available and the mainstay of treatment is fluid management with careful monitoring, organ support, and correction of metabolic derangement. Evidence with regards to the role of calcium homeostasis in dengue is limited. Low blood calcium levels have been demonstrated in dengue infection and hypocalcemia maybe more pronounced in more severe forms. The cause of hypocalcemia is likely to be multifactorial. Calcium...

  14. Measurements of intracellular calcium

    International Nuclear Information System (INIS)

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

  15. A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ho Chiang-Hong

    2011-02-01

    Full Text Available Abstract Background Hyperphosphatemia in patients with chronic kidney disease (CKD contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. Methods In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR 2 and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH levels. Results At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04. The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p p Conclusions In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. Trial Registration www.clinicaltrials.gov NCT00211978.

  16. 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...

  17. 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...

  18. Serum Calcium Level in Hypertension

    OpenAIRE

    Hazari, Mohammed Abdul Hannan; Arifuddin, Mehnaaz Sameera; Muzzakar, Syed; Reddy, Vontela Devender

    2012-01-01

    Background: The alterations in extracellular calcium level may influence intracellular calcium level and possibly play a role in the pathogenesis of essential hypertension. Aim: The purpose was to find out the association between serum calcium levels and hypertension; and to compare the serum calcium levels between normotensive controls, hypertensive subjects on calcium channel blockers, and hypertensive subjects on antihypertensive medication other than calcium channel blockers. Materials an...

  19. Colonic luminal surface retention of meloxicam microsponges delivered by erosion based colon-targeted matrix tablet.

    Science.gov (United States)

    Srivastava, Rishabh; Kumar, Deepesh; Pathak, Kamla

    2012-05-10

    The work was aimed at developing calcium-pectinate matrix tablet for colon-targeted delivery of meloxicam (MLX) microsponges. Modified quassi-emulsion solvent diffusion method was used to formulate microsponges (MS), based on 3(2) full factorial design. The effects of volume of dichloromethane and EudragitRS100 content (independent variables) were determined on the particle size, entrapment efficiency and %cumulative drug release of MS1-MS9. The optimized formulation, MS5 (d(mean)=44.47 μm, %EE=98.73, %CDR=97.32 and followed zero order release) was developed into colon-targeted matrix tablet using calcium pectinate as the matrix. The optimized colon-targeted tablet (MS5T2) shielded MLX loaded microsponges in gastrointestinal region and selectively delivered them to colon, as vizualized by vivo fluoroscopy in rabbits. The pharmacokinetic evaluation of MS5T2 in rabbits, revealed appearance of drug appeared in plasma after a lag time of 7h; a t(max) of 30 h with Fr=61.047%, thus presenting a formulation suitable for targeted colonic delivery. CLSM studies provided an evidence for colonic luminal retentive ability of microsponges at the end of 8h upon oral administration of MS5T2. Thus calcium pectinate matrix tablet loaded with MLX microsponges was developed as a promising system for the colon-specific delivery that has potential for use as an adjuvant therapy for colorectal cancer. PMID:22306039

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

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-min

    2004-01-01

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

  1. Study of the neutron decays of giant resonances excited by the inelastic scattering of {sup 36} Ar on {sup 90} Zr and {sup 94} Zr targets at 44 MeV/u: a signature of multiphonon states; Etude des decroissances par neutrons des resonances geantes excitees dans les reactions de diffusion inelastique d`{sup 36}Ar sur des cibles de {sup 90} Zr et {sup 94} Zr a 44MeV/u: une signature des etats multiphonons

    Energy Technology Data Exchange (ETDEWEB)

    Pascalon-Rozier, V.

    1997-01-13

    In inelastic heavy ion scattering, to angles near to the grazing angle, giant resonances (GR) are excited with very large differential cross sections. It has been shown that multiphonon states, states built with several GR quanta, can also been excited. These states can be revealed through the measurement of their decay by light particle emission. In this thesis, we report on the study of inelastic scattering of {sup 36}Ar at 44 MeV/u on target of {sup 90}Zr and {sup 94}Zr, measured in coincidence with neutrons detected with the EDEN multidetector. The analysis of the inelastic spectra show evidence for a structure at high excitation energy, exhibiting characteristics compatible with a two-photon excitation. The construction of missing energy spectra allows us to the study of the GR and the high energy structure. In both nuclei, the GR presents a direct decay branch of 8%, which yields informations on the microscopic structure of the resonance. A two phonon state, interpreted as two weakly coupled GR`s, built on one top of the other, and each phonon is expected to exhibit the same direct decay pattern as the GR. Such a simple decay is observed in the data, proving that the structure observed is due to the excitation of the two phonon state in both nuclei studied. Finally, we present a theoretical development based on Random Phase Approximation calculation, predicting that the two phonon state should be very harmonic. This result is in agreement with experimental studies of double phonon states over a large range of nuclei (from A = 12 to 208) carried out with several different probes. (author). 70 refs.

  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 calciu

  3. Neuronal calcium sparks and intracellular calcium “noise”

    OpenAIRE

    Melamed-Book, Naomi; Kachalsky, Sylvia G.; Kaiserman, Igor; Rahamimoff, Rami

    1999-01-01

    Intracellular calcium ions are involved in many forms of cellular function. To accommodate so many control functions, a complex spatiotemporal organization of calcium signaling has developed. In both excitable and nonexcitable cells, calcium signaling was found to fluctuate. Sudden localized increases in the intracellular calcium concentration—or calcium sparks—were found in heart, striated and smooth muscle, Xenopus Laevis oocytes, and HeLa and P12 cells. In the nervous system, intracellular...

  4. Should we prescribe calcium supplements for osteoporosis prevention?

    Science.gov (United States)

    Reid, Ian R

    2014-02-01

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

  5. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

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

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...... calcium binds silicon primarily as calcium silicates and less as potassium calcium silicates....

  6. 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.

  7. Koenimbin, a natural dietary compound of Murraya koenigii (L Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44+/CD24-/low: an in vitro study

    Directory of Open Access Journals (Sweden)

    Ahmadipour F

    2015-02-01

    Full Text Available Fatemeh Ahmadipour,1 Mohamed Ibrahim Noordin,1 Syam Mohan,2 Aditya Arya,1 Mohammadjavad Paydar,3 Chung Yeng Looi,3 Yeap Swee Keong,4 Ebrahimi Nigjeh Siyamak,4 Somayeh Fani,1 Maryam Firoozi,5 Chung Lip Yong,1 Mohamed Aspollah Sukari,6 Behnam Kamalidehghan1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Research Center, Jazan University, Jazan, Kingdom of Saudi Arabia; 3Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 5Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 6Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Malaysia Background: Inhibition of breast cancer stem cells has been shown to be an effective therapeutic strategy for cancer prevention. The aims of this work were to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L Spreng, in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer stem cells through apoptosis in vitro. Methods: Koenimbin-induced cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release were observed using high-content screening. Cell cycle arrest was examined using flow cytometry, while human apoptosis proteome profiler assays were used to investigate the mechanism of apoptosis. Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured, and nuclear factor kappa B (NF-κB activity was assessed using a high-content screening assay. Aldefluor™ and mammosphere formation assays were used to evaluate the effect of koenimbin on MCF7

  8. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Porta, Angela R.

    2000-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  11. Calcium wave of Brain Astrocytes

    Science.gov (United States)

    Cornell Bell, A. H.

    1997-03-01

    Time lapse confocal scanning laser microscopy was used to study hippocampal astrocyte cultures loaded with a calcium indicator, Fluo3-AM (4 uM). kThe neurotransmitter kainate (100uM) overwhelms the Na+-buffering capacity of astrocytes within 100 sec resulting in reversal of the Na+/Ca2+ exchanger. This results in a subcellular site where Ca2+ entering the cytoplasm contributes to a long-distance Ca2+ wave which travels at 20 um/sec without decrement. Image analysis has shown calcium waves not only at a high Kainate dose, but also at a low Kainate dose, e.g. 10uM. These are, however, shortlived and burried in an extremely noisy background and only detectable by analyzing the calcium waves images for spatio-temporal coherence. As the kainate dose increases, more large scale coherent structures with visible geometric features (spiral waves and target waves) can be observed. Multiple spiral waves are produced when the Kainate dose increases to 100 uM. These waves travel at a constant velocity across entire microscope fields for long time periods (>30 mins). Na+ channels have no effect on the Kainate wave. Voltage-gated Ca2+ channels are not involved and Ca2+ enters through reversal of the exchanger. Ca2+ release from stores does not contribute to the kainate wave. Removal of Na+ or Ca2+ from outside and the specific Na+/Ca2+ exchange inhibitor benzamil (10 uM) inhibit the kainate wave. A functional antibody to alpha6-Integrin which is localized to membrane regions between cells inhibits the spread of the kainate wave in a dose and time-dependent manner. Fluorescence Recovery after Photobleach (FRAP) techniques indicate that gap junctions remain open between cells. This would imply that Ca2+ or IP3 need not pass through the gap junction, but reversal of the exchanger would propel the Ca2+ wave at the cell surface.

  12. 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

  13. CALCIUM ISOTOPE COMPOSITION OF METEORITES, EARTH, AND MARS

    International Nuclear Information System (INIS)

    The relative abundances of calcium isotopes in the mass range 40-44 were measured in primitive and differentiated meteorites and igneous rocks from Earth and Mars in search of non-mass-dependent variations that could provide clues about early solar system processes. Most bulk samples of planetary materials have calcium isotopic compositions identical with Earth's within the current resolution of about 0.01% in 40Ca/44Ca. Possible exceptions include carbonaceous chondrites, some ordinary chondrites, and two samples of calcium-aluminum-rich inclusions, which have small excesses of 40Ca. The samples with 40Ca excesses are also known to have 50Ti and 135Ba excesses and 142Nd and 144Sm deficits. Collectively these data from refractory elements suggest that the planetary embryos represented by chondrites preserve isotopic heterogeneity that reflects different nucleosynthetic sources. No late admixture from a single nucleosynthetic source can explain all observations. The results are most compatible with variable proportions of material derived from Type II supernovae. The initial calcium isotope compositions of Earth and Mars are indistinguishable and similar to the 40Ca abundance found in some chondrites and all differentiated meteorites studied. It appears that isotopic heterogeneity in calcium was still present at the completion of disk formation but was homogenized during planetary accretion.

  14. Weak transition of 44Ca

    International Nuclear Information System (INIS)

    A study of the nuclear core contribution to the excited nuclear states was done, along with its theoretical evaluation and interpretation, in the light nuclei region. The 727 KeV gamma ray transition between the 1885 KeV O+ and 1157 KeV - 2+ states was detected, putting in evidence experimentally, the possibility of the 0+ state, characterized as core excitation, and found to be by + decay or electron capture from44,44mSc. The formation of the 2850 KeV state, due to 880 KeV transition from the 3667 KeV state, is re-discussed. The 564 KeV and 1684 KeV transitions from the 2850 KeV state to the 2285 KeV and 1157 KeV states, respectively, are also discussed. A new scheme is proposed for the 44Ca excited states. (Author)

  15. 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)

  16. Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2012-12-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

  17. N = (4,4 Supersymmetry and T-Duality

    Directory of Open Access Journals (Sweden)

    Malin Göteman

    2012-10-01

    Full Text Available A sigma model with four-dimensional target space parametrized by chiral and twisted chiral N =(2,2 superfields can be extended to N =(4,4 supersymmetry off-shell, but this is not true for a model of semichiral fields, where the N = (4,4 supersymmetry can only be realized on-shell. The two models can be related to each other by T-duality. In this paper we perform a duality transformation from a chiral and twisted chiral model with off-shell N = (4,4 supersymmetry to a semichiral model. We find that additional non-linear terms must be added to the original transformations to obtain a semichiral model with N =(4,4 supersymmetry, and that the algebra closes on-shell as a direct consequence of the T-duality.

  18. CALCIUM SOAP LUBRICANTS

    OpenAIRE

    Alaz, Izer; Tugce, Nefise; Devrim, Balköse

    2014-01-01

    The article studies the properties of calcium stearate (CaSt2) and lubricants produced on its basis. These lubricants were prepared using sodium stearate and calcium chloride by subsidence from aqueous solutions. The CaSt2 and the light fraction of crude oil were mixed together to obtain lubricating substances. The article shows that CaSt2 had the melting temperature of 142.8 C that is higher than the melting temperature of crude oil (128 C). The compositions of obtained lubricants were stu...

  19. Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2α, IRE1α, ATF6 and calmodulin kinase.

    Science.gov (United States)

    Merlot, Angelica M; Shafie, Nurul H; Yu, Yu; Richardson, Vera; Jansson, Patric J; Sahni, Sumit; Lane, Darius J R; Kovacevic, Zaklina; Kalinowski, Danuta S; Richardson, Des R

    2016-06-01

    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment. PMID:27059255

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

    Science.gov (United States)

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

  1. Allogeneic reconstitution after nonmyeloablative conditioning: mitigation of graft-versus-host and host-versus-graft reactivity by anti-CD44v6

    OpenAIRE

    Christ, Oliver; Günthert, Ursula; Schmidt, Dirk-Steffen; Zöller, Margot

    2002-01-01

    T-cell maturation is accelerated in transgenic mice expressing rat CD44v4-v7 on T cells, the effect being blocked by anti-CD44v6. This finding suggested functional activity of CD44v6 in thymocyte development. We tested the hypothesis by antibody blocking and using mice with targeted deletion of CD44v6/v7 exon products (CD44v6/v7(-/-)). When lethally irradiated CD44v6/v7-competent (CD44v6/v7(+/+)) mice were reconstituted syngeneically, higher numbers of CD44v6/v7(-/-) than CD44v6/v7(+/+) BMC w...

  2. SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce apoptosis.

    Science.gov (United States)

    Chami, M; Gozuacik, D; Lagorce, D; Brini, M; Falson, P; Peaucellier, G; Pinton, P; Lecoeur, H; Gougeon, M L; le Maire, M; Rizzuto, R; Bréchot, C; Paterlini-Bréchot, P

    2001-06-11

    By pumping calcium from the cytosol to the ER, sarco/endoplasmic reticulum calcium ATPases (SERCAs) play a major role in the control of calcium signaling. We describe two SERCA1 splice variants (S1Ts) characterized by exon 4 and/or exon 11 splicing, encoding COOH terminally truncated proteins, having only one of the seven calcium-binding residues, and thus unable to pump calcium. As shown by semiquantitative RT-PCR, S1T transcripts are differentially expressed in several adult and fetal human tissues, but not in skeletal muscle and heart. S1T proteins expression was detected by Western blot in nontransfected cell lines. In transiently transfected cells, S1T homodimers were revealed by Western blot using mildly denaturing conditions. S1T proteins were shown, by confocal scanning microscopy, to colocalize with endogenous SERCA2b into the ER membrane. Using ER-targeted aequorin (erAEQ), we have found that S1T proteins reduce ER calcium and reverse elevation of ER calcium loading induced by SERCA1 and SERCA2b. Our results also show that SERCA1 variants increase ER calcium leakage and are consistent with the hypothesis of a cation channel formed by S1T homodimers. Finally, when overexpressed in liver-derived cells, S1T proteins significantly induce apoptosis. These data reveal a further mechanism modulating Ca(2+) accumulation into the ER of nonmuscle cells and highlight the relevance of S1T proteins to the control of apoptosis. PMID:11402072

  3. A sensor for calcium uptake

    OpenAIRE

    Collins, Sean; Meyer, Tobias

    2010-01-01

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

  4. Children's Bone Health and Calcium

    Science.gov (United States)

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

  5. Tunable CD44-specific cellular retargeting with hyaluronic acid nanoshells

    DEFF Research Database (Denmark)

    Ebbesen, Morten F.; Olesen, Morten T. J.; Gjelstrup, Mikkel C.;

    2014-01-01

    Purpose In this work we specifically investigate the molecular weight (Mw) dependent combinatorial properties of hyaluronic acid (HA) for exhibiting stealth and targeting properties using different Mw HA nanoshells to tune nanoparticle retargeting to CD44-expressing cancer cells. Methods HA of...

  6. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

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

  7. 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...

  8. Calcium deposits in the common carotid artery

    International Nuclear Information System (INIS)

    Complete text of publication follows. Arterial calcification consists mainly of calcium apatite and takes place at two sites in the vessel wall: the intima and the media. Intimal calcification occurs exclusively within atherosclerotic plaques, while medial calcification may develop independently [1]. Ultrasound examination of the carotid arteries is performed routinely to assess pathological alterations. Large calcified plaques in the carotid arteries can be detected by B-mode ultrasonography easily as high frequency ultrasound does not penetrate calcium and have been investigated extensively. In this study our aim was to determine the calcium distribution in the vessel wall itself, excluding large plaques, and to make the first step towards investigating the relationship between the calcium distributional maps and the respective ultrasonic images. The carotid arteries of five elderly (age 71±9 years) and one young (age 27 years) deceased patients were excised at autopsy and were investigated with a medical ultrasound equipment in a tank containing saline solution. Scan sequences were videotaped and images of previously marked cross-sections were transferred to a computer. Small pieces of the arteries were cut and quench frozen. Sections of 60μm from the middle of the scanned segments (30mm proximal to the bifurcation) were cut in a cryostat. The cryosections were transferred to microprobe target holders. The elemental distribution of the samples were determined by particle induced X-ray emission (PIXE) at the Debrecen microprobe [2]. True elemental maps and absolute concentration values were evaluated with a new software (True Pixe Imaging) [3]. The average calcium content of the scanned areas varied between 1000 and 9000μg/g in the slices of the common carotid arteries of the elderly patients. In contrast, scanned areas in the slices from the young subject contained only 600-800μg/g calcium. The concentration of calcium could reach even 3.75% along the wide

  9. 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.

  10. 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...... renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis....

  11. 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.

