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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. 44gSc from metal calcium targets for PET

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  3. 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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

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

    2016-10-01

    We produced (43)Sc and (47)Sc via the (nat/44)Ca(α,x)-channel using a vertical beam coupled with a ceramic target box. After activation, the powdery CaO target material was dissolved in HCl in the target box in situ and remotely recovered as a radio-Sc solution. The respective yields of (43)Sc and (47)Sc following isolation via a precipitation method with a typical 0.22µm sterile filter were 54.8MBq/µAh (1.48mCi/µAh) and 780kBq/µAh (21.1µCi/µAh) at the end of separation (approximately 1.5h from the EOB). In addition, we discuss the recycling of target Ca. PMID:27472825

  6. 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

  7. 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)

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

    Science.gov (United States)

    Bonora, Massimo; Giorgi, Carlotta; Pinton, Paolo

    2015-09-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Brian L Jones

    2016-03-01

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

  11. 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.

  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. 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)

  14. 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.

  15. Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells

    Science.gov (United States)

    Hayward, Stephen L.; Wilson, Christina L.; Kidambi, Srivatsan

    2016-01-01

    Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study the uptake pathway in key cells in the brain including primary astrocytes, microglia, and human GBM cells. We observed that the HALNPs specifically target GBM cells over other brain cells due to higher expression of CD44 in tumor cells. Furthermore, CD44 driven HALNP uptake into GBM cells resulted in lysosomal evasion and increased efficacy of Doxorubicin, a model anti-neoplastic agent, while the astrocytes and microglia cells exhibited extensive HALNP-lysosome co-localization and decreased antineoplastic potency. In summary, novel CD44 targeted lipid based nanocarriers appear to be proficient in mediating site-specific delivery of drugs via CD44 receptors in GBM cells, with an improved therapeutic margin and safety. PMID:27120809

  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.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Vedrana eTadic

    2014-05-01

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

  20. Reaction rate sensitivity of 44Ti production in massive stars and implications of a thick target yield measurement of 40Ca(alpha,gamma)44Ti

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, R D; Sheets, S A; Burke, J T; Scielzo, N D; Rauscher, T; Norman, E B; Tumey, S; Brown, T A; Grant, P G; Hurst, A M; Phair, L; Stoyer, M A; Wooddy, T; Fisker, J L; Bleuel, D

    2010-02-16

    We evaluate two dominant nuclear reaction rates and their uncertainties that affect {sup 44}Ti production in explosive nucleosynthesis. Experimentally we develop thick-target yields for the {sup 40}Ca({alpha},{gamma}){sup 44}Ti reaction at E{sub {alpha}} = 4.13, 4.54, and 5.36 MeV using {gamma}-ray spectroscopy. At the highest beam energy, we also performed an activation measurement which agrees with the thick target result. From the measured yields a stellar reaction rate was developed that is smaller than current statistical-model calculations and recent experimental results, which would suggest lower {sup 44}Ti production in scenarios for the {alpha}-rich freeze out. Special attention has been paid to assessing realistic uncertainties of stellar reaction rates produced from a combination of experimental and theoretical cross sections. With such methods, we also develop a re-evaluation of the {sup 44}Ti({alpha},p){sup 47}V reaction rate. Using these two rates we carry out a sensitivity survey of {sup 44}Ti synthesis in eight expansions representing peak temperature and density conditions drawn from a suite of recent supernova explosion models. Our results suggest that the current uncertainty in these two reaction rates could lead to as large an uncertainty in {sup 44}Ti synthesis as that produced by different treatments of stellar physics.

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

    Science.gov (United States)

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

    2016-03-15

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

  2. 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

  3. 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...

  4. 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.

  5. 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.

  6. 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

  7. Lipid-based nanosystems for CD44 targeting in cancer treatment: recent significant advances, ongoing challenges and unmet needs.

    Science.gov (United States)

    Nascimento, Thais Leite; Hillaireau, Hervé; Vergnaud, Juliette; Fattal, Elias

    2016-07-01

    Extensive experimental evidence demonstrates the important role of hyaluronic acid (HA)-CD44 interaction in cell proliferation and migration, inflammation and tumor growth. Taking advantage of this interaction, the design of HA-modified nanocarriers has been investigated for targeting CD44-overexpressing cells with the purpose of delivering drugs to cancer or inflammatory cells. The effect of such modification on targeting efficacy is influenced by several factors. In this review, we focus on the impact of HA-modification on the characteristics of lipid-based nanoparticles. We try to understand how these modifications influence particle physicochemical properties, interaction with CD44 receptors, intracellular trafficking pathways, toxicity, complement/macrophage activation and pharmacokinetics. Our aim is to provide insight in tailoring particle modification by HA in order to design more efficient CD44-targeting lipid nanocarriers.

  8. 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.

  9. 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.

  10. The Interplay of Antigen Affinity, Internalization, and Pharmacokinetics on CD44-Positive Tumor Targeting of Monoclonal Antibodies.

    Science.gov (United States)

    Glatt, Dylan M; Beckford Vera, Denis R; Parrott, Matthew C; Luft, J Christopher; Benhabbour, S Rahima; Mumper, Russell J

    2016-06-01

    Monoclonal antibodies (mAbs) offer promise as effective tumor targeting and drug delivery agents for cancer therapy. However, comparative biological and clinical characteristics of mAbs targeting the same tumor-associated antigen (TAA) often differ widely. This study examined the characteristics of mAbs that impact tumor targeting using a panel of mAb clones specific to the cancer-associated cell-surface receptor and cancer stem cell marker CD44. CD44 mAbs were screened for cell-surface binding, antigen affinity, internalization, and CD44-mediated tumor uptake by CD44-positive A549 cells. It was hypothesized that high-affinity, rapidly internalizing CD44 mAbs would result in high tumor uptake and prolonged tumor retention. Although high-affinity clones rapidly bound and were internalized by A549 cells in vitro, an intermediate-affinity clone demonstrated significantly greater tumor uptake and retention than high-affinity clones in vivo. Systemic exposure, rather than high antigen affinity or rapid internalization, best associated with tumor targeting of CD44 mAbs in A549 tumor-bearing mice. PMID:27079967

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

    Science.gov (United States)

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

    2013-06-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

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

  19. 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.

  20. 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

  1. 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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

  3. 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.)

  4. Pinoresinol-4,4'-di-O-beta-D-glucoside from Valeriana officinalis root stimulates calcium mobilization and chemotactic migration of mouse embryo fibroblasts.

    Science.gov (United States)

    Do, Kee Hun; Choi, Young Whan; Kim, Eun Kyoung; Yun, Sung Ji; Kim, Min Sung; Lee, Sun Young; Ha, Jung Min; Kim, Jae Ho; Kim, Chi Dae; Son, Beung Gu; Kang, Jum Soon; Khan, Ikhlas A; Bae, Sun Sik

    2009-06-01

    Lignans are major constituents of plant extracts and have important pharmacological effects on mammalian cells. Here we showed that pinoresinol-4,4'-di-O-beta-D-glucoside (PDG) from Valeriana officinalis induced calcium mobilization and cell migration through the activation of lysophosphatidic acid (LPA) receptor subtypes. Stimulation of mouse embryo fibroblast (MEF) cells with 10 microM PDG resulted in strong stimulation of MEF cell migration and the EC(50) was about 2 microM. Pretreatment with pertussis toxin (PTX), an inhibitor of G(i) protein, completely blocked PDG-induced cell migration demonstrating that PDG evokes MEF cell migration through the activation of the G(i)-coupled receptor. Furthermore, pretreatment of MEF cells with Ki16425 (10 microM), which is a selective antagonist for LPA(1) and LPA(3) receptors, completely blocked PDG-induced cell migration. Likewise, PDG strongly induced calcium mobilization, which was also blocked by Ki16425 in a dose-dependent manner. Prior occupation of the LPA receptor with LPA itself completely blocked PDG-induced calcium mobilization. Finally, PDG-induced MEF cell migration was attenuated by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor such as LY294002. Cells lacking downstream mediator of PI3K such as Akt1 and Akt2 (DKO cells) showed loss of PDG-induced migration. Re-expression of Akt1 (but not Akt2) completely restored PDG-induced DKO cell migration. Given these results, we conclude that PDG is a strong inducer of cell migration. We suggest that the pharmacological action of PDG may occur through the activation of an LPA receptor whereby activation of PI3K/Akt signaling pathway mediates PDG-induced MEF cell migration.

