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Sample records for zinc induces dimerization

  1. Communication between the Zinc and Nickel Sites in Dimeric HypA: Metal Recognition and pH Sensing

    International Nuclear Information System (INIS)

    Herbst, R.; Perovic, I.; Martin-Diaconescu, V.; O'Brien, K.; Chivers, P.; Sondej Pochapsky, S.; Pochapsky, T.; Maroney, M.

    2010-01-01

    Helicobacter pylori, a pathogen that colonizes the human stomach, requires the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive this low pH environment. The maturation of both enzymes depends on the metallochaperone, HypA. HypA contains two metal sites, an intrinsic zinc site and a low-affinity nickel binding site. X-ray absorption spectroscopy (XAS) shows that the structure of the intrinsic zinc site of HypA is dynamic and able to sense both nickel loading and pH changes. At pH 6.3, an internal pH that occurs during acid shock, the zinc site undergoes unprecedented ligand substitutions to convert from a Zn(Cys) 4 site to a Zn(His) 2 (Cys) 2 site. NMR spectroscopy shows that binding of Ni(II) to HypA results in paramagnetic broadening of resonances near the N-terminus. NOEs between the β-CH 2 protons of Zn cysteinyl ligands are consistent with a strand-swapped HypA dimer. Addition of nickel causes resonances from the zinc binding motif and other regions to double, indicating more than one conformation can exist in solution. Although the structure of the high-spin, 5-6 coordinate Ni(II) site is relatively unaffected by pH, the nickel binding stoichiometry is decreased from one per monomer to one per dimer at pH = 6.3. Mutation of any cysteine residue in the zinc binding motif results in a zinc site structure similar to that found for holo-WT-HypA at low pH and is unperturbed by the addition of nickel. Mutation of the histidines that flank the CXXC motifs results in a zinc site structure that is similar to holo-WT-HypA at neutral pH (Zn(Cys) 4 ) and is no longer responsive to nickel binding or pH changes. Using an in vitro urease activity assay, it is shown that the recombinant protein is sufficient for recovery of urease activity in cell lysate from a HypA deletion mutant, and that mutations in the zinc-binding motif result in a decrease in recovered urease activity. The results are interpreted in terms of a model wherein HypA controls the

  2. Communication between the Zinc and Nickel Sites in Dimeric HypA: Metal Recognition and pH Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, R.; Perovic, I; Martin-Diaconescu, V; O’Brien, K; Chivers, P; Sondej Pochapsky, S; Pochapsky, T; Maroney, M

    2010-01-01

    Helicobacter pylori, a pathogen that colonizes the human stomach, requires the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive this low pH environment. The maturation of both enzymes depends on the metallochaperone, HypA. HypA contains two metal sites, an intrinsic zinc site and a low-affinity nickel binding site. X-ray absorption spectroscopy (XAS) shows that the structure of the intrinsic zinc site of HypA is dynamic and able to sense both nickel loading and pH changes. At pH 6.3, an internal pH that occurs during acid shock, the zinc site undergoes unprecedented ligand substitutions to convert from a Zn(Cys){sub 4} site to a Zn(His){sub 2}(Cys){sub 2} site. NMR spectroscopy shows that binding of Ni(II) to HypA results in paramagnetic broadening of resonances near the N-terminus. NOEs between the {beta}-CH{sub 2} protons of Zn cysteinyl ligands are consistent with a strand-swapped HypA dimer. Addition of nickel causes resonances from the zinc binding motif and other regions to double, indicating more than one conformation can exist in solution. Although the structure of the high-spin, 5-6 coordinate Ni(II) site is relatively unaffected by pH, the nickel binding stoichiometry is decreased from one per monomer to one per dimer at pH = 6.3. Mutation of any cysteine residue in the zinc binding motif results in a zinc site structure similar to that found for holo-WT-HypA at low pH and is unperturbed by the addition of nickel. Mutation of the histidines that flank the CXXC motifs results in a zinc site structure that is similar to holo-WT-HypA at neutral pH (Zn(Cys){sub 4}) and is no longer responsive to nickel binding or pH changes. Using an in vitro urease activity assay, it is shown that the recombinant protein is sufficient for recovery of urease activity in cell lysate from a HypA deletion mutant, and that mutations in the zinc-binding motif result in a decrease in recovered urease activity. The results are interpreted in terms of a model

  3. Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans

    Science.gov (United States)

    Kjellerup, Lasse; Winther, Anne-Marie L.; Wilson, Duncan; Fuglsang, Anja T.

    2018-01-01

    Zinc is an essential micronutrient, required for a range of zinc-dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo-5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc-signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However, zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen. PMID:29619016

  4. Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor

    International Nuclear Information System (INIS)

    Goffinont, S.; Davidkova, M.; Spotheim-Maurizot, M.

    2009-01-01

    The wild type lactose repressor of Escherichia coli is a tetrameric protein formed by two identical dimers. They are associated via a C-terminal 4-helix bundle (called tetramerization domain) whose stability is ensured by the interaction of leucine zipper motifs. Upon in vitro γ-irradiation the repressor losses its ability to bind the operator DNA sequence due to damage of its DNA-binding domains. Using an engineered dimeric repressor for comparison, we show here that irradiation induces also the change of repressor oligomerisation state from tetramer to dimer. The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain.

  5. Role of distonic dimer radical cations in the radiation-induced polymerisation of vinyl ethers

    International Nuclear Information System (INIS)

    Naumov, Sergej; Janovsky, Igor; Knolle, Wolfgang; Mehnert, Reiner

    2005-01-01

    The experimental low-temperature EPR results and the quantum chemical calculations suggest that dimer radical cations of cyclic and aliphatic vinyl ethers (VE) plays a key role in starting of radiation-induced polymerisation. The main species observed at high 2,3-dihydrofuran (DHF), 2,3-dihydropyran (DHP) and VE concentration is the dimer radical cation. In the case of cyclic VE the dimer radical cation transforms through H-abstraction from neutral molecule into a carbocation and radical, which could start both cationic and free-radical polymerisation. However, in the case of aliphatic VE no further reactive species, which could start polymerisation, were observed. This is caused (in agreement with experiment and quantum chemical calculations) by the very high stability of dimer radical cation and calculated endothermity of H-abstraction reaction by dimer radical cation from monomer

  6. Anion Photoelectron Spectroscopy of the Homogenous 2-Hydroxypyridine Dimer Electron Induced Proton Transfer System

    Science.gov (United States)

    Vlk, Alexandra; Stokes, Sarah; Wang, Yi; Hicks, Zachary; Zhang, Xinxing; Blando, Nicolas; Frock, Andrew; Marquez, Sara; Bowen, Kit; Bowen Lab JHU Team

    Anion photoelectron spectroscopic (PES) and density functional theory (DFT) studies on the dimer anion of (2-hydroxypyridine)2-are reported. The experimentally measured vertical detachment energy (VDE) of 1.21eV compares well with the theoretically predicted values. The 2-hydroxypyridine anionic dimer system was investigated because of its resemblance to the nitrogenous heterocyclic pyrimidine nucleobases. Experimental and theoretical results show electron induced proton transfer (EIPT) in both the lactim and lactam homogeneous dimers. Upon electron attachment, the anion can serve as the intermediate between the two neutral dimers. A possible double proton transfer process can occur from the neutral (2-hydroxypyridine)2 to (2-pyridone)2 through the dimer anion. This potentially suggests an electron catalyzed double proton transfer mechanism of tautomerization. Research supported by the NSF Grant No. CHE-1360692.

  7. Non-Ligand-Induced Dimerization is Sufficient to Initiate the Signalling and Endocytosis of EGF Receptor

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    George Kourouniotis

    2016-07-01

    Full Text Available The binding of epidermal growth factor (EGF to EGF receptor (EGFR stimulates cell mitogenesis and survival through various signalling cascades. EGF also stimulates rapid EGFR endocytosis and its eventual degradation in lysosomes. The immediate events induced by ligand binding include receptor dimerization, activation of intrinsic tyrosine kinase and autophosphorylation. However, in spite of intensified efforts, the results regarding the roles of these events in EGFR signalling and internalization is still very controversial. In this study, we constructed a chimeric EGFR by replacing its extracellular domain with leucine zipper (LZ and tagged a green fluorescent protein (GFP at its C-terminus. We showed that the chimeric LZ-EGFR-GFP was constitutively dimerized. The LZ-EGFR-GFP dimer autophosphorylated each of its five well-defined C-terminal tyrosine residues as the ligand-induced EGFR dimer does. Phosphorylated LZ-EGFR-GFP was localized to both the plasma membrane and endosomes, suggesting it is capable of endocytosis. We also showed that LZ-EGFR-GFP activated major signalling proteins including Src homology collagen-like (Shc, extracellular signal-regulated kinase (ERK and Akt. Moreover, LZ-EGFR-GFP was able to stimulate cell proliferation. These results indicate that non-ligand induced dimerization is sufficient to activate EGFR and initiate cell signalling and EGFR endocytosis. We conclude that receptor dimerization is a critical event in EGF-induced cell signalling and EGFR endocytosis.

  8. Zinc movement in the brain under kainate-induced seizures.

    Science.gov (United States)

    Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

    2003-05-01

    On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

  9. Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

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    Jackie Penn

    2015-02-01

    Full Text Available The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE and Bruch’s membrane (BM. However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.

  10. Zinc release contributes to hypoglycemia-induced neuronal death.

    Science.gov (United States)

    Suh, Sang Won; Garnier, Philippe; Aoyama, Koji; Chen, Yongmei; Swanson, Raymond A

    2004-08-01

    Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme that normally participates in DNA repair but promotes cell death when extensively activated. Endogenous, vesicular zinc in brain is released to the extracellular space under conditions causing neuronal depolarization. Here, we used a rat model of insulin-induced hypoglycemia to assess the role of zinc release in PARP-1 activation and neuronal death after severe hypoglycemia. Zinc staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and significantly reduced hypoglycemia-induced neuronal death. CaEDTA also attenuated the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in hippocampal neurons. These results suggest that zinc translocation is an intermediary step linking hypoglycemia to PARP-1 activation and neuronal death.

  11. Synthesis and characterization of monomeric and dimeric manganese(II and zinc(II complexes of pyridine-2-carbaldoxime

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    Jørgen Glerup

    2000-12-01

    Full Text Available The syntheses and characterization of two complexes of manganese(II and one complex of zinc(II with the ligand pyridine-2-carbaldoxime, C6H6N2O, are described. The monomeric manganese(II complex cis-[Mn(C6H6N2O 2Cl2] (1 crystallizes in the orthorhombic space group Pbcn with 4 formula units in a cell of dimensions a = 12.479(3 Å, b = 10.348(2 Å, and c = 11. 974(2 Å. The structure has been refined to a final value of the conventional R-factor of 0.0330 based on 1513 observed independent reflections. The analogous zinc(II complex, cis-[Zn(C6H6N2O2Cl2] (2 also crystallizes in the orthorhombic space group Pbcn with 4 formula units in a cell of dimensions a = 12.215(2 Å, b = 10.383(2 Å, and c = 12. 016(2 Å. The structure has been refined to a final value of the conventional R-factor of 0.0377 based on 1117 observed independent reflections. The two complexes are isostructural, with the central metal atom lying on a crystallographic 2-fold axis. Both complexes are approximately octahedral, the coordination being provided by two trans pyridine nitrogen atoms and two cis amine nitrogen atoms from the oxime ligands, and by two cis chlorides. The dimeric manganese(II complex [(C6H6N2O(CH3OHClMnCl2MnCl(CH3OH(C6H6N2O] (3 crystallizes in the monoclinic space group P21/n with 2 formula units in a cell of dimensions a = 7.895(2 Å, b = 11.196(3 Å, and c = 12. 544(2 Å, and b = 98.39(2o. The structure has been refined to a final value of the conventional R-factor of 0.0312 based on 1568 observed independent reflections. There is a crystallographic inversion center in the middle of the dimer relating one manganese center to the other. The geometry at each manganese(II center is again roughly octahedral, coordination being provided by two nitrogen atoms from the oxime ligand, a terminal chloride ion trans to the amine nitrogen, the oxygen atom of the coordinated methanol molecule, and two bridging chlorides that link the two halves of the dimer. The Mn

  12. Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK

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    Mark L. Westbroek

    2017-12-01

    Full Text Available Clustering of the B cell antigen receptor (BCR by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR, which binds the small molecule trimethoprim (TMP with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

  13. Zinc

    Science.gov (United States)

    ... Consumer Datos en español Health Professional Other Resources Zinc Fact Sheet for Consumers Have a question? Ask ... find out more about zinc? Disclaimer What is zinc and what does it do? Zinc is a ...

  14. ZINC-INDUCED HYPERLEPTINEMIA IN RATS RELATED TO THE AMELIORATION OF SUCROSE-INDUCED OBESITY WITH ZINC REPLETION

    International Nuclear Information System (INIS)

    HEIBASHY, M.I.; EL-NAHLA, A.M.; ASHOUR, I.; SALEH, SH.Y.A.

    2008-01-01

    Thirty adult albino rats (Rattus rattus) at 6 weeks of age were divided into three groups (ten for each). The first group was fed a standard laboratory diet for 8 weeks (control). The second group was made obese by giving them 32% sucrose solution in addition to the standard laboratory diet .The third group was received zinc supplementation (50 mg zinc acetate/ litre) with their sucrose solution. Body weight of all rats was measured weekly for 8 weeks. At 14 weeks of age, rats were killed and fasting blood samples were obtained. Serum glucose, insulin, cholesterol, triglyceride, leptin, tumour necrosis factor-α and zinc were measured.Results showed remarkable changes in body weights in sucrose fed rats only when compared to control and supplemented zinc rats group. Serum glucose, insulin, cholesterol and triglycerides were significantly increased in sucrose fed rats than both control and sucrose with zinc group. Serum leptin showed significant increase in sucrose fed rats than control and also showed higher significant value in sucrose fed rats supplemented with zinc comparing with sucrose fed rats and control ones. Tumour necrosis factor-? did not show any significant difference between all groups. Serum zinc concentration was decreased significantly in sucrose fed rats as compared to control. On the other hand, it was increased significantly in sucrose fed rats supplemented with zinc than other both groups. It could be concluded that zinc supplementation induced hyperleptinemia caused ameliorating effects in obese rats

  15. Zinc-induced protection against cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Early, J.L.; Schnell, R.C.

    1978-02-01

    Pretreatment of male rats with cadmium acetate potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic microsomal drug metabolism. Pretreatment of rats with zinc acetate protects against these alterations in drug action elicited by cadmium.

  16. Photoreactivation of ultraviolet radiation-induced pyrimidine dimers in neonatal BALB/c mouse skin

    International Nuclear Information System (INIS)

    Ananthaswamy, H.N.; Fisher, M.S.

    1981-01-01

    The numbers of ultraviolet light (uv)-induced pyrimidine dimers in the DNA of neonatal BALB/c mouse skin were measured by assessing the sensitivity of the DNA to Micrococcus luteus uv endonuclease. Irradiation of neonatal BALB/c mice with FS40 sunlamps caused a dose-dependent induction of endonuclease-sensitive sites (pyrimidine dimers) in DNA extracted from back skin. Exposure of these uv-irradiated neonatal mice to photoreactivating (PR) light (cool white fluorescent lamp and incandescent lamp) caused a reduction in the number of pyrimidine dimers in the DNA, as revealed by a shift in low-molecular-weight DNA to high-molecular-weight DNA. In contrast, DNA profiles of the skin of either uv-irradiated mice or uv-irradiated mice kept in the dark for the same duration as those exposed to PR light did not show a loss of uv-induced endonuclease-sensitive sites. Furthermore, reversing the order of treatment, i.e., administering PR light first and then uv, did not produce a reduction in pyrimidine dimers. These results demonstrate that PR or uv-induced pyrimidine dimers occurs in neonatal BALB/c mouse skin. The optimal wavelength range for in vivo PR appears to be in the visible region of the spectrum (greater than 400 nm). Although dimer formation could be detected in both dermis and epidermis, PR occurred only in the dermis. Furthermore, the PR phenomenon could not be detected in the skin of adult mice from the same inbred strain

  17. Antibody-induced dimerization activates the epidermal growth factor receptor tyrosine kinase

    NARCIS (Netherlands)

    Spaargaren, M.; Defize, L. H.; Boonstra, J.; de Laat, S. W.

    1991-01-01

    The relationship between epidermal growth factor receptor (EGF-R) protein tyrosine kinase activation and ligand-induced receptor dimerization was investigated using several bivalent anti-EGF-R antibodies directed against various receptor epitopes. In A431 membrane preparations and permeabilized

  18. Effect of serotonin on the yield of UV-induced thymine dimers in DNA

    International Nuclear Information System (INIS)

    Frajkin, G.Ya.; Strakhovskaya, M.G.; Ivanova, Eh.V.

    1985-01-01

    Using fluorescence method serotonin interaction with DNA is studied and bond constant Ksub(c)=4.2x10 4 M -1 is defined. It is shown that bound serotonin reduces yield of UV-induced thymine dimers. Value of efficient distance of protective serotonin effect constituting part of DNA chain of 4 base pairs, is determined

  19. DNA repair in B. subtilis: an inducible dimer-specific W-reactivation system

    International Nuclear Information System (INIS)

    Fields, P.I.; Yasbin, R.E.

    1982-01-01

    The W-reactivation system of Bacillus subtilis can repair pyrimidine dimers in bacteriophage DNA. This inducible repair system can be activated by treatment of the bacteria with uv, alkylating agents, cross-linking agents and gamma irradiation. However, bacteriophage treated with agents other than those that cause pyrimidine dimers to be produced was not repaired by this unique form of W-reactivation. In contrast, the W-reactivation system of Escherichia coli can repair a variety of damages placed in the bacteriophage DNA

  20. Preparation of gold nanoparticle dimers via streptavidin-induced interlinking

    International Nuclear Information System (INIS)

    Zon, Vera B.; Sachsenhauser, Matthias; Rant, Ulrich

    2013-01-01

    There is great interest in establishing efficient means of organizing nanoparticles into complex structures, especially in fields like nano-optical devices. One of the demonstrated routes uses biomolecular scaffolds, like the streptavidin–biotin system, to deterministically separate and structure particle complexes. However, controlled formation of streptavidin-linked nanoparticle dimers or trimers is challenging, and large aggregates are often formed under conditions that are difficult to regulate. Here, we studied the aggregates and interlinking kinetics of biotin-functionalized 20 nm gold nanoparticles in the presence of the interlinking protein, streptavidin. We found two different protein-linker concentration regions where small stable particle aggregates are formed: when the protein and nanoparticle concentrations are similar and when the protein to nanoparticle concentration ratio exceeds intermediate concentrations (10:1–100:1) that promote precipitation of large aggregates. We attribute this behavior to the limited availability of free-linker molecules and the limited availability of free ligand (biotin) on the particle surface for low and high protein concentrations, respectively. Furthermore, we show that the product can be additionally enriched up to 25 % through either centrifugation in sucrose or size-exclusion chromatography. These results provide additional understanding into the assembly of ligand-functionalized nanoparticles with water-soluble linkers and provide a facile way to produce well-defined small aggregates for potential use in, for instance, surface-enhanced spectroscopy

  1. Photoreactivation of UV-induced pyrimidine dimers and erythema in the marsupial Monodelphis domestica

    International Nuclear Information System (INIS)

    Ley, R.D.

    1985-01-01

    Post-UV treatment of the gray, short-tailed opossum Monodelphis domestica with photoreactivating light (320-400 nm) suppressed the appearance of UV-induced erythema as evidenced by an increase in the dose of UV required to elicit an erythemal response. Pre-UV exposure to photoreactivating light had no effect on the UV induction of erythema. The dose-response for the photoreversal of pyrimidine dimers in epidermal DNA of M. domestica was similar to that for the photoreactivation of erythema induction. These data not only support the notion that DNA is the primary chromophore involved in the induction of erythema but also identify pyrimidine dimers as the major DNA change responsible for its induction. These results also identify M. domestica as a useful whole-animal system with which to determine the role of pyrimidine dimers in other photobiological responses of mammalian skin

  2. UV light-induced cyclobutane pyrimidine dimers are mutagenic in mammalian cells

    International Nuclear Information System (INIS)

    Protic-Sabljic, M.; Tuteja, N.; Munson, P.J.; Hauser, J.; Kraemer, K.H.; Dixon, K.

    1986-01-01

    We used a simian virus 40-based shuttle vector plasmid, pZ189, to determine the role of pyrimidine cyclobutane dimers in UV light-induced mutagenesis in monkey cells. The vector DNA was UV irradiated and then introduced into monkey cells by transfection. After replication, vector DNA was recovered from the cells and tested for mutations in its supF suppressor tRNA marker gene by transformation of Escherichia coli carrying a nonsense mutation in the beta-galactosidase gene. When the irradiated vector was treated with E. coli photolyase prior to transfection, pyrimidine cyclobutane dimers were removed selectively. Removal of approximately 90% of the pyrimidine cyclobutane dimers increased the biological activity of the vector by 75% and reduced its mutation frequency by 80%. Sequence analysis of 72 mutants recovered indicated that there were significantly fewer tandem double-base changes and G X C----A X T transitions (particularly at CC sites) after photoreactivation of the DNA. UV-induced photoproducts remained (although at greatly reduced levels) at all pyr-pyr sites after photoreactivation, but there was a relative increase in photoproducts at CC and TC sites and a relative decrease at TT and CT sites, presumably due to a persistence of (6-4) photoproducts at some CC and TC sites. These observations are consistent with the fact that mutations were found after photoreactivation at many sites at which only cyclobutane dimers would be expected to occur. From these results we conclude that UV-induced pyrimidine cyclobutane dimers are mutagenic in DNA replicated in monkey cells

  3. Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.

    Science.gov (United States)

    Parekh, Chintan; Sahaghian, Arineh; Kim, William; Scholes, Jessica; Ge, Shundi; Zhu, Yuhua; Asgharzadeh, Shahab; Hollis, Roger; Kohn, Donald; Ji, Lingyun; Malvar, Jemily; Wang, Xiaoyan; Crooks, Gay

    2012-04-01

    The cytokine thrombopoietin (Tpo) plays a critical role in hematopoiesis by binding to the extracellular domain and inducing homodimerization of the intracellular signaling domain of its receptor, c-Mpl. Mpl homodimerization can also be accomplished by binding of a synthetic ligand to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. Unexpectedly, in contrast to Tpo stimulation, robust erythropoiesis is induced after dimerization of F36VMpl in human CD34+ progenitor cells. The goal of this study was to define the hematopoietic progenitor stages at which dimerization of intracellular Mpl induces erythropoiesis and the downstream molecular events that mediate this unanticipated effect. Dimerization (in the absence of erythropoietin and other cytokines) in human common myeloid progenitors and megakaryocytic erythroid progenitors caused a significant increase in CD34+ cells (p Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis through molecular mechanisms that are not shared by Tpo stimulation of endogenous Mpl. Copyright © 2012 AlphaMed Press.

  4. Far-UV-induced dimeric photoproducts in short oligonucleotides: sequence effects

    International Nuclear Information System (INIS)

    Douki, T.; Zalizniak, T.; Cadet, J.

    1997-01-01

    Cyclobutane pyrimidine dimers and pyrimidine (6-4)pyrimidone adducts represent the two major classes of far-UV-induced DNA photoproducts. Because of the lack of appropriate detection methods for each individual photoproduct, little is known about the effect of the sequence on their formaiton. In the present work, the photoproduct distribution obtained upon exposure of a series of dinucleoside monophosphate to 254 nm light was determined. (author)

  5. Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

    Science.gov (United States)

    Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

    2016-02-01

    ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

  6. Zinc

    Science.gov (United States)

    ... Some early research suggests that zinc supplementation increases sperm count, testosterone levels, and pregnancy rates in infertile men with low testosterone levels. Other research suggests that taking zinc can improve sperm shape in men with moderate enlargement of a ...

  7. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

    Directory of Open Access Journals (Sweden)

    Tine N Vinther

    Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

  8. Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.

    Science.gov (United States)

    Maini, Sabia; Fahlman, Brian M; Krol, Ed S

    2015-01-01

    Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  9. Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA

    International Nuclear Information System (INIS)

    Ley, R.D.

    1997-01-01

    Solar ultraviolet radiation (UVR) induces a number of pathologic conditions of mammalian skin including erythema, oedema, hyperplasia, sunburn cell formation and skin cancer. Consequently, UVR-induced DNA damage has been implicated as one of the photochemical events that results in the formation of these pathological changes. The ability of sunscreens to protect against UVR-induced DNA damage has not been well characterized especially with UVA (320-400 nm) wavelengths and UVA absorbers. In this paper we present results of a study aimed at determining the efficacy of two sunscreens at preventing the induction of pyrmidine dimers in basal cell DNA of mice exposed to solar-simulated UVR (SSUV) wavelengths (290-400 nm) or to UVA (320-400 nm). (author)

  10. Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA

    Energy Technology Data Exchange (ETDEWEB)

    Ley, R.D. [The Lovelace Institutes, Albuqeurque, NM (United States). Photomdecine Program; Fourtanier, A. [L`Oreal, Advanced Research, Clichy (France)

    1997-06-01

    Solar ultraviolet radiation (UVR) induces a number of pathologic conditions of mammalian skin including erythema, oedema, hyperplasia, sunburn cell formation and skin cancer. Consequently, UVR-induced DNA damage has been implicated as one of the photochemical events that results in the formation of these pathological changes. The ability of sunscreens to protect against UVR-induced DNA damage has not been well characterized especially with UVA (320-400 nm) wavelengths and UVA absorbers. In this paper we present results of a study aimed at determining the efficacy of two sunscreens at preventing the induction of pyrmidine dimers in basal cell DNA of mice exposed to solar-simulated UVR (SSUV) wavelengths (290-400 nm) or to UVA (320-400 nm). (author).

  11. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

    Energy Technology Data Exchange (ETDEWEB)

    Que, Emily L.; Bleher, Reiner; Duncan, Francesca E.; Kong, Betty Y.; Gleber, Sophie C.; Vogt, Stefan; Chen, Si; Garwin, Seth A.; Bayer, Amanda R.; Dravid, Vinayak P.; Woodruff, Teresa K.; O' Halloran, Thomas V.

    2014-12-15

    Fertilization of a mammalian egg initiates a series of 'zinc sparks' that are necessary to induce the egg-to-embryo transition. Despite the importance of these zinc-efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches that resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy-dispersive spectroscopy, X-ray fluorescence microscopy and three-dimensional elemental tomography for high-resolution elemental mapping. We show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each of which contains, on average, 10(6) zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. The discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes

  12. Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization.

    Science.gov (United States)

    Xu, Tao; Johnson, Cole A; Gestwicki, Jason E; Kumar, Anuj

    2010-11-01

    We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. One chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localization signal or nuclear export sequence). The second chimera consists of a target protein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapamycin associated protein 1 (FRAP1, also known as mTor). Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss-of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment.

  13. Changing POU dimerization preferences converts Oct6 into a pluripotency inducer.

    Science.gov (United States)

    Jerabek, Stepan; Ng, Calista Kl; Wu, Guangming; Arauzo-Bravo, Marcos J; Kim, Kee-Pyo; Esch, Daniel; Malik, Vikas; Chen, Yanpu; Velychko, Sergiy; MacCarthy, Caitlin M; Yang, Xiaoxiao; Cojocaru, Vlad; Schöler, Hans R; Jauch, Ralf

    2017-02-01

    The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  14. Carbon Monoxide (CO Released from Tricarbonyldichlororuthenium (II Dimer (CORM-2 in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

    Directory of Open Access Journals (Sweden)

    Katarzyna Magierowska

    Full Text Available The physiological gaseous molecule, carbon monoxide (CO becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II dimer (CORM-2 in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1 non-selective (indomethacin or selective cyclooxygenase (COX-1 (SC-560 and COX-2 (celecoxib inhibitors, 2 nitric oxide (NO synthase inhibitor L-NNA, 3 ODQ, a soluble guanylyl cyclase (sGC inhibitor, hemin, a heme oxygenase (HO-1 inductor or zinc protoporphyrin IX (ZnPPIX, an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g. significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric

  15. Pyrimidine dimers are not the principal pre-mutagenic lesions induced in lambda phage DNA by ultraviolet light

    International Nuclear Information System (INIS)

    Wood, R.D.

    1985-01-01

    Experiments were performed to examine the role of cyclobutyl pyrimidine dimers in the process of mutagenesis by ultraviolet light. Lambda phage DNA was irradiated with u.v. and then incubated with an Escherichia coli photoreactivating enzyme, which monomerizes cyclobutyl pyrimidine dimers upon exposure to visible light. The photoreactivated DNA was packaged into lambda phage particles, which were used to infect E. coli uvr - host cells that had been induced for SOS functions by ultraviolet irradiation. Photoreactivation removed most toxic lesions from irradiated phage, but did not change the frequency of induction of mutations to the clear-plaque phenotype. This implies that cyclobutyl pyrimidine dimers can be lethal, but usually do not serve as sites of mutations in the phage. The DNA sequences of mutants, derived from photoreactivated DNA showed that almost two-thirds (16/28) were transitions, the same fraction found for u.v. mutagenesis without photoreactivation. Thus the lesion inducing transitions is not the cyclobutyl pyrimidine dimer. Photoreactivation of SOS-induced host cells before infection with u.v.-irradiated phage reduced mutagenesis substantially. In this case, photoreversal of cyclobutyl dimers serves to reduce expression of the SOS functions that are required in targeted u.v. mutagenesis. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    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 of 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 zinc finger

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

    International Nuclear Information System (INIS)

    Sun, Xi; Zhou, Xixi; Du, Libo; Liu, Wenlan; Liu, Yang; Hudson, Laurie G.; Liu, Ke Jian

    2014-01-01

    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 of 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 zinc finger

  18. Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells.

