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Sample records for zinc 67 target

  1. Production of 64Cu and 67Cu radiopharmaceuticals using zinc target irradiated with accelerator neutrons

    NASA Astrophysics Data System (ADS)

    Kawabata, Masako; Hashimoto, Kazuyuki; Saeki, Hideya; Sato, Nozomi; Motoishi, Shoji; Nagai, Yasuki

    2014-09-01

    Copper radioisotopes have gained a lot of attention in radiopharmaceuticals owing to their unique decay characteristics. The longest half-life β emitter, 67Cu, is thought to be suitable for targeted radio-immunotherapy. Adequate production of 67Cu to meet the demands of clinical studies has not been fully established. Another attractive copper isotope, 64Cu has possible applications as a diagnostic imaging tracer combined with a therapeutic effect. This work proposes a production method using accelerator neutrons in which two copper radioisotopes can be produced: 1) 68Zn(n,x)67Cu and 2) 64Zn(n,p)64Cu using ~14 MeV neutrons generated by natC(d, n) reaction, both from natural or enriched zinc oxides. The generated 64,67Cu were separated from the target zinc oxide using a chelating and an anion exchange columns and were labelled with two widely studied chelators where the labelling efficiency was found to be acceptably good. The major advantage of this method is that a significant amount of 64,67Cu with a very few impurity radionuclides are produced which also makes the separation procedure simple. Provided an accelerator supplying an Ed = ~ 40 MeV, a wide application of 64,67Cu based drugs in nuclear medicine is feasible in the near future. We will present the characteristics of this production method using accelerator neutrons including the chemical separation processes.

  2. Thin-target excitation functions and optimisation of NCA 64Cu and 66,67Ga production by deuteron induced nuclear reactions on natural zinc target, for radiometabolic therapy and for PET

    NASA Astrophysics Data System (ADS)

    Groppi, F.; Bonardi, M. L.; Birattari, C.; Gini, L.; Mainardi, C.; Menapace, E.; Abbas, K.; Holzwarth, U.; Stroosnijder, R. M. F.

    2004-01-01

    A novel method for production of No-Carrier-Added 64Cu and 66,67Ga has been developed, based on reactions induced by deuterons up to 19 MeV on Zn target. HPGe and beta (by LSC) spectrometries proved very effective to determine radionuclidic purity of 64Cu and 66,67Ga fractions. Experimental specific activity for 64Cu was measured by ET-AAS and was of the order of 700 MBq · μg -1. Radiochemical yields for 64Cu and 66,67Ga were >80% and >99%.

  3. [Improvement in zinc nutrition due to zinc transporter-targeting strategy].

    PubMed

    Kambe, Taiho

    2016-07-01

    Adequate intake of zinc from the daily diet is indispensable to maintain health. However, the dietary zinc content often fails to fulfill the recommended daily intake, leading to zinc deficiency and also increases the risk of developing chronic diseases, particularly in elderly individuals. Therefore, increased attention is required to overcome zinc deficiency and it is important to improve zinc nutrition in daily life. In the small intestine, the zinc transporter, ZIP4, functions as a component that is essential for zinc absorption. In this manuscript, we present a brief overview regarding zinc deficiency. Moreover, we review a novel strategy, called "ZIP4-targeting", which has the potential to enable efficient zinc absorption from the diet. ZIP4-targeting strategy is possibly a major step in preventing zinc deficiency and improving human health.

  4. Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach.

    PubMed

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Gerdil, Adèle; Diemer, Hélène; Proamer, Fabienne; Collin-Faure, Véronique; Habert, Aurélie; Strub, Jean-Marc; Hanau, Daniel; Herlin, Nathalie; Carrière, Marie; Van Dorsselaer, Alain; Rabilloud, Thierry

    2014-06-07

    Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.

  5. Zinc

    MedlinePlus

    ... Using toothpastes containing zinc, with or without an antibacterial agent, appears to prevent plaque and gingivitis. Some ... is some evidence that zinc has some antiviral activity against the herpes virus. Low zinc levels can ...

  6. Targeted Zinc Delivery: A Novel Treatment for Prostate Cancer

    DTIC Science & Technology

    2010-06-01

    aconitase, which normally functions to oxidize citrate during the Krebs cycle . Because citrate is a principle component of seminal fluid, prostate...tissue, likely due to the metabolic effects of zinc in the Krebs cycle . That is, because zinc inhibits m- aconitase, loss of zinc allows for greater...secretory cells do not complete the oxidation of citrate in the mitochondria and the zinc-mediated inhibition of m-aconitase is crucial for the

  7. Zinc

    MedlinePlus

    ... Guidelines for Americans and the U.S. Department of Agriculture's MyPlate . Where can I find out more about ... on food sources of zinc: U.S. Department of Agriculture's (USDA’s) National Nutrient Database Nutrient List for zinc ( ...

  8. Zinc

    Zinc was recognized as an essential trace metal for humans during the studies of Iranian adolescent dwarfs in the early 1960s. Zinc metal existing as Zn2+ is a strong electron acceptor in biological systems without risks of oxidant damage to cells. Zn2+ functions in the structure of proteins and is ...

  9. Target development for 67Cu, 82Sr radionuclide production at the RIC-80 facility

    NASA Astrophysics Data System (ADS)

    Panteleev, V. N.; Barzakh, A. E.; Batist, L. Kh.; Fedorov, D. V.; Ivanov, V. S.; Krotov, S. A.; Molkanov, P. L.; Moroz, F. V.; Orlov, S. Yu.; Volkov, Yu. M.

    2018-01-01

    A high-current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed and commissioned at PNPI (Petersburg Nuclear Physics Institute). One of the main goals of cyclotron C-80 is the production of a wide spectrum of medical radionuclides for diagnostics and therapy. To date, the project development of a radioisotope facility RIC-80 (radioisotopes at cyclotron C-80) has been completed. The feature of the project is the use of a mass-separator combined with the ion-target device for obtaining ion beams of radioisotopes with a high purity of separation that is especially important for medical applications. The first results of a new high-temperature method for extracting 82Sr and 67Cu radioisotopes from irradiated targets have been presented.

  10. Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting.

    PubMed

    Hashimoto, Ayako; Ohkura, Katsuma; Takahashi, Masakazu; Kizu, Kumiko; Narita, Hiroshi; Enomoto, Shuichi; Miyamae, Yusaku; Masuda, Seiji; Nagao, Masaya; Irie, Kazuhiro; Ohigashi, Hajime; Andrews, Glen K; Kambe, Taiho

    2015-12-01

    Dietary zinc deficiency puts human health at risk, so we explored strategies for enhancing zinc absorption. In the small intestine, the zinc transporter ZIP4 functions as an essential component of zinc absorption. Overexpression of ZIP4 protein increases zinc uptake and thereby cellular zinc levels, suggesting that food components with the ability to increase ZIP4 could potentially enhance zinc absorption via the intestine. In the present study, we used mouse Hepa cells, which regulate mouse Zip4 (mZip4) in a manner indistinguishable from that in intestinal enterocytes, to screen for suitable food components that can increase the abundance of ZIP4. Using this ZIP4-targeting strategy, two such soybean extracts were identified that were specifically able to decrease mZip4 endocytosis in response to zinc. These soybean extracts also effectively increased the abundance of apically localized mZip4 in transfected polarized Caco2 and Madin-Darby canine kidney cells and, moreover, two apically localized mZip4 acrodermatitis enteropathica mutants. Soybean components were purified from one extract and soyasaponin Bb was identified as an active component that increased both mZip4 protein abundance and zinc levels in Hepa cells. Finally, we confirmed that soyasaponin Bb is capable of enhancing cell surface endogenous human ZIP4 in human cells. Our results suggest that ZIP4 targeting may represent a new strategy to improve zinc absorption in humans. © 2015 Authors; published by Portland Press Limited.

  11. Groundbased investigation of comet 67p/churyumov- gerasimenko, target of the spacecraft Mission Rosetta

    NASA Astrophysics Data System (ADS)

    de Almeida, A. A.; Trevisan Sanzovo, D.; Sanzovo, G. C.; Boczko, R.; Miguel Torres, R.

    In this work, we make a comparative study of Comet 67P/Churyumov-Gerasimenko, target of Mission Rosetta, with Comets 1P/Halley and Hyakutake(C/1996 B2). Water and gas) release rates are derived from visual magnitudes (mv), determined mostly by amateur astronomers, and listed in several issues of International Comet Quarterly(ICQ). We make a systematic and uniform analysis of continuum fluxes obtained at visual wavelengths and, using the framework of photometric theory of Newburn & Spinrad (1985, 1989), we estimate dust release rates, qd (in g/s), effective particle sizes, a (in micron), and dust-to-gas mass ratios, for this important sample of comets. We also determine the color excess of the dust particles, CE, relative to the Sun at wavelength ranges 477.0-524.0 nm in the 1996 return of Comet 67P/Churyumov-Gerasimenko, and 365.0-484.5 nm for Comets 1P/Halley and C/1996 B2.

  12. Ki-67 as a molecular target for therapy in an in vitro three-dimensional model for ovarian cancer.

    PubMed

    Rahmanzadeh, Ramtin; Rai, Prakash; Celli, Jonathan P; Rizvi, Imran; Baron-Lühr, Bettina; Gerdes, Johannes; Hasan, Tayyaba

    2010-11-15

    Targeting molecular markers and pathways implicated in cancer cell growth is a promising avenue for developing effective therapies. Although the Ki-67 protein (pKi-67) is a key marker associated with aggressively proliferating cancer cells and poor prognosis, its full potential as a therapeutic target has never before been successfully shown. In this regard, its nuclear localization presents a major hurdle because of the need for intracellular and intranuclear delivery of targeting and therapeutic moieties. Using a liposomally encapsulated construct, we show for the first time the specific delivery of a Ki-67-directed antibody and subsequent light-triggered death in the human ovarian cancer cell line OVCAR-5. Photoimmunoconjugate-encapsulating liposomes (PICEL) were constructed from anti-pKi-67 antibodies conjugated to fluorescein 5(6)-isothiocyanate, as a photoactivatable agent, followed by encapsulation in noncationic liposomes. Nucleolar localization of the PICELs was confirmed by confocal imaging. Photodynamic activation with PICELs specifically killed pKi-67-positive cancer cells both in monolayer and in three-dimensional (3D) cultures of OVCAR-5 cells, with the antibody TuBB-9 targeting a physiologically active form of pKi-67 but not with MIB-1, directed to a different epitope. This is the first demonstration of (a) the exploitation of Ki-67 as a molecular target for therapy and (b) specific delivery of an antibody to the nucleolus in monolayer cancer cells and in an in vitro 3D model system. In view of the ubiquity of pKi-67 in proliferating cells in cancer and the specificity of targeting in 3D multicellular acini, these findings are promising and the approach merits further investigation. Copyright © 2010 AACR.

  13. Ki-67 as a molecular target for therapy in an in vitro 3D model for ovarian cancer

    PubMed Central

    Rahmanzadeh, Ramtin; Rai, Prakash; Celli, Jonathan P.; Rizvi, Imran; Baron-Lühr, Bettina; Gerdes, Johannes; Hasan, Tayyaba

    2010-01-01

    Targeting molecular markers and pathways implicated in cancer cell growth is a promising avenue for developing effective therapies. Although the Ki-67 protein (pKi-67) is a key marker associated with aggressively proliferating cancer cells and poor prognosis, its full potential as a therapeutic target has never before been successfully demonstrated. In this regard, its nuclear localization presents a major hurdle because of the need for intracellular and intranuclear delivery of targeting and therapeutic moieties. Using a liposomally encapsulated construct, we demonstrate for the first time, the specific delivery of a Ki-67 directed antibody and subsequent light-triggered death in a human ovarian cancer cell line OVCAR-5. Photoimmunoconjugate encapsulating liposomes (PICELs) were constructed from anti-pKi-67 antibodies conjugated to fluorescein isothiocyanate, as a photoactivatable agent followed by encapsulation in non-cationic liposomes. Nucleolar localization of the PICELs was confirmed by confocal imaging. Photodynamic activation with PICELs specifically killed pKi-67 positive cancer cells both in monolayer and in 3D cultures of OVCAR-5 cells with the antibody TuBB-9 targeting a physiologically active form of pKi-67 but not with MIB-1, directed to a different epitope. This is the first demonstration of: - 1. the exploitation of Ki-67 as a molecular target for therapy and - 2. specific delivery of an antibody to the nucleolus in monolayer cancer cells and in an in vitro 3D model system. In view of the ubiquity of pKi-67 in proliferating cells in cancer and the specificity of targeting in 3D multicellular acini, these findings are promising and the approach merits further investigation. PMID:21045152

  14. Targeted light-inactivation of the Ki-67 protein using theranostic liposomes leads to death of proliferating cells

    NASA Astrophysics Data System (ADS)

    Rahmanzadeh, Ramtin; Rai, Prakash; Gerdes, Johannes; Hasan, Tayyaba

    2010-02-01

    Nanomedicine is beginning to impact the treatment of several diseases and current research efforts include development of integrated nano-constructs (theranostics) which serve as probes for imaging and therapy in addition to delivering macromolecules intracellularly. In cancer, there is a vital unmet need for effective alternative treatments with high specificity and low systemic toxicity. This can be achieved by targeting key molecular markers associated with cancer cells with reduced effective drug doses. Here, we show an innovative proof-of-principle approach for efficient killing of proliferating ovarian cancer cells by inactivating a protein associated with cell proliferation namely, the nuclear Ki-67 protein (pKi-67), using nanotechnology-based photodynamic therapy (PDT). Antibodies against pKi-67 are widely used as prognostic tools for tumor diagnosis. In this work, anti pKi-67 antibodies were first conjugated to fluorescein isothiocyanate (FITC) and then encapsulated inside liposomes. After incubation of OVCAR-5 ovarian cancer cells with these liposomes, confocal microscopy confirmed the localization of the antibodies to the nucleoli of the cells. Irradiation with a 488 nm laser led to a significant loss of cell viability. The specificity of this approach for pKi-67 positive cells was demonstrated in confluent human lung fibroblasts (MRC-5) where only a small population of cells stain positive for pKi-67 and only minimal cell death was observed. Taken together, our findings suggest that pKi-67 targeted with nano-platform is an attractive therapeutic target in cancer therapy.

  15. Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach

    PubMed Central

    2018-01-01

    Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers. PMID:29529862

  16. Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.

    PubMed

    Amato, Anastasia; Lucas, Xavier; Bortoluzzi, Alessio; Wright, David; Ciulli, Alessio

    2018-04-20

    Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers.

  17. Targeted Mutagenesis of Duplicated Genes in Soybean with Zinc-Finger Nucleases1[W][OA

    PubMed Central

    Curtin, Shaun J.; Zhang, Feng; Sander, Jeffry D.; Haun, William J.; Starker, Colby; Baltes, Nicholas J.; Reyon, Deepak; Dahlborg, Elizabeth J.; Goodwin, Mathew J.; Coffman, Andrew P.; Dobbs, Drena; Joung, J. Keith; Voytas, Daniel F.; Stupar, Robert M.

    2011-01-01

    We performed targeted mutagenesis of a transgene and nine endogenous soybean (Glycine max) genes using zinc-finger nucleases (ZFNs). A suite of ZFNs were engineered by the recently described context-dependent assembly platform—a rapid, open-source method for generating zinc-finger arrays. Specific ZFNs targeting DICER-LIKE (DCL) genes and other genes involved in RNA silencing were cloned into a vector under an estrogen-inducible promoter. A hairy-root transformation system was employed to investigate the efficiency of ZFN mutagenesis at each target locus. Transgenic roots exhibited somatic mutations localized at the ZFN target sites for seven out of nine targeted genes. We next introduced a ZFN into soybean via whole-plant transformation and generated independent mutations in the paralogous genes DCL4a and DCL4b. The dcl4b mutation showed efficient heritable transmission of the ZFN-induced mutation in the subsequent generation. These findings indicate that ZFN-based mutagenesis provides an efficient method for making mutations in duplicate genes that are otherwise difficult to study due to redundancy. We also developed a publicly accessible Web-based tool to identify sites suitable for engineering context-dependent assembly ZFNs in the soybean genome. PMID:21464476

  18. Synthetic Zinc Finger Proteins: The Advent of Targeted Gene Regulation and Genome Modification Technologies

    PubMed Central

    2015-01-01

    Conspectus The understanding of gene regulation and the structure and function of the human genome increased dramatically at the end of the 20th century. Yet the technologies for manipulating the genome have been slower to develop. For instance, the field of gene therapy has been focused on correcting genetic diseases and augmenting tissue repair for more than 40 years. However, with the exception of a few very low efficiency approaches, conventional genetic engineering methods have only been able to add auxiliary genes to cells. This has been a substantial obstacle to the clinical success of gene therapies and has also led to severe unintended consequences in several cases. Therefore, technologies that facilitate the precise modification of cellular genomes have diverse and significant implications in many facets of research and are essential for translating the products of the Genomic Revolution into tangible benefits for medicine and biotechnology. To address this need, in the 1990s, we embarked on a mission to develop technologies for engineering protein–DNA interactions with the aim of creating custom tools capable of targeting any DNA sequence. Our goal has been to allow researchers to reach into genomes to specifically regulate, knock out, or replace any gene. To realize these goals, we initially focused on understanding and manipulating zinc finger proteins. In particular, we sought to create a simple and straightforward method that enables unspecialized laboratories to engineer custom DNA-modifying proteins using only defined modular components, a web-based utility, and standard recombinant DNA technology. Two significant challenges we faced were (i) the development of zinc finger domains that target sequences not recognized by naturally occurring zinc finger proteins and (ii) determining how individual zinc finger domains could be tethered together as polydactyl proteins to recognize unique locations within complex genomes. We and others have since used

  19. Pentalysine β-Carbonylphthalocyanine Zinc: An Effective Tumor-Targeting Photosensitizer for Photodynamic Therapy

    PubMed Central

    Chen, Zhuo; Zhou, Shanyong; Chen, Jincan; Deng, Yicai; Luo, Zhipu; Chen, Hongwei; Hamblin, Michael R.

    2010-01-01

    Unsymmetrical phthalocyanine derivatives have been widely studied as photosensitizers for photodynamic therapy (PDT), targeting various tumor types. However, the preparation of unsymmetrical phthalocyanines is always a challenge due to the presence of many possible structural isomers. Herein we report a new unsymmetrical zinc phthalocyanine, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5), that was prepared in large quantity and high purity. This is a water-soluble cationic photosensitizer and maintains a high quantum yield of singlet oxygen generation similar to that of unsubstituted zinc phthalocyanine (ZnPc). Compared with anionic ZnPc counterparts, ZnPc-(Lys)5 shows a higher level cellular uptake and 20-fold higher phototoxicity toward tumor cells. Pharmacokinetics and PDT studies of ZnPc-(Lys)5 in S180 tumor-bearing mice showed a high ratio of tumor versus skin retention and significant tumor inhibition. This new molecular framework will allow synthetic diversity in the number of lysine residues incorporated and will facilitate future QSAR studies. PMID:20458713

  20. Methods for producing Cu-67 radioisotope with use of a ceramic capsule for medical applications

    SciT

    Ehst, David A.; Willit, James L.

    The present invention provides a method for producing Cu67 radioisotope suitable for use in medical applications. The method comprises irradiating a metallic zinc-68 (Zn68) target within a sealed ceramic capsule with a high energy gamma ray beam. After irradiation, the Cu67 is isolated from the Zn68 by any suitable method (e.g. chemical and or physical separation). In a preferred embodiment, the Cu67 is isolated by sublimation of the zinc in a ceramic sublimation tube to afford a copper residue containing Cu67. The Cu67 can be further purified by chemical means.

  1. Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers.

    PubMed

    Liu, Jian-Yong; Wang, Chen; Zhu, Chun-Hui; Zhang, Zhi-Hong; Xue, Jin-Ping

    2017-05-19

    Two novel glucosylated zinc(ІІ) phthalocyanines 7a-7b, as well as the acetyl-protected counterparts 6a-6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a-7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake. Upon illumination, both photosensitizers show high cytotoxicity with IC 50 as low as 0.032 µM toward MCF-7 cells, which are attributed to their high cellular uptake and low aggregation tendency in the biological media, promoting the generation of intracellular reactive oxygen species (ROS). Confocal laser fluorescence microscopic studies have also revealed that they have high and selective affinities to the lysosomes, but not the mitochondria, of MCF-7 cells. The results show that these two glucosylated zinc(II) phthalocyanines are potential anticancer agents for targeting photodynamic therapy.

  2. Expression of PFKFB3 and Ki67 in lung adenocarcinomas and targeting PFKFB3 as a therapeutic strategy.

    PubMed

    Li, Xiaoli; Liu, Jian; Qian, Li; Ke, Honggang; Yao, Chan; Tian, Wei; Liu, Yifei; Zhang, Jianguo

    2018-01-11

    Phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) catalyzes the synthesis of F2,6BP, which is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1): the rate-limiting enzyme of glycolysis. During tumorigenesis, PFKFB3 increases glycolysis, angiogenesis, and tumor progression. In this study, our aim was to investigate the significance of PFKFB3 and Ki67 in human lung adenocarcinomas and to target PFKFB3 as a therapeutic strategy. In this study, we determined the expression levels of PFKFB3 mRNA and proteins in cancerous and normal lung adenocarcinomas by quantitative reverse transcription PCR (qRT-PCR), Western blot analysis, and tissue microarray immunohistochemistry analysis, respectively. In human adenocarcinoma tissues, PFKFB3 and Ki67 protein levels were related to the clinical characteristics and overall survival. Both PFKFB3 mRNA and protein were significantly higher in lung adenocarcinoma cells (all P < 0.05). A high expression of PFKFB3 and Ki67 were associated with the degree of differentiation, TNM staging, lymph node metastasis, and survival. A high expression of PFKFB3 protein was an independent prognostic marker in lung adenocarcinoma. Subsequently, 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) was used as a selective antagonist of PFKFB3. Glycolytic flux was determined by measuring glucose uptake, F2,6BP, and lactate production. Cell viability, cell cycle, cell apoptosis, cell migration, and invasion were analyzed by MTT, flow cytometry, Western blot analysis, wound healing assay, and transwell chamber assay. By targeting PFKFB3, it inhibited cell viability and glycolytic activity. It also caused apoptosis and induced cell cycle arrest. Furthermore, the migration and invasion of A549 cells was inhibited. We conclude that PFKFB3 bears an oncogene-like regulatory element in lung adenocarcinoma progression. In the treatment of lung adenocarcinoma, targeting PFKFB3 would be a promising therapeutic strategy.

  3. Selective inhibitors of zinc-dependent histone deacetylases. Therapeutic targets relevant to cancer.

    PubMed

    Kollar, Jakub; Frecer, Vladimir

    2015-01-01

    Histone deacetylases (HDACs), which act on acetylated histones and/or other non-histone protein substrates, represent validated epigenetic targets for the treatment of cancer and other human diseases. The inhibition of HDAC activity was shown to induce cell cycle arrest, differentiation, apoptosis as well as a decrease in proliferation, angiogenesis, migration, and cell resistance to chemotherapy. Targeting single HDAC isoforms with selective inhibitors will help to reveal the role of individual HDACs in cancer development or uncover further biological consequences of protein acetylation. This review focuses on conventional zinc-containing HDACs. In its first part, the biological role of individual HDACs in various types of cancer is summarized. In the second part, promising HDAC inhibitors showing activity both in enzymatic and cell-based assays are surveyed with an emphasis on the inhibitors selective to the individual HDACs.

  4. Method of producing .sup.67 Cu

    DOEpatents

    O'Brien, Jr., Harold A.; Barnes, John W.; Taylor, Wayne A.; Thomas, Kenneth E.; Bentley, Glenn E.

    1984-01-01

    A method of producing carrier-free .sup.67 Cu by proton spallation combined with subsequent chemical separation and purification is disclosed. A target consisting essentially of pressed zinc oxide is irradiated with a high energy, high current proton beam to produce a variety of spallogenic nuclides, including .sup.67 Cu and other copper isotopes. The irradiated target is dissolved in a concentrated acid solution to which a palladium salt is added. In accordance with the preferred method, the spallogenic copper is twice coprecipitated with palladium, once with metallic zinc as the precipitating agent and once with hydrogen sulfide as the precipitating agent. The palladium/copper precipitate is then dissolved in an acid solution and the copper is separated from the palladium by liquid chromatography on an anion exchange resin.

  5. Method for producing /sup 67/Cu

    DOEpatents

    O'Brien, H.A. Jr.; Barnes, J.W.; Taylor, W.A.; Thomas, K.E.; Bentley, G.E.

    A method of producing carrier-free /sup 67/Cu by proton spallation combined with subsequent chemical separation and purification is disclosed. A target consisting essentially of pressed zinc oxide is irradiated with a high energy, high current proton beam to produce a variety of spallogenic nuclides, including /sup 67/Cu and other copper isotopes. The irradiated target is dissolved in a concentrated acid solution to which a palladium salt is added. In accordance with the preferred method, the spallogenic copper is twice coprecipitated with palladium, once with metallic zinc as the precipitating agent and once with hydrogen sulfide as the precipitating agent. The palladium/copper precipitate is then dissolved in an acid solution and the copper is separated from the palladium by liquid chromatography on an anion exchange resin.

  6. Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases

    PubMed Central

    Merlin, Christine; Beaver, Lauren E.; Taylor, Orley R.; Wolfe, Scot A.; Reppert, Steven M.

    2013-01-01

    The development of reverse-genetic tools in “nonmodel” insect species with distinct biology is critical to establish them as viable model systems. The eastern North American monarch butterfly (Danaus plexippus), whose genome is sequenced, has emerged as a model to study animal clocks, navigational mechanisms, and the genetic basis of long-distance migration. Here, we developed a highly efficient gene-targeting approach in the monarch using zinc-finger nucleases (ZFNs), engineered nucleases that generate mutations at targeted genomic sequences. We focused our ZFN approach on targeting the type 2 vertebrate-like cryptochrome gene of the monarch (designated cry2), which encodes a putative transcriptional repressor of the monarch circadian clockwork. Co-injections of mRNAs encoding ZFNs targeting the second exon of monarch cry2 into “one nucleus” stage embryos led to high-frequency nonhomologous end-joining-mediated, mutagenic lesions in the germline (up to 50%). Heritable ZFN-induced lesions in two independent lines produced truncated, nonfunctional CRY2 proteins, resulting in the in vivo disruption of circadian behavior and the molecular clock mechanism. Our work genetically defines CRY2 as an essential transcriptional repressor of the monarch circadian clock and provides a proof of concept for the use of ZFNs for manipulating genes in the monarch butterfly genome. Importantly, this approach could be used in other lepidopterans and “nonmodel” insects, thus opening new avenues to decipher the molecular underpinnings of a variety of biological processes. PMID:23009861

  7. Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates.

    PubMed

    Liu, Yu-Wei; Shia, Kak-Shan; Wu, Chien-Huang; Liu, Kuan-Liang; Yeh, Yu-Cheng; Lo, Chen-Fu; Chen, Chiung-Tong; Chen, Yun-Yu; Yeh, Teng-Kuang; Chen, Wei-Han; Jan, Jiing-Jyh; Huang, Yu-Chen; Huang, Chen-Lung; Fang, Ming-Yu; Gray, Brian D; Pak, Koon Y; Hsu, Tsu-An; Huang, Kuan-Hsun; Tsou, Lun K

    2017-07-19

    A series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using in vitro cytotoxicity and plasma stability studies, PS-binding assay, in vivo pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate 24 induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.

  8. Zinc-finger protein-targeted gene regulation: Genomewide single-gene specificity

    PubMed Central

    Tan, Siyuan; Guschin, Dmitry; Davalos, Albert; Lee, Ya-Li; Snowden, Andrew W.; Jouvenot, Yann; Zhang, H. Steven; Howes, Katherine; McNamara, Andrew R.; Lai, Albert; Ullman, Chris; Reynolds, Lindsey; Moore, Michael; Isalan, Mark; Berg, Lutz-Peter; Campos, Bradley; Qi, Hong; Spratt, S. Kaye; Case, Casey C.; Pabo, Carl O.; Campisi, Judith; Gregory, Philip D.

    2003-01-01

    Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for the study and treatment of disease. Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome. A ZFP TF repressor that binds an 18-bp recognition sequence within the promoter of the endogenous CHK2 gene gives a >10-fold reduction in CHK2 mRNA and protein. This level of repression was sufficient to generate a functional phenotype, as demonstrated by the loss of DNA damage-induced CHK2-dependent p53 phosphorylation. We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (CHK2) within the monitored genome in two different cell types. These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics. PMID:14514889

  9. Zinc Finger-Containing Cellular Transcription Corepressor ZBTB25 Promotes Influenza Virus RNA Transcription and Is a Target for Zinc Ejector Drugs.

    PubMed

    Chen, Shu-Chuan; Jeng, King-Song; Lai, Michael M C

    2017-10-15

    Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNA interference (RNAi) genomic library screen. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it. ZBTB25 interacted with the viral RNA-dependent RNA polymerase (RdRp) protein and modulated its transcription activity. In addition, ZBTB25 also functioned as a viral RNA (vRNA)-binding protein, binding preferentially to the U-rich sequence within the 5' untranslated region (UTR) of vRNA. Both protein-protein and protein-RNA interactions involving ZBTB25 facilitated viral RNA transcription and replication. In addition, ZBTB25 suppressed interferon production, further enhancing viral replication. ZBTB25-associated functions required an intact zinc finger domain and posttranslational SUMO-1 modification of ZBTB25. Furthermore, treatment with disulfiram (a zinc ejector) of ZBTB25-overexpressing cells showed significantly reduced IAV production as a result of reduced RNA synthesis. Our findings indicate that IAV usurps ZBTB25 for IAV RNA synthesis and serves as a novel and potential therapeutic antiviral target. IMPORTANCE IAV-induced seasonal influenza causes severe illness and death in high-risk populations. However, IAV has developed resistance to current antiviral drugs due to its high mutation rate. Therefore, development of drugs targeting cellular factors required for IAV replication is an attractive alternative for IAV therapy. Here, we discovered a cellular protein, ZBTB25, that enhances viral RdRp activity by binding to both viral RdRp and viral RNA to stimulate viral RNA synthesis. A unique feature of ZBTB25 in the regulation of

  10. Zinc Finger-Containing Cellular Transcription Corepressor ZBTB25 Promotes Influenza Virus RNA Transcription and Is a Target for Zinc Ejector Drugs

    PubMed Central

    Chen, Shu-Chuan; Jeng, King-Song

    2017-01-01

    ABSTRACT Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNA interference (RNAi) genomic library screen. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it. ZBTB25 interacted with the viral RNA-dependent RNA polymerase (RdRp) protein and modulated its transcription activity. In addition, ZBTB25 also functioned as a viral RNA (vRNA)-binding protein, binding preferentially to the U-rich sequence within the 5′ untranslated region (UTR) of vRNA. Both protein-protein and protein-RNA interactions involving ZBTB25 facilitated viral RNA transcription and replication. In addition, ZBTB25 suppressed interferon production, further enhancing viral replication. ZBTB25-associated functions required an intact zinc finger domain and posttranslational SUMO-1 modification of ZBTB25. Furthermore, treatment with disulfiram (a zinc ejector) of ZBTB25-overexpressing cells showed significantly reduced IAV production as a result of reduced RNA synthesis. Our findings indicate that IAV usurps ZBTB25 for IAV RNA synthesis and serves as a novel and potential therapeutic antiviral target. IMPORTANCE IAV-induced seasonal influenza causes severe illness and death in high-risk populations. However, IAV has developed resistance to current antiviral drugs due to its high mutation rate. Therefore, development of drugs targeting cellular factors required for IAV replication is an attractive alternative for IAV therapy. Here, we discovered a cellular protein, ZBTB25, that enhances viral RdRp activity by binding to both viral RdRp and viral RNA to stimulate viral RNA synthesis. A unique feature of ZBTB25 in the

  11. Inhibition of bacterial carbonic anhydrases and zinc proteases: from orphan targets to innovative new antibiotic drugs.

    PubMed

    Supuran, C T

    2012-01-01

    Zinc-containing enzymes, such as carbonic anhydrases (CAs) and metalloproteases (MPs) play critical functions in bacteria, being involved in various steps of their life cycle, which are important for survival, colonization, acquisition of nutrients for growth and proliferation, facilitation of dissemination, invasion and pathogenicity. The development of resistance to many classes of clinically used antibiotics emphasizes the need of new antibacterial drug targets to be explored. There is a wealth of data regarding bacterial CAs and zinc MPs present in many pathogenic species, such as Neisseria spp., Helycobacter pylori Escherichia coli, Mycobacterium tuberculosis, Brucella spp., Streptococcus pneumoniae, Salmonella enterica, Haemophilus influenzae, Listeria spp, Vibrio spp., Pseudomonas aeruginosa, Legionella pneumophila, Streptomyces spp., Clostridium spp., Enterococcus spp., etc. Some of these enzymes have been cloned, purified and characterized by crystallographic techniques. However, for the moment, few potent and specific inhibitors for bacterial MPs have been reported except for Clostridium histolyticum collagenase, botulinum and tetanus neurotoxin and anthrax lethal factor, which will be reviewed in this article. Bacteria encode α-,β-, and/or γ-CA families, but up to now only the first two classes have been investigated in some detail in different species. The α-CAs from Neisseria spp. and H. pylori as well as the β-class enzymes from E. coli, H. pylori, M. tuberculosis, Brucella spp., S. pneumoniae, S. enterica and H. influenzae have been cloned and characterized. The catalytic/inhibition mechanisms of these CAs are well understood as X-ray crystal structures are available for some of them, but no adducts of these enzymes with inhibitors have been characterized so far. In vitro and in vivo studies with various classes of inhibitors, such as anions, sulfonamides and sulfamates have been reported. Only for Neisseria spp., H. pylori, B. suis and S

  12. Zinc-finger Nuclease-induced Gene Repair With Oligodeoxynucleotides: Wanted and Unwanted Target Locus Modifications

    PubMed Central

    Radecke, Sarah; Radecke, Frank; Cathomen, Toni; Schwarz, Klaus

    2010-01-01

    Correcting a mutated gene directly at its endogenous locus represents an alternative to gene therapy protocols based on viral vectors with their risk of insertional mutagenesis. When solely a single-stranded oligodeoxynucleotide (ssODN) is used as a repair matrix, the efficiency of the targeted gene correction is low. However, as shown with the homing endonuclease I-SceI, ssODN-mediated gene correction can be enhanced by concomitantly inducing a DNA double-strand break (DSB) close to the mutation. Because I-SceI is hardly adjustable to cut at any desired position in the human genome, here, customizable zinc-finger nucleases (ZFNs) were used to stimulate ssODN-mediated repair of a mutated single-copy reporter locus stably integrated into human embryonic kidney-293 cells. The ZFNs induced faithful gene repair at a frequency of 0.16%. Six times more often, ZFN-induced DSBs were found to be modified by unfaithful addition of ssODN between the termini and about 60 times more often by nonhomologous end joining-related deletions and insertions. Additionally, ZFN off-target activity based on binding mismatch sites at the locus of interest was detected in in vitro cleavage assays and also in chromosomal DNA isolated from treated cells. Therefore, the specificity of ZFN-induced ssODN-mediated gene repair needs to be improved, especially regarding clinical applications. PMID:20068556

  13. Targeting Serous Epithelial Ovarian Cancer with Designer Zinc Finger Transcription Factors*

    PubMed Central

    Lara, Haydee; Wang, Yuhua; Beltran, Adriana S.; Juárez-Moreno, Karla; Yuan, Xinni; Kato, Sumie; Leisewitz, Andrea V.; Cuello Fredes, Mauricio; Licea, Alexei F.; Connolly, Denise C.; Huang, Leaf; Blancafort, Pilar

    2012-01-01

    Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers. PMID:22782891

  14. Targeted mutagenesis using zinc-finger nucleases in perennial fruit trees.

    PubMed

    Peer, Reut; Rivlin, Gil; Golobovitch, Sara; Lapidot, Moshe; Gal-On, Amit; Vainstein, Alexander; Tzfira, Tzvi; Flaishman, Moshe A

    2015-04-01

    Targeting a gene in apple or fig with ZFN, introduced by transient or stable transformation, should allow genome editing with high precision to advance basic science and breeding programs. Genome editing is a powerful tool for precise gene manipulation in any organism; it has recently been shown to be of great value for annual plants. Classical breeding strategies using conventional cross-breeding and induced mutations have played an important role in the development of new cultivars in fruit trees. However, fruit-tree breeding is a lengthy process with many limitations. Efficient and widely applied methods for targeted modification of fruit-tree genomes are not yet available. In this study, transgenic apple and fig lines carrying a zinc-finger nuclease (ZFNs) under the control of a heat-shock promoter were developed. Editing of a mutated uidA gene, following expression of the ZFN genes by heat shock, was confirmed by GUS staining and PCR product sequencing. Finally, whole plants with a repaired uidA gene due to deletion of a stop codon were regenerated. The ZFN-mediated gene modifications were stable and passed onto regenerants from ZFN-treated tissue cultures. This is the first demonstration of efficient and precise genome editing, using ZFN at a specific genomic locus, in two different perennial fruit trees-apple and fig. We conclude that targeting a gene in apple or fig with a ZFN introduced by transient or stable transformation should allow knockout of a gene of interest. Using this technology for genome editing allows for marker gene-independent and antibiotic selection-free genome engineering with high precision in fruit trees to advance basic science as well as nontransgenic breeding programs.