  5. 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.

  6. 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

  7. 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

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

    Science.gov (United States)

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

    2015-03-10

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

  9. 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

  10. 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.

  11. 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...

  12. 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.

  13. 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

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

    Science.gov (United States)

    Coxam, Véronique

    2007-11-01

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

  15. 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..

  16. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  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. 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.

  7. 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...

  8. 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.

  9. 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

    Our ability to design receptor-targeted nanocarriers aimed at drug release after endocytosis is limited by the current knowledge of intracellular nanoparticle (NP) trafficking. It is not clear if NP size, surface chemistry, and/or targeting of cell surface receptors changes the intracellular fate...

  10. 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

  11. 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

  12. 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...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2014-01-22

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

  17. 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

  18. 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

  19. 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

  20. 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

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

    Science.gov (United States)

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

    2015-07-17

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

  2. Calcium signaling and epilepsy.

    Science.gov (United States)

    Steinlein, Ortrud K

    2014-08-01

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

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

    Science.gov (United States)

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

    2016-01-19

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

  4. 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 ...

  5. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Jin Ock Kim

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

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

    Science.gov (United States)

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

    2015-11-13

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

  8. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Science.gov (United States)

    Maisel, Daniela; Birzele, Fabian; Voss, Edgar; Nopora, Adam; Bader, Sabine; Friess, Thomas; Goller, Bernhard; Laifenfeld, Daphna; Weigand, Stefan; Runza, Valeria

    2016-01-01

    CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages. PMID:27463372

  9. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Directory of Open Access Journals (Sweden)

    Daniela Maisel

    Full Text Available CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP of the malignant cells by macrophages.

  10. 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

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

    Science.gov (United States)

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

    2016-03-01

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

  12. 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

  13. 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

  14. 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 ...

  15. 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.

  16. 40 CFR 424.44-424.46 - [Reserved

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true 424.44-424.46 Section 424.44-424.46 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air...

  17. 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 ...

  18. 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 ...

  19. 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

  20. 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

  1. 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. ...

  2. 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 ...

  3. 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 ...

  4. 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

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

    OpenAIRE

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

    2012-01-01

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

  6. 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.

  7. 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.

  8. Altered calcium signaling in cancer cells.

    Science.gov (United States)

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

    2015-10-01

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

  9. Calcium source (image)

    Science.gov (United States)

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

  10. Calcium hydroxide poisoning

    Science.gov (United States)

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

  11. Calcium and bones (image)

    Science.gov (United States)

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

  12. Coronary Calcium Scan

    Science.gov (United States)

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

  13. Calcium Pyrophosphate Deposition (CPPD)

    Science.gov (United States)

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

  14. Calcium channel as a potential anticancer agent.

    Science.gov (United States)

    Kriazhev, L

    2009-11-01

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

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

    Science.gov (United States)

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

    2012-11-01

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

  16. 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 ...

  17. A modular approach to marine macrolide construction. 4. Assembly of C36-C51 and C29-C44 building blocks and evaluation of key coupling reactions targeting spongistatin 1 (altohyrtin A).

    Science.gov (United States)

    Ciblat, Stephane; Kim, Jungchul; Stewart, Catherine A; Wang, Jizhou; Forgione, Pat; Clyne, Dean; Paquette, Leo A

    2007-02-15

    Routes have been developed for the stereocontrolled elaboration of two highly functionalized sectors of spongistatin 1. The approach to ring F takes advantage of B-alkyl Suzuki-Miyaura coupling to install the C44-C45 bond. The E-ring pyran moiety was generated by acylation of an alpha-sulfonyl carbanion, the stereogenic centers of which were incorporated by sequential asymmetric aldol reactions. [structure: see text].

  18. 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...

  19. 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 ...

  20. 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 ...

  1. Environmental geochemistry of calcium isotopes: Applications of a new stable isotope approach

    Institute of Scientific and Technical Information of China (English)

    LIU Zhanmin; LIU Congqiang; HAN Guilin; WANG Zhongliang; XUE Zichen; SONG Zhaoliang; YANG Cheng

    2006-01-01

    This paper summarizes isotope fractionation mechanism, analytical method and applications in environmental geochemistry of calcium isotopes. Calcium isotopic composition can be used to constrain material sources and study geological and environmental processes as the isotopic composition of calcium44Ca) and fractionation processes depend on geochemical circumstances in nature. Recently, thanks to current advances in analytical technology of calcium isotopes, calcium isotopes are broadly used in biological and geochemical studies, such as the mechanism of plants imbibing nutrients through their roots, calcium transport in the environmental ecosystem, calcium cycle in oceans and paleo-oceans and paleo-climate. The elementary data show that δ44Ca values vary from -2.88‰ to 0.92‰ in natural samples.

  2. 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.

  3. 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

  4. 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.

  5. 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 ...

  6. 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.

  7. 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.

  8. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yi-Wen Hsieh

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

  17. 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...

  18. 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...

  19. 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

  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. 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

  2. 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

  3. 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)

  4. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

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

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone...... and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport...

  5. 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)

  6. [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

  7. 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.

  8. 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.

  9. Identification and characterization of RBM44 as a novel intercellular bridge protein.

    Directory of Open Access Journals (Sweden)

    Tokuko Iwamori

    Full Text Available Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells. We previously reported the identification of TEX14 as the first essential intercellular bridge protein, the demonstration that intercellular bridges are required for male fertility, and the finding that intercellular bridges utilize components of the cytokinesis machinery to form. Herein, we report the identification of RNA binding motif protein 44 (RBM44 as a novel germ cell intercellular bridge protein. RBM44 was identified by proteomic analysis after intercellular bridge enrichment using TEX14 as a marker protein. RBM44 is highly conserved between mouse and human and contains an RNA recognition motif of unknown function. RBM44 mRNA is enriched in testis, and immunofluorescence confirms that RBM44 is an intercellular bridge component. However, RBM44 only partially localizes to TEX14-positive intercellular bridges. RBM44 is expressed most highly in pachytene and secondary spermatocytes, but disappears abruptly in spermatids. We discovered that RBM44 interacts with itself and TEX14 using yeast two-hybrid, mammalian two-hybrid, and immunoprecipitation. To define the in vivo function of RBM44, we generated a targeted deletion of Rbm44 in mice. Rbm44 null male mice produce somewhat increased sperm, and show enhanced fertility of unknown etiology. Thus, although RBM44 localizes to intercellular bridges during meiosis, RBM44 is not required for fertility in contrast to TEX14.

  10. 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

  11. 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.

  12. 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...

  13. 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 di...