    Science.gov (United States)

    Daaboul, Doha; Rosenkranz, Eva; Uciechowski, Peter; Rink, Lothar

    2012-10-01

    Mild zinc deficiency in humans negatively affects IL-2 production resulting in declined percentages of cytolytic T cells and decreased NK cell lytic activity, which enhances the susceptibility to infections and malignancies. T-cell activation is critically regulated by zinc and the normal physiological zinc level in T-cells slightly lies below the optimal concentration for T-cell functions. A further reduction in zinc level leads to T-cell dysfunction and autoreactivity, whereas high zinc concentrations (100 μM) were shown to inhibit interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this study, we investigated the molecular mechanism by which zinc regulates the IL-1β-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient T-cells increased intracellular zinc levels by altering the expression of zinc transporters, particularly Zip10 and Zip12. A zinc signal was observed in the murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1β, measured by specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the phosphorylation of MAPK p38 and NF-κB subunit p65, which triggers the transcription of IL-2 and strongly increases its production. These results indicate that short-term zinc supplementation to zinc-deficient T-cells leads to a fast rise in zinc levels which subsequently enhance cytokine production. In conclusion, low and excessive zinc levels might be equally problematic for zinc-deficient subjects, and stabilized zinc levels seem to be essential to avoid negative concentration-dependent zinc effects on T-cell activation.

  19. Electron transfer reactions induced by the triplet state of thiacarbocyanine dimers

    International Nuclear Information System (INIS)

    Chibisov, Alexander K.; Slavnova, Tatyana D.; Goerner, Helmut

    2004-01-01

    The photoinduced electron transfer between either cationic 5,5 ' -dichloro-3,3 ' ,9-triethylthiacarbocyanine (1) or a structurally similar anionic dye (2) and appropriate donors, e.g. ascorbic acid, and acceptors, e.g. methyl viologen, was studied by ns-laser photolysis. In aqueous solution the dyes in the ground state are present as an equilibrated mixture of dimers and monomers, whereas the triplet state is mainly populated from dimers. The triplet states of both dimers and monomers are quenched by electron donors or acceptors and the rate constant for quenching is generally 2-4 times higher for dimers than for monomers. The kinetics of triplet decay and radical formation and decay as a result of primary and secondary electron transfer were analyzed. While the one-electron reduced dimer decays due to back reactions, the one-electron oxidized dimer rapidly dissociates into the monomer and the monomeric dye radical. For the dimeric dye/donor/acceptor systems the primary photoinduced electron transfer occurs either from the donor or to the acceptor yielding the dimeric dye radicals. The one-electron reduced dimer can be efficiently oxidized by acceptors, e.g. the rate constant for reaction of the dimeric dye radical of 1 with methyl viologen (photoreductive pathway of sensitization) is 1.6x10 9 M -1 s -1 . The photooxidative pathway of sensitization is more complicated; after dissociation of the dimeric dye radical, the monomeric dye radical is reduced in a secondary electron transfer from ascorbic acid, e.g. with a rate constant of 1x10 9 M -1 s -1 for 2, yielding the monomer. On increasing the donor concentration the photooxidative pathway of sensitization is switched to a photoreductive one

  20. Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

    Directory of Open Access Journals (Sweden)

    Dokter Wim

    2010-06-01

    Full Text Available Abstract Background Glucocorticoids (GCs control expression of a large number of genes via binding to the GC receptor (GR. Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT and mice that have lost the ability to form GR dimers (GRdim. Results The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions This study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

  1. Radiation induced structural changes in alpha-copper-zinc alloys

    International Nuclear Information System (INIS)

    Schuele, W.; Gieb, M.

    1991-01-01

    During irradiation of alpha-copper-zinc alloys with high energy electrons and protons a decrease of the electrical resistivity due to an increase of the degree of short range order is observed through radiation enhanced diffusion followed by an increase of the electrical resistivity through the formation of radiation induced interstitial clusters. The initial formation rate of interstitial clusters increases about linearly with the displacement rate for electron and proton irradiation. The largest initial formation rate is found between 60 and 130 0 C becoming negligibly small above 158 0 C and decreases drastically below 60 0 C. The dynamic steady state interstitial cluster concentration increases with decreasing irradiation temperature in the investigated temperature range between 158 and 40 0 C. Above 158 0 C the formation rate of interstitial clusters is negligibly small. Thus the transition temperature for radiation induced interstitial cluster formation is 158 0 C, depending mainly on the migration activation energy of vacancies. The radiation induced interstitial clusters are precipitates in those alloys in which the diffusion rate of the undersized component atoms via an interstitialcy diffusion mechanism is larger than that of the other atoms

  2. Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.

    Science.gov (United States)

    Chou, Susan S; Clegg, Michael S; Momma, Tony Y; Niles, Brad J; Duffy, Jodie Y; Daston, George P; Keen, Carl L

    2004-10-01

    Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

  3. Substrate-Induced Dimerization of Engineered Monomeric Variants of Triosephosphate Isomerase from Trichomonas vaginalis.

    Directory of Open Access Journals (Sweden)

    Samuel Lara-Gonzalez

    Full Text Available The dimeric nature of triosephosphate isomerases (TIMs is maintained by an extensive surface area interface of more than 1600 Å2. TIMs from Trichomonas vaginalis (TvTIM are held in their dimeric state by two mechanisms: a ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.

  4. Allergic contact dermatitis induced by zinc pyrithione in shampoo: a case report

    Directory of Open Access Journals (Sweden)

    Chih-Wei Hsieh

    2010-12-01

    Full Text Available Shampoo-induced allergic contact dermatitis is difficult to diagnose clinically because it can involve multiple and variable areas where the shampoo flows. Zinc pyrithione is a common active agent in medicated shampoo that is known to have good anti-dandruff and antifungal effects. Despite its low risk of sensitization, cases of allergic contact dermatitis still occur because of the popularity of such products. We report a 33-year-old man who developed pruritic rash on his scalp, face, neck, and hands after using a new shampoo containing zinc pyrithione. A patch test revealed a positive reaction to zinc pyrithione and personal shampoo containing zinc pyrithione.

  5. Colchicine induced intraneuronal free zinc accumulation and dentate granule cell degeneration.

    Science.gov (United States)

    Choi, Bo Young; Lee, Bo Eun; Kim, Jin Hee; Kim, Hyun Jung; Sohn, Min; Song, Hong Ki; Chung, Tae Nyoung; Suh, Sang Won

    2014-08-01

    Colchicine has been discovered to inhibit many inflammatory processes such as gout, familial Mediterranean fever, pericarditis and Behcet disease. Other than these beneficial anti-inflammatory effects, colchicine blocks microtubule-assisted axonal transport, which results in the selective loss of dentate granule cells of the hippocampus. The mechanism of the colchicine-induced dentate granule cell death and depletion of mossy fiber terminals still remains unclear. In the present study, we hypothesized that colchicine-induced dentate granule cell death may be caused by accumulation of labile intracellular zinc. 10 μg kg(-1) of colchicine was injected into the adult rat hippocampus and then brain sections were evaluated at 1 day or 1 week later. Neuronal cell death was evaluated by H&E staining or Fluoro-Jade B. Zinc accumulation and vesicular zinc were detected by N-(6-methoxy-8-quinolyl)-para-toluene sulfonamide (TSQ) staining. To test whether an extracellular zinc chelator can prevent this process, CaEDTA was injected into the hippocampus over a 5 min period with colchicine. To test whether other microtubule toxins also produce similar effects as colchicine, vincristine was injected into the hippocampus. The present study found that colchicine injection induced intracellular zinc accumulation in the dentate granule cells and depleted vesicular zinc from mossy fiber terminals. Injection of a zinc chelator, CaEDTA, did not block the zinc accumulation and neuronal death. Vincristine also produced intracellular zinc accumulation and neuronal death. These results suggest that colchicine-induced dentate granule cell death is caused by blocking axonal zinc flow and accumulation of intracellular labile zinc.

  6. Photorepair and excision repair removal of UV-induced pyrimidine dimers and (6-4) photoproducts in the tail fin of the Medaka, Oryzias latipes

    International Nuclear Information System (INIS)

    Funayama, Tomoo; Mitani, Hiroshi; Shima, Akihiro; Ishigaki, Yasuhito; Matsunaga, Tsukasa; Nikaido, Osamu.

    1994-01-01

    Induction and repair of UV-B induced DNA damage in the tail fin of the Medaka, were examined immunohistochemically and by the enzyme-linked immunosorbent assay (ELISA). UV-induced DNA damage was detected only in the outermost layer of epithelial cells and did not differ in fishes having different degree of melanization. Both pyrimidine dimers and (6-4) photoproducts in the fin cells were removed by excision repair in the dark, the excision of (6-4) photoproducts being about twice as efficient as that of pyrimidine dimers. The rate of excision repair of UV-induced lesions in fin tissue was three to four times that in cultured Medaka cells, OL32.. In the fin cells, reductions in the numbers of pyrimidine dimers and (6-4) photoproducts were seen after treatment with fluorescent light, whereas less reductions of pyrimidine dimers and no reductions of (6-4) photoproducts were observed in OL32 cells. (author)

  7. Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+

    Directory of Open Access Journals (Sweden)

    Nigou Jérôme

    2007-08-01

    Full Text Available Abstract Background The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase. Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. Results We determined the crystal structure, to 2.6 Å resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. Conclusion The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.

  8. Zinc-induced Self-association of Complement C3b and Factor H

    Science.gov (United States)

    Nan, Ruodan; Tetchner, Stuart; Rodriguez, Elizabeth; Pao, Po-Jung; Gor, Jayesh; Lengyel, Imre; Perkins, Stephen J.

    2013-01-01

    The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100 μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions showed that putative weak zinc binding sites with different capacities exist in all five proteins, in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much reduced at 60 μm zinc and even more so at >100 μm zinc. The removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc. Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment epithelial deposits in the retina as well as reducing the progression to advanced age-related macular degeneration in higher risk patients. PMID:23661701

  9. Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

    International Nuclear Information System (INIS)

    Masek, F.; Sedliakova, M.

    1978-01-01

    The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm 2 and at different time intervals with a second fluence of 500 ergs/mm 2 . After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr + and E.coli 15 555-7, but not in E.coli K12 SR20. (author)

  10. Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Masek, F; Sedliakova, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

    1978-11-15

    The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm/sup 2/ and at different time intervals with a second fluence of 500 ergs/mm/sup 2/. After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr/sup +/ and E.coli 15 555-7, but not in E.coli K12 SR20.

  11. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  12. Curcumin Attenuates Hepatotoxicity Induced by Zinc Oxide Nanoparticles in Rats

    Directory of Open Access Journals (Sweden)

    Layasadat Khorsandi

    2016-06-01

    Full Text Available Background: Zinc oxide nanoparticles (NZnO are increasingly used in modern life. Most metal nanoparticles have adverse effects on the liver. Aims: To explore the protective action of curcumin (Cur against hepatotoxicity induced by NZnO in rats. Study Design: Animal experimentation. Methods: Control group animals received normal saline, while the Cur group animals were treated with 200 mg/kg of Cur orally for 21 days. NZnO-intoxicated rats received 50 mg/kg of NZnO for 14 days by gavage method. In the NZnO+Cur group, rats were pretreated with Cur for 7 days before NZnO administration. Plasma activities of Alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP were measured as biomarkers of hepatotoxicity. Hepatic levels of malondialdehyde (MDA and superoxide dismutase (SOD and glutathione peroxidase (GPx activities were measured for detection of oxidative stress in liver tissue. Histological changes and apoptosis in liver tissue were studied by using Hematoxylin-eosin staining and the transferase dUTP nick end labeling (TUNEL method. Results: NZnO induced a significant increase in plasma AST (2.8-fold, ALT (2.7-fold and ALP (1.97-fold activity in comparison to the control group (p<0.01. NZnO increased MDA content and reduced SOD and GPx activities. NZnO caused liver damage including centrilobular necrosis and microvesicular steatosis. The percentage of apoptosis in hepatocytes was increased in NZnO-treated rats (p<0.01. Pre-treatment of Cur significantly reduced lipid peroxidation (39%, increased SOD (156% and GPx (26% activities, and attenuated ALT (47%, AST (41% and ALP (30% activities. Pre-treatment with Cur also decreased the histology changes and apoptotic index of hepatocytes (p<0.05. Conclusion: These findings indicate that Cur effectively protects against NZnO-induced hepatotoxicity in rats. However, future studies are required to propose Cur as a potential protective agent against hepatotoxicity

  13. Dissociative electron attachment and anion-induced dimerization in pyruvic acid

    Czech Academy of Sciences Publication Activity Database

    Zawadzki, Mateusz; Ranković, Miloš; Kočišek, Jaroslav; Fedor, Juraj

    2018-01-01

    Roč. 20, č. 10 (2018), s. 6838-6844 ISSN 1463-9076 R&D Projects: GA ČR GA17-04844S; GA ČR GJ16-10995Y Institutional support: RVO:61388955 Keywords : pyruvic acid * electron attachment * dimerization Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.123, year: 2016

  14. Radiation-induced tetramer-to-dimer transition of Esterichia coli lactose repressor

    Czech Academy of Sciences Publication Activity Database

    Goffinont, S.; Davídková, Marie; Spotheim-Maurizot, M.

    2009-01-01

    Roč. 386, č. 2 (2009), s. 300-304 ISSN 0006-291X R&D Projects: GA MŠk OC09012 Institutional research plan: CEZ:AV0Z10480505 Keywords : protein * DNA * radiation * oxidation * tetramer * dimer * lactose repressor Subject RIV: BO - Biophysics Impact factor: 2.548, year: 2009

  15. Distance within colloidal dimers probed by rotation-induced oscillations of scattered light

    NARCIS (Netherlands)

    van Vliembergen, R.W.L.; van IJzendoorn, L.J.; Prins, M.W.J.

    2016-01-01

    Aggregation processes of colloidal particles are of broad scientific and technological relevance. The earliest stage of aggregation, when dimers appear in an ensemble of single particles, is very important to characterize because it opens routes for further aggregation processes. Furthermore, it

  16. Chromium, Nickel and Zinc Induced Histopathological Alterations in ...

    African Journals Online (AJOL)

    Michael Horsfall

    fish, Labeo rohita to chlorides of chromium, nickel and zinc for 30 days. However ... toxicants such as salts of heavy metals, acids, organic matter ... nutritional supply becomes excessive. ... action), petrochemicals, and fertilizers and in steam.

  17. Radiation induced traps of zinc phosphate and phosphide

    International Nuclear Information System (INIS)

    Murali, K.R.; Rao, D.R.

    1980-01-01

    Thermoluminescence (TL) glow curve (TGC) method has been used to study the traps produced by X-irradiation in Zn 3 (PO 4 ) 2 and Zn 3 P 2 . Prominent TL glow peaks were observed at 100 0 and 360 0 C for zinc phosphate while for zinc phosphide only one glow peak at 245 0 C was observed, and in the latter case the TL output was in general quite low compared to zinc phosphate. The TL spectra for both the glow peaks of zinc phosphate indicated emission band in the region around 560 nm, while for zinc phosphide the emission occurred at 575 nm (in the temperature region 200-270 0 C). The low temperature glow peaks below 270 0 C were less stable compared to those above 300 0 C and were completely destroyed when the irradiated samples were stored in darkness for 24 hr at room temperature. Shining by 470 nm light however produced preferential bleaching of the two TL peaks at 100 and 360 0 C with no effect on the 245 0 C glow peak of zinc phosphide. It is concluded that during heat treatment large numbers of Zn-vacancies are formed due to which complexes like Zn-P are produced by irradiation and the TL traps destroyed in a radiative recombination process are related with these complexes. (author)

  18. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

    Science.gov (United States)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (Ptaurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (PTaurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (Ptaurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    International Nuclear Information System (INIS)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-01-01

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn 2+ and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase + was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights:

  20. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui, E-mail: Donghuixu007@163.com

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights:

  1. Hydrodynamic interactions induce movement against an external load in a ratchet dimer Brownian motor.

    Science.gov (United States)

    Fornés, José A

    2010-01-15

    We use the Brownian dynamics with hydrodynamic interactions simulation in order to describe the movement of a elastically coupled dimer Brownian motor in a ratchet potential. The only external forces considered in our system were the load, the random thermal noise and an unbiased thermal fluctuation. For a given set of parameters we observe direct movement against the load force if hydrodynamic interactions were considered.

  2. Apoptosis induced by pyrimidine dimer produced by ultraviolet irradiation in cultured cyprinodont cells. Analysis utilizing the evasion from photolysis

    International Nuclear Information System (INIS)

    Nishigaki, Reiko

    2000-01-01

    This is the review of author's investigations on the mechanism of apoptosis induced by UV irradiation in cultured cyprinodont cells highly expressing photolyases of cyclobutane pyrimidine dimer (CPD). Authors found out the evasion from photolysis by UV-induced apoptosis of which cascade had been thought irreversible: the cascade was reversible until the process of DNA fragmentation. In controlling the process, a mechanism to recognize CPD was found concerned. In those cells, morphological changes by UVC were reversible ones in apoptosis from which they evaded if CPD was repaired. Investigations on caspase, which playing important roles in apoptosis, revealed that the DEVD-cleaving enzyme activities were regulated by CPD quantity. However, differing from mammalian cells, elevation of caspase (-7, -3A and -3B) activities did not always induce the morphologic changes and DNA fragmentation. Further studies were thought necessary to elucidate the mechanism of apoptosis in those fish cells. (K.H.)

  3. Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4+, molecular crowding environment and jatrorrhizine derivatives.

    Science.gov (United States)

    Tan, Wei; Yi, Long; Zhu, Zhentao; Zhang, Lulu; Zhou, Jiang; Yuan, Gu

    2018-03-01

    A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K + , Na + and low concentration of NH 4 + (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH 4 + (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces. Specifically, two synthesized jatrorrhizine derivatives with terminal amine groups could also induce the dimerization of miR-1587 G-quadruplex and formed 1:1 and 2:1 complexes with the dimeric G-quadruplex. In contrast, jatrorrhizine could bind with the dimeric miR-1587 G-quadruplex, but could not induce dimerization of miR-1587 G-quadruplex. These results provide a new strategy to regulate the functions of miR-1587 through induction of G-quadruplex formation and dimerization. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila

    Directory of Open Access Journals (Sweden)

    Krisztina Hegedűs

    2014-01-01

    Full Text Available The large-scale turnover of intracellular material including organelles is achieved by autophagy-mediated degradation in lysosomes. Initiation of autophagy is controlled by a protein kinase complex consisting of an Atg1-family kinase, Atg13, FIP200/Atg17, and the metazoan-specific subunit Atg101. Here we show that loss of Atg101 impairs both starvation-induced and basal autophagy in Drosophila. This leads to accumulation of protein aggregates containing the selective autophagy cargo ref(2P/p62. Mapping experiments suggest that Atg101 binds to the N-terminal HORMA domain of Atg13 and may also interact with two unstructured regions of Atg1. Another HORMA domain-containing protein, Mad2, forms a conformational homodimer. We show that Drosophila Atg101 also dimerizes, and it is predicted to fold into a HORMA domain. Atg101 interacts with ref(2P as well, similar to Atg13, Atg8a, Atg16, Atg18, Keap1, and RagC, a known regulator of Tor kinase which coordinates cell growth and autophagy. These results raise the possibility that the interactions and dimerization of the putative HORMA domain protein Atg101 play critical roles in starvation-induced autophagy and proteostasis, by promoting the formation of protein aggregate-containing autophagosomes.

  5. Relativity-Induced Bonding Pattern Change in Coinage Metal Dimers M2 (M = Cu, Ag, Au, Rg).

    Science.gov (United States)

    Li, Wan-Lu; Lu, Jun-Bo; Wang, Zhen-Ling; Hu, Han-Shi; Li, Jun

    2018-05-07

    The periodic table provides a fundamental protocol for qualitatively classifying and predicting chemical properties based on periodicity. While the periodic law of chemical elements had already been rationalized within the framework of the nonrelativistic description of chemistry with quantum mechanics, this law was later known to be affected significantly by relativity. We here report a systematic theoretical study on the chemical bonding pattern change in the coinage metal dimers (Cu 2 , Ag 2 , Au 2 , Rg 2 ) due to the relativistic effect on the superheavy elements. Unlike the lighter congeners basically demonstrating ns- ns bonding character and a 0 g + ground state, Rg 2 shows unique 6d-6d bonding induced by strong relativity. Because of relativistic spin-orbit (SO) coupling effect in Rg 2 , two nearly degenerate SO states, 0 g + and 2 u , exist as candidate of the ground state. This relativity-induced change of bonding mechanism gives rise to various unique alteration of chemical properties compared with the lighter dimers, including higher intrinsic bond energy, force constant, and nuclear shielding. Our work thus provides a rather simple but clear-cut example, where the chemical bonding picture is significantly changed by relativistic effect, demonstrating the modified periodic law in heavy-element chemistry.

  6. Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells

    International Nuclear Information System (INIS)

    Chung, Hyewon; Yoon, Young Hee; Hwang, Jung Jin; Cho, Kyung Sook; Koh, Jae Young; Kim, June-Gone

    2009-01-01

    Ethambutol, an efficacious antituberculosis agent, can cause irreversible visual loss in a small but significant fraction of patients. However, the mechanism of ocular toxicity remains to be established. We previously reported that ethambutol caused severe vacuole formation in cultured retinal cells, and that the addition of zinc along with ethambutol aggravated vacuole formation whereas addition of the cell-permeable zinc chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), reduced vacuole formation. To investigate the origin of vacuoles and to obtain an understanding of drug toxicity, we used cultured primary retinal cells from newborn Sprague-Dawley rats and imaged ethambutol-treated cells stained with FluoZin-3, zinc-specific fluorescent dye, under a confocal microscope. Almost all ethambutol-induced vacuoles contained high levels of labile zinc. Double staining with LysoTracker or MitoTracker revealed that almost all zinc-containing vacuoles were lysosomes and not mitochondria. Intracellular zinc chelation with TPEN markedly blocked both vacuole formation and zinc accumulation in the vacuole. Immunocytochemistry with antibodies to lysosomal-associated membrane protein-2 (LAMP-2) and cathepsin D, an acid lysosomal hydrolase, disclosed lysosomal activation after exposure to ethambutol. Immunoblotting after 12 h exposure to ethambutol showed that cathepsin D was released into the cytosol. In addition, cathepsin inhibitors attenuated retinal cell toxicity induced by ethambutol. This is consistent with characteristics of lysosomal membrane permeabilization (LMP). TPEN also inhibited both lysosomal activation and LMP. Thus, accumulation of zinc in lysosomes, and eventual LMP, may be a key mechanism of ethambutol-induced retinal cell death

  7. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Science.gov (United States)

    Bunnell, Bryan E; Escobar, Jillian F; Bair, Kirsten L; Sutton, Mark D; Crane, John K

    2017-01-01

    Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  8. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Bryan E Bunnell

    Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  9. Fluorescent zinc sensor with minimized proton-induced interferences: photophysical mechanism for fluorescence turn-on response and detection of endogenous free zinc ions.

    Science.gov (United States)

    Kwon, Ji Eon; Lee, Sumin; You, Youngmin; Baek, Kyung-Hwa; Ohkubo, Kei; Cho, Jaeheung; Fukuzumi, Shunichi; Shin, Injae; Park, Soo Young; Nam, Wonwoo

    2012-08-20

    A new fluorescent zinc sensor (HNBO-DPA) consisting of 2-(2'-hydroxy-3'-naphthyl)benzoxazole (HNBO) chromophore and a di(2-picolyl)amine (DPA) metal chelator has been prepared and examined for zinc bioimaging. The probe exhibits zinc-induced fluorescence turn-on without any spectral shifts. Its crystal structure reveals that HNBO-DPA binds a zinc ion in a pentacoordinative fashion through the DPA and HNBO moieties. Steady-state photophysical studies establish zinc-induced deprotonation of the HNBO group. Nanosecond and femtosecond laser flash photolysis and electrochemical measurements provide evidence for zinc-induced modulation of photoinduced electron transfer (PeT) from DPA to HNBO. Thus, the zinc-responsive fluorescence turn-on is attributed to suppression of PeT exerted by deprotonation of HNBO and occupation of the electron pair of DPA, a conclusion that is further supported by density functional theory and time-dependent density functional theory (DFT/TD-DFT) calculations. Under physiological conditions (pH 7.0), the probe displays a 44-fold fluorescence turn-on in response to zinc ions with a K(d) value of 12 pM. The fluorescent response of the probe to zinc ions is conserved over a broad pH range with its excellent selectivity for zinc ions among biologically relevant metal ions. In particular, its sensing ability is not altered by divalent transition metal ions such as Fe(II), Cu(II), Cd(II), and Hg(II). Cell experiments using HNBO-DPA show its suitability for monitoring intracellular zinc ions. We have also demonstrated applicability of the probe to visualize intact zinc ions released from cells that undergo apoptosis. More interestingly, zinc-rich pools in zebrafish embryos are traced with HNBO-DPA during early developmental stages. The results obtained from the in vitro and in vivo imaging studies demonstrate the practical usefulness of the probe to detect zinc ions.

  10. Surface damage in cystine, an amino acid dimer, induced by keV ions.

    Science.gov (United States)

    Salles, R C M; Coutinho, L H; da Veiga, A G; Sant'Anna, M M; de Souza, G G B

    2018-01-28

    We have studied the interaction of an ion beam (17.6 keV F - ) with cystine, a dimer formed by the binding of two cysteine residues. Cystine can be considered as an ideal prototype for the study of the relevance of the disulfide (-S-S-) chemical bond in biomolecules. For the sake of comparison, the amino acid cysteine has also been subjected to the same experimental conditions. Characterization of the samples by XPS and NEXAFS shows that both pristine cystine and pristine cysteine are found as a dipolar ion (zwitterion). Following irradiation, the dimer and the amino acid show a tendency to change from the dipole ion form to the normal uncharged form. The largest spectral modification was observed in the high resolution XPS spectra obtained at around the N 1s core level for the two biomolecules. The 2p sulfur edge spectra of cysteine and cystine were much less sensitive to radiation effects. We suggest that the disulfide bond (-S-S-) remains stable before and after irradiation, contributing to the larger radiation stability of cystine as compared to the amino acid cysteine.

  11. Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.

    Directory of Open Access Journals (Sweden)

    Martin Zühlsdorf

    2015-07-01

    Full Text Available Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 Å, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino-acid residues encompassing two consecutive arginine residues (Arg136 and Arg137; both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 Å, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration-dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration-dependent equilibrium of monomeric and dimeric protease in solution.

  12. Shock-induced fast reactions of zinc nanoparticles and RDX

    Energy Technology Data Exchange (ETDEWEB)

    Xue Mian; Wu Jinghe; Ye Song; Yang Xiangdong [Institute of Atomic and Molecular Physics, Sichuan University, Chengdu 610065 (China); Hu Dong; Wang Yanping; Zhu Wenjun; Li Chengbing [National Key Laboratory for Shock Wave and Detonation Physics Research, Institute of Fluid Physics, CAEP, Mianyang 621900 (China)], E-mail: mi-anxue@163.com

    2008-02-21

    Fast reactions of zinc nanoparticles and RDX were investigated in normal incident shock waves. The emergence time and emission spectra intensity of partial products such as NO{sub 2}, H, C{sub 2}, O, CO, CH{sub 2}O, CO{sub 2}, H{sub 2}O and ZnO were observed by a TDS5054 oscilloscope. The results indicate that NO{sub 2} appears first in each experiment, which is in agreement with the theoretical results. The addition of zinc nanoparticles to RDX can not only shorten the ignition delay time by 20% but also double the shockwave diffusion velocity to 2180 {+-} 50 m s{sup -1} and triple the temperature to 2020 {+-} 60 K. The emergence time of products shortens by around 10-40% and the emission spectra intensity of H{sub 2}O and CH{sub 2}O rises by about three times and one times, respectively. CO{sub 2}, H{sub 2}O and O{sub 2} in various concentrations were introduced into the zinc-RDX reaction, respectively, which indicate that O{sub 2} made the ignition delay time shorten by over 30%, the effect of H{sub 2}O was not prominent while CO{sub 2} made the ignition delay time lag by around 30%. The results indicate that the Zn-O{sub 2} reaction mainly occurs in O{sub 2}, CO{sub 2} and H{sub 2}O.

  13. Shock-induced fast reactions of zinc nanoparticles and RDX

    International Nuclear Information System (INIS)

    Xue Mian; Wu Jinghe; Ye Song; Yang Xiangdong; Hu Dong; Wang Yanping; Zhu Wenjun; Li Chengbing

    2008-01-01

    Fast reactions of zinc nanoparticles and RDX were investigated in normal incident shock waves. The emergence time and emission spectra intensity of partial products such as NO 2 , H, C 2 , O, CO, CH 2 O, CO 2 , H 2 O and ZnO were observed by a TDS5054 oscilloscope. The results indicate that NO 2 appears first in each experiment, which is in agreement with the theoretical results. The addition of zinc nanoparticles to RDX can not only shorten the ignition delay time by 20% but also double the shockwave diffusion velocity to 2180 ± 50 m s -1 and triple the temperature to 2020 ± 60 K. The emergence time of products shortens by around 10-40% and the emission spectra intensity of H 2 O and CH 2 O rises by about three times and one times, respectively. CO 2 , H 2 O and O 2 in various concentrations were introduced into the zinc-RDX reaction, respectively, which indicate that O 2 made the ignition delay time shorten by over 30%, the effect of H 2 O was not prominent while CO 2 made the ignition delay time lag by around 30%. The results indicate that the Zn-O 2 reaction mainly occurs in O 2 , CO 2 and H 2 O

  14. Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice.

    Science.gov (United States)

    Shi, Fang; Sheng, Qin; Xu, Xinhua; Huang, Wenli; Kang, Y James

    2015-09-01

    Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model, in which the activation of collagenases is involved in the regression of liver fibrosis. MT plays a critical role in zinc sequestration in the liver suggesting its therapeutic effect would be mediated by zinc. The present study was undertaken to test the hypothesis that zinc supplementation suppresses liver fibrosis. Male Kunming mice subjected to bile duct ligation (BDL) resulted in liver fibrosis as assessed by increased α-smooth muscle actin (α-SMA) and collagen I production/deposition in the liver. Zinc supplementation was introduced 4 weeks after BDL surgery via intragastric administration once daily for 2 weeks resulting in a significant reduction in the collagen deposition in the liver and an increase in the survival rate. Furthermore, zinc suppressed gene expression of α-SMA and collagen I and enhanced the capacity of collagen degradation, as determined by the increased activity of total collagenases and elevated mRNA and protein levels of MMP13. Therefore, the results demonstrate that zinc supplementation suppresses BDL-induced liver fibrosis through both inhibiting collagen production and enhancing collagen degradation. © 2014 by the Society for Experimental Biology and Medicine.