  12. Concurrent Imaging of Synaptic Vesicle Recycling and Calcium Dynamics

    Science.gov (United States)

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

    2011-01-01

    Synaptic transmission involves the calcium dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2), and a presynaptically localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3) with a large dynamic range. The fluorescence of VGLUT1-mOr2 is quenched by the low pH of synaptic vesicles. Exocytosis upon electrical stimulation exposes the luminal mOr2 to the neutral extracellular pH and relieves fluorescence quenching. Reacidification of the vesicle upon endocytosis again reduces fluorescence intensity. Changes in fluorescence intensity thus monitor synaptic vesicle exo- and endocytosis, as demonstrated previously for the green VGLUT1-pHluorin. To monitor changes in calcium, we fused the synaptic vesicle protein synaptophysin to the recently improved calcium indicator GCaMP3. SyGCaMP3 is targeted to presynaptic varicosities, and exhibits changes in fluorescence in response to electrical stimulation consistent with changes in calcium concentration. Using real time imaging of both reporters expressed in the same synapses, we determine the time course of changes in VGLUT1 recycling in relation to changes in presynaptic calcium concentration. Inhibition of P/Q- and N-type calcium channels reduces calcium levels, as well as the rate of synaptic vesicle exocytosis and the fraction of vesicles released. PMID:22065946

  13. 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.

  14. Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells.

    Science.gov (United States)

    Aires, Antonio; Ocampo, Sandra M; Simões, Bruno M; Josefa Rodríguez, María; Cadenas, Jael F; Couleaud, Pierre; Spence, Katherine; Latorre, Alfonso; Miranda, Rodolfo; Somoza, Álvaro; Clarke, Robert B; Carrascosa, José L; Cortajarena, Aitziber L

    2016-02-12

    Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully  apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro. PMID:26754042

  15. Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells

    Science.gov (United States)

    Aires, Antonio; Ocampo, Sandra M.; Simões, Bruno M.; Josefa Rodríguez, María; Cadenas, Jael F.; Couleaud, Pierre; Spence, Katherine; Latorre, Alfonso; Miranda, Rodolfo; Somoza, Álvaro; Clarke, Robert B.; Carrascosa, José L.; Cortajarena, Aitziber L.

    2016-02-01

    Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.

  16. ACTION OF SILICATO OF CALCIUM AND MAGNESIUM IN THE REDUCTION Cercospora

    OpenAIRE

    Franciane Diniz Cogo; Gabriel Sergio Graciano; Katia Alves Campos

    2011-01-01

    The aim of this study was to evaluate the response of coffee plants (Coffea arabica) Catuaí IAC-44 with different doses of calcium silicate and magnesium in relation to incidence of Cercospora spot coffeicola and plant growth. The experiment was conducted in nursery seedling production of coffee from the Federal Institute of Southern Minas Gerais, Campus Machado, MG randomized blocks with five replications and the treatment used a source of silicon, calcium silicate and magnesium in doses - 0...

  17. Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune diseases.

    Science.gov (United States)

    Zöller, Margot; Gupta, Pooja; Marhaba, Rachid; Vitacolonna, Mario; Freyschmidt-Paul, Pia

    2007-07-01

    CD44 plays an important role in leukocyte extravasation, which is fortified in autoimmune diseases and delayed-type hypersensitivity (DTH) reactions. There is additional evidence that distinct CD44 isoforms interfere with the extravasation of selective leukocyte subsets. We wanted to explore this question in alopecia areata (AA), a hair-follicle centric autoimmune disease, and in a chronic eczema. The question became of interest because AA is treated efficiently by topical application of a contact sensitizer, such that a mild DTH reaction is maintained persistently. Aiming to support the therapeutic efficacy of a chronic eczema in AA by anti-CD44 treatment, it became essential to control whether a blockade of migration, preferentially of AA effector cells, could be achieved by CD44 isoform-specific antibodies. Anti-panCD44 and anti-CD44 variant 10 isoform (CD44v10) inhibited in vitro migration of leukocytes from untreated and allergen-treated, control and AA mice. In vivo, both antibodies interfered with T cell and monocyte extravasation into the skin; only anti-panCD44 prevented T cell homing into lymph nodes. Contributing factors are disease-dependent alterations in chemokine/chemokine receptor expression and a blockade of CD44 on endothelial cells and leukocytes. It is important that CD44 can associate with several integrins and ICAM-1. Associations depend on CD44 activation and vary with CD44 isoforms and leukocyte subpopulations. CD44 standard isoform preferentially associates with CD49d in T cells and CD44v10 with CD11b in monocytes. Accordingly, anti-panCD44 and anti-CD49d inhibit T cell, anti-CD11b, and anti-CD44v10 macrophage migration most efficiently. Thus, allergen treatment of AA likely can be supported by targeting AA T cells selectively via a panCD44-CD49d-bispecific antibody. PMID:17442857

  18. Fruit Calcium: Transport and Physiology

    Science.gov (United States)

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

    2016-01-01

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

  19. Fruit Calcium: Transport and Physiology.

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Summary There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcεRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signalling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcεRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signalling pathway and its downstream targets. PMID:25016314

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

    OpenAIRE

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

    2015-01-01

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

  2. Calcium and calcitonin responses to calcium infusion in type I diabetes mellitus.

    OpenAIRE

    Amado, J. A.; C. Gomez; Obaya, S.; Otero, M; Gonzalez-Macias, J

    1987-01-01

    We studied calcium and calcium and calcitonin responses to intravenous calcium infusion (3 mg of elemental calcium/kg of body weight in 10 minutes) in 21 type I diabetic males and 17 age-matched normal males. Baseline total calcium, parathyroid hormone and calcitonin levels were normal in the diabetic group, but ionized calcium was lowered. Cortical bone status and osteocalcin levels were normal, suggesting a normal osteoblastic function. Total calcium and ionized calcium responses to calcium...

  3. 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.

  4. 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...

  5. Can serum isotope levels accurately measure intestinal calcium absorption compared to gold-standard methods?

    OpenAIRE

    Vreede, Andrew P; Jones, Andrea N; Hansen, Karen E

    2015-01-01

    Background Low fractional calcium absorption (FCA) contributes to osteoporosis but is not measured clinically, as the gold-standard method requires administration of two calcium tracers and a subsequent 24-h urine collection. We evaluated alternate methods to measure FCA, compared to the gold standard method. Methods We administered two stable calcium isotope tracers (~8 mg oral 44Ca and ~3 mg intravenous 42Ca) with breakfast to 20 fasting post-menopausal women (Cohort 1) 59 ± 7 years old wit...

  6. Direct Imaging of Hippocampal Epileptiform Calcium Motifs Following Kainic Acid Administration in Freely Behaving Mice.

    Science.gov (United States)

    Berdyyeva, Tamara K; Frady, E Paxon; Nassi, Jonathan J; Aluisio, Leah; Cherkas, Yauheniya; Otte, Stephani; Wyatt, Ryan M; Dugovic, Christine; Ghosh, Kunal K; Schnitzer, Mark J; Lovenberg, Timothy; Bonaventure, Pascal

    2016-01-01

    novel drug screening paradigms and therapeutics designed to target and abolish abnormal patterns of both electrical and calcium excitation. PMID:26973444

  7. Reverse calcium affinity purification of Fab with calcium derivatized hydroxyapatite

    OpenAIRE

    Gagnon, Pete; Cheung, Chia-wei; Yazaki, Paul J.

    2009-01-01

    This study introduces the application of calcium-derivatized hydroxyapatite for purification of Fab. Fab binds to native hydroxyapatite but fails to bind to the calcium derivatized form. IgG, Fc, and most other protein contaminants bind to the calcium form. This supports Fab purification by a simple flow-through method that achieves greater than 95% purity from papain digests and mammalian cell culture supernatants. Alternatively, Fab can be concentrated on native hydroxyapatite then eluted s...

  8. Glycochenodeoxycholic acid inhibits calcium phosphate precipitation in vitro by preventing the transformation of amorphous calcium phosphate to calcium hydroxyapatite.

    OpenAIRE

    Qiu, S M; Wen, G.; Hirakawa, N; Soloway, R D; Hong, N K; Crowther, R S

    1991-01-01

    Calcium hydroxyapatite can be a significant component of black pigment gallstones. Diverse molecules that bind calcium phosphate inhibit hydroxyapatite precipitation. Because glycine-conjugated bile acids, but not their taurine counterparts, bind calcium phosphate, we studied whether glycochenodeoxycholic acid inhibits calcium hydroxyapatite formation. Glycochenodeoxycholic acid (2 mM) totally inhibited transformation of amorphous calcium phosphate microprecipitates to macroscopic crystalline...

  9. Calcium-dependent activation of Pyk2 by hypoxia.

    Science.gov (United States)

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

    2002-02-01

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

  10. Calcium – how and why?

    Indian Academy of Sciences (India)

    J K Jaiswal

    2001-09-01

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

  11. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk; Moilanen, A.; Norby, P.; Papadakis, K.; Posselt, D.; Sørensen, L. H.

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...

  12. Calcium Phosphate Biomaterials: An Update

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  13. 21 CFR 573.240 - Calcium periodate.

    Science.gov (United States)

    2010-04-01

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

  14. 21 CFR 573.260 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

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

  15. Calcium measurement methods

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-09-01

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

  16. 26 CFR 44.0-1 - Introduction.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 44.0-1 Section 44.0-1 Internal... ON WAGERING; EFFECTIVE JANUARY 1, 1955 Introduction § 44.0-1 Introduction. (a) In general. The... provisions of subtitle F of the Code (Procedure and Administration) which have special application to...

  17. 40 CFR 230.44 - Coral reefs.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Coral reefs. 230.44 Section 230.44... Aquatic Sites § 230.44 Coral reefs. (a) Coral reefs consist of the skeletal deposit, usually of calcareous... by increasing the level of suspended particulates. Coral organisms are extremely sensitive to...

  18. 12 CFR 561.44 - Security.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Security. 561.44 Section 561.44 Banks and... SAVINGS ASSOCIATIONS § 561.44 Security. The term security means any non-withdrawable account, note, stock... commonly known as a security, or any certificate of interest or participation in, temporary or...

  19. 7 CFR 930.44 - Quality control.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Quality control. 930.44 Section 930.44 Agriculture... MICHIGAN, NEW YORK, PENNSYLVANIA, OREGON, UTAH, WASHINGTON, AND WISCONSIN Order Regulating Handling Quality Control § 930.44 Quality control. (a) Quality standards. The Board may establish, with the approval of...

  20. 18 CFR 420.44 - Cooling water.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Cooling water. 420.44 Section 420.44 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-WATER SUPPLY CHARGES Charges; Exemptions § 420.44 Cooling water. Water...

  1. 45 CFR 96.44 - Community services.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Community services. 96.44 Section 96.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.44 Community services. (a) This section applies to...

  2. 30 CFR 44.6 - Service.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Service. 44.6 Section 44.6 Mineral Resources... RULES OF PRACTICE FOR PETITIONS FOR MODIFICATION OF MANDATORY SAFETY STANDARDS General § 44.6 Service... modification may be served personally or by first class mail to the last known address of the party....

  3. 29 CFR 452.44 - Dual unionism.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Dual unionism. 452.44 Section 452.44 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS... OF 1959 Candidacy for Office; Reasonable Qualifications § 452.44 Dual unionism. While the Act...

  4. 10 CFR 851.44 - Administrative appeal.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Administrative appeal. 851.44 Section 851.44 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Enforcement Process § 851.44 Administrative appeal. (a... calendar days from receipt of the final notice. (b) In order to exhaust administrative remedies...

  5. 4 CFR 4.4 - Incentive awards.

    Science.gov (United States)

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Incentive awards. 4.4 Section 4.4 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM EMPLOYEE PERFORMANCE AND UTILIZATION § 4.4 Incentive awards. The provisions of chapter 45 of title 5, United States Code and Office of Personnel Management...

  6. 27 CFR 44.254 - Shipping containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Shipping containers. 44.254 Section 44.254 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Requirements § 44.254 Shipping containers. Each shipping case, crate, or other container, in which cigars...

  7. 34 CFR 300.44 - Universal design.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Universal design. 300.44 Section 300.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND... DISABILITIES General Definitions Used in This Part § 300.44 Universal design. Universal design has the...

  8. 45 CFR 74.44 - Procurement procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Procurement procedures. 74.44 Section 74.44 Public... Suspension.” (See 45 CFR part 76.) (e) Recipients shall, on request, make available for the HHS awarding..., AND COMMERCIAL ORGANIZATIONS Post-Award Requirements Procurement Standards § 74.44...

  9. 48 CFR 44.307 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Reports. 44.307 Section 44... SUBCONTRACTING POLICIES AND PROCEDURES Contractors' Purchasing Systems Reviews 44.307 Reports. The ACO shall distribute copies of CPSR reports; notifications granting, withholding, or withdrawing system approval;...

  10. 29 CFR 44.3 - Election process.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Election process. 44.3 Section 44.3 Labor Office of the... WITH DEPARTMENT OF LABOR § 44.3 Election process. (a) Process. The Commissioner of Labor Statistics of... shall conduct the elections. The Commissioner shall provide a ballot containing the names of...

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

    Science.gov (United States)

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

  12. Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release.

    OpenAIRE

    Simon, S M; Llinás, R R

    1985-01-01

    Quantitative modeling indicates that, in presynaptic terminals, the intracellular calcium concentration profile during inward calcium current is characterized by discrete peaks of calcium immediately adjacent to the calcium channels. This restriction of intracellular calcium concentration suggests a remarkably well specified intracellular architecture such that calcium, as a second messenger, may regulate particular intracellular domains with a great degree of specificity.

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

    Directory of Open Access Journals (Sweden)

    Yubo Sun

    2014-01-01

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

  14. Calcium requirements for Chinese adults by cross-sectional statistical analyses of calcium balance studies: an individual participant data and aggregate data meta-regression

    Institute of Scientific and Technical Information of China (English)

    Fang Aiping; Li Keji; Shi Haoyu; He Jingjing; Li He

    2014-01-01

    Background Chinese dietary reference intakes for calcium are largely based on foreign studies.We undertook metaregression to estimate calcium requirements for Chinese adults derived from calcium balance data in Chinese adults.Methods We searched PubMed,Cochrane CENTRAL,and SinoMed from inception to March 5,2014,by using a structured search strategy.The bibliographies of any relevant papers and journals were also screened for potentially eligible studies.We extracted a standardized data set from studies in Chinese adults that reported calcium balance data.The relationship between calcium intake and output was examined by an individual participant data (IPD) and aggregate data (AD) meta-regression.Results We identified 11 metabolic studies in Chinese adults within 18-60 years of age.One hundred and forty-one IPD (n=35) expressed as mg/d,127 IPD (n=32) expressed as mg·kg body wt-1·d-1,and 44 AD (n=132) expressed as mg/d were collected.The models predicted a neutral calcium balance (defined as calcium output (Y) equal to calcium intake (C)) at intakes of 460 mg/d (Y=0.60C+183.98) and 8.27 mg·kg body wt-1·d-1 (Y=0.60C+3.33)for IPD,or 409 mg/d (Y=0.66C+139.00) for AD.Calcium requirements at upper intakes were higher than that at lower intakes in all these models.Conclusion Calcium requirement for Chinese adults 18-60 years of age approximately ranges between 400 mg/d and 500 mg/d when consuming traditional plant-based Chinese diets.

  15. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

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

  16. Calcium, vitamin D, and your bones

    Science.gov (United States)

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

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

    OpenAIRE

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

    1989-01-01

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

  18. Calcium transport in turtle bladder

    International Nuclear Information System (INIS)

    Unidirectional 45Ca fluxes were measured in the turtle bladder under open-circuit and short-circuit conditions. In the open-circuited state net calcium flux (JnetCa) was secretory (serosa to mucosa). Ouabain reversed JnetCa to an absorptive flux. Amiloride reduced both fluxes such that JnetCa was not significantly different from zero. Removal of mucosal sodium caused net calcium absorption; removal of serosal sodium caused calcium secretion. When bladders were short circuited, JnetCa decreased to approximately one-third of control value but remained secretory. When ouabain was added under short-circuit conditions, JnetCa was similar in magnitude and direction to ouabain under open-circuited conditions (i.e., absorptive). Tissue 45Ca content was ≅30-fold lower when the isotope was placed in the mucosal bath, suggesting that the apical membrane is the resistance barrier to calcium transport. The results obtained in this study are best explained by postulating a Ca2+-ATPase on the serosa of the turtle bladder epithelium and a sodium-calcium antiporter on the mucosa. In this model, the energy for calcium movement would be supplied, in large part, by the Na+-K+-ATPase. By increasing cell sodium, ouabain would decrease the activity of the mucosal sodium-calcium exchanger (or reverse it), uncovering active calcium transport across the serosa

  19. An Improved Calcium Flame Test.

    Science.gov (United States)

    Pearson, Robert S.

    1985-01-01

    Indicates that the true red color of calcium can be obtained (using the procedure described by Sorm and Logowski) if the calcium ion solution is mixed with an equal volume of saturated ammonium bromide solution. Suggestions for flame tests of other elements are also noted. (JN)

  20. A calcium isotope test of end-Permian ocean acidification using biogenic apatite

    Science.gov (United States)

    Hinojosa, J.; Brown, S. T.; DePaolo, D. J.; Paytan, A.; Shen, S.; Chen, J.; Payne, J.

    2011-12-01

    Submarine erosional truncation of uppermost Permian carbonate strata has been interpreted to reflect ocean acidification coincident with the end-Permian mass extinction. Although this scenario is consistent with carbon isotope and paleontological data, several alternative scenarios, such as ocean overturn or collapse of the biological pump, can also account for the carbon isotope and paleontological evidence. Calcium isotopes provide a geochemical proxy to test between acidification and alternative scenarios. Specifically, a negative shift in the calcium isotope composition (δ44/40Ca) of seawater is predicted under the acidification scenario but not the alternatives. The δ44/40Ca of carbonate rocks from south China exhibits a negative excursion of approximately 0.3%, but this shift could result from either a change in the δ44/40Ca of seawater or a change in carbonate mineralogy because calcite and aragonite exhibit substantially different fractionation factors relative to seawater. To test whether the negative shift in δ44/40Ca reflects seawater δ44/40Ca or carbonate mineralogy, we measured the δ44/40Ca of conodont microfossils (calcium hydroxyapatite) from the global stratotype section for the Permian-Triassic boundary at Meishan, China. The conodont δ44/40Ca record shows a negative excursion similar in stratigraphic position and magnitude to that previously observed in carbonate rocks. Parallel negative excursions in the δ44/40Ca of carbonate rocks and conodont microfossils cannot be accounted for by a change in carbonate mineralogy but are consistent with a negative shift in the δ44/40Ca of seawater. These data add further support for the ocean acidification scenario, pointing toward strong similarities between the greatest catastrophe in the history of animal life and anticipated global change during the 21st century.