  14. Effect of nano-calcium-enriched milk on calcium metabolism in ovariectomized rats.

    Science.gov (United States)

    Park, Heung-Sik; Ahn, Joungjwa; Kwak, Hae-Soo

    2008-09-01

    This study was designed to examine the effect of different kinds of calcium enrichment on serum and urine indices of mineral status in ovariectomized rats. Twenty-four 7-week-old Sprague-Dawley female rats were divided into four groups, ovariectomized, and fed diets containing the following: (1) Control, non-Ca-enriched milk; (2) OVX1, calcium carbonate-enriched milk; (3) OVX2, ionized Ca-enriched milk; and (4) OVX3, nano-Ca-enriched milk. After 18 weeks of feeding, the food efficiency ratio in the nano-Ca-fed group was significantly lower compared with those in the Control and OVX2 groups. There was no difference in serum and fecal Ca among the groups. The bone/total alkaline phosphatase ratio was significantly higher in rats fed milk enriched with nano-Ca (59%) and calcium carbonate (62%) than in control (44%) animals. Urinary Ca was the highest in the nano-Ca-enriched group; however, urinary excretions of deoxypyridinoline and hydroxyproline were significantly decreased in the nano-Ca-enriched group. The present results indicate that consumption of nano-Ca-enriched milk resulted in an increase of urinary excretion of calcium and a decrease in deoxypyridinoline and hydroxyproline in ovariectomized rats.

  15. 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...

  16. 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.

  17. 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 ...

  18. 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

  19. 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...

  20. Calcium aluminate in alumina

    Science.gov (United States)

    Altay, Arzu

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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. Calcium signaling in taste cells.

    Science.gov (United States)

    Medler, Kathryn F

    2015-09-01

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

  8. Expert review on coronary calcium

    Directory of Open Access Journals (Sweden)

    Matthew J Budoff

    2008-04-01

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

  9. Fruit Calcium: Transport and Physiology

    Directory of Open Access Journals (Sweden)

    Bradleigh eHocking

    2016-04-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

  11. 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 ...

  12. 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.

  13. 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...

  14. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2005-01-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  16. ERP44 inhibits human lung cancer cell migration mainly via IP3R2.

    Science.gov (United States)

    Huang, Xue; Jin, Meng; Chen, Ying-Xiao; Wang, Jun; Zhai, Kui; Chang, Yan; Yuan, Qi; Yao, Kai-Tai; Ji, Guangju

    2016-06-01

    Cancer cell migration is involved in tumour metastasis. However, the relationship between calcium signalling and cancer migration is not well elucidated. In this study, we used the human lung adenocarcinoma A549 cell line to examine the role of endoplasmic reticulum protein 44 (ERP44), which has been reported to regulate calcium release inside of the endoplasmic reticulum (ER), in cell migration. We found that the inositol 1,4,5-trisphosphate receptors (IP3Rs/ITPRs) inhibitor 2-APB significantly inhibited A549 cell migration by inhibiting cell polarization and pseudopodium protrusion, which suggests that Ca2+ is necessary for A549 cell migration. Similarly, the overexpression of ERP44 reduced intracellular Ca2+ release via IP3Rs, altered cell morphology and significantly inhibited the migration of A549 cells. These phenomena were primarily dependent on IP3R2 because wound healing in A549 cells with IP3R2 rather than IP3R1 or IP3R3 siRNA was markedly inhibited. Moreover, the overexpression of ERP44 did not affect the migration of the human neuroblastoma cell line SH-SY5Y, which mainly expresses IP3R1. Based on the above observations, we conclude that ERP44 regulates A549 cell migration mainly via an IP3R2-dependent pathway.

  17. Relation between tipburn appearance of Chinese cabbage and calcium content and location

    Directory of Open Access Journals (Sweden)

    Jan Borkowski

    2013-12-01

    Full Text Available In 2000-2001 investigations were carried out on the dependence between the tipburn appearance on Chinese cabbage and the content of calcium and its distribution in leaves. It was found that the highest concentration of calcium (to 4,4% occurred in outside leaves and the lowest was found in leaves inside the head (to 1,0 %. The marginal part in every outside leaf contained more calcium than midrib of leaf. This dependence weakly appeared in leaves wrapping the head and was absent inside the head, where often the calcium concentration was higher in the midrib part of leaf than in the margin part. Distinct differences in the calcium content in leaves of four culti vars of F1, Chinese cabbage: ´Bilko', ´Parkin', 'Kasumi' and 'Yamiko' were not found. These cultivars differed clearly in the susceptibility to the tipburn incidence which appearance depended also on the temperature stress.

  18. 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...

  19. 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...

  20. 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 Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Control § 930.44 Quality control. (a) Quality standards. The Board may establish, with the approval of...

  1. 44 CFR 206.438 - Project management.

    Science.gov (United States)

    2010-10-01

    ... management and accountability of funds as indicated in 44 CFR part 13. The State is responsible for ensuring... in 44 CFR part 13 apply to all grant assistance provided under this subpart. FEMA may elect to... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Project management....

  2. 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 Secretary of Labor PROCESS FOR ELECTING STATE AGENCY EMPLOYMENT STATISTICS REPRESENTATIVES FOR CONSULTATIONS WITH DEPARTMENT OF LABOR § 44.3 Election process. (a) Process. The Commissioner of Labor Statistics...

  3. 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... organisms present in growing portions of the reef. (b) Possible loss of values: The discharge of dredged...

  4. 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...

  5. 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...

  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. 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...

  8. 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....

  9. 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...

  10. 7 CFR 2902.44 - Corrosion preventatives.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Corrosion preventatives. 2902.44 Section 2902.44... Items § 2902.44 Corrosion preventatives. (a) Definition. Products designed to prevent the deterioration (corrosion) of metals. (b) Minimum biobased content. The preferred procurement product must have a...

  11. 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...

  12. 34 CFR 675.44 - Program description.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Program description. 675.44 Section 675.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL WORK-STUDY PROGRAMS Work-Colleges Program § 675.44 Program description....

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

    Directory of Open Access Journals (Sweden)

    Stefan Mihalas

    2011-01-01

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

  14. 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

  15. 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.

  16. 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.

  17. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid

    2013-07-01

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

  18. 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......

  19. 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...

  20. 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...

  1. 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

  2. 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...

  3. Hybrid calcium phosphate coatings for implants

    Science.gov (United States)

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

    2016-08-01

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

  4. 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.

  5. Molecular mechanisms of crystallization impacting calcium phosphate cements

    Science.gov (United States)

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

    2010-01-01

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

  6. 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...

  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 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.

  9. 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 ...

  10. 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 ...

  11. 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

  12. 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.

  13. 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...

  14. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

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

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...... in the char conversion process. Comprehensive global equilibrium calculations predicted important characteristics of the inorganic ash residue. Equilibrium calculations predict the formation of liquid salt if sufficient amounts of Ca are added and according to experiments as well as calculations calcium binds...

  15. 28 CFR 44.101 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Definitions. 44.101 Section 44.101... General § 44.101 Definitions. (a) Charge means a written statement under oath or affirmation that— (1... 8 U.S.C. 1255a(a)(1); (C) Admitted as a refugee under 8 U.S.C. 1157; or (D) Granted asylum under 8...

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

    Directory of Open Access Journals (Sweden)

    Borje E. Christopher Nordin

    2010-09-01

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

  17. 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...

  18. 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...

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

    Science.gov (United States)

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

    1996-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  1. 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

  2. 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.

  3. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    Science.gov (United States)

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

    2013-10-01

    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 patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  4. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness. PMID:7488645

  5. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

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

  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. 44 CFR 206.200 - General.