  15. Aluminum-doped zinc oxide thin films grown on various substrates using facing target sputtering system

    NASA Astrophysics Data System (ADS)

    Kim, Hwa-Min; Lee, Chang Hyun; Shon, Sun Young; Kim, Bong Hwan

    2017-11-01

    Aluminum-doped zinc oxide (AZO) films were fabricated on various substrates, such as glass, polyethylene naphthalate (PEN), and polyethylene terephthalate (PET), at room temperature using a facing target sputtering (FTS) system with hetero ZnO and Al2O3 targets, and their electrical and optical properties were investigated. The AZO film on glass exhibited compressive stress while the films on the plastic substrates showed tensile stress. These stresses negatively affected the crystalline quality of the AZO films, and it is suggested that the poor crystalline quality of the films may be related to the neutral Al-based defect complexes formed in the films; these complexes act as neutral impurity scattering centers. AZO films with good optoelectronic properties could be formed on the glass and plastic substrates by the FTS technique using the hetero targets. The AZO films deposited on the glass, PEN, and PET substrates showed very low resistivities, of 5.0 × 10-4 Ω cm, 7.0 × 10-4 Ω cm, and 7.4 × 10-4 Ω cm, respectively. Further, the figure merit of the AZO film formed on the PEN substrate in the visible range (400-700 nm) was significantly higher than that of the AZO film on PET and similar to that of the AZO film on glass. Finally, the average transmittances of the films in the visible range (400-700 nm) were 83.16% (on glass), 76.3% (on PEN), and 78.16% (on PET).

  16. Red fluorescent zinc oxide nanoparticle: A novel platform for cancer targeting

    DOE PAGES

    Hong, Hao; Wang, Fei; Zhang, Yin; ...

    2015-01-21

    Multifunctional zinc oxide (ZnO) nanoparticles (NPs) with well-integrated multimodality imaging capacities have generated increasing research interest in the past decade. However, limited progress has been made in developing ZnO NP-based multimodality tumor-imaging agents. In this paper, we developed novel red fluorescent ZnO NPs and described the successful conjugation of 64Cu ( t 1/2 = 12.7 h) and TRC105, a chimeric monoclonal antibody against CD105, to these ZnO NPs via well-developed surface engineering procedures. The produced dual-modality ZnO NPs were readily applicable for positron emission tomography (PET) imaging and fluorescence imaging of the tumor vasculature. Their pharmacokinetics and tumor-targeting efficacy/specificity inmore » mice bearing murine breast 4T1 tumor were thoroughly investigated. In conclusion, ZnO NPs with dual-modality imaging properties can serve as an attractive candidate for future cancer theranostics.« less

  17. Biofortified indica rice attains iron and zinc nutrition dietary targets in the field

    PubMed Central

    Trijatmiko, Kurniawan R.; Dueñas, Conrado; Tsakirpaloglou, Nikolaos; Torrizo, Lina; Arines, Felichi Mae; Adeva, Cheryl; Balindong, Jeanette; Oliva, Norman; Sapasap, Maria V.; Borrero, Jaime; Rey, Jessica; Francisco, Perigio; Nelson, Andy; Nakanishi, Hiromi; Lombi, Enzo; Tako, Elad; Glahn, Raymond P.; Stangoulis, James; Chadha-Mohanty, Prabhjit; Johnson, Alexander A. T.; Tohme, Joe; Barry, Gerard; Slamet-Loedin, Inez H.

    2016-01-01

    More than two billion people are micronutrient deficient. Polished grains of popular rice varieties have concentration of approximately 2 μg g−1 iron (Fe) and 16 μg g−1 zinc (Zn). The HarvestPlus breeding programs for biofortified rice target 13 μg g−1 Fe and 28 μg g−1 Zn to reach approximately 30% of the estimated average requirement (EAR). Reports on engineering Fe content in rice have shown an increase up to 18 μg g−1 in glasshouse settings; in contrast, under field conditions, 4 μg g−1 was the highest reported concentration. Here, we report on selected transgenic events, field evaluated in two countries, showing 15 μg g−1 Fe and 45.7 μg g−1 Zn in polished grain. Rigorous selection was applied to 1,689 IR64 transgenic events for insert cleanliness and, trait and agronomic performances. Event NASFer-274 containing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes showed a single locus insertion without a yield penalty or altered grain quality. Endosperm Fe and Zn enrichment was visualized by X-ray fluorescence imaging. The Caco-2 cell assay indicated that Fe is bioavailable. No harmful heavy metals were detected in the grain. The trait remained stable in different genotype backgrounds. PMID:26806528

  18. TNFα Post-Translationally Targets ZnT2 to Accumulate Zinc in Lysosomes.

    PubMed

    Hennigar, Stephen R; Kelleher, Shannon L

    2015-10-01

    Mammary epithelial cells undergo widespread lysosomal-mediated cell death (LCD) during early mammary gland involution. Recently, we demonstrated that tumor necrosis factor-α (TNFα), a cytokine released during early involution, redistributes the zinc (Zn) transporter ZnT2 to accumulate Zn in lysosomes and activate LCD and involution. The objective of this study is to determine how TNFα retargets ZnT2 to lysosomes. We tested the hypothesis that TNFα signaling dephosphorylates ZnT2 to uncover a highly conserved dileucine motif (L294L) in the C-terminus of ZnT2, allowing adaptor protein complex-3 (AP-3) to bind and traffic ZnT2 to lysosomes. Confocal micrographs showed that TNFα redistributed wild-type (WT) ZnT2 from late endosomes (Pearson's coefficient = 0.202 ± 0.05 and 0.097 ± 0.03; P<0.05) to lysosomes (0.292 ± 0.03 and 0.649 ± 0.03; P<0.0001), which increased lysosomal Zn (P<0.0001) and activated LCD (P<0.0001) compared to untreated cells. Mutation of the dileucine motif (L294V) eliminated the ability of TNFα to redistribute ZnT2 from late endosomes to lysosomes, increase lysosomal Zn, or activate LCD. Moreover, TNFα increased (P<0.05) AP-3 binding to wt ZnT2 but not to L294V immunoprecipitates. Finally, using phospho- and dephospho-mimetics of predicted phosphorylation sites (T281, T288, and S296), we found that dephosphorylated S296 was required to target ZnT2 to accumulate Zn in lysosomes and activate LCD. Our findings suggest that women with variation in the C-terminus of ZnT2 may be at risk for inadequate involution and breast disease due the inability to traffic ZnT2 to lysosomes. © 2015 Wiley Periodicals, Inc.

  19. Zinc Signals and Immunity.

    PubMed

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  20. Biofortified indica rice attains iron and zinc nutrition dietary targets in the field

    Iron (Fe) and zinc (Zn) deficiencies are the most prevalent micronutrient malnutrition globally1. Fe in rice has proven efficacious in improving serum ferritin concentration and body Fe levels2. Rapid progress in biofortification demonstrates the feasibility to enhance Fe in polished rice by expre...

  1. A rapid, generally applicable method to engineer zinc fingers illustrated by targeting the HIV-1 promoter.

    PubMed

    Isalan, M; Klug, A; Choo, Y

    2001-07-01

    DNA-binding domains with predetermined sequence specificity are engineered by selection of zinc finger modules using phage display, allowing the construction of customized transcription factors. Despite remarkable progress in this field, the available protein-engineering methods are deficient in many respects, thus hampering the applicability of the technique. Here we present a rapid and convenient method that can be used to design zinc finger proteins against a variety of DNA-binding sites. This is based on a pair of pre-made zinc finger phage-display libraries, which are used in parallel to select two DNA-binding domains each of which recognizes given 5 base pair sequences, and whose products are recombined to produce a single protein that recognizes a composite (9 base pair) site of predefined sequence. Engineering using this system can be completed in less than two weeks and yields proteins that bind sequence-specifically to DNA with Kd values in the nanomolar range. To illustrate the technique, we have selected seven different proteins to bind various regions of the human immunodeficiency virus 1 (HIV-1) promoter.

  2. Cu-67 Photonuclear Production

    NASA Astrophysics Data System (ADS)

    Starovoitova, Valeriia; Foote, Davy; Harris, Jason; Makarashvili, Vakhtang; Segebade, Christian R.; Sinha, Vaibhav; Wells, Douglas P.

    2011-06-01

    Cu-67 is considered as one of the most promising radioisotopes for cancer therapy with monoclonal antibodies. Current production schemes using high-flux reactors and cyclotrons do not meet potential market need. In this paper we discuss Cu-67 photonuclear production through the reaction Zn-68(γ,p)Cu-67. Computer simulations were done together with experiments to study and optimize Cu-67 yield in natural Zn target. The data confirms that the photonuclear method has potential to produce large quantities of the isotope with sufficient purity to be used in medical field.

  3. Directing an artificial zinc finger protein to new targets by fusion to a non-DNA-binding domain.

    PubMed

    Lim, Wooi F; Burdach, Jon; Funnell, Alister P W; Pearson, Richard C M; Quinlan, Kate G R; Crossley, Merlin

    2016-04-20

    Transcription factors are often regarded as having two separable components: a DNA-binding domain (DBD) and a functional domain (FD), with the DBD thought to determine target gene recognition. While this holds true for DNA bindingin vitro, it appears thatin vivoFDs can also influence genomic targeting. We fused the FD from the well-characterized transcription factor Krüppel-like Factor 3 (KLF3) to an artificial zinc finger (AZF) protein originally designed to target the Vascular Endothelial Growth Factor-A (VEGF-A) gene promoter. We compared genome-wide occupancy of the KLF3FD-AZF fusion to that observed with AZF. AZF bound to theVEGF-Apromoter as predicted, but was also found to occupy approximately 25,000 other sites, a large number of which contained the expected AZF recognition sequence, GCTGGGGGC. Interestingly, addition of the KLF3 FD re-distributes the fusion protein to new sites, with total DNA occupancy detected at around 50,000 sites. A portion of these sites correspond to known KLF3-bound regions, while others contained sequences similar but not identical to the expected AZF recognition sequence. These results show that FDs can influence and may be useful in directing AZF DNA-binding proteins to specific targets and provide insights into how natural transcription factors operate. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Zinc at glutamatergic synapses.

    PubMed

    Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

    2009-01-12

    It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

  5. Evaluation of iron and zinc bioavailability of beans targeted for biofortification using in vitro and in vivo models and their effect on the nutritional status of preschool children.

    PubMed

    Vaz-Tostes, Maria das Graças; Verediano, Thaisa Agrizzi; de Mejia, Elvira Gonzalez; Brunoro Costa, Neuza Maria

    2016-03-15

    Biofortified beans have been produced with higher nutrient concentrations. The objective was to evaluate the in vitro and in vivo iron and zinc bioavailability of common beans Pontal (PO), targeted for biofortification, compared with conventional Perola (PE) and their effects on the iron and zinc nutritional status of preschool children. In Caco-2 cells, PO and PE beans did not show differences in ferritin (PO, 13.1 ± 1.4; PE, 13.6 ± 1.4 ng mg(-1) protein) or zinc uptake (PO, 15.9 ± 1.5; PE, 15.5 ± 3.5 µmol mg(-1) protein). In the rat, PO and PE beans presented high iron bioavailability (PO, 109.6 ± 29.5; PE, 110.7 ± 13.9%). In preschool children, no changes were observed in iron and zinc nutritional status comparing before and after PO consumption (ferritin, 41.2 ± 23.2 and 28.9 ± 40.4 µg L(-1) ; hemoglobin, 13.7 ± 2.2 and 13.1 ± 3.2 g dL(-1) ; plasma zinc, 119.2 ± 24.5 and 133.9 ± 57.7 µg dL(-1) ; erythrocyte zinc, 53.5 ± 13.8 and 59.4 ± 17.1 µg g(-1) hemoglobin). Iron and zinc bioavailability in PO and PE beans was not statistically different using either cell culture, animal or human models. Efforts should focus on increasing mineral bioavailability of beans targeted for biofortification. © 2015 Society of Chemical Industry.

  6. Analysis of illegitimate genomic integration mediated by zinc-finger nucleases: implications for specificity of targeted gene correction

    PubMed Central

    2010-01-01

    Background Formation of site specific genomic double strand breaks (DSBs), induced by the expression of a pair of engineered zinc-finger nucleases (ZFNs), dramatically increases the rates of homologous recombination (HR) between a specific genomic target and a donor plasmid. However, for the safe use of ZFN induced HR in practical applications, possible adverse effects of the technology such as cytotoxicity and genotoxicity need to be well understood. In this work, off-target activity of a pair of ZFNs has been examined by measuring the ratio between HR and illegitimate genomic integration in cells that are growing exponentially, and in cells that have been arrested in the G2/M phase. Results A reporter cell line that contained consensus ZFN binding sites in an enhanced green fluorescent protein (EGFP) reporter gene was used to measure ratios between HR and non-homologous integration of a plasmid template. Both in human cells (HEK 293) containing the consensus ZFN binding sites and in cells lacking the ZFN binding sites, a 3.5 fold increase in the level of illegitimate integration was observed upon ZFN expression. Since the reporter gene containing the consensus ZFN target sites was found to be intact in cells where illegitimate integration had occurred, increased rates of illegitimate integration most likely resulted from the formation of off-target genomic DSBs. Additionally, in a fraction of the ZFN treated cells the co-occurrence of both specific HR and illegitimate integration was observed. As a mean to minimize unspecific effects, cell cycle manipulation of the target cells by induction of a transient G2/M cell cycle arrest was shown to stimulate the activity of HR while having little effect on the levels of illegitimate integration, thus resulting in a nearly eight fold increase in the ratio between the two processes. Conclusions The demonstration that ZFN expression, in addition to stimulating specific gene targeting by HR, leads to increased rates of

  7. Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

    PubMed

    Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

    2016-01-01

    Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

  8. Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets.

    PubMed

    Schwiebert, Erik M; Liang, Lihua; Cheng, Nai-Lin; Williams, Clintoria Richards; Olteanu, Dragos; Welty, Elisabeth A; Zsembery, Akos

    2005-12-01

    In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover, its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second, we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes in membrane potential.

  9. Zinc Signals and Immunity

    PubMed Central

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-01-01

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as “zinc waves”, and late homeostatic zinc signals regarding prolonged changes in intracellular zinc. PMID:29064429

  10. Zinc finger protein designed to target 2-long terminal repeat junctions interferes with human immunodeficiency virus integration.

    PubMed

    Sakkhachornphop, Supachai; Barbas, Carlos F; Keawvichit, Rassamee; Wongworapat, Kanlaya; Tayapiwatana, Chatchai

    2012-09-01

    Integration of the human immunodeficiency virus type 1 (HIV-1) genome into the host chromosome is a vital step in the HIV life cycle. The highly conserved cytosine-adenine (CA) dinucleotide sequence immediately upstream of the cleavage site is crucial for integrase (IN) activity. As this viral enzyme has an important role early in the HIV-1 replication cycle, interference with the IN substrate has become an attractive strategy for therapeutic intervention. We demonstrated that a designed zinc finger protein (ZFP) fused to green fluorescent protein (GFP) targets the 2-long terminal repeat (2-LTR) circle junctions of HIV-1 DNA with nanomolar affinity. We report now that 2LTRZFP-GFP stably transduced into 293T cells interfered with the expression of vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral red fluorescent protein (RFP), as shown by the suppression of RFP expression. We also used a third-generation lentiviral vector and pCEP4 expression vector to deliver the 2LTRZFP-GFP transgene into human T-lymphocytic cells, and a stable cell line for long-term expression studies was selected for HIV-1 challenge. HIV-1 integration and replication were inhibited as measured by Alu-gag real-time PCR and p24 antigen assay. In addition, the molecular activity of 2LTRZFP-GFP was evaluated in peripheral blood mononuclear cells. The results were confirmed by Alu-gag real-time PCR for integration interference. We suggest that the expression of 2LTRZFP-GFP limited viral integration on intracellular immunization, and that it has potential for use in HIV gene therapy in the future.

  11. Zinc Finger Protein Designed to Target 2-Long Terminal Repeat Junctions Interferes with Human Immunodeficiency Virus Integration

    PubMed Central

    Sakkhachornphop, Supachai; Barbas, Carlos F.; Keawvichit, Rassamee; Wongworapat, Kanlaya

    2012-01-01

    Abstract Integration of the human immunodeficiency virus type 1 (HIV-1) genome into the host chromosome is a vital step in the HIV life cycle. The highly conserved cytosine–adenine (CA) dinucleotide sequence immediately upstream of the cleavage site is crucial for integrase (IN) activity. As this viral enzyme has an important role early in the HIV-1 replication cycle, interference with the IN substrate has become an attractive strategy for therapeutic intervention. We demonstrated that a designed zinc finger protein (ZFP) fused to green fluorescent protein (GFP) targets the 2-long terminal repeat (2-LTR) circle junctions of HIV-1 DNA with nanomolar affinity. We report now that 2LTRZFP-GFP stably transduced into 293T cells interfered with the expression of vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral red fluorescent protein (RFP), as shown by the suppression of RFP expression. We also used a third-generation lentiviral vector and pCEP4 expression vector to deliver the 2LTRZFP-GFP transgene into human T-lymphocytic cells, and a stable cell line for long-term expression studies was selected for HIV-1 challenge. HIV-1 integration and replication were inhibited as measured by Alu-gag real-time PCR and p24 antigen assay. In addition, the molecular activity of 2LTRZFP-GFP was evaluated in peripheral blood mononuclear cells. The results were confirmed by Alu-gag real-time PCR for integration interference. We suggest that the expression of 2LTRZFP-GFP limited viral integration on intracellular immunization, and that it has potential for use in HIV gene therapy in the future. PMID:22429108

  12. Zinc Enzymes.

    ERIC Educational Resources Information Center

    Bertini, I.; And Others

    1985-01-01

    Discusses the role of zinc in various enzymes concerned with hydration, hydrolysis, and redox reactions. The binding of zinc to protein residues, properties of noncatalytic zinc(II) and catalytic zinc, and the reactions catalyzed by zinc are among the topics considered. (JN)

  13. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  14. Zinc and Autophagy

    PubMed Central

    Liuzzi, Juan P.; Guo, Liang; Yoo, Changwon; Stewart, Tiffanie S

    2014-01-01

    Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated.Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria.Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake. PMID:25012760

  15. 67Cu-Radiolabeling of a multimeric RGD peptide for αVβ3 integrin-targeted radionuclide therapy: stability, therapeutic efficacy, and safety studies in mice.

    PubMed

    Jin, Zhao-Hui; Furukawa, Takako; Ohya, Tomoyuki; Degardin, Mélissa; Sugyo, Aya; Tsuji, Atsushi B; Fujibayashi, Yasuhisa; Zhang, Ming-Rong; Higashi, Tatsuya; Boturyn, Didier; Dumy, Pascal; Saga, Tsuneo

    2017-04-01

    Copper-67 (Cu) is one of the most promising radionuclides for internal radiation therapy. Globally, several projects have recently been initiated for developing innovative approaches for the large-scale production of Cu. Encouraged by these, we performed Cu-radiolabeling of a tetrameric cyclic Arg-Gly-Asp (cRGD) peptide conjugate, cyclam-RAFT-c(-RGDfK-)4, which selectively targets αVβ3 integrin (αVβ3), the transmembrane receptor involved in tumor invasion, angiogenesis, and metastasis. We also evaluated the therapeutic potential and safety of this radiocompound. Cu, produced through the Ni(α, p)Cu reaction, was used for the radiolabeling of cyclam-RAFT-c(-RGDfK-)4 at 70°C for 10 min. The radiolabeling efficiency and product stability were assessed using reversed-phase high-performance liquid chromatography and/or thin-layer chromatography. Mice with subcutaneous αVβ3-positive U87MG-glioblastoma xenografts received a single intravenous injection of one of the following: Cu-cyclam-RAFT-c(-RGDfK-)4 (11.1 MBq), peptide control, or vehicle solution. The tumor volumes were measured, side effects were assessed in terms of body weight, routine hematology, and hepatic and renal functions, and the mouse radiation dosimetry was estimated. Cu-cyclam-RAFT-c(-RGDfK-)4 was produced with a radiochemical purity of 97.9±2.4% and a specific activity of 2.7±0.6 MBq/nmol and showed high in-vitro and in-vivo plasma stability. The administration of a single dose of Cu-cyclam-RAFT-c(-RGDfK-)4 resulted in significant tumor growth delay in comparison with that observed upon vehicle or peptide control administration, with an estimated tumor-absorbed dose of 0.712 Gy. No significant toxicity was observed in Cu-cyclam-RAFT-c(-RGDfK-)4-treated mice. Cu-cyclam-RAFT-c(-RGDfK-)4 would be a promising therapeutic agent for αVβ3 integrin-targeted internal radiotherapy.

  16. Purifying Properly Folded Cysteine-rich, Zinc Finger Containing Recombinant Proteins for Structural Drug Targeting Studies: the CH1 Domain of p300 as a Case Example

    PubMed Central

    Kim, Yong Joon; Kaluz, Stefan; Mehta, Anil; Weinert, Emily; Rivera, Shannon; Van Meir, Erwin G.

    2017-01-01

    The transcription factor Hypoxia-Inducible Factor (HIF) complexes with the coactivator p300, activating the hypoxia response pathway and allowing tumors to grow. The CH1 and CAD domains of each respective protein form the interface between p300 and HIF. Small molecule compounds are in development that target and inhibit HIF/p300 complex formation, with the goal of reducing tumor growth. High resolution NMR spectroscopy is necessary to study ligand interaction with p300-CH1, and purifying high quantities of properly folded p300-CH1 is needed for pursuing structural and biophysical studies. p300-CH1 has 3 zinc fingers and 9 cysteine residues, posing challenges associated with reagent compatibility and protein oxidation. A protocol has been developed to overcome such issues by incorporating zinc during expression and streamlining the purification time, resulting in a high yield of optimally folded protein (120 mg per 4 L expression media) that is suitable for structural NMR studies. The structural integrity of the final recombinant p300-CH1 has been verified to be optimal using onedimensional 1H NMR spectroscopy and circular dichroism. This protocol is applicable for the purification of other zinc finger containing proteins. PMID:28966947

  17. Gene targeting technologies in rats: zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats.

    PubMed

    Mashimo, Tomoji

    2014-01-01

    The laboratory rat has been widely used as an animal model in biomedical science for more than 150 years. Applying zinc-finger nucleases or transcription activator-like effector nucleases to rat embryos via microinjection is an efficient genome editing tool for generating targeted knockout rats. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonucleases have been used as an effective tool for precise and multiplex genome editing in mice and rats. In this review, the advantages and disadvantages of these site-specific nuclease technologies for genetic analysis and manipulation in rats are discussed. © 2013 The Author Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  18. Zinc-finger nuclease-mediated targeted insertion of reporter genes for quantitative imaging of gene expression in sea urchin embryos

    PubMed Central

    Ochiai, Hiroshi; Sakamoto, Naoaki; Fujita, Kazumasa; Nishikawa, Masatoshi; Suzuki, Ken-ichi; Matsuura, Shinya; Miyamoto, Tatsuo; Sakuma, Tetsushi; Shibata, Tatsuo; Yamamoto, Takashi

    2012-01-01

    To understand complex biological systems, such as the development of multicellular organisms, it is important to characterize the gene expression dynamics. However, there is currently no universal technique for targeted insertion of reporter genes and quantitative imaging in multicellular model systems. Recently, genome editing using zinc-finger nucleases (ZFNs) has been reported in several models. ZFNs consist of a zinc-finger DNA-binding array with the nuclease domain of the restriction enzyme FokI and facilitate targeted transgene insertion. In this study, we successfully inserted a GFP reporter cassette into the HpEts1 gene locus of the sea urchin, Hemicentrotus pulcherrimus. We achieved this insertion by injecting eggs with a pair of ZFNs for HpEts1 with a targeting donor construct that contained ∼1-kb homology arms and a 2A-histone H2B–GFP cassette. We increased the efficiency of the ZFN-mediated targeted transgene insertion by in situ linearization of the targeting donor construct and cointroduction of an mRNA for a dominant-negative form of HpLig4, which encodes the H. pulcherrimus homolog of DNA ligase IV required for error-prone nonhomologous end joining. We measured the fluorescence intensity of GFP at the single-cell level in living embryos during development and found that there was variation in HpEts1 expression among the primary mesenchyme cells. These findings demonstrate the feasibility of ZFN-mediated targeted transgene insertion to enable quantification of the expression levels of endogenous genes during development in living sea urchin embryos. PMID:22711830

  19. Experimental studies of the medical radioisotopes production in neutron spectra generated by 660 MeV protons and 1-8 GeV deuterons in massive uranium target

    NASA Astrophysics Data System (ADS)

    Zhadan, A.; Sotnikov, V.; Adam, J.; Solnyshkin, A.; Tyutyunnikov, S.; Voronko, V.; Zhivkov, P.; Zavorka, L.

    2017-06-01

    The possibility of medical radionuclide 64,67Cu production in spallation neutron spectrum induced by proton and deuteron beams has been studied. Experiments were performed on a massive natural uranium target at the accelerators Phasotron and Nuclotron JINR, Dubna. The main disadvantage of this method is a high 64Cu/67Cu ratio in the final product at EOB. Significantly reduce 64Cu/67Cu ratio is only possible if you use zinc target enriched with 68Zn or 67Zn. The MCNPX simulation of 67,64Cu production and definition of the theoretical limit of the specific activity of 67,64Cu by irradiation of natural zinc and zinc enriched by the 68 isotope were performed. The neutron flux density shouldnot be less than 5.1013 n/cm2/s if we want to obtain high specific activity (>200 GBq/mg) of 67Cu.

  20. Zinc starvation induces autophagy in yeast

    PubMed Central

    Kawamata, Tomoko; Horie, Tetsuro; Matsunami, Miou; Sasaki, Michiko; Ohsumi, Yoshinori

    2017-01-01

    Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome. In this study, we investigated how autophagy functions under zinc starvation. Zinc depletion induced non-selective autophagy, which is important for zinc-limited growth. Induction of autophagy by zinc starvation was not directly related to transcriptional activation of Zap1. Instead, TORC1 inactivation directed zinc starvation-induced autophagy. Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes. PMID:28264932

  1. Zinc starvation induces autophagy in yeast.

    PubMed

    Kawamata, Tomoko; Horie, Tetsuro; Matsunami, Miou; Sasaki, Michiko; Ohsumi, Yoshinori

    2017-05-19

    Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome. In this study, we investigated how autophagy functions under zinc starvation. Zinc depletion induced non-selective autophagy, which is important for zinc-limited growth. Induction of autophagy by zinc starvation was not directly related to transcriptional activation of Zap1. Instead, TORC1 inactivation directed zinc starvation-induced autophagy. Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Allosteric ligands for the pharmacologically important Flavivirus target (NS5) from ZINC database based on pharmacophoric points, free energy calculations and dynamics correlation.

    PubMed

    Khan, Abbas; Saleem, Shoaib; Idrees, Muhammad; Ali, Syed Shujait; Junaid, Muhammad; Chandra Kaushik, Aman; Wei, Dong-Qing

    2018-04-11

    Dengue virus belongs to a group of human pathogens, which causes different diseases, dengue hemorrhagic fever and dengue shock syndrome in humans. It possesses RNA as a genetic material and is replicated with the aid of NS5 protein. RNA-dependent RNA polymerase (RdRp) is an important domain of NS5 in the replication of that virus. The catalytic process activity of RdRp is making it an important target for antiviral chemical therapy. To date, No FDA drug has been approved and marketed for the treatment of diseases caused by Dengue virus. So, there is a dire need to advance an area of active antiviral inhibitors that is safe, less expensive and widely available. An experimentally validated complex of Dengue NS5 and compound 27 (6LS) were used as pharmacophoric input and hits were identified. We also used Molecular dynamics (MD) simulations alongside free energy and dynamics of the internal residues of the apo and holo systems to understand the binding mechanism. Our analysis resulted that the three inhibitors (ZINC72070002, ZINC6551486, and ZINC39588257) greatly affected the interior dynamics and residual signaling to dysfunction the replicative role of NS5. The interaction of these inhibitors caused the loss of the correlated motion of NS5 near to the N terminus and helped the stability of the binding complex. This investigation provided a methodological route to discover allosteric inhibitors against the epidemics of this Flaviviruses. Allosteric inhibitors are important and major assets in considering the development of the competitive and robust antiviral agents such as against Dengue viral infection. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. The haloarchaeal MCM proteins: bioinformatic analysis and targeted mutagenesis of the β7-β8 and β9-β10 hairpin loops and conserved zinc binding domain cysteines.

    PubMed

    Kristensen, Tatjana P; Maria Cherian, Reeja; Gray, Fiona C; MacNeill, Stuart A

    2014-01-01

    The hexameric MCM complex is the catalytic core of the replicative helicase in eukaryotic and archaeal cells. Here we describe the first in vivo analysis of archaeal MCM protein structure and function relationships using the genetically tractable haloarchaeon Haloferax volcanii as a model system. Hfx. volcanii encodes a single MCM protein that is part of the previously identified core group of haloarchaeal MCM proteins. Three structural features of the N-terminal domain of the Hfx. volcanii MCM protein were targeted for mutagenesis: the β7-β8 and β9-β10 β-hairpin loops and putative zinc binding domain. Five strains carrying single point mutations in the β7-β8 β-hairpin loop were constructed, none of which displayed impaired cell growth under normal conditions or when treated with the DNA damaging agent mitomycin C. However, short sequence deletions within the β7-β8 β-hairpin were not tolerated and neither was replacement of the highly conserved residue glutamate 187 with alanine. Six strains carrying paired alanine substitutions within the β9-β10 β-hairpin loop were constructed, leading to the conclusion that no individual amino acid within that hairpin loop is absolutely required for MCM function, although one of the mutant strains displays greatly enhanced sensitivity to mitomycin C. Deletions of two or four amino acids from the β9-β10 β-hairpin were tolerated but mutants carrying larger deletions were inviable. Similarly, it was not possible to construct mutants in which any of the conserved zinc binding cysteines was replaced with alanine, underlining the likely importance of zinc binding for MCM function. The results of these studies demonstrate the feasibility of using Hfx. volcanii as a model system for reverse genetic analysis of archaeal MCM protein function and provide important confirmation of the in vivo importance of conserved structural features identified by previous bioinformatic, biochemical and structural studies.

  4. The haloarchaeal MCM proteins: bioinformatic analysis and targeted mutagenesis of the β7-β8 and β9-β10 hairpin loops and conserved zinc binding domain cysteines

    PubMed Central

    Kristensen, Tatjana P.; Maria Cherian, Reeja; Gray, Fiona C.; MacNeill, Stuart A.

    2014-01-01

    The hexameric MCM complex is the catalytic core of the replicative helicase in eukaryotic and archaeal cells. Here we describe the first in vivo analysis of archaeal MCM protein structure and function relationships using the genetically tractable haloarchaeon Haloferax volcanii as a model system. Hfx. volcanii encodes a single MCM protein that is part of the previously identified core group of haloarchaeal MCM proteins. Three structural features of the N-terminal domain of the Hfx. volcanii MCM protein were targeted for mutagenesis: the β7-β8 and β9-β10 β-hairpin loops and putative zinc binding domain. Five strains carrying single point mutations in the β7-β8 β-hairpin loop were constructed, none of which displayed impaired cell growth under normal conditions or when treated with the DNA damaging agent mitomycin C. However, short sequence deletions within the β7-β8 β-hairpin were not tolerated and neither was replacement of the highly conserved residue glutamate 187 with alanine. Six strains carrying paired alanine substitutions within the β9-β10 β-hairpin loop were constructed, leading to the conclusion that no individual amino acid within that hairpin loop is absolutely required for MCM function, although one of the mutant strains displays greatly enhanced sensitivity to mitomycin C. Deletions of two or four amino acids from the β9-β10 β-hairpin were tolerated but mutants carrying larger deletions were inviable. Similarly, it was not possible to construct mutants in which any of the conserved zinc binding cysteines was replaced with alanine, underlining the likely importance of zinc binding for MCM function. The results of these studies demonstrate the feasibility of using Hfx. volcanii as a model system for reverse genetic analysis of archaeal MCM protein function and provide important confirmation of the in vivo importance of conserved structural features identified by previous bioinformatic, biochemical and structural studies. PMID:24723920

  5. Inhibitors incorporating zinc-binding groups target the GlcNAc-PI de-N-acetylase in Trypanosoma brucei, the causative agent of African sleeping sickness.

    PubMed

    Abdelwahab, Nuha Z; Crossman, Arthur T; Sullivan, Lauren; Ferguson, Michael A J; Urbaniak, Michael D

    2012-03-01

    Disruption of glycosylphosphatidylinositol biosynthesis is genetically and chemically validated as a drug target against the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. The N-acetylglucosamine-phosphatidylinositol de-N-acetylase (deNAc) is a zinc metalloenzyme responsible for the second step of glycosylphosphatidylinositol biosynthesis. We recently reported the synthesis of eight deoxy-2-C-branched monosaccharides containing carboxylic acid, hydroxamic acid, or N-hydroxyurea substituents at the C2 position that may act as zinc-binding groups. Here, we describe the synthesis of a glucocyclitol-phospholipid incorporating a hydroxamic acid moiety and report the biochemical evaluation of the monosaccharides and the glucocyclitol-phospholipid as inhibitors of the trypanosome deNAc in the cell-free system and against recombinant enzyme. Monosaccharides with carboxylic acid or hydroxamic acid substituents were found to be the inhibitors of the trypanosome deNAc with IC(50) values 0.1-1.5mM and the glucocyclitol-phospholipid was found to be a dual inhibitor of the deNAc and the α1-4-mannose transferase with an apparent IC(50)= 19±0.5μm. © 2011 John Wiley & Sons A/S.