  1. Calcium isotopes in wine

    Science.gov (United States)

    Holmden, C. E.

    2011-12-01

    The δ 44/40Ca values of bottled wine vary between -0.76% to -1.55% on the seawater scale and correlate weakly with inverse Ca concentration and Mg/Ca ratio, such that the lowest δ 44/40Ca values have the highest Ca concentrations and lowest Mg/Ca ratios. The correlation is notable in the sense that the measured wines include both whites and reds sampled from different wine growing regions of the world, and cover a wide range of quality. Trends among the data yield clues regarding the cause of the observed isotopic fractionation. White wines, and wines generally perceived to be of lower quality, have lower δ 44/40Ca values compared to red wines and wines of generally perceived higher quality. Quality was assessed qualitatively through sensory evaluation, price, and scores assigned by critics. The relationship between δ 44/40Ca and wine quality was most apparent when comparing wines of one varietal from one producer from the same growing region. In the vineyard, wine quality is related to factors such as the tonnage of the crop and the ripeness of the grapes at the time of harvesting, the thickness of the skins for reds, the age of the vines, as well as the place where the grapes were grown (terroir). Quality is also influenced by winemaking practices such as fermentation temperature, duration of skin contact, and barrel ageing. Accordingly, the relationship between δ 44/40Ca and wine quality may originate during grape ripening in the vineyard or during winemaking in the cellar. We tested the grape ripening hypothesis using Merlot grapes sampled from a vineyard in the Okanagan, British Columbia, using sugar content (degrees Brix) as an indicator of ripeness. The grapes were separated into pulp, skin, and pip fractions and were analyzed separately. Thus far, there is no clear evidence for a systematic change in δ 44/40Ca values associated with progressive ripening of grapes in the vineyard. On the day of harvesting, the δ 44/40Ca value of juice squeezed from

  2. Phototheranostics of CD44-positive cell populations in triple negative breast cancer

    Science.gov (United States)

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M.

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  3. Phototheranostics of CD44-positive cell populations in triple negative breast cancer.

    Science.gov (United States)

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44(high)/CD24(low), and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  4. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    OpenAIRE

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

    2011-01-01

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

  5. MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells

    International Nuclear Information System (INIS)

    Dysregulated expression and splicing of cell adhesion marker CD44 is found in many types of cancer. In prostate cancer (PC) specifically, the standard isoform (CD44s) has been found to be downregulated compared with benign tissue whereas predominant variant isoform CD44v7-10 is upregulated. Mitogen-activated protein kinase pathways and paracrine calcitonin are two common factors linked to dysregulated expression and splicing of CD44 in cancer. Calcitonin has been found to increase proliferation and invasion in PC acting through the protein kinase A pathway. In androgen-independent PC with known high CD44v7-10 expression, CD44 total and CD44v7-10 RNA or protein were assessed in response to exogenous and endogenous calcitonin and to inhibitors of protein kinase A, MEK, JNK, or p38 kinase. Benign cells and calcitonin receptor-negative PC cells were also tested. MEK or p38 but not JNK reduced CD44 total RNA by 40%–65% in cancer and benign cells. Inhibition of protein kinase A reduced CD44 total and v7-10 protein expression. In calcitonin receptor-positive cells only, calcitonin increased CD44 variant RNA and protein by 3 h and persisting to 48 h, apparently dependent on an uninhibited p38 pathway. Cells with constitutive CT expression showed an increase in CD44v7-10 mRNA but a decrease in CD44 total RNA. The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing

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

    International Nuclear Information System (INIS)

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

  7. Simvastatin inhibits CD44 fragmentation in chondrocytes.

    Science.gov (United States)

    Terabe, Kenya; Takahashi, Nobunori; Takemoto, Toki; Knudson, Warren; Ishiguro, Naoki; Kojima, Toshihisa

    2016-08-15

    In human osteoarthritic chondrocytes, the hyaluronan receptor CD44 undergoes proteolytic cleavage at the cell surface. CD44 cleavage is thought to require transit of CD44 into cholesterol-rich lipid rafts. The purpose of this study was to investigate whether statins exert a protective effect on articular chondrocytes due to diminution of cholesterol. Three model systems of chondrocytes were examined including human HCS-2/8 chondrosarcoma cells, human osteoarthritic chondrocytes and normal bovine articular chondrocytes. Treatment with IL-1β + Oncostatin M resulted in a substantial increase in CD44 fragmentation in each of the three chondrocyte models. Pre-incubation with simvastatin prior to treatment with IL-1β + Oncostatin M decreased the level of CD44 fragmentation, decreased the proportion of CD44 that transits into the lipid raft fractions, decreased ADAM10 activity and diminished the interaction between CD44 and ADAM10. In HCS-2/8 cells and bovine articular chondrocytes, fragmentation of CD44 was blocked by the knockdown of ADAM10. Inhibition of CD44 fragmentation by simvastatin also resulted in improved retention of pericellular matrix. Addition of cholesterol and farnesyl-pyrophosphate reversed the protective effects of simvastatin. Thus, the addition of simvastatin exerts positive effects on chondrocytes including reduced CD44 fragmentation and enhanced the retention of pericellular matrix. PMID:27242325

  8. Calcium intake and hypertension among obese adults in United States: associations and implications explored.

    Science.gov (United States)

    Chen, Y; Strasser, S; Cao, Y; Wang, K-S; Zheng, S

    2015-09-01

    The relationship between calcium intake and hypertension is receiving increased research attention. The prevalence of hypertension is high among the obese populations. Calcium is a mineral that influences blood pressure. The aim of the study was to examine the association between calcium intake and hypertension in a large nationally representative sample of obese American adults. A total of 14,408 obese adults aged 20 years or older were obtained from the 1999-2010 National Health and Nutrition Examination Survey. Analysis of variance and linear regression models were used to examine relationships between calcium intake and systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). Multiple logistic regression models were used to examine the association between calcium intake and hypertension after adjusting for potential confounders and interactions, including: age, race, education level, alcohol use, smoking, diabetes status, sodium intake and potassium intake. Calcium intake was significantly lower for the hypertensive group compared with the normotensive group (Pobese female young adults aged 20-44 years and among non-diabetic obese adults. Based on ordinary linear regression analysis, a significant inverse relationship was detected, SBP and DBP decreased if calcium intake increased (SBP: regression coefficient estimate=-0.015, Pintake was negatively associated with the probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI): 0.74-0.87, Pintake in youngest adults (age 20-44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI: 0.64-0.93, Pintake and probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55-0.84, Pobese adults. The protective effect of calcium intake and hypertension was found significantly in obese non-diabetic adults (OR: OR=0.77, 95% CI: 0.67-0.89, Pobese diabetic adults. SBP, DBP and calcium intake were log transformed for both ordinary linear regression analysis and

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

    Institute of Scientific and Technical Information of China (English)

    Nasrin NFJATBAKHSH; Zhong-ping FENG

    2011-01-01

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

  10. 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.

  11. 22 CFR 142.44 - Academic adjustments.

    Science.gov (United States)

    2010-04-01

    ... OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Postsecondary Education § 142.44 Academic... recipient's education program or activity. (c) Course examinations. In its examinations or other...

  12. 22 CFR 217.44 - Academic adjustments.

    Science.gov (United States)

    2010-04-01

    ... PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Postsecondary Education § 217.44 Academic... recipient's education program or activity. (c) Course examinations. In its course examinations or...

  13. 45 CFR 84.44 - Academic adjustments.

    Science.gov (United States)

    2010-10-01

    ... HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Postsecondary Education § 84.44... recipient's education program or activity. (c) Course examinations. In its course examinations or...

  14. Soluble CD44 interacts with intermediate filament protein vimentin on endothelial cell surface.

    Science.gov (United States)

    Päll, Taavi; Pink, Anne; Kasak, Lagle; Turkina, Marina; Anderson, Wally; Valkna, Andres; Kogerman, Priit

    2011-01-01

    CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12-37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells. PMID:22216242

  15. Calcium channel blocking activity of fruits of callistemon citrinus

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2015-01-01

    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 dy...

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

    Science.gov (United States)

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

    2012-06-01

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

  18. Variability of calcium absorption

    International Nuclear Information System (INIS)

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

  19. Evolution and functional diversity of the Calcium Binding Proteins (CaBPs

    Directory of Open Access Journals (Sweden)

    Lee P Haynes

    2012-02-01

    Full Text Available The mammalian central nervous system (CNS exhibits a remarkable ability to process, store and transfer information. Key to these activities is the use of highly regulated and unique patterns of calcium signals encoded by calcium channels and decoded by families of specific calcium-sensing proteins. The largest family of eukaryotic calcium sensors are those related to the small EF-hand containing protein calmodulin (CaM. In order to maximise the usefulness of calcium as a signalling species and to permit the evolution and fine tuning of the mammalian CNS, families of related proteins have arisen that exhibit characteristic calcium binding properties and tissue-, cellular- and sub-cellular distribution profiles. The Calcium Binding Proteins (CaBPs represent one such family of vertebrate specific calmodulin like proteins that have emerged in recent years as important regulators of essential neuronal target proteins. Bioinformatic analyses indicate that the CaBPs consist of two subfamilies and that the ancestral members of these are CaBP1 and CaBP8. The CaBPs have distinct intracellular localisations based on different targeting mechanisms including a novel type-II transmembrane domain in CaBPs 7 and 8. Recent work has led to the identification of new target interactions and possible functions for the CaBPs suggesting that they have multiple physiological roles with relevance for the normal functioning of the CNS.

  20. Calcium-sensitive immunoaffinity chromatography

    DEFF Research Database (Denmark)

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

    2014-01-01

    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......Ab. This antibody was characterized by binding to CL-LK at hypo- and physiological calcium concentrations and dissociated from CK-LK at hyperphysiological concentrations of calcium. We purified CL-LK from plasma to a purity of 41% and a yield of 38%, resulting in a purification factor of more than 88......,000 in a single step. To evaluate the efficiency of this new purification scheme, we purified CL-LK using the same calcium-sensitive mAb in combination with acidic elution buffer and by using calcium-dependent anti-CL-K1 mAbs in combination with EDTA elution buffer. We found that calcium...

  1. 16 CFR 4.4 - Service.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Service. 4.4 Section 4.4 Commercial... Service. (a) By the Commission. (1) Service of complaints, initial decisions, final orders and other..., registered or certified, and mailed; service under this provision is complete upon delivery of the...

  2. 44 CFR 206.438 - Project management.

    Science.gov (United States)

    2010-10-01

    ... Project management. (a) General. The State serving as grantee has primary responsibility for project management and accountability of funds as indicated in 44 CFR part 13. The State is responsible for ensuring... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Project management....

  3. 20 CFR 901.44 - Hearings.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Hearings. 901.44 Section 901.44 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF ACTUARIAL SERVICES UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 Suspension or Termination of...

  4. 38 CFR 4.44 - The bones.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false The bones. 4.44 Section 4... DISABILITIES Disability Ratings The Musculoskeletal System § 4.44 The bones. The osseous abnormalities incident... convalescence, and progress of recovery with development of permanent residuals. With shortening of a long...

  5. 27 CFR 44.187 - Shipping containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Shipping containers. 44.187 Section 44.187 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Shipping containers. Each shipping case, crate, or other container in which tobacco products, or...

  6. 44 CFR 78.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 78.3... ASSISTANCE § 78.3 Responsibilities. (a) Federal. The Administrator will allocate available funds to each FEMA... approval; and (5) Submit performance and financial reports to FEMA in compliance with 44 CFR 13.40 and...

  7. 36 CFR 1210.44 - Procurement procedures.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Procurement procedures. 1210.44 Section 1210.44 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION GENERAL RULES UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER...

  8. 45 CFR 2543.44 - Procurement procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Procurement procedures. 2543.44 Section 2543.44 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements...

  9. Cutoff dependence in lattice phi44 theory

    International Nuclear Information System (INIS)

    The author discusses corrections to the high temperature expansion of the lattice phi44 theory in 4 + epsilon dimensions using the renormalization group. He works with vertex functions, whose expansion is derived from an effective Lagrangian for large-cutoff behaviour. He concludes that the numerical phi44 results offer a test of the idea of asymptotic freedom. (HSI)

  10. 10 CFR 430.44 - Consolidation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Consolidation. 430.44 Section 430.44 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Petitions To Exempt State... common parties, common questions of fact and law, and where such consolidation would expedite or...

  11. 27 CFR 44.69 - Assessment.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Assessment. 44.69 Section..., WITHOUT PAYMENT OF TAX, OR WITH DRAWBACK OF TAX General § 44.69 Assessment. Whenever any person required... amount is nominal or the result of an evident mathematical error, no such assessment shall be made...

  12. 44 CFR 206.204 - Project performance.

    Science.gov (United States)

    2010-10-01

    ... accordance with 44 CFR 13.21, Payment. (c) Time limitations for completion of work—(1) Deadlines. The project... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Project performance. 206.204... § 206.204 Project performance. (a) General. This section describes the policies and...

  13. 27 CFR 44.227 - Customs procedure.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Customs procedure. 44.227..., WITHOUT PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Drawback of Tax § 44.227 Customs procedure. The customs... having inspected the articles and supervised the lading thereof on the export carrier, the...

  14. A genetic polymorphism (rs17251221 in the calcium-sensing receptor gene (CASR is associated with stone multiplicity in calcium nephrolithiasis.

    Directory of Open Access Journals (Sweden)

    Yii-Her Chou

    Full Text Available Calcium nephrolithiasis is one of the most common causes of renal stones. While the prevalence of this disease has increased steadily over the last 3 decades, its pathogenesis is still unclear. Previous studies have indicated that a genetic polymorphism (rs17251221 in the calcium-sensing receptor gene (CASR is associated with the total serum calcium levels. In this study, we collected DNA samples from 480 Taiwanese subjects (189 calcium nephrolithiasis patients and 291 controls for genotyping the CASR gene. Our results indicated no significant association between the CASR polymorphism (rs17251221 and the susceptibility of calcium nephrolithiasis. However, we found a significant association between rs17251221 and stone multiplicity. The risk of stone multiplicity was higher in patients with the GG+GA genotype than in those with the AA genotype (chi-square test: P = 0.008; odds ratio  =  4.79; 95% confidence interval, 1.44-15.92; Yates' correction for chi-square test: P = 0.013. In conclusion, our results provide evidence supporting the genetic effects of CASR on the pathogenesis of calcium nephrolithiasis.

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

    Institute of Scientific and Technical Information of China (English)

    Emanuel; E; Strehler

    2011-01-01

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

  16. Asante Calcium Green and Asante Calcium Red--novel calcium indicators for two-photon fluorescence lifetime imaging.

    Directory of Open Access Journals (Sweden)

    Karolina Jahn

    Full Text Available For a comprehensive understanding of cellular processes and potential dysfunctions therein, an analysis of the ubiquitous intracellular second messenger calcium is of particular interest. This study examined the suitability of the novel Ca2+-sensitive fluorescent dyes Asante Calcium Red (ACR and Asante Calcium Green (ACG for two-photon (2P-excited time-resolved fluorescence measurements. Both dyes displayed sufficient 2P fluorescence excitation in a range of 720-900 nm. In vitro, ACR and ACG exhibited a biexponential fluorescence decay behavior and the two decay time components in the ns-range could be attributed to the Ca(2+-free and Ca(2+-bound dye species. The amplitude-weighted average fluorescence decay time changed in a Ca(2+-dependent way, unraveling in vitro dissociation constants K(D of 114 nM and 15 nM for ACR and ACG, respectively. In the presence of bovine serum albumin, the absorption and steady-state fluorescence behavior of ACR was altered and its biexponential fluorescence decay showed about 5-times longer decay time components indicating dye-protein interactions. Since no ester derivative of ACG was commercially available, only ACR was evaluated for 2P-excited fluorescence lifetime imaging microscopy (2P-FLIM in living cells of American cockroach salivary glands. In living cells, ACR also exhibited a biexponential fluorescence decay with clearly resolvable short (0.56 ns and long (2.44 ns decay time components attributable to the Ca(2+-free and Ca(2+-bound ACR species. From the amplitude-weighted average fluorescence decay times, an in situ K(D of 180 nM was determined. Thus, quantitative [Ca(2+]i recordings were realized, unraveling a reversible dopamine-induced [Ca(2+]i elevation from 21 nM to 590 nM in salivary duct cells. It was concluded that ACR is a promising new Ca(2+ indicator dye for 2P-FLIM recordings applicable in diverse biological systems.

  17. Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin.

    Science.gov (United States)

    Xiong, Hui; Du, Shi; Ni, Jiang; Zhou, Jianping; Yao, Jing

    2016-07-01

    Dual-targeted nanoparticles have been increasingly used to realize greater anti-proliferation effect by attacking double key sites of tumor cells. In order to retain nuclei inhibition effect and enhance DOX-induced apoptosis by mitochondrial pathway simultaneously, hyaluronic acid (HA) modified hydroxyapatite (HAP) nanoparticles (HAP-HA), the functional calcium-based tumor targeting nanoparticles, have been developed. In this nanosystem, HA acts as an active tumor-targeting ligand to bind the CD44 receptors which are overexpressed on the surface of tumor cells while HAP can load and deliver DOX to both nuclei and mitochondria of tumor cells. In this study, DOX-loaded HAP-HA nanoparticles (DOX/HAP-HA) exhibited satisfactory drug loading efficiency which was up to 214.55 ± 51.05 μg mg(-1) and showed a uniform nano-scaled particle size. The mitochondrial and nuclei targetability of DOX/HAP-HA was confirmed by confocal laser scanning microscopy analyses. Besides, western blot assay demonstrated that DOX/HAP-HA could markedly enhance mitochondrial cytochrome C leakage and thereby activate apoptotic cascade associated with it. In addition, in vivo anti-tumor efficacy and toxicity evaluation of DOX/HAP-HA indicated that DOX/HAP-HA was more effective and less harmful compared to other groups. DOX/HAP-HA might be a new promising targeted delivery system for effective cancer therapy. PMID:27105438

  18. Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite-calcium pectinate

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Raj Kumar, E-mail: duttafcy@iitr.ernet.in; Sahu, Saurabh, E-mail: saurabhsahu12@gmail.com [Indian Institute of Technology Roorkee, Analytical Chemistry Laboratory, Department of Chemistry (India); Reddy, V. R., E-mail: vrreddy@csr.res.in [UGC-DAE Consortium for Scientific Research (India)

    2012-08-15

    A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100-200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 {+-} 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and {sup 57}Fe Moessbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Moessbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV-Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

  19. Novel function of perforin in negatively regulating CD4+T cell activation by affecting calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Enguang Bi; Kairui Mao; Jia Zou; Yuhan Zheng; Bing Sun; Chunjian Huang; Yu Hu; Xiaodong Wu; Weiwen Deng; Guomei Lin; Zhiduo Liu; Lin Tian; Shuhui Sun

    2009-01-01

    Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic Tlymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4+ T cell func-tion remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4+ T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell prolifera-tion and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD44 T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFATI. Our results indicate that perforin plays a negative role in regulating CD4+ T cell activation and immune response by affecting TCR-dependent Ca2+ signaling.