    Science.gov (United States)

    2010-10-01

    ... to State and Local Governments,” published at 44 CFR part 13, place requirements on the State in its... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false General. 206.200 Section 206.200 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF...

  8. 44 CFR 206.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... and emergencies declared by the President before November 23, 1988 were published in 44 CFR part 205... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 206.1 Section 206.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND...

  9. 44 CFR 71.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... structure prior to November 16, 1990; and (2) The start of construction (see 44 CFR part 59) took place... as by a private sector insurance company under the Write Your Own Program as authorized by 44 CFR... 18, 1982, and as of November 16, 1990, is “new construction” unless it meets the following...

  10. 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...

  11. 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)

  12. 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...

  13. 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...

  14. 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...

  15. 48 CFR 44.204 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ... contract, awarded on the basis of adequate price competition or whose prices are set by law or regulation... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract clauses. 44.204 Section 44.204 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT...

  16. 27 CFR 44.249 - Lottery features.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Lottery features. 44.249... Requirements § 44.249 Lottery features. No certificate, coupon, or other device purporting to be or to represent a ticket, chance, share, or an interest in, or dependent on, the event of a lottery shall...

  17. 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...

  18. 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... notice thereof has been sent to the parties, the Administrative Law Judge may make a decision against...

  19. 7 CFR 906.44 - Safeguards.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Safeguards. 906.44 Section 906.44 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... pursuant to § 906.41 or § 906.42 from entering channels of trade for other than the specific...

  20. 19 CFR 151.44 - Storage tanks.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Storage tanks. 151.44 Section 151.44 Customs... Storage tanks. (a) Plans and gauge tables. When petroleum or petroleum products subject to duty at a specific rate per barrel are imported in bulk in tank vessels and are to be transferred into shore...

  1. 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)

  2. Biodegradable magnetic calcium phosphate nanoformulation for cancer therapy.

    Science.gov (United States)

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

    2014-05-01

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

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

    Science.gov (United States)

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong; Zhou, Xianguang; Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing; Wang, Jiandong; Zhang, Longjiang; Teng, Zhaogang; Lu, Guangming

    2015-03-01

    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.

  4. 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

  5. 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

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

    Science.gov (United States)

    Hool, Livia C; Corry, Ben

    2007-04-01

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

  7. 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

  8. 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

  9. Are Ti44-Producing Supernovae Exceptional?

    CERN Document Server

    The, L S; Diehl, R; Hartmann, D H; Iyudin, A F; Leising, M D; Meyer, B S; Motizuki, Y; Schönfelder, V

    2006-01-01

    According to standard models supernovae produce radioactive $^{44}$Ti, which should be visible in gamma-rays following decay to $^{44}$Ca for a few centuries. $^{44}Ti production is believed to be the source of cosmic $^{44}$Ca, whose abundance is well established. Yet, gamma-ray telescopes have not seen the expected young remnants of core collapse events. The $^{44}$Ti mean life of $\\tau \\simeq$ 89 y and the Galactic supernova rate of $\\simeq$ 3/100 y imply $\\simeq$ several detectable $^{44}Ti gamma-ray sources, but only one is clearly seen, the 340-year-old Cas A SNR. Furthermore, supernovae which produce much $^{44}Ti are expected to occur primarily in the inner part of the Galaxy, where young massive stars are most abundant. Because the Galaxy is transparent to gamma-rays, this should be the dominant location of expected gamma-ray sources. Yet the Cas A SNR as the only one source is located far from the inner Galaxy (at longitude 112 degree). We evaluate the surprising absence of detectable supernovae fro...

  10. 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.

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

    Science.gov (United States)

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

    2007-02-01

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

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Allison Sargoy

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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Mitochondrial calcium uptake.

    Science.gov (United States)

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

    2013-06-25

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

  1. 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...

  2. 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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  4. Aggregation of Phosphoinositides at Phisiological Calcium Concentrations

    Science.gov (United States)

    Kazadi Badiambile, Adolphe; Forstner, Martin B.

    2012-02-01

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

  5. 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...

  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. 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

  8. 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

  9. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  10. 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.

  11. 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

  12. 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...

  13. moco: Fast Motion Correction for Calcium Imaging

    Directory of Open Access Journals (Sweden)

    Alexander eDubbs

    2016-02-01

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

  14. 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.

  15. The symphony of autophagy and calcium signaling.

    Science.gov (United States)

    Yao, Zhiyuan; Klionsky, Daniel J

    2015-01-01

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

  16. Octupole strength in the neutron-rich calcium isotopes

    CERN Document Server

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

    2016-01-01

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

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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

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

    Science.gov (United States)

    Hayer, Stefanie N; Bading, Hilmar

    2015-02-27

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

  3. 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

  4. 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.

  5. Polymorphism of felodipine co-crystals with 4,4'-bipyridine

    DEFF Research Database (Denmark)

    Surov, Artem Olegovich; Solanko, Katarzyna A.; Bond, Andrew;

    2014-01-01

    The calcium-channel blocking agent felodipine (Fel) forms co-crystals with 4,4′-bipyridine (BP) with 1:1 and 2:1 molar ratios. The [Fel + BP] (1:1) co-crystal exists in two polymorphic forms. Differential scanning calorimetry and solution calorimetry show that form I of the [Fel + BP] (1:1) co......-crystal is the most thermodynamically stable phase. The difference in the crystal lattice energies between different polymorphs of the co-crystal is found to be comparable with that between the polymorphic forms of pure felodipine. The enthalpies of formation of the co-crystals are small, which indicates...

  6. 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.

  7. 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.

  8. 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

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

    Science.gov (United States)

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

    1997-01-01

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

  10. Decalcification of calcium polycarbophil in rats.

    Science.gov (United States)

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

    1997-03-01

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

  11. Familial hypocalciuric hypercalcemia and calcium sensing receptor

    DEFF Research Database (Denmark)

    Mrgan, Monija; Nielsen, Sanne; Brixen, Kim

    2014-01-01

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

  12. 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 ...

  13. 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 ...

  14. 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.

  15. Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry.

    Science.gov (United States)

    Ohmura, Mitsuyo; Hishiki, Takako; Yamamoto, Takehiro; Nakanishi, Tsuyoshi; Kubo, Akiko; Tsuchihashi, Kenji; Tamada, Mayumi; Toue, Sakino; Kabe, Yasuaki; Saya, Hideyuki; Suematsu, Makoto

    2015-04-30

    CD44 expressed in cancer cells was shown to stabilize cystine transporter (xCT) that uptakes cystine and excretes glutamate to supply cysteine as a substrate for reduced glutathione (GSH) for survival. While targeting CD44 serves as a potentially therapeutic stratagem to attack cancer growth and chemoresistance, the impact of CD44 targeting in cancer cells on metabolic systems of tumors and host tissues in vivo remains to be fully determined. This study aimed to reveal effects of CD44 silencing on alterations in energy metabolism and sulfur-containing metabolites in vitro and in vivo using capillary electrophoresis-mass spectrometry and quantitative imaging mass spectrometry (Q-IMS), respectively. In an experimental model of xenograft transplantation of human colon cancer HCT116 cells in superimmunodeficient NOG mice, snap-frozen liver tissues containing metastatic tumors were examined by Q-IMS. As reported previously, short hairpin CD44 RNA interference (shCD44) in cancer cells caused significant regression of tumor growth in the host liver. Under these circumstances, the CD44 knockdown suppressed polyamines, GSH and energy charges not only in metastatic tumors but also in the host liver. In culture, HCT116 cells treated with shCD44 decreased total amounts of methionine-pool metabolites including spermidine and spermine, and reactive cysteine persulfides, suggesting roles of these metabolites for cancer growth. Collectively, these results suggest that CD44 expressed in cancer accounts for a key regulator of metabolic interplay between tumor and the host tissue. PMID:25461272