  6. Zinc Information

    MedlinePlus

    ... for Eye Conditions Clinical Digest: Hepatitis C and Dietary Supplements Related Resources From Other Agencies Age-Related Eye Disease Study 2 (AREDS2) ( NEI ) Can Zinc Be Harmful? ( ODS ) Zinc ( ODS ) Follow NCCIH: Read our disclaimer ...

  7. Arabidopsis VARIEGATED 3 encodes a chloroplast-targeted, zinc-finger protein required for chloroplast and palisade cell development.

    PubMed

    Naested, Henrik; Holm, Agnethe; Jenkins, Tom; Nielsen, H Bjørn; Harris, Cassandra A; Beale, Michael H; Andersen, Mathias; Mant, Alexandra; Scheller, Henrik; Camara, Bilal; Mattsson, Ole; Mundy, John

    2004-09-15

    The stable, recessive Arabidopsis variegated 3 (var3) mutant exhibits a variegated phenotype due to somatic areas lacking or containing developmentally retarded chloroplasts and greatly reduced numbers of palisade cells. The VAR3 gene, isolated by transposon tagging, encodes the 85.9 kDa VAR3 protein containing novel repeats and zinc fingers described as protein interaction domains. VAR3 interacts specifically in yeast and in vitro with NCED4, a putative polyene chain or carotenoid dioxygenase, and both VAR3 and NCED4 accumulate in the chloroplast stroma. Metabolic profiling demonstrates that pigment profiles are qualitatively similar in wild type and var3, although var3 accumulates lower levels of chlorophylls and carotenoids. These results indicate that VAR3 is a part of a protein complex required for normal chloroplast and palisade cell development.

  8. MiRNA-101 inhibits oral squamous-cell carcinoma growth and metastasis by targeting zinc finger E-box binding homeobox 1

    PubMed Central

    Wu, Baolei; Lei, Delin; Wang, Lei; Yang, Xinjie; Jia, Sen; Yang, Zihui; Shan, Chun; Yang, Xi; Zhang, Chenping; Lu, Bin

    2016-01-01

    MicroRNAs (miRNAs) are implicated in the pathogenesis of oral squamous-cell carcinoma (OSCC). miR-101 is involved in the development and progression of OSCC, but the biological functions and underlying molecular mechanisms of this miRNA remain largely unknown. In this study, we showed that miR-101 was underexpressed in OSCC tissues and cell lines. miR-101 downregulation was inversely correlated with zinc finger E-box binding homeobox 1 (ZEB1) expression, lymph-node metastasis, and poor prognosis in OSCC patients. Enhanced expression of miR-101 significantly inhibited OSCC cell proliferation, apoptosis resistance, migration and invasion in vitro, and suppressed tumor growth and lung metastasis in vivo. Bioinformatics analyses showed that miR-101 directly targeted ZEB1, as confirmed by a dual-luciferase reporter assay. The inhibitory effects of miR-101 on OSCC growth and metastasis were attenuated and phenocopied by ZEB1 overexpression and knockdown, respectively. Overall, our findings indicated that miRNA-101 reduced OSCC growth and metastasis by targeting ZEB1 and provided new evidence of miR-101 as a potential therapeutic target for OSCC patients. PMID:27429852

  9. In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA

    PubMed Central

    Landau, Dustin J; Brooks, Elizabeth Drake; Perez-Pinera, Pablo; Amarasekara, Hiruni; Mefferd, Adam; Li, Songtao; Bird, Andrew; Gersbach, Charles A; Koeberl, Dwight D

    2016-01-01

    Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P < 0.04). Furthermore, transgene integration has been confirmed by sequencing in the majority of the mice treated with both vectors. Targeted alleles were 4.6-fold more common in livers of mice with GSD Ia, as compared with normal littermates, at 8 months following vector administration (P < 0.02). This suggests a selective advantage for vector-transduced hepatocytes following ZFN-mediated integration of the G6Pase vector. A short-term experiment also showed that 3-month-old mice receiving the ZFN had significantly-improved biochemical correction, in comparison with mice that received the donor vector alone. These data suggest that the use of ZFNs to drive integration of G6Pase at a safe harbor locus might improve vector persistence and efficacy, and lower mortality in GSD Ia. PMID:26865405

  10. STS-67 crew insignia

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Observation and remote exploration of the Universe in the ultraviolet wavelengths of light are the focus of the STS-67/ASTRO-2 mission, as depicted in the crew patch designed by the crew members. The insignia shows the ASTRO-2 telescopes in the Space Shuttle Endeavour's payload bay, orbiting high above Earth's atmosphere. The three sets of rays, diverging from the telescope on the patch atop the Instrument Pointing System (IPS), correspond to the three ASTRO-2 telescopes - the Hopkins Ultraviolet Telescope (HUT), The Ultraviolet Imaging Telescope (UIT), and the Wisconsin Ultraviolet Photo-Polarimeter Experiment (WUPPE). The telescopes are coaligned to simultaneously view the same astronomical object, as shown by the convergence of rays on the NASA symbol. This symbol also represents the excellence of the union of the NASA teams and the universality's in the exploration of the universe through astronomy. The celestial targets of ASTRO-2 include the observation of planets, stars and gala

  11. Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8: a direct comparison with radio-iodinated Exendin-4.

    PubMed

    Eriksson, Olof; Korsgren, Olle; Selvaraju, Ram Kumar; Mollaret, Marjorie; de Boysson, Yann; Chimienti, Fabrice; Altai, Mohamed

    2018-01-01

    The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion. In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution. The evaluation was performed in a direct comparison with radio-iodinated Exendin-4. Transcription of the ZnT8 mRNA was higher in islets of Langerhans compared to exocrine tissue. Ab31 targeted ZnT8 in the cytosol and on the plasma membrane with 108 nM affinity. Ab31 was successfully radiolabeled with iodine-125 with high yield and > 95% purity. [ 125 I]Ab31 binding to insulinoma and pancreas was higher than for [ 125 I]Exendin-4, but could only by partially competed away by 200 nM Ab31 in excess. The in vivo uptake of [ 125 I]Ab31 was higher than [ 125 I]Exendin-4 in most tissues, mainly due to slower clearance from blood. We report a first-in-class ZnT8 imaging ligand for pancreatic imaging. Development with respect to ligand miniaturization and radionuclide selection is required for further progress. Transcription analysis indicates ZnT8 as a suitable target for visualization of the human endocrine pancreas.

  12. Zinc Absorption by Young Adults from Supplemental Zinc Citrate Is Comparable with That from Zinc Gluconate and Higher than from Zinc Oxide123

    PubMed Central

    Wegmüller, Rita; Tay, Fabian; Zeder, Christophe; Brnić, Marica; Hurrell, Richard F.

    2014-01-01

    The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with 67Zn and 70Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6–71.0) and was not different from that from zinc gluconate with 60.9% (50.6–71.7). Absorption from zinc oxide at 49.9% (40.9–57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627. PMID:24259556

  13. Indium oxide co-doped with tin and zinc: A simple route to highly conducting high density targets for TCO thin-film fabrication

    NASA Astrophysics Data System (ADS)

    Saadeddin, I.; Hilal, H. S.; Decourt, R.; Campet, G.; Pecquenard, B.

    2012-07-01

    Indium oxide co-doped with tin and zinc (ITZO) ceramics have been successfully prepared by direct sintering of the powders mixture at 1300 °C. This allowed us to easily fabricate large highly dense target suitable for sputtering transparent conducting oxide (TCO) films, without using any cold or hot pressing techniques. Hence, the optimized ITZO ceramic reaches a high relative bulk density (˜ 92% of In2O3 theoretical density) and higher than the well-known indium oxide doped with tin (ITO) prepared under similar conditions. All X-ray diagrams obtained for ITZO ceramics confirms a bixbyte structure typical for In2O3 only. This indicates a higher solubility limit of Sn and Zn when they are co-doped into In2O3 forming a solid-solution. A very low value of electrical resistivity is obtained for [In2O3:Sn0.10]:Zn0.10 (1.7 × 10-3 Ω cm, lower than ITO counterpart) which could be fabricated to high dense ceramic target suing pressure-less sintering.

  14. Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells

    PubMed Central

    Zhao, Yong; Li, Lan; Min, Ling-Jiang; Zhu, Lian-Qin; Sun, Qing-Yuan; Zhang, Hong-Fu; Liu, Xin-Qi; Zhang, Wei-Dong; Ge, Wei; Wang, Jun-Jie; Liu, Jing-Cai

    2016-01-01

    Zinc oxide (ZnO) nanoparticles (NPs) have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 μg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 μg/ml and ZnSO4-10 μg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 μg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 μg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways. PMID:27196542

  15. Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells.

    PubMed

    Zhao, Yong; Li, Lan; Min, Ling-Jiang; Zhu, Lian-Qin; Sun, Qing-Yuan; Zhang, Hong-Fu; Liu, Xin-Qi; Zhang, Wei-Dong; Ge, Wei; Wang, Jun-Jie; Liu, Jing-Cai; Hao, Zhi-Hui

    2016-01-01

    Zinc oxide (ZnO) nanoparticles (NPs) have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 μg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 μg/ml and ZnSO4-10 μg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 μg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 μg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways.

  16. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2002-12-03

    A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  17. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2003-10-28

    A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  18. Pectin-zinc-chitosan-polyethylene glycol colloidal nano-suspension as a food grade carrier for colon targeted delivery of resveratrol.

    PubMed

    Andishmand, Hashem; Tabibiazar, Mahnaz; Mohammadifar, Mohammad Amin; Hamishehkar, Hamed

    2017-04-01

    The aim of the present study was to develop chitosan-zinc-pectinate-polyethylene glycol (PEG) nanoparticles (NPs) for colon-targeted delivery of resveratrol. The effects of pectin:ZnCl 2 :chitosan (PZnC) % w/v, pH and ionic strength of media, and addition of PEG on the colloidal stability and release behavior of resveratrol from NPs were examined by Zeta potential, particle size analyzer, scanning electron microscopy (SEM), and Fourier transform-infrared (FTIR) methods. The particle size and Zeta potential of PZnC NPs in the ratio of 10:1:3% w/v were 399±18nm and +25±1mV, respectively. The addition of PEG to PZnC as a solvent for resveratrol (10% w/v) noticeably decreased the size of NPs to approximately 83±4nm. More than 63% of the resveratrol was encapsulated into the developed NPs; furthermore, a low amount of resveratrol was released during one month, using simulated juice model (pH=4) as investigated by High Performance Liquid Chromatography (HPLC) analysis of resveratrol.The remaining resveratrol in NPs (∼49%) was released in simulated colon fluid in the presence of pectinase. These NPs can be introduced as a novel platform for successful colon delivery of resveratrol in fruit juice matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Observations of interstellar zinc

    NASA Technical Reports Server (NTRS)

    Jura, M.; York, D.

    1981-01-01

    The International Ultraviolet Explorer observations of interstellar zinc toward 10 stars are examined. It is found that zinc is at most only slightly depleted in the interstellar medium; its abundance may serve as a tracer of the true metallicity in the gas. The local interstellar medium has abundances that apparently are homogeneous to within a factor of two, when integrated over paths of about 500 pc, and this result is important for understanding the history of nucleosynthesis in the solar neighborhood. The intrinsic errors in detecting weak interstellar lines are analyzed and suggestions are made as to how this error limit may be lowered to 5 mA per target observation.

  20. Effects of HAb18G/CD147 knockout on hepatocellular carcinoma cells in vitro using a novel zinc-finger nuclease-targeted gene knockout approach.

    PubMed

    Li, Hong-Wei; Yang, Xiang-Min; Tang, Juan; Wang, Shi-Jie; Chen, Zhi-Nan; Jiang, Jian-Li

    2015-03-01

    HAb18G/CD147 belongs to the immunoglobulin superfamily and predominantly functions as an inducer of matrix metalloproteinase secretion for tumor invasion and metastasis. This study was designed to investigate the effects of HAb18G/CD147 knockout on hepatocellular carcinoma cells using zinc-finger nuclease (ZFNs)-targeted gene knockout approach. The HCC cell line SMMC-7721 was used for ZFNs-targeted cleavage of the HAb18G/CD147 gene. RT-PCR and Western blot assays were used to detect HAb18G/CD147 expression. HAb18G phenotypic changes following HAb18G/CD147 knockout in SMMC-K7721 cells were assessed using tumor cell adhesion, invasion, migration and colony formation and flow cytometric assays. These data demonstrated that tumor cell adhesion, invasion, migration, and colony formation capabilities of SMMC-K7721 were significantly reduced compared to parental cells or SMMC-7721 with re-expression of HAb18G/CD147 protein transfected with HAb18G/CD147 cDNA. Moreover, knockout of HAb18G/CD147 expression also induced SMMC-K7721 cells to undergo apoptosis compared to SMMC-7721 and SMMC-R7721 (P < 0.01). Molecularly, protein expression of p53 was induced in these cells, but re-expression of HAb18G/CD147 reduced p53 levels in SMMC-R7721 cells, possibly through inhibition of the PI3K-Akt-MDM2 signaling pathway. The findings provide a novel insight into the mechanisms underlying HAb18G/CD147-induced progression of HCC cells.

  1. The Zinc Transporter Zip5 (Slc39a5) Regulates Intestinal Zinc Excretion and Protects the Pancreas against Zinc Toxicity

    PubMed Central

    Geiser, Jim; De Lisle, Robert C.; Andrews, Glen K.

    2013-01-01

    Background ZIP5 localizes to the baso-lateral membranes of intestinal enterocytes and pancreatic acinar cells and is internalized and degraded coordinately in these cell-types during periods of dietary zinc deficiency. These cell-types are thought to control zinc excretion from the body. The baso-lateral localization and zinc-regulation of ZIP5 in these cells are unique among the 14 members of the Slc39a family and suggest that ZIP5 plays a role in zinc excretion. Methods/Principal Findings We created mice with floxed Zip5 genes and deleted this gene in the entire mouse or specifically in enterocytes or acinar cells and then examined the effects on zinc homeostasis. We found that ZIP5 is not essential for growth and viability but total knockout of ZIP5 led to increased zinc in the liver in mice fed a zinc-adequate (ZnA) diet but impaired accumulation of pancreatic zinc in mice fed a zinc-excess (ZnE) diet. Loss-of-function of enterocyte ZIP5, in contrast, led to increased pancreatic zinc in mice fed a ZnA diet and increased abundance of intestinal Zip4 mRNA. Finally, loss-of-function of acinar cell ZIP5 modestly reduced pancreatic zinc in mice fed a ZnA diet but did not impair zinc uptake as measured by the rapid accumulation of 67zinc. Retention of pancreatic 67zinc was impaired in these mice but the absence of pancreatic ZIP5 sensitized them to zinc-induced pancreatitis and exacerbated the formation of large cytoplasmic vacuoles containing secretory protein in acinar cells. Conclusions These studies demonstrate that ZIP5 participates in the control of zinc excretion in mice. Specifically, they reveal a paramount function of intestinal ZIP5 in zinc excretion but suggest a role for pancreatic ZIP5 in zinc accumulation/retention in acinar cells. ZIP5 functions in acinar cells to protect against zinc-induced acute pancreatitis and attenuate the process of zymophagy. This suggests that it may play a role in autophagy. PMID:24303081

  2. Synthesis and Evaluation of a Novel 64Cu- and 67Ga-Labeled Neurokinin 1 Receptor Antagonist for in Vivo Targeting of NK1R-Positive Tumor Xenografts.

    PubMed

    Zhang, Hanwen; Kanduluru, Ananda Kumar; Desai, Pooja; Ahad, Afruja; Carlin, Sean; Tandon, Nidhi; Weber, Wolfgang A; Low, Philip S

    2018-04-18

    Neurokinin 1 receptor (NK1R) is expressed in gliomas and neuroendocrine malignancies and represents a promising target for molecular imaging and targeted radionuclide therapy. The goal of this study was to synthesize and evaluate a novel NK1R ligand (NK1R-NOTA) for targeting NK1R-expressing tumors. Using a carboxymethyl moiety linked to L-733060 as a starting reagent, NK1R-NOTA was synthesized in a three-step reaction and then labeled with 64 Cu (or 67 Ga for in vitro studies) in the presence of CH 3 COONH 4 buffer. The radioligand affinity and cellular uptake were evaluated with NK1R-transduced HEK293 cells (HEK293-NK1R) and NK1R nontransduced HEK293 cells (HEK293-WT) and their xenografts. Radiolabeled NK1R-NOTA was obtained with a radiochemical purity of >95% and specific activities of >7.0 GBq/μmol for 64 Cu and >5.0 GBq/μmol for 67 Ga. Both 64 Cu- and 67 Ga-labeled NK1R-NOTA demonstrated high levels of uptake in HEK293-NK1R cells, whereas co-incubation with an excess of NK1R ligand L-733060 reduced the level of uptake by 90%. Positron emission tomography (PET) imaging showed that [ 64 Cu]NK1R-NOTA had a accumulated rapidly in HEK293-NK1R xenografts and a 10-fold lower level of uptake in HEK293-WT xenografts. Radioactivity was cleared by gastrointestinal tract and urinary systems. Biodistribution studies confirmed that the tumor-to-organ ratios were ≥5 for all studied organs at 1 h p.i., except kidneys, liver, and intestine, and that the tumor-to-intestine and tumor-to-kidney ratios were also improved 4 and 20 h post-injection. [ 64 Cu]NK1R-NOTA is a promising ligand for PET imaging of NK1R-expressing tumor xenografts. Delayed imaging with [ 64 Cu]NK1R-NOTA improves image contrast because of the continuous clearance of radioactivity from normal organs.

  3. Ga-67 cardiac uptake

    SciT

    Lin, D.S.; Tipton, R.E.

    1983-12-01

    A case of positive Ga-67 image due to tuberculous pericarditis is presented. The pattern and distribution of the uptake suggested that the concentration of the activity was mainly in the inflamed pericardium. The known causes of Ga-67 cardiac uptake were reviewed, and a differential diagnosis is given.

  4. STS-67 crew insignia

    1994-10-01

    STS067-S-001 (October 1994) --- Observation and remote exploration of the Universe in the ultraviolet wavelengths of light are the focus of the STS-67/ASTRO-2 mission, as depicted in the crew patch designed by the crew members. The insignia shows the ASTRO-2 telescopes in the space shuttle Endeavour's payload bay, orbiting high above Earth's atmosphere. The three sets of rays, diverging from the telescope on the patch atop the Instrument Pointing System (IPS), correspond to the three ASTRO-2 telescopes -- the Hopkins Ultraviolet Telescope (HUT), the Ultraviolet Imaging Telescope (UIT), and the Wisconsin Ultraviolet Photo-Polarimeter Experiment (WUPPE). The telescopes are co-aligned to simultaneously view the same astronomical object, as shown by the convergence of rays on the NASA symbol. This symbol also represents the excellence of the union of the NASA teams and universality's in the exploration of the universe through astronomy. The celestial targets of ASTRO-2 include the observation of planets, stars and galaxies shown in the design. The two small atoms represent the search in the ultraviolet spectrum for the signature of primordial helium in intergalactic space left over from the Big Bang. The observations performed on ASTRO-2 will contribute to man's knowledge and understanding of the vast universe, from the planets in out system to the farthest reaches of space. The NASA insignia design for space shuttle flights is reserved for use by the astronauts and for other official use as the NASA Administrator may authorize. Public availability has been approved only in the forms of illustrations by the various news media. When and if there is any change in this policy, which is not anticipated, the change will be publicly announced. Photo credit: NASA

  5. Zinc in Infection and Inflammation

    PubMed Central

    Gammoh, Nour Zahi; Rink, Lothar

    2017-01-01

    Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli. PMID:28629136

  6. Zinc in Infection and Inflammation.

    PubMed

    Gammoh, Nour Zahi; Rink, Lothar

    2017-06-17

    Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

  7. Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

    PubMed Central

    Botchkina, Galina I.; Zuniga, Edison S.; Rowehl, Rebecca H.; Park, Rosa; Bhalla, Rahuldev; Bialkowska, Agnieszka B.; Johnson, Francis; Golub, Lorne M.; Zhang, Yu; Ojima, Iwao; Shroyer, Kenneth R.

    2013-01-01

    Background Prostate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs) is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs. Principal Findings The CD133high/CD44high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor growth. Four of six PPT2 and 3 of 6 PC3MM2 tumors have shown the absence of viable cells in residual tumors. In vitro, SBT-1214 (100nM-1µM; for 72 hr) induced about 60% cell death in CD133high/CD44+/high cells cultured on collagen I in stem cell medium (in contrast, the same doses of paclitaxel increased proliferation of these cells). The cytotoxic effects were increased when SBT-1214 was combined with the CMC2.24. A stem cell-specific PCR array assay revealed that this drug combination mediated massive inhibition of multiple constitutively up-regulated stem cell-related genes, including key pluripotency transcription factors. Importantly, this drug combination induced expression of p21 and p53, which were absent in CD133high/CD44high cells. Viable cells that survived this treatment regimen were no longer able to induce secondary spheroids, exhibited significant morphological abnormalities and died in 2-5 days. Conclusions We report here that the SBT-1214 alone, or in combination with CMC2.24, possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells. This drug combination efficiently inhibits expression of the majority of stem cell-related genes and pluripotency transcription

  8. Zinc cyanide

    Integrated Risk Information System (IRIS)

    Zinc cyanide ; CASRN 557 - 21 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effe

  9. Zinc phosphide

    Integrated Risk Information System (IRIS)

    Zinc phoshide ; CASRN 1314 - 84 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  10. The zinc paradigm for metalloneurochemistry.

    PubMed

    Barr, Chelsea A; Burdette, Shawn C

    2017-05-09

    Neurotransmission and sensory perception are shaped through metal ion-protein interactions in various brain regions. The term "metalloneurochemistry" defines the unique field of bioinorganic chemistry focusing on these processes, and zinc has been the leading target of metalloneurochemists in the almost 15 years since the definition was introduced. Zinc in the hippocampus interacts with receptors that dictate ion flow and neurotransmitter release. Understanding the intricacies of these interactions is crucial to uncovering the role that zinc plays in learning and memory. Based on receptor similarities and zinc-enriched neurons (ZENs) in areas of the brain responsible for sensory perception, such as the olfactory bulb (OB), and dorsal cochlear nucleus (DCN), zinc participates in odor and sound perception. Development and improvement of methods which allow for precise detection and immediate manipulation of zinc ions in neuronal cells and in brain slices will be critical in uncovering the synaptic action of zinc and, more broadly, the bioinorganic chemistry of cognition. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. Zinc and its importance for human health: An integrative review

    PubMed Central

    Roohani, Nazanin; Hurrell, Richard; Kelishadi, Roya; Schulin, Rainer

    2013-01-01

    Since its first discovery in an Iranian male in 1961, zinc deficiency in humans is now known to be an important malnutrition problem world-wide. It is more prevalent in areas of high cereal and low animal food consumption. The diet may not necessarily be low in zinc, but its bio-availability plays a major role in its absorption. Phytic acid is the main known inhibitor of zinc. Compared to adults, infants, children, adolescents, pregnant, and lactating women have increased requirements for zinc and thus, are at increased risk of zinc depletion. Zinc deficiency during growth periods results in growth failure. Epidermal, gastrointestinal, central nervous, immune, skeletal, and reproductive systems are the organs most affected clinically by zinc deficiency. Clinical diagnosis of marginal Zn deficiency in humans remains problematic. So far, blood plasma/serum zinc concentration, dietary intake, and stunting prevalence are the best known indicators of zinc deficiency. Four main intervention strategies for combating zinc deficiency include dietary modification/diversification, supplementation, fortification, and bio-fortification. The choice of each method depends on the availability of resources, technical feasibility, target group, and social acceptance. In this paper, we provide a review on zinc biochemical and physiological functions, metabolism including, absorption, excretion, and homeostasis, zinc bio-availability (inhibitors and enhancers), human requirement, groups at high-risk, consequences and causes of zinc deficiency, evaluation of zinc status, and prevention strategies of zinc deficiency. PMID:23914218

  12. Zinc activates damage-sensing TRPA1 ion channels.

    PubMed

    Hu, Hongzhen; Bandell, Michael; Petrus, Matt J; Zhu, Michael X; Patapoutian, Ardem

    2009-03-01

    Zinc is an essential biological trace element. It is required for the structure or function of over 300 proteins, and it is increasingly recognized for its role in cell signaling. However, high concentrations of zinc have cytotoxic effects, and overexposure to zinc can cause pain and inflammation through unknown mechanisms. Here we show that zinc excites nociceptive somatosensory neurons and causes nociception in mice through TRPA1, a cation channel previously shown to mediate the pungency of wasabi and cinnamon through cysteine modification. Zinc activates TRPA1 through a unique mechanism that requires zinc influx through TRPA1 channels and subsequent activation via specific intracellular cysteine and histidine residues. TRPA1 is highly sensitive to intracellular zinc, as low nanomolar concentrations activate TRPA1 and modulate its sensitivity. These findings identify TRPA1 as an important target for the sensory effects of zinc and support an emerging role for zinc as a signaling molecule that can modulate sensory transmission.

  13. Zinc and the modulation of redox homeostasis

    PubMed Central

    Oteiza, Patricia I.

    2012-01-01

    Zinc, a redox inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintain the cell redox balance through different mechanisms including: i) the regulation of oxidant production and metal-induced oxidative damage; ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione and other thiol oxidant species; iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and act per se scavenging oxidants; iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue disfunction in cell and animal models of zinc deficiency, stress the relevant role of zinc in the preservation of cell redox homeostasis. However, while the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the involved molecules, targets and mechanisms are still partially known and the subject of active research. PMID:22960578

  14. 67P, Singing Comet

    NASA Astrophysics Data System (ADS)

    Smirnova, Ekaterina

    2017-04-01

    I would like to propose to present a short science-art-music collaboration film called "67P, Singing Comet" (5:27 min). If time of the session will allow, prior to the film I would like to make a slide show introduction to this project, highlighting the inspiration - the mission Rosetta by the European Space Agency (ESA) - and the artistic collaboration that took place in creating this piece. Inspired by the ESA Rosetta mission to the comet 67P, Ekaterina Smirnova (artist and project director, New York), Lee Mottram (clarinetist, Wales), Takuto Fukuda (composer, Japan) and Brian Hekker (video editor, New York) collaborated to create a unique atmospheric piece. Water and the origins of life throughout the Universe (specifically the Earth) is an element of the mission and the focus of Ekaterina's artistic vision. Ekaterina literally and figuratively paints a sensory assemblage using a combination of synthetic and natural elements to shape this artistic creation. To paint her watercolor works she is using a replica of the water found on the comet and implementing her own heartbeat into the music to create a recognizable inward sound of life. The Electro-Acoustic composition by Takuto Fukuda features an electronically manipulated performance by clarinetist Lee Mottram. The piece ceremoniously begins with reverberant bursts of low-register atonal bells transporting the listener to their ethereal inner origins of body and mind. The imagination takes the experience to an unknown destination as it gains speed gliding through the visual and audible textures of space and time. The comet's water similarly reacts with an ebb and flow thawing ice to potentially give life a chance as it is thrust along an orbit around the Sun. Near then far from the heat the comet forms frozen particles from vapors as it reaches it's furthest stretches creating an aerodynamic tail of icicles that slowly dissipate in a cycle that repeats itself until the comet's ultimate collision with an

  15. Lithium in M67

    NASA Technical Reports Server (NTRS)

    Hobbs, L. M.; Pilachowski, Catherine

    1986-01-01

    Echelle spectra recorded at the Li I 6707-A line are reported for seven main-sequence members and one cool subgiant in M67. The spectral types of the seven dwarfs studied range from about F8 at the turnoff point to about G5. The principal result is that the average lithium abundance in the three hottest main-sequence stars is 0.45 x 10 to the -9th. Any enrichment of lithium in the gas of the Galactic disk in the last 5 Gyr therefore has not exceeded a factor of about two and probably is entirely negligible, when the corresponding results for NGC 752 and the Hyades are taken into account.

  16. Update on zinc biology.

    PubMed

    Solomons, Noel W

    2013-01-01

    Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation. Copyright © 2013 S. Karger AG, Basel.

  17. Production of zinc pellets

    DOEpatents

    Cooper, J.F.

    1996-11-26

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries. 6 figs.

  18. Production of zinc pellets

    DOEpatents

    Cooper, John F.

    1996-01-01

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries.

  19. Dietary phytate, zinc and hidden zinc deficiency.

    PubMed

    Sandstead, Harold H; Freeland-Graves, Jeanne H

    2014-10-01

    Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Method of capturing or trapping zinc using zinc getter materials

    SciT

    Hunyadi Murph, Simona E.; Korinko, Paul S.

    2017-07-11

    A method of trapping or capturing zinc is disclosed. In particular, the method comprises a step of contacting a zinc vapor with a zinc getter material. The zinc getter material comprises nanoparticles and a metal substrate.

  1. Zinc oxide overdose

    MedlinePlus

    Zinc oxide is an ingredient in many products. Some of these are certain creams and ointments used ... prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone eats one of ...

  2. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  3. COPPER-64 Production Studies with Natural Zinc Targets at Deuteron Energy up to 19 Mev and Proton Energy from 141 Down to 31 Mev

    NASA Astrophysics Data System (ADS)

    Bonardi, Mauro L.; Birattari, Claudio; Groppi, Flavia; Song Mainard, Hae; Zhuikov, Boris L.; Kokhanyuk, Vladimir M.; Lapshina, Elena V.; Mebel, Michail V.; Menapace, Enzo

    2004-07-01

    High specific activity no-carrier-added 64Cu is a β-/β+ emitting radionuclide of increasing interest for PET imaging, as well as systemic and targeted radioimmunotherapy of tumors. Its peculiarity of intense Auger emitter is still under investigation. The cross-sections for production of 64Cu from Zn target of natural isotopic composition were measured in the deuteron energy range from threshold up to 19 MeV and proton energy range from 141 down to 31 MeV. The stacked-foil technique was used at both K=38 cyclotron of JRC-Ispra of CEC, Italy and 160 MeV intersection point of INR proton-LINAC in Troitsk, Russia. Several Ga, Zn, Cu, Ni, Co, V, Fe and Mn radionuclides were detected in Zn targets at the EOB. Optimized irradiation conditions are reported as a function of deuteron energy and energy loss into the Zn target, as well as target irradiation time and cooling time after radiochemistry. The activity of n.c.a. 64Cu was measured through its only γ emission of 1346 keV (i.e. 0.473 % intensity) both by instrumental and radiochemical methods, due to the non-specificity of annihilation radiation at 511 keV. To this last purpose, it was necessary to carry out a selective radiochemical separation of GaIII radionuclides by liquid/liquid extraction from the bulk of irradiated Zn targets and other spallation products, which remained in the 7 M HCl aqueous phase. Anion exchange chromatography tests had been carried out to separate the 64Cu from all others radionuclides in n.c.a. form. Theoretical calculations of cross-sections were performed with codes EMPIRE II and PENELOPE for deuteron reactions and CEF model and HMS-ALICE hybrid model for proton reactions. The theoretical results are presented and compared with the experimental values.

  4. Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

    SciT

    Sun, Xi; Zhou, Xixi; Du, Libo

    2014-01-15

    Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects ofmore » arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of

  5. Zinc oxyfluoride transparent conductor

    DOEpatents

    Gordon, Roy G.

    1991-02-05

    Transparent, electrically conductive and infrared-reflective films of zinc oxyfluoride are produced by chemical vapor deposition from vapor mixtures of zinc, oxygen and fluorine-containing compounds. The substitution of fluorine for some of the oxygen in zinc oxide results in dramatic increases in the electrical conductivity. For example, diethyl zinc, ethyl alcohol and hexafluoropropene vapors are reacted over a glass surface at 400.degree. C. to form a visibly transparent, electrically conductive, infrared reflective and ultraviolet absorptive film of zinc oxyfluoride. Such films are useful in liquid crystal display devices, solar cells, electrochromic absorbers and reflectors, energy-conserving heat mirrors, and antistatic coatings.

  6. Pseudomonas aeruginosa Trent and zinc homeostasis.

    PubMed

    Davies, Corey B; Harrison, Mark D; Huygens, Flavia

    2017-09-01

    Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Novel theranostic zinc phthalocyanine-phospholipid complex self-assembled nanoparticles for imaging-guided targeted photodynamic treatment with controllable ROS production and shape-assisted enhanced cellular uptake.

    PubMed

    Ma, Jinyuan; Li, Yang; Liu, Guihua; Li, Ai; Chen, Yilin; Zhou, Xinyi; Chen, Dengyue; Hou, Zhenqing; Zhu, Xuan

    2018-02-01

    The novel drug delivery system based on self-assembly of zinc phthalocyanine-soybean phosphatidylcholine (ZnPc-SPC) complex was developed by a co-solvent method followed by a nanoprecipitaion technique. DSPE-PEG-methotrexate (DSPE-PEG-MTX) was introduced on the surface of ZnPc-SPC self-assembled nanoparticles (ZS) to endow them with folate receptor-targeting property. NMR, XRD, FTIR, and UV-vis-NIR analysis demonstrated the weak molecular interaction between ZnPc and SPC. The ZS functionalized with DSPE-PEG-MTX (ZSPM) was successfully constructed with an average particle size of ∼170nm, a narrow size distribution, and could remain physiologically stable for at least 7days. In vitro cellular uptake and cytotoxicity studies demonstrated that ZSPM exhibited stronger cellular uptake efficacy and photodynamic cytotoxicity against HeLa and MCF-7 cells than ZS functionalized with DSPE-mPEG (ZSP) and free ZnPc. More importantly, ZSPM showed the enhanced accumulation effect at the tumor region compared with ZSP by the active-plus-passive targeting via enhanced permeability and retention (EPR) effect and folate receptor-mediated endocytosis. Furthermore, in vivo antitumor effect and histological analysis demonstrated the superior tumor growth inhibition effect of ZSPM. In addition, the needle-shape ZSP (ZSPN) exhibited better in vitro cellular uptake and in vivo tumor accumulation compared with ZSP due to the shape-assisted effect. Moreover, the interesting off-on switch effect of reactive oxygen species (ROS) production of ZnPc-SPC complex-based nanoparticles was discovered to achieve photodynamic treatment in a controllable way. These findings suggested that the ZnPc-SPC complex-based self-assembled nanoparticles could serve as a promising and effective formulation to achieve tumor-targeting fluorescence imaging and enhanced photodynamic treatment. Copyright © 2017. Published by Elsevier B.V.

  8. Reduction of zinc emissions from buildings; the policy of Amsterdam.

    PubMed

    Gouman, E

    2004-01-01

    In Amsterdam zinc coming from the roofs and gutters of the buildings accounts for about 50% of the zinc emissions into the surface water (i.e. canals and rivers). This causes water and sediment pollution. Dumping strongly polluted sediment costs ten times more then dumping less polluted mud. Therefore the City of Amsterdam has developed a policy for reducing the zinc emissions from buildings based on the current environmental legislation and the current national targets for surface water quality. Zinc roofs on new and renovated buildings are not permitted. Run off water from zinc roofs of existing buildings is allowed to contain a maximum of 200 microg/l zinc. For the zinc gutters of houses, Amsterdam will promote measures to reduce zinc emissions. To investigate the feasibility of measures, research has been carried out on the zinc emissions of gutters and the effect of covering gutters with an impermeable foil. This research shows clearly that covering zinc gutters with EPDM foil reduces the zinc emissions by 90% from 8.5 to 0.88 gram per square metre per year including the atmospheric deposition.