  20. 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.

  1. Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    resistant towards anti-CD44 induced apoptosis. Our data show that CD44 is epigenetically regulated in lymphoma and undergoes de novo methylation in distinct lymphoma subtypes like BL. Thus CD44 may be a promising new epigenetic marker for diagnosis and a potential therapeutic target for the treatment of specific lymphoma subtypes

  2. Radiolabeling of DOTATOC with the long-lived positron emitter {sup 44}Sc

    Energy Technology Data Exchange (ETDEWEB)

    Pruszynski, Marek; Majkowska-Pilip, Agnieszka [Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warszawa (Poland); Loktionova, Natalia S.; Eppard, Elisabeth [Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Roesch, Frank, E-mail: frank.roesch@uni-mainz.de [Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany)

    2012-06-15

    The positron-emitting radionuclide {sup 44}Sc with a half-life of 3.97 h and a {beta}{sup +} branching of 94.3% is of potential interest for clinical PET. As so far it is available from a {sup 44}Ti/{sup 44}Sc generator in Mainz, where long-lived {sup 44}Ti decays to no-carrier-added (nca) {sup 44}Sc. The {sup 44}Sc is a trivalent metal cation and should be suitable for complexation with many well established bifunctional chelators conjugated to peptides or other molecular targeting vectors. Thus, the aim of this work was to investigate the potential of {sup 44}Sc for labeling of DOTA-conjugated peptides. DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotide (DOTATOC) was used as a model molecule to study and optimize labeling procedure. Reaction parameters such as buffer conditions, concentration of peptide, pH range, reaction temperature and time were optimized. Addition of 21 nmol of DOTATOC to {sup 44}Sc in ammonium acetate buffer pH 4.0 provided labeling yields >98% within 25 min of heating in an oil-bath at 95 Degree-Sign C. This time can be reduced to 3 min only by applying microwave supported heating. {sup 44}Sc-DOTATOC was found to be stable in 0.9% NaCl, PBS pH 7.4, fetal calf and human serums, and also in the presence of competing metal cations (Fe{sup 3+}, Ca{sup 2+}, Cu{sup 2+}, Mg{sup 2+}), as well as other ligand competitors, like EDTA and DTPA, even after almost 25 h incubation at 37 Degree-Sign C. Present study shows that nca {sup 44}Sc forms stable complexes with the macrocyclic ligand DOTA and that {sup 44}Sc-DOTATOC and analog targeting vectors may be synthesized for further preclinical and clinical investigations. - Highlights: Black-Right-Pointing-Pointer Labeling of somatostatin analouges with positron emitter {sup 44}Sc was tested. Black-Right-Pointing-Pointer DOTATOC was labeled with {sup 44}Sc isotope. Black-Right-Pointing-Pointer Optimal conditions for {sup 44}Sc-DOTATOC synthesis were found. Black-Right-Pointing-Pointer Stability of {sup 44}Sc

  3. Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Directory of Open Access Journals (Sweden)

    Pham Phuc V

    2011-12-01

    Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

  4. "Caged calcium" in Aplysia pacemaker neurons. Characterization of calcium-activated potassium and nonspecific cation currents

    OpenAIRE

    1989-01-01

    We have studied calcium-activated potassium current, IK(Ca), and calcium-activated nonspecific cation current, INS(Ca), in Aplysia bursting pacemaker neurons, using photolysis of a calcium chelator (nitr-5 or nitr-7) to release "caged calcium" intracellularly. A computer model of nitr photolysis, multiple buffer equilibration, and active calcium extrusion was developed to predict volume-average and front-surface calcium concentration transients. Changes in arsenazo III absorbance were used to...

  5. Alpha clustering in Ti isotopes: 40,44,48Ca + α resonant scattering

    Directory of Open Access Journals (Sweden)

    Bailey Sam

    2016-01-01

    Full Text Available Measurements were made of the 4He(40,44,48Ca,α resonant scattering reactions at 180° and up to Ec.m. ~ 11.5MeV, using the Thick Target Inverse Kinematics technique. These measurements are discussed, with a focus on assessing their usefulness for investigating α-clustering in medium mass 44,48,52Ti nuclei.

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

    Directory of Open Access Journals (Sweden)

    Isidro Vitoria

    2014-07-01

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

  7. Effect of Preharvest Calcium Treatments on Sweet Cherry Fruit Quality

    OpenAIRE

    Deniz EROGUL

    2014-01-01

    In this study, the effects of different foliar calcium compounds on fruit cracking and quality of sweet cherry variety ‘0900 Ziraat’ were investigated. Calcium caseinate, calcium chloride, calcium hydroxide and calcium nitrate were used as foliar sprays. Calcium applications reduced the cracking index 38% to 66% compared to cherries that did not receive foliar treatment. The most efficient applications for decreasing cracking were calcium hydroxide and calcium chloride. Calcium chloride and c...

  8. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-Trong Minh; Williams, George S.B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  9. Novel Mechanism of Cytotoxicity for the Selective Selenosemicarbazone, 2-Acetylpyridine 4,4-Dimethyl-3-selenosemicarbazone (Ap44mSe): Lysosomal Membrane Permeabilization.

    Science.gov (United States)

    Al-Eisawi, Zaynab; Stefani, Christian; Jansson, Patric J; Arvind, Akanksha; Sharpe, Philip C; Basha, Maram T; Iskander, George M; Kumar, Naresh; Kovacevic, Zaklina; Lane, Darius J R; Sahni, Sumit; Bernhardt, Paul V; Richardson, Des R; Kalinowski, Danuta S

    2016-01-14

    Selenosemicarbazones show marked antitumor activity. However, their mechanism of action remains unknown. We examined the medicinal chemistry of the selenosemicarbazone, 2-acetylpyridine 4,4-dimethyl-3-selenosemicarbazone (Ap44mSe), and its iron and copper complexes to elucidate its mechanisms of action. Ap44mSe demonstrated a pronounced improvement in selectivity toward neoplastic relative to normal cells compared to its parent thiosemicarbazone. It also effectively depleted cellular Fe, resulting in transferrin receptor-1 up-regulation, ferritin down-regulation, and increased expression of the potent metastasis suppressor, N-myc downstream regulated gene-1. Significantly, Ap44mSe limited deleterious methemoglobin formation, highlighting its usefulness in overcoming toxicities of clinically relevant thiosemicarbazones. Furthermore, Cu-Ap44mSe mediated intracellular reactive oxygen species generation, which was attenuated by the antioxidant, N-acetyl-L-cysteine, or Cu sequestration. Notably, Ap44mSe forms redox active Cu complexes that target the lysosome to induce lysosomal membrane permeabilization. This investigation highlights novel structure-activity relationships for future chemotherapeutic design and underlines the potential of Ap44mSe as a selective anticancer/antimetastatic agent. PMID:26645570

  10. Isotope targets prepared by vapor deposition

    International Nuclear Information System (INIS)

    As the state of the art for producing thin films has developed, the parameters set by the experiments have in turn become more stringent. Often these targets must be of high purity, extremely thin, self-supporting, and of accurately determined thickness. In addition, the target material may be an expensive isotope which must be reduced to elemental form at the time of vapor deposition. Methods of producing some of these targets will be discussed with such examples as calcium, magnesium and boron

  11. Aging and calcium as an environmental factor.

    Science.gov (United States)

    Fujita, T

    1985-12-01

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

  12. Transport of Calcium Ions into Mitochondria.

    Science.gov (United States)

    Xu, Zhaolong; Zhang, Dayong; He, Xiaolan; Huang, Yihong; Shao, Hongbo

    2016-06-01

    To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles in plant productivity and quality. Cytoplasmic calcium ions access into outer mitochondrial membrane (OMM) from voltage dependent anion-selective channel (VDAC) and were absorbed into inner mitochondrial membrane (IMM) by mitochondrial calcium uniporter (MCU), rapid mitochondrial calcium uptake (RaM) or mitochondrial ryanodine receptor (mRyR). Although both mitochondria and the mechanisms of calcium transport have been extensively studied, but there are still long-standing or even new challenges. Here we review the history and recent discoveries of the mitochondria calcium ions channel complex involved calcium assimilation, and discuss the role of calcium ions into mitochondria. PMID:27252588

  13. Expression and significance of CD44 and p-AKT in pancreatic head cancer

    OpenAIRE

    Xiaoping, Li; Xiaowei, Zhang; Leizhen, Zheng; Weijian, Guo

    2015-01-01

    Background CD44 and phosphorylated AKT (p-AKT) is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 and p-AKT has been reported to correlate with poor prognosis of pancreatic cancer in most literatures. The purpose of this study is to investigate the roles of CD44 and p-AKT in pancreatic head cancer and their correlation with the prognosis of pancreatic head cancer patients. Methods Forty-eight pancreatic head cancer samples were c...

  14. Optimizing calcium selective fluorimetric nanospheres.

    Science.gov (United States)

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

    2015-11-01

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

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

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

    -type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article......Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L...

  16. Isomorfic Substitutions of Calcium by Strontium in Calcium Hydroxyapatite

    International Nuclear Information System (INIS)

    By means of homogeneous precipitation it has been possible to synthesize crystalline solid solutions of calcium strontium hydroxyapatite from aqueous solutions. The lattice constants for the solid solutions were measured in the range Ca9Sr(PO4)6(OH)2 - CaSr9(PO4)6(OH)2. The investigations show that the discrimination of strontium against calcium is considerably smaller than reported elsewhere (1). Strontium is preferentially built into the c-axis direction of the apatite lattice

  17. Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics

    OpenAIRE

    Ueda, Yukari; Taira, Zenei

    2013-01-01

    We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 mg/kg, and is not affected by anions. Results after oral calcium administration of 150 mg/kg showed that the intes...

  18. moco: Fast Motion Correction for Calcium Imaging.

    Science.gov (United States)

    Dubbs, Alexander; Guevara, James; Yuste, Rafael

    2016-01-01

    Motion correction is the first step in a pipeline of algorithms to analyze calcium imaging videos and extract biologically relevant information, for example the network structure of the neurons therein. Fast motion correction is especially critical for closed-loop activity triggered stimulation experiments, where accurate detection and targeting of specific cells in necessary. We introduce a novel motion-correction algorithm which uses a Fourier-transform approach, and a combination of judicious downsampling and the accelerated computation of many L 2 norms using dynamic programming and two-dimensional, fft-accelerated convolutions, to enhance its efficiency. Its accuracy is comparable to that of established community-used algorithms, and it is more stable to large translational motions. It is programmed in Java and is compatible with ImageJ. PMID:26909035

  19. Multimodal encoding in a simplified model of intracellular calcium signaling

    OpenAIRE

    De Pitta`, Maurizio; Volman, Vladislav; Levine, Herbert; Ben-Jacob, Eshel

    2009-01-01

    Many cells use calcium signalling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca2+ signalling, much effort has been devoted to understand the functional role of Ca2+ responses and to decipher how their complex dynamics is regulated by the biochemical network of Ca2+-related signal transduction pathways. Experimental observations show that Ca2+ signals in response t...

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

    OpenAIRE

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

    2016-01-01

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

  1. Remodeling of Calcium Handling in Human Heart Failure

    OpenAIRE

    Lou, Qing; Janardhan, Ajit; Efimov, Igor R.

    2012-01-01

    Heart failure (HF) is an increasing public health problem accelerated by a rapidly aging global population. Despite considerable progress in managing the disease, the development of new therapies for effective treatment of HF remains a challenge. To identify targets for early diagnosis and therapeutic intervention, it is essential to understand the molecular and cellular basis of calcium handling and the signaling pathways governing the functional remodeling associated with HF in humans. Calc...

  2. Octupole strength in the neutron-rich calcium isotopes

    CERN Document Server

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

    2016-01-01

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

  3. Brain Metastasis is Predetermined in Early-Stages of Cutaneous Melanoma by CD44v6 Expression through Epigenetic Regulation of the Spliceosome

    OpenAIRE

    Marzese, Diego M.; Liu, Michelle; Huynh, Jamie L.; Hirose, Hajime; Donovan, Nicholas C.; Huynh, Kelly T.; Kiyohara, Eiji; Chong, Kelly; Cheng, David; Tanaka, Ryo; Morton, Donald L.; Barkhoudarian, Garni; Daniel F. Kelly; Hoon, Dave S.B.

    2014-01-01

    Melanoma brain metastasis (MBM) is frequent and has a very poor prognosis with no current predictive factors or therapeutic molecular targets. Our study unravels the molecular alterations of cell-surface glycoprotein CD44 variants during melanoma progression to MBM. High expression of CD44 splicing variant 6 (CD44v6) in primary melanoma (PRM) and regional lymph node metastases from AJCC Stage IIIC patients significantly predicts MBM-development. The expression of CD44v6 also enhances the migr...

  4. Calcium Supplementation to Prevent Preeclampsia: Translating Guidelines into Practice in Low-Income Countries.

    Science.gov (United States)

    Omotayo, Moshood O; Dickin, Katherine L; O'Brien, Kimberly O; Neufeld, Lynnette M; De Regil, Luz Maria; Stoltzfus, Rebecca J

    2016-03-01

    The WHO issued a strong recommendation that pregnant women be provided calcium supplements to prevent preeclampsia. This is the first recommended nutritional intervention to prevent this condition, a leading cause of maternal mortality globally. As health systems seek to implement this new intervention, a number of issues require further clarification and guidance, including dosage regimen, supplement formulation, and alignment with other antenatal nutritional interventions. We summarize key evidence on the above points and offer our views on good practices. Most developing countries have low calcium intake, so where habitual calcium intake is unknown, calcium supplements are likely beneficial. In our view, policymakers and program planners should consider adopting doses between 1.0 and 1.5 g elemental calcium/d, depending on the local average and variation in dietary calcium intake, logistical feasibility, and acceptability in the target population. Prudent practice would entail daily administration as calcium carbonate administered in divided doses of not >500 mg elemental calcium per dose. For ease of prescribing and adherence, calcium [as with iron and folic acid (IFA)] should be administered routinely to pregnant women from the earliest contact in pregnancy until delivery. Calcium's acute inhibitory effect on iron absorption translates to minimal effects in clinical studies. Therefore, to simplify the regimen and facilitate adherence, providers should not counsel that calcium and IFA pills must be taken separately. Although further research will shed more light on clinical and programmatic issues, policies can be implemented with ongoing revision as we continue to learn what works to improve maternal and newborn health. PMID:26980810

  5. Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

    Directory of Open Access Journals (Sweden)

    Phuc PV

    2011-06-01

    Full Text Available Pham Van Phuc, Phan Lu Chinh Nhan, Truong Hai Nhung, Nguyen Thanh Tam, Nguyen Minh Hoang, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim NgocLaboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, VietnamBackground: Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24- phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells.Methods: In this study, we reduced CD44 expression in CD44+CD24- breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24- breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug.Results: The proliferation of CD44 downregulated CD44+CD24- breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups.Conclusions: It would appear that expression of CD44 is integral among the CD44+CD24- cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.Keywords: antitumor drugs, breast cancer stem cells, CD44, CD44+CD24- cells, doxorubicin

  6. Calcium and lithium ion production for laser ion source

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-23

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

  7. Calcium and lithium ion production for laser ion source

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-15

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

  8. Calcium and lithium ion production for laser ion source

    International Nuclear Information System (INIS)

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

  9. Calcium and lithium ion production for laser ion source

    Science.gov (United States)

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

    2016-02-01

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

  10. Effect of calcium chloride addition on ice cream structure and quality.

    Science.gov (United States)

    Costa, F F; Resende, J V; Abreu, L R; Goff, H D

    2008-06-01

    The influence of calcium fortification by the addition of calcium chloride on quality parameters of ice cream based on physical properties was investigated, as was the effect of kappa-carrageenan at modifying the effects of this calcium fortification. Four ice cream mixes of conventional composition, with added kappa-carrageenan (0 or 0.025%) and added calcium chloride (0 or 4.4 g L(-1) = 40 mM of added Ca(2+)), were prepared. Modulated temperature-differential scanning calorimetry was used to investigate the effect of calcium chloride on the nucleation temperature, enthalpy of melting, and freezing point depression. The protein composition of 15.4% (wt/wt) reconstituted skim milk powder solutions with or without 4.4 g L(-1) added CaCl(2) and in the supernatant after ultracentrifugation was determined. Fat particle size distributions in ice cream were characterized by light scattering. Ice crystal sizes before and after temperature cycling were determined by cold-stage light microscopy. The results demonstrated that the addition of calcium chloride led to a substantial increase in ice crystal sizes and in fat partial coalescence, which were exacerbated by the addition of kappa-carrageenan. These results can be explained by the interaction between Ca(2+) ions and casein micelles, rather than any effects on freezing point depression. The calcium ions led to a more compact micelle, less serum beta-casein, and high fat destabilization, all of which would be expected to reduce macromolecular structure and volume occupancy in the unfrozen phase, which led to increased rates of ice recrystallization. PMID:18487638

  11. Intestinal absorption of calcium from foodstuffs as compared to a pharmaceutical preparation.

    Science.gov (United States)

    Werner, E; Hansen, Ch; Roth, P; Kaltwasser, J P

    1999-01-01

    Only few data are available on intestinal calcium absorption from foodstuffs and composite meals in humans. The aim of the study was to compare intraindividually the calcium absorption from milk and from a breakfast with that from a pharmaceutical calcium preparation of equal calcium content. In 8 healthy volunteers between 44 and 58 years of age, the intestinal calcium absorption was measured in randomized order applying the double isotope technique from: (1) 500ml of fresh milk (equivalent to 620mg Ca), (2) a test meal composed of 250 g curd, 150g yoghurt, 3 slices pineapple, 2 breakfast rolls, 2 cups of coffee, 10g of coffee cream, 20g butter, 50g jam and 20g honey (equivalent to 580mg Ca), and (3) a lactogluconate effervescent tablet (equivalent to 500mgCa). All test doses were given on an empty stomach and labelled with 20mg 44Ca. Simultaneously, 5mg 42Ca in a sterile isotonic solution were injected intravenously. The mean values of the absorbed fractions are 24.0% +/- 5.4% (mean +/-SD), 17.9% +/- 7.1%, and 28.7% +/- 9.1% for the milk, for the meal and for the tablet respectively. The data show that less calcium is absorbed from foodstuffs as compared to a preparation of optimal bioavailability. But in this study only the difference between absorption from the milk and from the meal was statistically significant. Therefore, it is possible to obtain a sufficient calcium supply of the human body also by properly selected foodstuffs. PMID:10902536

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

    Science.gov (United States)

    Hoth, M; Penner, R

    1993-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    LIUZhong-Yang; WANGChang-Xing; 等

    2002-01-01

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

  14. Calcium phosphate in catheter encrustation.

    Science.gov (United States)

    Cox, A J; Harries, J E; Hukins, D W; Kennedy, A P; Sutton, T M

    1987-02-01

    Encrusted catheters from nine female patients were the source of samples of deposits which were examined by X-ray diffraction, atomic absorption spectroscopy, infra-red spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. In eight samples the only crystalline phase which could be clearly distinguished by X-ray diffraction was ammonium magnesium orthophosphate hexahydrate, NH4MgPO4 X 6H2O, which occurs naturally as the mineral struvite. However, atomic absorption spectroscopy revealed an appreciable concentration of calcium in all samples. Calcium phosphates have previously been detected in catheter deposits. Infra-red and EXAFS spectra were consistent with the calcium phosphate being present as a poorly crystalline hydroxyapatite. Thus the deposits appear to consist of a mixture of crystalline struvite and a form of hydroxyapatite which is not fully crystalline. PMID:3030487

  15. African Studies Abstracts Online: number 44, 2013

    OpenAIRE

    African Studies Centre

    2013-01-01

    ASA Online provides a quarterly overview of journal articles and edited works on Africa in the field of the social sciences and the humanities available in the ASC library. Issue 44 (2013). African Studies Centre, Leiden.