  16. Tight interconnection and multi-level control of Arabidopsis MYB44 in MAPK cascade signalling.

    Science.gov (United States)

    Persak, Helene; Pitzschke, Andrea

    2013-01-01

    Abiotic stress poses a huge, ever-increasing problem to plants and agriculture. The dissection of signalling pathways mediating stress tolerance is a prerequisite to develop more resistant plant species. Mitogen-activated protein kinase (MAPK) cascades are universal signalling modules. In Arabidopsis, the MAPK MPK3 and its upstream regulator MAPK kinase MKK4 initiate the adaptation response to numerous abiotic and biotic stresses. Yet, molecular steps directly linked with MKK4-MPK3 activation are largely unknown. Starting with a yeast-two-hybrid screen for interacting partners of MKK4, we identified a transcription factor, MYB44. MYB44 is controlled at multiple levels by and strongly inter-connected with MAPK signalling. As we had shown earlier, stress-induced expression of the MYB44 gene is regulated by a MPK3-targeted bZIP transcription factor VIP1. At the protein level, MYB44 interacts with MPK3 in vivo. MYB44 is phosphorylated by MPK3 in vitro at a single residue, Ser145. Although replacement of Ser145 by a non-phosphorylatable (S145A) or phosphomimetic (S145D) residue did not alter MYB44 subcellular localisation, dimerization behaviour nor DNA-binding characteristics, abiotic stress tolerance tests in stable transgenic Arabidopsis plants clearly related S145 phosphorylation to MYB44 function: Compared to Arabidopsis wild type plants, MYB44 overexpressing lines exhibit an enhanced tolerance to osmotic stress and are slightly more sensitive to abscisic acid. Interestingly, overexpression of the S145A variant revealed that impaired phosphorylation does not render the MYB44 protein non-functional. Instead, S145A lines are highly sensitive to abiotic stress, and thereby remarkably similar to mpk3-deficient plants. Its in vivo interaction with the nuclear sub-pools of both MPK3 and MKK4 renders MYB44 the first plant transcription factor to have a second function as putative MAPK cascade scaffolding protein.

  17. 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

  18. 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.

  19. 21 CFR 184.1210 - Calcium oxide.

    Science.gov (United States)

    2010-04-01

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

  20. 21 CFR 184.1185 - Calcium acetate.

    Science.gov (United States)

    2010-04-01

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

  1. 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...

  2. 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…

  3. 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

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

    Science.gov (United States)

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

    2016-01-01

    There is a pandemic of lifestyle-related diseases. In both developed and lesser developed countries of the world, an inadequacy of calcium intake and low vitamin D status is common. In this chapter, we explore a mechanistic framework that links calcium and vitamin D status to chronic conditions including obesity, systemic inflammation, endothelial dysfunction, dyslipidemia and cardiovascular disease, and type 2 diabetes mellitus. We also update the available clinical evidence, mainly from randomized controlled trials, to provide a synthesis of evidence in favor or against these hypotheses. There is consistent data to support calcium increasing whole body fat oxidation and increasing fecal fat excretion, while there is good cellular evidence for vitamin D reducing inflammation. Clinical trials support a marginal reduction in circulating lipids and some meta-analysis support an increase in insulin sensitivity following vitamin D. However, these mechanistic pathways and intermediate biomarkers of disease do not consistently transcribe into measurable health outcomes. Cementing the benefits of calcium and vitamin D for extraskeletal health needs a reexamination of the target 25(OH)D level to be achieved and the minimum duration of future trials. PMID:26944102

  5. 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....

  6. 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....

  7. 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)...

  8. 21 CFR 582.5210 - Calcium oxide.

    Science.gov (United States)

    2010-04-01

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

  9. 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

  10. 21 CFR 582.1210 - Calcium oxide.

    Science.gov (United States)

    2010-04-01

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

  11. 21 CFR 582.6185 - Calcium acetate.

    Science.gov (United States)

    2010-04-01

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

  12. 21 CFR 582.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

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

  13. 21 CFR 182.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

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

  14. 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)....

  15. 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.

  16. 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

  17. 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...

  18. 44 CFR 352.28 - Reimbursement.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reimbursement. 352.28 Section 352.28 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS COMMERCIAL NUCLEAR POWER PLANTS: EMERGENCY PREPAREDNESS PLANNING...

  19. 44 CFR 351.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 351.1 Section 351.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS RADIOLOGICAL EMERGENCY PLANNING AND PREPAREDNESS General § 351.1 Purpose. This part sets...

  20. 44 CFR 351.2 - Scope.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Scope. 351.2 Section 351.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS RADIOLOGICAL EMERGENCY PLANNING AND PREPAREDNESS General § 351.2 Scope. The emergency planning...

  1. 44 CFR 201.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 201.1 Section 201.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE MITIGATION PLANNING § 201.1 Purpose. (a) The purpose of this part is to...

  2. 44 CFR 350.3 - Background.

    Science.gov (United States)

    2010-10-01

    ... coordinate civil emergency planning, management and assistance functions and to represent the President in... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Background. 350.3 Section 350.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF...

  3. 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... technical advice and guidance to States and their political subdivisions for organizing and preparing...

  4. 45 CFR 400.44 - Restriction.

    Science.gov (United States)

    2010-10-01

    ... Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Immigration Status and Identification of Refugees Documentation of Refugee Status § 400.44 Restriction. An applicant for asylum is...

  5. 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...

  6. 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...

  7. 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...

  8. 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....

  9. 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...

  10. 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)...

  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 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... HOMELAND SECURITY GENERAL RULEMAKING; POLICY AND PROCEDURES General § 1.8 Regulations review. (a) As part... and keep updated a plan for periodic review of existing rules at least within 10 years from date...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 44 CFR 60.26 - Local coordination.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Local coordination. 60.26 Section 60.26 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Flood-Related Erosion-Prone Areas § 60.26 Local coordination. (a) Local flood plain, mudslide...

  2. 44 CFR 150.9 - Funding.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Funding. 150.9 Section 150.9 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY FIRE PREVENTION AND CONTROL PUBLIC SAFETY AWARDS TO PUBLIC SAFETY OFFICERS § 150.9 Funding....

  3. 44 CFR 13.25 - Program income.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Program income. 13.25 Section... LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 13.25 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from...

  4. 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...

  5. 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...

  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... Programs or Activities Prohibited § 19.540 Advertising. A recipient shall not in any advertising related...

  7. 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...

  8. 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...

  9. 44 CFR 9.4 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 9.4 Section 9.4... GENERAL FLOODPLAIN MANAGEMENT AND PROTECTION OF WETLANDS § 9.4 Definitions. The following definitions... Management Agency (FEMA). Agency Assistance means grants for projects or planning activities, loans, and...

  10. 44 CFR 352.1 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 352.1 Section 352.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS COMMERCIAL NUCLEAR POWER PLANTS: EMERGENCY PREPAREDNESS PLANNING § 352.1...

  11. 44 CFR 353.3 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 353.3 Section 353.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... LICENSEE RADIOLOGICAL EMERGENCY PLANS AND PREPAREDNESS § 353.3 Definitions. As used in this part,...