  9. Selective Sensitization of Zinc Finger Protein Oxidation by Reactive Oxygen Species through Arsenic Binding*

    PubMed Central

    Zhou, Xixi; Cooper, Karen L.; Sun, Xi; Liu, Ke J.; Hudson, Laurie G.

    2015-01-01

    Cysteine oxidation induced by reactive oxygen species (ROS) on redox-sensitive targets such as zinc finger proteins plays a critical role in redox signaling and subsequent biological outcomes. We found that arsenic exposure led to oxidation of certain zinc finger proteins based on arsenic interaction with zinc finger motifs. Analysis of zinc finger proteins isolated from arsenic-exposed cells and zinc finger peptides by mass spectrometry demonstrated preferential oxidation of C3H1 and C4 zinc finger configurations. C2H2 zinc finger proteins that do not bind arsenic were not oxidized by arsenic-generated ROS in the cellular environment. The findings suggest that selectivity in arsenic binding to zinc fingers with three or more cysteines defines the target proteins for oxidation by ROS. This represents a novel mechanism of selective protein oxidation and demonstrates how an environmental factor may sensitize certain target proteins for oxidation, thus altering the oxidation profile and redox regulation. PMID:26063799

  10. Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

    Flinn, J.M.; Hunter, D.; Linkous, D.H.; Lanzirotti, A.; Smith, L.N.; Brightwell, J.; Jones, B.F.

    2005-01-01

    Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (??SXRF) confirmed that brain zinc levels were increased by adding ZnCO 3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function. ?? 2004 Elsevier Inc. All rights reserved.

  11. Human eosinophils are direct targets to nanoparticles: Zinc oxide nanoparticles (ZnO) delay apoptosis and increase the production of the pro-inflammatory cytokines IL-1β and IL-8.

    PubMed

    Silva, Luis Rafael; Girard, Denis

    2016-09-30

    Zinc oxide NPs (ZnO) have been recently proposed as novel candidates for the treatment of allergic inflammatory diseases. Paradoxically, recent data suggested that ZnO could cause eosinophilic airway inflammation in rodents. Despite the above observations, there are currently no studies reporting direct interaction between a given NP and human eosinophils themselves. In this study, freshly isolated human eosinophils were incubated with ZnO and several cellular functions were studied. We found that ZnO delay human eosinophil apoptosis, partially by inhibiting caspases and by preventing caspase-4 and Bcl-xL degradation. ZnO do not induce production of reactive oxygen species but increase de novo protein synthesis. In addition, ZnO were found to increase the production of the proinflammatory IL-1β and IL-8 cytokines. Using a pharmacological approach, we demonstrated that inhibition of caspase-1 reversed the ability of ZnO to induce IL-1β and IL-8 production, whereas inhibition of caspase-4 only reversed that of IL-8. Our results indicate the necessity of conducting studies to determine the potential of using NP as nanotherapies, particularly in diseases in which eosinophils may be involved. We conclude that, indeed, human eosinophils represent potential new direct targets to NPs, ZnO in the present case. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

    SciT

    Plapp, Bryce V.; Savarimuthu, Baskar Raj; Ferraro, Daniel J.

    During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentatemore » chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ~1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.« less

  13. Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

    PubMed Central

    2017-01-01

    During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5′-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2′-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ∼1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water. PMID:28640600

  14. Zinc Deficiency Impacts CO2 Assimilation and Disrupts Copper Homeostasis in Chlamydomonas reinhardtii*

    PubMed Central

    Malasarn, Davin; Kropat, Janette; Hsieh, Scott I.; Finazzi, Giovanni; Casero, David; Loo, Joseph A.; Pellegrini, Matteo; Wollman, Francis-André; Merchant, Sabeeha S.

    2013-01-01

    Zinc is an essential nutrient because of its role in catalysis and in protein stabilization, but excess zinc is deleterious. We distinguished four nutritional zinc states in the alga Chlamydomonas reinhardtii: toxic, replete, deficient, and limited. Growth is inhibited in zinc-limited and zinc-toxic cells relative to zinc-replete cells, whereas zinc deficiency is visually asymptomatic but distinguished by the accumulation of transcripts encoding ZIP family transporters. To identify targets of zinc deficiency and mechanisms of zinc acclimation, we used RNA-seq to probe zinc nutrition-responsive changes in gene expression. We identified genes encoding zinc-handling components, including ZIP family transporters and candidate chaperones. Additionally, we noted an impact on two other regulatory pathways, the carbon-concentrating mechanism (CCM) and the nutritional copper regulon. Targets of transcription factor Ccm1 and various CAH genes are up-regulated in zinc deficiency, probably due to reduced carbonic anhydrase activity, validated by quantitative proteomics and immunoblot analysis of Cah1, Cah3, and Cah4. Chlamydomonas is therefore not able to grow photoautotrophically in zinc-limiting conditions, but supplementation with 1% CO2 restores growth to wild-type rates, suggesting that the inability to maintain CCM is a major consequence of zinc limitation. The Crr1 regulon responds to copper limitation and is turned on in zinc deficiency, and Crr1 is required for growth in zinc-limiting conditions. Zinc-deficient cells are functionally copper-deficient, although they hyperaccumulate copper up to 50-fold over normal levels. We suggest that zinc-deficient cells sequester copper in a biounavailable form, perhaps to prevent mismetallation of critical zinc sites. PMID:23439652

  15. Improved zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, P.N. Jr.

    1988-06-21

    The invention comprises an improved rechargeable zinc-air cell/battery having recirculating alkaline electrolyte and a zinc electrode comprising a porous foam support material which carries the active zinc electrode material. 5 figs.

  16. The zinc dyshomeostasis hypothesis of Alzheimer's disease.

    PubMed

    Craddock, Travis J A; Tuszynski, Jack A; Chopra, Deepak; Casey, Noel; Goldstein, Lee E; Hameroff, Stuart R; Tanzi, Rudolph E

    2012-01-01

    microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline.

  17. Zinc in Entamoeba invadens.

    NASA Technical Reports Server (NTRS)

    Morgan, R. S.; Sattilaro, R. F.

    1972-01-01

    Atomic absorption spectroscopy, electron microprobe analysis, and dithizone staining of trophozoites and cysts of Entamoeba invadens demonstrate that these cells have a high concentration of zinc (approximately one picogram per cell or 1% of their dry weight). In the cysts of this organism, the zinc is confined to the chromatoid bodies, which previous work has shown to contain crystals of ribosomes. The chemical state and function of this zinc are unknown.

  18. Zinc and Chlamydia trachomatis

    SciT

    Sugarman, B.; Epps, L.R.

    1985-07-01

    Zinc was noted to have significant effects upon the infection of McCoy cells by each of two strains of Chlamydia trachomatis. With a high or low Chlamydia inoculant, the number of infected cells increased up to 200% utilizing supplemental zinc (up to 1 x 10/sup -4/ M) in the inoculation media compared with standard Chlamydia cultivation media (8 x 10/sup -6/ M zinc). Ferric chloride and calcium chloride did not effect any such changes. Higher concentrations of zinc, after 2 hr of incubation with Chlamydia, significantly decreased the number of inclusions. This direct effect of zinc on the Chlamydia remainedmore » constant after further repassage of the Chlamydia without supplemental zinc, suggesting a lethal effect of the zinc. Supplemental zinc (up to 10/sup -4/ M) may prove to be a useful addition to inoculation media to increase the yield of culturing for Chlamydia trachomatis. Similarly, topical or oral zinc preparations used by people may alter their susceptibility to Chamydia trachomatis infections.« less

  19. Zinc triggers microglial activation

    PubMed Central

    Kauppinen, Tiina M.; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A.

    2009-01-01

    Microglia are resident immune cells of the central nervous system. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, “amoeboid” morphology and release matrix metalloproteinases, reactive oxygen species, and other pro-inflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here we show that zinc directly triggers microglial activation. Microglia transfected with an NF-kB reporter gene showed a several-fold increase in NF-kB activity in response to 30 μM zinc. Cultured mouse microglia exposed to 15 – 30 μM zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-κB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-κB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders. PMID:18509044

  20. Zinc triggers microglial activation.

    PubMed

    Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

    2008-05-28

    Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

  1. [Zinc and chronic enteropathies].

    PubMed

    Giorgi, P L; Catassi, C; Guerrieri, A

    1984-01-01

    In recent years the nutritional importance of zinc has been well established; its deficiency and its symptoms have also been recognized in humans. Furthermore, Acrodermatitis Enteropathica has been isolated, a rare but severe disease, of which skin lesions, chronic diarrhoea and recurring infections are the main symptoms. The disease is related to the malfunctioning of intestinal absorption of zinc and can be treated by administering pharmacological doses of zinc orally. Good dietary sources of zinc are meat, fish and, to a less extent, human milk. The amount of zinc absorbed in the small intestine is influenced by other nutrients: some compounds inhibit this process (dietary fiber, phytate) while others (picolinic acid, citric acid), referred to as Zn-binding ligands (ZnBL) facilitate it. Citric acid is thought to be the ligand which accounts for the high level of bioavailability of zinc in human milk. zinc absorption occurs throughout the small intestine, not only in the prossimal tract (duodenum and jejunum) but also in the distal tract (ileum). Diarrhoea is one of the clinical manifestations of zinc deficiency, thus many illnesses distinguished by chronic diarrhoea entail a bad absorption of zinc. In fact, in some cases of chronic enteropathies in infants, like coeliac disease and seldom cystic fibrosis, a deficiency of zinc has been isolated. Some of the symptoms of Crohn's disease, like retarded growth and hypogonadism, have been related to hypozinchemia which is present in this illness. Finally, it is possible that some of the dietary treatments frequently used for persistent post-enteritis diarrhoea (i.e. cow's milk exclusion, abuse and misuse of dietary fiber like carrot and carub powder, use of soy formula) can constitute a scarce supply of zinc and therefore could promote the persistency of diarrhoea itself.

  2. Changes in zinc status and zinc transporters expression in whole blood of patients with Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Florea, Daniela; Molina-López, Jorge; Hogstrand, Christer; Lengyel, Imre; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Planells, Elena

    2018-09-01

    Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of many nutrients and especially zinc, depleting their body reserves. This study was designed to assess the zinc status in critical care patients with systemic inflammatory response syndrome (SIRS), comparing them with a group of healthy people, and studying the association with expression of zinc transporters. This investigation was a prospective, multicentre, comparative, observational and analytic study. Twelve critically ill patients from different hospitals and 12 healthy subjects from Granada, Spain, all with informed consent were recruited. Data on daily nutritional assessment, ICU severity scores, inflammation, clinical and nutritional parameters, plasma and blood cell zinc concentrations, and levels of transcripts for zinc transporters in whole blood were taken at admission and at the seventh day of the ICU stay. Zinc levels on critical ill patient are diminish comparing with the healthy control (HS: 0.94 ± 0.19; CIPF: 0.67 ± 0.16 mg/dL). The 58% of critical ill patients showed zinc plasma deficiency at beginning of study while 50.0% of critical ill after 7 days of ICU stay. ZnT7, ZIP4 and ZIP9 were the zinc transporters with highest expression in whole blood. In general, all zinc transporters were significantly down-regulated (P < 0.05) in the critical ill population at admission in comparison with healthy subjects. Severity scores and inflammation were significantly associated (P < 0.05) with zinc plasma levels, and zinc transporters ZIP3, ZIP4, ZIP8, ZnT6, ZnT7. Expression of 11 out of 24 zinc transporters was analysed, and ZnT1, ZnT4, ZnT5 and ZIP4, which were downregulated by more than 3-fold in whole blood of patients. In summary, in our study an alteration of zinc status was related with the severity-of-illness scores and inflammation in critical ill patients since admission in ICU stay. SIRS

  3. Environmental exposure of road borders to zinc.

    PubMed

    Blok, J

    2005-09-15

    The emissions of zinc along roads originating from tyre wear, corrosion of safety fence and other traffic-related sources have been quantified and validated by measured long-term loads in road run-off and airborne solids (drift) for 29 published case studies. The distribution pattern over the road border at various distances from the edge of the paved surface is assessed on the basis of 38 published case studies with measured concentrations in soil. For the impact assessment, the road border is differentiated into a zone that is part of the "technosphere" and the "target zone" beyond that technosphere that can be considered as part of the receiving environment. The "technosphere" of the road includes the central reservation, the hard and the soft shoulder or, if one or both shoulders are not present, the so-called obstacle "free zone" that is defined by road engineers. Pollution within the technosphere may require appropriate management of solid disposal and isolation from groundwater to prevent further distribution of pollutants to the environment. In the target zone along regional roads, the zinc load is about 4 mg/m(2) year and this is of the same order of magnitude as that of atmospheric deposition in areas beyond the influence of roads (background). In the target zone along highways, the zinc load is increased in comparison to the background deposition. The average load of about 38 mg/m(2) year is similar to that in fertilised agricultural land. Because most of the emitted zinc stays in the technosphere, the total amount entering this target zone along highways is limited. From the 140 tons of zinc per year that is released from tyre wear in The Netherlands, 64 tons is emitted in the urban area, 6.5 tons reaches to the target zones of all roads and only 1.1 tons of zinc will enter the target zone along highways. This amount will be further decreased by the application of porous asphalt in the near future. The emission from safety fence corrosion does not enter

  4. Chelating ionic liquids for reversible zinc electrochemistry.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2013-05-21

    Advanced, high energy-density, metal-air rechargeable batteries, such as zinc-air, are of intense international interest due to their important role in energy storage applications such as electric and hybrid vehicles, and to their ability to deal with the intermittency of renewable energy sources such as solar and wind. Ionic liquids offer a number of ideal thermal and physical properties as potential electrolytes in such large-scale energy storage applications. We describe here the synthesis and characterisation of a family of novel "chelating" ILs designed to chelate and solubilize the zinc ions to create electrolytes for this type of battery. These are based on quaternary alkoxy alkyl ammonium cations of varying oligo-ether side chains and anions such as p-toluene sulfonate, bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that increasing the ether chain length in the cation from two to four oxygens can increase the ionic conductivity and reduce the melting point from 67 °C to 15 °C for the tosylate system. Changing the anion also plays a significant role in the nature of the zinc deposition electrochemistry. We show that zinc can be reversibly deposited from [N(222(20201))][NTf2] and [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively, but not in the case of tosylate based ILs. This indicates that the [NTf2] is a weaker coordinating anion with the zinc cation, compared to the tosylate anion, allowing the coordination of the ether chain to dominate the behavior of the deposition and stripping of zinc ions.

  5. Space Shuttle mission: STS-67

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Space Shuttle Endeavor, scheduled to launch March 2, 1995 from NASA's Kennedy Space Center, will conduct NASA's longest Shuttle flight prior to date. The mission, designated STS-67, has a number of experiments and payloads, which the crew, commanded by Stephen S. Oswald, will have to oversee. This NASA press kit for the mission contains a general background (general press release, media services information, quick-look facts page, shuttle abort modes, summary timeline, payload and vehicle weights, orbital summary, and crew responsibilities); cargo bay payloads and activities (Astro 2, Get Away Special Experiments); in-cabin payloads (Commercial Minimum Descent Altitude Instrumentation Technology Associates Experiments, protein crystal growth experiments, Middeck Active Control Experiment, and Shuttle Amateur Radio Experiment); and the STS-67 crew biographies. The payloads and experiments are described and summarized to give an overview of the goals, objectives, apparatuses, procedures, sponsoring parties, and the assigned crew members to carry out the tasks.

  6. Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort.

    PubMed

    Martinez, Sabrina S; Campa, Adriana; Li, Yinghui; Fleetwood, Christina; Stewart, Tiffanie; Ramamoorthy, Venkataraghavan; Baum, Marianna K

    2017-04-01

    Background: Oxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target. Objective: We aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort. Methods: A prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected adults with a mean ± SD age of 47.08 ± 7.67 y from the MASH cohort and followed for a median of 34 mo. Blood was collected for plasma zinc and measures were used to calculate the fibrosis-4 (FIB-4) score (aspartate amino transferase, alanine aminotransferase, and platelets). Plasma zinc deficiency was defined as <0.75 mg/L. Total DNA was extracted from peripheral blood mononuclear cells and mitochondrial DNA (mtDNA) 8-hydroxyguanosine (8-oxo-dG) was determined. Adjusted mixed models were used to assess the relations between zinc, stage of liver disease, and oxidative stress over time and compared between HIV and HIV/HCV groups. Results: Zinc concentrations (β: -0.368, SE = 0.172; P = 0.033) and deficiency were associated with lower FIB-4 scores over time (β: 0.381, SE = 0.118; P = 0.001). Compared with those who were not zinc deficient, zinc-deficient participants had an increased risk of having more-progressed liver disease (OR: 1.91; 95% CI: 1.15, 3.16; P = 0.012). Higher mtDNA 8-oxo-dG was associated with zinc deficiency (β: 0.049, SE = 0.024; P = 0.044) and higher FIB-4 scores over time (β: 0.597, SE = 0.168, P < 0.001). Conclusions: Lower plasma zinc concentrations were associated with liver fibrosis progression and mitochondrial oxidative stress in the HIV and HIV/HCV groups. Zinc may play a role in the impact of liver disease outcomes. © 2017 American Society for Nutrition.

  7. Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort1234

    PubMed Central

    Martinez, Sabrina S; Campa, Adriana; Li, Yinghui; Fleetwood, Christina; Stewart, Tiffanie; Ramamoorthy, Venkataraghavan; Baum, Marianna K

    2017-01-01

    Background: Oxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target. Objective: We aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort. Methods: A prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)–coinfected adults with a mean ± SD age of 47.08 ± 7.67 y from the MASH cohort and followed for a median of 34 mo. Blood was collected for plasma zinc and measures were used to calculate the fibrosis-4 (FIB-4) score (aspartate amino transferase, alanine aminotransferase, and platelets). Plasma zinc deficiency was defined as <0.75 mg/L. Total DNA was extracted from peripheral blood mononuclear cells and mitochondrial DNA (mtDNA) 8-hydroxyguanosine (8-oxo-dG) was determined. Adjusted mixed models were used to assess the relations between zinc, stage of liver disease, and oxidative stress over time and compared between HIV and HIV/HCV groups. Results: Zinc concentrations (β: −0.368, SE = 0.172; P = 0.033) and deficiency were associated with lower FIB-4 scores over time (β: 0.381, SE = 0.118; P = 0.001). Compared with those who were not zinc deficient, zinc-deficient participants had an increased risk of having more-progressed liver disease (OR: 1.91; 95% CI: 1.15, 3.16; P = 0.012). Higher mtDNA 8-oxo-dG was associated with zinc deficiency (β: 0.049, SE = 0.024; P = 0.044) and higher FIB-4 scores over time (β: 0.597, SE = 0.168, P < 0.001). Conclusions: Lower plasma zinc concentrations were associated with liver fibrosis progression and mitochondrial oxidative stress in the HIV and HIV/HCV groups. Zinc may play a role in the impact of liver disease outcomes. PMID:28228506

  8. Zinc stress induces copper depletion in Acinetobacter baumannii.

    PubMed

    Hassan, Karl A; Pederick, Victoria G; Elbourne, Liam D H; Paulsen, Ian T; Paton, James C; McDevitt, Christopher A; Eijkelkamp, Bart A

    2017-03-11

    The first row transition metal ions zinc and copper are essential to the survival of many organisms, although in excess these ions are associated with significant toxicity. Here, we examined the impact of zinc and copper stress on Acinetobacter baumannii, a common opportunistic pathogen. We show that extracellular zinc stress induces a copper-specific depletion phenotype in A. baumannii ATCC 17978. Supplementation with copper not only fails to rescue this phenotype, but further exacerbates the copper depletion. Extensive analysis of the A. baumannii ATCC 17978 genome identified 13 putative zinc/copper resistance efflux pumps. Transcriptional analyses show that four of these transporters are responsive to zinc stress, five to copper stress and seven to the combination of zinc and copper stress, thereby revealing a likely foundation for the zinc-induced copper starvation in A. baumannii. In addition, we show that zinc and copper play crucial roles in management of oxidative stress and the membrane composition of A. baumannii. Further, we reveal that zinc and copper play distinct roles in macrophage-mediated killing of this pathogen. Collectively, this study supports the targeting of metal ion homeostatic mechanisms as an effective antimicrobial strategy against multi-drug resistant bacterial pathogens.

  9. Zinc binding groups for histone deacetylase inhibitors.

    PubMed

    Zhang, Lei; Zhang, Jian; Jiang, Qixiao; Zhang, Li; Song, Weiguo

    2018-12-01

    Zinc binding groups (ZBGs) play a crucial role in targeting histone deacetylase inhibitors (HDACIs) to the active site of histone deacetylases (HDACs), thus determining the potency of HDACIs. Due to the high affinity to the zinc ion, hydroxamic acid is the most commonly used ZBG in the structure of HDACs. An alternative ZBG is benzamide group, which features excellent inhibitory selectivity for class I HDACs. Various ZBGs have been designed and tested to improve the activity and selectivity of HDACIs, and to overcome the pharmacokinetic limitations of current HDACIs. Herein, different kinds of ZBGs are reviewed and their features have been discussed for further design of HDACIs.

  10. Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

    PubMed Central

    Maret, Wolfgang

    2017-01-01

    About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic β- and α-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the patho-biochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of β-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions. PMID:28401081

  11. Designing Hydrolytic Zinc Metalloenzymes

    PubMed Central

    2015-01-01

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  12. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, Toshifumi

    1997-01-01

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate .alpha.-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal.

  13. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, T.

    1997-02-18

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate {alpha}-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal. 33 figs.

  14. Comet 67P's Pitted Surface

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-11-01

    High-resolution imagery of comet 67P ChuryumovGerasimenko has revealed that its surface is covered in active pits some measuring hundreds of meters both wide and deep! But what processes caused these pits to form?Pitted LandscapeESAs Rosetta mission arrived at comet 67P in August 2014. As the comet continued its journey around the Sun, Rosetta extensively documented 67Ps surface through high-resolution images taken with the on-board instrument NavCam. These images have revealed that active, circular depressions are a common feature on the comets surface.In an attempt to determine how these pits formed, an international team of scientists led by Olivier Mousis (Laboratory of Astrophysics of Marseille) has run a series of simulations of a region of the comet the Seth region that contains a 200-meter-deep pit. These simulations include the effects of various phase transitions, heat transfer through the matrix of ices and dust, and gas diffusion throughout the porous material.Escaping VolatilesAdditional examples of pitted areas on 67Ps northern-hemisphere surface include the Ash region and the Maat region (both imaged September 2014 by NavCam) [Mousis et al. 2015]Previous studies have already eliminated two potential formation mechanisms for the pits: impacts (the sizes of the pits werent right) and erosion due to sunlight (the pits dont have the right shape). Mousis and collaborators assume that the pits are instead caused by the depletion of volatile materials chemical compounds with low boiling points either via explosive outbursts at the comets surface, or via sinkholes opening from below the surface. But what process causes the volatiles to deplete when the comet heats?The authors simulations demonstrate that volatiles trapped beneath the comets surface either in icy structures called clathrates or within amorphous ice can be suddenly released as the comet warms up. The team shows that the release of volatiles from these two structures can create 200-meter

  15. New Production Routes for Medical Isotopes 64Cu and 67Cu Using Accelerator Neutrons

    NASA Astrophysics Data System (ADS)

    Kin, Tadahiro; Nagai, Yasuki; Iwamoto, Nobuyuki; Minato, Futoshi; Iwamoto, Osamu; Hatsukawa, Yuichi; Segawa, Mariko; Harada, Hideo; Konno, Chikara; Ochiai, Kentaro; Takakura, Kosuke

    2013-03-01

    We have measured the activation cross sections producing 64Cu and 67Cu, promising medical radioisotopes for molecular imaging and radioimmunotherapy, by bombarding a natural zinc sample with 14 MeV neutrons. We estimated the production yields of 64Cu and 67Cu by fast neutrons from \\text{natC(d,n) with 40 MeV 5 mA deuterons. We used the present result together with the evaluated cross section of Zn isotopes. The calculated 64Cu yield is 1.8 TBq (175 g 64Zn) for 12 h of irradiation; the yields of 67Cu by 67Zn(n,p)67Cu and 68Zn(n,x)67Cu were 249 GBq (184 g 67Zn) and 287 GBq (186 g 68Zn) at the end of 2 days of irradiation, respectively. From the results, we proposed a new route to produce 67Cu with very little radionuclide impurity via the 68Zn(n,x)67Cu reaction, and showed the 64Zn(n,p)64Cu reaction to be a promising route to produce 64Cu. Both 67Cu and 64Cu are noted to be produced using fast neutrons.

  16. 46 CFR 67.70 - Original owner.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Original owner. 67.70 Section 67.70 Shipping COAST GUARD... Acceptable Title Evidence; Waiver § 67.70 Original owner. The builder's certification described in § 67.99 serves as evidence of the original owner's title to a vessel. ...

  17. The zinc-binding region (ZBR) fragment of Emi2 can inhibit APC/C by targeting its association with the coactivator Cdc20 and UBE2C-mediated ubiquitylation

    PubMed Central

    Shoji, Shisako; Muto, Yutaka; Ikeda, Mariko; He, Fahu; Tsuda, Kengo; Ohsawa, Noboru; Akasaka, Ryogo; Terada, Takaho; Wakiyama, Motoaki; Shirouzu, Mikako; Yokoyama, Shigeyuki

    2014-01-01

    Anaphase-promoting complex or cyclosome (APC/C) is a multisubunit ubiquitin ligase E3 that targets cell-cycle regulators. Cdc20 is required for full activation of APC/C in M phase, and mediates substrate recognition. In vertebrates, Emi2/Erp1/FBXO43 inhibits APC/C-Cdc20, and functions as a cytostatic factor that causes long-term M phase arrest of mature oocytes. In this study, we found that a fragment corresponding to the zinc-binding region (ZBR) domain of Emi2 inhibits cell-cycle progression, and impairs the association of Cdc20 with the APC/C core complex in HEK293T cells. Furthermore, we revealed that the ZBR fragment of Emi2 inhibits in vitro ubiquitin chain elongation catalyzed by the APC/C cullin-RING ligase module, the ANAPC2–ANAPC11 subcomplex, in combination with the ubiquitin chain-initiating E2, E2C/UBE2C/UbcH10. Structural analyses revealed that the Emi2 ZBR domain uses different faces for the two mechanisms. Thus, the double-faced ZBR domain of Emi2 antagonizes the APC/C function by inhibiting both the binding with the coactivator Cdc20 and ubiquitylation mediated by the cullin-RING ligase module and E2C. In addition, the tail region between the ZBR domain and the C-terminal RL residues [the post-ZBR (PZ) region] interacts with the cullin subunit, ANAPC2. In the case of the ZBR fragment of the somatic paralogue of Emi2, Emi1/FBXO5, these inhibitory activities against cell division and ubiquitylation were not observed. Finally, we identified two sets of key residues in the Emi2 ZBR domain that selectively exert each of the dual Emi2-specific modes of APC/C inhibition, by their mutation in the Emi2 ZBR domain and their transplantation into the Emi1 ZBR domain. PMID:25161877

  18. Zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, Jr., Philip N.

    1989-01-01

    An improved zinc electrode is disclosed for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed which utilizes the improved zinc electrode and further includes an alkaline electrolyte within said battery circulating through the passageways in the zinc electrode and an external electrolyte circulation means which has an electrolyte reservoir external to the battery case including filter means to filter solids out of the electrolyte as it circulates to the external reservoir and pump means for recirculating electrolyte from the external reservoir to the zinc electrode.

  19. New production cross sections for the theranostic radionuclide 67Cu

    NASA Astrophysics Data System (ADS)

    Pupillo, Gaia; Sounalet, Thomas; Michel, Nathalie; Mou, Liliana; Esposito, Juan; Haddad, Férid

    2018-01-01

    The cross sections of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to a low-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%) was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga. Nuclear cross sections were measured in the energy range 35-70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the software TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.

  20. Disruption of zinc neuromodulation by Aß oligomers: therapeutic implications.

    PubMed

    Vogler, Emily C; Busciglio, Jorge

    2014-01-01

    So far, therapeutics focusing on reducing levels of amyloid beta for treatment of Alzheimer's disease have not been successful in completing clinical trials to come to market, suggesting the need of a wider perspective and the consideration of novel targets of intervention to slow or halt the progression of this disease. One such target is soluble amyloid beta in oligomeric forms, which have been demonstrated to bind with high affinity to zinc released during synaptic activity. This review considers the interaction of AβO and zinc and the role of zinc in neurotransmission along with possible neurotoxic effects of this interaction. Finally, it also discusses recent experimental data in animal models that have translated into potential treatments for AD based on the modulation of hyperexcitability and zinc homeostasis.

  1. Computational exploration of zinc binding groups for HDAC inhibition.

    PubMed

    Chen, Kai; Xu, Liping; Wiest, Olaf

    2013-05-17

    Histone deacetylases (HDACs) have emerged as important drug targets in epigenetics. The most common HDAC inhibitors use hydroxamic acids as zinc binding groups despite unfavorable pharmacokinetic properties. A two-stage protocol of M05-2X calculations of a library of 48 fragments in a small model active site, followed by QM/MM hybrid calculations of the full enzyme with selected binders, is used to prospectively select potential bidentate zinc binders. The energetics and interaction patterns of several zinc binders not previously used for the inhibition of HDACs are discussed.

  2. 99. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    99. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, LOOKING NORTH. NOTE ONE STYLE OF DENVER AGITATOR IN LOWER RIGHT CELL. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

  3. Suppression of zinc dendrites in zinc electrode power cells

    NASA Technical Reports Server (NTRS)

    Damjanovic, A.; Diggle, J. W.

    1970-01-01

    Addition of various tetraalkyl quarternary ammonium salts, to alkaline zincate electrolyte of cell, prevents formation of zinc dendrites during charging of zinc electrode. Electrode capacity is not impaired and elimination of dendrites prolongs cell life.

  4. Three diverse target preparations: 14C (12 mg/cm 2), 71Ga 24Mg (12 mg/cm 271Ga, 3 mg/cm 224Mg), and 66,67Zn (1.8-14.9 mg/cm 2)

    NASA Astrophysics Data System (ADS)

    Lozowski, W. R.

    1989-10-01

    A natural-carbon analog of fluffy, intractable 14C powder was produced. With it, a method was developed to produce a pressed disk of 14C of 12.7-mg/cm 2 thickness and 1.27-cm diameter, bound with 2.1 wt.% of adhesive. Aluminized Mylar cover foils and a fritted-disc filter were used to contain the target for ( overlinep, p') experiments. Reduction of 71Ga 2O 3 to the metal was accomplished with an efficiency of 94.3% in a small electroplating cell. Magnesium was chosen as the companion element because 50 at.% could be tolerated in the (p, n) experiment, and GaMg has a melting point of 646 K. A 1.27-cm diameter target, supported at the edge by a Mg foil, was produced in several simple steps. Directly rollable 66,67Zn foils were obtained from an electroplating cell with a Pt screen anode and a highly polished tungsten-carbide cathode. Plating times of 3 h provided metal-recovery efficiencies ranging from 94.2 to 96.5%. The as-deposited foils had many holes but were hole-free and shiny after reduction of 25% by pack rolling.

  5. Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: Inefficacy of genetic or pharmacological disruption of COX-2

    PubMed Central

    Fong, Louise Y.Y.; Jiang, Yubao; Riley, Maurisa; Liu, Xianglan; Smalley, Karl J.; Guttridge, Denis C.; Farber, John L.

    2009-01-01

    Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced for-estomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive bio-markers COX-2, nuclear factor (NF)-κ B p65 and leukotriene A4 hydrolase (LTA4H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-2−/− forestomachs displayed strong LTA4H immunostaining, indicating activation of an alter-native pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. PMID:17985342

  6. Zinc Absorption from Representative Diet in a Chinese Elderly Population Using Stable Isotope Technique.

    PubMed

    Li, Ya Jie; Li, Min; Liu, Xiao Bing; Ren, Tong Xiang; Li, Wei Dong; Yang, Chun; Wu, Meng; Yang, Lin Li; Ma, Yu Xia; Wang, Jun; Piao, Jian Hua; Yang, Li Chen; Yang, Xiao Guang

    2017-06-01

    To determine the dietary zinc absorption in a Chinese elderly population and provide the basic data for the setting of zinc (Zn) recommended nutrient intakes (RNI) for Chinese elderly people. A total of 24 elderly people were recruited for this study and were administered oral doses of 3 mg 67Zn and 1.2 mg dysprosium on the fourth day. The primary macronutrients, energy, and phytic acid in the representative diet were examined based on the Chinese National Standard Methods. Fecal samples were collected during the experimental period and analyzed for zinc content, 67Zn isotope ratio, and dysprosium content. The mean (± SD) zinc intake from the representative Chinese diet was 10.6 ± 1.5 mg/d. The phytic acid-to-zinc molar ratio in the diet was 6.4. The absorption rate of 67Zn was 27.9% ± 9.2%. The RNI of zinc, which were calculated by the absorption rate in elderly men and women, were 10.4 and 9.2 mg/d, respectively. This study got the dietary Zn absorption in a Chinese elderly population. We found that Zn absorption was higher in elderly men than in elderly women. The current RNI in elderly female is lower than our finding, which indicates that more attention is needed regarding elderly females' zinc status and health. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  7. Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems

    PubMed Central

    Toren, Amos; Pismenyuk, Tatyana; Yalon, Michal; Freedman, Shani; Simon, Amos J.; Fisher, Tamar; Moshe, Itai; Reichardt, Juergen K.V.; Constantini, Shlomi; Mardor, Yael; Last, David; Guez, David; Daniels, Dianne; Assoulin, Moria; Mehrian-Shai, Ruty

    2016-01-01

    Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant reduction in tumor volume in TMZ/zinc treated mice relative to treatment with TMZ alone. Our results suggest that zinc may serve as a potentiator of TMZ therapy in GBM patients. PMID:27556862

  8. Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems.

    PubMed

    Toren, Amos; Pismenyuk, Tatyana; Yalon, Michal; Freedman, Shani; Simon, Amos J; Fisher, Tamar; Moshe, Itai; Reichardt, Juergen K V; Constantini, Shlomi; Mardor, Yael; Last, David; Guez, David; Daniels, Dianne; Assoulin, Moria; Mehrian-Shai, Ruty

    2016-11-15

    Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant reduction in tumor volume in TMZ/zinc treated mice relative to treatment with TMZ alone. Our results suggest that zinc may serve as a potentiator of TMZ therapy in GBM patients.

  9. Zinc titanate sorbents

    DOEpatents

    Gupta, R.P.; Gangwal, S.K.; Jain, S.C.

    1998-02-03

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750 to about 950 C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 microns, and about 1 part titanium dioxide having a median particle size of less than about 1 micron. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  10. Zinc titanate sorbents

    DOEpatents

    Gupta, Raghubir P.; Gangwal, Santosh K.; Jain, Suresh C.