  16. 44 CFR 10.11 - Environmental information.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Environmental information. 10... Environmental information. Interested persons may contact the Environmental Officer or the Regional Administrator for information regarding FEMA's compliance with NEPA....

  17. 44 CFR 204.42 - Eligible costs.

    Science.gov (United States)

    2010-10-01

    ... under State law and procedure and complying with 44 CFR part 13. (b) Equipment and supplies. Eligible... the firefighting effort or activities. This includes minimal repairs to bulldozer lines, camps,...

  18. Calcium Binding by Ro 60 Multiple Antigenic Peptides on PVDF Membrane.

    Science.gov (United States)

    Kurien, Biji T; Bachmann, Michael P

    2015-01-01

    Antibodies directed against ribonucleoprotein (RNP) particles are observed in systemic lupus erythematosus. Ro RNP particle is one such target. It is composed of a 60 kDa protein (Ro 60 or SS-A) that is non-covalently associated with at least one of the four short uridine-rich RNAs (the hY RNAs). Previously, we showed that multiple antigenic peptides (MAPs) made from the sequence of the Ro 60 autoantigen could be used, using double-immunodiffusion studies, enzyme-linked immunosorbant assay, affinity chromatography, and surface plasmon resonance, to show intramolecular and intermolecular protein-protein interaction within the Ro 60 RNP particle. We also observed that calcium is important in mediating this interaction. We hypothesized, therefore, that 60 kDa Ro is a calcium-binding protein. To investigate this, we electrophoresed 60 kDa Ro MAPs, transferred them to PVDF membrane, and assayed calcium binding using the Quin-2 system. Several Ro 60 MAPs were found to bind calcium using this assay, as well as bovine serum albumin, another calcium-binding protein. However, a MAP constructed from the Sm autoantigen did not bind to calcium. These data, along with our observation regarding the involvement of calcium in protein-protein interaction occurring between Ro 60 antigen and Ro 60 MAPs, makes us propose that Ro 60 antigen is a calcium-binding protein. PMID:26139264

  19. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Zhou, Xianguang [National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing 210016 (China); Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Wang, Jiandong [Department of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Zhang, Longjiang [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Teng, Zhaogang, E-mail: tzg@fudan.edu.cn [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Lu, Guangming, E-mail: cjr.luguangming@vip.163.com [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2015-03-30

    Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer.

  20. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer

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

    Science.gov (United States)

    Chu, J.

    1971-01-01

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

  2. Tumoral calcium pyrophosphate deposition disease

    International Nuclear Information System (INIS)

    A report of two patients in which a soft tissue mass, initially regarded as a malignant tumor, was shown to be the result of calcium pyrophosphate deposition disease. The first case, a woman aged 71 years, presented with a mass involving the right fifth finger. In the second case, also a women aged 71 years, the lesion involved the tissues adjacent to the right hip. Each lesion consisted of a mass of highly cellular tissue containing deposits of calcium pyrophosphate dihydrate crystals. The clinical, radiological, and pathological features of the two cases are compared with those of seven similar cases reported in the literature. (orig.)

  3. The Incredible, Embryological Egg: Calcium and Strontium Isotopes Recapitulate Ontogeny

    Science.gov (United States)

    Gordon, G. W.; Skulan, J. L.

    2011-12-01

    Embryological development reflects evolutionary history. Understanding the processes of fetal growth is important for curing human birth defects and predicting damage to ecosystems from environmental insults. Tracing enzymatic and hormonal gradients during development, and correlating them to genetic cues dominate modern embryology. Previous work done tracing the mass transfer of elements has generally been limited to isotope spikes in vitro. Natural mass-dependent Ca and Sr isotopic ratios and radiogenic Sr isotopes have the potential to reveal both source and biochemical mechanism information about processes in vivo, but have not previously been extensively explored. The process when a hen lays a fertilized egg that becomes a chick includes formation and dissolution of calcium phosphate (bone) and calcium carbonate (shell). Skulan and DePaolo (1999) showed that chickens have 2% δ44/42Ca between a hen's bones and an egg white; this span represents more than 80% of the entire range of natural Ca isotope variation and illustrates there is significant variation to investigate. A striking feature of archosaurian development that also occurs in many mammals, including humans, is mass transfer of calcium from mother to embryo. The yolk of the domestic hen matures over 7-9 days, but the albumen, shell membranes and shell form in less than 20 hours. Domestic laying hens are at the physiological limit of egg production and selective breeding is no longer an effective method of increasing egg production. 60-75% of the shell's ~1.5 g of calcium comes from dietary sources, while 25-40% comes from the hen's medullary bone. Medullary bone is spicules formed in the marrow of long bones, and is a store of dietary calcium rapidly available for eggshell secretion. During in ovo development, the embryo's skeleton is formed from calcium in the yolk and by bulk dissolution of the eggshell's inner aspect via carbonic anhydrase in a process that has an effect on bone density similar to

  4. Complex formation ions calcium with macromolecules pectin

    International Nuclear Information System (INIS)

    In clause the mechanism of sorption of ions of calcium by macromolecules of pectin is opened. Is shown, that the linkage of ions of calcium descends on acid bunches of pectin, and process carries cooperative character

  5. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Devkanya Dutta

    2000-12-01

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

  6. Dairy Dilemma: Are You Getting Enough Calcium?

    Science.gov (United States)

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

  7. Calcium, vitamin D, and your bones

    Science.gov (United States)

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

  8. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

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

  9. Calcium channel blockers and Alzheimer's disease★

    OpenAIRE

    Tan, Yi; Deng, Yulin; Qing, Hong

    2012-01-01

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

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

    Science.gov (United States)

    Liang, Willmann

    2008-01-01

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

  11. Electrophysical properties of calcium orthovanadate

    International Nuclear Information System (INIS)

    The electron conductivity, dielectric permeability and magnetic susceptibility of calcium orthovanadate are studied. It is shown that structural transformations bring about changes in the nature of electrophysical properties of Ca3(VO4)2 and cause the charge redistribution in VO43- anion groups

  12. The Validity and Reliability of the Turkish Version of the Obsessive Beliefs Questionnaire-44 (OBQ-44)

    OpenAIRE

    Murat BOYSAN; Lütfullah BEŞİROĞLU; Nuralay ÇETİNKAYA; Atli, Abdullah; Adem AYDIN

    2010-01-01

    Objective: Cognitive factors have a central place in the etiology and persistenceof obsessive-compulsive disorder (OCD). The aim of the study was to evaluatepsychometric properties of the Turkish version of the ObsessiveBeliefs Questionnaire-44 (OBQ-44). Original factor structure of the OBQ-44 anddiscrimination characteristic of the instrument between OCD patients andnonclinical population were evaluated extensively in Turkish sample.Methods: Data were collected from 175 healthy subjects and ...

  13. 48 CFR 53.301-44 - Standard Form 44, Purchase Order-Invoice-Voucher.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Standard Form 44, Purchase Order-Invoice-Voucher. 53.301-44 Section 53.301-44 Federal Acquisition Regulations System FEDERAL..., Purchase Order—Invoice—Voucher. EC01MY91.021 EC01MY91.022 EC01MY91.023 EC01MY91.024...

  14. 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)....

  15. 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)....

  16. 21 CFR 582.5217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

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

  17. 21 CFR 582.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... 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... Additives § 582.1191 Calcium carbonate. (a) Product. Calcium carbonate. (b) Conditions of use....

  18. 21 CFR 582.5191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... 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... Supplements 1 § 582.5191 Calcium carbonate. (a) Product. Calcium carbonate. (b) Conditions of use....

  19. 21 CFR 73.1070 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Calcium carbonate. 73.1070 Section 73.1070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1070 Calcium carbonate. (a) Identity. (1) The color additive calcium carbonate is a fine,...

  20. 21 CFR 582.1205 - Calcium hydroxide.

    Science.gov (United States)

    2010-04-01

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

  1. 21 CFR 182.2227 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

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

  2. 21 CFR 582.2227 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

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

  3. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

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

  4. Lactulose stimulates calcium absorption in postmenopausal women

    NARCIS (Netherlands)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  6. Half-life of {sup 44}Ti

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, I.; Kutschera, W.; Castagnoli, G. [Instituto di Cosmogeofisica, Torino (Italy); Paul, M. [Hebrew Univ., Jerusalem (Israel)

    1995-08-01

    The measurement of the {sup 44}Ti half-life, started 3 years ago, is still continuing. The goal of this measurement is to determine the half-life of {sup 44}Ti, which is {approximately}52 y, to a precision of {approximately}5%. An accurate value of this half-life is of interest to cosmologists who need it to determine the production of heavy elements in supernova. Three sets of samples - a pure 200-nCi {sup 44}Ti sample, a pure 300-nCi {sup 60}Co source, and a mixed {sup 44}Ti-{sup 60}Co source of similar strength - were prepared and their spectra are being measured with Ge spectrometers at Argonne, Torino and Jerusalem. Each sample is counted for a period of 2 days, at approximate intervals of 4 months. The room background is also measured for the same length of time. We hope to start data analysis at the end of summer and obtain a value for the {sup 44}Ti half-life.

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

    Science.gov (United States)

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

    2015-10-01

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

  8. Sodium/Calcium Exchangers Selectively Regulate Calcium Signaling in Mouse Taste Receptor Cells

    OpenAIRE

    Szebenyi, Steven A.; Laskowski, Agnieszka I.; Medler, Kathryn F.

    2010-01-01

    Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium release from intracellular stores while other stimuli depolarize taste cells to cause calcium influx through voltage-gated calcium channels (VGCCs). While the signaling mechanisms that initiate calcium signals have been described in taste cells, the calcium clearance mechanisms (CCMs) that contrib...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    BACKGROUND: Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation...... offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium...... electroporation and electrochemotherapy. METHODS: The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore...

  10. Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics

    OpenAIRE

    Zenei Taira, Zenei

    2013-01-01

    Yukari Ueda, Zenei TairaFaculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, JapanAbstract: We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 ...

  11. ACTION OF SILICATO OF CALCIUM AND MAGNESIUM IN THE REDUCTION Cercospora

    Directory of Open Access Journals (Sweden)

    Franciane Diniz Cogo

    2011-07-01

    Full Text Available The aim of this study was to evaluate the response of coffee plants (Coffea arabica Catuaí IAC-44 with different doses of calcium silicate and magnesium in relation to incidence of Cercospora spot coffeicola and plant growth. The experiment was conducted in nursery seedling production of coffee from the Federal Institute of Southern Minas Gerais, Campus Machado, MG randomized blocks with five replications and the treatment used a source of silicon, calcium silicate and magnesium in doses - 0 (control, 75, 150, 225 300 g/m2. The application of silicon in the soil causes the reduction to Cercospora coffeicola. The application of calcium silicate and magnesium affect the growth characteristics and was effective in inducing gray leaf spot, via ground coffee seedlings in nurseries.

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

    OpenAIRE

    C.J. Van Dijk; D.C. Lourens

    2001-01-01

    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 anio...

  13. Calcium signals and calcium channels in osteoblastic cells

    Science.gov (United States)

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

    1998-01-01

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

  14. 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.

  15. Fluoride-containing nanoporous calcium-silicate MTA cements for endodontics and oral surgery: Early fluorapatite formation in a phosphate-containing solution

    OpenAIRE

    Gandolfi, M.G.; Taddei, P.; Siboni, F.; Modena, E.; Ginebra Molins, Maria Pau; Prati, Claudio

    2011-01-01

    Gandolfi MG, Taddei P, Siboni F, Modena E, Ginebra MP, Prati C. Fluoride-containing nanoporous calcium-silicate MTA cements for endodontics and oral surgery: early fluorapatite formation in a phosphate-containing solution. International Endodontic Journal, 44, 938–949, 2011. Aim To test the chemical–physical properties and apatite-forming ability of experimental fluoride-doped calcium silicate cements designed to create novel bioactive materials for use in endodontics ...

  16. Substitution of calcium by strontium within selected calcium phosphates

    Science.gov (United States)

    Rokita, E.; Hermes, C.; Nolting, H.-F.; Ryczek, J.

    1993-06-01

    Sr incorporation in the molecules of amorphous calcium phosphate, apatitic tricalcium phosphate, hydroxyapatite, octacalcium phosphate and dicalcium phosphate dihydrate was investigated. The concentration of Sr ranged from 225 to 1010 μ g / g, i.e. it overlapped with the physiological range of Sr concentrations in human bone. The leading experimental technique was extended X-ray absorption fine structure (EXAFS) at the Sr K edge. Results of these studies demonstrated the following: (1) Sr incorporation in the calcium phosphates is compound-dependent, (2) the coordination of incorporated Sr atoms in the Ca-P molecules is similar to that of Ca atoms, but interatomic distances are ≈0.015 nm larger, (3) in apatitic tricalcium phosphate, hydroxyapatite and octacalcium phosphate lattices Sr atoms may occupy selected Ca sites, which was not the case for dicalcium phosphate dihydrate, (4) in the apatite lattice Sr atoms are coordinated by 6 PO 4 tetrahedrals and (5) EXAFS spectra at the K edge of the incorporated Sr may be used to distinguish the structures of amorphous calcium phosphate, dicalcium phosphate dihydrate as well as apatite and its derivatives (apatitic tricalcium phosphate, octacalcium phosphate).

  17. 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.

  18. Influence of the neutron numbers of projectile and target on the evaporation residue cross sections in hot fusion reactions

    Science.gov (United States)

    Zhu, Long; Su, Jun; Zhang, Feng-Shou

    2016-06-01

    Within the framework of a dinuclear system model, the influence of projectile and target neutron number on capture cross section, fusion probability, and survival probability for the reactions S,3634+238U and 48Ca+Pu 239 ,240 ,242 ,244 are investigated. The calculated excitation functions are in good agreement with the experimental data. To synthesize more unknown neutron-deficient isotopes of already-known superheavy elements, the possibility of using lighter calcium isotopes to induce hot fusion reactions is investigated and the maximal evaporation residual cross sections for Ca 44 ,46 ,48 -induced hot fusion reactions to produce unknown neutron-deficient superheavy nuclei with Z =112 -116 are predicted.

  19. USING CALCIUM CARBONATE WHISKERS AS PAPERMAKING FILLER

    Directory of Open Access Journals (Sweden)

    Xiaoyu Chen

    2011-05-01

    Full Text Available Whiskers, having large length/diameter ratio, are fiber-shaped single crystals. The technical possibility of using calcium carbonate whiskers as papermaking filler to replace conventional powder-like calcium carbonate was investigated. The results showed that it may be feasible to use calcium carbonate whisker as papermaking filler. Compared with conventional precipitated calcium carbonate, calcium carbonate whisker had higher retention efficiency. The use of calcium carbonate whisker also favorably affected the strength properties of paper sheets. A model was proposed to suggest the mechanism for paper strength improvement. The whiskers filled in paper sheets could increase the friction between fibers, thus increasing bonding strength. Moreover, the strength properties of paper were further improved because calcium carbonate whiskers were partly embedded in pulp fiber walls.