  12. 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... Administrator that identified weaknesses have been corrected. 1 See § 350.2 for definitions of...

  13. 44 CFR 350.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 350.2 Section 350.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... § 350.2 Definitions. As used in this part, the following terms are defined: (a) Administrator means...

  14. 44 CFR 201.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 201.2 Section 201.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE MITIGATION PLANNING § 201.2 Definitions. Administrator means the head of...

  15. 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...

  16. 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 Section 150.7 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Selection process. (a) President's Award. Nominations for the President's Award shall be reviewed,...

  17. 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 Section 150.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Nomination process. (a) The Nominating Officials nominating Firefighters and Civil Defense Officers...

  18. 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...

  19. 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...

  20. 44 CFR 8.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 8.1 Section 8.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... the extent that these regulations affect members of the public, these policies are to be published...

  1. 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... initial fee, if necessary, will be published as a notice in the Federal Register. (b) For requests...

  2. 44 CFR 12.11 - Public notice.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Public notice. 12.11 Section 12.11 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... and purpose of the committee, should be published in the Federal Register at least 15 days prior...

  3. 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 Section 5.25 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... are not published in the Federal Register. (c) Administrative staff manuals and instructions to...

  4. 44 CFR 13.34 - Copyrights.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Copyrights. 13.34 Section 13.34 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND..., publish or otherwise use, and to authorize others to use, for Federal Government purposes: (a)...

  5. 44 CFR 1.7 - Regulations agendas.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Regulations agendas. 1.7 Section 1.7 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Regulations published in April and October of each year. (b) In accordance with 5 U.S.C. 605, the...

  6. 44 CFR 12.9 - Closed meetings.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Closed meetings. 12.9 Section 12.9 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... availability of such annual reports shall be published in accordance with § 12.11 of this part....

  7. 44 CFR 206.32 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 206.32 Section 206.32 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... the FEMA-State Agreement and published in the Federal Register....

  8. 44 CFR 5.28 - Indexes.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Indexes. 5.28 Section 5.28 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... described in § 5.25. FEMA will publish quarterly and make available copies of each index or...

  9. 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...

  10. 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...

  11. 44 CFR 331.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 331.1 Section 331.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... SURPLUS AREAS § 331.1 Purpose. Success of the national defense program depends upon efficient use of...

  12. 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...

  13. 44 CFR 206.113 - Eligibility factors.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Eligibility factors. 206.113 Section 206.113 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Households § 206.113 Eligibility factors. (a) Conditions of eligibility. In general, FEMA may...

  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 5.41 - FEMA publications.

    Science.gov (United States)

    2010-10-01

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

  17. 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,...

  18. 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...

  19. 44 CFR 19.450 - Athletics.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Athletics. 19.450 Section 19.450 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... activity involved is a contact sport. However, where a recipient operates or sponsors a team in...

  20. 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...

  1. 44 CFR 6.81 - Additional copies.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Additional copies. 6.81... HOMELAND SECURITY GENERAL IMPLEMENTATION OF THE PRIVACY ACT OF 1974 Fees § 6.81 Additional copies. A reasonable number of additional copies shall be provided for the applicable fee to a requestor who...

  2. 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...

  3. 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...

  4. 44 CFR 11.79 - Attorney's fees.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Attorney's fees. 11.79... HOMELAND SECURITY GENERAL CLAIMS Personnel Claims Regulations § 11.79 Attorney's fees. No more than 10 per... shall be paid or delivered to or received by any agent or attorney on account of services rendered...

  5. 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,...

  6. 44 CFR 18.105 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 18.105 Section 18.105 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... an individual, corporation, company, association, authority, firm, partnership, society, State,...

  7. 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...

  8. 44 CFR 295.21 - Allowable compensation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable compensation. 295... OF HOMELAND SECURITY CERRO GRANDE FIRE ASSISTANCE CERRO GRANDE FIRE ASSISTANCE Compensation Available Under the CGFAA § 295.21 Allowable compensation. (a) Allowable compensation. The CGFAA provides for...

  9. 44 CFR 19.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Compensation. 19.515 Section... Programs or Activities Prohibited § 19.515 Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other...

  10. 27 CFR 44.182 - Lottery features.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Lottery features. 44.182... Lottery features. No certificate, coupon, or other device purporting to be or to represent a ticket, chance, share, or an interest in, or dependent on, the event of a lottery shall be contained in,...

  11. 44 CFR 5.3 - Definitions.

    Science.gov (United States)

    2010-10-01

    ..., functions, policies, decisions, procedures, operations, or other activities of FEMA or because of the... 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...

  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 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...

  16. 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...

  17. 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....

  18. 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...

  19. 44 CFR 204.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... information on the procedures for the declaration and grants management processes for the Fire Management... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 204.1 Section 204.1 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND...

  20. 44 CFR 206.31 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Purpose. 206.31 Section 206.31 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The Declaration Process § 206.31 Purpose....

  1. 44 CFR 206.38 - Presidential determination.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Presidential determination. 206.38 Section 206.38 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The Declaration Process §...

  2. 44 CFR 206.39 - Notification.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Notification. 206.39 Section 206.39 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The Declaration Process § 206.39 Notification....

  3. 44 CFR 206.46 - Appeals.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Appeals. 206.46 Section 206.46 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The Declaration Process § 206.46 Appeals....

  4. 44 CFR 302.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ..., added by Public Law 97-86. Title V calls for an improved civil defense program that includes: (1) A..., contributes to, and does not detract from attack-related civil defense preparedness.” Also 44 CFR part 312... participating State's total civil defense program and of related State and local laws, executive...

  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 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...

  7. 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...

  8. 24 CFR 26.44 - Protective orders.

    Science.gov (United States)

    2010-04-01

    ... HEARING PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.44 Protective... respect to discovery sought by an opposing party or with respect to the hearing, seeking to limit the..., or undue burden or expense because: (1) The discovery sought is unreasonably cumulative...

  9. 44 CFR 62.5 - Premium refund.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Premium refund. 62.5 Section... OF CLAIMS Issuance of Policies § 62.5 Premium refund. A Standard Flood Insurance Policyholder whose... has been paid or is pending, the full premium shall be refunded for the current policy year, and...

  10. 7 CFR 1735.44 - Prepayment premiums.

    Science.gov (United States)

    2010-01-01

    ... premiums on loans guaranteed by RUS. See 7 CFR part 1610 for prepayment premiums on RTB loans. See RUS Bulletin 320-12 for additional information. This CFR part supersedes those portions of RUS Bulletin 320-12... 7 Agriculture 11 2010-01-01 2010-01-01 false Prepayment premiums. 1735.44 Section...

  11. 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,...

  12. 44 CFR 334.3 - Background.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Background. 334.3 Section 334.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... adversaries shape the nature and gravity of the threat as well as its likelihood and timing of...

  13. 44 CFR 206.225 - Emergency work.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Emergency work. 206.225 Section 206.225 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... that a threat exists, including identification and evaluation of the threat and recommendations of...

  14. 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.

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

    Science.gov (United States)

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

    1990-12-01

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

  16. 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.

  17. 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.

  18. 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.