    1998-01-01

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750.degree. C. to about 950.degree. C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 .mu., and about 1 part titanium dioxide having a median particle size of less than about 1 .mu.. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  11. 14 CFR 67.3 - Issue.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Issue. 67.3 Section 67.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION General § 67.3 Issue. A person who meets the medical standards prescribed in this...

  12. 14 CFR 67.3 - Issue.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Issue. 67.3 Section 67.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION General § 67.3 Issue. A person who meets the medical standards prescribed in this...

  13. 14 CFR 67.3 - Issue.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Issue. 67.3 Section 67.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION General § 67.3 Issue. A person who meets the medical standards prescribed in this...

  14. 14 CFR 67.3 - Issue.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Issue. 67.3 Section 67.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION General § 67.3 Issue. A person who meets the medical standards prescribed in this...

  15. 14 CFR 67.3 - Issue.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Issue. 67.3 Section 67.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION General § 67.3 Issue. A person who meets the medical standards prescribed in this...

  16. 38 CFR 4.67 - Pelvic bones.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Pelvic bones. 4.67 Section 4.67 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.67 Pelvic bones. The variability of residuals...

  17. 38 CFR 4.67 - Pelvic bones.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Pelvic bones. 4.67 Section 4.67 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.67 Pelvic bones. The variability of residuals...

  18. 38 CFR 4.67 - Pelvic bones.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Pelvic bones. 4.67 Section 4.67 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.67 Pelvic bones. The variability of residuals...

  19. 38 CFR 4.67 - Pelvic bones.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Pelvic bones. 4.67 Section 4.67 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.67 Pelvic bones. The variability of residuals...

  20. 38 CFR 4.67 - Pelvic bones.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Pelvic bones. 4.67 Section 4.67 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.67 Pelvic bones. The variability of residuals...

  1. 7 CFR 932.67 - Effective time.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Effective time. 932.67 Section 932.67 Agriculture... Regulating Handling Miscellaneous Provisions § 932.67 Effective time. The provisions of this subpart, as well as any amendments to this subpart, shall become effective at such time as the Secretary may declare...

  2. 7 CFR 932.67 - Effective time.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Effective time. 932.67 Section 932.67 Agriculture... Regulating Handling Miscellaneous Provisions § 932.67 Effective time. The provisions of this subpart, as well as any amendments to this subpart, shall become effective at such time as the Secretary may declare...

  3. 7 CFR 932.67 - Effective time.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Effective time. 932.67 Section 932.67 Agriculture... Regulating Handling Miscellaneous Provisions § 932.67 Effective time. The provisions of this subpart, as well as any amendments to this subpart, shall become effective at such time as the Secretary may declare...

  4. 7 CFR 932.67 - Effective time.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Effective time. 932.67 Section 932.67 Agriculture... Regulating Handling Miscellaneous Provisions § 932.67 Effective time. The provisions of this subpart, as well as any amendments to this subpart, shall become effective at such time as the Secretary may declare...

  5. 7 CFR 932.67 - Effective time.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Effective time. 932.67 Section 932.67 Agriculture... Regulating Handling Miscellaneous Provisions § 932.67 Effective time. The provisions of this subpart, as well as any amendments to this subpart, shall become effective at such time as the Secretary may declare...

  6. 36 CFR 6.7 - Mining wastes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Mining wastes. 6.7 Section 6.7 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SOLID WASTE DISPOSAL SITES IN UNITS OF THE NATIONAL PARK SYSTEM § 6.7 Mining wastes. (a) Solid waste from mining...

  7. 36 CFR 6.7 - Mining wastes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Mining wastes. 6.7 Section 6.7 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SOLID WASTE DISPOSAL SITES IN UNITS OF THE NATIONAL PARK SYSTEM § 6.7 Mining wastes. (a) Solid waste from mining...

  8. 36 CFR 6.7 - Mining wastes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Mining wastes. 6.7 Section 6.7 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SOLID WASTE DISPOSAL SITES IN UNITS OF THE NATIONAL PARK SYSTEM § 6.7 Mining wastes. (a) Solid waste from mining...

  9. 36 CFR 6.7 - Mining wastes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Mining wastes. 6.7 Section 6.7 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SOLID WASTE DISPOSAL SITES IN UNITS OF THE NATIONAL PARK SYSTEM § 6.7 Mining wastes. (a) Solid waste from mining...

  10. 46 CFR 67.41 - Governmental entity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Governmental entity. 67.41 Section 67.41 Shipping COAST... DOCUMENTATION OF VESSELS Citizenship Requirements for Vessel Documentation § 67.41 Governmental entity. A governmental entity is a citizen for the purpose of obtaining a vessel document if it is an entity of the...

  11. 46 CFR 67.41 - Governmental entity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Governmental entity. 67.41 Section 67.41 Shipping COAST... DOCUMENTATION OF VESSELS Citizenship Requirements for Vessel Documentation § 67.41 Governmental entity. A governmental entity is a citizen for the purpose of obtaining a vessel document if it is an entity of the...

  12. 14 CFR 67.111 - Cardiovascular.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.111 Section 67.111... STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.111 Cardiovascular. Cardiovascular... disease that has required treatment or, if untreated, that has been symptomatic or clinically significant...

  13. 14 CFR 67.311 - Cardiovascular.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.311 Section 67.311... STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.311 Cardiovascular. Cardiovascular... disease that has required treatment or, if untreated, that has been symptomatic or clinically significant...

  14. 14 CFR 67.211 - Cardiovascular.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.211 Section 67.211... STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.211 Cardiovascular. Cardiovascular... any of the following: (a) Myocardial infarction; (b) Angina pectoris; (c) Coronary heart disease that...

  15. 21 CFR 1316.67 - Final order.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Final order. 1316.67 Section 1316.67 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Hearings § 1316.67 Final order. As soon as practicable after the presiding officer...

  16. 28 CFR 90.67 - Grantee reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Grantee reporting. 90.67 Section 90.67 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) VIOLENCE AGAINST WOMEN Arrest Policies in Domestic Violence Cases § 90.67 Grantee reporting. Each grantee receiving funds under this subpart shall...

  17. 33 CFR 67.40-25 - Penalty.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Penalty. 67.40-25 Section 67.40-25 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Notification § 67.40-25 Penalty. The...

  18. 33 CFR 67.01-30 - Equivalents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Equivalents. 67.01-30 Section 67.01-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES General Requirements § 67.01-30...

  19. 33 CFR 67.50-1 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Scope. 67.50-1 Section 67.50-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES District Regulations § 67.50-1 Scope. (a) The...

  20. 33 CFR 67.35-1 - Procedure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Procedure. 67.35-1 Section 67.35-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Applications § 67.35-1 Procedure. (a) An...

  1. 33 CFR 67.40-25 - Penalty.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Penalty. 67.40-25 Section 67.40-25 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Notification § 67.40-25 Penalty. The...

  2. 33 CFR 67.01-30 - Equivalents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Equivalents. 67.01-30 Section 67.01-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES General Requirements § 67.01-30...

  3. 33 CFR 67.35-1 - Procedure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Procedure. 67.35-1 Section 67.35-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Applications § 67.35-1 Procedure. (a) An...

  4. 25 CFR 67.3 - Information collection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Information collection. 67.3 Section 67.3 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT PREPARATION OF A ROLL OF INDEPENDENT SEMINOLE INDIANS OF FLORIDA § 67.3 Information collection. The information collection requirement contained...

  5. 10 CFR 39.67 - Radiation surveys.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Radiation surveys. 39.67 Section 39.67 Energy NUCLEAR... Requirements § 39.67 Radiation surveys. (a) The licensee shall make radiation surveys, including but not limited to the surveys required under paragraphs (b) through (e) of this section, of each area where...

  6. 10 CFR 39.67 - Radiation surveys.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Radiation surveys. 39.67 Section 39.67 Energy NUCLEAR... Requirements § 39.67 Radiation surveys. (a) The licensee shall make radiation surveys, including but not limited to the surveys required under paragraphs (b) through (e) of this section, of each area where...

  7. 10 CFR 39.67 - Radiation surveys.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Radiation surveys. 39.67 Section 39.67 Energy NUCLEAR... Requirements § 39.67 Radiation surveys. (a) The licensee shall make radiation surveys, including but not limited to the surveys required under paragraphs (b) through (e) of this section, of each area where...

  8. 10 CFR 39.67 - Radiation surveys.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Radiation surveys. 39.67 Section 39.67 Energy NUCLEAR... Requirements § 39.67 Radiation surveys. (a) The licensee shall make radiation surveys, including but not limited to the surveys required under paragraphs (b) through (e) of this section, of each area where...

  9. 10 CFR 39.67 - Radiation surveys.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Radiation surveys. 39.67 Section 39.67 Energy NUCLEAR... Requirements § 39.67 Radiation surveys. (a) The licensee shall make radiation surveys, including but not limited to the surveys required under paragraphs (b) through (e) of this section, of each area where...

  10. 49 CFR 511.67 - Settlement order.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Settlement order. 511.67 Section 511.67... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ADJUDICATIVE PROCEDURES Settlement Procedure in Cases of Violation of Average Fuel Economy Standards § 511.67 Settlement order. If, in accordance with this subpart, the...

  11. 46 CFR 67.220 - Requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Requirements. 67.220 Section 67.220 Shipping COAST GUARD... Filing and Recording of Instruments-Bills of Sale and Related Instruments § 67.220 Requirements. An instrument in the nature of a bill of sale or a deed of gift must: (a) Meet all of the requirements of...

  12. 46 CFR 67.220 - Requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Requirements. 67.220 Section 67.220 Shipping COAST GUARD... Filing and Recording of Instruments-Bills of Sale and Related Instruments § 67.220 Requirements. An instrument in the nature of a bill of sale or a deed of gift must: (a) Meet all of the requirements of...

  13. 46 CFR 67.220 - Requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Requirements. 67.220 Section 67.220 Shipping COAST GUARD... Filing and Recording of Instruments-Bills of Sale and Related Instruments § 67.220 Requirements. An instrument in the nature of a bill of sale or a deed of gift must: (a) Meet all of the requirements of...

  14. 46 CFR 67.39 - Corporation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Corporation. 67.39 Section 67.39 Shipping COAST GUARD... Citizenship Requirements for Vessel Documentation § 67.39 Corporation. (a) For the purpose of obtaining a registry or a recreational endorsement, a corporation meets citizenship requirements if: (1) It is...

  15. 46 CFR 67.39 - Corporation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Corporation. 67.39 Section 67.39 Shipping COAST GUARD... Citizenship Requirements for Vessel Documentation § 67.39 Corporation. (a) For the purpose of obtaining a registry or a recreational endorsement, a corporation meets citizenship requirements if: (1) It is...

  16. 46 CFR 67.39 - Corporation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Corporation. 67.39 Section 67.39 Shipping COAST GUARD... Citizenship Requirements for Vessel Documentation § 67.39 Corporation. (a) For the purpose of obtaining a registry or a recreational endorsement, a corporation meets citizenship requirements if: (1) It is...

  17. 46 CFR 67.39 - Corporation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  18. 46 CFR 67.39 - Corporation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Corporation. 67.39 Section 67.39 Shipping COAST GUARD... Citizenship Requirements for Vessel Documentation § 67.39 Corporation. (a) For the purpose of obtaining a registry or a recreational endorsement, a corporation meets citizenship requirements if: (1) It is...

  19. 46 CFR 310.67 - Academy regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Academy regulations. 310.67 Section 310.67 Shipping... Training of Midshipmen at the United States Merchant Marine Academy § 310.67 Academy regulations. The Superintendent of the Academy is delegated authority to issue all regulations necessary for the accomplishment of...

  20. 14 CFR 67.413 - Medical records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Medical records. 67.413 Section 67.413 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Certification Procedures § 67.413 Medical records. (a) Whenever the...

  1. 14 CFR 67.413 - Medical records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Medical records. 67.413 Section 67.413 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Certification Procedures § 67.413 Medical records. (a) Whenever the...

  2. 14 CFR 67.413 - Medical records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Medical records. 67.413 Section 67.413 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Certification Procedures § 67.413 Medical records. (a) Whenever the...

  3. 25 CFR 67.3 - Information collection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Information collection. 67.3 Section 67.3 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT PREPARATION OF A ROLL OF INDEPENDENT SEMINOLE INDIANS OF FLORIDA § 67.3 Information collection. The information collection requirement contained...

  4. 49 CFR 585.67 - Records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Records. 585.67 Section 585.67 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION... Phase-in Reporting Requirements § 585.67 Records. Each manufacturer must maintain records of the Vehicle...

  5. 49 CFR 585.67 - Records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Records. 585.67 Section 585.67 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION... Phase-in Reporting Requirements § 585.67 Records. Each manufacturer must maintain records of the Vehicle...

  6. 49 CFR 585.67 - Records.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Records. 585.67 Section 585.67 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION... Phase-in Reporting Requirements § 585.67 Records. Each manufacturer must maintain records of the Vehicle...

  7. 49 CFR 585.67 - Records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Records. 585.67 Section 585.67 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION... Phase-in Reporting Requirements § 585.67 Records. Each manufacturer must maintain records of the Vehicle...

  8. 49 CFR 386.67 - Judicial review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Judicial review. 386.67 Section 386.67... Decision § 386.67 Judicial review. (a) Any party to the underlying proceeding, who, after an administrative... service of the Final Agency Order, petition for review of the order in the United States Court of Appeals...

  9. 14 CFR 33.67 - Fuel system.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.67 Fuel system. (a) With... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Fuel system. 33.67 Section 33.67... protection of the engine fuel system against foreign particles in the fuel. The applicant must show: (i) That...

  10. 14 CFR 33.67 - Fuel system.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.67 Fuel system. (a) With... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Fuel system. 33.67 Section 33.67... protection of the engine fuel system against foreign particles in the fuel. The applicant must show: (i) That...

  11. 14 CFR 67.209 - Neurologic.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Neurologic. 67.209 Section 67.209... STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.209 Neurologic. Neurologic... neurologic condition that the Federal Air Surgeon, based on the case history and appropriate, qualified...

  12. 14 CFR 67.209 - Neurologic.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Neurologic. 67.209 Section 67.209... STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.209 Neurologic. Neurologic... neurologic condition that the Federal Air Surgeon, based on the case history and appropriate, qualified...

  13. 14 CFR 67.109 - Neurologic.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Neurologic. 67.109 Section 67.109... STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.109 Neurologic. Neurologic standards... neurologic condition that the Federal Air Surgeon, based on the case history and appropriate, qualified...

  14. 14 CFR 67.309 - Neurologic.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Neurologic. 67.309 Section 67.309... STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.309 Neurologic. Neurologic standards... neurologic condition that the Federal Air Surgeon, based on the case history and appropriate, qualified...

  15. 14 CFR 67.109 - Neurologic.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Neurologic. 67.109 Section 67.109... STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.109 Neurologic. Neurologic standards... neurologic condition that the Federal Air Surgeon, based on the case history and appropriate, qualified...

  16. 14 CFR 67.309 - Neurologic.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Neurologic. 67.309 Section 67.309... STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.309 Neurologic. Neurologic standards... neurologic condition that the Federal Air Surgeon, based on the case history and appropriate, qualified...

  17. 10 CFR 501.67 - Petition redesignations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Petition redesignations. 501.67 Section 501.67 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Exemptions and Certifications § 501.67 Petition redesignations. OFE, with the petitioner's approval, will redesignate an...

  18. 30 CFR 7.67 - Construction test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Construction test. 7.67 Section 7.67 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.67 Construction test...

  19. 7 CFR 1780.67 - Performing construction.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Performing construction. 1780.67 Section 1780.67..., Constructing and Inspections § 1780.67 Performing construction. Owners are encouraged to accomplish construction through contracts with qualified contractors. Owners may accomplish construction by using their...

  20. 7 CFR 1780.67 - Performing construction.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Performing construction. 1780.67 Section 1780.67..., Constructing and Inspections § 1780.67 Performing construction. Owners are encouraged to accomplish construction through contracts with qualified contractors. Owners may accomplish construction by using their...

  1. 40 CFR 421.67 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 421.67 Section 421.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS NONFERROUS METALS MANUFACTURING POINT SOURCE CATEGORY Secondary Copper Subcategory § 421.67 [Reserved] ...

  2. 40 CFR 421.67 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true [Reserved] 421.67 Section 421.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS NONFERROUS METALS MANUFACTURING POINT SOURCE CATEGORY Secondary Copper Subcategory § 421.67 [Reserved] ...

  3. 19 CFR 111.67 - Hearing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Hearing. 111.67 Section 111.67 Customs Duties U.S... Revocation § 111.67 Hearing. (a) Hearing officer. The hearing officer must be an administrative law judge... right to examine all exhibits offered at the hearing and will have the right to cross-examine witnesses...

  4. 40 CFR 420.67 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 420.67 Section 420.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Continuous Casting Subcategory § 420.67 [Reserved] ...

  5. 25 CFR 67.6 - Application forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... application form is filed by a sponsor, the name and address of the sponsor and the sponsor's relationship to... 25 Indians 1 2011-04-01 2011-04-01 false Application forms. 67.6 Section 67.6 Indians BUREAU OF... SEMINOLE INDIANS OF FLORIDA § 67.6 Application forms. (a) Application forms to be filed by or for...

  6. 25 CFR 67.6 - Application forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... application form is filed by a sponsor, the name and address of the sponsor and the sponsor's relationship to... 25 Indians 1 2014-04-01 2014-04-01 false Application forms. 67.6 Section 67.6 Indians BUREAU OF... SEMINOLE INDIANS OF FLORIDA § 67.6 Application forms. (a) Application forms to be filed by or for...

  7. 25 CFR 67.6 - Application forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... application form is filed by a sponsor, the name and address of the sponsor and the sponsor's relationship to... 25 Indians 1 2012-04-01 2011-04-01 true Application forms. 67.6 Section 67.6 Indians BUREAU OF... SEMINOLE INDIANS OF FLORIDA § 67.6 Application forms. (a) Application forms to be filed by or for...

  8. 25 CFR 67.6 - Application forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... application form is filed by a sponsor, the name and address of the sponsor and the sponsor's relationship to... 25 Indians 1 2013-04-01 2013-04-01 false Application forms. 67.6 Section 67.6 Indians BUREAU OF... SEMINOLE INDIANS OF FLORIDA § 67.6 Application forms. (a) Application forms to be filed by or for...

  9. 30 CFR 7.67 - Construction test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Construction test. 7.67 Section 7.67 Mineral... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.67 Construction test. The constuction test is to be performed on the blasting unit subsequent to the output energy test of...

  10. 30 CFR 7.67 - Construction test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Construction test. 7.67 Section 7.67 Mineral... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.67 Construction test. The constuction test is to be performed on the blasting unit subsequent to the output energy test of...

  11. 30 CFR 7.67 - Construction test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Construction test. 7.67 Section 7.67 Mineral... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.67 Construction test. The constuction test is to be performed on the blasting unit subsequent to the output energy test of...

  12. 44 CFR 67.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 67.2 Section 67.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... ELEVATION DETERMINATIONS § 67.2 Definitions. The definitions set forth in part 59 of this subchapter are...

  13. 36 CFR 910.67 - Square guidelines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Square guidelines. 910.67 Section 910.67 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.67 Square guidelines. Square Guidelines establish the Corporation's...

  14. 36 CFR 910.67 - Square guidelines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Square guidelines. 910.67 Section 910.67 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.67 Square guidelines. Square Guidelines establish the Corporation's...

  15. 36 CFR 910.67 - Square guidelines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Square guidelines. 910.67 Section 910.67 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.67 Square guidelines. Square Guidelines establish the Corporation's...

  16. 36 CFR 910.67 - Square guidelines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Square guidelines. 910.67 Section 910.67 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.67 Square guidelines. Square Guidelines establish the Corporation's...

  17. 14 CFR 67.413 - Medical records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Medical records. 67.413 Section 67.413 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Certification Procedures § 67.413 Medical records. (a) Whenever the...

  18. 14 CFR 67.413 - Medical records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Medical records. 67.413 Section 67.413 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Certification Procedures § 67.413 Medical records. (a) Whenever the...

  19. 46 CFR 67.36 - Trust.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Trust. 67.36 Section 67.36 Shipping COAST GUARD... Citizenship Requirements for Vessel Documentation § 67.36 Trust. (a) For the purpose of obtaining a registry or recreational endorsement, a trust arrangement meets citizenship requirements if: (1) Each of its...

  20. 28 CFR 90.67 - Grantee reporting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Grantee reporting. 90.67 Section 90.67 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) VIOLENCE AGAINST WOMEN Arrest Policies in Domestic Violence Cases § 90.67 Grantee reporting. Each grantee receiving funds under this subpart shall...

  1. 29 CFR 2570.67 - Summary decision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Summary decision. 2570.67 Section 2570.67 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR ADMINISTRATION... ERISA Section 502(c)(2) § 2570.67 Summary decision. For 502(c)(2) civil penalty proceedings, this...

  2. History of zinc in agriculture

    Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, over 20 years would past before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure a parakeratosis in swine. In 1958, it wa...

  3. Recovering Zinc From Discarded Tires

    NASA Technical Reports Server (NTRS)

    Du Fresne, E. R.

    1984-01-01

    Zinc sulfate monohydrate sold at profit. Shredded tire material steeped in three sulfuric acid baths to extract zinc. Final product removed by evaporating part of solution until product crystallizes out. Recovered as zinc sulfate monohydrate and sold as fertilizer or for general use.

  4. Photovoltaic cells employing zinc phosphide

    DOEpatents

    Barnett, Allen M.; Catalano, Anthony W.; Dalal, Vikram L.; Masi, James V.; Meakin, John D.; Hall, Robert B.

    1984-01-01

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  5. AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of Huntington's Disease.

    PubMed

    Billes, Viktor; Kovács, Tibor; Hotzi, Bernadette; Manzéger, Anna; Tagscherer, Kinga; Komlós, Marcell; Tarnóci, Anna; Pádár, Zsolt; Erdős, Attila; Bjelik, Annamaria; Legradi, Adam; Gulya, Károly; Gulyás, Balázs; Vellai, Tibor

    2016-05-07

    Autophagy, a lysosome-mediated self-degradation process of eukaryotic cells, serves as a main route for the elimination of cellular damage [1-3]. Such damages include aggregated, oxidized or misfolded proteins whose accumulation can cause various neurodegenerative pathologies, including Huntington's disease (HD). Here we examined whether enhanced autophagic activity can alleviate neurophatological features in a Drosophila model of HD (the transgenic animals express a human mutant Huntingtin protein with a long polyglutamine repeat, 128Q). We have recently identified an autophagy-enhancing small molecule, AUTEN-67 (autophagy enhancer 67), with potent neuroprotective effects [4]. AUTEN-67 was applied to induce autophagic activity in the HD model used in this study. We showed that AUTEN-67 treatment interferes with the progressive accumulation of ubiquitinated proteins in the brain of Drosophila transgenic for the pathological 128Q form of human Huntingtin protein. The compound significantly improved the climbing ability and moderately extended the mean life span of these flies. Furthermore, brain tissue samples from human patients diagnosed for HD displayed increased levels of the autophagy substrate SQSTM1/p62 protein, as compared with controls. These results imply that AUTEN-67 impedes the progression of neurodegenerative symptoms characterizing HD, and that autophagy is a promising therapeutic target for treating this pathology. In humans, AUTEN-67 may have the potential to delay the onset and decrease the severity of HD.

  6. Volcano warning systems: Chapter 67

    Gregg, Chris E.; Houghton, Bruce F.; Ewert, John W.

    2015-01-01

    Messages conveying volcano alert level such as Watches and Warnings are designed to provide people with risk information before, during, and after eruptions. Information is communicated to people from volcano observatories and emergency management agencies and from informal sources and social and environmental cues. Any individual or agency can be both a message sender and a recipient and multiple messages received from multiple sources is the norm in a volcanic crisis. Significant challenges to developing effective warning systems for volcanic hazards stem from the great diversity in unrest, eruption, and post-eruption processes and the rapidly advancing digital technologies that people use to seek real-time risk information. Challenges also involve the need to invest resources before unrest to help people develop shared mental models of important risk factors. Two populations of people are the target of volcano notifications–ground- and aviation-based populations, and volcano warning systems must address both distinctly different populations.

  7. Doped zinc oxide microspheres

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

  8. Zinc and Compounds

    Integrated Risk Information System (IRIS)

    Zinc and Compounds ; CASRN 7440 - 66 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  9. Doped zinc oxide microspheres

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-12-14

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

  10. Zinc sulfide liquefaction catalyst

    DOEpatents

    Garg, Diwakar

    1984-01-01

    A process for the liquefaction of carbonaceous material, such as coal, is set forth wherein coal is liquefied in a catalytic solvent refining reaction wherein an activated zinc sulfide catalyst is utilized which is activated by hydrogenation in a coal derived process solvent in the absence of coal.

  11. Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

    PubMed

    Girish, Banavara Narasimhamurthy; Rajesh, Gopalakrishna; Vaidyanathan, Kannan; Balakrishnan, Vallath

    2009-11-05

    A major role of the pancreas in zinc homeostasis has been suggested. To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; P<0.001), and in tropical chronic pancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, P<0.001). Erythrocyte zinc levels were significantly lower in diabetic patients as compared to non-diabetics (P=0.036). This study demonstrates zinc deficiency in chronic pancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

  12. Zinc supplementation in public health.

    PubMed

    Penny, Mary Edith

    2013-01-01

    Zinc is necessary for physiological processes including defense against infections. Zinc deficiency is responsible for 4% of global child morbidity and mortality. Zinc supplements given for 10-14 days together with low-osmolarity oral rehydration solution (Lo-ORS) are recommended for the treatment of childhood diarrhea. In children aged ≥ 6 months, daily zinc supplements reduce the duration of acute diarrhea episodes by 12 h and persistent diarrhea by 17 h. Zinc supplements could reduce diarrhea mortality in children aged 12-59 months by an estimated 23%; they are very safe but are associated with an increase in vomiting especially with the first dose. Heterogeneity between the results of trials is not understood but may be related to dose and the etiology of the diarrhea infection. Integration of zinc and Lo-ORS into national programs is underway but slowly, procurement problems are being overcome and the greatest challenge is changing health provider and caregiver attitudes to diarrhea management. Fewer trials have been conducted of zinc adjunct therapy in severe respiratory tract infections and there is as yet insufficient evidence to recommend addition of zinc to antibiotic therapy. Daily zinc supplements for all children >12 months of age in zinc deficient populations are estimated to reduce diarrhea incidence by 11-23%. The greatest impact is in reducing multiple episodes of diarrhea. The effect on duration of diarrheal episodes is less clear, but there may be up to 9% reduction. Zinc is also efficacious in reducing dysentery and persistent diarrhea. Zinc supplements may also prevent pneumonia by about 19%, but heterogeneity across studies has not yet been explained. When analyses are restricted to better quality studies using CHERG (Child Health Epidemiology Reference Group) methodology, zinc supplements are estimated to reduce diarrheal deaths by 13% and pneumonia deaths by 20%. National-level programs to combat childhood zinc deficiency should be

  13. Gallium-67 uptake in meningeal sarcoidosis

    SciT

    Ayres, J.G.; Hicks, B.H.; Maisey, M.N.

    1986-07-01

    A case of sarcoidosis limited to the central nervous system is described in which the diagnosis was suggested by high Ga-67 uptake in the cranial and spinal meninges. The diagnosis was confirmed by meningeal biopsy. Treatment with oral corticosteroids resulted in clinical improvement and marked reduction in Ga-67 uptake in the meninges. This is the first reported case of the central nervous system sarcoid diagnosed by Ga-67 imaging.

  14. Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

    PubMed

    Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

    2015-12-01

    A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

  15. Zinc in human health: effect of zinc on immune cells.

    PubMed

    Prasad, Ananda S

    2008-01-01

    Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency. Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 [Th(0)] cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor alpha(IL-2Ralpha) were due to decreased activation of nuclear factor-kappaB (NF-kappaB) in zinc deficient cells. Decreased NF-kappaB activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappaB to DNA, decreased level of NF-kappaB p105 (the precursor of NF-kappaB p50) mRNA, decreased kappaB inhibitory protein (IkappaB) phosphorylation, and decreased Ikappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF

  16. Interaction Between Yeasts and Zinc

    NASA Astrophysics Data System (ADS)

    Nicola, Raffaele De; Walker, Graeme

    Zinc is an essential trace element in biological systems. For example, it acts as a cellular membrane stabiliser, plays a critical role in gene expression and genome modification and activates nearly 300 enzymes, including alcohol dehydrogenase. The present chapter will be focused on the influence of zinc on cell physiology of industrial yeast strains of Saccharomyces cerevisiae, with special regard to the uptake and subsequent utilisation of this metal. Zinc uptake by yeast is metabolism-dependent, with most of the available zinc translocated very quickly into the vacuole. At cell division, zinc is distributed from mother to daughter cells and this effectively lowers the individual cellular zinc concentration, which may become zinc depleted at the onset of the fermentation. Zinc influences yeast fermentative performance and examples will be provided relating to brewing and wine fermentations. Industrial yeasts are subjected to several stresses that may impair fermentation performance. Such stresses may also impact on yeast cell zinc homeostasis. This chapter will discuss the practical implications for the correct management of zinc bioavailability for yeast-based biotechnologies aimed at improving yeast growth, viability, fermentation performance and resistance to environmental stresses

  17. Zinc and Zinc Transporters: Novel Regulators of Ventricular Myocardial Development.

    PubMed

    Lin, Wen; Li, Deqiang

    2018-06-01

    Ventricular myocardial development is a well-orchestrated process involving different cardiac structures, multiple signal pathways, and myriad proteins. Dysregulation of this important developmental event can result in cardiomyopathies, such as left ventricle non-compaction, which affect the pediatric population and the adults. Human and mouse studies have shed light upon the etiology of some cardiomyopathy cases and highlighted the contribution of both genetic and environmental factors. However, the regulation of ventricular myocardial development remains incompletely understood. Zinc is an essential trace metal with structural, enzymatic, and signaling function. Perturbation of zinc homeostasis has resulted in developmental and physiological defects including cardiomyopathy. In this review, we summarize several mechanisms by which zinc and zinc transporters can impact the regulation of ventricular myocardial development. Based on our review, we propose that zinc deficiency and mutations of zinc transporters may underlie some cardiomyopathy cases especially those involving ventricular myocardial development defects.

  18. Observations of interstellar zinc

    NASA Technical Reports Server (NTRS)

    York, D. G.; Jura, M.

    1982-01-01

    IUE observations toward 10 stars have shown that zinc is not depleted in the interstellar medium by more than a factor of two, suggesting that its abundance may serve as a tracer of the true metallicity in the gas. A result pertinent to the history of nucleosynthesis in the solar neighborhood is that the local interstellar medium has abundances that appear to be homogeneous to within a factor of two, when integrated over paths of about 500 pc.

  19. 36 CFR 6.7 - Mining wastes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Mining wastes. 6.7 Section 6... DISPOSAL SITES IN UNITS OF THE NATIONAL PARK SYSTEM § 6.7 Mining wastes. (a) Solid waste from mining includes but is not limited to mining overburden, mining byproducts, solid waste from the extraction...

  20. 21 CFR 1250.67 - Watering equipment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Watering equipment. 1250.67 Section 1250.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION INTERSTATE CONVEYANCE...

  1. 22 CFR 67.3 - Management.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Management. 67.3 Section 67.3 Foreign Relations....3 Management. (a) NED's operations and staff are managed by a President selected by the Board of... Office of the President provides policy direction and is responsible for day-to-day management of the...

  2. 22 CFR 67.3 - Management.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Management. 67.3 Section 67.3 Foreign Relations....3 Management. (a) NED's operations and staff are managed by a President selected by the Board of... Office of the President provides policy direction and is responsible for day-to-day management of the...

  3. 22 CFR 67.3 - Management.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Management. 67.3 Section 67.3 Foreign Relations....3 Management. (a) NED's operations and staff are managed by a President selected by the Board of... Office of the President provides policy direction and is responsible for day-to-day management of the...

  4. 22 CFR 67.3 - Management.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Management. 67.3 Section 67.3 Foreign Relations....3 Management. (a) NED's operations and staff are managed by a President selected by the Board of... Office of the President provides policy direction and is responsible for day-to-day management of the...

  5. 7 CFR 920.67 - Agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Agents. 920.67 Section 920.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN CALIFORNIA Miscellaneous...

  6. 7 CFR 920.67 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 920.67 Section 920.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN CALIFORNIA Miscellaneous...

  7. 7 CFR 920.67 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 920.67 Section 920.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN CALIFORNIA Miscellaneous...

  8. 7 CFR 920.67 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 920.67 Section 920.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN CALIFORNIA Miscellaneous...

  9. 22 CFR 67.3 - Management.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Management. 67.3 Section 67.3 Foreign Relations....3 Management. (a) NED's operations and staff are managed by a President selected by the Board of... Office of the President provides policy direction and is responsible for day-to-day management of the...

  10. 7 CFR 920.67 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 920.67 Section 920.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN CALIFORNIA Miscellaneous...

  11. 25 CFR 67.15 - Special instructions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Area Director, the Assistant Secretary may issue special instructions not inconsistent with the... 25 Indians 1 2010-04-01 2010-04-01 false Special instructions. 67.15 Section 67.15 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT PREPARATION OF A ROLL OF INDEPENDENT...

  12. 19 CFR 111.67 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... oaths for general purposes or in customs matters. The other party to the hearing will be given a... 19 Customs Duties 1 2013-04-01 2013-04-01 false Hearing. 111.67 Section 111.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS BROKERS...

  13. 19 CFR 111.67 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... oaths for general purposes or in customs matters. The other party to the hearing will be given a... 19 Customs Duties 1 2014-04-01 2014-04-01 false Hearing. 111.67 Section 111.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS BROKERS...

  14. 19 CFR 111.67 - Hearing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... oaths for general purposes or in customs matters. The other party to the hearing will be given a... 19 Customs Duties 1 2012-04-01 2012-04-01 false Hearing. 111.67 Section 111.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS BROKERS...

  15. 7 CFR 925.67 - Derogation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Derogation. 925.67 Section 925.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  16. 7 CFR 925.67 - Derogation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Derogation. 925.67 Section 925.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  17. 7 CFR 925.67 - Derogation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Derogation. 925.67 Section 925.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  18. 7 CFR 925.67 - Derogation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Derogation. 925.67 Section 925.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  19. 7 CFR 925.67 - Derogation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Derogation. 925.67 Section 925.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  20. 42 CFR 67.20 - Confidentiality.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... activities under this subpart is protected by section 903(c) of the PHS Act. Specifically: (a) No information... 42 Public Health 1 2013-10-01 2013-10-01 false Confidentiality. 67.20 Section 67.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY...

  1. 42 CFR 67.104 - Confidentiality.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... protected by section 903(c) of the PHS Act. Specifically: (a) No information obtained in the course of... 42 Public Health 1 2013-10-01 2013-10-01 false Confidentiality. 67.104 Section 67.104 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING...

  2. 42 CFR 67.104 - Confidentiality.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... protected by section 903(c) of the PHS Act. Specifically: (a) No information obtained in the course of... 42 Public Health 1 2011-10-01 2011-10-01 false Confidentiality. 67.104 Section 67.104 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING...

  3. 42 CFR 67.104 - Confidentiality.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... protected by section 903(c) of the PHS Act. Specifically: (a) No information obtained in the course of... 42 Public Health 1 2014-10-01 2014-10-01 false Confidentiality. 67.104 Section 67.104 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING...