  15. Water-induced adsorption of carbon monoxide and oxygen on the gold dimer cation.

    Science.gov (United States)

    Ito, Tomonori; Patwari, G Naresh; Arakawa, Masashi; Terasaki, Akira

    2014-09-18

    It is demonstrated, using tandem mass spectrometry and ion trap, that preadsorption of a H2O molecule on the gold dimer cation, Au2(+), enhances adsorption of CO and O2 molecules, which is otherwise inert toward these molecules. The rate of adsorption of CO on Au2(H2O)(+) was found to be higher by 2 orders of magnitude relative to bare Au2(+). The enhancement of the CO adsorption rate is due to the presence of a reaction channel, which cleaves the Au-Au bond, leading to the formation of Au(H2O)(CO)(+). Such an observation can be attributed to weakening of the Au-Au bond upon adsorption of a water molecule. Further, it was also observed that preadsorption of H2O leads to dramatic enhancement of O2 adsorption on the Au2(+) ion, which can be attributed to the changes in the electron density following water adsorption.

  16. Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2017-01-01

    Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl 3 ) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO 4 ) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

  17. UV-B-inducible and temperature-sensitive photoreactivation of cyclobutane pyrimidine dimers in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Pang, Qishen; Hays, J.B.

    1991-01-01

    Removal of cyclobutane pyrimidine dimers (CBPDs) in vivo from the DNA of UV-irradiated eight-leaf seedlings of Arabidopsis thaliana was rapid in the presence of visible light (half-life about 1 hour); removal of CBPDs in the dark, presumably via excision repair, was an order of magnitude slower. Extracts of plants contained significant photolyase in vitro, as assayed by restoration of transforming activity to UV-irradiated Escherichia coli plasmids; activity was maximal from four-leaf to 12-leaf stages. UV-B treatment of seedlings for 6 hours increased photolyase specific activity in extracts twofold. Arabidopsis photolyase was markedly temperature-sensitive, both in vitro (half-life at 30C about 12 minutes) and in vivo (half-life at 30C, 30 to 45 minutes). The wavelength dependency of the photoreactivation cross-section showed a broad peak at 375 to 400 nm, and is thus similar to that for maize pollen; it overlaps bacterial and yeast photolyase action spectra

  18. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    International Nuclear Information System (INIS)

    Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

    2012-01-01

    Highlights: ► Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. ► Quercetin forms a heterodimer through oxidation in media with serum. ► The quercetin heterodimer does not kill MDA-MB-231 cells. ► Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. ► Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin’s ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  19. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  20. Protective effect of zinc aspartate against acetaminophen induced hepato-renal toxicity in albino rats

    International Nuclear Information System (INIS)

    Mohamed, E.T.; Said, A.I.; El-Sayed, S.A.

    2011-01-01

    Zinc is an essential nutrient that is required in humans and animals for many physiological functions, including antioxidant functions. The evidence to date indicates that zinc is an important element that links antioxidant system and tissue damage. Acetaminophen (AP), a widely used analgesic and antipyretic, produces hepatocyte and renal tubular necrosis in human and animals following overdose. In human, AP is one of the most common causes of acute liver failure as a result of accidental or deliberate overdose. Moreover, the initial event in AP toxicity is a toxic metabolic injury with the release of free radicals and subsequent cellular death by necrosis and apoptosis. This study was designed to evaluate the potential protective role of zinc aspartate in case of acetaminophen induced hepato-renal toxicity in rats. A total number of 32 adult male albino rats were divided into 4 equal groups: group I (control group), group II (zinc aspartate treated group), group III (acetaminophen treated group; by a single oral dose of 750 mg/kg body weight) and group IV acetaminophen plus zinc treated group; (zinc aspartate was intraperitoneally given one hour after acetaminophen administration in a dose of 30 mg/kg body weight). Serum levels of: alanine aminotransferase, aspartate aminotransferase, direct bilirubin, blood urea nitrogen, creatinine, uric acid, xanthine oxidase (XO), glutathione (GSH), malonaldehyde (MDA) and nitric oxide (NO) were assessed in all groups. The results of this study showed that treatment with acetaminophen alone (group III) produced a significant increase in serum levels of the liver enzymes and direct bilirubin. Moreover, in the same group there was a significant increase in the blood urea nitrogen and serum creatinine compared to the control group. In addition, there was a significant increase in XO and MDA and a significant decrease in GSH and NO level. Injection of rats with zinc aspartate after acetaminophen treatment could produce a

  1. Nanosized zinc oxide particles induce neural stem cell apoptosis

    International Nuclear Information System (INIS)

    Deng Xiaoyong; Luan Qixia; Wu Minghong; Zhang Haijiao; Jiao Zheng; Chen Wenting; Wang Yanli

    2009-01-01

    Given the intensive application of nanoscale zinc oxide (ZnO) materials in our life, growing concerns have arisen about its unintentional health and environmental impacts. In this study, the neurotoxicity of different sized ZnO nanoparticles in mouse neural stem cells (NSCs) was investigated. A cell viability assay indicated that ZnO nanoparticles manifested dose-dependent, but no size-dependent toxic effects on NSCs. Apoptotic cells were observed and analyzed by confocal microscopy, transmission electron microscopy examination, and flow cytometry. All the results support the viewpoint that the ZnO nanoparticle toxicity comes from the dissolved Zn 2+ in the culture medium or inside cells. Our results highlight the need for caution during the use and disposal of ZnO manufactured nanomaterials to prevent the unintended environmental and health impacts.

  2. Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

    Science.gov (United States)

    Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

    2016-10-01

    Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

  3. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

  4. The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

    International Nuclear Information System (INIS)

    Al-Damegh, Mona Abdalla

    2007-01-01

    Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

  5. The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus.

    Science.gov (United States)

    Yang, Fan; Li, Bing; Dong, Xiaoming; Cui, Wenpeng; Luo, Ping

    2017-07-01

    Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3β phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Chiou, Shyh-Shin, E-mail: chiouss@kmu.edu.tw [Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Department of Pediatrics, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China); Wang, Sophie Sheng-Wen; Wu, Deng-Chyang [Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Lin, Ying-Chu [School of Dentistry, College of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Kao, Li-Pin [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China)

    2013-07-26

    We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  7. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Directory of Open Access Journals (Sweden)

    Naoto Yamaguchi

    2013-07-01

    Full Text Available We report here that the Jun dimerization protein 2 (JDP2 plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2 and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS. JDP2 associates with Nrf2 and MafK (Nrf2-MafK to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  8. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

    Directory of Open Access Journals (Sweden)

    Tsung-I Chen

    Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

  9. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    Science.gov (United States)

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  10. Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, M.; Thomsen, Pernille Sjølin

    2001-01-01

    , and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs......, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All......The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured...

  11. Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal

    International Nuclear Information System (INIS)

    Parris, C.N.; Kraemer, K.H.

    1993-01-01

    The authors compared the contribution to mutagenesis on Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repair-deficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of >200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, the data suggest that prevention of UV-induced skin cancers is associated with proficient repair of nondimer photoproducts. 38 refs., 3 figs., 2 tabs

  12. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

    Science.gov (United States)

    Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

    2007-02-01

    Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

  13. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    International Nuclear Information System (INIS)

    Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

    2013-01-01

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ m ). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in

  14. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2013-04-15

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

  15. Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

    Science.gov (United States)

    Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang

    2012-07-01

    LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

  16. Zinc promotes the death of hypoxic astrocytes by upregulating hypoxia-induced hypoxia-inducible factor-1alpha expression via poly(ADP-ribose) polymerase-1.

    Science.gov (United States)

    Pan, Rong; Chen, Chen; Liu, Wen-Lan; Liu, Ke-Jian

    2013-07-01

    Pathological release of excess zinc ions has been implicated in ischemic brain cell death. However, the underlying mechanisms remain to be elucidated. In stroke, ischemia-induced zinc release and hypoxia-inducible factor-1 (HIF-1) accumulation concurrently occur in the ischemic tissue. The present study tests the hypothesis that the presence of high intracellular zinc concentration is a major cause of modifications to PARP-1 and HIF-1α during hypoxia, which significantly contributes to cell death during ischemia. Primary cortical astrocytes and C8-D1A cells were exposed to different concentrations of zinc chloride. Cell death rate and protein expression of HIF-1 and Poly(ADP-ribose) polymerase (PARP)-1 were examined after 3-h hypoxic treatment. Although 3-h hypoxia or 100 μM of zinc alone did not induce noticeable cytotoxicity, their combination led to a dramatic increase in astrocytic cell death in a zinc-concentration-dependent manner. Exposure of astrocytes to hypoxia for 3 h remarkably increased the levels of intracellular zinc and HIF-1α protein, which was further augmented by added exogenous zinc. Notably, HIF-1α knockdown blocked zinc-induced astrocyte death. Moreover, knockdown of PARP-1, another important protein in the response of hypoxia, attenuated the overexpression of HIF-1α and reduced the cell death rate. Our studies show that zinc promotes hypoxic cell death through overexpression of the hypoxia response factor HIF-1α via the cell fate determine factor PARP-1 modification, which provides a novel mechanism for zinc-mediated ischemic brain injury. © 2013 John Wiley & Sons Ltd.

  17. Photoreactivation and excision repair of UV induced pyrimidine dimers in the unicellular cyanobacterium Gloeocapsa alpicola (Synechocystis PCC 6308)

    International Nuclear Information System (INIS)

    O'Brien, P.A.; Houghton, J.A.

    1982-01-01

    The survival curve obtained after UV irradiation of the unicellular cyanobacterium Synechocystis is typical of a DNA repair competent organism. Inhibition of DNA replication, by incubating cells in the dark, increased resistance to the lethal effects of UV at higher fluences. Exposure of irradiated cells to near ultraviolet light (350-500 nm) restored viability to pre-irradiation levels. In order to measure DNA repair activity, techniques have been developed for the chromatographic analysis of pyrimidine dimers in synechocystis. The specificity of this method was established using a haploid strain of Saccharomyces cerevisiae. In accordance with the physiological responses of irradiated cells to photoreactivating light, pyrimidine dimers were not detected after photoreactivation treatment. Incubation of irradiated cells under non-photoreactivating growth conditions for 15h resulted in complete removal of pyrimidine dimers. It is concluded that Synechocystis contains photoreactivation and excision repair systems for the removal of pyrimidine dimers. (author)

  18. Template Dimerization Promotes an Acceptor Invasion-Induced Transfer Mechanism during Human Immunodeficiency Virus Type 1 Minus-Strand Synthesis

    OpenAIRE

    Balakrishnan, Mini; Roques, Bernard P.; Fay, Philip J.; Bambara, Robert A.

    2003-01-01

    The biochemical mechanism of template switching by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the role of template dimerization were examined. Homologous donor-acceptor template pairs derived from the HIV-1 untranslated leader region and containing the wild-type and mutant dimerization initiation sequences (DIS) were used to examine the efficiency and distribution of transfers. Inhibiting donor-acceptor interaction was sufficient to reduce transfers in DIS-containin...

  19. Relativistic effects in the intermolecular interaction-induced nuclear magnetic resonance parameters of xenon dimer

    DEFF Research Database (Denmark)

    Hanni, Matti; Lantto, Perttu; Ilias, Miroslav

    2007-01-01

    Relativistic effects on the 129Xe nuclear magnetic resonance shielding and 131Xe nuclear quadrupole coupling (NQC) tensors are examined in the weakly bound Xe2 system at different levels of theory including the relativistic four-component Dirac-Hartree-Fock (DHF) method. The intermolecular...... interaction-induced binary chemical shift d, the anisotropy of the shielding tensor ?s, and the NQC constant along the internuclear axis ?ll are calculated as a function of the internuclear distance. DHF shielding calculations are carried out using gauge-including atomic orbitals. For comparison, the full...... is obtained for d and ?s in Xe2. For these properties, the currently most complete theoretical description is obtained by a piecewise approximation where the uncorrelated relativistic DHF results obtained close to the basis-set limit are corrected, on the one hand, for NR correlation effects and, on the other...

  20. A novel mechanism for the pyruvate protection against zinc-induced cytotoxicity: mediation by the chelating effect of citrate and isocitrate.

    Science.gov (United States)

    Sul, Jee-Won; Kim, Tae-Youn; Yoo, Hyun Ju; Kim, Jean; Suh, Young-Ah; Hwang, Jung Jin; Koh, Jae-Young

    2016-08-01

    Intracellular accumulation of free zinc contributes to neuronal death in brain injuries such as ischemia and epilepsy. Pyruvate, a glucose metabolite, has been shown to block zinc neurotoxicity. However, it is largely unknown how pyruvate shows such a selective and remarkable protective effect. In this study, we sought to find a plausible mechanism of pyruvate protection against zinc toxicity. Pyruvate almost completely blocked cortical neuronal death induced by zinc, yet showed no protective effects against death induced by calcium (ionomycin, NMDA) or ferrous iron. Of the TCA cycle intermediates, citrate, isocitrate, and to a lesser extent oxaloacetate, protected against zinc toxicity. We then noted with LC-MS/MS assay that exposure to pyruvate, and to a lesser degree oxaloacetate, increased levels of citrate and isocitrate, which are known zinc chelators. While pyruvate added only during zinc exposure did not reduce zinc toxicity, citrate and isocitrate added only during zinc exposure, as did extracellular zinc chelator CaEDTA, completely blocked it. Furthermore, addition of pyruvate after zinc exposure substantially reduced intracellular zinc levels. Our results suggest that the remarkable protective effect of pyruvate against zinc cytotoxicity may be mediated indirectly by the accumulation of intracellular citrate and isocitrate, which act as intracellular zinc chelators.

  1. Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

    Directory of Open Access Journals (Sweden)

    Thiago B Kirsten

    Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

  2. Alterations in Somatostatin Cells and Biochemical Parameters Following Zinc Supplementation in Gastrointestinal Tissue of St reptozotocin-Induced Diabetic Rats

    International Nuclear Information System (INIS)

    Bolkent, Sema; Bolkent, Sehnaz; Yanardag, Refiye; Mutlu, Ozgur; Yildirim, Sukriye

    2006-01-01

    Chronic hyperglycemia in diabetes is a major causative factor of free radical generation which further leads to many secondary diabetic complications via the damage to cellular proteins, membrane lipids, and nucleic acids. Zinc is an essential trace element in all living systems and plays a structural role in many proteins and enzymes. Somatostatin is known to have inhibitory effects on various gastrointestinal functions. Therefore, we determined somatostatin protein production and secretion levels, and biochemical and light microscopical changes following zinc supplementation in the gastrointestinal tract of streptozotocin (STZ)-diabetic rats. The animals were divided into four groups: Group I: control (untreated) animals; Group II: control animals given zinc sulfate; Group III: diabetic animals; and Group IV: diabetic animals given zinc sulfate. Zinc sulfate was given to the animals by gavage at a daily dose of 100 mg/kg body weight for 60 days. Diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg/kg. For histological studies, stomach and duodenum tissues were fixed in Bouin solution and sections stained with Masson’s trichrome and Periodic-Acid-Schiff. Tissue homogenates were used for protein, lipid peroxidation (LPO), glutathione (GSH), and nonenzymatic glycosylation (NEG) analyses. Zinc supplementation to the STZ-diabetic rats revealed the protective effect of zinc on these parameters. Zinc supplementation may contribute to prevent at least some complications of diabetes mellitus

  3. Relativistic effects in the intermolecular interaction-induced nuclear magnetic resonance parameters of xenon dimer.

    Science.gov (United States)

    Hanni, Matti; Lantto, Perttu; Ilias, Miroslav; Jensen, Hans Jorgen Aagaard; Vaara, Juha

    2007-10-28

    Relativistic effects on the (129)Xe nuclear magnetic resonance shielding and (131)Xe nuclear quadrupole coupling (NQC) tensors are examined in the weakly bound Xe(2) system at different levels of theory including the relativistic four-component Dirac-Hartree-Fock (DHF) method. The intermolecular interaction-induced binary chemical shift delta, the anisotropy of the shielding tensor Deltasigma, and the NQC constant along the internuclear axis chi( parallel) are calculated as a function of the internuclear distance. DHF shielding calculations are carried out using gauge-including atomic orbitals. For comparison, the full leading-order one-electron Breit-Pauli perturbation theory (BPPT) is applied using a common gauge origin. Electron correlation effects are studied at the nonrelativistic (NR) coupled-cluster singles and doubles with perturbational triples [CCSD(T)] level of theory. The fully relativistic second-order Moller-Plesset many-body perturbation (DMP2) theory is used to examine the cross coupling between correlation and relativity on NQC. The same is investigated for delta and Deltasigma by BPPT with a density functional theory model. A semiquantitative agreement between the BPPT and DHF binary property curves is obtained for delta and Deltasigma in Xe(2). For these properties, the currently most complete theoretical description is obtained by a piecewise approximation where the uncorrelated relativistic DHF results obtained close to the basis-set limit are corrected, on the one hand, for NR correlation effects and, on the other hand, for the BPPT-based cross coupling of relativity and correlation. For chi( parallel), the fully relativistic DMP2 results obtain a correction for NR correlation effects beyond MP2. The computed temperature dependence of the second virial coefficient of the (129)Xe nuclear shielding is compared to experiment in Xe gas. Our best results, obtained with the piecewise approximation for the binary chemical shift combined with the

  4. The protective role of Gamma-Tocopherol and zinc cysteine against oxidative stress induced by gamma irradiation in albino rats

    International Nuclear Information System (INIS)

    Anis, L.M.

    2004-01-01

    The present study aimed to evaluate the capability of α tocopherol (naturally occurring antioxidant) and zinc cysteine against radiation induced oxidative stress. α Tocopherol was dissolved in corn oil and g, to the animals for ten successive days at a dose of 20 mg/kg b weight/day. Zinc cysteine was delivered to rats via intraperitoneal inject at a concentration of 25 mg/kg body weight/day for two successive days, rats were exposed to whole body gamma irradiation at a dose level of Gy. The activities of super oxide dismutase (SOD) and catalase and also concentrations of reduced glutathione (GSH) and malonaldehyde (Mi . were determined in the blood. The levels of metallothionein, zinc and copper were estimated in the serum, liver and kidney of the tested animals. The obtained results revealed that administration of a-tocopherol and zinc cysteine before gamma radiation exposure diminish significantly the decrease in blood SOD and catalase activities as compared to untreated irradiated rats. Also, the decrease in blood GSH concentration was less manifested and the decrease in the level of MDA was significant. The pre-gamma irradiation administration of zinc cysteine induced significant changes in the levels of metallothionein compared to both a-tocopherol supplemented and gamma irradiated rat groups. The amelioration occurred in the levels of zinc and copper postulated the positive role of vitamin E and zinc cysteine in alleviating all the levels of these elements

  5. Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis.

    Science.gov (United States)

    Yang, Qiaohong; Gupta, Romi

    2018-01-19

    UV is one of the major causes of DNA damage induced apoptosis. However, cancer cells adopt alternative mechanisms to evade UV-induced apoptosis. To identify factors that protect cancer cells from UV-induced apoptosis, we performed a genome wide short-hairpin RNA (shRNA) screen, which identified Zinc finger protein 598 (ZNF598) as a key regulator of UV-induced apoptosis. Here, we show that UV irradiation transcriptionally upregulates ZNF598 expression. Additionally, ZNF598 knockdown in cancer cells inhibited UV-induced apoptosis. In our study, we observe that ELK1 mRNA level as well as phosphorylated ELK1 levels was up regulated upon UV irradiation, which was necessary for UV irradiation induced upregulation of ZNF598. Cells expressing ELK1 shRNA were also resistant to UV-induced apoptosis, and phenocopy ZNF598 knockdown. Upon further investigation, we found that ZNF598 knockdown inhibits UV-induced apoptotic gene expression, which matches with decrease in percentage of annexin V positive cell. Similarly, ectopic expression of ZNF598 promoted apoptotic gene expression and also increased annexin V positive cells. Collectively, these results demonstrate that ZNF598 is a UV irradiation regulated gene and its loss results in resistance to UV-induced apoptosis.

  6. Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

    Science.gov (United States)

    Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F

    2012-05-01

    Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca. © 2011 Blackwell Verlag GmbH.

  7. Identification of autophagy genes participating in zinc-induced necrotic cell death in Saccharomyces cerevisiae.

    Science.gov (United States)

    Dziedzic, Slawomir A; Caplan, Allan B

    2011-05-01

    Eukaryotes use a common set of genes to perform two mechanistically similar autophagic processes. Bulk autophagy harvests proteins nonselectively and reuses their constitutents when nutrients are scarce. In contrast, different forms of selective autophagy target protein aggregates or damaged organelles that threaten to interfere with growth. Yeast uses one form of selective autophagy, called cytoplasm-to-vacuole targeting (Cvt), to engulf two vacuolar enzymes in Cvt vesicles ("CVT-somes") within which they are transported to vacuoles for maturation. While both are dispensable normally, bulk and selective autophagy help sustain life under stressful conditions. Consistent with this view, knocking out several genes participating in Cvt and specialized autophagic pathways heightened the sensitivity of Saccharomyces cerevisiae to inhibitory levels of Zn(2+). The loss of other autophagic genes, and genes responsible for apoptotic cell death, had no such effect. Unexpectedly, the loss of members of a third set of autophagy genes heightened cellular resistance to zinc as if they encoded proteins that actively contributed to zinc-induced cell death. Further studies showed that both sensitive and resistant strains accumulated similar amounts of H2O2 during zinc treatments, but that more sensitive strains showed signs of necrosis sooner. Although zinc lethality depended on autophagic proteins, studies with several reporter genes failed to reveal increased autophagic activity. In fact, microscopy analysis indicated that Zn(2+) partially inhibited fusion of Cvt vesicles with vacuoles. Further studies into how the loss of autophagic processes suppressed necrosis in yeast might reveal whether a similar process could occur in plants and animals.

  8. Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure.

    Science.gov (United States)

    Kirsten, Thiago B; Queiroz-Hazarbassanov, Nicolle; Bernardi, Maria M; Felicio, Luciano F

    2015-06-01

    Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS),which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism.We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia.Materials and methods:We evaluated the effects of LPS and zinc on female reproductive performance. Communication,which is impaired in autism,was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker.Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction.Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls.Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments.The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway.

  9. Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

    Science.gov (United States)

    Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

    2008-02-22

    One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

  10. Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions.

    Science.gov (United States)

    Kumar, Vinod; Singh, Brajesh Kumar; Chauhan, Amit Kumar; Singh, Deepali; Patel, Devendra Kumar; Singh, Chetna

    2016-07-01

    Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration.

  11. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Kocdor H

    2015-07-01

    Full Text Available Hilal Kocdor,1,2 Halil Ates,1 Suleyman Aydin,3 Ruksan Cehreli,1 Firat Soyarat,2 Pinar Kemanli,2 Duygu Harmanci,2 Hakan Cengiz,2 Mehmet Ali Kocdor4 1Institute of Oncology, Dokuz Eylul University, 2Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir Turkey; 3Department of Biochemistry, Firat University School of Medicine, Elazig, 4Department of Surgery, School of Medicine, Dokuz Eylul University, Izmir, Turkey Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549 and p53-null (H1299 cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50 values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM.Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells. Keywords: lung cancer, zinc, docetaxel, A549, H1299

  12. Cytotoxicant-induced trophoblast dysfunction and abnormal pregnancy outcomes: role of zinc and metallothionein.

    Science.gov (United States)

    McAleer, Mary Frances; Tuan, Rocky S

    2004-12-01

    Normal trophoblast function, including implantation, hormone production, and formation of the selectively permeable maternofetal barrier, is essential for the establishment and maintenance of the fetoplacental unit and proper fetal development. Maternal cytotoxicant exposure causes the destruction of these cells, especially the terminally differentiated syncytiotrophoblasts, and results in a myriad of poor pregnancy outcomes. These outcomes range from intrauterine growth retardation and malformation to spontaneous abortion or stillbirth. There is recent evidence that the metal-binding protein, metallothionein, is involved in the protection of human trophoblastic cells from heavy metal-induced and severe oxidative stress-induced apoptosis. Metallothionein, with its unique biochemical structure, can both bind essential metal ions, such as the transcription modulator zinc, and yet allow their ready displacement by toxic nonessential metal ions or damaging free radicals. These properties suggest that metallothionein may be responsible not only for sequestering the cytotoxic agents, but also for altering signal transduction in the affected cells. Here, we review several identified causes of adverse pregnancy outcomes (specifically, prenatal exposure to cigarette smoke and alcohol, gestational infection, and exposure to environmental contaminants), discuss the role of zinc in modulating the cellular response to these toxic insults, and then propose how metallothionein may function to mediate this protective response. Published 2005 Wiley-Liss, Inc.

  13. One-Pot Click Access to a Cyclodextrin Dimer-Based Novel Aggregation Induced Emission Sensor and Monomer-Based Chiral Stationary Phase

    Directory of Open Access Journals (Sweden)

    Xiaoli Li

    2016-11-01

    Full Text Available A ‘two birds, one stone’ strategy was developed via a one-pot click reaction to simultaneously prepare a novel cyclodextrin (CD dimer based aggregation induced emission (AIE sensor (AIE-DCD and a monomer based chiral stationary phase (CSP-MCD for chiral high performance liquid chromatography (CHPLC. AIE-DCD was found to afford satisfactory AIE response for specific detection of Zn2+ with a detection limit of 50 nM. CSP-MCD exhibits excellent enantioseparation ability toward dansyl amino acids, where the resolution of dansyl amino leucine reaches 5.43.

  14. Aflatoxin B1 Induced Systemic Toxicity in Poultry and Rescue Effects of Selenium and Zinc.

    Science.gov (United States)

    Mughal, Muhammad Jameel; Peng, Xi; Kamboh, Asghar Ali; Zhou, Yi; Fang, Jing

    2017-08-01

    Among many challenges, exposure to aflatoxins, particularly aflatoxin B 1 (AFB 1 ), is one of the major concerns in poultry industry. AFB 1 intoxication results in decreased meat/egg production, hepatotoxicity, nephrotoxicity, disturbance in gastrointestinal tract (GIT) and reproduction, immune suppression, and increased disease susceptibility. Selenium (Se) and zinc (Zn), in dietary supplementation, offer easy, cost-effective, and efficient ways to neutralize the toxic effect of AFB 1 . In the current review, we discussed the impact of AFB 1 on poultry industry, its biotransformation, and organ-specific noxious effects, along with the action mechanism of AFB 1 -induced toxicity. Moreover, we explained the biological and detoxifying roles of Se and Zn in avian species as well as the protection mechanism of these two trace elements. Ultimately, we discussed the use of Se and Zn supplementation against AFB 1 -induced toxicity in poultry birds.

  15. Zinc Vacancy-Induced Room-Temperature Ferromagnetism in Undoped ZnO Thin Films

    Directory of Open Access Journals (Sweden)

    Hongtao Ren

    2012-01-01

    Full Text Available Undoped ZnO thin films are prepared by polymer-assisted deposition (PAD and treated by postannealing at different temperatures in oxygen or forming gases (95%  Ar+5% H2. All the samples exhibit ferromagnetism at room temperature (RT. SQUID and positron annihilation measurements show that post-annealing treatments greatly enhance the magnetizations in undoped ZnO samples, and there is a positive correlation between the magnetization and zinc vacancies in the ZnO thin films. XPS measurements indicate that annealing also induces oxygen vacancies that have no direct relationship with ferromagnetism. Further analysis of the results suggests that the ferromagnetism in undoped ZnO is induced by Zn vacancies.

  16. Oxidation-induced spin reorientation in Co adatoms and CoPd dimers on Ni/Cu(100)

    Science.gov (United States)

    Chen, K.; Beeck, T.; Fiedler, S.; Baev, I.; Wurth, W.; Martins, M.

    2016-04-01

    Ultrasmall magnetic clusters and adatoms are of strong current interest because of their possible use in future technological applications. Here, we demonstrate that the magnetic coupling between the adsorbates and the substrate can be significantly changed through oxidation. The magnetic properties of Co adatoms and CoPd dimers deposited on a remanently magnetized Ni/Cu(100) substrate have been investigated by x-ray absorption and x-ray magnetic circular dichroism spectroscopy at the Co L2 ,3 edges. Using spectral differences, pure and oxidized components are distinguished, and their respective magnetic moments are determined. The Co adatoms and the CoPd dimers are coupled ferromagnetically to the substrate, while their oxides, Co-O and CoPd-O, are coupled antiferromagnetically to the substrate. Along with the spin reorientation from the pure to the oxidized state, the magnetic moment of the adatom is highly reduced from Co to Co-O. In contrast, the magnetic moment of the dimer is of similar order for CoPd and CoPd-O.

  17. Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats.

    Science.gov (United States)

    Nazarizadeh, Ali; Asri-Rezaie, Siamak

    2016-08-01

    In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were divided into two healthy and diabetic groups, randomly. Each major group was further subdivided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.

  18. Field-induced phase transition in a metalorganic spin-dimer system-a potential model system to study Bose-Einstein condensation of magnons

    International Nuclear Information System (INIS)

    Tsui, Y.; Bruehl, A.; Removic-Langer, K.; Pashchenko, V.; Wolf, B.; Donath, G.; Pikul, A.; Kretz, T.; Lerner, H.-W.; Wagner, M.; Salguero, A.; Saha-Dasgupta, T.; Rahaman, B.; Valenti, R.; Lang, M.

    2007-01-01

    We report on the results obtained from studying electron spin resonance, magnetic susceptibility, specific heat and thermal expansion experiments on a metalorganic spin-dimer system, C 36 H 48 Cu 2 F 6 N 8 O 12 S 2 (TK91). According to the first principle Density Functional Theory calculations, the compound represents a 3D-coupled dimer system with intradimer coupling J 1 /k B ∼ 10K and interdimer couplings J 2 /k B ∼J 3 /k B ∼ 1K. The measurements have been performed on both pressed powder and single-crystal samples in external magnetic fields up to 12T and at low temperatures down to ∼ 0.2K. Susceptibility measurements reveal a spin-gap behavior consistent with the theoretical results. Furthermore, clear indications of a field-induced phase transition have been observed. A similar field-induced phase transition was also detected in an inorganic compound TlCuCl 3 and was interpreted as Bose-Einstein condensation (BEC) of magnons. The possibility of changing both the intradimer and interdimer couplings in TK91 by chemical substitutions makes the system a potentially good system to study BEC of magnons

  19. Zinc-induced differential oxidative stress and antioxidant responses in Chlorella sorokiniana and Scenedesmus acuminatus.