  20. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    Directory of Open Access Journals (Sweden)

    Choksi Krishna

    2011-03-01

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

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

    OpenAIRE

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

    2016-01-01

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

  2. CERN: Fixed target targets

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-01-15

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

  4. The Validity and Reliability of the Turkish Version of the Obsessive Beliefs Questionnaire-44 (OBQ-44

    Directory of Open Access Journals (Sweden)

    Murat BOYSAN

    2010-09-01

    Full Text Available Objective: Cognitive factors have a central place in the etiology and persistenceof obsessive-compulsive disorder (OCD. The aim of the study was to evaluatepsychometric properties of the Turkish version of the ObsessiveBeliefs Questionnaire-44 (OBQ-44. Original factor structure of the OBQ-44 anddiscrimination characteristic of the instrument between OCD patients andnonclinical population were evaluated extensively in Turkish sample.Methods: Data were collected from 175 healthy subjects and 62 patients with OCDwho applied to the Psychiatry Clinic at Yüzüncü Y›l University. Subjects wereadministered the SCID-I, the Obsessive Beliefs Questionnaire-44 (OBQ-44, thePadua Inventory (PI-41, the Yale-Brown Obsessive Compulsive Scale (Y-BOKS,the Metacognitions Questionnaire-30 (MCQ-30, the Thought Action Fusion Scale(TAFS, the White Bear Suppression Inventory (WBSI, the Penn Inventory ofScrupulosity (PIOS, the Penn State Worry Questionnaire (PSWQ, and theBeck Depression Inventory (BDI. Data were analyzed in order to evaluate thereliability and validity of the OBQ-44.Results: The three-factor original structure tested using confirmatory factoranalysis was observed to be highly consistent with the data obtained from thestudy. OCD patients reported significantly higher scores on OBQ-44 rather thancontrols. Correlations of the OBQ-44 scores with psychological variables weregenerally significant. Inner consistency coefficient for the OBQ-44 was α0,95 andtest-retest correlation between two points at 30-day time course was r=0.79.Conclusion: The Turkish version of the OBQ-44 has adequate validity and reliability inclinical and nonclinical Turkish sample.(Archives of Neuropsychiatry 2010; 47: 216-22

  5. [Calcium pyrophosphate dihydrate deposition disease].

    Science.gov (United States)

    Koitschev, C; Kaiserling, E; Koitschev, A

    2003-08-01

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

  6. Sputter target

    Science.gov (United States)

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

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

  7. 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....

  8. 44 CFR 150.3 - Nomination process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Nomination process. 150.3... Nomination process. (a) The Nominating Officials nominating Firefighters and Civil Defense Officers shall... earliest practicable date after the performance of the act or acts for which the nomination is...

  9. 44 CFR 62.22 - Judicial review.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Judicial review. 62.22 Section 62.22 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... ADJUSTMENT OF CLAIMS Claims Adjustment, Claims Appeals, and Judicial Review § 62.22 Judicial review. (a)...

  10. 44 CFR 295.43 - Judicial review.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Judicial review. 295.43... Judicial review. As an alternative to arbitration, a Claimant dissatisfied with the outcome of an Administrative Appeal may seek judicial review of the decision by bringing a civil lawsuit against FEMA in...

  11. 44 CFR 6.57 - Judicial review.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Judicial review. 6.57 Section... SECURITY GENERAL IMPLEMENTATION OF THE PRIVACY ACT OF 1974 Requests To Amend Records § 6.57 Judicial review... requestor may seek judicial review of that determination. A civil action must be filed in the...

  12. 44 CFR 7.15 - Judicial review.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Judicial review. 7.15 Section...-Assisted Programs-General § 7.15 Judicial review. Action taken pursuant to section 602 of the Act is subject to judicial review as provided in section 603 of the Act....

  13. 44 CFR 19.405 - Housing.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Housing. 19.405 Section 19... Prohibited § 19.405 Housing. (a) Generally. A recipient shall not, on the basis of sex, apply different rules... related to housing, except as provided in this section (including housing provided only to...

  14. 44 CFR 206.3 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 206.3 Section 206.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE General § 206.3 Policy. It is the policy of FEMA to...

  15. 44 CFR 327.3 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 327.3 Section 327.3... PREPAREDNESS POLICY ON USE OF GOVERNMENT-OWNED INDUSTRIAL PLANT EQUIPMENT BY PRIVATE INDUSTRY (DMO-10A) § 327.3 Policy. (a) General. (1) Primary reliance for defense production shall be placed upon private...

  16. 44 CFR 206.341 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 206.341 Section 206... SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE Coastal Barrier Resources Act § 206.341 Policy. It shall be the policy of FEMA to achieve the goals of CBRA in carrying out disaster relief on units of...

  17. 44 CFR 312.3 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 312.3 Section 312.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... Policy. (a) It is the policy of FEMA to provide a means of assistance to States and their...

  18. 44 CFR 12.3 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 12.3 Section 12.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL ADVISORY COMMITTEES § 12.3 Policy. In determining whether an advisory committee should be...

  19. 44 CFR 331.2 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 331.2 Section 331.2... SURPLUS AREAS § 331.2 Policy. (a) It is the policy of the Federal Government to award appropriate... locating procurement where the needed labor force and facilities are fully available. (b) This policy...

  20. 44 CFR 334.2 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 334.2 Section 334.2... PREPAREDNESS GRADUATED MOBILIZATION RESPONSE § 334.2 Policy. (a) As established in Executive Order 12656, the policy of the United States is to have sufficient emergency response capabilities at all levels...

  1. 44 CFR 10.4 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 10.4 Section 10.4... GENERAL ENVIRONMENTAL CONSIDERATIONS General § 10.4 Policy. (a) FEMA shall act with care to assure that... mitigation and flood insurance, it does so in a manner consistent with national environmental policies....

  2. 44 CFR 295.2 - Policy.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 295.2 Section 295.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY CERRO GRANDE FIRE ASSISTANCE CERRO GRANDE FIRE ASSISTANCE General § 295.2 Policy. It is our policy...

  3. 44 CFR 9.2 - Policy.

    Science.gov (United States)

    2010-10-01

    ... Agency to provide leadership in floodplain management and the protection of wetlands. Further, the Agency... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 9.2 Section 9.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND...

  4. 44 CFR 79.9 - Grant administration.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Grant administration. 79.9... § 79.9 Grant administration. (a) The Grantee must follow FEMA grant requirements, including submission of performance and financial status reports, and shall follow adequate competitive...

  5. 44 CFR 206.365 - Loan administration.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Loan administration. 206.365... administration. (a) Funding. (1) FEMA will disburse funds to the local government when requested, generally in... government shall submit a copy of its most recent financial report (if not submitted previously)...

  6. 44 CFR 206.375 - Loan administration.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Loan administration. 206.375... administration. (a) Funding. (1) FEMA will disburse funds to the local government when requested, generally in... government shall submit a copy of its most recent financial report (if not submitted previously)...

  7. 44 CFR 13.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Financial reporting. 13.41... Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of this section... supplementary or other forms as may from time to time be authorized by OMB, for: (i) Submitting...

  8. 44 CFR 5.25 - Available materials.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Available materials. 5.25... Agency Information, Rules, Orders, Policies, and Similar Material § 5.25 Available materials. FEMA materials which are available under this subpart are as follows: (a) Final opinions and orders made in...

  9. 44 CFR 79.5 - Application process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Application process. 79.5 Section 79.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... § 79.5 Application process. (a) Applicant or grantee. (1) States will be notified of the...

  10. 44 CFR 352.29 - Appeal process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Appeal process. 352.29 Section 352.29 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Participation § 352.29 Appeal process. (a) Any interested party may appeal a determination made by the...

  11. 44 CFR 10.7 - Planning.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Planning. 10.7 Section 10.7... GENERAL ENVIRONMENTAL CONSIDERATIONS Agency Implementing Procedures § 10.7 Planning. (a) Early planning. The Regional Administrator shall integrate the NEPA process with other planning at the...

  12. 44 CFR 71.4 - Documentation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Documentation. 71.4 Section... LEGISLATION § 71.4 Documentation. (a) In order to obtain a new policy of flood insurance for a structure which... protected area,” the owner of the structure must submit the documentation described in this section in...

  13. 44 CFR 206.151 - Food commodities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Food commodities. 206.151... Food commodities. (a) The Administrator will assure that adequate stocks of food will be ready and... section, the Administrator may direct the Secretary of Agriculture to purchase food commodities...

  14. 44 CFR 402.2 - Restricted commodities.

    Science.gov (United States)

    2010-10-01

    ... Positive List (15 CFR part 399) (as amended from time to time) of the Comprehensive Export Schedule of the... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Restricted commodities. 402.2... SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.2 Restricted commodities. The...

  15. 44 CFR 312.5 - Personnel.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Personnel. 312.5 Section 312... SECURITY PREPAREDNESS USE OF CIVIL DEFENSE PERSONNEL, MATERIALS, AND FACILITIES FOR NATURAL DISASTER PURPOSES § 312.5 Personnel. FEMA contributes to the development and support of emergency...

  16. 44 CFR 19.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.310 Section... RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 19.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 19.300 through...

  17. 44 CFR 19.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.510 Section... Programs or Activities Prohibited § 19.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where...

  18. 42 CFR 414.44 - Transition rules.

    Science.gov (United States)

    2010-10-01

    ... § 414.44 Transition rules. (a) Adjusted historical payment basis—(1) All services other than radiology and nuclear medicine services. For all physician services other than radiology services, furnished in... prevailing charge applied in the fee schedule area for the service in CY 1991, as determined by CMS...

  19. 44 CFR 12.7 - Charter.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Charter. 12.7 Section 12.7 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... also be furnished at the time of filing to the Library of Congress, Exchange and Gift Division,...

  20. 27 CFR 30.44 - Weighing containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Weighing containers. 30.44... Weighing containers. (a) Weighing containers of more than 10 wine gallons. The weight of containers having.... (b) Weighing containers of 10 wine gallons or less. The weight for containers of a capacity of...

  1. 44 CFR 350.9 - Exercises.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Exercises. 350.9 Section 350.9 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... its boundaries or is within the 10-mile plume exposure pathway Emergency Planning Zone of such...

  2. 44 CFR 15.8 - Gambling.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Gambling. 15.8 Section 15.8... CENTER § 15.8 Gambling. We prohibit participating in games for money or other personal property, including the operation of gambling devices, the conduct of a lottery or pool, or the sale or purchase...

  3. 44 CFR 13.32 - Equipment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Equipment. 13.32 Section 13... LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 13.32 Equipment. (a) Title. Subject to the obligations and conditions set forth in this section, title to equipment acquired under...

  4. 44 CFR 75.11 - Standards.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Standards. 75.11 Section 75... PROPERTIES UNDER SELF-INSURANCE PLAN Standards for Exemption § 75.11 Standards. (a) In order to be exempt... hazards which are covered under the Standard Flood Insurance Policy. (3) Provide coverage to...

  5. 44 CFR 9.5 - Scope.

    Science.gov (United States)

    2010-10-01

    ..., as amended, and the issuance of an exception to a community under 44 CFR 60.6(b). (See also § 9.9(e... and 306; (2) Emergency Support Teams (section 304); (3) Unemployment Assistance (section 407); (4... structure is one which has previously sustained structural damage from flooding due to a major disaster...

  6. 44 CFR 9.18 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 9.18... HOMELAND SECURITY GENERAL FLOODPLAIN MANAGEMENT AND PROTECTION OF WETLANDS § 9.18 Responsibilities. (a) Regional Administrators' responsibilities. Regional Administrators shall, for all actions falling...

  7. 44 CFR 10.5 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 10.5... Responsibilities. (a) The Regional Administrators shall, for each action not categorically excluded from this... impact statements and assign lead agency responsibility when more than one FEMA office or...

  8. 44 CFR 207.4 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 207.4... HOMELAND SECURITY DISASTER ASSISTANCE MANAGEMENT COSTS § 207.4 Responsibilities. (a) General. This section identifies key responsibilities of FEMA and grantees in carrying out section 324 of the Stafford Act, 42...

  9. 44 CFR 206.362 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 206.362 Section 206.362 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Responsibilities. (a) The local government shall submit the financial information required by FEMA in...

  10. 44 CFR 79.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 79.3... § 79.3 Responsibilities. (a) Federal Emergency Management Agency (FEMA). Administer and provide... responsibilities of the “State” as the term is used in this part, as applicant or grantee, described in...

  11. 44 CFR 201.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 201.3... HOMELAND SECURITY DISASTER ASSISTANCE MITIGATION PLANNING § 201.3 Responsibilities. (a) General. This section identifies the key responsibilities of FEMA, States, and local/tribal governments in carrying...

  12. 44 CFR 206.372 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 206.372 Section 206.372 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Responsibilities. (a) The local government shall submit the financial information required by FEMA in...

  13. 44 CFR 323.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 323.3...) § 323.3 Responsibilities. (a) As stated in The National Plan for Emergency Preparedness, the direction of resources mobilization is a Federal responsibility. However, in the period immediately...

  14. Photovoltaic barometer 44% of growth in 2000

    International Nuclear Information System (INIS)

    During the year 2000, worldwide production of solar cells increased by 44% and installed capacity in the European Union rose by 29%. This trend should be reinforced in 2001 with new national programmes pertaining to grid-linked photovoltaic systems coming into effect and due to the increasing involvement of the big oil industrial groups in the sector. (author)

  15. 44 CFR 19.525 - Fringe benefits.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Fringe benefits. 19.525... Programs or Activities Prohibited § 19.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance,...

  16. 44 CFR 80.13 - Application information.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Application information. 80.13 Section 80.13 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT... deed restriction language, which shall be consistent with the FEMA model deed restriction that...

  17. 44 CFR 13.11 - State plans.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false State plans. 13.11 Section 13.11 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... provisions, (2) Repeat the assurance language in the statutes or regulations, or (3) Develop its own...

  18. 44 CFR 1.8 - Regulations review.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Regulations review. 1.8 Section 1.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... the rule from the public; (3) The complexity of the rule, including need for review of language...

  19. 44 CFR 80.21 - Closeout requirements.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Closeout requirements. 80.21 Section 80.21 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... restriction language to meet the requirements of this part; (b) A photo of each property site after...

  20. 44 CFR 19.235 - Statutory amendments.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Statutory amendments. 19.235 Section 19.235 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... of factors related to the individual's personal appearance, poise, and talent. The pageant,...

  1. 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...

  2. 44 CFR 16.160 - Communications.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Communications. 16.160... ACTIVITIES CONDUCTED BY THE FEDERAL EMERGENCY MANAGEMENT AGENCY § 16.160 Communications. (a) The agency shall take appropriate steps to ensure effective communication with applicants, participants, personnel...

  3. 44 CFR 7.942 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Mediation. 7.942 Section 7..., Conciliation, and Enforcement Procedures § 7.942 Mediation. (a) FEMA will promptly refer to a mediation agency... participate in the mediation process to the extent necessary to reach an agreement or for the mediator to...

  4. 44 CFR 295.42 - Arbitration.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Arbitration. 295.42 Section... SECURITY CERRO GRANDE FIRE ASSISTANCE CERRO GRANDE FIRE ASSISTANCE Dispute Resolution § 295.42 Arbitration. (a) Initiating arbitration. A Claimant who is dissatisfied with the outcome of the...

  5. 44 CFR 59.4 - References.

    Science.gov (United States)

    2010-10-01

    ... 1954, as amended by the Housing and Community Development Act of 1974 (24 CFR 600.72). (12) Executive... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false References. 59.4 Section 59.4... References. (a) The following are statutory references for the National Flood Insurance Program, under...

  6. 44 CFR 5.46 - Fee schedule.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Fee schedule. 5.46 Section 5... SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION Fees § 5.46 Fee schedule. (a) Manual searches for... schedule programs, such as but not limited to the Government Printing Office or the National...

  7. 44 CFR 72.3 - Fee schedule.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Fee schedule. 72.3 Section 72.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... PROCESSING MAP CHANGES § 72.3 Fee schedule. (a) For requests for CLOMRs, LOMRs, and PMRs based on...

  8. 44 CFR 295.41 - Administrative appeal.

    Science.gov (United States)

    2010-10-01

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

  9. 44 CFR 68.9 - Admissible evidence.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Admissible evidence. 68.9 Section 68.9 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... admissible. (b) Documentary and oral evidence shall be admissible. (c) Admissibility of non-expert...

  10. 44 CFR 5.3 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 5.3 Section 5.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... means all books, papers, maps, photographs, or other documentary materials, regardless of physical...

  11. 44 CFR 300.3 - Financial assistance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Financial assistance. 300.3... HOMELAND SECURITY PREPAREDNESS DISASTER PREPAREDNESS ASSISTANCE § 300.3 Financial assistance. (a) The... responsibilities for IFG, crisis counseling, mass care or other functional responsibilities; (7) Training for...

  12. 44 CFR 150.7 - Selection process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Selection process. 150.7... Selection process. (a) President's Award. Nominations for the President's Award shall be reviewed, and... cause an evaluation and selection of the nominees to be made in accordance with the requirements...

  13. HI in Group Interactions: HCG 44

    CERN Document Server

    Hess, Kelley M; Yahya, Sahba; Leisman, Lukas; Serra, Paolo; Lucero, Danielle M; Passmoor, Sean S; Carignan, Claude

    2016-01-01

    Extending deep observations of the neutral atomic hydrogen (HI) to the environment around galaxy groups can reveal a complex history of group interactions which is invisible to studies that focus on the stellar component. Hickson Compact Group 44 (HCG 44) is a nearby example and we have combined HI data from the Karoo Array Telescope, Westerbork Synthesis Radio Telescope, and Arecibo Legacy Fast ALFA survey, in order to achieve high column density sensitivity (N_HI < 2x10^18 cm^-2) to the neutral gas over a large field-of-view beyond the compact group itself. We find the giant HI tail north of HCG 44 contains 1.1x10^9 M_Sun of gas and extends 450 kpc from the compact group: twice as much mass and 33% further than previously detected. However, the additional gas is still unable to account for the known HI deficiency of HCG 44. The tail likely formed through a strong tidal interaction and HI clouds in the tail have survived for 1 Gyr or more after being stripped. This has important implications for understan...

  14. 44 CFR 206.345 - Exceptions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Exceptions. 206.345 Section 206.345 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF..., and of the access thereto; (4) Repair of facilities for scientific research, including but not...

  15. 44 CFR 67.8 - Appeal procedure.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Appeal procedure. 67.8 Section 67.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... technical or scientific data submitted by the community that tend to negate or contradict the...

  16. 44 CFR 7.10 - Compliance information.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Compliance information. 7.10... in FEMA-Assisted Programs-General § 7.10 Compliance information. (a) Cooperation and assistance. The... such information, as the responsible agency official or his designee may determine to be necessary...

  17. 44 CFR 5.6 - Congressional information.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Congressional information. 5... HOMELAND SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION General Provisions § 5.6 Congressional information. Nothing in this part authorizes withholding information from the Congress except when...

  18. 44 CFR 321.8 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reports. 321.8 Section 321.8... ADMINISTRATION) § 321.8 Reports. The Department of Defense, Department of Energy, and Maritime Administration shall furnish the Administrator of the Federal Emergency Management Agency with reports on items...