  19. H I in Group Interactions: HCG 44

    Science.gov (United States)

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

    2016-09-01

    Extending deep observations of the neutral atomic hydrogen (H I) 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 H I data from the Karoo Array Telescope, Westerbork Synthesis Radio Telescope, and Arecibo Legacy Fast ALFA survey, in order to achieve high column density sensitivity (NHI gas over a large field-of-view beyond the compact group itself. We find the giant H I tail north of HCG 44 contains 1.1 × 109 M⊙ 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 H I deficiency of HCG 44. The tail likely formed through a strong tidal interaction and H I clouds in the tail have survived for 1 Gyr or more after being stripped. This has important implications for understanding the survival of neutral clouds in the intragroup and circumgroup medium, and we discuss their survival in the context of simulations of cold gas in hot halos. HCG 44 is one of a growing number of galaxy groups found to have more extended H I in the intragroup and circumgroup medium than previously measured. Our results provide constraints for simulations on the properties of galaxy group halos, and reveal a glimpse of what will be seen by future powerful H I telescopes and surveys.

  20. 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...

  1. 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.

  2. 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 ...

  3. Store-operated calcium signaling in neutrophils.

    Science.gov (United States)

    Clemens, Regina A; Lowell, Clifford A

    2015-10-01

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

  4. 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.

  5. Stable icosahedral phase in Mg44Zn44Gd12 alloy

    Institute of Scientific and Technical Information of China (English)

    WANG Xudong; DU Wenbo; WANG Zhaohui; LIU Ke; LI Shubo

    2012-01-01

    The microstructure of the as-cast Mg44Zn44Gd12 alloy was investigated by using X-ray diffraction (XRD),differentical scanning (DSC),scanning electron microscopy (SEM) and a detailed transmission electron microscope.The XRD,DSC and SEM results indicated that the as-cast Mg44Zn44Gd12 alloy were mainly composed of three types of phases:the primary solidification phase,the dendritic phase and the eutectic phase.The primary solidification phase had an icosahedral structure.The dendritic phase was the W-phase,and cutectic structure phase was the Mg7Zn3 phase.Microstructures of icosahedral phase (I-phase),W-phase and Mg7Zn3 phase in MguZn44Gd12 alloy were investigated.The results indicated that the I-phase in Mg44Zn44Gd12 alloy was a face-centered icosahedral quasicrystal with stoichiometric composition of Mg42Zn50Gd8 which had an excellent thermal stability up to 420℃.The solid solution of the Gd gradually decreased during solidification,which played an important role in activating the formation of Mg7Zn3 phase and W-phase from icosahedral phases.

  6. 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.

  7. 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...

  8. 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

  9. 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.

  10. [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

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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.

  16. 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

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

    Science.gov (United States)

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

    2012-06-25

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

  18. 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

  19. 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

  20. 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

  1. Effect of Calcium Sources and Particle Size on Performance and Eggshell Quality in Laying Hens

    Directory of Open Access Journals (Sweden)

    Arzu Erol Tunç

    2015-01-01

    Full Text Available An experiment was conducted to determine the effect of different combination calcium sources and particle size on performance and egg shell quality in layer hens. In the experiment, 198 brown laying hens at 44 week of age were randomly assigned into 11 treatments groups. The experimental diets consisted of different calcium sources (Fine limestone, large limestone, large oyster shell and large egg shell and their different combination. The experimental unit consisted of a groups of three hens, thus each treatment was replicated six times. Different calcium sources and particle size addition to the laying hens diet had no significantly effect on body weight gain, egg production, egg mass, feed intake, feed conversion ratio, egg specific gravity, egg shell weight, egg shell thickness and egg shell breaking strength but egg weight had significantly affected by the treatments. The significantly highest egg weight was found in laying hens fed with 50 % fine limestone and 50 % large limestone. Dietary different Ca sources had a significant effect on Ca, P and Mg as mineral contents of eggshell and tibia. In the present study, when dietary large calcium sources (limestone, oyster shell and egg shell had no effect on performance and eggshell quality parameters in laying hens. However, dietary containing at least 50 % large calcium sources had positive effect on mineral contents of tibia.

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

    Directory of Open Access Journals (Sweden)

    Bading Hilmar

    2007-07-01

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

  3. 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

  4. [Calcium supplementation uncovering lactose intolerance - a case report].

    Science.gov (United States)

    Trifina, Eva; Geissler, Dietmar; Zwettler, Elisabeth; Klaushofer, Klaus; Mikosch, Peter

    2012-03-01

    A 44 yr-old female with osteoporosis had no relevant gastrointestinal symptoms and did not avoid any specific food. However, after prescription of a lactose-rich calcium supplementation, clinical symptoms suspicious for lactose intolerance occurred, which were thereafter confirmed by a lactose tolerance test. Lactose intolerance may present with only slight or subtle symptoms. Drugs containing lactose may induce or increase gastrointestinal symptoms in patients with lactose intolerance. In case of gastrointestinal symptoms occurring after the initiation of drugs containing lactose, the possibility of lactose intolerance should be considered and tested by lactose tolerance test or genetic testing for the LCT (-13910) polymorphism. Due to the prevalence of about 15-25% lactose intolerance in the Austrian population, lactose free drugs should be prescribed as widely as possible.

  5. 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...

  6. 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...

  7. 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.

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

    Science.gov (United States)

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

    2006-04-01

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

  9. Calcium binding proteins and calcium signaling in prokaryotes.

    Science.gov (United States)

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

    2015-03-01

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

  10. Sintering of calcium phosphate bioceramics.

    Science.gov (United States)

    Champion, E

    2013-04-01

    Calcium phosphate ceramics have become of prime importance for biological applications in the field of bone tissue engineering. This paper reviews the sintering behaviour of these bioceramics. Conventional pressureless sintering of hydroxyapatite, Ca10(PO4)6(OH)2, a reference compound, has been extensively studied. Its physico-chemistry is detailed. It can be seen as a competition between two thermally activated phenomena that proceed by solid-state diffusion of matter: densification and grain growth. Usually, the objective is to promote the first and prevent the second. Literature data are analysed from sintering maps (i.e. grain growth vs. densification). Sintering trajectories of hydroxyapatite produced by conventional pressureless sintering and non-conventional techniques, including two-step sintering, liquid phase sintering, hot pressing, hot isostatic pressing, ultrahigh pressure, microwave and spark plasma sintering, are presented. Whatever the sintering technique may be, grain growth occurs mainly during the last step of sintering, when the relative bulk density reaches 95% of the maximum value. Though often considered very advantageous, most assisted sintering techniques do not appear very superior to conventional pressureless sintering. Sintering of tricalcium phosphate or biphasic calcium phosphates is also discussed. The chemical composition of calcium phosphate influences the behaviour. Similarly, ionic substitutions in hydroxyapatite or in tricalcium phosphate create lattice defects that modify the sintering rate. Depending on their nature, they can either accelerate or slow down the sintering rate. The thermal stability of compounds at the sintering temperature must also be taken into account. Controlled atmospheres may be required to prevent thermal decomposition, and flash sintering techniques, which allow consolidation at low temperature, can be helpful. PMID:23212081

  11. Altered calcium signaling following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    John Thomas Weber

    2012-04-01

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

  12. 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

  13. 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

  14. 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.

  15. 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...

  16. 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...

  17. 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 ...

  18. Calcium

    Science.gov (United States)

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

  19. 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.

  20. Bis(4,4′-bipyridinium dodecatungstosilicate 4,4′-bipyridine hexahydrate

    Directory of Open Access Journals (Sweden)

    Quan Zhao

    2008-10-01

    Full Text Available The title compound, (C10H10N22[SiW12O40]·C10H8N2·6H2O or (4,4′-bipyH22[SiW12O40].(4,4′-bipy·6H2O (4,4′-bipy is 4,4′-bipyridine, was prepared under hydrothermal conditions. The asymmetric unit contains a discrete Keggin-type [SiW12O40]4− anion (located on a twofold axis, one 4,4′-bipy (located on a twofold axis, two (4,4′-bipyH22+ cations and six uncoordinated water molecules. The polyoxoanion is constructed from a central SiO4 tetrahedron which shares its O atoms with four trinuclear W3O13 groups, each of which is made up of three edge-sharing WO6 octahedra. The water molecules and [SiW12O40]4− anions are linked through hydrogen bonds.