    Science.gov (United States)

    Hamed, Seham M; Zinta, Gaurav; Klöck, Gerd; Asard, Han; Selim, Samy; AbdElgawad, Hamada

    2017-06-01

    Algae are frequently exposed to toxic metals, and zinc (Zn) is one of the major toxicants present. We exposed two green microalgae, Chlorella sorokiniana and Scenedesmus acuminatus, to sub-lethal concentrations (1.0 and 0.6mM) of Zn for seven days. Algal responses were analysed at the level of growth, oxidative stress, and antioxidants. Growth parameters such as cell culture yield and pigment content were less affected by Zn in C. sorokiniana, despite the fact that this alga accumulated more zinc than S. acuminatus. Also, C. sorokiniana, but not S. acuminatus, was able to acclimatize during long-term exposure to toxic concentrations of the test metals (specific growth rate (µ) was 0.041/day and total chlorophyll was 14.6mg/mL). Although, Zn induced oxidative stress in both species, C. sorokiniana experienced less stress than S. acuminatus. This could be explained by a higher accumulation of antioxidants in C. sorokiniana, where flavonoids, polyphenols, tocopherols, glutathione (GSH) and ascorbate (ASC) content increased. Moreover, antioxidant enzymes glutathione S transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), peroxidase (POX) and ascorbate peroxidase (APX), showed increased activities in C. sorokiniana. In addition to, and probably also underlying, the higher Zn tolerance in C. sorokiniana, this alga also showed higher Zn biosorption capacity. Use of C. sorokiniana as a bio-remediator, could be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Zinc Ameliorate Oxidative Stress and Hormonal Disturbance Induced by Methomyl, Abamectin, and Their Mixture in Male Rats

    Directory of Open Access Journals (Sweden)

    Sameeh A. Mansour

    2017-12-01

    Full Text Available Exposure to mixtures of toxicants (e.g., pesticides is common in real life and a subject of current concern. The present investigation was undertaken to assess some toxicological effects in male rats following exposure to methomyl (MET, abamectin (ABM, and their combination (MET+ABM, and to evaluate the ameliorative effect of zinc co-administration. Three groups of rats were designated for MET, ABM, and the mixture treatments. Three other groups were designated for zinc in conjunction with the pesticides. Additionally, one group received water only (control, and the other represented a positive zinc treatment. The obtained results revealed that MET was acutely more toxic than ABM. The tested pesticides induced significant elevation in lipid peroxidation and catalase levels, while declined the levels of the other tested parameters e.g., Superoxide dismutase (SOD, Glutathione-S-transferase (GST, Glutathione peroxidase (GPx, Glutathione reductase (GR, Cytochrome P450 (CYP450, testosterone, and thyroxine. Biochemical alterations induced by the mixture were greater than those recorded for each of the individual insecticides. The joint action analysis, based on the obtained biochemical data, revealed the dominance of antagonistic action among MET and ABM. Zinc supplementation achieved noticeable ameliorative effects. It was concluded that zinc may act as a powerful antioxidant, especially in individuals who are occupationally exposed daily to low doses of such pesticides.

  1. ZINC-INDUCED EGF RECEPTOR SIGNALING REQUIRES SRC-MEDIATED PHOSPHORYLATION OF THE EGF RECEPTOR ON TYROSINE 845 (Y845)

    Science.gov (United States)

    ZINC-INDUCED EGF RECEPTOR SIGNALING REQUIRES Src-MEDIATED PHOSPHORYLATION OF THE EGF RECEPTOR ON TYROSINE 845 (Y845)Weidong Wu1, Lee M. Graves2, Gordon N. Gill3 and James M. Samet4 1Center for Environmental Medicine and Lung Biology; 2Department of Pharmacology, University o...

  2. Template Dimerization Promotes an Acceptor Invasion-Induced Transfer Mechanism during Human Immunodeficiency Virus Type 1 Minus-Strand Synthesis

    Science.gov (United States)

    Balakrishnan, Mini; Roques, Bernard P.; Fay, Philip J.; Bambara, Robert A.

    2003-01-01

    The biochemical mechanism of template switching by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the role of template dimerization were examined. Homologous donor-acceptor template pairs derived from the HIV-1 untranslated leader region and containing the wild-type and mutant dimerization initiation sequences (DIS) were used to examine the efficiency and distribution of transfers. Inhibiting donor-acceptor interaction was sufficient to reduce transfers in DIS-containing template pairs, indicating that template dimerization, and not the mere presence of the DIS, promotes efficient transfers. Additionally, we show evidence that the overall transfer process spans an extended region of the template and proceeds through a two-step mechanism. Transfer is initiated through an RNase H-facilitated acceptor invasion step, while synthesis continues on the donor template. The invasion then propagates towards the primer terminus by branch migration. Transfer is completed with the translocation of the primer terminus at a site distant from the invasion point. In our system, most invasions initiated before synthesis reached the DIS. However, transfer of the primer terminus predominantly occurred after synthesis through the DIS. The two steps were separated by 60 to 80 nucleotides. Sequence markers revealed the position of primer terminus switch, whereas DNA oligomers designed to block acceptor-cDNA interactions defined sites of invasion. Within the region of homology, certain positions on the template were inherently more favorable for invasion than others. In templates with DIS, the proximity of the acceptor facilitates invasion, thereby enhancing transfer efficiency. Nucleocapsid protein enhanced the overall efficiency of transfers but did not alter the mechanism. PMID:12663778

  3. Thioredoxin-albumin fusion protein prevents copper enhanced zinc-induced neurotoxicity via its antioxidative activity.

    Science.gov (United States)

    Tanaka, Ken-Ichiro; Shimoda, Mikako; Chuang, Victor T G; Nishida, Kento; Kawahara, Masahiro; Ishida, Tatsuhiro; Otagiri, Masaki; Maruyama, Toru; Ishima, Yu

    2018-01-15

    Zinc (Zn) is a co-factor for a vast number of enzymes, and functions as a regulator for immune mechanism and protein synthesis. However, excessive Zn release induced in pathological situations such as stroke or transient global ischemia is toxic. Previously, we demonstrated that the interaction of Zn and copper (Cu) is involved in the pathogenesis of Alzheimer's disease and vascular dementia. Furthermore, oxidative stress has been shown to play a significant role in the pathogenesis of various metal ions induced neuronal death. Thioredoxin-Albumin fusion (HSA-Trx) is a derivative of thioredoxin (Trx), an antioxidative protein, with improved plasma retention and stability of Trx. In this study, we examined the effect of HSA-Trx on Cu 2+ /Zn 2+ -induced neurotoxicity. Firstly, HSA-Trx was found to clearly suppress Cu 2+ /Zn 2+ -induced neuronal cell death in mouse hypothalamic neuronal cells (GT1-7 cells). Moreover, HSA-Trx markedly suppressed Cu 2+ /Zn 2+ -induced ROS production and the expression of oxidative stress related genes, such as heme oxygenase-1. In contrast, HSA-Trx did not affect the intracellular levels of both Cu 2+ and Zn 2+ after Cu 2+ /Zn 2+ treatment. Finally, HSA-Trx was found to significantly suppress endoplasmic reticulum (ER) stress response induced by Cu 2+ /Zn 2+ treatment in a dose dependent manner. These results suggest that HSA-Trx counteracted Cu 2+ /Zn 2+ -induced neurotoxicity by suppressing the production of ROS via interfering the related gene expressions, in addition to the highly possible radical scavenging activity of the fusion protein. Based on these findings, HSA-Trx has great potential as a promising therapeutic agent for the treatment of refractory neurological diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Experimental study and nuclear model calculations of {sup 3}He-induced nuclear reactions on zinc

    Energy Technology Data Exchange (ETDEWEB)

    Al-Abyad, M.; Mohamed, Gehan Y. [Nuclear Research Centre, Atomic Energy Authority, Physics Department (Cyclotron Facility), Cairo (Egypt); Ditroi, F.; Takacs, S.; Tarkanyi, F. [Hungarian Academy of Sciences (ATOMKI), Institute for Nuclear Research, Debrecen (Hungary)

    2017-05-15

    Excitation functions of {sup 3}He-induced nuclear reactions on natural zinc were measured using the standard stacked-foil technique and high-resolution gamma-ray spectrometry. From their threshold energies up to 27 MeV, the cross-sections for {sup nat}Zn ({sup 3}He,xn) {sup 69}Ge, {sup nat}Zn({sup 3}He,xnp) {sup 66,67,68}Ga, and {sup nat}Zn({sup 3}He,x){sup 62,65}Zn reactions were measured. The nuclear model codes TALYS-1.6, EMPIRE-3.2 and ALICE-IPPE were used to describe the formation of these products. The present data were compared with the theoretical results and with the available experimental data. Integral yields for some important radioisotopes were determined. (orig.)

  5. Elimination of zinc-65 from the brain under kainate-induced seizures.

    Science.gov (United States)

    Takeda, Atsushi; Hirate, Maki; Oku, Naoto

    2004-04-01

    On the basis of the previous evidence that 65Zn concentrations in the brain of EL (epilepsy) mice was affected by induction of seizures, 65Zn movement in the brain was quantitatively evaluated in ddY mice treated with kainate. Six days after intravenous injection of 65ZnCl2, mice were intraperitoneally injected with kainate (10 mg/kg x 6 times in 2 weeks). Myoclonic jerks were observed during treatment with kainate. Twenty days after 65Zn injection, 65Zn distribution in the brain was compared between the kainite-treated and control mice. 65Zn distribution in the brain of the kainate-treated mice was overall lower than in the control mice. 65Zn concentration was significantly decreased in the frontal cortex, hippocampal CA1, thalamus and hypothalamus by treatment with kainate. These results demonstrate that kainate-induced seizures are linked to decreased zinc concentrations in the brain.

  6. Zinc regulates Nox1 expression through a NF-κB and mitochondrial ROS dependent mechanism to induce senescence of vascular smooth muscle cells.

    Science.gov (United States)

    Salazar, G; Huang, J; Feresin, R G; Zhao, Y; Griendling, K K

    2017-07-01

    The role of oxidative stress and inflammation in the development and progression of cardiovascular diseases (CVD) is well established. Increases in oxidative stress can further exacerbate the inflammatory response and lead to cellular senescence. We previously reported that angiotensin II (Ang II) and zinc increase reactive oxygen species (ROS) and cause senescence of vascular smooth muscle cells (VSMCs) and that senescence induced by Ang II is a zinc-dependent process. Zinc stimulated NADPH oxidase (Nox) activity; however, the role of Nox isoforms in zinc effects was not determined. Here, we show that downregulation of Nox1, but not Nox4, by siRNA prevented both Ang II- and zinc-induced senescence in VSMCs. On the other hand, overexpression of Nox1 induced senescence, which was associated with reduced proliferation, reduced expression of telomerase and increased DNA damage. Zinc increased Nox1 protein expression, which was inhibited by chelation of zinc with TPEN and by overexpression of the zinc exporters ZnT3 and ZnT10. These transporters work to reduce cytosolic zinc, suggesting that increased cytosolic zinc mediates Nox1 upregulation. Other metals including copper, iron, cobalt and manganese failed to upregulate Nox1, suggesting that this pathway is zinc specific. Nox1 upregulation was inhibited by actinomycin D (ACD), an inhibitor of transcription, by inhibition of NF-κB, a known Nox1 transcriptional regulator and by N-acetyl cysteine (NAC) and MitoTEMPO, suggesting that NF-κB and mitochondrial ROS mediate zinc effects. Supporting this idea, we found that zinc increased NF-κB activation in the cytosol, stimulated the translocation of the p65 subunit to the nucleus, and that zinc accumulated in mitochondria increasing mitochondrial ROS, measured using MitoSox. Further, zinc-induced senescence was reduced by inhibition of NF-κB or reduction of mitochondrial ROS with MitoTEMPO. NF-κB activity was also reduced by MitoTEMPO, suggesting that mitochondrial ROS

  7. Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform

    Directory of Open Access Journals (Sweden)

    Yi Ting

    2012-11-01

    Full Text Available Abstract It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG and that exposure of zinc ion (Zn2+ to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our

  8. Blue light-induced LOV domain dimerization enhances the affinity of Aureochrome 1a for its target DNA sequence

    Science.gov (United States)

    Heintz, Udo; Schlichting, Ilme

    2016-01-01

    The design of synthetic optogenetic tools that allow precise spatiotemporal control of biological processes previously inaccessible to optogenetic control has developed rapidly over the last years. Rational design of such tools requires detailed knowledge of allosteric light signaling in natural photoreceptors. To understand allosteric communication between sensor and effector domains, characterization of all relevant signaling states is required. Here, we describe the mechanism of light-dependent DNA binding of the light-oxygen-voltage (LOV) transcription factor Aureochrome 1a from Phaeodactylum tricornutum (PtAu1a) and present crystal structures of a dark state LOV monomer and a fully light-adapted LOV dimer. In combination with hydrogen/deuterium-exchange, solution scattering data and DNA-binding experiments, our studies reveal a light-sensitive interaction between the LOV and basic region leucine zipper DNA-binding domain that together with LOV dimerization results in modulation of the DNA affinity of PtAu1a. We discuss the implications of these results for the design of synthetic LOV-based photosensors with application in optogenetics. DOI: http://dx.doi.org/10.7554/eLife.11860.001 PMID:26754770

  9. Disparate roles of zinc in chemical hypoxia-induced neuronal death

    Directory of Open Access Journals (Sweden)

    Sujeong eKim

    2015-01-01

    Full Text Available Accumulating evidence has provided a causative role of zinc (Zn2+ in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2, deferoxamine (3 mM DFX, and sodium azide (2 mM NaN3, we evaluated whether Zn2+ is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn2+ release/accumulation in viable neurons. The immediate addition of the Zn2+ chelator, CaEDTA or N,N,N’N’-tetrakis-(2-pyridylmethyl ethylenediamine (TPEN, prevented the intracellular Zn2+ load and CoCl2-induced neuronal death, but neither 3-hour-later Zn2+ chelation nor a non-Zn2+ chelator ZnEDTA (1 mM demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn2+ rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn2+ release/accumulation is common during chemical hypoxia, Zn2+ might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

  10. Disparate roles of zinc in chemical hypoxia-induced neuronal death.

    Science.gov (United States)

    Kim, Sujeong; Seo, Jung-Woo; Oh, Shin Bi; Kim, So Hee; Kim, Inki; Suh, Nayoung; Lee, Joo-Yong

    2015-01-01

    Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

  11. The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.

    Science.gov (United States)

    Arsenault, Patrick R; Song, Daisheng; Chung, Yu Jin; Khurana, Tejvir S; Lee, Frank S

    2016-09-15

    Prolyl hydroxylase domain protein 2 (PHD2) (also known as EGLN1) is a key oxygen sensor in mammals that posttranslationally modifies hypoxia-inducible factor α (HIF-α) and targets it for degradation. In addition to its catalytic domain, PHD2 contains an evolutionarily conserved zinc finger domain, which we have previously proposed recruits PHD2 to the HSP90 pathway to promote HIF-α hydroxylation. Here, we provide evidence that this recruitment is critical both in vitro and in vivo We show that in vitro, the zinc finger can function as an autonomous recruitment domain to facilitate interaction with HIF-α. In vivo, ablation of zinc finger function by a C36S/C42S Egln1 knock-in mutation results in upregulation of the erythropoietin gene, erythrocytosis, and augmented hypoxic ventilatory response, all hallmarks of Egln1 loss of function and HIF stabilization. Hence, the zinc finger ordinarily performs a critical positive regulatory function. Intriguingly, the function of this zinc finger is impaired in high-altitude-adapted Tibetans, suggesting that their adaptation to high altitude may, in part, be due to a loss-of-function EGLN1 allele. Thus, these findings have important implications for understanding both the molecular mechanism of the hypoxic response and human adaptation to high altitude. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Hydrogen-Induced Adsorption of Carbon Monoxide on the Gold Dimer Cation: A Joint Experimental and DFT Investigation.

    Science.gov (United States)

    Vojkovic, Marin; Rayane, Driss; Antoine, Rodolphe; Broyer, Michel; Allouche, Abdul-Rahman; Mignon, Pierre; Dugourd, Philippe

    2017-06-15

    It is demonstrated, using tandem mass spectrometry and radio frequency ion trap, that the adsorption of a H atom on the gold dimer cation, Au 2 H + , prevents its dissociation and allows for adsorption of CO. Reaction kinetics are measured by employing a radio frequency ion trap, where Au 2 + and CO interact for a given reaction time. The effect of a hydrogen atom is evaluated by comparing reaction rate constants measured for Au 2 + and Au 2 H + . The theoretical results for the adsorption of CO molecules and their reaction characteristics with Au 2 + and Au 2 H + are found to agree with the experimental findings. The joint investigations provide insights into hydrogen atom adsorption effects and consequent reaction mechanisms.

  13. New developments in porphyrin-like macrocyclic chemistry: a novel family of dibenzotetraaza[14]annulene-based cofacial dimers.

    Science.gov (United States)

    Zwoliński, K M; Eilmes, J

    2016-03-14

    The first known homoleptic cofacial dimers, based on covalently linked dibenzotetraaza[14]annulenes, were synthesized in reasonable 35-40% yields, without recourse to high-dilution techniques. Dinuclear zinc(ii) dimer showed strong binding affinity toward DABCO. Site-selective monometallation of the dimer, triggered by the linkers' structure, was observed, allowing access to heterobimetallic co-receptors.

  14. Nonlinear absorption dynamics using field-induced surface hopping: zinc porphyrin in water.

    Science.gov (United States)

    Röhr, Merle I S; Petersen, Jens; Wohlgemuth, Matthias; Bonačić-Koutecký, Vlasta; Mitrić, Roland

    2013-05-10

    We wish to present the application of our field-induced surface-hopping (FISH) method to simulate nonlinear absorption dynamics induced by strong nonresonant laser fields. We provide a systematic comparison of the FISH approach with exact quantum dynamics simulations on a multistate model system and demonstrate that FISH allows for accurate simulations of nonlinear excitation processes including multiphoton electronic transitions. In particular, two different approaches for simulating two-photon transitions are compared. The first approach is essentially exact and involves the solution of the time-dependent Schrödinger equation in an extended manifold of excited states, while in the second one only transiently populated nonessential states are replaced by an effective quadratic coupling term, and dynamics is performed in a considerably smaller manifold of states. We illustrate the applicability of our method to complex molecular systems by simulating the linear and nonlinear laser-driven dynamics in zinc (Zn) porphyrin in the gas phase and in water. For this purpose, the FISH approach is connected with the quantum mechanical-molecular mechanical approach (QM/MM) which is generally applicable to large classes of complex systems. Our findings that multiphoton absorption and dynamics increase the population of higher excited states of Zn porphyrin in the nonlinear regime, in particular in solution, provides a means for manipulating excited-state properties, such as transient absorption dynamics and electronic relaxation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Proton microprobe analysis of zinc in skeletal tissues. [Proton induced x-ray emission analysis

    Energy Technology Data Exchange (ETDEWEB)

    Doty, S B; Jones, K W; Kraner, H W; Shroy, R E; Hanson, A L

    1980-06-01

    A proton microprobe with windowless exit port was used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage.

  16. Zinc salt enhances gastroprotective activity of risperidone in indomethacin-induced gastric ulcer.

    Science.gov (United States)

    Oluwole, F S; Onwuchekwa, C

    2016-09-01

    Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways. The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5. There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology. These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

  17. Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes.

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    Justin D Mallet

    Full Text Available Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD and pyrimidine (6-4 pyrimidone photoproducts (6-4PP. These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced.

  18. Stilbene induced inhibition of androgen receptor dimerization: implications for AR and ARΔLBD-signalling in human prostate cancer cells.

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    Wolfgang Streicher

    Full Text Available BACKGROUND: Advanced castration resistant prostate cancer (CRPC is often characterized by an increase of C-terminally truncated, constitutively active androgen receptor (AR variants. Due to the absence of a ligand binding domain located in the AR-C-terminus, these receptor variants (also termed ARΔLBD are unable to respond to all classical forms of endocrine treatments like surgical/chemical castration and/or application of anti-androgens. METHODOLOGY: In this study we tested the effects of the naturally occurring stilbene resveratrol (RSV and (E-4-(2, 6-Difluorostyryl-N, N-dimethylaniline, a fluorinated dialkylaminostilbene (FIDAS on AR- and ARΔLBD in prostate cancer cells. The ability of the compounds to modulate transcriptional activity of AR and the ARΔLBD-variant Q640X was shown by reporter gene assays. Expression of endogenous AR and ARΔLBD mRNA and protein levels were determined by qRT-PCR and Western Blot. Nuclear translocation of AR-molecules was analyzed by fluorescence microscopy. AR and ARΔLBD/Q640X homo-/heterodimer formation was assessed by mammalian two hybrid assays. Biological activity of both compounds in vivo was demonstrated using a chick chorioallantoic membrane xenograft assay. RESULTS: The stilbenes RSV and FIDAS were able to significantly diminish AR and Q640X-signalling. Successful inhibition of the Q640X suggests that RSV and FIDAS are not interfering with the AR-ligand binding domain like all currently available anti-hormonal drugs. Repression of AR and Q640X-signalling by RSV and FIDAS in prostate cancer cells was caused by an inhibition of the AR and/or Q640X-dimerization. Although systemic bioavailability of both stilbenes is very low, both compounds were also able to downregulate tumor growth and AR-signalling in vivo. CONCLUSION: RSV and FIDAS are able to inhibit the dimerization of AR and ARΔLBD molecules suggesting that stilbenes might serve as lead compounds for a novel generation of AR-inhibitors.

  19. Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

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    Raul Hernandes Bortolin

    Full Text Available Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM, and T1DM plus zinc supplementation (T1DMS. Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus, and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic

  20. Studies on zinc-induced pancreatic exocrine insufficiency and its consequences in the chick

    International Nuclear Information System (INIS)

    Lue, J.

    1989-01-01

    Experiments were conducted to investigate the nature of zinc (Zn)-induced pancreatic exocrine damage, some of its consequences and its interaction with other nutrients, especially selenium (Se) and vitamin E (VE) in the chick. When fed excess Zn, the chick pancreas accumulated as much as an order of magnitude more Zn than the liver on a unit weight basis. The levels of activities of pancreatic secretory enzymes were significantly reduced by excess dietary Zn and distortion of the acinar pancreas structure, losses of zymogen granules and varying degree of fibrotic infiltration were observed histologically. The reduction of the level of pancreatic secretory enzyme activities was accompanied by a reduction of the quantity of enzyme proteins rather than a modification of enzyme activity. The rate of synthesis of pancreatic amylase, as assessed by the incorporation of 3 H-leucine, was significantly decreased by excess dietary Zn. As consequences of Zn-induced pancreatic damage, the digestibility of dietary starch and tissue VE status were decreased, the latter effect being caused primarily by an impaired utilization of dietary source of the vitamin as determined by the appearance of 3 H-α-tocopherol in the blood after an oral dose. Excess dietary Zn increased the Se status of the pancreas, but not those of the plasma and the liver. Supranutritional levels of Se and/or VE did not protect the pancreas against Zn-induced damage, nor did Se-deficiency exacerbate this damage. An in vitro inhibitory effect of Zn and some heavy metal ions on α-amylase activity was discovered and characterized by a non-competitive mechanism. This inhibitory effect could become an important modular of utilization of dietary starch under conditions of Zn toxicosis

  1. Calcium, zinc and vitamin E ameliorate cadmium-induced renal oxidative damage in albino Wistar rats

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    Pradeepkiran Jangampalli Adi

    Full Text Available This study was aimed to examine the protective effects of supplementation with calcium + zinc (Ca + Zn or vitamin E (Vit-E on Cd-induced renal oxidative damage. Young albino Wistar rats (180 ± 10 g (n = 6 control rats, Cd, Cd + Ca + Zn, and Cd + Vit-E experimental groups and the experimental period was 30 days. Rats were exposed to Cd (20 mg/kg body weight alone treated as Cd treated group and the absence or presence of Ca + Zn (2 mg/kg each or Vit-E (20 mg/kg body weight supplementation treated as two separate groups. The activities of the stress marker enzymes superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPx, glutathione-S-transferase (GST and lipid peroxidase (LPx were determined in renal mitochondrial fractions of experimental rats. We observed quantitative changes in SOD isoenzymatic patterns by non-denaturing PAGE analysis, and quantified band densities. These results showed that Cd exposure leads to decreases in SOD, CAT, GR, and GPx activities and a concomitant increase in LPx and GST activities. Ca + Zn and Vit-E administration with Cd significantly reversed Cd-induced perturbations in oxidative stress marker enzymes. However, Vit-E showed more inhibitory activity against Cd than did Ca + Zn, and it protected against Cd-induced nephrotoxicity. Keywords: Cadmium (Cd, Oxidative stress, Lipid peroxidation, Nephrotoxicity, PAGE analysis

  2. Obtention of zinc polymethacrylate via free radicals induced by gamma radiation

    International Nuclear Information System (INIS)

    Urena N, F.; Flores E, J.

    2000-01-01

    The objective of this work was to synthesise the monomer of zinc methacrylate and subsequently to carry out the polymerization reaction with the purpose to obtain the compound desired, the zinc polymethacrylate. For this it was used a gamma radiation source, 60 Co, as initiator of the polymerization reaction. (Author)

  3. Effect of DHA and CoenzymeQ10 Against Aβ- and Zinc-Induced Mitochondrial Dysfunction in Human Neuronal Cells

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    Nadia Sadli

    2013-07-01

    Full Text Available Background: Beta-amyloid (Aβ protein is a key factor in the pathogenesis of Alzheimer's disease (AD and it has been reported that mitochondria is involved in the biochemical pathway by which Aβ can lead to neuronal dysfunction. Coenzyme Q10 (CoQ10 is an essential cofactor involved in the mitochondrial electron transport chain and has been suggested as a potential therapeutic agent in AD. Zinc toxicity also affects cellular energy production by decreasing oxygen consumption rate (OCR and ATP turnover in human neuronal cells, which can be restored by the neuroprotective effect of docosahexaenoic acid (DHA. Method: In the present study, using Seahorse XF-24 Metabolic Flux Analysis we investigated the effect of DHA and CoQ10 alone and in combination against Aβ- and zinc-mediated changes in the mitochondrial function of M17 neuroblastoma cell line. Results: Here, we observed that DHA is specifically neuroprotective against zinc-triggered mitochondrial dysfunction, but does not directly affect Aβ neurotoxicity. CoQ10 has shown to be protective against both Aβ- and zinc-induced alterations in mitochondrial function. Conclusion: Our results indicate that DHA and CoQ10 may be useful for the prevention, treatment and management of neurodegenerative diseases such as AD.

  4. Lactose binding to human galectin-7 (p53-induced gene 1) induces long-range effects through the protein resulting in increased dimer stability and evidence for positive cooperativity

    Science.gov (United States)

    Ermakova, Elena; Miller, Michelle C; Nesmelova, Irina V; López-Merino, Lara; Berbís, Manuel Alvaro; Nesmelov, Yuri; Tkachev, Yaroslav V; Lagartera, Laura; Daragan, Vladimir A; André, Sabine; Cañada, F Javier; Jiménez-Barbero, Jesús; Solís, Dolores; Gabius, Hans-Joachim; Mayo, Kevin H

    2013-01-01

    The product of p53-induced gene 1 is a member of the galectin family, i.e., galectin-7 (Gal-7). To move beyond structural data by X-ray diffraction, we initiated the study of the lectin by nuclear magnetic resonance (NMR) and circular dichroism spectroscopies, and molecular dynamics (MD) simulations. In concert, our results indicate that lactose binding to human Gal-7 induces long-range effects (minor conformational shifts and changes in structural dynamics) throughout the protein that result in stabilization of the dimer state, with evidence for positive cooperativity. Monte Carlo fits of 15N-Gal-7 HSQC titrations with lactose using a two-site model yield K1 = 0.9 ± 0.6 × 103 M−1 and K2 = 3.4 ± 0.8 × 103 M−1. Ligand binding-induced stabilization of the Gal-7 dimer was supported by several lines of evidence: MD-based calculations of interaction energies between ligand-loaded and ligand-free states, gel filtration data and hetero-FRET spectroscopy that indicate a highly reduced tendency for dimer dissociation in the presence of lactose, CD-based thermal denaturation showing that the transition temperature of the lectin is significantly increased in the presence of lactose, and saturation transfer difference (STD) NMR using a molecular probe of the monomer state whose presence is diminished in the presence of lactose. MD simulations with the half-loaded ligand-bound state also provided insight into how allosteric signaling may occur. Overall, our results reveal long-range effects on Gal-7 structure and dynamics, which factor into entropic contributions to ligand binding and allow further comparisons with other members of the galectin family. PMID:23376190

  5. Liquid crystal dimers

    CERN Document Server

    Kumar Pal, Santanu

    2017-01-01

    This book covers in-depth discussion of design principles, synthesis and thermal behavior of all types of liquid crystal (LC) dimers. The text presents recent advances in the field of LC dimers consisting of different mesogenic units such as calamitic, discotic and bent-core molecules. It starts with a chapter on the introduction of liquid crystal dimers, including their odd-even behavior, basic classification of dimers and common mesophases in dimers. The text shows how the molecular architectures are being used to develop new materials to study a range of interesting phenomena such as the biaxial nematic phase containing rod-like and disc-like mesogenic units. Finally, the text presents perspectives related to technological relevance of these dimers such as dopants in LC display mixtures exhibiting faster relaxation time, strong flexoelectric coupling and others to effect control over the properties of these materials.

  6. Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Bai D

    2017-09-01

    . Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-H2AX, p53, and LC3 and downregulation of Bcl-2. Conclusion: The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades. Keywords: zinc oxide nanoparticles, human ovarian cancer cells SKOV3, mitochondrial membrane potential, apoptosis, DNA fragmentation, autophagy

  7. Zinc supplementation alleviates the progression of diabetic nephropathy by inhibiting the overexpression of oxidative-stress-mediated molecular markers in streptozotocin-induced experimental rats.