  4. 42 CFR 67.20 - Confidentiality.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... activities under this subpart is protected by section 903(c) of the PHS Act. Specifically: (a) No information... 42 Public Health 1 2011-10-01 2011-10-01 false Confidentiality. 67.20 Section 67.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY...

  5. 42 CFR 67.20 - Confidentiality.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... activities under this subpart is protected by section 903(c) of the PHS Act. Specifically: (a) No information... 42 Public Health 1 2014-10-01 2014-10-01 false Confidentiality. 67.20 Section 67.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY...

  6. 42 CFR 67.104 - Confidentiality.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... protected by section 903(c) of the PHS Act. Specifically: (a) No information obtained in the course of... 42 Public Health 1 2012-10-01 2012-10-01 false Confidentiality. 67.104 Section 67.104 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING...

  7. 42 CFR 67.20 - Confidentiality.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... activities under this subpart is protected by section 903(c) of the PHS Act. Specifically: (a) No information... 42 Public Health 1 2012-10-01 2012-10-01 false Confidentiality. 67.20 Section 67.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY...

  8. 42 CFR 67.20 - Confidentiality.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... activities under this subpart is protected by section 903(c) of the PHS Act. Specifically: (a) No information... 42 Public Health 1 2010-10-01 2010-10-01 false Confidentiality. 67.20 Section 67.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY...

  9. 19 CFR 115.67 - Approval certificate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Approval certificate. 115.67 Section 115.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS...

  10. 19 CFR 115.67 - Approval certificate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Approval certificate. 115.67 Section 115.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS...

  11. 19 CFR 115.67 - Approval certificate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Approval certificate. 115.67 Section 115.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS...

  12. 19 CFR 115.67 - Approval certificate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Approval certificate. 115.67 Section 115.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS...

  13. 19 CFR 115.67 - Approval certificate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Approval certificate. 115.67 Section 115.67 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS...

  14. 42 CFR 67.104 - Confidentiality.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Confidentiality. 67.104 Section 67.104 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY FOR HEALTH CARE POLICY AND RESEARCH GRANTS AND CONTRACTS Peer Review of Contracts for Health...

  15. 42 CFR 67.11 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Definitions. 67.11 Section 67.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY FOR HEALTH CARE POLICY AND RESEARCH GRANTS AND CONTRACTS Research Grants for Health Services Research...

  16. 42 CFR 67.11 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Definitions. 67.11 Section 67.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY FOR HEALTH CARE POLICY AND RESEARCH GRANTS AND CONTRACTS Research Grants for Health Services Research...

  17. 42 CFR 67.102 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Definitions. 67.102 Section 67.102 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING AGENCY FOR HEALTH CARE POLICY AND RESEARCH GRANTS AND CONTRACTS Peer Review of Contracts for Health Services...

  18. 7 CFR 987.67 - Confidential information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Confidential information. 987.67 Section 987.67... information. All data or other information constituting a trade secret or disclosing a trade position or... the Committee and information which would reveal the circumstances of a single handler shall be...

  19. 33 CFR 67.40-5 - Waivers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sound signal have been modified or waived, constitutes a hazard to marine navigation, he or she is... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Waivers. 67.40-5 Section 67.40-5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO...

  20. 33 CFR 67.40-5 - Waivers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sound signal have been modified or waived, constitutes a hazard to marine navigation, he or she is... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Waivers. 67.40-5 Section 67.40-5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO...

  1. 40 CFR 61.67 - Emission tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 9 2014-07-01 2014-07-01 false Emission tests. 61.67 Section 61.67... Emission tests. (a) Unless a waiver of emission testing is obtained under § 61.13, the owner or operator of a source to which this subpart applies shall test emissions from the source, (1) Within 90 days of...

  2. 40 CFR 61.67 - Emission tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 9 2013-07-01 2013-07-01 false Emission tests. 61.67 Section 61.67... Emission tests. (a) Unless a waiver of emission testing is obtained under § 61.13, the owner or operator of a source to which this subpart applies shall test emissions from the source, (1) Within 90 days of...

  3. 32 CFR 154.67 - Access restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Access restrictions. 154.67 Section 154.67 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE... restrictions. Access to personnel security investigative reports and personnel security clearance determination...

  4. 44 CFR 67.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Definitions. 67.2 Section 67.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program APPEALS FROM PROPOSED FLOOD...

  5. 44 CFR 67.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Definitions. 67.2 Section 67.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program APPEALS FROM PROPOSED FLOOD ELEVATION...

  6. 46 CFR 67.33 - Individual.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Individual. 67.33 Section 67.33 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS DOCUMENTATION OF VESSELS...-born, naturalized, or a derivative citizen of the United States, or otherwise qualifies as a United...

  7. 41 CFR 50-204.67 - Oxygen.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 1 2012-07-01 2009-07-01 true Oxygen. 50-204.67 Section..., Vapors, Fumes, Dusts, and Mists § 50-204.67 Oxygen. The in-plant transfer, handling, storage, and utilization of oxygen as a liquid or a compressed gas shall be in accordance with Compressed Gas Association...

  8. 41 CFR 50-204.67 - Oxygen.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 1 2013-07-01 2013-07-01 false Oxygen. 50-204.67..., Vapors, Fumes, Dusts, and Mists § 50-204.67 Oxygen. The in-plant transfer, handling, storage, and utilization of oxygen as a liquid or a compressed gas shall be in accordance with Compressed Gas Association...

  9. 41 CFR 50-204.67 - Oxygen.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Oxygen. 50-204.67 Section..., Vapors, Fumes, Dusts, and Mists § 50-204.67 Oxygen. The in-plant transfer, handling, storage, and utilization of oxygen as a liquid or a compressed gas shall be in accordance with Compressed Gas Association...

  10. 41 CFR 50-204.67 - Oxygen.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Oxygen. 50-204.67 Section..., Vapors, Fumes, Dusts, and Mists § 50-204.67 Oxygen. The in-plant transfer, handling, storage, and utilization of oxygen as a liquid or a compressed gas shall be in accordance with Compressed Gas Association...

  11. 41 CFR 50-204.67 - Oxygen.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 1 2014-07-01 2014-07-01 false Oxygen. 50-204.67..., Vapors, Fumes, Dusts, and Mists § 50-204.67 Oxygen. The in-plant transfer, handling, storage, and utilization of oxygen as a liquid or a compressed gas shall be in accordance with Compressed Gas Association...

  12. Zinc Signal in Brain Diseases.

    PubMed

    Portbury, Stuart D; Adlard, Paul A

    2017-11-23

    The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer's disease or negative outcomes following brain injury.

  13. ZNT7 binds to CD40 and influences CD154-triggered p38 MAPK activity in B lymphocytes-a possible regulatory mechanism for zinc in immune function

    Zinc deficiency impairs immune system leading to frequent infections. Although it is known that zinc plays critical roles in maintaining healthy immune function, the underlying molecular targets are largely unknown. In this study, we showed that zinc is important for the CD154-CD40-mediated activati...

  14. Short-Term Subclinical Zinc Deficiency in Weaned Piglets Affects Cardiac Redox Metabolism and Zinc Concentration.

    PubMed

    Brugger, Daniel; Windisch, Wilhelm M

    2017-04-01

    Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism. Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets. Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d. Measurements included cardiac parameters of antioxidative capacity, stress-associated gene expression, and tissue zinc status. Analyses comprised (linear, broken-line) regression models and Pearson correlation coefficients. Results: Glutathione and α-tocopherol concentrations as well as catalase, glutathione reductase, B-cell lymphoma 2-associated X protein, and caspase 9 gene expression plateaued in response to reduction in dietary zinc from 88.0 to 57.6, 36.0, 36.5, 41.3, 55.3, and 33.8 mg/kg, respectively ( P < 0.0001). Further reduction in dietary zinc promoted a linear decrease of glutathione and α-tocopherol (30 and 0.6 nmol/mg dietary Zn, respectively; P < 0.05) and a linear increase of gene expression [0.02, 0.01, 0.003, and 0.02 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05)]. Tissue zinc declined linearly with reduction in dietary zinc (0.21 mg tissue Zn/mg dietary Zn; P = 0.004) from 88.0 to 42.7 mg/kg ( P < 0.0001), below which it linearly increased inversely to further reduction in dietary zinc (0.57 mg tissue Zn/mg dietary Zn; P = 0.006). H 2 O 2 -detoxification activity and metallothionein 1A gene expression decreased linearly with reduction in dietary zinc from 88.0 to 28.1 mg/kg [0.02 mU and 0.008 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05]. Fas cell-surface death receptor, etoposide-induced 2.4 and cyclin-dependent kinase inhibitor 1A gene expression correlated

  15. Remediation of arsenic and lead with nanocrystalline zinc sulfide.

    PubMed

    Piquette, Alan; Cannon, Cody; Apblett, Allen W

    2012-07-27

    Nanocrystalline (1.7 ± 0.3 nm) zinc sulfide with a specific surface area up to 360 m(2) g(-1) was prepared from the thermal decomposition of a single-source precursor, zinc ethylxanthate. Zinc ethylxanthate decomposes to cubic zinc sulfide upon exposure to temperatures greater than or equal to 125 °C. The resulting zinc sulfide was tested as a water impurity extractant. The target impurities used in this study were As(5+), As(3+), and Pb(2+). The reaction of the nanocrystalline ZnS with Pb(2+) proceeds as a replacement reaction where solid PbS is formed and Zn(2+) is released into the aqueous system. Removal of lead to a level of less than two parts per billion is achievable. The results of a detailed kinetics experiment between the ZnS and Pb(2+) are included in this study. Unlike the instance of lead, both As(5+) and As(3+) adsorb on the surface of the ZnS extractant as opposed to an ion-exchange process. An uptake capacity of > 25 mg g(-1) for the removal of As(5+) is possible. The uptake of As(3+) appears to proceed by a slower process than that of the As(5+) with a capacity of nearly 20 mg g(-1). The nanocrystalline zinc sulfide was extremely successful for the removal of arsenic and lead from simulated oil sand tailing pond water.

  16. Zinc supplementation for tinnitus.

    PubMed

    Person, Osmar C; Puga, Maria Es; da Silva, Edina Mk; Torloni, Maria R

    2016-11-23

    Tinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus can cause deterioration in their quality of life. At present no specific therapy for tinnitus has been found to be satisfactory in all patients. In recent decades, a number of reports have suggested that oral zinc supplementation may be effective in the management of tinnitus. Since zinc has a role in cochlear physiology and in the synapses of the auditory system, there is a plausible mechanism of action for this treatment. To evaluate the effectiveness and safety of oral zinc supplementation in the management of patients with tinnitus. The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 July 2016. Randomised controlled trials comparing zinc supplementation versus placebo in adults (18 years and over) with tinnitus. We used the standard methodological procedures recommended by Cochrane. Our primary outcome measures were improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire, and adverse effects. Secondary outcomes were quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters, change in tinnitus loudness, change in overall severity of tinnitus and change in thresholds on pure tone audiometry. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. We included three trials involving a total of 209 participants. The studies were at moderate to high risk of bias. All included studies had differences in participant selection criteria, length of follow-up and outcome measurement

  17. Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.

    PubMed

    Moezzi, Amir; Cortie, Michael; McDonagh, Andrew

    2016-04-25

    Thermal decomposition of layered zinc hydroxide double salts provides an interesting alternative synthesis for particles of zinc oxide. Here, we examine the sequence of changes occurring as zinc hydroxide chloride monohydrate (Zn5(OH)8Cl2·H2O) is converted to crystalline ZnO by thermal decomposition. The specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A complicating and important factor in this process is that the thermal decomposition of zinc hydroxide chloride is also accompanied by the formation of volatile zinc-containing species under certain conditions. We show that this volatile compound is anhydrous ZnCl2 and its formation is moisture dependent. Therefore, control of atmospheric moisture is an important consideration that affects the overall efficiency of ZnO production by this process.

  18. Uptake and partitioning of zinc in Lemnaceae.

    PubMed

    Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

    2011-11-01

    Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility.

  19. 16 CFR 5.67 - Sanctions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Disciplinary Actions Concerning Postemployment Conflict of Interest § 5.67 Sanctions. In the case of any...), the Commission may order such disciplinary action as it deems warranted, including: (a) Reprimand; (b...

  20. Ki67 and proliferation in breast cancer.

    PubMed

    Pathmanathan, Nirmala; Balleine, Rosemary L

    2013-06-01

    New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.

  1. 33 CFR 67.01-5 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES General Requirements § 67.01-5..., drilling barges submerged on location, breakwater barges submerged on location, artificial islands and all...

  2. 33 CFR 67.01-5 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES General Requirements § 67.01-5..., drilling barges submerged on location, breakwater barges submerged on location, artificial islands and all...

  3. 33 CFR 67.01-1 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES General Requirements § 67.01-1 Scope. (a) The... maintained maritime aids to navigation on the artificial islands and structures which are erected on or over...

  4. 33 CFR 67.01-1 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES General Requirements § 67.01-1 Scope. (a) The... maintained maritime aids to navigation on the artificial islands and structures which are erected on or over...

  5. 21 CFR 640.67 - Laboratory tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.67 Laboratory tests. Each unit of Source Plasma shall be tested for evidence of infection due to communicable disease agents as required...

  6. 21 CFR 640.67 - Laboratory tests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.67 Laboratory tests. Each unit of Source Plasma shall be tested for evidence of infection due to communicable disease agents as required...

  7. 21 CFR 640.67 - Laboratory tests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.67 Laboratory tests. Each unit of Source Plasma shall be tested for evidence of infection due to communicable disease agents as required...

  8. 21 CFR 640.67 - Laboratory tests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.67 Laboratory tests. Each unit of Source Plasma shall be tested for evidence of infection due to communicable disease agents as required...

  9. 21 CFR 640.67 - Laboratory tests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.67 Laboratory tests. Each unit of Source Plasma shall be tested for evidence of infection due to communicable disease agents as required...

  10. 7 CFR 1767.67 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (CONTINUED) ACCOUNTING REQUIREMENTS FOR RUS ELECTRIC BORROWERS Preservation of Records § 1767.67 General. (a... account, contracts, records, memoranda, documents, papers, and correspondence prepared by or on behalf of...

  11. 49 CFR 585.67 - Records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Phase-in Reporting Requirements § 585.67 Records. Each manufacturer must maintain records of the Vehicle Identification Number for each vehicle for which information is reported under § 585.66(b)(2) until December 31...

  12. 44 CFR 67.8 - Appeal procedure.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program APPEALS FROM PROPOSED FLOOD ELEVATION DETERMINATIONS § 67.8 Appeal procedure. (a) If a community appeals the proposed flood...

  13. 44 CFR 67.8 - Appeal procedure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program APPEALS FROM PROPOSED FLOOD ELEVATION DETERMINATIONS § 67.8 Appeal procedure. (a) If a community appeals the proposed flood elevation...

  14. An International Ki67 Reproducibility Study

    PubMed Central

    2013-01-01

    Background In breast cancer, immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management. However, lack of consistency across laboratories has limited Ki67’s value. A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance. Toward that goal, we conducted a Ki67 reproducibility study. Methods Eight laboratories received 100 breast cancer cases arranged into 1-mm core tissue microarrays—one set stained by the participating laboratory and one set stained by the central laboratory, both using antibody MIB-1. Each laboratory scored Ki67 as percentage of positively stained invasive tumor cells using its own method. Six laboratories repeated scoring of 50 locally stained cases on 3 different days. Sources of variation were analyzed using random effects models with log2-transformed measurements. Reproducibility was quantified by intraclass correlation coefficient (ICC), and the approximate two-sided 95% confidence intervals (CIs) for the true intraclass correlation coefficients in these experiments were provided. Results Intralaboratory reproducibility was high (ICC = 0.94; 95% CI = 0.93 to 0.97). Interlaboratory reproducibility was only moderate (central staining: ICC = 0.71, 95% CI = 0.47 to 0.78; local staining: ICC = 0.59, 95% CI = 0.37 to 0.68). Geometric mean of Ki67 values for each laboratory across the 100 cases ranged 7.1% to 23.9% with central staining and 6.1% to 30.1% with local staining. Factors contributing to interlaboratory discordance included tumor region selection, counting method, and subjective assessment of staining positivity. Formal counting methods gave more consistent results than visual estimation. Conclusions Substantial variability in Ki67 scoring was observed among some of the world’s most experienced laboratories. Ki67 values and cutoffs for clinical decision-making cannot be transferred between laboratories without

  15. Gastric gallium-67 uptake in gastritis

    SciT

    Yeh, E.L.; Tisdale, P.L.; Zielonka, J.S.

    1983-12-01

    Even though Ga-67 imaging has been used widely in the diagnosis of malignant as well as inflammatory lesions, its uptake in the stomach has been reported in the literature mainly in gastric lymphoma and carcinoma. As shown in this case, intense gastric uptake of the radionuclide may be seen in common gastritis without malignancy. Perhaps the benign gastric uptake of Ga-67 deserves more emphasis.

  16. Zinc supplementation for the treatment of measles in children.

    PubMed

    Awotiwon, Ajibola A; Oduwole, Olabisi; Sinha, Anju; Okwundu, Charles I

    2017-06-20

    absence of fever between children who received zinc supplements and those who did not (HR 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. We assessed the overall quality of the evidence as very low. We could not draw any definitive conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in children with measles.

  17. Nutrition intervention strategies to combat zinc deficiency in developing countries.

    PubMed

    Gibson, R S; Ferguson, E L

    1998-06-01

    Widespread zinc deficiency is likely to exist in developing countries where staple diets are predominantly plant based and intakes of animal tissues are low. The severe negative consequences of zinc deficiency on human health in developing countries, however, have only recently been recognized. An integrated approach employing targeted supplementation, fortification and dietary strategies must be used to maximize the likelihood of eliminating zinc deficiency at a national level in developing countries. Supplementation is appropriate only for populations whose zinc status must be improved over a relatively short time period, and when requirements cannot be met from habitual dietary sources. As well, the health system must be capable of providing consistent supply, distribution, delivery and consumption of the zinc supplement to the targeted groups. Uncertainties still exist about the type, frequency, and level of supplemental zinc required for prevention and treatment of zinc deficiency. Salts that are readily absorbed and at levels that will not induce antagonistic nutrient interactions must be used. At a national level, fortification with multiple micronutrients could be a cost effective method for improving micronutrient status, including zinc, provided that a suitable food vehicle which is centrally processed is available. Alternatively, fortification could be targeted for certain high risk groups (e.g. complementary foods for infants). Efforts should be made to develop protected fortificants for zinc, so that potent inhibitors of zinc absorption (e.g. phytate) present either in the food vehicle and/or indigenous meals do not compromise zinc absorption. Fortification does not require any changes in the existing food beliefs and practices for the consumer and, unlike supplementation, does not impose a burden on the health sector. A quality assurance programme is required, however, to ensure the quality of the fortified food product from production to consumption

  18. Zinc as a Gatekeeper of Immune Function

    PubMed Central

    Wessels, Inga; Maywald, Martina; Rink, Lothar

    2017-01-01

    After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function. PMID:29186856

  19. Dietary and non-dietary factors associated with serum zinc in Indian women.

    PubMed

    Herbst, Catherine A; Menon, Kavitha C; Ferguson, Elaine L; Thomson, Christine D; Bailey, Karl; Gray, Andrew R; Zodpey, Sanjay; Saraf, Abhay; Das, Prabir Kumar; Skeaff, Sheila A

    2014-10-01

    Women in low-income settings, common in India, are at risk of inadequate zinc intake due to poor diet quality and low consumption of flesh foods rich in zinc. The aims of this study were to assess the prevalence of zinc status of non-pregnant rural and tribal women living in central India and to identify dietary and non-dietary factors associated with the biochemical zinc status of these women. Rural and tribal non-pregnant women 18-30 years of age were selected using proportion to population sampling near Nagpur, Maharashtra, India. Sociodemographic, biochemical (serum zinc), clinical, and dietary data (1-day interactive 24-h recall) were collected. The mean age of women (n = 109; rural = 52; tribal = 56) was 23.2 years and mean BMI was 17.9 kg/m(2). The majority of the participants identified as being non-vegetarian (72 %). The mean ± SD serum zinc concentration was 10.8 ± 1.6 μmol/L, and 52 % of participants had a low serum zinc concentration according to the International Zinc Nutrition Consultative Group (IZiNCG). The median (first and third quartile) energy, zinc intake, and phytate/zinc molar ratio was 5.4 (4.2, 6.7) MJ/day, 5.3 (3.8, 7.0) mg/day, and 26 (22, 28), respectively. Zinc intakes were well below IZiNCG recommendations for dietary zinc of 9 mg/day for non-pregnant women aged 14-18 years and 7 mg/day for non-pregnant women aged ≥ 19 years. Using linear regression analysis to identify non-dietary and dietary factors associated with serum zinc, a significant association was only found for current lactation (p = 0.012) and energy intake (p < 0.001). Diets low in energy with poor bioavailability of dietary zinc are likely to be the primary cause of the high proportion of Indian women with zinc deficiency.

  20. 67P Through the Lens of Art

    NASA Astrophysics Data System (ADS)

    Smirnova, Ekaterina; ESA, The Open University, OSIRIS

    2016-10-01

    I am an artist, who is deeply inspired by science. Since the landing of the robotic probe Philae on the comet I have been working on an art project called 67P. Having a goal of discovering our place in the universe, I chose ESA's Rosetta mission as a successful example of such discovery. During the conference I'd like to expand the dialogue to include an artistic research of the comet 67P. I invite the participants to explore 67P through the lens of art and create inspirational reciprocity in between two spheres, creative and scientific. New ideas often originate when two vocabularies are smashed together. Via this path we perhaps will be able to get a new way of exploring the topic of cometary science.During the conference I'd like to present:- 67p artwork in the art section- poster outlining the major focuses of my projectArt project focuses:- 67P water:In the art studio I re-create water that is close in composition to the water on the comet, by enriching it with D2O. With this water I paint large scale paintings, based on the photographs by Rosetta (OSIRIS, Nav. Cam.).- spectroscopic data:Inspired by data from OSIRIS, I create an additional layer to my work using augmented reality to reveal a "hidden" from the view layer. I am making a parallel with the idea that some scientific information could be viewed only by using special instruments, in this case - instruments on board of Rosetta spacecraft, such as OSIRIS. You will be able to see a virtual layer on top of my paintings using a readily available instrument - your cellphone. Red, Green and Blue colors, of particular wavelength, will be introduced to the monochromatic paintings.- magnetometer readings:International music collaboration inspired by the "Singing comet" composition, based on the magnetometer data of 67P will be offered for any interested spectators.- 67P smell:In collaboration with The Open University, UK, postcards with a smell of the comet were created, introducing the chemical components of

  1. Regeneration of zinc chloride hydrocracking catalyst

    DOEpatents

    Zielke, Clyde W.

    1979-01-01

    Improved rate of recovery of zinc values from the solids which are carried over by the effluent vapors from the oxidative vapor phase regeneration of spent zinc chloride catalyst is achieved by treatment of the solids with both hydrogen chloride and calcium chloride to selectively and rapidly recover the zinc values as zinc chloride.

  2. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

  3. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

  4. Measurements of 67Ga production cross section induced by protons on natZn in the low energy range from 1.678 to 2.444 MeV

    NASA Astrophysics Data System (ADS)

    Wachter, J. A.; Miranda, P. A.; Morales, J. R.; Cancino, S. A.; Correa, R.

    2015-02-01

    The experimental production cross section for the reaction natZn(p,x)67Ga has been measured in the energy range from 1.678 to 2.444 MeV. The methodology used in this work is based on characteristic X-ray emitted after irradiation by the daughter nuclei that decays by electron capture (EC) and the use of a complementary PIXE experiment. By doing so, expressions needed to determine cross section values are simplified since experimental factors such as geometric setup and an detector efficiency are avoided. 67Ga is a radionuclide particularly suited for this method since it decays by electron capture in 100% and the subsequent characteristic X-ray emission is easily detected. Natural zinc targets were fabricated by PVD technique and afterwards their thicknesses were determined by Rutherford Backscattering Spectrometry. Cross sections measurements were carried out by using the Van de Graaff accelerator located at Faculty of Sciences, University of Chile. It was found that our data for the natZn(p,x)67Ga reaction are, in general, in good agreement when compared to existing experimental data and to those calculated ALICE/ASH nuclear code. On the other hand, values predicted by Talys-1.6 are showing systematically lower magnitudes than our measured data.

  5. Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial

    PubMed Central

    Veenemans, Jacobien; Milligan, Paul; Prentice, Andrew M.; Schouten, Laura R. A.; Inja, Nienke; van der Heijden, Aafke C.; de Boer, Linsey C. C.; Jansen, Esther J. S.; Koopmans, Anna E.; Enthoven, Wendy T. M.; Kraaijenhagen, Rob J.; Demir, Ayse Y.; Uges, Donald R. A.; Mbugi, Erasto V.; Savelkoul, Huub F. J.; Verhoef, Hans

    2011-01-01

    prevalence of zinc deficiency (plasma zinc concentration <9.9 µmol/L) was high at baseline (67% overall; 60% in those without inflammation) and strongly reduced by zinc supplementation. Conclusions We found no evidence from this trial that zinc supplementation protected against malaria. Trial Registration ClinicalTrials.gov NCT00623857 Please see later in the article for the Editors' Summary. PMID:22131908

  6. Mineral resource of the month: zinc

    Tolcin, Amy C.

    2009-01-01

    The article provides information on zinc, the fourth most-widely consumed metal. It traces the first use of zinc with the Romans' production of brass. It describes the presence of zinc in Earth's crust and the importance of sphalerite as a source of zinc and other some minor metal production. The production and consumption of zinc as well as the commercial and industrial uses of this metal are also discussed.

  7. Zinc: an essential but elusive nutrient123

    PubMed Central

    King, Janet C

    2011-01-01

    Zinc is essential for multiple aspects of metabolism. Physiologic signs of zinc depletion are linked with diverse biochemical functions rather than with a specific function, which makes it difficult to identify biomarkers of zinc nutrition. Nutrients, such as zinc, that are required for general metabolism are called type 2 nutrients. Protein and magnesium are examples of other type 2 nutrients. Type 1 nutrients are required for one or more specific functions: examples include iron, vitamin A, iodine, folate, and copper. When dietary zinc is insufficient, a marked reduction in endogenous zinc loss occurs immediately to conserve the nutrient. If zinc balance is not reestablished, other metabolic adjustments occur to mobilize zinc from small body pools. The location of those pools is not known, but all cells probably have a small zinc reserve that includes zinc bound to metallothionein or zinc stored in the Golgi or in other organelles. Plasma zinc is also part of this small zinc pool that is vulnerable to insufficient intakes. Plasma zinc concentrations decline rapidly with severe deficiencies and more moderately with marginal depletion. Unfortunately, plasma zinc concentrations also decrease with a number of conditions (eg, infection, trauma, stress, steroid use, after a meal) due to a metabolic redistribution of zinc from the plasma to the tissues. This redistribution confounds the interpretation of low plasma zinc concentrations. Biomarkers of metabolic zinc redistribution are needed to determine whether this redistribution is the cause of a low plasma zinc rather than poor nutrition. Measures of metallothionein or cellular zinc transporters may fulfill that role. PMID:21715515

  8. A dynamic model for predicting growth in zinc-deficient stunted infants given supplemental zinc.

    PubMed

    Wastney, Meryl E; McDonald, Christine M; King, Janet C

    2018-05-01

    Zinc deficiency limits infant growth and increases susceptibility to infections, which further compromises growth. Zinc supplementation improves the growth of zinc-deficient stunted infants, but the amount, frequency, and duration of zinc supplementation required to restore growth in an individual child is unknown. A dynamic model of zinc metabolism that predicts changes in weight and length of zinc-deficient, stunted infants with dietary zinc would be useful to define effective zinc supplementation regimens. The aims of this study were to develop a dynamic model for zinc metabolism in stunted, zinc-deficient infants and to use that model to predict the growth response when those infants are given zinc supplements. A model of zinc metabolism was developed using data on zinc kinetics, tissue zinc, and growth requirements for healthy 9-mo-old infants. The kinetic model was converted to a dynamic model by replacing the rate constants for zinc absorption and excretion with functions for these processes that change with zinc intake. Predictions of the dynamic model, parameterized for zinc-deficient, stunted infants, were compared with the results of 5 published zinc intervention trials. The model was then used to predict the results for zinc supplementation regimes that varied in the amount, frequency, and duration of zinc dosing. Model predictions agreed with published changes in plasma zinc after zinc supplementation. Predictions of weight and length agreed with 2 studies, but overpredicted values from a third study in which other nutrient deficiencies may have been growth limiting; the model predicted that zinc absorption was impaired in that study. The model suggests that frequent, smaller doses (5-10 mg Zn/d) are more effective for increasing growth in stunted, zinc-deficient 9-mo-old infants than are larger, less-frequent doses. The dose amount affects the duration of dosing necessary to restore and maintain plasma zinc concentration and growth.

  9. The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling

    PubMed Central

    Lee, Sung Ryul; Noh, Su Jin; Pronto, Julius Ryan; Jeong, Yu Jeong; Kim, Hyoung Kyu; Song, In Sung; Xu, Zhelong; Kwon, Hyog Young; Kang, Se Chan; Sohn, Eun-Hwa; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari

    2015-01-01

    Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+. PMID:26330751

  10. Serum thymulin in human zinc deficiency.

    PubMed Central

    Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

    1988-01-01

    The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

  11. Stabilized nickel-zinc battery

    SciT

    Himy, A.; Wagner, O.C.

    An alkaline nickel-zinc cell which has (1) a nickel-nickel hydroxide cathode; (2) a zinc-zinc oxide anode containing (A) a corrosion inhibitor such as PBO, SNO2, Tl2O3, in(OH)3 or mixtures thereof; (B) a slight corrosion accelerator such as cdo, bi2o3, ga2o3, or mixtures thereof; and (C) a zinc active material; (3) a mass-transport separator; (4) an alkaline electrolyte; and (5) means for charging the cell with an interrupted current having a frequency of from more than zero to 16 hertz with a rest period of not less than 60 milliseconds. Another desirable feature is the use of a pressure-cutoff switch tomore » terminate charging when the internal pressure of the cell reaches a selected value in the range of from 5 to 8 psig.« less

  12. Zinc toxicology following particulate inhalation

    PubMed Central

    Cooper, Ross G.

    2008-01-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl2 inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection. PMID:20040991

  13. 45 CFR 1321.67 - Service contributions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING Service Requirements § 1321.67 Service contributions. (a) For services rendered with funding under the Older Americans Act, the area agency on aging shall assure that each...

  14. 37 CFR 41.67 - Appellant's brief.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  15. 44 CFR 67.8 - Appeal procedure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... technical or scientific data submitted by the community that tend to negate or contradict the information... FLOOD ELEVATION DETERMINATIONS § 67.8 Appeal procedure. (a) If a community appeals the proposed flood... to an independent scientific body or appropriate Federal agency for advice. (c) The final...

  16. 44 CFR 67.8 - Appeal procedure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... technical or scientific data submitted by the community that tend to negate or contradict the information... FLOOD ELEVATION DETERMINATIONS § 67.8 Appeal procedure. (a) If a community appeals the proposed flood... to an independent scientific body or appropriate Federal agency for advice. (c) The final...

  17. 14 CFR 33.67 - Fuel system.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.67 Fuel system. (a) With fuel supplied to the engine at the flow and pressure specified by the applicant, the engine must...

  18. 14 CFR 33.67 - Fuel system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.67 Fuel system. (a) With fuel supplied to the engine at the flow and pressure specified by the applicant, the engine must...

  19. Pharmaceutical experiment aboard STS-67 mission

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Astronaut William G. Gregory, pilot, works with a pharmaceutical experiment on the middeck of the Earth-orbiting Space Shuttle Endeavour during the STS-67 mission. Commercial Materials Dispersion Apparatus Instruments Technology Associates Experiments (CMIX-03) includes not only pharmaceutical, but also biotechnology, cell biology, fluids, and crystal growth investigation

  20. 33 CFR 401.67 - Explosive vessels.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Dangerous Cargo § 401.67 Explosive vessels. A vessel carrying explosives, either Government or commercial, as defined in the Dangerous Cargo Act of the United States and in the International Maritime Dangerous Goods Code, Class 1, Divisions 1.1 to 1.5 inclusive...

  1. 33 CFR 401.67 - Explosive vessels.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Dangerous Cargo § 401.67 Explosive vessels. A vessel carrying explosives, either Government or commercial, as defined in the Dangerous Cargo Act of the United States and in the International Maritime Dangerous Goods Code, Class 1, Divisions 1.1 to 1.5 inclusive...

  2. 33 CFR 401.67 - Explosive vessels.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Dangerous Cargo § 401.67 Explosive vessels. A vessel carrying explosives, either Government or commercial, as defined in the Dangerous Cargo Act of the United States and in the International Maritime Dangerous Goods Code, Class 1, Divisions 1.1 to 1.5 inclusive...

  3. 40 CFR 146.67 - Operating requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... serving as a water supply, place a notice in a newspaper of general circulation. (2) The Director may... 146.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED... steps to determine the presence or absence of a leak; and (3) Notify the Director within 24 hours after...

  4. 14 CFR 33.67 - Fuel system.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.67 Fuel system. (a) With... range with the fuel initially saturated with water at 80 °F (27 °C) and having 0.025 fluid ounces per gallon (0.20 milliliters per liter) of free water added and cooled to the most critical condition for...

  5. 46 CFR 67.142 - Penalties.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Documentation; Mortgagee Consent; Validation § 67.142 Penalties. (a) An owner or operator of a vessel with a... fact during the application process for or application process to renew a fishery endorsement of the... information or knowingly conceals a material fact during the application process for or application process to...

  6. 46 CFR 67.142 - Penalties.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Documentation; Mortgagee Consent; Validation § 67.142 Penalties. (a) An owner or operator of a vessel with a... fact during the application process for or application process to renew a fishery endorsement of the... information or knowingly conceals a material fact during the application process for or application process to...

  7. 46 CFR 67.142 - Penalties.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Documentation; Mortgagee Consent; Validation § 67.142 Penalties. (a) An owner or operator of a vessel with a... fact during the application process for or application process to renew a fishery endorsement of the... information or knowingly conceals a material fact during the application process for or application process to...

  8. 46 CFR 67.142 - Penalties.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Documentation; Mortgagee Consent; Validation § 67.142 Penalties. (a) An owner or operator of a vessel with a... fact during the application process for or application process to renew a fishery endorsement of the... information or knowingly conceals a material fact during the application process for or application process to...

  9. 46 CFR 67.142 - Penalties.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Documentation; Mortgagee Consent; Validation § 67.142 Penalties. (a) An owner or operator of a vessel with a... fact during the application process for or application process to renew a fishery endorsement of the... information or knowingly conceals a material fact during the application process for or application process to...