  19. 44 CFR 401.3 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reports. 401.3 Section 401.3... RESTRICTIONS (T-1) § 401.3 Reports. Persons subject to this order shall submit such reports to the Assistant... Reports Act....

  20. 44 CFR 327.5 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reports. 327.5 Section 327.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... Reports. Such reports of operations under this order as may be required by the Federal...

  1. 44 CFR 206.343 - Scope.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Scope. 206.343 Section 206.343 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... orientation which is unrelated to development is not subject to the requirements of these regulations....

  2. 44 CFR 19.500 - Employment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Employment. 19.500 Section 19.500 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... from leaves of absence, leave for pregnancy, childbirth, false pregnancy, termination of...

  3. 44 CFR 19.300 - Admission.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Admission. 19.300 Section 19.300 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... against or exclude any person on the basis of pregnancy, childbirth, termination of pregnancy, or...

  4. 44 CFR 9.4 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... Disaster Relief Act of 1974 (42 U.S.C. 5145 and 5146). See 44 CFR part 205, subpart E. Enhance means to... resource values (agriculture, aquaculture, forestry). New Construction means the construction of a new... Places or a State Inventory of Historic Places. Support means to encourage, allow, serve or...

  5. 44 CFR 209.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... project, in accordance with FEMA guidance and using a FEMA-approved methodology. FEMA will review the... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 209.2 Section 209.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF...

  6. 44 CFR 19.540 - Advertising.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Advertising. 19.540 Section 19.540 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR...

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

    Science.gov (United States)

    Nakata, Paul A

    2012-04-01

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

  8. Serum calcium in pulmonary tuberculosis

    OpenAIRE

    Subhash C. Sharma

    1981-01-01

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

  9. Drying dichloromethane over calcium hydride

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Lucas Kinard, Kurtis Kasper & Antonios Mikos ### Abstract This protocol describes the drying of dichloromethane by a simple 10 step procedure. One can implement this protocol using common lab glass and lab equipment. First, dichloromethane is refluxed with calcium hydride to remove water. Then, dichloromethane is distilled to separate it from the byproducts of the reflux reaction. This procedure can be implemented in 1 day. ### Introduction In many instances i...

  10. 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

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

    Science.gov (United States)

    O'Day, Danton H; Myre, Michael A

    2004-08-01

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

  12. 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.

  13. Serotonin and calcium homeostasis during the transition period.

    Science.gov (United States)

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

    2016-07-01

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

  14. The role of calcium in human aging.

    Science.gov (United States)

    Beto, Judith A

    2015-01-01

    Calcium is an essential nutrient that is necessary for many functions in human health. Calcium is the most abundant mineral in the body with 99% found in teeth and bone. Only 1% is found in serum. The serum calcium level is tightly monitored to remain within normal range by a complex metabolic process. Calcium metabolism involves other nutrients including protein, vitamin D, and phosphorus. Bone formation and maintenance is a lifelong process. Early attention to strong bones in childhood and adulthood will provide more stable bone mass during the aging years. Research has shown that adequate calcium intake can reduce the risk of fractures, osteoporosis, and diabetes in some populations. The dietary requirements of calcium and other collaborative nutrients vary slightly around the world. Lactose intolerance due to lactase deficiency is a common cause of low calcium intake. Strategies will be discussed for addressing this potential barrier to adequate intake. The purpose of this narrative review is a) to examine the role of calcium in human health, b) to compare nutrient requirements for calcium across lifecycle groups and global populations, c) to review relationships between calcium intake, chronic disease risk, and fractures, and d) to discuss strategies to address diet deficiencies and lactose intolerance. PMID:25713787

  15. Rapid screening assay for calcium bioavailability studies

    International Nuclear Information System (INIS)

    Calcium bioavailability has been studied by numerous techniques. The authors report here the use of the gamma emitting isotope of calcium (47Ca) in a whole body retention assay system. In this system, calcium sources are administered by oral gavage and subsequent counts are determined and corrected for isotopic decay. Unlike iron and zinc retention curves, which exhibit a 2-3 day equilibration period, calcium reaches equilibration after 24 hours. Autoradiographic analysis of the femurs indicate that the newly absorbed calcium is rapidly distributed to the skeletal system. Moreover, the isotope is distributed along the entire bone. Comparisons of calcium bioavailability were made using intrinsic/extrinsic labeled milk from two species i.e. rat and goat as well as CaCO3. In addition, extrinsic labeled cow milk was examined. In the rat, the extrinsic labeled calcium from milk was better absorbed than the intrinsic calcium. This was not the case in goat milk or the calcium carbonate which exhibited no significant differences. Chromatographic analysis of the labeled milk indicates a difference in distribution of the 47Ca. From these data, the authors recommend the use of this assay system in calcium bioavailability studies. The labeling studies and comparisons indicate caution should be used, however, in labeling techniques and species milk comparison

  16. CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Hong Soon Kang

    Full Text Available CD44 is a multifunctional membrane receptor implicated in the regulation of several biological processes, including inflammation. CD44 expression is elevated in liver and white adipose tissue (WAT during obesity suggesting a possible regulatory role for CD44 in metabolic syndrome. To study this hypothesis, we examined the effect of the loss of CD44 expression on the development of various features of metabolic syndrome using CD44 null mice. Our study demonstrates that CD44-deficient mice (CD44KO exhibit a significantly reduced susceptibility to the development of high fat-diet (HFD-induced hepatic steatosis, WAT-associated inflammation, and insulin resistance. The decreased expression of genes involved in fatty acid synthesis and transport (Fasn and Cd36, de novo triglyceride synthesis (Mogat1, and triglyceride accumulation (Cidea, Cidec appears in part responsible for the reduced hepatic lipid accumulation in CD44KO(HFD mice. In addition, the expression of various inflammatory and cell matrix genes, including several chemokines and its receptors, osteopontin, and several matrix metalloproteinases and collagen genes was greatly diminished in CD44KO(HFD liver consistent with reduced inflammation and fibrogenesis. In contrast, lipid accumulation was significantly increased in CD44KO(HFD WAT, whereas inflammation as indicated by the reduced infiltration of macrophages and expression of macrophage marker genes, was significantly diminished in WAT of CD44KO(HFD mice compared to WT(HFD mice. CD44KO(HFD mice remained considerably more insulin sensitive and glucose tolerant than WT(HFD mice and exhibited lower blood insulin levels. Our study indicates that CD44 plays a critical role in regulating several aspects of metabolic syndrome and may provide a new therapeutic target in the management of insulin resistance.

  17. STIM1 is a Calcium Sensor Specialized for Digital Signaling

    OpenAIRE

    Bird, Gary S.; Hwang, Sung-Yong; Smyth, Jeremy T.; Fukushima, Miwako; Boyles, Rebecca R.; Putney, James W.

    2009-01-01

    When cells are activated by calcium-mobilizing agonists at low, physiological concentrations, the resulting calcium signals generally take the form of repetitive regenerative discharges of stored calcium, termed calcium oscillations [1]. These intracellular calcium oscillations have long fascinated biologists as representing a mode of digitized intracellular signaling. Recent work has highlighted the role of calcium influx as an essential component of calcium oscillations [2]. This influx occ...

  18. Relationship of Calcium with Renal, Intestinal and Hormonal Status in Healthy Women

    International Nuclear Information System (INIS)

    The present study was performed on 38 healthy female volunteers to assess the role of renal, intestinal and hormonal control of calcium level in female with different ages. Women were divided into 4 groups: 25-35 years (12 females), 36-43 years (9 females), 44-49 years (10 females) and 55-59 years (7 females). From the fasting blood sample at the mid menstrual cycle (first three groups), the following parameters were determined: Hemoglobin, fasting blood sugar, creatinine, uric acid, calcium, inorganic phosphorus, magnesium, vitamin B12, folic acid, testosterone, progesterone, prolactin, thyroxin, female Follicle stimulating hormone (FSH) ,and Luteinizing hormone LH. Significant increase in uric acid and creatinine, and significant decrease of folic acid and vitamin B12 were detected among the last group. In addition, there are several significant correlations between calcium and other parameters tested in the first three groups while, no any significant correlation was detected in the last group. These results denoted that increased calcium excretion due to partial renal insufficiency in the elder females could play a role in calcium homeostasis rather than intestinal absorption

  19. Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3.

    Directory of Open Access Journals (Sweden)

    Modesto J Remuiñán

    Full Text Available Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB. Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This 'genetic phenotype' was further confirmed by a 'chemical phenotype', whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice.

  20. Software Spectral Correlator for the 44-Element Ooty Radio Telescope

    CERN Document Server

    Prasad, Peeyush

    2011-01-01

    A Spectral Correlator is the main component of the real time signal processing for a Radio Telescope array. The correlation of signals received at each element with every other element of the array is a classic case of an application requiring a complete graph connectivity between its data sources, as well as a very large number of simple operations to carry out the correlation. Datarates can be extremely large in order to achieve high sensitivities required for the detection of weak celestial signals. Hence, correlators are prime targets for HPC implementations. In this paper, we present the design and implementation of a massively parallel software spectral Correlator for a 44 element array. The correlator handles ~735 MB/s of incoming data from the 44 spatially distributed sources, and concurrently sustains a computational load of ~100 Gflops. We first describe how we partition the large incoming data stream into grouped datasets suited for transport over high speed serial networks, as well as ideal for pr...

  1. 44 CFR 206.207 - Administrative and audit requirements.

    Science.gov (United States)

    2010-10-01

    ... administrative requirements of 44 CFR parts 13 and 206; (H) Compliance with the audit requirements of 44 CFR part... in FEMA regulations at 44 CFR part 13 or OMB Circular A-110 as appropriate. (2) Federal audit. In accordance with 44 CFR part 13, FEMA may elect to conduct a Federal audit of the disaster assistance grant...

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

    Science.gov (United States)

    Romanchik-Cerpovicz, Joelle E; McKemie, Rebecca J

    2007-03-01

    Fortification helps provide adequate nutrients for individuals not meeting daily needs. Foods may be fortified with calcium to assist individuals with lactose intolerance and others preferring not to consume traditional forms of dairy. This study examined the quality of all-purpose wheat-flour tortillas fortified with calcium lactate, calcium carbonate, or calcium citrate. These tortillas were compared to similarly prepared nonfortified flour tortillas (control) and commercial nonfortified flour tortillas. Calcium-fortified tortillas contained 114 mg elemental calcium per standard serving (48 g tortilla), an 8.6-fold increase compared to nonfortified tortillas. Moisture contents and rollabilities of all tortillas were similar. Consumers (N=87) evaluated each tortilla in duplicate using a hedonic scale and reported liking the appearance, texture, flavor, aftertaste, and overall acceptability of all tortillas. However, the appearance of control tortillas was preferred over commercial tortillas (Ptortillas or those fortified with calcium carbonate was preferred over the control (Ptortillas, suggesting that appearance and aftertaste may not influence willingness to purchase. Overall, this study shows that fortification of flour tortillas with various forms of calcium is a feasible alternative calcium source. PMID:17324671

  3. Target capture and target ghosts

    Science.gov (United States)

    Auerbach, Steven P.

    1996-05-01

    Optimal detection methods for small targets rely on whitened matched filters, which convolve the measured data with the signal model, and whiten the result with the noise covariance. In real-world implementations of such filters, the noise covariance must be estimated from the data, and the resulting covariance estimate may be corrupted by presence of the target. The resulting loss in SNR is called 'target capture'. Target capture is often thought to be a problem only for bright targets. This presentation shows that target capture also arises for dim targets, leading to an SNR loss which is independent of target strength and depends on the averaging method used to estimate the noise covariance. This loss is due to a 'coherent beat' between the true noise and that portion of the estimated noise covariance due to the target. This beat leads to 'ghost targets', which diminish the target SNR by producing a negative target ghost at the target's position. A quantitative estimate of this effect will be given, and shown to agree with numerical results. The effect of averaging on SNR is also discussed for data scenes with synthetic injected targets, in cases where the noise covariance is estimated using 'no target' data. For these cases, it is shown that the so-called 'optimal' filter, which uses the true noise covariance, is actually worse than a 'sub-optimal' filter which estimates the noise from scene. This apparent contradiction is resolved by showing that the optimal filter is best if the same filter is used for many scenes, but is outperformed by a filter adapted to a specific scene.

  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. PMID:19400592

  5. 44 BWR Waste Package Loading Curve Evaluation

    International Nuclear Information System (INIS)

    The objective of this calculation is to evaluate the required minimum burnup as a function of average initial boiling water reactor (BWR) assembly enrichment that would permit loading of fuel into a potential 44 BWR waste package (WP). The potential WP design is illustrated in Attachment I. The scope of this calculation covers a range of initial enrichments from 1.5 through 5.0 weight percent U-235, and a burnup range of 0 through 50 GWd/mtU

  6. 44 BWR Waste Package Loading Curve Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    J.M. Scaglione

    2001-11-05

    The objective of this calculation is to evaluate the required minimum burnup as a function of average initial boiling water reactor (BWR) assembly enrichment that would permit loading of fuel into a potential 44 BWR waste package (WP). The potential WP design is illustrated in Attachment I. The scope of this calculation covers a range of initial enrichments from 1.5 through 5.0 weight percent U-235, and a burnup range of 0 through 50 GWd/mtU.

  7. LERF Basin 44 Process Test Plan

    Energy Technology Data Exchange (ETDEWEB)

    LUECK, K.J.

    1999-08-31

    This document presents a plan to process a portion of the Liquid Effluent Retention Facility (LERF) Basin 44 wastewater through the 200 Area Effluent Treatment Facility (ETF). The objective of this process test is to determine the most effective/efficient method to treat the wastewater currently stored in LERF Basin 44. The process test will determine the operational parameters necessary to comply with facility effluent discharge permit limits (Ecology 1995) and the Environmental Restoration Disposal Facility (ERDF) acceptance criteria (BHI-00139), while achieving ALARA goals and maintaining the integrity of facility equipment. A major focus of the test plan centers on control of contamination due to leaks and/or facility maintenance. As a pre-startup item, all known leaks will be fixed before the start of the test. During the course of the test, a variety of contamination control measures will be evaluated for implementation during the treatment of the remaining Basin 44 inventory. Of special interest will be techniques and tools used to prevent contamination spread during sampling and when opening contaminated facility equipment/piping. At the conclusion of the test, a post ALARA review will be performed to identify lessons learned from the test run which can be applied to the treatment of the remaining Basin 44 inventory. The volume of wastewater to be treated during this test run is 500,000 gallons. This volume limit is necessary to maintain the ETF radiological inventory limits per the approved authorization basis. The duration of the process test is approximately 30 days.

  8. Biphasic calcium phosphate in periapical surgery

    OpenAIRE

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

    2008-01-01

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

  9. Gravity, Calcium, And Bone: Update, 1989

    Science.gov (United States)

    Arnaud, Sara B.; Morey-Holton, Emily

    1992-01-01

    Report reviews short-term flight and ground-based experiments on effects of 1 g and 0 g on skeletal adaptation, calcium metabolism, and growth processes. Results indicate two principal components of calcium metabolism-calcium endocrine system and bone - respond within days to changes in orientation of body in gravitation and to weightlessness. Effects of spaceflight or bed rest on biomechanics of bones more severe than on total body bone mass.

  10. Gravity, calcium, and bone - Update, 1989

    Science.gov (United States)

    Arnaud, Sara B.; Morey-Holton, Emily

    1990-01-01

    Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

  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...... FHH, while in homozygous patients as well as in compound heterozygous or dominant negative heterozygous patients, it may result in neonatal severe hyperparathyroidism (NSHPT). Parathyroid surgery is not indicated in FHH and does not lower plasma calcium unless total parathyroidectomy is performed, in...

  12. Overbased Calcium sulfonate Detergent Technology Overview

    Institute of Scientific and Technical Information of China (English)

    MA Qing-gao; MUIR Ronald J.

    2009-01-01

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

  13. Calcium carboorthovanadate - a new compound with the apa

    International Nuclear Information System (INIS)

    Data on calcium carboorthovanadate, Ca10(VO4)6CO3, a new compound with an appatite structure based on calcium orthovanadate, are reported. The synthesis has been conducted in a stoichiometric mixture of finely ground calcium carbonate and calcium orthovanadate. It is found that calcium carboorthovanadate belongs to the hexagonal syngony and has an apatite structure. An analysis of the infrared spectra of initial compounds and calcium carboorthovanadate confirmed the presence of carbonate (CO3)2- and orthovanadate (VO4)3 groupings in the latter. On heating in air, beginning with 450 deg C calcium carboorthovanadate decomposes at a slow rate into calcium oxide, calcium orthovanadate, and carbon dioxide

  14. Elastic and inelastic {alpha}-scattering cross-sections obtained with the 44 MeV fixed energy Saclay cyclotron on separated targets of {sup 24}Mg, {sup 25}Mg, {sup 26}Mg, {sup 40}Ca, {sup 46}Ti, {sup 48}Ti, {sup 50}Ti, {sup 52}Cr, {sup 54}Fe, {sup 56}Fe, {sup 58}Fe, {sup 58}Ni, {sup 60}Ni, {sup 62}Ni, {sup 64}Ni, {sup 63}Cu, {sup 65}Cu, {sup 64}Zn, {sup 112}Sn, {sup 114}Sn, {sup 116}Sn, {sup 118}Sn, {sup 120}Sn, {sup 122}Sn, {sup 124}Sn and {sup 208}Pb using the Saclay fixed-energy cyclotron; Sections efficaces differentielles elastiques et inelastiques obtenues par diffusion de particules {alpha} de 44 MeV sur des cibles de {sup 24}Mg, {sup 25}Mg, {sup 26}Mg, {sup 40}Ca, {sup 46}Ti, {sup 48}Ti, {sup 50}Ti, {sup 52}Cr, {sup 54}Fe, {sup 56}Fe, {sup 58}Fe, {sup 58}Ni, {sup 60}Ni, {sup 62}Ni, {sup 64}Ni, {sup 63}Cu, {sup 65}Cu, {sup 64}Zn, {sup 112}Sn, {sup 114}Sn, {sup 116}Sn, {sup 118}Sn, {sup 120}Sn, {sup 122}Sn, {sup 124}Sn et {sup 208}Pb au cyclotron a energie fixe de saclay

    Energy Technology Data Exchange (ETDEWEB)

    Bruge, G. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires. Departement de physique nucleaire, service de physique nucleaire a moyenne energie

    1967-01-01

    This report contains elastic and inelastic {alpha}-scattering cross-sections obtained with the 44 MeV fixed energy Saclay cyclotron on Mg, Ca, Ti, Cr, Fe, Ni, Co, Zn, Sn and Pb enriched targets. (author) [French] Ce rapport contient les tableaux des sections efficaces differentielles obtenues par diffusion elastique et inelastique des particules {alpha} de 44 MeV, fournies par le cyclotron a energie fixe de Saclay, sur des cibles d'isotopes separes de Mg, Ca, Ti, Cr, Fe, Ni, Co, Zn, Sn et Pb. (auteur)

  15. Calcium supplements: do they help or harm?

    Science.gov (United States)

    Manson, Joann E; Bassuk, Shari S

    2014-01-01

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

  16. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be...