    Science.gov (United States)

    Barman, Susmita; Pradeep, Seetur R; Srinivasan, Krishnapura

    2018-04-01

    Zinc deficiency during diabetes projects a role for zinc nutrition in the management of diabetic nephropathy. The current study explored whether zinc supplementation protects against diabetic nephropathy through modulation of kidney oxidative stress and stress-induced expression related to the inflammatory process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were exposed to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed a significant reversal of increased kidney weight and creatinine clearance. There was a significant reduction in hyperlipidemic condition along with improved PUFA:SFA ratio in the renal tissue. Expression of the lipid oxidative marker and expression of inflammatory markers, cytokines, fibrosis factors and apoptotic regulatory proteins observed in diabetic kidney were beneficially modulated by zinc supplementation, the ameliorative effect being concomitant with elevated antiapoptosis. There was a significant reduction in advanced glycation, expression of the receptor of the glycated products and oxidative stress markers. Zinc supplementation countered the higher activity and expression of polyol pathway enzymes in the kidney. Overexpression of the glucose transporters, as an adaptation to the increased need for glucose transport in diabetic condition, was minimized by zinc treatment. The pathological abnormalities in the renal architecture of diabetic animals were corrected by zinc intervention. Thus, dietary zinc supplementation has a significant beneficial effect in the control of diabetic nephropathy. This was exerted through a protective influence on oxidative-stress-induced cytokines, inflammatory proliferation and consequent renal injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Zinc-induced hemolytic anemia caused by ingestion of pennies by a pup

    International Nuclear Information System (INIS)

    Latimer, K.S.; Jain, A.V.; Inglesby, H.B.; Clarkson, W.D.; Johnson, G.B.

    1989-01-01

    A 4-month-old Pomeranian pup was examined because of anorexia, salivation, and persistent vomiting. Initial laboratory testing revealed marked hemolytic anemia with spherocytosis. Survey abdominal radiography revealed 4 metal objects which, when removed by gastrotomy, were identified as pennies. Of 4 pennies, 3 were minted since 1983 and were heavily pitted over the surface and rim. Partially digested pennies were composed of a copper-plated high zinc concentration alloy. Further laboratory testing indicated a marked increase in serum zinc concentration in the pup (28.8 mg/L), confirming metal toxicosis. Serum zinc concentrations decreased during recovery

  9. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

    Science.gov (United States)

    Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

    2017-06-01

    Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Site-specific analysis of UV-induced cyclobutane pyrimidine dimers in nucleotide excision repair-proficient and -deficient hamster cells: Lack of correlation with mutational spectra

    International Nuclear Information System (INIS)

    Vreeswijk, Maaike P.G.; Meijers, Caro M.; Giphart-Gassler, Micheline; Vrieling, Harry; Zeeland, Albert A. van; Mullenders, Leon H.F.; Loenen, Wil A.M.

    2009-01-01

    Irradiation of cells with UVC light induces two types of mutagenic DNA photoproducts, i.e. cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). To investigate the relationship between the frequency of UV-induced photolesions at specific sites and their ability to induce mutations, we quantified CPD formation at the nucleotide level along exons 3 and 8 of the hprt gene using ligation-mediated PCR, and determined the mutational spectrum of 132 UV-induced hprt mutants in the AA8 hamster cell line and of 165 mutants in its nucleotide excision repair-defective derivative UV5. In AA8 cells, transversions predominated with a strong strand bias towards thymine-containing photolesions in the non-transcribed strand. As hamster AA8 cells are proficient in global genome repair of 6-4PP but selectively repair CPD from the transcribed strand of active genes, most mutations probably resulted from erroneous bypass of CPD in the non-transcribed strand. However, the relative incidence of CPD and the positions where mutations most frequently arose do not correlate. In fact some major damage sites hardly gave rise to the formation of mutations. In the repair-defective UV5 cells, mutations were almost exclusively C > T transitions caused by photoproducts at PyC sites in the transcribed strand. Even though CPD were formed at high frequencies at some TT sites in UV5, these photoproducts did not contribute to mutation induction at all. We conclude that, even in the absence of repair, large variations in the level of induction of CPD at different sites throughout the two exons do not correspond to frequencies of mutation induction.

  11. Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.

    Science.gov (United States)

    Crowell, Kristen T; Kelleher, Shannon L; Soybel, David I; Lang, Charles H

    2016-11-01

    Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc-adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post-CLP Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E-BP1. Acutely, sepsis increased TNF-α and IL-6 mRNA in muscle, and the increase in TNF-α was significantly greater in ZM mice. However, muscle protein synthesis and 4E-BP1 phosphorylation returned to baseline 5 days post-CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF-α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. The lack of effects of zinc and nitric oxide in initial state of pilocarpine-induced seizures.

    Science.gov (United States)

    Noyan, Behzat; Jensen, Morten Skovgaard; Danscher, Gorm

    2007-07-01

    In this study we investigated whether intracerebroventricular (i.c.v.) injection of L-NAME (a nitric oxide synthase inhibitor) or CaEDTA (an extracellular zinc chelator) or the combination of the two could affect the initial phase of pilocarpine induced (2 h) seizures. Two groups of rats were used. Animals from both groups were given with i.c.v. injections of either saline (10 microl), L-NAME (150 microg/10 microl), CaEDTA (100 mM/10 microl) or L-NAME and CaEDTA. One group received pilocarpine HCl (380 mg/kg i.p.) the other served as control. Pilocarpine HCl was injected intraperitoneally 10 min later. The behavior of the animals was observed for 2h and the intensity of their seizures was scored. The rats were then sacrificed and their brains were removed and analyzed for zinc ions by using the immersion autometallography and the TSQ fluorescence staining. All the animals which received pilocarpine HCl developed seizures. Despite treatment with L-NAME and/or CaEDTA we found that the latency and the intensity of seizures were similar in both groups investigated. The distribution of stainable zinc ions and the intensity of staining in hippocampus were not affected by pilocarpine and found unchanged after L-NAME and/or CaEDTA injections in both the control animals and the pilocarpine treated animals. The data suggest that the nitric oxide system and zinc ions do not affect pilocarpine-induced seizures in their initial state.

  13. Singlet fission in pentacene dimers

    Science.gov (United States)

    Zirzlmeier, Johannes; Lehnherr, Dan; Coto, Pedro B.; Chernick, Erin T.; Casillas, Rubén; Basel, Bettina S.; Thoss, Michael; Tykwinski, Rik R.; Guldi, Dirk M.

    2015-01-01

    Singlet fission (SF) has the potential to supersede the traditional solar energy conversion scheme by means of boosting the photon-to-current conversion efficiencies beyond the 30% Shockley–Queisser limit. Here, we show unambiguous and compelling evidence for unprecedented intramolecular SF within regioisomeric pentacene dimers in room-temperature solutions, with observed triplet quantum yields reaching as high as 156 ± 5%. Whereas previous studies have shown that the collision of a photoexcited chromophore with a ground-state chromophore can give rise to SF, here we demonstrate that the proximity and sufficient coupling through bond or space in pentacene dimers is enough to induce intramolecular SF where two triplets are generated on one molecule. PMID:25858954

  14. Protective Role of L- Carnitine and Zinc against γ-Radiation induced Cardiac and testicular Disorders in Albino Rats

    International Nuclear Information System (INIS)

    Ramadan, F. L.; Abdel-Monem, D.D.; Ismail, N.H.

    2013-01-01

    L-Carnitine is a dipeptide amino acid necessary for fat metabolism, it provides energy by transporting long-chain fatty acids to mitochondria to act as a fuel and it is considered a powerful antioxidant. In addition, zinc is an essential mineral which helps to increase the secretion of male sex hormones and raises the sperm count, so its combination with L-carnitine is useful for the fertility process. The present study aims to evaluate the potency of L-carnitine and zinc as radio- protective and curative agent pre and after exposure to γ-radiation through biochemical, histological, morphological abnormalities of sperms and DNA damage in the sperms induced by γ-irradiation by comet assay. Animals received L-carnitine (LC) and zinc (Zn) orally at the dose 9.45 mg/100 gm body wt./day for successive 20 days and then exposed to whole body gamma radiation at the dose 4 Gy (1 Gy for 4 days, day after day) on the 7th day from treatment with antioxidant. Histological examinations of heart and testis tissues showed that administration of LC and Zn have attenuated radiation induced damage and improved tissues architecture. Moreover, the observed amelioration in the tissues was accompanied by a remarkable decrease of their lipid peroxide levels (malondialdehyde (MDA)), together with an increase in glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities. Hormonal determinations of serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) which carried out for fertility assessment showed that whole body γ-irradiation of rats induced significant decrease in serum testosterone while FSH and LH were significantly increased as compared with control group. On the other hand, irradiation caused significant elevation in the total number of abnormal head, and / or tail of sperms in comparison to the control rats. The comet assay showed that exposure to γ-radiation induced DNA damage of sperms (tail moment values).

  15. Molecular recognition of epothilones by microtubules and tubulin dimers revealed by biochemical and NMR approaches.

    Science.gov (United States)

    Canales, Angeles; Nieto, Lidia; Rodríguez-Salarichs, Javier; Sánchez-Murcia, Pedro A; Coderch, Claire; Cortés-Cabrera, Alvaro; Paterson, Ian; Carlomagno, Teresa; Gago, Federico; Andreu, José M; Altmann, Karl-Heinz; Jiménez-Barbero, Jesús; Díaz, J Fernando

    2014-04-18

    The binding of epothilones to dimeric tubulin and to microtubules has been studied by means of biochemical and NMR techniques. We have determined the binding constants of epothilone A (EpoA) and B (EpoB) to dimeric tubulin, which are 4 orders of magnitude lower than those for microtubules, and we have elucidated the conformation and binding epitopes of EpoA and EpoB when bound to tubulin dimers and microtubules in solution. The determined conformation of epothilones when bound to dimeric tubulin is similar to that found by X-ray crystallographic techniques for the binding of EpoA to the Tubulin/RB3/TTL complex; it is markedly different from that reported for EpoA bound to zinc-induced sheets obtained by electron crystallography. Likewise, only the X-ray structure of EpoA bound to the Tubulin/RB3/TTL complex at the luminal site, but not the electron crystallography structure, is compatible with the results obtained by STD on the binding epitope of EpoA bound to dimeric tubulin, thus confirming that the allosteric change (structuring of the M-loop) is the biochemical mechanism of induction of tubulin assembly by epothilones. TR-NOESY signals of EpoA bound to microtubules have been obtained, supporting the interaction with a transient binding site with a fast exchange rate (pore site), consistent with the notion that epothilones access the luminal site through the pore site, as has also been observed for taxanes. Finally, the differences in the tubulin binding affinities of a series of epothilone analogues has been quantitatively explained using the newly determined binding pose and the COMBINE methodology.

  16. Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14 from target cells in its apoptosis-inducing activity

    Directory of Open Access Journals (Sweden)

    Satoru Yui

    2002-01-01

    Full Text Available Background: Calprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner.

  17. Obtention of zinc polymethacrylate via free radicals induced by gamma radiation; Obtencion del polimetacrilato de zinc via radicales libres inducidos por radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Urena N, F.; Flores E, J. [Departamento de Fisica, Instituto Nacional de Investigaciones Nucleares, C.P. 52045 Estado de Mexico (Mexico)

    2000-07-01

    The objective of this work was to synthesise the monomer of zinc methacrylate and subsequently to carry out the polymerization reaction with the purpose to obtain the compound desired, the zinc polymethacrylate. For this it was used a gamma radiation source, {sup 60} Co, as initiator of the polymerization reaction. (Author)

  18. Localized frustration and binding-induced conformational change in recognition of 5S RNA by TFIIIA zinc finger.

    Science.gov (United States)

    Tan, Cheng; Li, Wenfei; Wang, Wei

    2013-12-19

    Protein TFIIIA is composed of nine tandemly arranged Cys2His2 zinc fingers. It can bind either to the 5S RNA gene as a transcription factor or to the 5S RNA transcript as a chaperone. Although structural and biochemical data provided valuable information on the recognition between the TFIIIIA and the 5S DNA/RNA, the involved conformational motions and energetic factors contributing to the binding affinity and specificity remain unclear. In this work, we conducted MD simulations and MM/GBSA calculations to investigate the binding-induced conformational changes in the recognition of the 5S RNA by the central three zinc fingers of TFIIIA and the energetic factors that influence the binding affinity and specificity at an atomistic level. Our results revealed drastic interdomain conformational changes between these three zinc fingers, involving the exposure/burial of several crucial DNA/RNA binding residues, which can be related to the competition between DNA and RNA for the binding of TFIIIA. We also showed that the specific recognition between finger 4/finger 6 and the 5S RNA introduces frustrations to the nonspecific interactions between finger 5 and the 5S RNA, which may be important to achieve optimal binding affinity and specificity.

  19. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    International Nuclear Information System (INIS)

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-01-01

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair

  20. Mixed dimers, ch. 7

    International Nuclear Information System (INIS)

    Deursen, A.P.J. van; Reuss, J.

    1976-01-01

    An attempt has been made to detect mixed dimers in nozzle beams of mixtures; NeAr and HeNe dimers were observed with sufficient intensity to determine the total collision cross section. A similar attempt for H 2 Ar was partially hampered by the circumstance that the corresponding HAr + ion must be detected on the wing of the thousand times larger Ar + peak. The search for H 2 He, H 2 Ne and HeAr dimers was not successful, due to masking ion peaks, H 5 + for HHe + , 21 Ne + for H 20 Ne + , and CO 2 + for HeAr + . (Auth.)

  1. 2-Ethynylpyridine dimers

    DEFF Research Database (Denmark)

    Bakarić, Danijela; Spanget-Larsen, Jens

    2018-01-01

    are used to study possible 2-EP dimer structures as well as their distribution in an inert solvent such as tetrachloroethene. Experimentally, the ≡C–H stretching vibration of the 2-EPmonomer absorbs close to 3300 cm−1, whereas a broad band withmaximum around 3215 cm−1 emerges as the concentration rises...... model with counterpoise correction predict that the two most stable dimers are of the pi-stacked variety, closely followed by dimers with intermolecular ≡C–H···N hydrogen bonding; the predicted red shifts of the ≡C–H stretching wavenumbers due to hydrogen bonding are in the range 54 – 120 cm–1...

  2. Selenium-induced autometallographic demonstration of endogenous zinc in organs of the rainbow trout, Salmo gairdneri

    DEFF Research Database (Denmark)

    Baatrup, E

    1989-01-01

    , the intestine, and the gills, whereas, no such grains were found in preparations from fish having received 1 ppm Se. The use of selenium for the histochemical demonstration of endogenous zinc versus exogenous metals is discussed. Also, consideration is given to the question of which part of the total tissue......Autometallographic (AMG) silver enhancement of endogenous zinc was studied in seven organs of the rainbow trout Salmo gairdneri. Groups of trout were injected intraperitoneally with sodium selenite in doses ranging from 0.08 to 25 ppm, administered 1 h before being killed. The concentration...

  3. Changes in signal transducer and activator of transcription 3 (STAT3) dynamics induced by complexation with pharmacological inhibitors of Src homology 2 (SH2) domain dimerization.

    Science.gov (United States)

    Resetca, Diana; Haftchenary, Sina; Gunning, Patrick T; Wilson, Derek J

    2014-11-21

    The activity of the transcription factor signal transducer and activator of transcription 3 (STAT3) is dysregulated in a number of hematological and solid malignancies. Development of pharmacological STAT3 Src homology 2 (SH2) domain interaction inhibitors holds great promise for cancer therapy, and a novel class of salicylic acid-based STAT3 dimerization inhibitors that includes orally bioavailable drug candidates has been recently developed. The compounds SF-1-066 and BP-1-102 are predicted to bind to the STAT3 SH2 domain. However, given the highly unstructured and dynamic nature of the SH2 domain, experimental confirmation of this prediction was elusive. We have interrogated the protein-ligand interaction of STAT3 with these small molecule inhibitors by means of time-resolved electrospray ionization hydrogen-deuterium exchange mass spectrometry. Analysis of site-specific evolution of deuterium uptake induced by the complexation of STAT3 with SF-1-066 or BP-1-102 under physiological conditions enabled the mapping of the in silico predicted inhibitor binding site to the STAT3 SH2 domain. The binding of both inhibitors to the SH2 domain resulted in significant local decreases in dynamics, consistent with solvent exclusion at the inhibitor binding site and increased rigidity of the inhibitor-complexed SH2 domain. Interestingly, inhibitor binding induced hot spots of allosteric perturbations outside of the SH2 domain, manifesting mainly as increased deuterium uptake, in regions of STAT3 important for DNA binding and nuclear localization. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    KAUST Repository

    Kim, Jeong Joo

    2016-04-09

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

  5. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    KAUST Repository

    Kim, Jeong  Joo; Lorenz, Robin; Arold, Stefan T.; Reger, Albert  S.; Sankaran, Banumathi; Casteel, Darren  E.; Herberg, Friedrich  W.; Kim, Choel

    2016-01-01

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

  6. Experimental observation of zinc dialkyl dithiophosphate (ZDDP)-induced iron sulphide formation

    Energy Technology Data Exchange (ETDEWEB)

    Soltanahmadi, Siavash, E-mail: s.soltanahmadi@leeds.ac.uk [Institute of Functional Surfaces, School of Mechanical Engineering, University of Leeds, LS2 9JT (United Kingdom); Morina, Ardian [Institute of Functional Surfaces, School of Mechanical Engineering, University of Leeds, LS2 9JT (United Kingdom); Eijk, Marcel C.P. van; Nedelcu, Ileana [SKF Engineering and Research Centre, 3430 DT Nieuwegein (Netherlands); Neville, Anne [Institute of Functional Surfaces, School of Mechanical Engineering, University of Leeds, LS2 9JT (United Kingdom)

    2017-08-31

    Graphical abstract: Chemical analysis of ZDDP-induced tribofilm under severe boundary lubricated regime in nano and micro-meter scales.▪ - Highlights: • A ZDDP-derived locally formed iron-sulphide layer is detected on the steel surface. • The iron-sulphide is a 5–10 nm thin distinct layer at steel-phosphate interface. • Near the surface-crack site the elemental distribution of the tribofilm is altered. • Sulphur concentration is enhanced in the iron-sulphide layer near the cracked-site. • ZDDP elements are detected inside the crack with a greater contribution of sulphur. - Abstract: Zinc dialkyl dithiophosphate (ZDDP) as a well-known anti-wear additive enhances the performance of the lubricant beyond its wear-protection action, through its anti-oxidant and Extreme Pressure (EP) functionality. In spite of over thirty years of research attempting to reveal the mechanism of action of ZDDP, there are still some uncertainties around the exact mechanisms of its action. This is especially the case with the role of sulphide layer formed in the tribofilm and its impact on surface fatigue. Although iron sulphide on the substrate is hypothesised in literature to form as a separate layer, there has been no concrete experimental observation on the distribution of the iron sulphide as a dispersed precipitate, distinct layer at the steel substrate or both. It remains to be clarified whether the iron sulphide layer homogeneously covers the surface or locally forms at the surface. In the current study a cross section of the specimen after experiment was prepared and has been investigated with Transmission Electron Microscopy (TEM) and Energy-Dispersive X-ray (EDX) elemental analysis. A 5–10 nm iron sulphide layer is visualised on the interface as a separate layer underneath the phosphate layer with an altered distribution of tribofilm elements near the crack site. The iron sulphide interface layer is more visible near the crack site where the concentration of the

  7. Experimental observation of zinc dialkyl dithiophosphate (ZDDP)-induced iron sulphide formation

    International Nuclear Information System (INIS)

    Soltanahmadi, Siavash; Morina, Ardian; Eijk, Marcel C.P. van; Nedelcu, Ileana; Neville, Anne

    2017-01-01

    Graphical abstract: Chemical analysis of ZDDP-induced tribofilm under severe boundary lubricated regime in nano and micro-meter scales.▪ - Highlights: • A ZDDP-derived locally formed iron-sulphide layer is detected on the steel surface. • The iron-sulphide is a 5–10 nm thin distinct layer at steel-phosphate interface. • Near the surface-crack site the elemental distribution of the tribofilm is altered. • Sulphur concentration is enhanced in the iron-sulphide layer near the cracked-site. • ZDDP elements are detected inside the crack with a greater contribution of sulphur. - Abstract: Zinc dialkyl dithiophosphate (ZDDP) as a well-known anti-wear additive enhances the performance of the lubricant beyond its wear-protection action, through its anti-oxidant and Extreme Pressure (EP) functionality. In spite of over thirty years of research attempting to reveal the mechanism of action of ZDDP, there are still some uncertainties around the exact mechanisms of its action. This is especially the case with the role of sulphide layer formed in the tribofilm and its impact on surface fatigue. Although iron sulphide on the substrate is hypothesised in literature to form as a separate layer, there has been no concrete experimental observation on the distribution of the iron sulphide as a dispersed precipitate, distinct layer at the steel substrate or both. It remains to be clarified whether the iron sulphide layer homogeneously covers the surface or locally forms at the surface. In the current study a cross section of the specimen after experiment was prepared and has been investigated with Transmission Electron Microscopy (TEM) and Energy-Dispersive X-ray (EDX) elemental analysis. A 5–10 nm iron sulphide layer is visualised on the interface as a separate layer underneath the phosphate layer with an altered distribution of tribofilm elements near the crack site. The iron sulphide interface layer is more visible near the crack site where the concentration of the

  8. Zinc-Dependent Protection of Tobacco and Rice Cells From Aluminum-Induced Superoxide-Mediated Cytotoxicity

    Science.gov (United States)

    Lin, Cun; Hara, Ayaka; Comparini, Diego; Bouteau, François; Kawano, Tomonori

    2015-01-01

    Al3+ toxicity in growing plants is considered as one of the major factors limiting the production of crops on acidic soils worldwide. In the last 15 years, it has been proposed that Al3+ toxicity are mediated with distortion of the cellular signaling mechanisms such as calcium signaling pathways, and production of cytotoxic reactive oxygen species (ROS) causing oxidative damages. On the other hand, zinc is normally present in plants at high concentrations and its deficiency is one of the most widespread micronutrient deficiencies in plants. Earlier studies suggested that lack of zinc often results in ROS-mediated oxidative damage to plant cells. Previously, inhibitory action of Zn2+ against lanthanide-induced superoxide generation in tobacco cells have been reported, suggesting that Zn2+ interferes with the cation-induced ROS production via stimulation of NADPH oxidase. In the present study, the effect of Zn2+ on Al3+-induced superoxide generation in the cell suspension cultures of tobacco (Nicotiana tabacum L., cell-line, BY-2) and rice (Oryza sativa L., cv. Nipponbare), was examined. The Zn2+-dependent inhibition of the Al3+-induced oxidative burst was observed in both model cells selected from the monocots and dicots (rice and tobacco), suggesting that this phenomenon (Al3+/Zn2+ interaction) can be preserved in higher plants. Subsequently induced cell death in tobacco cells was analyzed by lethal cell staining with Evans blue. Obtained results indicated that presence of Zn2+ at physiological concentrations can protect the cells by preventing the Al3+-induced superoxide generation and cell death. Furthermore, the regulation of the Ca2+ signaling, i.e., change in the cytosolic Ca2+ ion concentration, and the cross-talks among the elements which participate in the pathway were further explored. PMID:26648960

  9. D-dimer Test

    Science.gov (United States)

    ... 1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pagana, Kathleen D. & Pagana, ... www.itxm.org . Titus, K. (2003 January). Identity crisis persists: which D-dimer? CAP Today , In the ...

  10. Dimers in nucleating vapors

    Science.gov (United States)

    Lushnikov, A. A.; Kulmala, M.

    1998-09-01

    The dimer stage of nucleation may affect considerably the rate of the nucleation process at high supersaturation of the nucleating vapor. Assuming that the dimer formation limits the nucleation rate, the kinetics of the particle formation-growth process is studied starting with the definition of dimers as bound states of two associating molecules. The partition function of dimer states is calculated by summing the Boltzmann factor over all classical bound states, and the equilibrium population of dimers is found for two types of intermolecular forces: the Lennard-Jones (LJ) and rectangular well+hard core (RW) potentials. The principle of detailed balance is used for calculating the evaporation rate of dimers. The kinetics of the particle formation-growth process is then investigated under the assumption that the trimers are stable with respect to evaporation and that the condensation rate is a power function of the particle mass. If the power exponent λ=n/(n+1) (n is a non-negative integer), the kinetics of the process is described by a finite set of moments of particle mass distribution. When the characteristic time of the particle formation by nucleation is much shorter than that of the condensational growth, n+2 universal functions of a nondimensional time define the kinetic process. These functions are calculated for λ=2/3 (gas-to-particle conversion in the free molecular regime) and λ=1/2 (formation of islands on surfaces).

  11. Zinc triggers microglial activation.

    Science.gov (United States)

    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.

  12. Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity.

    Science.gov (United States)

    Nakatani, Yuichi; Yamazaki, Masatoshi; Chazin, Walter J; Yui, Satoru

    2005-10-24

    S100A8/A9 (calprotectin), which is released by neutrophils under inflammatory conditions, has the capacity to induce apoptosis in various cells. We previously reported that S100A8/A9 induces apoptosis of EL-4 lymphoma cells via the uptake of extracellular zinc in a manner similar to DTPA, a membrane-impermeable zinc chelator. In this study, S100A8/A9-induced apoptosis was examined in several cell lines that are weakly sensitive to DTPA, suggesting S100A8/A9 is directly responsible for apoptosis in these cells. Since zinc inhibits apoptosis of MM46, one of these cells, the regulation by zinc of the capacity of S100A8/A9 to bind MM46 cells was studied. When MM46 cells were incubated with S100A8/A9 in standard or zinc-depleted medium, the amounts of S100A8/A9 bound to cells was markedly lower at 3 h than at 1 h. In contrast, when MM46 cells were incubated with S100A8/A9 in the presence of high levels of zinc, binding to cells was the same at 1 and 3 h. When the cells were permeabilized with saponin prior to analysis, a larger amount of cell-associated S100A8/A9 was detected at 3 h. The amount was further increased in cells treated with chloroquine, suggesting that S100A8/A9 was internalized and degraded in lysosomes. Although it has been reported that S100A8/A9 binds to heparan sulfate on cell membranes, the amount of S100A8/A9 bound to MM46 cells was not reduced by heparinase treatment, but was reduced by trypsin treatment. These results suggest that S100A8/A9 induces apoptosis by direct binding to MM46 cells, and that this activity is regulated by zinc.

  13. Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response

    Directory of Open Access Journals (Sweden)

    Daniela eHellwig

    2016-05-01

    Full Text Available As part of the innate immune system, natural killer (NK cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can contribute to fungal clearance, neither the activation of NK cells by fungal pathogens nor the effects of perforin on fungal cells are well understood. In a dual approach, we have studied the global gene expression pattern of primary and cytokine activated NK cells after co-incubation with C. albicans and the transcriptomic adaptation of C. albicans to perforin exposure. NK cells responded to the fungal pathogen with an up-regulation of genes involved in immune signaling and release of cytokines. Furthermore, we observed a pronounced increase of genes involved in glycolysis and glycolysis inhibitor 2-deoxy-D-glucose impaired C. albicans induced NK cell activation. This strongly indicates that metabolic adaptation is a major part of the NK cell response to C. albicans infections. In the fungal pathogen, perforin induced a strong up-regulation of several fungal genes involved in the zinc depletion response, such as PRA1 and ZRT1. These data suggest that fungal zinc homeostasis is linked to the reaction to perforin secreted by NK cells. However, deletion mutants in PRA1 and ZRT1 did not show altered susceptibility to perforin.

  14. Synthesis of ZnO nanocoatings by decomposition of zinc acetate induced by electrons emitted by indium

    Energy Technology Data Exchange (ETDEWEB)

    Svoboda, Ladislav [Department of Chemistry, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Institute of Environmental Technologies, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Dvorský, Richard [Department of Physics, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Regional Materials Science and Technology Centre, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Nanotechnology Centre, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Praus, Petr, E-mail: petr.praus@vsb.cz [Department of Chemistry, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Institute of Environmental Technologies, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Matýsek, Dalibor [Institute of Geological Engineering, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Bednář, Jiří [Nanotechnology Centre, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic)

    2016-12-01

    Graphical abstract: - Highlights: • Hexagonal ZnO was synthetized by the decomposition of zinc acetate under UV light. • Source of photogenerated electron was an indium plate. • ZnO nanocoatings were deposited on surface of silica nanoparticles. • Mean thickness of the ZnO nanocoatings was estimated by DLS at 13 nm. - Abstract: In this work, a new method for the synthesis of ZnO nanocoatings is presented. It was tested for the nanocoating of silica nanoparticles forming core/shell SiO{sub 2}/ZnO nanoparticles by the decomposition of zinc acetate in silica aqueous nanodispersions induced by electrons generated by a plate indium photocathode, which was irradiated with a UV Hg lamp with maximum intensity at the wavelength of 245 nm. The ZnO nanocoatings were examined by X-ray diffraction (XRD), UV–Vis diffuse reflectance spectroscopy (DRS), photoluminescence spectroscopy (PLS), dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that ZnO of hexagonal structure formed nanocoatings with the mean thickness of 13 nm. The photocatalytic activity of ZnO nanocoatings was verified by the photocatalytic decomposition of methylene blue (MB). Such nanocoating procedure based on the electron-induced decomposition of suitable metal salts could be a promising method for various applications in nanotechnology.h.

  15. Inducible nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers in the cell cycle of the budding yeast Saccharomyces cerevisiae: evidence that inducible NER is confined to the G1 phase of the mitotic cell cycle

    International Nuclear Information System (INIS)

    Scott, A.D.; Waters, R.

    1997-01-01

    We previously reported on an inducible component of nucleotide excision repair in Saccharomyces cerevisiae that is controlled by the RAD16 gene. Here we describe a study of this event at the MAT alpha and HML alpha mating-type loci and on the transcribed (TS) and nontranscribed (NTS) strands of the RAD16 gene. Events were examined at various stages of the mitotic cycle in cells synchronised by centrifugal elutriation. Repair of cyclobutane pyrimidine dimers (CPDs) following a single UV dose does not vary significantly in different stages of the mitotic cell cycle. CPDs are removed more rapidly from the transcriptionally active MAT alpha locus than from the silent HML alpha locus, and the TS of RAD16 is repaired faster than the NTS in all stages of the cycle following a single UV irradiation. Enhanced excision of CPDs at MAT alpha and HML alpha can be induced only in the G1 and early S stages of the cell cycle. Here prior irradiation of cells with 25 J/m 2 enhances the removal of CPDs following a second UV dose of 70 J/m 2 . The level of enhancement of repair does not differ significantly between MAT alpha and HML alpha in G1. Enhanced removal of CPDs is absent when cells receive the inducing dose in late S or G2/M. Repair of CPDs in both strands of RAD16 is similarly enhanced only if cells receive the initial irradiation in G1 and early S. The level of enhanced removal of CPDs is not significantly different in the TS and NTS of RAD16 either in asynchronous cells or in cells preirradiated in G1 and early S. It has been shown by others that UV-induced expression of RAD16 remains at high levels if cells are held in G1 by treatment with alpha factor. Therefore the increase in RAD16 transcript levels in G1 may be responsible for the ability to enhance NER solely in this stage of the cell cycle

  16. Photoreactivation of ultraviolet light-induced damage in cultured fish cells as revealed by increased colony forming ability and decreased content of pyrimidine dimers

    International Nuclear Information System (INIS)

    Shima, A.; Ikenaga, M.; Egami, N.