  10. Production of no-carrier-added 64Cu from zinc metal irradiated under boron shielding.

    PubMed

    Zinn, K R; Chaudhuri, T R; Cheng, T P; Morris, J S; Meyer, W A

    1994-02-01

    Positron emission tomography offers advantages for radioimmunodiagnosis of cancer but requires radionuclides of appropriate half-life that have high specific activity and high radio-purity. This work was designed to develop a viable method to produce and purify 64Cu, which has high specific activity, for positron emission tomography. 64Cu was produced at the University of Missouri Research Reactor by the nuclear reaction, 64Zn(n,p)64Cu. Highly pure zinc metal (99.9999%) was irradiated in a specially designed boron nitrite lined container, which minimized thermal neutron reactions during irradiation. A new two-step procedure was developed to chemically separate the no-carrier-added 64Cu from the zinc metal target. 64Cu recovery for 24 runs averaged 0.393 (+/- 0.007) mCi per milligram of zinc irradiated. The boron-lined irradiation container reduced unwanted zinc radionuclides 14.3-fold. Zinc radionuclides and non-radioactive zinc were separated successfully from the 64Cu. The new separation technique was fast (2 hours total time) and highly efficient for removing the zinc. The zinc separation factor for this technique averaged 8.5 x 10(-8), indicating less than 0.0000085% of the zinc remained after separation. Thus far, the highest 64Cu specific activity at end of irradiation was 683 Ci/mg Cu, with an average of 512 Ci/mg Cu for the last six analyzed runs. The boron-lined irradiation container has sufficient capacity for 75-fold larger-sized zinc targets (up to 45 g). The new separation technique was excellent for separating 64Cu, which appears to be a radionuclide with great potential for positron emission tomography.

  11. Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

    PubMed

    Takeda, Atsushi; Kanno, Shingo; Sakurada, Naomi; Ando, Masaki; Oku, Naoto

    2008-10-01

    The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. (c) 2008 Wiley-Liss, Inc.

  12. Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

    PubMed

    Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

    2016-05-01

    There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.

    PubMed

    Ding, Xiaofeng; Zhou, Xixi; Cooper, Karen L; Huestis, Juliana; Hudson, Laurie G; Liu, Ke Jian

    2017-09-15

    Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR-induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite-inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite's role in DNA repair inhibition and co-carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Zinc in innate and adaptive tumor immunity

    PubMed Central

    2010-01-01

    Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order. PMID:21087493

  15. Zinc for the common cold.

    PubMed

    Singh, Meenu; Das, Rashmi R

    2011-02-16

    The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. To assess the effect of zinc on common cold symptoms. We searched CENTRAL (2010, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May week 3, 2010) and EMBASE (1974 to June 2010). Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. Two review authors independently extracted data and assessed trial quality. We included 13 therapeutic trials (966 participants) and two preventive trials (394 participants). Intake of zinc is associated with a significant reduction in the duration (standardized mean difference (SMD) -0.97; 95% confidence interval (CI) -1.56 to -0.38) (P = 0.001), and severity of common cold symptoms (SMD -0.39; 95% CI -0.77 to -0.02) (P = 0.04). There was a significant difference between the zinc and control group for the proportion of participants symptomatic after seven days of treatment (OR 0.45; 95% CI 0.2 to 1.00) (P = 0.05). The incidence rate ratio (IRR) of developing a cold (IRR 0.64; 95% CI 0.47 to 0.88) (P = 0.006), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.59; 95% CI 0.97 to 2.58) (P = 0.06), bad taste (OR 2.64; 95% CI 1.91 to 3.64) (P < 0.00001) and nausea (OR 2.15; 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. Zinc administered within 24 hours of onset of symptoms reduces the duration and severity of the common cold in healthy people. When supplemented for at least five months, it reduces cold

  16. A new, simple and precise method for measuring cyclotron proton beam energies using the activity vs. depth profile of zinc-65 in a thick target of stacked copper foils.

    PubMed

    Asad, A H; Chan, S; Cryer, D; Burrage, J W; Siddiqui, S A; Price, R I

    2015-11-01

    The proton beam energy of an isochronous 18MeV cyclotron was determined using a novel version of the stacked copper-foils technique. This simple method used stacked foils of natural copper forming 'thick' targets to produce Zn radioisotopes by the well-documented (p,x) monitor-reactions. Primary beam energy was calculated using the (65)Zn activity vs. depth profile in the target, with the results obtained using (62)Zn and (63)Zn (as comparators) in close agreement. Results from separate measurements using foil thicknesses of 100, 75, 50 or 25µm to form the stacks also concurred closely. Energy was determined by iterative least-squares comparison of the normalized measured activity profile in a target-stack with the equivalent calculated normalized profile, using 'energy' as the regression variable. The technique exploits the uniqueness of the shape of the activity vs. depth profile of the monitor isotope in the target stack for a specified incident energy. The energy using (65)Zn activity profiles and 50-μm foils alone was 18.03±0.02 [SD] MeV (95%CI=17.98-18.08), and 18.06±0.12MeV (95%CI=18.02-18.10; NS) when combining results from all isotopes and foil thicknesses. When the beam energy was re-measured using (65)Zn and 50-μm foils only, following a major upgrade of the ion sources and nonmagnetic beam controls the results were 18.11±0.05MeV (95%CI=18.00-18.23; NS compared with 'before'). Since measurement of only one Zn monitor isotope is required to determine the normalized activity profile this indirect yet precise technique does not require a direct beam-current measurement or a gamma-spectroscopy efficiency calibrated with standard sources, though a characteristic photopeak must be identified. It has some advantages over published methods using the ratio of cross sections of monitor reactions, including the ability to determine energies across a broader range and without need for customized beam degraders. Copyright © 2015 Elsevier Ltd. All rights

  17. Gallium-67 imaging in muscular sarcoidosis

    SciT

    Edan, G.; Bourguet, P.; Delaval, P.

    1984-07-01

    A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

  18. STS-67 in-flight crew portrait

    1995-03-03

    The STS-67/ASTRO-2 crew members pose for their traditional inflight portrait on the aft flight deck of the Earth orbiting Space Shuttle Endeavour. Left to right in the front are astronauts Tamara E. Jernigan, payload commander; Steven S. Oswald, mission commander; and William G. Gregory, pilot. Left to right on the back row are astronaut Wendy B. Lawrence, flight engineer; payload specialists Ronald A. Parise and Samuel T. Durrance; and John M. Grunsfeld, mission specialist.

  19. Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc.

    PubMed

    Cao, Kun; Li, Nan; Wang, Hongcui; Cao, Xin; He, Jiaojiao; Zhang, Bing; He, Qing-Yu; Zhang, Gong; Sun, Xuesong

    2018-04-20

    Zinc is an essential metal in bacteria. One important bacterial zinc transporter is AdcA, and most bacteria possess AdcA homologs that are single-domain small proteins due to better efficiency of protein biogenesis. However, a double-domain AdcA with two zinc-binding sites is significantly overrepresented in Streptococcus species, many of which are major human pathogens. Using molecular simulation and experimental validations of AdcA from Streptococcus pyogenes , we found here that the two AdcA domains sequentially stabilize the structure upon zinc binding, indicating an organization required for both increased zinc affinity and transfer speed. This structural organization appears to endow Streptococcus species with distinct advantages in zinc-depleted environments, which would not be achieved by each single AdcA domain alone. This enhanced zinc transport mechanism sheds light on the significance of the evolution of the AdcA domain fusion, provides new insights into double-domain transporter proteins with two binding sites for the same ion, and indicates a potential target of antimicrobial drugs against pathogenic Streptococcus species. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. 33 CFR 67.10-5 - Location requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Location requirements. 67.10-5 Section 67.10-5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO... signals § 67.10-5 Location requirements. The sound signal required by §§ 67.20-10, 67.25-10, and 67.30-10...

  1. 33 CFR 67.10-1 - Apparatus requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apparatus requirements. 67.10-1 Section 67.10-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO... signals § 67.10-1 Apparatus requirements. The sound signal required by §§ 67.20-10, 67.25-10, and 67.30-10...

  2. 33 CFR 67.10-1 - Apparatus requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Apparatus requirements. 67.10-1 Section 67.10-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO... signals § 67.10-1 Apparatus requirements. The sound signal required by §§ 67.20-10, 67.25-10, and 67.30-10...

  3. Zinc supplementation for the treatment of measles in children.

    PubMed

    Awotiwon, Ajibola A; Oduwole, Olabisi; Sinha, Anju; Okwundu, Charles I

    2015-03-20

    Measles is still an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles. We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to June week 3, 2014), EMBASE (1974 to June 2014), CINAHL (1981 to June 2014), LILACS (1982 to June 2014), Web of Science (1985 to June 2014) and BIOSIS Previews (1985 to June 2014). We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to identify unpublished and ongoing studies. Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles. Two review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions and other study characteristics using a standardised data extraction form. We used the risk ratio (RR) and hazard ratio as measures of effect with 95% confidence intervals (CI). We included only one study and we did not conduct any meta-analysis. One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed that there was no significant difference in mortality between the two groups (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.01 to 8.14). Also, there was no significant difference in time to absence of fever between the two groups (hazard ratio (HR) 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. The overall quality of the evidence can be described as very low. We cannot draw any definite conclusions

  4. Copper, iron and zinc absorption, retention and status of young women fed vitamin B-6 deficient diets

    SciT

    Turnlund, J.R.; Keyes, W.R.; Hudson, C.A.

    1991-03-11

    A study was conducted in young women to determine the effect of vitamin B-6 deficient diets on copper, iron and zinc metabolism. Young women were confined to a metabolic research unit for 84 and 98 days. They were fed a vitamin B-6 deficient formula diet initially, followed by food diet containing four increasing levels of vitamin B-6. Copper, iron and zinc absorption, retention and status were determined at intervals throughout the study. Absorption was determined using the stable isotopes {sup 65}Cu, {sup 54}Fe, and {sup 67}Zn. Status was based on serum copper and zinc, hemoglobin, hematocrit and mean corpuscular volume.more » Copper absorption averaged 18 {plus minus} 1% during vitamin B-6 depletion, significantly lower than 24 {plus minus} 1% during repletion, but serum copper was not affected and balance was positive. Iron absorption was not impaired significantly by vitamin B-6 deficient diets, but status declined during the depletion period. Zinc absorption averaged 40 {plus minus} 2% during depletion and 27 {plus minus} 2% during repletion. Zinc absorption and retention were significantly greater during vitamin B-6 depletion, but serum zinc declined suggesting the absorbed zinc was not available for utilization. The results suggest that vitamin B-6 depletion of young women may inhibit copper absorption, affect iron status and alter zinc metabolism. The effects of vitamin B-6 depletion differ markedly among these elements.« less

  5. Oxidative stress in newly-hatched Chorthippus brunneus--the effects of zinc treatment during diapause, depending on the female's age and its origins.

    PubMed

    Augustyniak, Maria; Babczyńska, Agnieszka; Augustyniak, Michał

    2011-09-01

    The responses of glutathione, glutathione S-transferases (GSTs), and catalase (CAT) were determined in 1-day-old larvae of Chorthippus brunneus Thunberg, 1815, a grasshopper exposed to zinc during diapause, from unpolluted (Pilica) or polluted (Olkusz, Szopienice) sites. The aim of the work was to search for differences among populations of the insects as a result of various multistress pressures in their habitats. The question of zinc toxicity in the context of energy allocation was also considered. Zinc caused a decrease in glutathione concentration in the body of zinc-treated larvae. Significant differences between control and zinc-treated groups were confirmed for young females' progeny from Pilica and Olkusz as well as old females' progeny from Olkusz. GSTs activity was generally not influenced by zinc. It is possible that GSTs were not the most important target of zinc action. On the contrary, the influence of zinc on CAT activity was found. The increase in CAT activity after zinc treatment was similar for all studied populations. An increase in CAT activity after zinc exposure seems to be the most universal reaction. CAT activity in zinc-treated grasshoppers may explain the mechanism of zinc toxicity based on reactive oxygen forms generation. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Zinc for the common cold.

    PubMed

    Singh, Meenu; Das, Rashmi R

    2013-06-18

    The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted in high-income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance. In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov. Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. Two review authors independently extracted data and assessed trial quality. Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) -1.03, 95% confidence interval (CI) -1.72 to -0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD -1.06, 95% CI -2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a

  7. History of Zinc in Agriculture12

    PubMed Central

    Nielsen, Forrest H.

    2012-01-01

    Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, >20 y would pass before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure parakeratosis in swine. In 1958, it was reported that zinc deficiency induced poor growth, leg abnormalities, poor feathering, and parakeratosis in chicks. In the 1960s, zinc supplementation was found to alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was established that nearly one half of the soils in the world may be zinc deficient, causing decreased plant zinc content and production that can be prevented by zinc fertilization. In many of these areas, zinc deficiency is prevented in grazing livestock by zinc fertilization of pastures or by providing salt licks. For livestock under more defined conditions, such as poultry, swine, and dairy and finishing cattle, feeds are easily supplemented with zinc salts to prevent deficiency. Today, the causes and consequences of zinc deficiency and methods and effects of overcoming the deficiency are well established for agriculture. The history of zinc in agriculture is an outstanding demonstration of the translation of research into practical application. PMID:23153732

  8. Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

    PubMed

    Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

    2016-09-01

    The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. Light-Inducible Gene Regulation with Engineered Zinc Finger Proteins

    PubMed Central

    Polstein, Lauren R.; Gersbach, Charles A.

    2014-01-01

    The coupling of light-inducible protein-protein interactions with gene regulation systems has enabled the control of gene expression with light. In particular, heterodimer protein pairs from plants can be used to engineer a gene regulation system in mammalian cells that is reversible, repeatable, tunable, controllable in a spatiotemporal manner, and targetable to any DNA sequence. This system, Light-Inducible Transcription using Engineered Zinc finger proteins (LITEZ), is based on the blue light-induced interaction of GIGANTEA and the LOV domain of FKF1 that drives the localization of a transcriptional activator to the DNA-binding site of a highly customizable engineered zinc finger protein. This chapter provides methods for modifying LITEZ to target new DNA sequences, engineering a programmable LED array to illuminate cell cultures, and using the modified LITEZ system to achieve spatiotemporal control of transgene expression in mammalian cells. PMID:24718797

  10. Molecular Mechanism of MicroRNA-200c Regulating Transforming Growth Factor-β (TGF-β)/SMAD Family Member 3 (SMAD3) Pathway by Targeting Zinc Finger E-Box Binding Homeobox 1 (ZEB1) in Hypospadias in Rats.

    PubMed

    Qian, Chong; Dang, Xiangyang; Wang, Xianglin; Xu, Wei; Pang, Guijian; Chen, Yifeng; Liu, Chengbei

    2016-10-29

    BACKGROUND The aim of this study was to explore effects of microRNA-200c regulating TGF-β/Smad3 pathway by targeting Zeb1 on the occurrence and development of hypospadias and to evaluate the relationship between microRNA-200c and occurrence of hypospadias. MATERIAL AND METHODS Pregnant rats with a gestational age of 12 days were allocated into 2 groups; one received gavage of DEHP-contained soybean oil (1 ml/day, 8 days; Group A) and the other had gavage of normal soybean oil (1 ml/day, 8 days; Group B). Baby rats with hypospadias from Group A were assigned to the model group (n=20) and healthy baby rats from Group B were assigned to the control group (n=20). Real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blot analysis were performed to detect microRNA-200c, Zeb1, TGF-β, and Smad3 mRNA and protein expressions in the model group (n=20) and the control group (n=20). The relationship between microRNA-200c and Zeb1 was detected using a dual-luciferase reporter gene experiment. After the in vitro intervention experiment in fetal rat penises, Western blot was used to detect the expression of Zeb1, TGF-β, and Smad3. RESULTS In the model group, microRNA-200c was expressed at a low level, and microRNA-200c expression in control group was 2.1 times higher than in the model group (P<0.05). When compared with the control group, mRNA expressions, protein expressions, and positive rates of Zeb1, TGF-β, and Smad3 were higher in the model group (all P<0.01). Luciferase gene report determined that Zeb1 is a target gene of microRNA-200c. The in vitro intervention experiment in fetal rat penises found that a high concentration of microRNA-200c inhibited hypospadias occurrence by suppressing the expression of Zeb1, TGF-β, and Smad3. CONCLUSIONS MicroRNA-200c was expressed in hypospadias penis tissues at low levels and was negatively correlated with Zeb1 expression. MicroRNA-200c up-regulated Zeb1 expression to regulate the TGF

  11. Molecular Mechanism of MicroRNA-200c Regulating Transforming Growth Factor-β (TGF-β)/SMAD Family Member 3 (SMAD3) Pathway by Targeting Zinc Finger E-Box Binding Homeobox 1 (ZEB1) in Hypospadias in Rats

    PubMed Central

    Qian, Chong; Dang, Xiangyang; Wang, Xianglin; Xu, Wei; Pang, Guijian; Chen, Yifeng; Liu, Chengbei

    2016-01-01

    Background The aim of this study was to explore effects of microRNA-200c regulating TGF-β/Smad3 pathway by targeting Zeb1 on the occurrence and development of hypospadias and to evaluate the relationship between microRNA-200c and occurrence of hypospadias. Material/Methods Pregnant rats with a gestational age of 12 days were allocated into 2 groups; one received gavage of DEHP-contained soybean oil (1 ml/day, 8 days; Group A) and the other had gavage of normal soybean oil (1 ml/day, 8 days; Group B). Baby rats with hypospadias from Group A were assigned to the model group (n=20) and healthy baby rats from Group B were assigned to the control group (n=20). Real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blot analysis were performed to detect microRNA-200c, Zeb1, TGF-β, and Smad3 mRNA and protein expressions in the model group (n=20) and the control group (n=20). The relationship between microRNA-200c and Zeb1 was detected using a dual-luciferase reporter gene experiment. After the in vitro intervention experiment in fetal rat penises, Western blot was used to detect the expression of Zeb1, TGF-β, and Smad3. Results In the model group, microRNA-200c was expressed at a low level, and microRNA-200c expression in control group was 2.1 times higher than in the model group (P<0.05). When compared with the control group, mRNA expressions, protein expressions, and positive rates of Zeb1, TGF-β, and Smad3 were higher in the model group (all P<0.01). Luciferase gene report determined that Zeb1 is a target gene of microRNA-200c. The in vitro intervention experiment in fetal rat penises found that a high concentration of microRNA-200c inhibited hypospadias occurrence by suppressing the expression of Zeb1, TGF-β, and Smad3. Conclusions MicroRNA-200c was expressed in hypospadias penis tissues at low levels and was negatively correlated with Zeb1 expression. MicroRNA-200c up-regulated Zeb1 expression to regulate the TGF-β/Smad3

  12. Zinc finger proteins in cancer progression.

    PubMed

    Jen, Jayu; Wang, Yi-Ching

    2016-07-13

    Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression.

  13. Evaluation of zinc coating procedures : final report.

    DOT National Transportation Integrated Search

    1978-01-01

    This research project was conducted in order to compare the existing procedure of zinc coating by hot-dip galvanizing with the other zinc coating systems of painting and electroplating. : Hardware coated by these processes was exposed to varied labor...

  14. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization

    SciT

    Ichida, Yu, E-mail: ichida-y@ncchd.go.jp; Utsunomiya, Yuko; Onodera, Masafumi

    2016-03-18

    Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remainsmore » unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. - Highlights: • ZFP809 has three consensus linkers between the zinc fingers. • Linkers are required for ZFP809 to silence transgene expression driven by MLV-LTR. • Linkers affect the precise nuclear localization of ZFP809.« less

  15. Zinc Biochemistry: From a Single Zinc Enzyme to a Key Element of Life12

    PubMed Central

    Maret, Wolfgang

    2013-01-01

    The nutritional essentiality of zinc for the growth of living organisms had been recognized long before zinc biochemistry began with the discovery of zinc in carbonic anhydrase in 1939. Painstaking analytical work then demonstrated the presence of zinc as a catalytic and structural cofactor in a few hundred enzymes. In the 1980s, the field again gained momentum with the new principle of “zinc finger” proteins, in which zinc has structural functions in domains that interact with other biomolecules. Advances in structural biology and a rapid increase in the availability of gene/protein databases now made it possible to predict zinc-binding sites from metal-binding motifs detected in sequences. This procedure resulted in the definition of zinc proteomes and the remarkable estimate that the human genome encodes ∼3000 zinc proteins. More recent developments focus on the regulatory functions of zinc(II) ions in intra- and intercellular information transfer and have tantalizing implications for yet additional functions of zinc in signal transduction and cellular control. At least three dozen proteins homeostatically control the vesicular storage and subcellular distribution of zinc and the concentrations of zinc(II) ions. Novel principles emerge from quantitative investigations on how strongly zinc interacts with proteins and how it is buffered to control the remarkably low cellular and subcellular concentrations of free zinc(II) ions. It is fair to conclude that the impact of zinc for health and disease will be at least as far-reaching as that of iron. PMID:23319127

  16. Zinc finger nuclease technology: advances and obstacles in modelling and treating genetic disorders.

    PubMed

    Jabalameli, Hamid Reza; Zahednasab, Hamid; Karimi-Moghaddam, Amin; Jabalameli, Mohammad Reza

    2015-03-01

    Zinc finger nucleases (ZFNs) are engineered restriction enzymes designed to target specific DNA sequences within the genome. Assembly of zinc finger DNA-binding domain to a DNA-cleavage domain enables the enzyme machinery to target unique locus in the genome and invoke endogenous DNA repair mechanisms. This machinery offers a versatile approach in allele editing and gene therapy. Here we discuss the architecture of ZFNs and strategies for generating targeted modifications within the genome. We review advances in gene therapy and modelling of the disease using these enzymes and finally, discuss the practical obstacles in using this technology. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Comet 67P Seen by Kepler

    2016-10-07

    The European Space Agency's Rosetta mission concluded its study of comet 67P/Churyumov-Gerasimenko on Sept. 30, 2016. NASA's planet-hunting Kepler spacecraft observed the comet during the final month of the Rosetta mission, while the comet was not visible from Earth. This animation is composed of images from Kepler of the comet. From Sept. 7 through Sept. 20, the Kepler spacecraft, operating in its K2 mission, fixed its gaze on comet 67P. From the distant vantage point of Kepler, the comet's nucleus and tail could be observed. The long-range view from Kepler complements the closeup view of the Rosetta spacecraft, providing context for the high-resolution investigation Rosetta performed as it descended closer and closer to the comet. During the two-week period of study, Kepler took a picture of the comet every 30 minutes. The animation shows a period of 29.5 hours of observation from Sept. 17 thru Sept. 18. The comet is seen passing through Kepler's field of view from top right to bottom left, as outlined by the diagonal strip. The white dots represent stars and other regions in space studied during K2's tenth observing campaign. As a comet travels through space it sheds a tail of gas and dust. The more material that is shed, the more surface area there is to reflect sunlight. A comet's activity level can be obtained by measuring the reflected sunlight. Analyzing the Kepler data, scientists will be able to determine the amount of mass lost each day as comet 67P travels through the solar system. An animation is available at http://photojournal.jpl.nasa.gov/catalog/PIA21072

  18. Official STS-67 preflight crew portrait

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Official STS-67 preflight crew portrait. In front are astronauts (left to right) Stephen S. Oswald, mission commander; Tamara E. Jernigan, payload commander; and William G. Gregory, pilot. In the back are (left to right) Ronald A. Parise, payload specialist; astronauts Wendy B. Lawrence, and John Grunsfeld, both mission specialists; and Samuel T. Durrance, payload specialist. Dr. Durrance is a research scientist in the Department of Physics and Astronomy at Johns Hopkins University, Baltimore, Maryland. Dr. Parise is a senior scientist in the Space Observatories Department, Computer Sciences Corporation, Silver Spring, Maryland. Both payload specialists flew aboard the Space Shuttle Columbia for STS-35/ASTRO-1 mission in December 1990.

  19. Gallium-67 imaging in muscular sarcoidosis

    SciT

    Edan, G.; Bourguet, P.; Delaval, P.

    1984-07-01

    A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid muscle disease but is consistent with the rarity of clinical evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

  20. Low-Resistivity Zinc Selenide for Heterojunctions

    NASA Technical Reports Server (NTRS)

    Stirn, R. J.

    1986-01-01

    Magnetron reactive sputtering enables doping of this semiconductor. Proposed method of reactive sputtering combined with doping shows potential for yielding low-resistivity zinc selenide films. Zinc selenide attractive material for forming heterojunctions with other semiconductor compounds as zinc phosphide, cadmium telluride, and gallium arsenide. Semiconductor junctions promising for future optoelectronic devices, including solar cells and electroluminescent displays. Resistivities of zinc selenide layers deposited by evaporation or chemical vapor deposition too high to form practical heterojunctions.

  1. Zinc oxide varistors and/or resistors

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-07-27

    Varistors and/or resistors are described that include doped zinc oxide gel microspheres. The doped zinc oxide gel microspheres preferably have from about 60 to about 95% by weight zinc oxide and from about 5 to about 40% by weight dopants based on the weight of the zinc oxide. The dopants are a plurality of dopants selected from silver salts, boron oxide, silicon oxide and hydrons oxides of aluminum, bismuth, cobalt, chromium, manganese, nickel, and antimony.

  2. Zinc oxide varistors and/or resistors

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    Varistors and/or resistors that includes doped zinc oxide gel microspheres. The doped zinc oxide gel microspheres preferably have from about 60 to about 95% by weight zinc oxide and from about 5 to about 40% by weight dopants based on the weight of the zinc oxide. The dopants are a plurality of dopants selected from silver salts, boron oxide, silicon oxide and hydrons oxides of aluminum, bismuth, cobalt, chromium, manganese, nickel, and antimony.

  3. Cytosolic labile zinc: a marker for apoptosis in the developing rat brain.

    PubMed

    Lee, Joo-Yong; Hwang, Jung Jin; Park, Mi-Ha; Koh, Jae-Young

    2006-01-01

    Cytosolic zinc accumulation was thought to occur specifically in neuronal death (necrosis) following acute injury. However, a recent study demonstrated that zinc accumulation also occurs in adult rat neurons undergoing apoptosis following target ablation, and in vitro experiments have shown that zinc accumulation may play a causal role in various forms of apoptosis. Here, we examined whether intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis during development. Embryonic and newborn Sprague-Dawley rat brains were double-stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) detection of apoptosis and immunohistochemical detection of stage-specific neuronal markers, such as nestin, proliferating cell nuclear antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results revealed that apoptotic cell death occurred in neurons of diverse stages (neural stem cells, and dividing, young and adult neurons) throughout the brain during the embryonic and early postnatal periods. Further staining of brain sections with acid fuchsin or zinc-specific fluorescent dyes showed that all of the apoptotic neurons were acidophilic and contained labile zinc in their cell bodies. Cytosolic zinc accumulation was also observed in cultured cortical neurons undergoing staurosporine- or sodium nitroprusside (SNP)-induced apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) reduced SNP-induced apoptosis but not staurosporine-induced apoptosis, indicating that cytosolic zinc accumulation does not play a causal role in all forms of apoptosis. Finally, the specific cytosolic zinc accumulation may have a practical application as a relatively simple marker for neurons undergoing developmental apoptosis.

  4. Zinc transporter-1 concentrates at the postsynaptic density of hippocampal synapses.

    PubMed

    Sindreu, Carlos; Bayés, Álex; Altafaj, Xavier; Pérez-Clausell, Jeús

    2014-03-07

    Zinc concentrates at excitatory synapses, both at the postsynaptic density and in a subset of glutamatergic boutons. Zinc can modulate synaptic plasticity, memory formation and nociception by regulating transmitter receptors and signal transduction pathways. Also, intracellular zinc accumulation is a hallmark of degenerating neurons in several neurological disorders. To date, no single zinc extrusion mechanism has been directly localized to synapses. Based on the presence of a canonical PDZ I motif in the Zinc Transporter-1 protein (ZnT1), we hypothesized that ZnT1 may be targeted to synaptic compartments for local control of cytosolic zinc. Using our previously developed protocol for the co-localization of reactive zinc and synaptic proteins, we further asked if ZnT1 expression correlates with presynaptic zinc content in individual synapses. Here we demonstrate that ZnT1 is a plasma membrane protein that is enriched in dendritic spines and in biochemically isolated synaptic membranes. Hippocampal CA1 synapses labelled by postembedding immunogold showed over a 5-fold increase in ZnT1 concentration at synaptic junctions compared with extrasynaptic membranes. Subsynaptic analysis revealed a peak ZnT1 density on the postsynaptic side of the synapse, < 10 nm away from the postsynaptic membrane. ZnT1 was found in the vast majority of excitatory synapses regardless of the presence of vesicular zinc in presynaptic boutons. Our study has identified ZnT1 as a novel postsynaptic density protein, and it may help elucidate the role of zinc homeostasis in synaptic function and disease.

  5. Zinc transporter-1 concentrates at the postsynaptic density of hippocampal synapses

    PubMed Central

    2014-01-01

    Background Zinc concentrates at excitatory synapses, both at the postsynaptic density and in a subset of glutamatergic boutons. Zinc can modulate synaptic plasticity, memory formation and nociception by regulating transmitter receptors and signal transduction pathways. Also, intracellular zinc accumulation is a hallmark of degenerating neurons in several neurological disorders. To date, no single zinc extrusion mechanism has been directly localized to synapses. Based on the presence of a canonical PDZ I motif in the Zinc Transporter-1 protein (ZnT1), we hypothesized that ZnT1 may be targeted to synaptic compartments for local control of cytosolic zinc. Using our previously developed protocol for the co-localization of reactive zinc and synaptic proteins, we further asked if ZnT1 expression correlates with presynaptic zinc content in individual synapses. Findings Here we demonstrate that ZnT1 is a plasma membrane protein that is enriched in dendritic spines and in biochemically isolated synaptic membranes. Hippocampal CA1 synapses labelled by postembedding immunogold showed over a 5-fold increase in ZnT1 concentration at synaptic junctions compared with extrasynaptic membranes. Subsynaptic analysis revealed a peak ZnT1 density on the postsynaptic side of the synapse, < 10 nm away from the postsynaptic membrane. ZnT1 was found in the vast majority of excitatory synapses regardless of the presence of vesicular zinc in presynaptic boutons. Conclusions Our study has identified ZnT1 as a novel postsynaptic density protein, and it may help elucidate the role of zinc homeostasis in synaptic function and disease. PMID:24602382

  6. Characterization of the response to zinc deficiency in the cyanobacterium Anabaena sp. strain PCC 7120.

    PubMed

    Napolitano, Mauro; Rubio, Miguel Ángel; Santamaría-Gómez, Javier; Olmedo-Verd, Elvira; Robinson, Nigel J; Luque, Ignacio

    2012-05-01

    Zur regulators control zinc homeostasis by repressing target genes under zinc-sufficient conditions in a wide variety of bacteria. This paper describes how part of a survey of duplicated genes led to the identification of the open reading frame all2473 as the gene encoding the Zur regulator of the cyanobacterium Anabaena sp. strain PCC 7120. All2473 binds to DNA in a zinc-dependent manner, and its DNA-binding sequence was characterized, which allowed us to determine the relative contribution of particular nucleotides to Zur binding. A zur mutant was found to be impaired in the regulation of zinc homeostasis, showing sensitivity to elevated concentrations of zinc but not other metals. In an effort to characterize the Zur regulon in Anabaena, 23 genes containing upstream putative Zur-binding sequences were identified and found to be regulated by Zur. These genes are organized in six single transcriptional units and six operons, some of them containing multiple Zur-regulated promoters. The identities of genes of the Zur regulon indicate that Anabaena adapts to conditions of zinc deficiency by replacing zinc metalloproteins with paralogues that fulfill the same function but presumably with a lower zinc demand, and with inducing putative metallochaperones and membrane transport systems likely being involved in the scavenging of extracellular zinc, including plasma membrane ABC transport systems and outer membrane TonB-dependent receptors. Among the Zur-regulated genes, the ones showing the highest induction level encode proteins of the outer membrane, suggesting a primary role for components of this cell compartment in the capture of zinc cations from the extracellular medium.

  7. Zinc supplementation in children with cystic fibrosis

    Cystic fibrosis (CF) leads to malabsorption of macro- and micronutrients. Symptomatic zinc deficiency has been reported in CF but little is known about zinc homeostasis in children with CF. Zinc supplementation (Zn suppl) is increasingly common in children with CF but it is not without theoretcial r...

  8. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... amounts consistent with good manufacturing practice. (d) Labeling. The color additive and any mixtues... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc...). It is principally composed of Zn. (2) Color additive mixtures for drug use made with zinc oxide may...

  9. 21 CFR 582.5997 - Zinc sulfate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

  10. 21 CFR 582.5997 - Zinc sulfate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

  11. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from...

  12. 21 CFR 182.8997 - Zinc sulfate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc sulfate. 182.8997 Section 182.8997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of...

  13. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions...

  14. 21 CFR 182.8988 - Zinc gluconate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc gluconate. 182.8988 Section 182.8988 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8988 Zinc gluconate. (a) Product. Zinc gluconate. (b...

  15. 21 CFR 182.8991 - Zinc oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc oxide. 182.8991 Section 182.8991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8991 Zinc oxide. (a) Product. Zinc oxide. (b) Conditions of use...

  16. 21 CFR 73.2991 - Zinc oxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Zinc oxide. 73.2991 Section 73.2991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2991 Zinc oxide. (a) Identity and specifications. The color additive zinc oxide shall conform in...

  17. 21 CFR 582.5991 - Zinc oxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc oxide. 582.5991 Section 582.5991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5991 Zinc oxide. (a) Product. Zinc...

  18. 21 CFR 73.2991 - Zinc oxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Zinc oxide. 73.2991 Section 73.2991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2991 Zinc oxide. (a) Identity and specifications. The color additive zinc oxide shall conform in...

  19. 21 CFR 582.5991 - Zinc oxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc oxide. 582.5991 Section 582.5991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5991 Zinc oxide. (a) Product. Zinc...

  20. 21 CFR 582.5997 - Zinc sulfate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

  1. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is...

  2. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use. This...

  3. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use. This...

  4. 21 CFR 582.5997 - Zinc sulfate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

  5. 21 CFR 182.8991 - Zinc oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc oxide. 182.8991 Section 182.8991 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8991 Zinc oxide. (a) Product. Zinc oxide. (b) Conditions of use. This substance is generally recognized as safe when used in...

  6. 21 CFR 558.78 - Bacitracin zinc.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Bacitracin zinc. 558.78 Section 558.78 Food and... in Animal Feeds § 558.78 Bacitracin zinc. (a) Specifications. Type A medicated articles containing bacitracin zinc equivalent to 10, 25, 40, or 50 grams per pound bacitracin. (b) Approvals. See No. 046573 in...

  7. 21 CFR 582.5991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc oxide. 582.5991 Section 582.5991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5991 Zinc oxide. (a) Product. Zinc oxide. (b) Conditions of use. This substance is generally...

  8. 21 CFR 582.5988 - Zinc gluconate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc gluconate. 582.5988 Section 582.5988 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5988 Zinc gluconate. (a) Product. Zinc gluconate. (b) Conditions of use. This substance is...

  9. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is generally recognized as safe when used in...

  10. 21 CFR 182.8997 - Zinc sulfate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc sulfate. 182.8997 Section 182.8997 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is generally recognized as safe when used in...

  11. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chick...

  12. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chick...

  13. 21 CFR 73.2991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Zinc oxide. 73.2991 Section 73.2991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2991 Zinc oxide. (a) Identity and specifications. The color additive zinc oxide shall conform in identity and specifications to the requirements of § 73.1991...

  14. 21 CFR 558.78 - Bacitracin zinc.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Bacitracin zinc. 558.78 Section 558.78 Food and... in Animal Feeds § 558.78 Bacitracin zinc. (a) Specifications. Type A medicated articles containing bacitracin zinc equivalent to 10, 25, 40, or 50 grams per pound bacitracin. (b) Approvals. See No. 046573 in...