  17. Peroxisome is a reservoir of intracellular calcium.

    Science.gov (United States)

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

    2006-07-01

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

  18. How calcium makes endocytic receptors attractive

    DEFF Research Database (Denmark)

    Andersen, Christian B F; Moestrup, Søren K

    2014-01-01

    receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect the...... receptor calcium sites....

  19. Calcium and magnesium silicate hydrates

    International Nuclear Information System (INIS)

    Deep geological disposals are planed to discard long-lived intermediate-level and high-level radioactive wastes. Clay-based geological barriers are expected to limit the ingress of groundwater and to reduce the mobility of radioelements. In the interaction zone between the cement and the clay based material alteration can occur. Magnesium silicate hydrates (M-S-H) have been observed due to the reaction of magnesium sulfate containing groundwater with cements or in the interaction zone between low-pH type cement and clays. M-S-H samples synthesized in the laboratory showed that M-S-H has a variable composition within 0.7 ≤ Mg/Si ≤ 1.5. TEM/EDS analyses show an homogeneous gel with no defined structure. IR and 29Si NMR data reveal a higher polymerization degree of the silica network in M-S-H compared to calcium silicate hydrates (C-S-H). The presence of mainly Q3 silicate tetrahedrons in M-S-H indicates a sheet like or a triple-chain silica structure while C-S-H is characterised by single chain-structure. The clear difference in the silica structure and the larger ionic radius of Ca2+ (1.1 Angstrom) compared to Mg2+ (0.8 Angstrom) make the formation of an extended solid solution between M-S-H and C-S-H gel improbable. In fact, the analyses of synthetic samples containing both magnesium and calcium in various ratios indicate the formation of separate M-S-H and C-S-H gels with no or very little uptake of magnesium in CS-H or calcium in M-S-H

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2005-01-01

    Spontaneous calcium oscillations in mushroom bodies of late stage pupal and adult Drosophila brains have been implicated in memory consolidation during olfactory associative learning. This study explores the cellular mechanisms regulating calcium dynamics in Kenyon cells, principal neurons in mushroom bodies. Fura-2 imaging shows that Kenyon cells cultured from late stage Drosophila pupae generate spontaneous calcium transients in a cell autonomous fashion, at a frequency similar to calcium o...

  3. The Electronic Structure of Calcium

    DEFF Research Database (Denmark)

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

    1981-01-01

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

  4. Physicochemical investigation of calcium bromtechnetate

    International Nuclear Information System (INIS)

    Calcium hexabromotechnetate is extracted for the first time and its composition corresponding to the CaTcBr6 formula is determined. Using the thermal analysis method the anhydrous salt stability boundaries are found. The X-ray phase analysis has shown the compound to be isostructural with (NH4)2TcI6 and has a rhombic b.c.c. crystal lattice with the following parameters: a=10.39+-0.01, b=7.34+-0.01 and c=7.45+-0.001A. At 380-420 deg C CaTcBr6 decomposes to Tc, CaBr2 and Br

  5. Calcium Imaging Perspectives in Plants

    Directory of Open Access Journals (Sweden)

    Chidananda Nagamangala Kanchiswamy

    2014-03-01

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

  6. Barium calcium hydroxyapatite solid solutions

    International Nuclear Information System (INIS)

    The replacement of calcium by barium in the hydroxyapatite structure by solid-state reaction at different temperatures and by precipitation from an aqueous system has been investigated by X-ray diffraction and i.r. absorption analyses. The products obtained by solid-state reaction at 1200 deg C are solid solutions over the range of barium concentration 60 to 100 atom %. The lattice dimensions and the i.r. frequencies of the solid solutions vary linearly with the atom % of barium. Only small amounts of barium can be incorporated in hydroxyapatite by precipitation from the aqueous system. (author)

  7. Calcium

    Science.gov (United States)

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

  8. Calcium

    Science.gov (United States)

    ... eliminates in urine, feces, and sweat. These include consumption of alcohol- and caffeine-containing beverages as well as intake ... and older 2,000 mg Pregnant and breastfeeding teens 3,000 mg Pregnant and breastfeeding adults 2, ...

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

    Institute of Scientific and Technical Information of China (English)

    Wei-chiao CHANG

    2006-01-01

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

  10. ANTIHYPERTENSIVE TREATMENT IN ELDERLY PATIENTS WITH DIHYDROPYRIDINE CALCIUM ANTAGONISTS

    Directory of Open Access Journals (Sweden)

    Y. A. Karpov

    2016-01-01

    Full Text Available The proofs of necessity of active arterial hypertension (AH treatment in elderly patients are given. Peculiarities of pathogenesis of AH in elderly patients, connected predominantly with loss of big arteries elasticity and reasoning widely spread of isolated systolic AH in these patients, are discussed. Advantages of dihydropyridine calcium antagonists (DPCA for AH treatment in elderly patients are proved, safety of treatment with DPCA is discussed. Data of clinical studies is analyzed. Analysis of target levels of blood pressure for antihypertensive treatment in elderly hypertensive patients is made. As a conclusion DPCA are the medicines of choice for AH treatment in elderly patients.

  11. Lung cancer tumorigenicity and drug resistance are maintained through ALDHhiCD44hi tumor initiating cells

    OpenAIRE

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-01-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patien...

  12. The Calcium Triplet metallicity calibration for galactic bulge stars

    CERN Document Server

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

    We investigated the effect of calcium ion on the adsorption of humic acid (HA) (as a target pollutant) by powered activated carbon. The HA adsorption isotherms at different pH and kinetics of two different solutions including HA alone and HA doped Ca(2+), were performed. It was showed that the adsorption capacity of powdered activated carbon (PAC) for HA was markedly enhanced when Ca(2+) was doped into HA. Also, HA and Ca(2+) taken as nitrate were tested on the uptake of each other respectively and it was showed that the adsorbed amounts of both of them were significantly promoted when HA and calcium co-existed. Furthermore, the adsorbed amount of HA slightly decreased with the increasing of Ca(2+) concentration, whereas the amount of calcium increased with the increasing of HA concentration, but all above the amounts without addition. Finally, the change of pH before and after adsorption process is studied. In the two different solutions including HA alone and HA doped Ca(2+), pH had a small rise, but the extent of pH of later solution was bigger. PMID:25078809

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

    International Nuclear Information System (INIS)

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

  15. Functional and pharmacological consequences of the distribution of voltage-gated calcium channels in the renal blood vessels

    DEFF Research Database (Denmark)

    Hansen, P B L

    2013-01-01

    usually associated with vascular contractility. However, the L-, T- and P-/Q-types of calcium channels are present in the renal vasculature and are differentially involved in controlling vascular contractility, thereby contributing to regulation of kidney function and blood pressure. In the preglomerular...... to preferential efferent vasodilation, reduction of glomerular pressure and proteinuria. Therefore, renovascular T-type channels might provide novel therapeutic targets, and may have superior renoprotective effects compared to conventional calcium blockers....

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

    OpenAIRE

    MacKenzie, Elizabeth L.; Tsuji, Yoshiaki

    2008-01-01

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

  17. Differential regulation of calcium signalling pathways by components of Piper methysticum (‘Awa)

    Science.gov (United States)

    Shimoda, L.M.N; Showman, A.; Baker, J.D.; Lange, I.; Koomoa, D.L.; Stokes, A.J.; Borris, R.P.; Turner, H.

    2015-01-01

    Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally-prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally-prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and –insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava. PMID:25640812

  18. Comparison of radioisotopic studied calcium metabolism in the orally administered and inhaled cadmium rat

    International Nuclear Information System (INIS)

    The radioisotopic study of calcium metabolism in the rat after oral administration of cadmium, 8 mg/kg during 13 weeks, has shown two different effects of this ion: 1) in the intestine, cadmium inhibits the absorption of calcium by active transport; 2) in the deep bone compartment, the decrease of the bone calcium used for the crystallization and slowly exchangeable with the calcium central pool (serum, extracellular and soft tissues calcium) is combined with a reduction of the exchange rates between the two compartments. When administered through a microparticle aerosol inhalation (1 mg/m3 of air, 30 mn a day, during 12 weeks), cadmium's main target organ is the deep bone compartment. For both modes of administration, the slowing down of osteogenesis is confirmed by a drop in serum alkaline phosphatase after a four weeks period which reflects a decrease of the osteoblastic activity. Therefore it appears that the effects on bones observed during the chronic oral cadmium administration, do not result from a malabsorption of intestine calcium but also from the very action the Cd++ ion on the bone crystallization process

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  20. Calcium and Vitamin D: Important at Every Age

    Science.gov (United States)

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

  1. Clinical validation of dialysable calcium in relation to other methods of serum calcium measurement.

    OpenAIRE

    Prince, R. L.; Langton, S R

    1985-01-01

    Dialysable calcium (CaD) values were measured by a simple technique not interfered with by protein bound calcium and validation attempted by comparison with concentrations of ionised calcium (CaI) and clinical categorisation. CaD values were also compared with total calcium (CaT) and albumin adjusted calcium (CaA) concentrations. The normal ranges for CaD, CaT, CaA, and CaI were calculated from the results in healthy blood donors. In 50 normal subjects CaD was more highly correlated with CaI ...

  2. An Intracellular Calcium Oscillations Model Including Mitochondrial Calcium Cycling

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-Min; LIU Zeng-Rong

    2005-01-01

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

  3. Low-energy electron scattering from calcium

    International Nuclear Information System (INIS)

    Full text: The B-spline R-matrix method (BSR) is used to investigate the integrated cross sections (ICS) of elastic electron scattering from neutral calcium in the ultra-low energy range from threshold to 0.5 eV. The close-coupling expansion includes 39 bound states of neutral calcium, covering all states from the ground state to 4s8s 1S. The computational model was described in detail. Briefly, we generate an accurate target description by using multiconfiguration expansions, accounting for both valence and core-valence correlations. Very importantly, we use term-dependent valence orbitals, which are optimized individually for the various states of interest. We also account for relaxation of the core orbitals, due to the deep penetration of the 3d orbital. As a result, we have a set of normalized orthogonal one-electron orbitals for each state, but the orbitals from different sets do not form an orthonormal basis. In this work we compared the total and partial electron-impact cross sections from Ca in the ultra-low energy region, calculated in two different R-matrix approaches: the present BSR method and R-matrix with pseudostates method (RMPS). As seen from our calculations, basic difference between the cross sections in two R-matrix approaches comes mainly from the dominated 2Po partial wave. In the same time, partial cross sections for the 2Se and 2De partial waves in these two methods practically coincide. In the present work we also have compared the total BSR39 and RMPS cross sections with experimental data of Romaniuk et al.. Overall, the agreement between both R-matrix (BSR39 and RMPS) results and the experimental data is satisfactory, although a few discrepancies remain. We have compared 2Se, 2Po and 2De partial eigen-phases of electron-impact scattering from Ca at low energies region between most recent calculations: BSR39 (the present calculation), RMPS and the method of static-exchange formalism. Again, the largest discrepancy between different methods

  4. Bone Up on the Need for Calcium.

    Science.gov (United States)

    Mann, Peggy

    1987-01-01

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

  5. 21 CFR 182.8217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

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

  6. 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.

  7. Calcium Free Asbestos for Fuel Cells

    Science.gov (United States)

    Snitzer, B. A.

    1983-01-01

    Organic-acid salt removes unwanted calcium without weakening asbestos. Asbestos mixed with disodium ethylene diamine tetraacetic acid (disodium EDTA) in water and agitated for 2 hours. After disodium EDTA solution is drained away, asbestos contains only 0.02 to 0.1 percent calcium. Fiber structure of asbestos unaffected.

  8. Stochastic models of intracellular calcium signals

    International Nuclear Information System (INIS)

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

  9. Stochastic Kinetics of Intracellular Calcium Oscillations

    Institute of Scientific and Technical Information of China (English)

    陈昌胜; 曾仁端

    2003-01-01

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

  10. 21 CFR 172.410 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium silicate. 172.410 Section 172.410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Anticaking Agents § 172.410 Calcium...

  11. Engineering calcium oxalate crystal formation in Arabidopsis

    Science.gov (United States)

    Many plants accumulate crystals of calcium oxalate. Just how these crystals form remains unknown. To gain insight into the mechanisms regulating calcium oxalate crystal formation, a crystal engineering approach was initiated utilizing the non-crystal accumulating plant, Arabidopsis. The success of t...

  12. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-10

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

  13. Particularities of thermal expansion of calcium vanadates

    International Nuclear Information System (INIS)

    Temperature dependence of unit cell parameters of calcium vanadates Ca(VO3)2, Ca2V2O7 and Ca3(VO4)2 is studied. It is shown that lattice parameters of meta- and pyrovanadates change monotonously. Lattice parameters of calcium orthovanadate change sharply and unmonotonously at 400-500 deg C

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  16. Functional Differences Between Human NKp44— and NKp44+ RORC+ Innate Lymphoid Cells

    Directory of Open Access Journals (Sweden)

    Kerim eHoorweg

    2012-04-01

    Full Text Available Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC that participate in innate and adaptive immune responses as well as in lymphoid tissue (re modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells differentially produce IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44— IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the second trimester. NKp44— ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC have the capacity to swiftly initiate cytokine transcription indicating that secondary human lymphoid organs function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  17. Experiments on the formation of titanium-44 in supernovae

    International Nuclear Information System (INIS)

    In this thesis the astrophysically interesting resonance triplet of the 40Ca(α,γ)44Ti reaction at 4.5 MeV has been studied. For this purpose energies of proton and α beams provided by 3 MV Tandetron at Helmholtz-Zentrum Dresden-Rossendorf have been calibrated. Excitation functions of energy regions near the resonances and in-beam spectra of four different targets have been measured. The 40Ca(p,γ)41Sc reaction has been used to scan the structure of the activated targets. Afterwards their activity has been measured in the underground laboratory Felsenkeller Dresden. Hence the sum of resonance strengths at laboratory α energies of 4497 and 4510 keV of (12.8±2.3) eV has been determined as well as the sum of the total triplet strength, including 4523 keV, of (12.0±2.0) eV. In the case of the first resonance, the uncertainty was decreased from 19% to 18 %. Furthermore the results of this work establish a basis for reaching much lower uncertainties in the future.

  18. 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...

  19. Alpha-1 giardin is an annexin with highly unusual calcium-regulated mechanisms.

    Science.gov (United States)

    Weeratunga, Saroja K; Osman, Asiah; Hu, Nien-Jen; Wang, Conan K; Mason, Lyndel; Svärd, Staffan; Hope, Greg; Jones, Malcolm K; Hofmann, Andreas

    2012-10-19

    Alpha-giardins constitute the annexin proteome (group E annexins) in the intestinal protozoan parasite Giardia and, as such, represent the evolutionary oldest eukaryotic annexins. The dominance of alpha-giardins in the cytoskeleton of Giardia with its greatly reduced actin content emphasises the importance of the alpha-giardins for the structural integrity of the parasite, which is particularly critical in the transformation stage between cyst and trophozoite. In this study, we report the crystal structures of the apo- and calcium-bound forms of α1-giardin, a protein localised to the plasma membrane of Giardia trophozoites that has recently been identified as a vaccine target. The calcium-bound crystal structure of α1-giardin revealed the presence of a type III site in the first repeat as known from other annexin structures, as well as a novel calcium binding site situated between repeats I and IV. By means of comparison, the crystal structures of three different alpha-giardins known to date indicate that these proteins engage different calcium coordination schemes, among each other, as well as compared to annexins of groups A-D. Evaluation of the calcium-dependent binding to acidic phosphoplipid membranes revealed that this process is not only mediated but also regulated by the environmental calcium concentration. Uniquely within the large family of annexins, α1-giardin disengages from the phospholipid membrane at high calcium concentrations possibly due to formation of a dimeric species. The observed behaviour is in line with changing calcium levels experienced by the parasite during excystation and may thus provide first insights into the molecular mechanisms underpinning the transformation and survival of the parasite in the host. PMID:22796298

  20. MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes

    Science.gov (United States)

    Wu, Junnan; Zheng, Chunxia; Wang, Xiao; Yun, Shifeng; Zhao, Yue; Liu, Lin; Lu, Yuqiu; Ye, Yuting; Zhu, Xiaodong; Zhang, Changming; Shi, Shaolin; Liu, Zhihong

    2015-01-01

    Calcium/calcineurin signaling is critical for normal cellular physiology. Abnormalities in this pathway cause many diseases, including podocytopathy; therefore, understanding the mechanisms that underlie the regulation of calcium/calcineurin signaling is essential. Here, we showed that critical components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s). We found that these 5 genes are highly expressed as mRNA, but the level of the proteins is low in normal podocytes. Conversely, protein levels were markedly elevated in podocytes from rats treated with puromycin aminonucleoside (PAN) and from patients with focal segmental glomerulosclerosis (FSGS). In both FSGS patients and PAN-treated rats, miR-30s were downregulated in podocytes. In cultured podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and calcineurin activity. Moreover, NFATC3 nuclear translocation, synaptopodin degradation, integrin β3 (ITGB3) activation, and actin fiber loss, which are downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but blocked by the calcineurin inhibitor FK506. Podocyte-specific expression of the miR-30 sponge in mice increased calcium/calcineurin pathway component protein expression and calcineurin activity. The mice developed podocyte foot process effacement and proteinuria, which were prevented by FK506. miR-30s also regulated calcium/calcineurin signaling in cardiomyocytes. Together, our results identify miR-30s as essential regulators of calcium/calcineurin signaling. PMID:26436650