    1981-01-01

    Cultured cells derived from a goldfish were irradiated with 254 nm ultraviolet light. Cell survival and splitting of pyrimidine dimers after photoreactivation treatment with white fluorescent lamps were examined by colony forming ability and by a direct dimer assay, respectively. When UV-irradiated (5 J/m 2 ) cells were illuminated by photoreactivating light, cell survival was enhanced up to a factor of 9(40 min) followed by a decline after prolonged exposures. Exposure of UV-irradiated (15 J/m 2 ) cells to radiation from white fluorescent lamps reduced the amounts of thymine-containing dimers in a photoreactivating fluence dependent manner, up to about 60% reduction at 120 min exposure. Keeping UV-irradiated cells in the dark for up to 120 min did not affect either cell survival or the amount of pyrimidine dimers in DNA, indicating that there were not detectable levels of a dark-repair system in the cells under our conditions. Correlation between photoreactivation of colony forming ability and photoreactivation of the pyrimidine dimers was demonstrated, at least at relatively low fluences of photoreactivating light. (author)

  17. Photoreactivation of ultraviolet light-induced damage in cultured fish cells as revealed by increased colony forming ability and decreased content of pyrimidine dimers

    Energy Technology Data Exchange (ETDEWEB)

    Shima, A. (Shiga University of Medical Science, Otsu (Japan)); Ikenaga, M. (Osaka Univ. (Japan). Faculty of Medicine); Nikaido, O.; Takebe, H. (Kyoto Univ. (Japan)); Egami, N. (Tokyo Univ. (Japan). Faculty of Science)

    1981-03-01

    Cultured cells derived from a goldfish were irradiated with 254 nm ultraviolet light. Cell survival and splitting of pyrimidine dimers after photoreactivation treatment with white fluorescent lamps were examined by colony forming ability and by a direct dimer assay, respectively. When UV-irradiated (5 J/m/sup 2/) cells were illuminated by photoreactivating light, cell survival was enhanced up to a factor of 9(40 min) followed by a decline after prolonged exposures. Exposure of UV-irradiated (15 J/m/sup 2/) cells to radiation from white fluorescent lamps reduced the amounts of thymine-containing dimers in a photoreactivating fluence dependent manner, up to about 60% reduction at 120 min exposure. Keeping UV-irradiated cells in the dark for up to 120 min did not affect either cell survival or the amount of pyrimidine dimers in DNA, indicating that there were not detectable levels of a dark-repair system in the cells under our conditions. Correlation between photoreactivation of colony forming ability and photoreactivation of the pyrimidine dimers was demonstrated, at least at relatively low fluences of photoreactivating light.

  18. Modulations of anisotropic optical transmission on alumina-doped zinc oxide surface by femtosecond laser induced ripples

    Science.gov (United States)

    Lu, Yanhui; Jiang, Lan; Sun, Jingya; Cao, Qiang; Wang, Qingsong; Han, Weina; Lu, Yongfeng

    2018-04-01

    This study demonstrated that femtosecond-laser-induced ripples on an alumina-doped zinc oxide (AZO) film with space intervals of approximately 340 and 660 nm exhibit modulations of anisotropic optical transmission. At low laser fluence, ripples can not affect the original absorption peak of AZO film, but at higher laser fluence, the absorption peak of AZO film is disappeared due to the modulation by femtosecond laser induced ripples. Moreover, the relationship between the anisotropic optical transmission and the features of nanostructures is discussed. Ripples with a space interval of approximately 660 nm have a higher ability to block light than nanostructures with a space interval of approximately 340 nm. These observations indicate that anisotropic optical transmission has potential applications in the field of optoelectronics.

  19. Induced superhydrophobic and antimicrobial character of zinc metal modified ceramic wall tile surfaces

    Science.gov (United States)

    Özcan, Selçuk; Açıkbaş, Gökhan; Çalış Açıkbaş, Nurcan

    2018-04-01

    Hydrophobic surfaces are also known to have antimicrobial effect by restricting the adherence of microorganisms. However, ceramic products are produced by high temperature processes resulting in a hydrophilic surface. In this study, an industrial ceramic wall tile glaze composition was modified by the inclusion of metallic zinc powder in the glaze suspension applied on the pre-sintered wall tile bodies by spraying. The glazed tiles were gloss fired at industrially applicable peak temperatures ranging from 980 °C to 1100 °C. The fired tile surfaces were coated with a commercial fluoropolymer avoiding water absorption. The surfaces were characterized with SEM, EDS, XRD techniques, roughness, sessile water drop contact angle, surface energy measurements, and standard antimicrobial tests. The surface hydrophobicity and the antimicrobial activity results were compared with that of unmodified, uncoated gloss fired wall tiles. A superhydrophobic contact angle of 150° was achieved at 1000 °C peak temperature due to the formation of micro-structured nanocrystalline zinc oxide granules providing a specific surface topography. At higher peak temperatures the hydrophobicity was lost as the specific granular surface topography deteriorated with the conversion of zinc oxide granules to the ubiquitous willemite crystals embedded in the glassy matrix. The antimicrobial efficacy also correlated with the hydrophobic character.

  20. Photoionization of helium dimers

    International Nuclear Information System (INIS)

    Havermeier, Tilo

    2010-01-01

    The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

  1. Surface nanostructuring by ion-induced localized plasma expansion in zinc oxide

    Energy Technology Data Exchange (ETDEWEB)

    El-Said, A. S., E-mail: elsaid@kfupm.edu.sa, E-mail: a.s.el-said@hzdr.de [Physics Department, King Fahd University of Petroleum and Minerals, Dhahran 31261 (Saudi Arabia); Institute of Ion Beam Physics and Materials Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden (Germany); Physics Department, Faculty of Science, Mansoura University, 35516 Mansoura (Egypt); Moslem, W. M. [Department of Physics, Faculty of Science, Port Said University, Port Said 42521 (Egypt); Centre for Theoretical Physics, British University in Egypt (BUE), El-Shorouk City, Cairo (Egypt); Djebli, M. [Theoretical Physics Laboratory, Faculty of Physics USTHB, B.P. 32 Bab Ezzour, 16079 Algiers (Algeria)

    2014-06-09

    Creation of hillock-like nanostructures on the surface of zinc oxide single crystals by irradiation with slow highly charged ions is reported. At constant kinetic energy, the nanostructures were only observed after irradiation with ions of potential energies above a threshold between 19.1 keV and 23.3 keV. The size of the nanostructures increases as a function of potential energy. A plasma expansion approach is used to explain the nanostructures creation. The calculations showed that the surface nanostructures became taller with the increase of ionic temperature. The influence of charged cluster formation and the relevance of their polarity are discussed.

  2. Surface nanostructuring by ion-induced localized plasma expansion in zinc oxide

    International Nuclear Information System (INIS)

    El-Said, A. S.; Moslem, W. M.; Djebli, M.

    2014-01-01

    Creation of hillock-like nanostructures on the surface of zinc oxide single crystals by irradiation with slow highly charged ions is reported. At constant kinetic energy, the nanostructures were only observed after irradiation with ions of potential energies above a threshold between 19.1 keV and 23.3 keV. The size of the nanostructures increases as a function of potential energy. A plasma expansion approach is used to explain the nanostructures creation. The calculations showed that the surface nanostructures became taller with the increase of ionic temperature. The influence of charged cluster formation and the relevance of their polarity are discussed.

  3. Selenium-induced autometallographic demonstration of endogenous zinc in organs of the rainbow trout, Salmo gairdneri

    DEFF Research Database (Denmark)

    Baatrup, E

    1989-01-01

    of selenium obtained by each organ was determined by gamma-spectrometry, and compared with the autometallographic deposition of silver grains. The relative accumulation of selenium in the organs was: liver greater than spleen greater than kidney greater than intestine greater than gills greater than brain......, the intestine, and the gills, whereas, no such grains were found in preparations from fish having received 1 ppm Se. The use of selenium for the histochemical demonstration of endogenous zinc versus exogenous metals is discussed. Also, consideration is given to the question of which part of the total tissue...

  4. Administration of Zinc plus Cyclo-(His-Pro Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2017-01-01

    Full Text Available The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro (ZC on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ-induced diabetes. ZC (27 mg/kg was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase or 45 (late phase days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

  5. Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

    International Nuclear Information System (INIS)

    Do, To Uyen; Ho, Bay; Shih, Shyh-Jen; Vaughan, Andrew

    2012-01-01

    Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient

  6. Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

    Energy Technology Data Exchange (ETDEWEB)

    Do, To Uyen [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Ho, Bay; Shih, Shyh-Jen [Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Vaughan, Andrew, E-mail: Andrew.vaughan@ucdmc.ucdavis.edu [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States)

    2012-12-15

    Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient.

  7. Cuz1/Ynl155w, a Zinc-dependent Ubiquitin-binding Protein, Protects Cells from Metalloid-induced Proteotoxicity*

    Science.gov (United States)

    Hanna, John; Waterman, David; Isasa, Marta; Elsasser, Suzanne; Shi, Yuan; Gygi, Steven; Finley, Daniel

    2014-01-01

    Protein misfolding is a universal threat to cells. The ubiquitin-proteasome system mediates a cellular stress response capable of eliminating misfolded proteins. Here we identify Cuz1/Ynl155w as a component of the ubiquitin system, capable of interacting with both the proteasome and Cdc48. Cuz1/Ynl155w is regulated by the transcription factor Rpn4, and is required for cells to survive exposure to the trivalent metalloids arsenic and antimony. A related protein, Yor052c, shows similar phenotypes, suggesting a multicomponent stress response pathway. Cuz1/Ynl155w functions as a zinc-dependent ubiquitin-binding protein. Thus, Cuz1/Ynl155w is proposed to protect cells from metalloid-induced proteotoxicity by delivering ubiquitinated substrates to Cdc48 and the proteasome for destruction. PMID:24297164

  8. Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity.

    Science.gov (United States)

    Yui, Satoru; Nakatani, Yuichi; Hunter, Michael J; Chazin, Walter J; Yamazaki, Masatoshi

    2002-06-01

    Calprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner. The present study was undertaken to elucidate which subunit is responsible for the apoptosis-inducing activity, and to explore the mechanism of zinc-reversible apoptosis induction. The apoptosis-inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL-4 lymphoma cells in vitro. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut-off dialysis membrane. The cytotoxicity of rhMRP14 against EL-4 cells was first detected at 10 microM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 microM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 microM). When the cells were cultured in divalent cation-depleted medium, each dose-response curve was shifted to about a four-fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane-impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time-course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions. These data indicate that calprotectin has higher specific activity to induce apoptosis than the Individual subunits, and that the mechanism is exclusion of zinc

  9. A novel cold-inducible zinc finger protein from soybean, SCOF-1, enhances cold tolerance in transgenic plants.

    Science.gov (United States)

    Kim, J C; Lee, S H; Cheong, Y H; Yoo, C M; Lee, S I; Chun, H J; Yun, D J; Hong, J C; Lee, S Y; Lim, C O; Cho, M J

    2001-02-01

    Cold stress on plants induces changes in the transcription of cold response genes. A cDNA clone encoding C2H2-type zinc finger protein, SCOF-1, was isolated from soybean. The transcription of SCOF-1 is specifically induced by low temperature and abscisic acid (ABA) but not by dehydration or high salinity. Constitutive overexpression of SCOF-1 induced cold-regulated (COR) gene expression and enhanced cold tolerance of non-acclimated transgenic Arabidopsis and tobacco plants. SCOF-1 localized to the nucleus but did not bind directly to either C-repeat/dehydration (CRT/DRE) or ABA responsive element (ABRE), cis-acting DNA regulatory elements present in COR gene promoters. However, SCOF-1 greatly enhanced the DNA binding activity of SGBF-1, a soybean G-box binding bZIP transcription factor, to ABRE in vitro. SCOF-1 also interacted with SGBF-1 in a yeast two-hybrid system. The SGBF-1 transactivated the beta-glucuronidase reporter gene driven by the ABRE element in Arabidopsis leaf protoplasts. Furthermore, the SCOF-1 enhanced ABRE-dependent gene expression mediated by SGBF-1. These results suggest that SCOF-1 may function as a positive regulator of COR gene expression mediated by ABRE via protein-protein interaction, which in turn enhances cold tolerance of plants.

  10. Rapid method for detecting base damage in DNA of mammalian cells: assay of U. V. -induced pyrimidine dimers in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, P E [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit; Jansson, G; Ahnstroem, G

    1978-11-01

    Simple and rapid techniques are described for the detection of pyrimidine dimers in DNA. Human cells derived from embryonic lung tissue were UV-irradiated and subjected to either an osmotic shock procedure or detergent lysis, then treated with UV-endonuclease from Micrococcus luteus and the DNA partially denatured by treatment with weak alkali. Brief sonication reduced the molecular weight of the DNA, and the single- and double-stranded DNA could then be separated by hydroxylapatite chromatography. Approximately 40% of the expected number of pyrimidine dimers were detected by the enzyme treatment technique. The mean value of numbers of strand breaks per 10/sup 9/ dalton per J/m/sup 2/ was approximately 50% of the expected value. The method has advantages of speed and reproducibility and a large reduction in the quantities of materials used, particularly at the scintillation-counting stage.

  11. Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation

    International Nuclear Information System (INIS)

    Dambara, Atsushi; Morinaga, Takatoshi; Fukuda, Naoyuki; Yamakawa, Yoshinori; Kato, Takuya; Enomoto, Atsushi; Asai, Naoya; Murakumo, Yoshiki; Matsuo, Seiichi; Takahashi, Masahide

    2007-01-01

    GZF1 is a zinc finger protein induced by glial cell-line-derived neurotrophic factor (GDNF). It is a sequence-specific transcriptional repressor with a BTB/POZ (Broad complex, Tramtrack, Bric a brac/Poxvirus and zinc finger) domain and ten zinc finger motifs. In the present study, we used immunoprecipitation and mass spectrometry to identify nucleolin as a GZF1-binding protein. Deletion analysis revealed that zinc finger motifs 1-4 of GZF1 mediate its association with nucleolin. When zinc fingers 1-4 were deleted from GZF1 or nucleolin expression was knocked down by short interference RNA (siRNA), nuclear localization of GZF1 was impaired. These results suggest that nucleolin is involved in the proper subcellular distribution of GZF1. In addition, overexpression of nucleolin moderately inhibited the transcriptional repressive activity of GZF1 whereas knockdown of nucleolin expression by siRNA enhanced its activity. Thus, the repressive activity of GZF1 is modulated by the level at which nucleolin is expressed. Finally, we found that knockdown of GZF1 and nucleolin expression markedly impaired cell proliferation. These findings suggest that the physiological functions of GZF1 may be regulated by the protein's association with nucleolin

  12. Investigation on the negative bias illumination stress-induced instability of amorphous indium-tin-zinc-oxide thin film transistors

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jaeman; Kim, Dae Geun; Kim, Dong Myong; Choi, Sung-Jin; Kim, Dae Hwan, E-mail: byungdu.ahn@samsung.com, E-mail: drlife@kookmin.ac.kr [School of Electrical Engineering, Kookmin University, Seoul 136-702 (Korea, Republic of); Lim, Jun-Hyung; Lee, Je-Hun; Ahn, Byung Du, E-mail: byungdu.ahn@samsung.com, E-mail: drlife@kookmin.ac.kr [Samsung Display Co., Ltd., Yongin, Gyeonggi-Do 446-711 (Korea, Republic of); Kim, Yong-Sung [Korea Research Institute of Standards and Science, Yuseong, Daejeon 305-340 (Korea, Republic of)

    2014-10-13

    The quantitative analysis of mechanism on negative bias illumination stress (NBIS)-induced instability of amorphous indium-tin-zinc-oxide thin-film transistor (TFT) was suggested along with the effect of equivalent oxide thickness (EOT) of gate insulator. The analysis was implemented through combining the experimentally extracted density of subgap states and the device simulation. During NBIS, it was observed that the thicker EOT causes increase in both the shift of threshold voltage and the variation of subthreshold swing as well as the hump-like feature in a transfer curve. We found that the EOT-dependence of NBIS instability can be clearly explicated with the donor creation model, in which a larger amount of valence band tail states is transformed into either the ionized oxygen vacancy V{sub O}{sup 2+} or peroxide O{sub 2}{sup 2−} with the increase of EOT. It was also found that the V{sub O}{sup 2+}-related extrinsic factor accounts for 80%–92% of the total donor creation taking place in the valence band tail states while the rest is taken by the O{sub 2}{sup 2–} related intrinsic factor. The ratio of extrinsic factor compared to the total donor creation also increased with the increase of EOT, which could be explained by more prominent oxygen deficiency. The key founding of our work certainly represents that the established model should be considered very effective for analyzing the instability of the post-indium-gallium-zinc-oxide (IGZO) ZnO-based compound semiconductor TFTs with the mobility, which is much higher than those of a-IGZO TFTs.

  13. Comparative Study of Different Methods to Determine the Role of Reactive Oxygen Species Induced by Zinc Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Nigar A. Najim

    2016-08-01

    Full Text Available Accumulation of reactive oxygen species (ROS followed by an increase in oxidative stress is associated with cellular responses to nanoparticle induced cell damages. Finding the best method for assessing intracellular ROS production is the key step in the detection of oxidative stress induced injury. This study evaluates and compares four different methods for the measurement of intracellular ROS generation using fluorogenic probe, 2´,7´-dichlorofluorescein diacetate (DCFH-DA. Hydrogen peroxide (H2O2 was utilised as a positive control to assess the reactivity of the probe. Spherically shaped zinc oxide (ZnO nanoparticles with an average particle size of 85.7 nm were used to determine the diverse roles of ROS in nanotoxicity in Hs888Lu and U937 cell lines. The results showed that different methods exhibit different patterns of ROS measurement. In conclusion this study found that the time point at which the DCFH-DA is added to the reaction, the incubation time and the oxidative species that is responsible for the oxidation of DCFH, have impact on the intracellular ROS measurement.

  14. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Science.gov (United States)

    Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

    2013-04-01

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  15. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Faddah, L. M.; Baky, Nayira A. Abdel [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia); Mohamed, Azza M., E-mail: azzamohamed99@yahoo.com [King Abdulaziz University, Biochemistry Department, Faculty of Science for Girls (Saudi Arabia); Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M. [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia)

    2013-04-15

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-{alpha}, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  16. Nanosized zinc oxide particles do not promote DHPN-induced lung carcinogenesis but cause reversible epithelial hyperplasia of terminal bronchioles.

    Science.gov (United States)

    Xu, Jiegou; Futakuchi, Mitsuru; Alexander, David B; Fukamachi, Katsumi; Numano, Takamasa; Suzui, Masumi; Shimizu, Hideo; Omori, Toyonori; Kanno, Jun; Hirose, Akihiko; Tsuda, Hiroyuki

    2014-01-01

    Zinc oxide (ZnO) is known to induce lung toxicity, including terminal bronchiolar epithelial hyperplasia, which gives rise to concerns that nanosized ZnO (nZnO) might lead to lung carcinogenesis. We studied the tumor promoting activity of nZnO by an initiation-promotion protocol using human c-Ha-ras proto-oncogene transgenic rats (Hras128 rats). The rats were given 0.2 % N-nitrosobis(2-hydroxypropyl)amine (DHPN) in the drinking water for 2 weeks and then treated with 0.5 ml of 250 or 500 μg/ml nZnO suspension by intra-pulmonary spraying once every 2 weeks for a total of 7 times. Treatment with nZnO particles did not promote DHPN-induced lung carcinogenesis. However, nZnO dose-dependently caused epithelial hyperplasia of terminal bronchioles (EHTB) and fibrosis-associated interstitial pneumonitis (FAIP) that were independent of DHPN treatment. Tracing the fate of EHTB lesions in wild-type rats indicated that the hyperplastic lesions almost completely disappeared within 12 weeks after the last nZnO treatment. Since nZnO particles were not found in the lung and ZnCl2 solution induced similar lung lesions and gene expression profiles, the observed lesions were most likely caused by dissolved Zn(2+). In summary, nZnO did not promote carcinogenesis in the lung and induced EHTB and FAIP lesions that regressed rapidly, probably due to clearance of surplus Zn(2+) from the lung.

  17. Zinc Oxide Nanoparticle Induces Microglial Death by NADPH-Oxidase-Independent Reactive Oxygen Species as well as Energy Depletion.

    Science.gov (United States)

    Sharma, Anuj Kumar; Singh, Vikas; Gera, Ruchi; Purohit, Mahaveer Prasad; Ghosh, Debabrata

    2017-10-01

    Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death. The present study showed that the 24 h inhibitory concentration 50 (IC 50 ) of ZnO-NP for microglia is 6.6 μg/ml. Early events following ZnO-NP exposure involved increase in intracellular calcium level as well as reactive oxygen species (ROS). Neither of NADPH oxidase inhibitors, apocynin, (APO) and diphenyleneiodonium chloride (DPIC) were able to reduce the ROS level and rescue microglia from ZnO-NP toxicity. In contrary, N-acetyl cysteine (NAC) showed opposite effect. Exogenous supplementation of superoxide dismutase (SOD) reduced ROS significantly even beyond control level but partially rescued microglial viability. Interestingly, pyruvate supplementation rescued microglia near to control level. Following 10 h of ZnO-NP exposure, intracellular ATP level was measured to be almost 50 % to the control. ZnO-NP-induced ROS as well as ATP depletion both disturbed mitochondrial membrane potential and subsequently triggered the apoptotic pathway. The level of apoptosis-inducing proteins was measured by western blot analysis and found to be upregulated. Taken together, we have deciphered that ZnO-NP induced microglial apoptosis by NADPH oxidase-independent ROS as well as ATP depletion.

  18. γ-irradiation induced zinc ferrites and their enhanced room-temperature ammonia gas sensing properties

    Science.gov (United States)

    Raut, S. D.; Awasarmol, V. V.; Ghule, B. G.; Shaikh, S. F.; Gore, S. K.; Sharma, R. P.; Pawar, P. P.; Mane, R. S.

    2018-03-01

    Zinc ferrite (ZnFe2O4) nanoparticles (NPs), synthesized using a facile and cost-effective sol-gel auto-combustion method, were irradiated with 2 and 5 kGy γ-doses using 60Co as a radioactive source. Effect of γ-irradiation on the structure, morphology, pore-size and pore-volume and room-temperature (300 K) gas sensor performance has been measured and reported. Both as-synthesized and γ-irradiated ZnFe2O4 NPs reveal remarkable gas sensor activity to ammonia in contrast to methanol, ethanol, acetone and toluene volatile organic gases. The responses of pristine, 2 and 5 kGy γ-irradiated ZnFe2O4 NPs are respectively 55%, 66% and 81% @100 ppm concentration of ammonia, signifying an importance of γ-irradiation for enhancing the sensitivity, selectivity and stability of ZnFe2O4 NPs as ammonia gas sensors. Thereby, due to increase in surface area and crystallinity on γ-doses, the γ-irradiation improves the room-temperature ammonia gas sensing performance of ZnFe2O4.

  19. The Geometry-Induced Superhydrophobic Property of Carpet-like Zinc Films

    International Nuclear Information System (INIS)

    Liang Li-Xing; Deng Yuan; Wang Yao

    2013-01-01

    Carpet-like zinc films with unique nanowires are fabricated by using a simple physical evaporation method. The definite morphologies of the films endow the superhydrophobic material with a contact angle of about 157.9°, and by additional modification of CF 3 (CF 2 ) 7 CH 2 CH 2 Si(OCH 3 ) 3 the water adhesive force could be tuned from 58.3 μN to 14.6 μN. In order to analyze the controllable adhesion of superhydrophobic Zn films, we study the microstructure and chemical compositions of the films by x-ray diffraction SEM, TEM, HRTEM and EDAX. Furthermore, a model based on the balance of micro-surface energy is proposed to illustrate the relationship of the geometry and wettability properties of the films. The model provides new insights into how to design-oriented microchannels and micro-protuberance on material surfaces, which is of benefit for controlling their ability of caught-collection in air bubbles and water-pinning collection

  20. Laser-induced optical effects in triglycine-zinc chloride single crystals

    International Nuclear Information System (INIS)

    Wojciechowski, A.; Kityk, I.V.; Lakshminarayana, G.; Fuks-Janczarek, I.; Berdowski, J.; Berdowska, E.; Tylczynski, Z.

    2010-01-01

    The influence of irradiation by a cw 532 nm laser on the behavior of the absorption and optical second harmonic generation of triglicyne-zinc chloride crystal has been studied. Additional absorption bands correlate well with the time of the cw laser exposure. These lines occur at 260 nm, 305 nm, and, with small intensity, at 355 nm. The remaining part of the spectra shows substantially less changes. According to the performed quantum chemical simulations, one may expect that the observed dependences and the stability of the observed photoinduced changes are caused by formation of polarized electron-phonon states and the principal role should belong here to the electron-phonon anharmonicities, which cause the effects described by the non-polar third rank polar tensor like optical second harmonic generation. The increasing optical SHG signal shows a clear correlation with the behavior of the green laser-532 nm. It is important principal that for the blue laser-405 nm, the SHG effect is substantially less. This may reflect that the additional absorption maxima may be responsible for the non-linear optical effects. The effect demonstrates a slow time decay.

  1. Serendipitous discovery of light-induced (In Situ) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor.

    Science.gov (United States)

    Bongard, Robert D; Lepley, Michael; Thakur, Khushabu; Talipov, Marat R; Nayak, Jaladhi; Lipinski, Rachel A Jones; Bohl, Chris; Sweeney, Noreena; Ramchandran, Ramani; Rathore, Rajendra; Sem, Daniel S

    2017-05-31

    Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC 50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC 50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common

  2. Preventive effect of zinc on nickel-induced oxidative liver injury in rats

    African Journals Online (AJOL)

    MIDOU

    2013-12-18

    Dec 18, 2013 ... induced oxidative liver injury and lipid peroxidation probably due to its antioxidant proprieties. ... enzyme in every enzyme classification (Coyle et al.,. 2002). Others .... control group had a regular histological structure with a.

  3. Characterization and metal-induced gene transcription of two new copper zinc superoxide dismutases in the solitary ascidian Ciona intestinalis

    International Nuclear Information System (INIS)

    Ferro, Diana; Franchi, Nicola; Mangano, Valentina; Bakiu, Rigers; Cammarata, Matteo; Parrinello, Nicolò; Santovito, Gianfranco; Ballarin, Loriano

    2013-01-01

    Highlights: •Ciona intestinalis express two copper-zinc superoxide dismutases (Cu,Zn SODs), one extracellular (Ci-SODa) and one intracellular isoform (Ci-SODb). •Promoters contain consensus sequences similar to mammalian MRE. •Metal exposure results in a significant increase of gene transcription: ci-soda is induced especially by copper and zinc, the increase of ci-sodb transcription is more evident after cadmium exposure. •Genes are mostly transcribed in circulating hemocytes and in ovarian follicular cells. -- Abstract: Antioxidant enzymes are known to protect living organisms against the oxidative stress risk, also induced by metals. In the present study, we describe the purification and molecular characterization of two Cu,Zn superoxide dismutases (SODs), referred to as Ci-SODa and Ci-SODb, from Ciona intestinalis, a basal chordate widely distributed in temperate shallow seawater. The putative amino acid sequences were compared with Cu,Zn SODs from other metazoans and phylogenetic analyses indicate that the two putative Ci-SODs are more related to invertebrate SODs than vertebrate ones. Both phylogenetic and preliminary homology modeling analyses suggest that Ci-SODa and Ci-SODb are extracellular and intracellular isoform, respectively. The mRNA of the two Cu,Zn SODs was localized in hemocytes and in ovarian follicular cells, as revealed by in situ hybridization. The time course of SOD mRNA levels in the presence of three different metals showed upregulation of ci-soda and inhibition of ci-sodb. Spectrophotometric analysis confirms the presence of SOD activity in Ciona tissues. Our in silico analyses of the ci-soda promoter region revealed putative consensus sequences similar to mammalian metal-responsive elements (MRE), suggesting that the transcription of these genes directly depends on metals. These data emphasize the importance of complex metal regulation of ci-soda and ci-sodb transcription, as components of an efficient detoxification pathway

  4. Characterization and metal-induced gene transcription of two new copper zinc superoxide dismutases in the solitary ascidian Ciona intestinalis

    Energy Technology Data Exchange (ETDEWEB)

    Ferro, Diana [Department of Biology, University of Padova, Padova (Italy); Institute for Evolution and Biodiversity, Westfälische Wilhelms-Universität, Münster (Germany); Franchi, Nicola [Department of Biology, University of Padova, Padova (Italy); Department of Biological, Chemical, Pharmaceutical Science and Technology, University of Palermo, Palermo (Italy); Mangano, Valentina [Department of Biological, Chemical, Pharmaceutical Science and Technology, University of Palermo, Palermo (Italy); Bakiu, Rigers [Department of Crop Production, Agricultural University of Tirana, Tirana (Albania); Cammarata, Matteo; Parrinello, Nicolò [Department of Biological, Chemical, Pharmaceutical Science and Technology, University of Palermo, Palermo (Italy); Santovito, Gianfranco, E-mail: gianfranco.santovito@unipd.it [Department of Biology, University of Padova, Padova (Italy); Ballarin, Loriano [Department of Biology, University of Padova, Padova (Italy)

    2013-09-15

    Highlights: •Ciona intestinalis express two copper-zinc superoxide dismutases (Cu,Zn SODs), one extracellular (Ci-SODa) and one intracellular isoform (Ci-SODb). •Promoters contain consensus sequences similar to mammalian MRE. •Metal exposure results in a significant increase of gene transcription: ci-soda is induced especially by copper and zinc, the increase of ci-sodb transcription is more evident after cadmium exposure. •Genes are mostly transcribed in circulating hemocytes and in ovarian follicular cells. -- Abstract: Antioxidant enzymes are known to protect living organisms against the oxidative stress risk, also induced by metals. In the present study, we describe the purification and molecular characterization of two Cu,Zn superoxide dismutases (SODs), referred to as Ci-SODa and Ci-SODb, from Ciona intestinalis, a basal chordate widely distributed in temperate shallow seawater. The putative amino acid sequences were compared with Cu,Zn SODs from other metazoans and phylogenetic analyses indicate that the two putative Ci-SODs are more related to invertebrate SODs than vertebrate ones. Both phylogenetic and preliminary homology modeling analyses suggest that Ci-SODa and Ci-SODb are extracellular and intracellular isoform, respectively. The mRNA of the two Cu,Zn SODs was localized in hemocytes and in ovarian follicular cells, as revealed by in situ hybridization. The time course of SOD mRNA levels in the presence of three different metals showed upregulation of ci-soda and inhibition of ci-sodb. Spectrophotometric analysis confirms the presence of SOD activity in Ciona tissues. Our in silico analyses of the ci-soda promoter region revealed putative consensus sequences similar to mammalian metal-responsive elements (MRE), suggesting that the transcription of these genes directly depends on metals. These data emphasize the importance of complex metal regulation of ci-soda and ci-sodb transcription, as components of an efficient detoxification pathway

  5. Zinc Deficiency Induces Apoptosis via Mitochondrial p53- and Caspase-Dependent Pathways in Human Neuronal Precursor Cells

    Science.gov (United States)

    Seth, Rohit; Corniola, Rikki S.; Gower-Winter, Shannon D.; Morgan, Thomas J., Jr.; Bishop, Brian; Levenson, Cathy W.