  15. 21 CFR 182.8988 - Zinc gluconate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc gluconate. 182.8988 Section 182.8988 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8988 Zinc gluconate. (a) Product. Zinc gluconate. (b) Conditions of use. This substance is generally recognized as safe when used...

  16. 21 CFR 182.8991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc oxide. 182.8991 Section 182.8991 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8991 Zinc oxide. (a) Product. Zinc oxide. (b) Conditions of use. This substance is generally recognized as safe when used in...

  17. 21 CFR 182.8988 - Zinc gluconate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc gluconate. 182.8988 Section 182.8988 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8988 Zinc gluconate. (a) Product. Zinc gluconate. (b) Conditions of use. This substance is generally recognized as safe when used...

  18. 21 CFR 582.5988 - Zinc gluconate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc gluconate. 582.5988 Section 582.5988 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5988 Zinc gluconate. (a) Product. Zinc gluconate. (b) Conditions of use. This substance is...

  19. 21 CFR 582.5991 - Zinc oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc oxide. 582.5991 Section 582.5991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5991 Zinc oxide. (a) Product. Zinc oxide. (b) Conditions of use. This substance is generally...

  20. 21 CFR 182.8997 - Zinc sulfate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc sulfate. 182.8997 Section 182.8997 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is generally recognized as safe when used in...

  1. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is...

  2. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc chloride. 182.8985 Section 182.8985 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is generally recognized as safe when used in...

  3. Effect of Zinc in Enteropathogenic Escherichia coli Infection▿ †

    PubMed Central

    Crane, John K.; Naeher, Tonniele M.; Shulgina, Irina; Zhu, Chengru; Boedeker, Edgar C.

    2007-01-01

    Enteropathogenic Escherichia coli (EPEC) infection triggers the release of ATP from host intestinal cells, and the ATP is broken down to ADP, AMP, and adenosine in the lumen of the intestine. Ecto-5′-nucleotidase (CD73) is the main enzyme responsible for the conversion of 5′-AMP to adenosine, which triggers fluid secretion from host intestinal cells and also has growth-promoting effects on EPEC bacteria. In a recent study, we examined the role of the host enzyme CD73 in EPEC infection by testing the effect of ecto-5′-nucleotidase inhibitors. Zinc was a less potent inhibitor of ecto-5′-nucleotidase in vitro than the nucleotide analog α,β-methylene-ADP, but in vivo, zinc was much more efficacious in preventing EPEC-induced fluid secretion in rabbit ileal loops than α,β-methylene-ADP. This discrepancy between the in vitro and in vivo potencies of the two inhibitors prompted us to search for potential targets of zinc other than ecto-5′-nucleotidase. Zinc, at concentrations that produced little or no inhibition of EPEC growth, caused a decrease in the expression of EPEC protein virulence factors, such as bundle-forming pilus (BFP), EPEC secreted protein A, and other EPEC secreted proteins, and reduced EPEC adherence to cells in tissue culture. The effects of zinc were not mimicked by other transition metals, such as manganese, iron, copper, or nickel, and the effects were not reversed by an excess of iron. Quantitative real-time PCR showed that zinc reduced the abundance of the RNAs encoded by the bfp gene, by the plasmid-encoded regulator (per) gene, by the locus for the enterocyte effacement (LEE)-encoded regulator (ler) gene, and by several of the esp genes. In vivo, zinc reduced EPEC-induced fluid secretion into ligated rabbit ileal loops, decreased the adherence of EPEC to rabbit ileum, and reduced histopathological damage such as villus blunting. Some of the beneficial effects of zinc on EPEC infection appear to be due to the action of the metal on

  4. Ferritin: a zinc detoxicant and a zinc ion donor.

    PubMed Central

    Price, D; Joshi, J G

    1982-01-01

    Rats were injected with 1 mg of Zn2+ as zinc sulfate or 2 mg of Cd2+ as cadmium sulfate per kg of body weight on a daily basis. After seven injections, ferritin and metallothionein were isolated from the livers of the rats. Significant amounts of zinc were associated with ferritin. Incubation of such ferritin with apoenzymes of calf intestinal alkaline phosphatase, yeast phosphoglucomutase, and yeast aldolase restored their enzymic activity. The amount of zinc injected was insufficient to stimulate significant synthesis of metallothionein, but similar experiments with injection of cadmium did stimulate the synthesis of metallothionein. The amount of Zn2+ in ferritin of Cd-injected rats was greater than that in ferritin in Zn-injected rats, which was greater than that in ferritin of normal rats. Thus at comparable protein concentration ferritin from Cd-injected rats was a better Zn2+ donor than was ferritin from Zn-injected or normal animals. Ferritin is a normal constituent of several tissues, whereas metallothionein is synthesized under metabolic stress. Thus ferritin may function as a "metal storage and transferring agent" for iron and for zinc. It is suggested that ferritin probably serves as the initial chelator for Zn2+ and perhaps other metal ions as well and that under very high toxic levels of metal ions the synthesis of metallothionein is initiated as the second line of defense. PMID:6212927

  5. 46 CFR 67.101 - Waiver of evidence of build.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Waiver of evidence of build. 67.101 Section 67.101... DOCUMENTATION OF VESSELS Build Requirements for Vessel Documentation § 67.101 Waiver of evidence of build. (a) A vessel owner applying for documentation unable to obtain the evidence of build required by § 67.99 may...

  6. Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

    To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

  7. Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.

    PubMed

    Ladd, Fernando V L; Ladd, Aliny A B L; Ribeiro, Antônio Augusto C M; Costa, Samuel B C; Coutinho, Bruna P; Feitosa, George André S; de Andrade, Geanne M; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C; Castro, Ibraim C; Oliveira, Bruna B; Guerrant, Richard L; Lima, Aldo Angelo M; Oriá, Reinaldo B

    2010-06-01

    The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.

    PubMed

    Hemilä, Harri

    2017-05-01

    To compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in common cold treatment and to examine the dose-dependency of the effect. Meta-analysis. Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method. Seven randomised trials with 575 participants with naturally acquired common colds. Duration of the common cold. The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192-207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: -29 to + 32). Properly composed zinc gluconate lozenges may be as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold. Common cold patients may be encouraged to try zinc lozenges for treating their colds. The optimal lozenge composition and dosage scheme need to be investigated further.

  9. Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory deficits in a mouse model of Alzheimer's disease.

    PubMed

    Wang, Yue; Wu, Zheng; Bai, Yu-Ting; Wu, Gang-Yi; Chen, Gong

    2017-10-10

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia. However, whether Gad67 is involved in AD pathology has not been well studied. Here, we investigate the functional role of GAD67 in an AD mouse model with Gad67 haploinsufficiency that is caused by replacing one allele of Gad67 with green fluorescent protein (GFP) gene during generation of GAD67-GFP mice. To genetically reduce GAD67 in AD mouse brains, we crossed the Gad67 haploinsufficient mice (GAD67-GFP +/- ) with 5xFAD mice (harboring 5 human familial AD mutations in APP and PS1 genes) to generate a new line of bigenic mice. Immunostaining, ELISA, electrophysiology and behavior test were applied to compare the difference between groups. We found that reduction of GAD67 resulted in a significant decrease of amyloid β production in 5xFAD mice. Concurrently, the abnormal astrocytic GABA and tonic GABA currents, as well as the microglial reactivity were significantly reduced in the 5xFAD mice with Gad67 haploinsufficiency. Importantly, the olfactory memory deficit of 5xFAD mice was rescued by Gad67 haploinsufficiency. Our results demonstrate that GAD67 plays an important role in AD pathology, suggesting that GAD67 may be a potential drug target for modulating the progress of AD.

  10. Zinc transport and diabetes risk.

    PubMed

    Pearson, Ewan

    2014-04-01

    Genome-wide association studies have previously identified variants in SLC30A8, encoding the zinc transporter ZnT8, associated with diabetes risk. A rare variant association study has now established the direction of effect, surprisingly showing that loss-of-function mutations in SLC30A8 are protective against diabetes.

  11. Improved colorimetric determination of serum zinc.

    PubMed

    Johnson, D J; Djuh, Y Y; Bruton, J; Williams, H L

    1977-07-01

    We show how zinc may easily be quantified in serum by first using an optimum concentration of guanidine hydrochloride to cause release of zinc from proteins, followed by complexation of released metals with cyanide. The cyanide complex of zinc is preferentially demasked with chloral hydrate, followed by a colorimetric reaction between zinc and 4-(2-pyridylazo)resorcinol. This is a sensitive water-soluble ligand; its complex with zinc has an absorption maximum at 497 nm. Values found by this technique compare favorably with those obtained by atomic absorption spectroscopy.

  12. The Rosetta Mission to Comet 67P/ Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Buratti, Bonnie J.

    2017-06-01

    As remnant bodies left over from the formation of the Solar System, comets offer clues to the physical conditions and architecture of the protosolar nebula. The Rosetta spacecraft, which included an orbiter and a lander that were built and managed by the European Space Agency with NASA contributing four instruments and scientific expertise, was the first mission to orbit and study a comet through a perihelion passage. The targeted Jupiter-family comet 67P/ Churyumov-Gerasimenko, is seemingly two distinct planetesimals stuck together. The comet has not melted or been processed substantially, except for its outer layers, which consist of reaccreted dust and a crust of heated, devolatized, and annealed refractory materials and organics. The exceptionally low density (0.53 gm/cc) of 67P/ implies it is a rubble pile. The comet also appears to contain a hierarchy of building blocks: smaller spherically shaped meter-sized bodies can be seen in its interior, and even smaller cm-sized pebbles were imaged by the camera as the spacecraft made a soft crash landing on the comet’s surface on 30 September 2016. The unexpected discovery of molecular oxygen, nitrogen, and hydrogen imply that 67P/ was formed under cold conditions not exceeding 30K. The discovery of many organic compounds, including the amino acid glycine, lends support to the idea that comets, which originate in the Kuiper Belt and the Oort Cloud, brought the building blocks of life to Earth. More laboratory data on organic compounds would help to identify additional organic compounds on the comet. The differences between cometary and terrestrial D/H ratios suggest that comets are not the primary source of terrestrial water, although data on more comets is needed to confirm this result.Besides being primordial objects offering a window into the formation of solar systems, comets are astrophysical laboratories, ejecting dust and charged particles into the plasma comprising the solar wind. Several unusual phenomena

  13. Official STS-67 preflight crew portrait

    1994-12-01

    STS067-S-002 (December 1994) --- Five NASA astronauts and two payload specialists from the private sector have been named to fly aboard the Space Shuttle Endeavour for the STS-67/ASTRO-2 mission, scheduled for March 1995. In front are astronauts (left to right) Stephen S. Oswald, mission commander; Tamara E. Jernigan, payload commander; and William G. Gregory, pilot. In the back are (left to right) Ronald A. Parise, payload specialist; astronauts Wendy B. Lawrence, and John M. Grunsfeld, both mission specialists; and Samuel T. Durrance, payload specialist. Dr. Durrance is a research scientist in the Department of Physics and Astronomy at Johns Hopkins University, Baltimore, Maryland. Dr. Parise is a senior scientist in the Space Observatories Department, Computer Sciences Corporation, Silver Spring, Maryland. Both payload specialist's flew aboard the Space Shuttle Columbia for the STS-35/ASTRO-1 mission in December 1990.

  14. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.

    PubMed

    Cortese-Krott, Miriam M; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D; Suschek, Christoph V

    2014-01-01

    Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation.

  15. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway

    PubMed Central

    Matsunaga, Mayu; Takeda, Taka-aki

    2017-01-01

    More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review. PMID:29048339

  16. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

    PubMed

    Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

    2017-10-19

    More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

  17. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

    PubMed Central

    Cortese-Krott, Miriam M.; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.; Suschek, Christoph V.

    2014-01-01

    Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. PMID:25180171

  18. Interaction of zinc with dental mineral.

    PubMed

    Ingram, G S; Horay, C P; Stead, W J

    1992-01-01

    As some currently available toothpastes contain zinc compounds, the reaction of zinc with dental mineral and its effect on crystal growth rates were studied using three synthetic calcium-deficient hydroxyapatites (HAP) as being representative of dental mineral. Zinc was readily acquired by all HAP samples in the absence of added calcium, the amount adsorbed being proportional to the HAP surface area; about 9 mumol Zn/m2 was adsorbed at high zinc concentrations. As zinc was acquired, calcium was released, consistent with 1:1 Ca:Zn exchange. Soluble calcium reduced zinc uptake and similarly, calcium post-treatment released zinc. Pretreatment of HAP with 0.5 mM zinc reduced its subsequent ability to undergo seeded crystal growth, as did extracts of a toothpaste containing 0.5% zinc citrate, even in the presence of saliva. The reverse reaction, i.e. displacement of adsorbed zinc by salivary levels of calcium, however, indicates the mechanism by which zinc can reduce calculus formation in vivo by inhibiting plaque mineralisation without adversely affecting the anti-caries effects of fluoride.

  19. Zinc Therapy in Dermatology: A Review

    PubMed Central

    Mahajan, Vikram K.; Mehta, Karaninder S.; Chauhan, Pushpinder S.

    2014-01-01

    Zinc, both in elemental or in its salt forms, has been used as a therapeutic modality for centuries. Topical preparations like zinc oxide, calamine, or zinc pyrithione have been in use as photoprotecting, soothing agents or as active ingredient of antidandruff shampoos. Its use has expanded manifold over the years for a number of dermatological conditions including infections (leishmaniasis, warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders (melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc is well-established in human zinc deficiency syndromes including acrodermatitis enteropathica, it is only in recent years that importance of zinc as a micronutrient essential for infant growth and development has been recognized. The paper reviews various dermatological uses of zinc. PMID:25120566

  20. Zinc-The key to preventing corrosion

    Kropschot, S.J.; Doebrich, Jeff L.

    2011-01-01

    Centuries before it was identified as an element, zinc was used to make brass (an alloy of zinc and copper) and for medicinal purposes. Metallic zinc and zinc oxide were produced in India sometime between the 11th and 14th centuries and in China in the 17th century, although the discovery of pure metallic zinc is credited to the German chemist Andreas Marggraf, who isolated the element in 1746. Refined zinc metal is bluish-white when freshly cast; it is hard and brittle at most temperatures and has relatively low melting and boiling points. Zinc alloys readily with other metals and is chemically active. On exposure to air, it develops a thin gray oxide film (patina), which inhibits deeper oxidation (corrosion) of the metal. The metal's resistance to corrosion is an important characteristic in its use.

  1. Association between Maternal Zinc Status, Dietary Zinc Intake and Pregnancy Complications: A Systematic Review

    PubMed Central

    Wilson, Rebecca L.; Grieger, Jessica A.; Bianco-Miotto, Tina; Roberts, Claire T.

    2016-01-01

    Adequate zinc stores in the body are extremely important during periods of accelerated growth. However, zinc deficiency is common in developing countries and low maternal circulating zinc concentrations have previously been associated with pregnancy complications. We reviewed current literature assessing circulating zinc and dietary zinc intake during pregnancy and the associations with preeclampsia (PE); spontaneous preterm birth (sPTB); low birthweight (LBW); and gestational diabetes (GDM). Searches of MEDLINE; CINAHL and Scopus databases identified 639 articles and 64 studies were reviewed. In 10 out of 16 studies a difference was reported with respect to circulating zinc between women who gave birth to a LBW infant (≤2500 g) and those who gave birth to an infant of adequate weight (>2500 g), particularly in populations where inadequate zinc intake is prevalent. In 16 of our 33 studies an association was found between hypertensive disorders of pregnancy and circulating zinc; particularly in women with severe PE (blood pressure ≥160/110 mmHg). No association between maternal zinc status and sPTB or GDM was seen; however; direct comparisons between the studies was difficult. Furthermore; only a small number of studies were based on women from populations where there is a high risk of zinc deficiency. Therefore; the link between maternal zinc status and pregnancy success in these populations cannot be established. Future studies should focus on those vulnerable to zinc deficiency and include dietary zinc intake as a measure of zinc status. PMID:27754451

  2. Effects of serum zinc level on tinnitus.

    PubMed

    Berkiten, Güler; Kumral, Tolgar Lütfi; Yıldırım, Güven; Salturk, Ziya; Uyar, Yavuz; Atar, Yavuz

    2015-01-01

    The aim of this study was to assess zinc levels in tinnitus patients, and to evaluate the effects of zinc deficiency on tinnitus and hearing loss. One-hundred patients, who presented to an outpatient clinic with tinnitus between June 2009 and 2014, were included in the study. Patients were divided into three groups according to age: Group I (patients between 18 and 30years of age); Group II (patients between 31 and 60years of age); and Group III (patients between 61 and 78years of age). Following a complete ear, nose and throat examination, serum zinc levels were measured and the severity of tinnitus was quantified using the Tinnitus Severity Index Questionnaire (TSIQ). Patients were subsequently asked to provide a subjective judgment regarding the loudness of their tinnitus. The hearing status of patients was evaluated by audiometry and high-frequency audiometry. An average hearing sensitivity was calculated as the mean value of hearing thresholds between 250 and 20,000Hz. Serum zinc levels between 70 and 120μg/dl were considered normal. The severity and loudness of tinnitus, and the hearing thresholds of the normal zinc level and zinc-deficient groups, were compared. Twelve of 100 (12%) patients exhibited low zinc levels. The mean age of the zinc-deficient group was 65.41±12.77years. Serum zinc levels were significantly lower in group III (p<0.01). The severity and loudness of tinnitus were greater in zinc-deficient patients (p=0.011 and p=0.015, respectively). Moreover, the mean thresholds of air conduction were significantly higher in zinc-deficient patients (p=0.000). We observed that zinc levels decrease as age increases. In addition, there was a significant correlation between zinc level and the severity and loudness of tinnitus. Zinc deficiency was also associated with impairments in hearing thresholds. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The biological inorganic chemistry of zinc ions.

    PubMed

    Krężel, Artur; Maret, Wolfgang

    2016-12-01

    The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: Zn(II). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the "mobile" zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide (ZnO). In most investigations, reference is made to zinc or Zn 2+ without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn 2+ differs from s-block cations such as Ca 2+ with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is

  4. Optical properties of particles collected by COSIMA around 67P/Churyumov Gerasimenko

    NASA Astrophysics Data System (ADS)

    Langevin, Yves; Hilchenbach, Martin; Vincendon, Mathieu; Merouane, Sihane; Hornung, Klaus; Cosima Team

    2017-04-01

    The COSIMA TOF-SIMS spectrometer aboard Rosetta has collected nearly 40,000 particles in orbit around 67P/Churyumov-Gerasimenko from August 2014 to September 2016. These particles have been identified using the COSISCOPE optical microscope, which imaged the 10 mm x 10 mm targets before and after exposure to the cometary environment with a resolution of 14 µm / pixel [1

  5. STS-67 Space Shuttle mission report

    NASA Technical Reports Server (NTRS)

    Fricke, Robert W., Jr.

    1995-01-01

    The STS-67 Space Shuttle Program Mission Report provides the results of the orbiter vehicle performance evaluation during this sixty-eighth flight of the Shuttle Program, the forty-third flight since the return to flight, and the eighth flight of the Orbiter vehicle Endeavour (OV-105). In addition, the report summarizes the payload activities and the performance of the External Tank (ET), Solid Rocket Booster (SRB), Reusable Solid Rocket Motor (RSRM), and the Space Shuttle Main Engines (SSME). The serial numbers of the other elements of the flight vehicle were ET-69 for the ET; 2012, 2033, and 2031 for SSME's 1, 2, and 3, respectively; and Bl-071 for the SRB's. The left-hand RSRM was designated 360W043A, and the right-hand RSRM was designated 360L043B. The primary objective of this flight was to successfully perform the operations of the ultraviolet astronomy (ASTRO-2) payload. Secondary objectives of this flight were to complete the operations of the Protein Crystal Growth - Thermal Enclosure System (PCG-TES), the Protein Crystal Growth - Single Locker Thermal Enclosure System (PCG-STES), the Commercial Materials Dispersion Apparatus ITA Experiments (CMIX), the Shuttle Amateur Radio Experiment-2 (SAREX-2), the Middeck Active Control Experiment (MACE), and two Get-Away Special (GAS) payloads.

  6. Mechanisms of zinc binding to the solute-binding protein AztC and transfer from the metallochaperone AztD.

    PubMed

    Neupane, Durga P; Avalos, Dante; Fullam, Stephanie; Roychowdhury, Hridindu; Yukl, Erik T

    2017-10-20

    Bacteria can acquire the essential metal zinc from extremely zinc-limited environments by using ATP-binding cassette (ABC) transporters. These transporters are critical virulence factors, relying on specific and high-affinity binding of zinc by a periplasmic solute-binding protein (SBP). As such, the mechanisms of zinc binding and release among bacterial SBPs are of considerable interest as antibacterial drug targets. Zinc SBPs are characterized by a flexible loop near the high-affinity zinc-binding site. The function of this structure is not always clear, and its flexibility has thus far prevented structural characterization by X-ray crystallography. Here, we present intact structures for the zinc-specific SBP AztC from the bacterium Paracoccus denitrificans in the zinc-bound and apo-states. A comparison of these structures revealed that zinc loss prompts significant structural rearrangements, mediated by the formation of a sodium-binding site in the apo-structure. We further show that the AztC flexible loop has no impact on zinc-binding affinity, stoichiometry, or protein structure, yet is essential for zinc transfer from the metallochaperone AztD. We also found that 3 His residues in the loop appear to temporarily coordinate zinc and then convey it to the high-affinity binding site. Thus, mutation of any of these residues to Ala abrogated zinc transfer from AztD. Our structural and mechanistic findings conclusively identify a role for the AztC flexible loop in zinc acquisition from the metallochaperone AztD, yielding critical insights into metal binding by AztC from both solution and AztD. These proteins are highly conserved in human pathogens, making this work potentially useful for the development of novel antibiotics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Zinc Regulation of Aminopeptidase B Involved in Neuropeptide Production

    PubMed Central

    Hwang, Shin-Rong; Hook, Vivian

    2009-01-01

    Aminopeptidase B (AP-B) is a metallopeptidase that removes basic residues from the N-termini of neuropeptide substrates in secretory vesicles. This study assessed zinc regulation of AP-B activity, since secretory vesicles contain endogenous zinc. AP-B was inhibited by zinc at concentrations typically present in secretory vesicles. Zinc effects were dependent on concentration, incubation time, and the molar ratio of zinc to enzyme. AP-B activity was recovered upon removal of zinc. AP-B with zinc became susceptible to degradation by trypsin, suggesting that zinc alters enzyme conformation. Zinc regulation demonstrates the metallopeptidase property of AP-B. PMID:18571504

  8. Method for the regeneration of spent molten zinc chloride

    DOEpatents

    Zielke, Clyde W.; Rosenhoover, William A.

    1981-01-01

    In a process for regenerating spent molten zinc chloride which has been used in the hydrocracking of coal or ash-containing polynuclear aromatic hydrocarbonaceous materials derived therefrom and which contains zinc chloride, zinc oxide, zinc oxide complexes and ash-containing carbonaceous residue, by incinerating the spent molten zinc chloride to vaporize the zinc chloride for subsequent condensation to produce a purified molten zinc chloride: an improvement comprising the use of clay in the incineration zone to suppress the vaporization of metals other than zinc. Optionally water is used in conjunction with the clay to further suppress the vaporization of metals other than zinc.

  9. [Zinc and treatment of diarrhoea].

    PubMed

    Fontaine, O

    2006-06-01

    Recently WHO and UNICEF issued a joint statement revising guidelines for clinical management of diarrhoea. These updated recommendations take into account new research findings showing the beneficial effects of oral rehydration salts (ORS) containing lower concentrations of glucose and salts and of zinc supplementation. In combination with prevention and treatment of dehydration with appropriate fluids, breastfeeding, continued feeding and selective use of antibiotics, these two advances can drastically diminish the number of child deaths by reducing the duration and severity of diarrhoeal episodes and lowering their incidence. The purpose of this report is to present the research findings that demonstrated the efficacy of zinc supplementation in the management of diarrhoea and led to revision of WHO/UNCEF guidelines.

  10. Development of Biodegradable Zinc Oxide Nanowires Targeting Breast Cancer Metastasis

    DTIC Science & Technology

    2013-09-01

    of highly-specificity anti-CD146 monoclonal antibody. 2. Bioconjugation of YY146 to a chelating moiety (NOTA) for the radiolabeling with 64Cu and...vivo investigation of 64Cu -NOTA-ZnO-PEG-TRC105 in 4T1 tumor bearing mice. A serial of coronal PET images about 4T1 tumor-bearing mice at 0.5, 3, 17...and 24 post-injection of 64Cu -NOTA-ZnO-PEG-TRC105, 64Cu -NOTA-ZnO-PEG and TRC105 before 64Cu -NOTA-ZnO-PEG-TRC105 (i.e., blocking). Tumors are

  11. Dietary zinc and iron intake and risk of depression: A meta-analysis.

    PubMed

    Li, Zongyao; Li, Bingrong; Song, Xingxing; Zhang, Dongfeng

    2017-05-01

    The associations between dietary zinc and iron intake and risk of depression remain controversial. Thus, we carried out a meta-analysis to evaluate these associations. A systematic search was performed in PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases for relevant studies up to January 2017. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. A total of 9 studies for dietary zinc intake and 3 studies for dietary iron intake were finally included in present meta-analysis. The pooled RRs with 95% CIs of depression for the highest versus lowest dietary zinc and iron intake were 0.67 (95% CI: 0.58-0.76) and 0.57 (95% CI: 0.34-0.95), respectively. In subgroup analysis by study design, the inverse association between dietary zinc intake and risk of depression remained significant in the cohort studies and cross-sectional studies. The pooled RRs (95% CIs) for depression did not substantially change in the influence analysis and subgroup analysis by adjustment for body mass index (BMI). The present meta-analysis indicates inverse associations between dietary zinc and iron intake and risk of depression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  12. Zinc and lead detoxifying abilities of humic substances relevant to environmental bacterial species.

    PubMed

    Perelomov, L V; Sarkar, Binoy; Sizova, O I; Chilachava, K B; Shvikin, A Y; Perelomova, I V; Atroshchenko, Y M

    2018-04-30

    The effect of humic substances (HS) and their different fractions (humic acids (HA) and hymatomelanic acids (HMA)) on the toxicity of zinc and lead to different strains of bacteria was studied. All tested bacteria demonstrated a lower resistance to zinc than lead showing minimum inhibitory concentrations of 0.1 - 0.3mM and 0.3-0.5mM, respectively. The highest resistance to lead was characteristic of Pseudomonas chlororaphis PCL1391 and Rhodococcus RS67, while Pseudomonas chlororaphis PCL1391 showed the greatest resistance to zinc. The combined fractions of HS and HA alone reduced zinc toxicity at all added concentrations of the organic substances (50 - 200mgL -1 ) to all microorganisms, while hymatomelanic acids reduced zinc toxicity to Pseudomonas chlororaphis PCL1391 at 200mgL -1 organic concentration only. The HS fractions imparted similar effects on lead toxicity also. This study demonstrated that heavy metal toxicity to bacteria could be reduced through complexation with HS and their fractions. This was particularly true when the metal-organic complexes held a high stability, and low solubility and bioavailability. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. The C. elegans Tailless/TLX transcription factor nhr-67 controls neuronal identity and left/right asymmetric fate diversification.

    PubMed

    Sarin, Sumeet; Antonio, Celia; Tursun, Baris; Hobert, Oliver

    2009-09-01

    An understanding of the molecular mechanisms of cell fate determination in the nervous system requires the elucidation of transcriptional regulatory programs that ultimately control neuron-type-specific gene expression profiles. We show here that the C. elegans Tailless/TLX-type, orphan nuclear receptor NHR-67 acts at several distinct steps to determine the identity and subsequent left/right (L/R) asymmetric subtype diversification of a class of gustatory neurons, the ASE neurons. nhr-67 controls several broad aspects of sensory neuron development and, in addition, triggers the expression of a sensory neuron-type-specific selector gene, che-1, which encodes a zinc-finger transcription factor. Subsequent to its induction of overall ASE fate, nhr-67 diversifies the fate of the two ASE neurons ASEL and ASER across the L/R axis by promoting ASER and inhibiting ASEL fate. This function is achieved through direct expression activation by nhr-67 of the Nkx6-type homeobox gene cog-1, an inducer of ASER fate, that is inhibited in ASEL through the miRNA lsy-6. Besides controlling bilateral and asymmetric aspects of ASE development, nhr-67 is also required for many other neurons of diverse lineage history and function to appropriately differentiate, illustrating the broad and diverse use of this type of transcription factor in neuronal development.

  14. Zinc and its transporters, pancreatic beta cells, and insulin metabolism

    Zinc is an essential trace metal for life. Two families of zinc transporters, SLC30A (ZnT) and SLC39A (ZIP) are required for maintaining cellular zinc homeostasis. ZnTs function to decrease cytoplasmic zinc concentrations whereas ZIPs do the opposite. Expression of zinc transporters can be tissue/ce...

  15. The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.

    PubMed

    Corbi, N; Libri, V; Fanciulli, M; Tinsley, J M; Davies, K E; Passananti, C

    2000-06-01

    Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.

  16. Gallium 67 scintigraphy in glomerular disease

    SciT

    Bakir, A.A.; Lopez-Majano, V.; Levy, P.S.

    1988-12-01

    To evaluate the diagnostic usefulness of gallium 67 scintigraphy in glomerular disease, 45 patients with various glomerulopathies, excluding lupus nephritis and renal vasculitis, were studied. Persistent renal visualization 48 hours after the gallium injection, a positive scintigram, was graded as + (less than), ++ (equal to), and +++ (greater than) the hepatic uptake. Positive scintigrams were seen in ten of 16 cases of focal segmental glomerulosclerosis, six of 11 cases of proliferative glomerulonephritis, and one case of minimal change, and one of two cases of membranous nephropathy; also in three of six cases of sickle glomerulopathy, two cases of diabeticmore » neuropathy, one of two cases of amyloidosis, and one case of mild chronic allograft rejection. The 25 patients with positive scans were younger than the 20 with negative scans (31 +/- 12 v 42 +/- 17 years; P less than 0.01), and exhibited greater proteinuria (8.19 +/- 7.96 v 2.9 +/- 2.3 S/d; P less than 0.01) and lower serum creatinine values (2 +/- 2 v 4.1 +/- 2.8 mg/dL; P less than 0.01). The amount of proteinuria correlated directly with the intensity grade of the gallium image (P less than 0.02), but there was no correlation between the biopsy diagnosis and the outcome of the gallium scan. It was concluded that gallium scintigraphy is not useful in the differential diagnosis of the glomerular diseases under discussion. Younger patients with good renal function and heavy proteinuria are likely to have a positive renal scintigram regardless of the underlying glomerulopathy.« less

  17. 46 CFR 5.67 - Physician-patient privilege.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Physician-patient privilege. 5.67 Section 5.67 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC MARINE INVESTIGATION REGULATIONS-PERSONNEL ACTION Statement of Policy and Interpretation § 5.67 Physician-patient privilege. For...

  18. 33 CFR 110.67 - Delaware River, Essington, Pa.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Delaware River, Essington, Pa. 110.67 Section 110.67 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.67 Delaware River, Essington, Pa. North of...

  19. 33 CFR 110.67 - Delaware River, Essington, Pa.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Delaware River, Essington, Pa. 110.67 Section 110.67 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.67 Delaware River, Essington, Pa. North of...

  20. 33 CFR 110.67 - Delaware River, Essington, Pa.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Delaware River, Essington, Pa. 110.67 Section 110.67 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.67 Delaware River, Essington, Pa. North of...

  1. 33 CFR 110.67 - Delaware River, Essington, Pa.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Delaware River, Essington, Pa. 110.67 Section 110.67 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.67 Delaware River, Essington, Pa. North of...

  2. 33 CFR 110.67 - Delaware River, Essington, Pa.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Delaware River, Essington, Pa. 110.67 Section 110.67 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.67 Delaware River, Essington, Pa. North of...

  3. 36 CFR 228.67 - Information collection requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false Information collection requirements. 228.67 Section 228.67 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.67 Information...

  4. 36 CFR 228.67 - Information collection requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Information collection requirements. 228.67 Section 228.67 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.67 Information...

  5. 36 CFR 228.67 - Information collection requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Information collection requirements. 228.67 Section 228.67 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.67 Information...

  6. 36 CFR 228.67 - Information collection requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Information collection requirements. 228.67 Section 228.67 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.67 Information...

  7. 36 CFR 228.67 - Information collection requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Information collection requirements. 228.67 Section 228.67 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.67 Information...

  8. 31 CFR 6.7 - Delegations of authority.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Delegations of authority. 6.7 Section 6.7 Money and Finance: Treasury Office of the Secretary of the Treasury APPLICATIONS FOR AWARDS UNDER THE EQUAL ACCESS TO JUSTICE ACT General Provisions § 6.7 Delegations of authority. The Director...

  9. 33 CFR 67.20-10 - Sound signal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sound signal. 67.20-10 Section 67.20-10 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Class âAâ Requirements § 67.20-10 Sound...

  10. 33 CFR 67.10-15 - Approval of sound signals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Approval of sound signals. 67.10... Sound signals § 67.10-15 Approval of sound signals. (a) The Coast Guard approves a sound signal if: (1) It meets the requirements for sound signals in § 67.10-1 (a), (b), (c), (d), and (e) when tested...

  11. 28 CFR 51.67 - Disposition of petition.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Disposition of petition. 51.67 Section 51.67 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED Petition To Change Procedures § 51.67 Disposition...

  12. 28 CFR 51.67 - Disposition of petition.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Disposition of petition. 51.67 Section 51.67 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED Petition To Change Procedures § 51.67 Disposition...

  13. 40 CFR Appendix C to Part 67 - Computer Program

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 16 2013-07-01 2013-07-01 false Computer Program C Appendix C to Part 67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) EPA APPROVAL OF STATE NONCOMPLIANCE PENALTY PROGRAM Pt. 67, App. C Appendix C to Part 67—Computer Program Note...

  14. 40 CFR Appendix C to Part 67 - Computer Program

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Computer Program C Appendix C to Part 67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) EPA APPROVAL OF STATE NONCOMPLIANCE PENALTY PROGRAM Pt. 67, App. C Appendix C to Part 67—Computer Program Note...

  15. 40 CFR Appendix C to Part 67 - Computer Program

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Computer Program C Appendix C to Part 67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) EPA APPROVAL OF STATE NONCOMPLIANCE PENALTY PROGRAM Pt. 67, App. C Appendix C to Part 67—Computer Program Note...

  16. 7 CFR 953.67 - Proceedings after termination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Proceedings after termination. 953.67 Section 953.67 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... SOUTHEASTERN STATES Order Regulating Handling Effective Time and Termination § 953.67 Proceedings after...

  17. 33 CFR 67.35-5 - Contents of application.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Contents of application. 67.35-5 Section 67.35-5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Applications § 67.35-5 Contents of...

  18. 33 CFR 67.50-30 - Ninth Coast Guard District.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Ninth Coast Guard District. 67.50-30 Section 67.50-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES District Regulations § 67...

  19. 33 CFR 67.50-30 - Ninth Coast Guard District.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Ninth Coast Guard District. 67.50-30 Section 67.50-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES District Regulations § 67...

  20. 33 CFR 67.50-15 - Fifth Coast Guard District.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Fifth Coast Guard District. 67.50-15 Section 67.50-15 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES District Regulations § 67...