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-07-01

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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  5. 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.

  6. 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

  7. 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...

  8. Catalytic pyrolysis using UZM-44 aluminosilicate zeolite

    Energy Technology Data Exchange (ETDEWEB)

    Nicholas, Christopher P; Boldingh, Edwin P

    2013-12-17

    A new family of aluminosilicate zeolites designated UZM-44 has been synthesized. These zeolites are represented by the empirical formula Na.sub.nM.sub.m.sup.k+T.sub.tAl.sub.1-xE.sub.xSi.sub.yO.sub.z where "n" is the mole ratio of Na to (Al+E), M represents a metal or metals from zinc, Group 1, Group 2, Group 3 and or the lanthanide series of the periodic table, "m" is the mole ratio of M to (Al+E), "k" is the average charge of the metal or metals M, T is the organic structure directing agent or agents, and E is a framework element such as gallium. The process involves contacting a carbonaceous biomass feedstock with UZM-44 at pyrolysis conditions to produce pyrolysis gases comprising hydrocarbons. The catalyst catalyzes a deoxygenation reaction converting oxygenated hydrocarbons into hydrocarbons and removing the oxygen as carbon oxides and water. A portion of the pyrolysis gases is condensed to produce low oxygen biomass-derived pyrolysis oil.

  9. Catalytic pyrolysis using UZM-44 aluminosilicate zeolite

    Energy Technology Data Exchange (ETDEWEB)

    Nicholas, Christopher P; Boldingh, Edwin P

    2014-04-29

    A new family of aluminosilicate zeolites designated UZM-44 has been synthesized. These zeolites are represented by the empirical formula. Na.sub.nM.sub.m.sup.k+T.sub.tAl.sub.1-xE.sub.xSi.sub.yO.sub.z where "n" is the mole ratio of Na to (Al+E), M represents a metal or metals from zinc, Group 1, Group 2, Group 3 and or the lanthanide series of the periodic table, "m" is the mole ratio of M to (Al+E), "k" is the average charge of the metal or metals M, T is the organic structure directing agent or agents, and E is a framework element such as gallium. The process involves contacting a carbonaceous biomass feedstock with UZM-44 at pyrolysis conditions to produce pyrolysis gases comprising hydrocarbons. The catalyst catalyzes a deoxygenation reaction converting oxygenated hydrocarbons into hydrocarbons and removing the oxygen as carbon oxides and water. A portion of the pyrolysis gases is condensed to produce low oxygen biomass-derived pyrolysis oil.

  10. 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.)

  11. Calcium signaling in pluripotent stem cells.

    Science.gov (United States)

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

    2012-04-28

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

  12. Presynaptic calcium signalling in cerebellar mossy fibres

    Directory of Open Access Journals (Sweden)

    Louiza B Thomsen

    2010-02-01

    Full Text Available Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A TTX-sensitive fast Na+ spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none tetrodotoxin (TTX -sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than one second affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

  13. 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...

  14. 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.

  15. Experiments on the formation of titanium-44 in supernovae; Experimente zur Entstehung von Titan-44 in Supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Konrad

    2012-11-01

    In this thesis the astrophysically interesting resonance triplet of the {sup 40}Ca({alpha},{gamma}){sup 44}Ti reaction at 4.5 MeV has been studied. For this purpose energies of proton and {alpha} 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 {sup 40}Ca(p,{gamma}){sup 41}Sc 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 {alpha} 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.

  16. 40 CFR 155.44 - Establish schedules for registration review.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Establish schedules for registration review. 155.44 Section 155.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... on its website....

  17. 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.

  18. 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 ...

  19. 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)

  20. 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

  1. 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.

  2. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

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

  3. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

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

    1991-01-01

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

  4. 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.

  5. 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.

  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. 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...

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

    Directory of Open Access Journals (Sweden)

    Han Wang

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

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

    Directory of Open Access Journals (Sweden)

    Sandra Tavares da Silva

    2013-06-01

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

  10. 10 CFR 60.44 - Changes, tests, and experiments.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Changes, tests, and experiments. 60.44 Section 60.44... REPOSITORIES Licenses License Issuance and Amendment § 60.44 Changes, tests, and experiments. (a)(1) Following... experiments not described in the application, without prior Commission approval, provided the change, test,...

  11. 26 CFR 44.6419-1 - Credit or refund generally.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Credit or refund generally. 44.6419-1 Section 44... Application to the Taxes on Wagering § 44.6419-1 Credit or refund generally. (a) Overpayment of wagering tax... refund on Form 843 or take credit for such overpayment against the tax due on a subsequent monthly...

  12. 27 CFR 44.3 - Delegations of the Administrator.

    Science.gov (United States)

    2010-04-01

    ... Administrator's Authorities in 27 CFR Part 44, Exportation of Tobacco Products and Cigarette Papers and Tubes... Administrator. 44.3 Section 44.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Administrator. Most of the regulatory authorities of the Administrator contained in this part are delegated...

  13. 45 CFR 4.4 - Acknowledgement of mailed process.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Acknowledgement of mailed process. 4.4 Section 4.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.4 Acknowledgement of mailed process. The Department will not provide a receipt or other acknowledgement of...

  14. 42 CFR 4.4 - Use of Library facilities.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Use of Library facilities. 4.4 Section 4.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.4 Use of Library facilities. (a) General. The Library facilities are available to...

  15. 36 CFR 4.4 - Report of motor vehicle accident.

    Science.gov (United States)

    2010-07-01

    ... accident. 4.4 Section 4.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR VEHICLES AND TRAFFIC SAFETY § 4.4 Report of motor vehicle accident. (a) The operator of a motor vehicle involved in an accident resulting in property damage, personal injury or death shall report...

  16. 49 CFR 655.44 - Post-accident testing.

    Science.gov (United States)

    2010-10-01

    ... Safety Administration rule 49 CFR 389.303(a)(1) or (b)(1). (ii) The employer shall also drug and alcohol... 49 Transportation 7 2010-10-01 2010-10-01 false Post-accident testing. 655.44 Section 655.44... of Testing § 655.44 Post-accident testing. (a) Accidents. (1) Fatal accidents. (i) As soon...

  17. 28 CFR 32.44 - Hearing Officer determination.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Hearing Officer determination. 32.44 Section 32.44 Judicial Administration DEPARTMENT OF JUSTICE PUBLIC SAFETY OFFICERS' DEATH, DISABILITY, AND EDUCATIONAL ASSISTANCE BENEFIT CLAIMS Hearing Officer Determinations § 32.44 Hearing Officer determination....

  18. 19 CFR 191.44 - Destruction under Customs supervision.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Destruction under Customs supervision. 191.44 Section 191.44 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) DRAWBACK Rejected Merchandise § 191.44 Destruction under...

  19. 36 CFR 7.44 - Canyonlands National Park.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Canyonlands National Park. 7.44 Section 7.44 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.44 Canyonlands National Park. (a)...

  20. 40 CFR 406.44 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... § 406.44 Pretreatment standards for existing sources. Any existing source subject to this subpart that introduces process wastewater pollutants into a publicly owned treatment works must comply with 40 CFR part... sources. 406.44 Section 406.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...