    2015-01-01

    Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent…

  6. Isolation and properties of strains of Micrococcus (Deinococcus) radiodurans unable to excise ultraviolet light-induced pyrimidine dimers from DNA: evidence for two excision pathways

    International Nuclear Information System (INIS)

    Moseley, B.E.B.; Evans, D.M.

    1983-01-01

    A mutant of Deinococcus (formerly Micrococcus) radiodurans sensitive to both the lethal effect of mitomycin C and the mutagenic effect of simple alkylating agents, but having wild-type resistance to UV light, was treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Three strains were isolated that were UV-sensitive, but had wild-type resistance to the lethal effect of methyl methanesulphonate and all were shown to be unable to excise pyrimidine dimers. The three strains UVS9, UVS25 and UVS78 had, in addition to the mutation in mtcA, mutations in loci designated uvsC, uvsD and uvsE, respectively. When the mutant mtcA gene was replaced by its wild-type allele in all three strains they became UV- and mitomycin C-resistant. On incubating the double mutants UVS9, UVS25 and UVS78 with wild-type DNA about 50% of the transformants selected for UV resistance were mitomycin C-sensitive and about 50% resistant depending on whether the mutant mtcA or the uvsC, D or E genes had been replaced by their wild-type alleles. Although strains mutant singly in uvsC, D or E were UV-resistant the rates of excision of pyrimidine dimers differed between them and was slower in all of them than in the wild-type and strain 302. (author)

  7. Alkane dimers interaction

    DEFF Research Database (Denmark)

    Ferrighi, Lara; Madsen, Georg Kent Hellerup; Hammer, Bjørk

    2010-01-01

    The interaction energies of a series of n-alkane dimers, from methane to decane, have been investigated with Density Functional Theory (DFT), using the MGGA-M06-L density functional. The results are compared both to the available wavefunction-based values as well as to dispersion corrected DFT...... values. The MGGA-M06-L density functional is a semi-local functional designed and has proven to provide accurate estimates of dispersion interactions for several systems at moderate computational cost. In the present application, it reproduces the trends obtained by the more expensive wavefunction...

  8. Identification and characterization of a salt stress-inducible zinc finger protein from Festuca arundinacea

    Directory of Open Access Journals (Sweden)

    Martin Ruth C

    2012-01-01

    Full Text Available Abstract Background Increased biotic and abiotic plant stresses due to climate change together with an expected global human population of over 9 billion by 2050 intensifies the demand for agricultural production on marginal lands. Soil salinity is one of the major abiotic stresses responsible for reduced crop productivity worldwide and the salinization of arable land has dramatically increased over the last few decades. Consequently, as land becomes less amenable for conventional agriculture, plants grown on marginal soils will be exposed to higher levels of soil salinity. Forage grasses are a critical component of feed used in livestock production worldwide, with many of these same species of grasses being utilized for lawns, erosion prevention, and recreation. Consequently, it is important to develop a better understanding of salt tolerance in forage and related grass species. Findings A gene encoding a ZnF protein was identified during the analysis of a salt-stress suppression subtractive hybridization (SSH expression library from the forage grass species Festuca arundinacea. The expression pattern of FaZnF was compared to that of the well characterized gene for delta 1-pyrroline-5-carboxylate synthetase (P5CS, a key enzyme in proline biosynthesis, which was also identified in the salt-stress SSH library. The FaZnF and P5CS genes were both up-regulated in response to salt and drought stresses suggesting a role in dehydration stress. FaZnF was also up-regulated in response to heat and wounding, suggesting that it might have a more general function in multiple abiotic stress responses. Additionally, potential downstream targets of FaZnF (a MAPK [Mitogen-Activated Protein Kinase], GST [Glutathione-S-Transferase] and lipoxygenase L2 were found to be up-regulated in calli overexpressing FaZnF when compared to control cell lines. Conclusions This work provides evidence that FaZnF is an AN1/A20 zinc finger protein that is involved in the regulation

  9. Chloroquine is a zinc ionophore.

    Directory of Open Access Journals (Sweden)

    Jing Xue

    Full Text Available Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780. Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.

  10. Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism.

    Science.gov (United States)

    Marquet, R; Baudin, F; Gabus, C; Darlix, J L; Mougel, M; Ehresmann, C; Ehresmann, B

    1991-05-11

    The retroviral genome consists of two identical RNA molecules joined close to their 5' ends by the dimer linkage structure. Recent findings indicated that retroviral RNA dimerization and encapsidation are probably related events during virion assembly. We studied the cation-induced dimerization of HIV-1 RNA and results indicate that all in vitro generated HIV-1 RNAs containing a 100 nucleotide domain downstream from the 5' splice site are able to dimerize. RNA dimerization depends on the concentration of RNA, mono- and multivalent cations, the size of the monovalent cation, temperature, and pH. Up to 75% of HIV-1 RNA is dimeric in the presence of spermidine. HIV-1 RNA dimer is fairly resistant to denaturing agents and unaffected by intercalating drugs. Antisense HIV-1 RNA does not dimerize but heterodimers can be formed between HIV-1 RNA and either MoMuLV or RSV RNA. Therefore retroviral RNA dimerization probably does not simply proceed through mechanisms involving Watson-Crick base-pairing. Neither adenine and cytosine protonation, nor quartets containing only guanines appear to determine the stability of the HIV-1 RNA dimer, while quartets involving both adenine(s) and guanine(s) could account for our results. A consensus sequence PuGGAPuA found in the putative dimerization-encapsidation region of all retroviral genomes examined may participate in the dimerization process.

  11. Fast light-induced reversible wettability of a zinc oxide nanorod array coated with a thin gold layer

    Science.gov (United States)

    Wei, Yuefan; Du, Hejun; Kong, Junhua; Tran, Van-Thai; Koh, Jia Kai; Zhao, Chenyang; He, Chaobin

    2017-11-01

    Zinc oxide (ZnO) has gained much attention recently due to its excellent physical and chemical properties, and has been extensively studied in energy harvesting applications such as photovoltaic and piezoelectric devices. In recent years, its reversible wettability has also attracted increasing interest. The wettability of ZnO nanostructures with various morphologies has been studied. However, to the best of our knowledge, there is still a lack of investigations on further modifications on ZnO to provide more benefits than pristine ZnO. Comprehensive studies on the reversible wettability are still needed. In this study, a ZnO nanorod array was prepared via a hydrothermal process and subsequently coated with thin gold layers with varied thickness. The morphologies and structures, optical properties and wettability were investigated. It is revealed that the ZnO-Au system possesses recoverable wettability upon switching between visible-ultraviolet light and a dark environment, which is verified by the contact angle change. The introduction of the thin gold layer to the ZnO nanorod array effectively increases the recovery rate of the wettability. The improvements are attributed to the hierarchical structures, which are formed by depositing thin gold layers onto the ZnO nanorod array, the visible light sensitivity due to the plasmonic effect of the deposited gold, as well as the fast charge-induced surface status change upon light illumination or dark storage. The improvement is beneficial to applications in environmental purification, energy harvesting, micro-lenses, and smart devices.

  12. Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1.

    Science.gov (United States)

    Maywald, Martina; Rink, Lothar

    2017-08-01

    The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [ 3 H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF-10, and IRF-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 µM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4 + CD25 + Foxp3 + and CD4 + CD25 + CTLA-4 + T cells (p zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.

  13. Moniliophthora perniciosa necrosis- and ethylene-inducing protein 2 (MpNep2 as a metastable dimer in solution: structural and functional implications.

    Directory of Open Access Journals (Sweden)

    Guilherme A P de Oliveira

    Full Text Available Understanding how Nep-like proteins (NLPs behave during the cell cycle and disease progression of plant pathogenic oomycetes, fungi and bacteria is crucial in light of compelling evidence that these proteins play a role in Witches` Broom Disease (WBD of Theobroma cacao, one of the most important phytopathological problems to afflict the Southern Hemisphere. The crystal structure of MpNep2, a member of the NLP family and the causal agent of WBD, revealed the key elements for its activity. This protein has the ability to refold after heating and was believed to act as a monomer in solution, in contrast to the related homologs MpNep1 and NPP from the oomyceteous fungus Phytophthora parasitica. Here, we identify and characterize a metastable MpNep2 dimer upon over-expression in Escherichia coli using different biochemical and structural approaches. We found using ultra-fast liquid chromatography that the MpNep2 dimer can be dissociated by heating but not by dilution, oxidation or high ionic strength. Small-angle X-ray scattering revealed a possible tail-to-tail interaction between monomers, and nuclear magnetic resonance measurements identified perturbed residues involved in the putative interface of interaction. We also explored the ability of the MpNep2 monomer to refold after heating or chemical denaturation. We observed that MpNep2 has a low stability and cooperative fold that could be an explanation for its structure and activity recovery after stress. These results can provide new insights into the mechanism for MpNep2's action in dicot plants during the progression of WBD and may open new avenues for the involvement of NLP- oligomeric species in phytopathological disorders.

  14. Moniliophthora perniciosa necrosis- and ethylene-inducing protein 2 (MpNep2) as a metastable dimer in solution: structural and functional implications.

    Science.gov (United States)

    de Oliveira, Guilherme A P; Pereira, Elen G; Dias, Cristiano V; Souza, Theo L F; Ferretti, Giulia D S; Cordeiro, Yraima; Camillo, Luciana R; Cascardo, Júlio; Almeida, Fabio C; Valente, Ana Paula; Silva, Jerson L

    2012-01-01

    Understanding how Nep-like proteins (NLPs) behave during the cell cycle and disease progression of plant pathogenic oomycetes, fungi and bacteria is crucial in light of compelling evidence that these proteins play a role in Witches` Broom Disease (WBD) of Theobroma cacao, one of the most important phytopathological problems to afflict the Southern Hemisphere. The crystal structure of MpNep2, a member of the NLP family and the causal agent of WBD, revealed the key elements for its activity. This protein has the ability to refold after heating and was believed to act as a monomer in solution, in contrast to the related homologs MpNep1 and NPP from the oomyceteous fungus Phytophthora parasitica. Here, we identify and characterize a metastable MpNep2 dimer upon over-expression in Escherichia coli using different biochemical and structural approaches. We found using ultra-fast liquid chromatography that the MpNep2 dimer can be dissociated by heating but not by dilution, oxidation or high ionic strength. Small-angle X-ray scattering revealed a possible tail-to-tail interaction between monomers, and nuclear magnetic resonance measurements identified perturbed residues involved in the putative interface of interaction. We also explored the ability of the MpNep2 monomer to refold after heating or chemical denaturation. We observed that MpNep2 has a low stability and cooperative fold that could be an explanation for its structure and activity recovery after stress. These results can provide new insights into the mechanism for MpNep2's action in dicot plants during the progression of WBD and may open new avenues for the involvement of NLP- oligomeric species in phytopathological disorders.

  15. Selective amine catalysed steroidal dimerization

    Indian Academy of Sciences (India)

    of cholesterol is the formation of a green colour in concentrated sulphuric acid, and this was shown to be due to a polyenyl steroidal dimer carbocation.7–9 Many dimeric and oligomeric steroids exhibit interesting micellular, detergent and liquid crystal behaviour.10,11. Most of the steroidal dimmers are also well-known.

  16. Zinc-induced embrittlement in nickel-base superalloys by simulation and experiment

    Science.gov (United States)

    Otis, Richard; Waje, Mahesh; Lindwall, Greta; Jefferson, Tiffany; Lange, Jeremy; Liu, Zi-Kui

    2017-09-01

    The high cost of Re has driven interest in processes for recovering Re from scrap superalloy parts. In this work thermodynamic modelling is used to study Zn-induced embrittlement of a superalloy and to direct experiments. Treating superalloy powder with Zn vapour reduces the average particle size after milling from approximately ?m to 0.5-10 ?m, vs. ?m for untreated powder. Simulations predict the required treatment time to increase with temperature. Agreement between predictions and experiments suggests that an embrittling liquid forms in less than an hour of Zn vapour treatment between 950-1000 ?C and partial pressures of Zn between 14-34 kPa (2-5 psi).

  17. Zinc Supplementation against Eimeria acervulina-Induced Oxidative Damage in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Nedyalka V. Georgieva

    2011-01-01

    Full Text Available This study was undertaken to determine the dietary supplements of Zn containing diet on the antioxidant status in chickens experimentally infected with Eimeria acervulina. The antioxidant status was monitored via determination of MDA concentrations and erythrocyte SOD and CAT activities, as well as vitamin E, vitamin C, Cu, and Zn in liver, muscle, and serum. The results showed increased MDA (<.05, CAT (<.001, and decreased SOD (<.001 in the infected birds. Significant changes in Cu and Zn concentrations and dramatically reduction of vitamin C and E concentrations in the infected chickens were found. The observed deviations in the studied enzymes and nonenzymatic parameters evidence the occurrence of oxidative stress following the infection and impaired antioxidant status of chickens, infected with Eimeria acervulina. Our results proved the ameliorating role of CuZn(OH3Cl (0.170 g per kg food against Eimeria acervulina-induced oxidative damage in infected chickens.

  18. Dimer-based model for heptaspanning membrane receptors.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferré, Sergi; Fuxe, Kjell; Cortés, Antonio; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2005-07-01

    The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.

  19. Yashada bhasma (Zinc calx) and Tankana (Borax) inhibit Propionibacterium acne and suppresses acne induced inflammation in vitro.

    Science.gov (United States)

    Sandeep Varma, R; Shamsia, S; Thiyagarajan, O S; Vidyashankar, S; Patki, P S

    2014-08-01

    Yashada bhasma (YB) and Tankana (TA) are well characterized minerals used in traditional medicine for the treatment of various skin ailments. Yashada bhasma and TA are a unique preparation of zinc and borax, respectively. The study was conducted to evaluate the in vitro inhibitory effect of YB, TA and its combination (YBTA) on Propionibacterium acne growth and P. acne-induced inflammation. The minerals were tested for anti-P. acne activity by disc diffusion and broth microdilution methods. The effect of these minerals on P. acne induced TNF-α and IL-8 production and gene expression were studied in THP-1 cells. In vitro toxicity was tested on human keratinocytes (HaCaT) and mouse embryonic fibroblasts (NIH3T3) using MTT assay. The minimum inhibitory concentrations (MIC values) for YB, TA and YBTA against P. acne were 0.1 ± 0.2, 1.9 ± 0.5 and 0.3 ± 0.5 mg mL(-1) , respectively. YB, TA and YBTA inhibited TNFα by 57.57%, 59.09% and 68.93% and IL-8 production by 48.76%, 47.92% and 51.13% in P. acne-stimulated THP-1 cells, respectively. The CTC50 values on HaCaT and NIH3T3 was 17.44 ± 0.5 and 16.37 ± 0.2 μg mL(-1) for YB, 1023.03 ± 4.0 and 1286.17 ± 4.4 μg mL(-1) for TA and 89.12 ± 2.3 and 111.58 ± 3.5 μg mL(-1) for YBTA, respectively. The present study revealed the inhibitory effect of YB, TA and YBTA on P. acne growth and inflammation. Clinical studies have suggested the anti-acne benefits of formulations containing YB and TA. The findings obtained from the present in vitro studies provide evidence to support the mechanism of anti-acne properties of YB and TA. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  20. The synthetic epoxyquinoids jesterone dimer and epoxyquinone A monomer induce apoptosis and inhibit REL (human c-Rel) DNA binding in an IkappaBalpha-deficient diffuse large B-cell lymphoma cell line.

    Science.gov (United States)

    Liang, Mei-Chih; Bardhan, Sujata; Porco, John A; Gilmore, Thomas D

    2006-09-08

    The NF-kappaB transcription factor signaling pathway is constitutively active in many human cancers, and inhibition of this pathway can often kill cancer cells by inducing apoptosis. In this study, we show that two synthetic epoxyquinoids, jesterone dimer (JD) and epoxyquinone A monomer (EqM), are equally effective at inhibiting the growth of two human lymphoma cell lines that have constitutively nuclear REL (human c-Rel) DNA-binding complexes, but either express (SUDHL-4 cells) or do not express (RC-K8 cells) the NF-kappaB inhibitor IkappaBalpha. Furthermore, in these cells, both JD and EqM dose-dependently induced apoptosis, inhibited REL DNA-binding activity, and converted REL to a high molecular weight form. In A293 cells, JD and EqM inhibited the DNA-binding activity of overexpressed REL, but not p50. Replacement of Cys-27 with Ser in REL reduced JD- and EqM-mediated inhibition of REL DNA-binding activity. These results suggest that JD and EqM can induce apoptosis in IkappaBalpha-deficient lymphoma cells through a mechanism involving direct inhibition of transcription factor REL.

  1. Zinc, nitrogen and salinity interaction on agronomic traits and some ...

    African Journals Online (AJOL)

    use

    2011-11-23

    Nov 23, 2011 ... percentage decreased due to nitrogen, zinc and salinity in the first year but .... Analysis of variance on canola traits affected by nitrogen, zinc and salinity at ...... a result less of the latter are available for fat synthesis ... Na+ and Cl- in plant tissues, effects of nitrogen and zinc ... Zinc alleviates cadmium-induced.

  2. A bipyridine-ligated zinc(II) complex with bridging flavonolate ligation: synthesis, characterization, and visible-light-induced CO release reactivity.

    Science.gov (United States)

    Sorenson, Shayne; Popova, Marina; Arif, Atta M; Berreau, Lisa M

    2017-09-01

    Metal-flavonolate compounds are of significant current interest as synthetic models for quercetinase enzymes and as bioactive compounds of importance to human health. Zinc-3-hydroxyflavonolate compounds, including those of quercetin, kampferol, and morin, generally exhibit bidentate coordination to a single Zn II center. The bipyridine-ligated zinc-flavonolate compound reported herein, namely bis(μ-4-oxo-2-phenyl-4H-chromen-3-olato)-κ 3 O 3 :O 3 ,O 4 ;κ 3 O 3 ,O 4 :O 3 -bis[(2,2'-bipyridine-κ 2 N,N')zinc(II)] bis(perchlorate), {[Zn 2 (C 15 H 9 O 3 ) 2 (C 10 H 8 N 2 ) 2 ](ClO 4 ) 2 } n , (1), provides an unusual example of bridging 3-hydroxyflavonolate ligation in a dinuclear metal complex. The symmetry-related Zn II centers of (1) exhibit a distorted octahedral geometry, with weak coordination of a perchlorate anion trans to the bridging deprotonated O atom of the flavonolate ligand. Variable-concentration conductivity measurements provide evidence that, when (1) is dissolved in CH 3 CN, the complex dissociates into monomers. 1 H NMR resonances for (1) dissolved in d 6 -DMSO were assigned via HMQC to the H atoms of the flavonolate and bipyridine ligands. In CH 3 CN, (1) undergoes quantitative visible-light-induced CO release with a quantum yield [0.004 (1)] similar to that exhibited by other mononuclear zinc-3-hydroxyflavonolate complexes. Mass spectroscopic identification of the [(bpy) 2 Zn(O-benzoylsalicylate)] + ion provides evidence of CO release from the flavonol and of ligand exchange at the Zn II center.

  3. Theoretical studies of the pressure-induced zinc-blende to cinnabar phase transition in CdTe and thermodynamical properties of each phase

    International Nuclear Information System (INIS)

    Brik, M.G.; Łach, P.; Karczewski, G.; Wojtowicz, T.; Kamińska, A.; Suchocki, A.

    2013-01-01

    Luminescence of CdTe quantum dots embedded in ZnTe is quenched at pressure of about 4.5 GPa in the high-pressure experiments. This pressure-induced quenching is attributed to the “zinc-blende–cinnabar” phase transition in CdTe, which was confirmed by the first-principles calculations. Theoretical analysis of the pressure at which the phase transition occurs for CdTe was performed using the CASTEP module of Materials Studio package with both generalized gradient approximation (GGA) and local density approximation (LDA). The calculated phase transition pressures are equal to about 4.4 GPa and 2.6 GPa, according to the GGA and LDA calculations, respectively, which is in a good agreement with the experimental value. Theoretically estimated value of the pressure coefficient of the band-gap luminescence in zinc-blende structure is in very good agreement with that recently measured in the QDs structures. The calculated Debye temperature, elastic constants and specific heat capacity for the zinc-blend structure agree well with the experimental data; the data for the cinnabar phase are reported here for the first time to the best of the authors' knowledge. - Highlights: • Quenching of luminescence of CdTe quantum dots embedded in ZnTe is theoretically explained. • The theoretical calculation of elastic and thermodynamic properties of CdTe by two types of ab-initio methods. • Theoretical calculations of some optical properties of CdTe under pressure in zinc-blende and cinnabar phases

  4. Collisional properties of weakly bound heteronuclear dimers

    NARCIS (Netherlands)

    Marcelis, B.; Kokkelmans, S.J.J.M.F.; Shlyapnikov, G.V.; Petrov, D.S.

    2008-01-01

    We consider collisional properties of weakly bound heteronuclear molecules (dimers) formed in a two-species mixture of atoms with a large mass difference. We focus on dimers containing light fermionic atoms as they manifest collisional stability due to an effective dimer-dimer repulsion originating

  5. Presence of the propeptide on recombinant lysosomal dipeptidase controls both activation and dimerization.

    Science.gov (United States)

    Dolenc, Iztok; Pain, Roger; Turk, Vito

    2007-01-01

    Lysosomal dipeptidase catalyzes the hydrolysis of dipeptides with unsubstituted terminals. It is a homodimer and binds zinc. Dimerization is an important issue in understanding the enzyme's function. In this study, we investigated the influence of the propeptide on the folding and dimerization of recombinant lysosomal dipeptidase. For this purpose, we separately cloned and overexpressed the mature protein and the proenzyme. The overexpressed proteins were localized exclusively to insoluble inclusion bodies. Refolding of the urea-solubilized inclusion bodies showed that only dipeptidase lacking the propeptide was dimeric. The soluble renatured proenzyme was a monomer, although circular dichroism and fluorescence spectra of the proenzyme indicated the formation of secondary and tertiary structure. The propeptide thus controls dimerization, as well as activation, of lysosomal dipeptidase.

  6. Dynamics of the water dimer + nitric oxide collision

    Energy Technology Data Exchange (ETDEWEB)

    Ree, Jong Baik [Dept. of Chemistry Education, Chonnam National University, Gwangju (Korea, Republic of); Kim, Yoo Hang [Dept. of Chemistry, Inha University, Incheon (Korea, Republic of); Shin, Hyung Kyu [Dept. of Chemistry, University of Nevada, Nevada (Korea, Republic of)

    2017-02-15

    Collision-induced intermolecular energy transfer and intramolecular vibrational redistribution in the collision of a water dimer and nitric oxide are studied by use of quasiclassical procedures. Intermolecular energy flow is shown to occur mainly through a direct-mode mechanism transferring relatively large amounts in strong collisions. About a quarter of the energy initially deposited in the dimer transfers to the ground state NO, while the rest redistributes among internal motions of the collision system. The main portion of initial energy deposited in the dimer redistributes in the stretches of the donor monomer through the 1:1 resonance followed by in the bend through the 1:2 resonance. Energy transfer from the excited NO to the ground-state dimer is equally efficient, transferring more than half the initial excitation to the donor monomer, the efficiency that is attributed to the internal modes operating as energy reservoirs. The hydrogen bond shares about 15% of the initial excitation stored in both dimer-to-NO and NO-to-dimer processes as a result of strong coupling of the hydrogen bond with the proton-donor OH bond of the monomer. A small fraction of collisions proceeds through a complex-mode mechanism and lead to NO dissociation, the dissociated O atom showing a propensity to form a new hydrogen bond.

  7. Hydrodynamic Torques and Rotations of Superparamagnetic Bead Dimers

    Science.gov (United States)

    Pease, Christopher; Etheridge, J.; Wijesinghe, H. S.; Pierce, C. J.; Prikockis, M. V.; Sooryakumar, R.

    Chains of micro-magnetic particles are often rotated with external magnetic fields for many lab-on-a-chip technologies such as transporting beads or mixing fluids. These applications benefit from faster responses of the actuated particles. In a rotating magnetic field, the magnetization of superparamagnetic beads, created from embedded magnetic nano-particles within a polymer matrix, is largely characterized by induced dipoles mip along the direction of the field. In addition there is often a weak dipole mop that orients out-of-phase with the external rotating field. On a two-bead dimer, the simplest chain of beads, mop contributes a torque Γm in addition to the torque from mip. For dimers with beads unbound to each other, mop rotates individual beads which generate an additional hydrodynamic torque on the dimer. Whereas, mop directly torques bound dimers. Our results show that Γm significantly alters the average frequency-dependent dimer rotation rate for both bound and unbound monomers and, when mop exceeds a critical value, increases the maximum dimer rotation frequency. Models that include magnetic and hydrodynamics torques provide good agreement with the experimental findings over a range of field frequencies.

  8. Green Synthesized Zinc Oxide (ZnO Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System

    Directory of Open Access Journals (Sweden)

    Kamal K. Panda

    2017-05-01

    Full Text Available Zinc oxide nanoparticles (ZnONP-GS were synthesised from the precursor zinc acetate (Zn(CH3COO2 through the green route using the milky latex from milk weed (Calotropis gigantea L. R. Br by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX, transmission electron microscopy (TEM, and X-ray diffraction (XRD. Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich and cationic Zn2+ from Zn(CH3COO2 were tested in a dose range of 0–100 mg·L−1 for their potency (i to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O2•−, H2O2 and •OH, cell death, and lipid peroxidation; (ii to modulate the activities of antioxidant enzymes: catalase (CAT, superoxide dismutase (SOD, guaiacol peroxidase (GPX, and ascorbate peroxidase (APX; and (iii to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn2+ alone.

  9. Green Synthesized Zinc Oxide (ZnO) Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System.

    Science.gov (United States)

    Panda, Kamal K; Golari, Dambaru; Venugopal, A; Achary, V Mohan M; Phaomei, Ganngam; Parinandi, Narasimham L; Sahu, Hrushi K; Panda, Brahma B

    2017-05-18

    Zinc oxide nanoparticles (ZnONP-GS) were synthesised from the precursor zinc acetate (Zn(CH₃COO)₂) through the green route using the milky latex from milk weed ( Calotropis gigantea L. R. Br) by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich) and cationic Zn 2+ from Zn(CH₃COO)₂ were tested in a dose range of 0-100 mg·L -1 for their potency (i) to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O₂ •- , H₂O₂ and • OH), cell death, and lipid peroxidation; (ii) to modulate the activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), and ascorbate peroxidase (APX); and (iii) to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn 2+ alone.

  10. Defect induced modification of structural, topographical and magnetic properties of zinc ferrite thin films by swift heavy ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan, Lisha [Department of Physics, Cochin University of Science and Technology, Cochin 682022 (India); Inter University Accelerator Center, New Delhi 110067 (India); Joy, P.A. [National Chemical Laboratory, Pune (India); Vijaykumar, B. Varma; Ramanujan, R.V. [School of Materials Science and Engineering, Nanyang Technological University (Singapore); Anantharaman, M.R., E-mail: mraiyer@gmail.com [Department of Physics, Cochin University of Science and Technology, Cochin 682022 (India)

    2017-04-01

    Highlights: • Zinc ferrite films exhibited room temperature ferrimagnetic property. • On ion irradiation amorphisation of films were observed. • The surface morphology undergoes changes with ion irradiation. • The saturation magnetisation decreases on ion irradiation. - Abstract: Swift heavy ion irradiation provides unique ways to modify physical and chemical properties of materials. In ferrites, the magnetic properties can change significantly as a result of swift heavy ion irradiation. Zinc ferrite is an antiferromagnet with a Neel temperature of 10 K and exhibits anomalous magnetic properties in the nano regime. Ion irradiation can cause amorphisation of zinc ferrite thin films; thus the role of crystallinity on magnetic properties can be examined. The influence of surface topography in these thin films can also be studied. Zinc ferrite thin films, of thickness 320 nm, prepared by RF sputtering were irradiated with 100 MeV Ag ions. Structural characterization showed amorphisation and subsequent reduction in particle size. The change in magnetic properties due to irradiation was correlated with structural and topographical effects of ion irradiation. A rough estimation of ion track radius is done from the magnetic studies.

  11. Dimerization and oligomerization of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Ryder, L Rebekka; Steinø, Anne

    2003-01-01

    protein. Using PAGE, urea gradient gel electrophoresis, capillary electrophoresis and MS, we show that dimerization through the SH group can be induced by lowering the pH to 5-6, heating, or under conditions that favour partial unfolding such as urea concentrations above 2.6 m or SDS concentrations above...... that favour partial unfolding or an intramolecular local conformational change that allows oligomerization, resulting in a heterogeneous mixture of oligomers consisting of up to 10 calreticulin monomers. The oligomeric calreticulin was very stable, but oligomerization was partially reversed by addition of 8 m...

  12. Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

    DEFF Research Database (Denmark)

    Nygaard, Sanne Bjørn; Larsen, Agnete; Knuhtsen, Astrid

    2014-01-01

    BACKGROUND: Zinc is essential for the activities of pancreatic β-cells, especially insulin storage and secretion. Insulin secretion leads to co-release of zinc which contributes to the paracrine communication in the pancreatic islets. Zinc-transporting proteins (zinc-regulated transporter, iron......-regulated transporter-like proteins [ZIPs] and zinc transporters [ZnTs]) and metal-buffering proteins (metallothioneins, MTs) tightly regulate intracellular zinc homeostasis. The present study investigated how modulation of cellular zinc availability affects β-cell function using INS-1E cells. RESULTS: Using INS-1E...... cells, we found that zinc supplementation and zinc chelation had significant effects on insulin content and insulin secretion. Supplemental zinc within the physiological concentration range induced insulin secretion. Insulin content was reduced by zinc chelation with N,N,N',N-tektrakis(2-pyridylmethyl...

  13. Zinc in Infection and Inflammation

    Directory of Open Access Journals (Sweden)

    Nour Zahi Gammoh

    2017-06-01

    Full Text Available 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.

  14. Zinc in Infection and Inflammation.

    Science.gov (United States)

    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.

  15. Hydrothermal synthesis of zinc(II)-phosphonate coordination polymers with different dimensionality (0D, 2D, 3D) and dimensionality change in the solid phase (0D→3D) induced by temperature

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Zapico, Eva; Montejo-Bernardo, Jose; Fernández-González, Alfonso; García, José R., E-mail: jrgm@uniovi.es; García-Granda, Santiago

    2015-05-15

    Three new zinc(II) coordination polymers, [Zn(HO{sub 3}PCH{sub 2}CH{sub 2}COO)(C{sub 12}H{sub 8}N{sub 2})(H{sub 2}O)] (1), [Zn{sub 3}(O{sub 3}PCH{sub 2}CH{sub 2}COO){sub 2}(C{sub 12}H{sub 8}N{sub 2})](H{sub 2}O){sub 3.40} (2) and [Zn{sub 5}(HO{sub 3}PCH{sub 2}CH{sub 2}COO){sub 2}(O{sub 3}PCH{sub 2}CH{sub 2}COO){sub 2}(C{sub 12}H{sub 8}N{sub 2}){sub 4}](H{sub 2}O){sub 0.32} (3), with different structural dimensionality (0D, 2D and 3D, respectively) have been prepared by hydrothermal synthesis, and their structures were determined by single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic system (P2{sub 1}/c) forming discrete dimeric units bonded through H-bonds, while compounds 2 and 3 crystallize in the triclinic (P−1) and the monoclinic (C2/c) systems, respectively. Compound 3, showing three different coordination numbers (4, 5 and 6) for the zinc atoms, has also been obtained by thermal treatment of 1 (probed by high-temperature XRPD experiments). The crystalline features of these compounds, related to the coordination environments for the zinc atoms in each structure, provoke the increase of the relative fluorescence for 2 and 3, compared to the free phenanthroline. Thermal analysis (TG and DSC) and XPS studies have been also carried out for all compounds. - Graphical abstract: Three new coordination compounds of zinc with 2-carboxyethylphosphonic acid (H{sub 2}PPA) and phenanthroline have been obtained by hydrothermal synthesis. The crystalline structure depends on the different coordination environments of the zinc atoms (see two comparative Zn{sub 6}-moieties). The influence of the different coordination modes of H{sub 2}PPA with the central atom in all structures have been studied, being found new coordination modes for this ligand. Several compounds show a significant increase in relative fluorescence with respect to the free phenanthroline. - Highlights: • Compounds have been obtained modifying the reaction time and the rate of

  16. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

    Science.gov (United States)

    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  17. Adventures in holographic dimer models

    International Nuclear Information System (INIS)

    Kachru, Shamit; Karch, Andreas; Yaida, Sho

    2011-01-01

    We abstract the essential features of holographic dimer models, and develop several new applications of these models. Firstly, semi-holographically coupling free band fermions to holographic dimers, we uncover novel phase transitions between conventional Fermi liquids and non-Fermi liquids, accompanied by a change in the structure of the Fermi surface. Secondly, we make dimer vibrations propagate through the whole crystal by way of double trace deformations, obtaining nontrivial band structure. In a simple toy model, the topology of the band structure experiences an interesting reorganization as we vary the strength of the double trace deformations. Finally, we develop tools that would allow one to build, in a bottom-up fashion, a holographic avatar of the Hubbard model.

  18. Stepwise "Dark Photoswitching" of Photochromic Dimers in a Junction

    DEFF Research Database (Denmark)

    Olsen, Stine Tetzschner; Hansen, Thorsten; Nielsen, Mogens Brøndsted

    2017-01-01

    -induced switching) has been termed dark photoswitching and was observed for the dihydroazulene–vinylheptafulvene couple in a junction. In this theoretical study, we expand this concept to dimeric structures containing two dihydroazulene units linked through meta- or para-phenylene bridges and anchored...

  19. Mutability of bacteriophage M13 by ultraviolet light: role of pyrimidine dimers

    International Nuclear Information System (INIS)

    Schaaper, R.M.; Glickman, B.W.

    1982-01-01

    The role of pyrimidine dimers in mutagenesis by ultraviolet light was examined by measuring the UV-induced reversion of six different bacteriophage M13 amber mutants for which the neighboring DNA sequences are known. The mutational response at amber (TAG) codons preceded by a guanine or adenine (where no pyrimidine dimer can be formed) were compared with those preceded by thymine or cytosine (where dimer formation is possible). Equivalent levels of UV-induced mutagenesis were observed at both kinds of sites. This observation demonstrates that there is no requirement for a pyrimidine dimer directly at the site of UV-induced mutation in this single-stranded DNA phage. UV irradiation of the phage was also performed in the presence of Ag + ions, which specifically sensitize the DNA to dimer formation. The two methods of irradiation, when compared at equal survival levels (and presumably equal dimer frequencies), produced equivalent frequencies of reversion of the amber phage. We believe these results indicate that while the presence of pyrimidine dimers may be a prerequisite for UV mutagenesis, the actual mutagenic event can occur at a site some distance removed from a dimer. (orig.)

  20. Study of DNA Origami Dimerization and Dimer Dissociation Dynamics and of the Factors that Limit Dimerization.

    Science.gov (United States)

    Liber, Miran; Tomov, Toma E; Tsukanov, Roman; Berger, Yaron; Popov, Mary; Khara, Dinesh C; Nir, Eyal

    2018-06-01

    Organizing DNA origami building blocks into higher order structures is essential for fabrication of large structurally and functionally diverse devices and molecular machines. Unfortunately, the yields of origami building block attachment reactions are typically not sufficient to allow programed assembly of DNA devices made from more than a few origami building blocks. To investigate possible reasons for these low yields, a detailed single-molecule fluorescence study of the dynamics of rectangular origami dimerization and origami dimer dissociation reactions is conducted. Reactions kinetics and yields are investigated at different origami and ion concentrations, for different ion types, for different lengths of bridging strands, and for the "sticky end" and "weaving welding" attachment techniques. Dimerization yields are never higher than 86%, which is typical for such systems. Analysis of the dynamic data shows that the low yield cannot be explained by thermodynamic instability or structural imperfections of the origami constructs. Atomic force microscopy and gel electrophoresis evidence reveal self-dimerization of the origami monomers, likely via blunt-end interactions made possible by the presence of bridging strands. It is suggested that this mechanism is the major factor that inhibits correct dimerization and means to overcome it are discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Pyrimidine dimer excision in human cells and skin cancer

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Smith, D.P.; Waters, R.

    1977-01-01

    We have compared three different methods for estimating the induction and removal of uv induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after uv doses of 5-20 J/m 2 50% of the dimers are removed by 24 hours after irradiation. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after 5 J/m 2 . After higher doses it probably takes even longer fr such complete removal to be seen

  2. Fano resonances in heterogeneous dimers of silicon and gold nanospheres

    Science.gov (United States)

    Zhao, Qian; Yang, Zhong-Jian; He, Jun

    2018-06-01

    We theoretically investigate the optical properties of dimers consisting of a gold nanosphere and a silicon nanosphere. The absorption spectrum of the gold sphere in the dimer can be significantly altered and exhibits a pronounced Fano profile. Analytical Mie theory and numerical simulations show that the Fano profile is induced by constructive and destructive interference between the incident electric field and the electric field of the magnetic dipole mode of the silicon sphere in a narrow wavelength range. The effects of the silicon sphere size, distance between the two spheres, and excitation configuration on the optical responses of the dimers are studied. Our study reveals the coherent feature of the electric fields of magnetic dipole modes in dielectric nanostructures and the strong interactions of the coherent fields with other nanophotonic structures.

  3. Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.

    Science.gov (United States)

    Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G; Jian Liu, Ke

    2013-08-01

    Arsenic enhances the genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic cocarcinogenesis, and DNA repair proteins such as poly(ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlying arsenic inhibition of DNA repair. We report herein that arsenite-generated ROS/RNS inhibits PARP-1 activity in cells. Cellular exposure to arsenite, as well as hydrogen peroxide and NONOate (nitric oxide donor), decreased PARP-1 zinc content, enzymatic activity, and PARP-1 DNA binding. Furthermore, the effects of arsenite on PARP-1 activity, DNA binding, and zinc content were partially reversed by the antioxidant ascorbic acid, catalase, and the NOS inhibitor, aminoguanidine. Most importantly, arsenite incubation with purified PARP-1 protein in vitro did not alter PARP-1 activity or DNA-binding ability, whereas hydrogen peroxide or NONOate retained PARP-1 inhibitory activity. These results strongly suggest that cellular generation of ROS/RNS plays an important role in arsenite inhibition of PARP-1 activity, leading to the loss of PARP-1 DNA-binding ability and enzymatic activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Modified ionic liquid cold-induced aggregation dispersive liquid-liquid microextraction followed by atomic absorption spectrometry for trace determination of zinc in water and food samples

    International Nuclear Information System (INIS)

    Zeeb, M.; Sadeghi, M.

    2011-01-01

    We report on a new method for the microextraction and determination of zinc (II). The ion is accumulated via ionic-liquid cold-induced aggregation dispersive liquid-liquid microextraction (IL-CIA-DLLME) followed by flame atomic absorption spectrometry (FAAS). The ionic liquid (IL) 1-hexyl-3-methylimidazolium hexafluorophosphate is dispersed into a heated sample solution containing sodium hexafluorophosphate as a common ion source. The solution is then placed in an ice-water bath upon which a cloudy solution forms due to the decrease of the solubility of the IL. Zinc is complexed with 8-hydroxyquinoline and extracted into the IL. The enriched phase is dissolved in a diluting agent and introduced to the FAAS. The method is not influenced by variations in the ionic strength of the sample solution. Factors affecting the performance were evaluated and optimized. At optimum conditions, the limit of detection is 0.18 μg L -1 , and the relative standard deviation is 3.0% (at n=5). The method was validated by recovery experiments and by analyzing a certified reference material and successfully applied to the determination of Zn (II) in water and food samples. (author)

  5. Kinetics of DNA tile dimerization.

    Science.gov (United States)

    Jiang, Shuoxing; Yan, Hao; Liu, Yan

    2014-06-24

    Investigating how individual molecular components interact with one another within DNA nanoarchitectures, both in terms of their spatial and temporal interactions, is fundamentally important for a better understanding of their physical behaviors. This will provide researchers with valuable insight for designing more complex higher-order structures that can be assembled more efficiently. In this report, we examined several spatial factors that affect the kinetics of bivalent, double-helical (DH) tile dimerization, including the orientation and number of sticky ends (SEs), the flexibility of the double helical domains, and the size of the tiles. The rate constants we obtained confirm our hypothesis that increased nucleation opportunities and well-aligned SEs accelerate tile-tile dimerization. Increased flexibility in the tiles causes slower dimerization rates, an effect that can be reversed by introducing restrictions to the tile flexibility. The higher dimerization rates of more rigid tiles results from the opposing effects of higher activation energies and higher pre-exponential factors from the Arrhenius equation, where the pre-exponential factor dominates. We believe that the results presented here will assist in improved implementation of DNA tile based algorithmic self-assembly, DNA based molecular robotics, and other specific nucleic acid systems, and will provide guidance to design and assembly processes to improve overall yield and efficiency.

  6. Dimers in Piecewise Temperleyan Domains

    Science.gov (United States)

    Russkikh, Marianna

    2018-03-01

    We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

  7. Magnetic-field induced Bose-Einstein condensation of magnons and critical behavior in interacting spin dimer system TlCuCl3

    International Nuclear Information System (INIS)

    Yamada, F.; Ono, T.; Tanaka, H.; Misguich, G.; Oshikawa, M.; Sakakibara, T.

    2008-01-01

    Magnetization measurements were performed to investigate the critical behavior of the field-induced magnetic ordering in gapped spin system TlCuCl 3 . The critical density of the magnons was obtained as a function of temperature and the magnon-magnon interaction constant was evaluated. The experimental phase boundary for T ≤ 5 K agrees almost perfectly with the magnon Bose-Einstein condensation (BEC) theory based on the Hartree-Fock approximation with realistic dispersion relations. The phase boundary can be described by the power law [H N (T)-H c ] ∝ T φ . With decreasing fitting temperature range, the critical exponent φ decreases and converges at φ(BEC) = 3/2 predicted by the magnon BEC theory. (authors)

  8. Symptomatic zinc deficiency in experimental zinc deprivation.

    OpenAIRE

    Taylor, C M; Goode, H F; Aggett, P J; Bremner, I; Walker, B E; Kelleher, J

    1992-01-01

    An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkal...

  9. Protective effect of ginger and zinc chloride mixture on the liver and kidney alterations induced by malathion toxicity.

    Science.gov (United States)

    Baiomy, Ahmed A; Attia, Hossam F; Soliman, Mohamed M; Makrum, Omar

    2015-03-01

    This study was carried out on four groups of male Wistar rats, 10 rats per group. Group I got open access to food intake and water with normal balanced diet. Group II was administered 400 mg ginger per kg body weight (BW) and zinc chloride (ZnCl2) (300 mg/L) diluted in tap water for 4 months. Group III was administered malathion at a dose of 50 mg/kg BW/day in 0.2 mL corn oil via gavages for 4 months. This dose equal to 1/50 of the LD50. Group IV was given a mixture of 400 mg ginger per kg BW and ZnCl2 (300 mg/L) diluted in tap water in addition to 100 mg malathion/kg BW for 4 months. The liver showed histopathological changes include congestion, edema, and leucocytic infiltrations which were ameliorated by the addition of ginger and ZnCl2 mixture. The kidney showed cloudy swelling and hydropic degeneration of the renal tubules. These changes were ameliorated by the addition of ginger and ZnCl2 mixture. Ki67 immunoreactivity was localized in the cytoplasm and nuclear membrane. Its expression was estimated as the percentage of cells positively stained by the antibody in the different groups. In conclusion, malathion was toxic to the liver and kidney and must be avoided and protected by the addition of ginger and zinc mixture. © The Author(s) 2015.

  10. Rubidium dimers in paraffin-coated cells

    International Nuclear Information System (INIS)

    Acosta, V M; Windes, D; Corsini, E; Ledbetter, M P; Karaulanov, T; Budker, D; Jarmola, A; Auzinsh, M; Rangwala, S A; Jackson Kimball, D F

    2010-01-01

    Measurements were made to determine the density of rubidium dimer vapor in paraffin-coated cells. The number density of dimers and atoms in similar paraffin-coated and uncoated cells was measured by optical spectroscopy. Due to the relatively low melting point of paraffin, a limited temperature range of 43-80 0 C was explored, with the lower end corresponding to a dimer density of less than 10 7 cm -3 . With 1 min integration time, a sensitivity to dimer number density of better than 10 6 cm -3 was achieved. No significant difference in dimer density between the cells was observed.

  11. Unphosphorylated rhabdoviridae phosphoproteins form elongated dimers in solution.

    Science.gov (United States)

    Gerard, Francine C A; Ribeiro, Euripedes de Almeida; Albertini, Aurélie A V; Gutsche, Irina; Zaccai, Guiseppe; Ruigrok, Rob W H; Jamin, Marc

    2007-09-11

    The phosphoprotein (P) is an essential component of the replication machinery of rabies virus (RV) and vesicular stomatitis virus (VSV), and the oligomerization of P, potentially controlled by phosphorylation, is required for its function. Up to now the stoichiometry of phosphoprotein oligomers has been controversial. Size exclusion chromatography combined with detection by multiangle laser light scattering shows that the recombinant unphosphorylated phosphoproteins from VSV and from RV exist as dimers in solution. Hydrodynamic analysis indicates that the dimers are highly asymmetric, with a Stokes radius of 4.8-5.3 nm and a frictional ratio larger than 1.7. Small-angle neutron scattering experiments confirm the dimeric state and the asymmetry of the structure and yield a radius of gyration of about 5.3 nm and a cross-sectional radius of gyration of about 1.6-1.8 nm. Similar hydrodynamic properties and molecular dimensions were obtained with a variant of VSV phosphoprotein in which Ser60 and Thr62 are substituted by Asp residues and which has been reported previously to mimic phosphorylation by inducing oligomerization and activating transcription. Here, we show that this mutant also forms a dimer with hydrodynamic properties and molecular dimensions similar to those of the wild type protein. However, incubation at 30 degrees C for several hours induced self-assembly of both wild type and mutant proteins, leading to the formation of irregular filamentous structures.

  12. Formation of thymine containing dimers in skin exposed to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, B E [Dundee Univ. (UK)

    1978-01-01

    Nuclear DNA appears to be the major molecular target for the inhibitory, mutagenic and lethal effects of ultraviolet radiation on cells in culture. Cyclobutyl dimers between adjacent pyrimidine bases, the major photochemical lesions for these effects in prokaryotes, also play a part in UVR effects on eukaryotes cells. Pyrimidine dimers have been isolated from in vivo UV-irradiated guinea pig and mouse skin. The wavelength dependence for dimer induction is similar to that for acute skin reactions but no direct causal relationship has been established. Sunlight UVR may induce dimers in skin DNA. Excision of dimers from mouse skin in vivo is deficient as it is for most rodent cells in culture; human cell excision is efficient and the difficulties in interpretation of UV-carcinogenesis results with mice in terms of human skin cancer are therefore increased.

  13. Fiber optic D dimer biosensor

    Science.gov (United States)

    Glass, Robert S.; Grant, Sheila A.

    1999-01-01

    A fiber optic sensor for D dimer (a fibrinolytic product) can be used in vivo (e.g., in catheter-based procedures) for the diagnosis and treatment of stroke-related conditions in humans. Stroke is the third leading cause of death in the United States. It has been estimated that strokes and stroke-related disorders cost Americans between $15-30 billion annually. Relatively recently, new medical procedures have been developed for the treatment of stroke. These endovascular procedures rely upon the use of microcatheters. These procedures could be facilitated with this sensor for D dimer integrated with a microcatheter for the diagnosis of clot type, and as an indicator of the effectiveness, or end-point of thrombolytic therapy.

  14. The Protective Roles of Zinc and Magnesium in Cadmium-Induced Renal Toxicity in Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Nasim Babaknejad

    2014-12-01

    Full Text Available Background: Cadmium (Cd is a heavy metal that has widespread use. It enters the food chain in different ways, including soil and water. Cadmium can cause dysfunction of different body organs. Zinc (Zn and magnesium (Mg supplementation can have protective effects against cadmium toxicity due to their antagonistic and antioxidants properties. This study examines the influence of supplemental Zn and Mg on Cd renal toxicity. Methods: Young male Wistar rats were divided into six groups of five. The Cd group received 1 mg Cd/kg and the control group received 0.5 mg/kg normal saline (i.p.. The other four groups were administered 1 mg/kg Cd+0.5 mg/kg Zn, 1 mg/kg Cd+1.5 mg/kg Zn, 1 mg/kg Cd+ 0.5 mg/kg Mg, and 1 mg/kg Cd+ 1.5 mg/kg Mg (i.p. for 21 days. Then, serum sodium, potassium, urea, creatinine, and protein levels were measured. Results: The results indicated that creatinine and protein levels decreased while urea, sodium, and potassium levels increased as a result of Cd exposure. Co-administered Cd and Zn and Mg decreased urea and increased sodium serum level in comparison to the cadmium group. Treatment by Mg, contrary to co-administered Cd and Zn, reduced serum protein level compared to the cadmium group. Compared to the cadmium treated group, Zn and Mg treatment enhanced serum creatinine level and reduced serum potassium level. Conclusion: The findings seem to suggest that zinc and magnesium compounds, due to their antagonistic and antioxidant activities, can protect Cd renal toxic effects in a dose-dependent manner.

  15. BWR fuel experience with zinc injection

    International Nuclear Information System (INIS)

    Levin, H.A.; Garcia, S.E.

    1995-01-01

    In 1982 a correlation between low primary recirculation system dose rates in BWR's and the presence of ionic zinc in reactor water was identified. The source of the zinc was primarily from Admiralty brass condensers. Plants with brass condensers are called ''natural zinc'' plants. Brass condensers were also a source of copper that was implicated in crude induced localized corrosion (CILC) fuel failures. In 1986 the first BWR intentionally injected zinc for the benefits of dose rate control. Although zinc alone was never implicated in fuel degradation of failures, a comprehensive fuel surveillance program was initiated to monitor fuel performance. Currently there are 14 plants that are injecting zinc. Six of these plants are also on hydrogen water chemistry. This paper describes the effect on both Zircaloy corrosion and the cruding characteristics as a result of these changes in water chemistry. Fuel rod corrosion was found to be independent of the specific water chemistry of the plants. The corrosion behavior was the same with the additions of zinc alone or zinc plus hydrogen and well within the operating experience for fuel without either of these additions. No change was observed in the amounts of crude deposited on the fuel rods, both for the adherent and loosely held deposits. One of the effects of the zinc addition was the trend to form more of the zinc rich iron spinel in the fuel deposits rather than the hematite deposits that are predominantly formed with non additive water chemistry

  16. Zinc and the modulation of redox homeostasis

    Science.gov (United States)

    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

  17. Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

    Science.gov (United States)

    Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

    2006-01-01

    The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus. PMID:16707664

  18. Analysis of hepatitis C virus RNA dimerization and core-RNA interactions.

    Science.gov (United States)

    Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

    2006-01-01

    The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3'-untranslated region (3'-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623-2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3'-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus.

  19. The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus.

    Science.gov (United States)

    Hu, Yan-Dan; Pang, Wei; He, Cong-Cong; Lu, Hao; Liu, Wei; Wang, Zi-Yu; Liu, Yan-Qiang; Huang, Cheng-Yu; Jiang, Yu-Gang

    2017-11-01

    This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus. The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR. Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P zinc-deficient diet during 0∼2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency.

  20. Effect of zinc treatment on intestinal motility in experimentally ...

    African Journals Online (AJOL)

    Effect of zinc treatment on intestinal motility in experimentally induced diarrhea in rats. ... Zinc supplementation is a critical new intervention for treating diarrheal episodes in children. Recent studies suggest that administration of zinc along with new low osmolarity oral rehydration solutions / salts (ORS) can reduce the ...

  1. Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

    Science.gov (United States)

    Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

    2018-01-24

    Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

  2. Effects of metformin treatment on Iron, Zinc and Copper status concentration in the serum of female rats with induced polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Muhsin S. G. Al-Moziel

    2013-07-01

    Full Text Available This study conducted to investigate the effects of metformin drug on serum Iron, Zinc and Copper concentration in Estradiol Valerate(EV induced polycystic ovary syndrome(PCOS in virgin rats. Thirty virgin rats were randomly allotted to constitute Normal control (NC-I group and induced polycystic ovary (PCO-I and PCO-II groups having 10 rats in each group. Rats from NC-I group were administered intramuscularly with 0.2 ml of corn oil whereas polycystic ovary was induced in rats from PCO-I and PCO-II groups by administering single intra-muscular injection of estradiol Valerate 4mg/rat. The rats from PCO-I and PCO-II groups were left for 60 days for development of polycystic ovary syndrome. Animals from PCO-I group were then administered with 0.2 ml normal saline as oral gavage for 15 days, these animals were kept as PCO control group animals whereas those from PCO-II groups received metformin (50mg/kg B.wt as oral gavage for 15 days, these animals served as metformin treated PCO group animals. All the rats were thereafter sacrificed for collecting blood from inferior vena-cava. Serum samples from each rat were assessed for iron, zinc and copper status in each experimental group. The results revealed a significant (p≤0.05 increase in serum Fe and Zn and a significant (p≤0.05 decrease in serum Cu concentration in PCO group 1 compared with control non-treated group. The PCO group2 treated with metformin showed a significant (p≤0.05 decrease in serum Fe concentration as compared with those in animals from group NC-I and PCO-I. While, no significant differences were found in serum Zn concentration between all treated groups. On the other hand, a significant (p≤0.05 increase in serum Cu concentration appeared in metformin treated group compared with PCO group 1 which appears significant decrease compared with control group.

  3. Influence of soil zinc concentrations on zinc sensitivity and functional diversity of microbial communities

    International Nuclear Information System (INIS)

    Lock, K.; Janssen, C.R.

    2005-01-01

    Pollution induced community tolerance (PICT) is based on the phenomenon that toxic effects reduce survival of the most sensitive organisms, thus increasing community tolerance. Community tolerance for a contaminant is thus a strong indicator for the presence of that contaminant at the level of adverse concentrations. Here we assessed PICT in 11 soils contaminated with zinc runoff from galvanised electricity pylons and 11 reference soils sampled at 10 m distance from these pylons. Using PICT, the influence of background concentration and bioavailability of zinc on zinc sensitivity and functional diversity of microbial communities was assessed. Zinc sensitivity of microbial communities decreased significantly with increasing zinc concentrations in pore water and calcium chloride extracted fraction while no significant relationship was found with total zinc concentration in the soil. It was also found that functional diversity of microbial communities decreased with increasing zinc concentrations, indicating that increased tolerance is indeed an undesirable phenomenon when environmental quality is considered. The hypothesis that zinc sensitivity of microbial communities is related to background zinc concentration in pore water could not be confirmed. - Zinc sensitivity of microbial communities and functional diversity decrease with increasing zinc concentration in the pore water

  4. OsDOG, a gibberellin-induced A20/AN1 zinc-finger protein, negatively regulates gibberellin-mediated cell elongation in rice.

    Science.gov (United States)

    Liu, Yaju; Xu, Yunyuan; Xiao, Jun; Ma, Qibin; Li, Dan; Xue, Zhen; Chong, Kang

    2011-07-01

    The A20/AN1 zinc-finger proteins (ZFPs) play pivotal roles in animal immune responses and plant stress responses. From previous gibberellin (GA) microarray data and A20/AN1 ZFP family member association, we chose Oryza sativa dwarf rice with overexpression of gibberellin-induced gene (OsDOG) to examine its function in the GA pathway. OsDOG was induced by gibberellic acid (GA(3)) and repressed by the GA-synthesis inhibitor paclobutrazol. Different transgenic lines with constitutive expression of OsDOG showed dwarf phenotypes due to deficiency of cell elongation. Additional GA(1) and real-time PCR quantitative assay analyses confirmed that the decrease of GA(1) in the overexpression lines resulted from reduced expression of GA3ox2 and enhanced expression of GA2ox1 and GA2ox3. Adding exogenous GA rescued the constitutive expression phenotypes of the transgenic lines. OsDOG has a novel function in regulating GA homeostasis and in negative maintenance of plant cell elongation in rice. Copyright © 2011 Elsevier GmbH. All rights reserved.

  5. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    International Nuclear Information System (INIS)

    Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

    2013-01-01

    The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

  6. The induction and repair of cyclobutane thymidine dimers in human skin

    International Nuclear Information System (INIS)

    Roza, L.; Erasmus Univ., Rotterdam; Vermeulen, W.; Schans, G.P. van der; Lohman, P.H.M.

    1987-01-01

    The most important detrimental effect of ultraviolet radiation (UV) on the living cell, so far known, is the induction of damage in the DNA. The major photoproducts induced in DNA by UV-C (200-280 nm) and UV-B (280-315 nm) are the cyclobutane-type pyrimidine dimers, which have been implicated in UV-induced mutagenesis and carcinogenesis. Dimer lesions in DNA of cells may be repaired in the dark by a multi-enzyme process (excision repair), or via a light dependent enzymatic reaction known as photoreactivation (phr) which is specific for pyrimidine dimers. Although phr has been found to occur in a wide range of organisms, studies on the presence of phr in mammalian cells have yielded conflicting results. To investigate repair of pyrimidine dimers in human skin cells irradiated in vivo, a specific and sensitive detection method was developed based on a monoclonal antibody directed against thymidine dimers. Application together with a fluorescent immunostaining permits the direct detection of thymidine dimers in human skin cells. The method is used in studies aimed at a better understanding of the role of these lesions in the process of carcinogenesis. A report is given on the isolation and characterization of the antibodies, and their application in a study on the induction of pyrimidine dimers in human skin and on photorepair in cultured cells. 10 refs.; 2 figs

  7. Lithium-ion induced conformational change of 5,17-bis(9-fluorenyl)-25,26,27,28-tetrapropoxy calix[4]arene resulting in an egg-shaped dimeric clathrate

    DEFF Research Database (Denmark)

    Faldt, A.; Krebs, Frederik C; Jørgensen, Mikkel

    2000-01-01

    Synthesis and structural investigation of a 5,17-bis(9-fluorenyl)-25,26,27,28-tetrapropoxy calix[4]arene and its lithium complex salt that forms a dimeric clathrate with a molecule of solvent inside a cavity. At least three different interactions were identified as being responsible for the forma...

  8. Zinc Signals and Immunity.

    Science.gov (United States)

    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.

  9. Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

    Science.gov (United States)

    Foster, Meika; Samman, Samir

    2012-01-01

    In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination. PMID:22852057

  10. Alignment and Imaging of the CS2 Dimer Inside Helium Nanodroplets

    Science.gov (United States)

    Pickering, James D.; Shepperson, Benjamin; Hübschmann, Bjarke A. K.; Thorning, Frederik; Stapelfeldt, Henrik

    2018-03-01

    The carbon disulphide (CS2) dimer is formed inside He nanodroplets and identified using fs laser-induced Coulomb explosion, by observing the CS2+ ion recoil velocity. It is then shown that a 160 ps moderately intense laser pulse can align the dimer in advantageous spatial orientations which allow us to determine the cross-shaped structure of the dimer by analysis of the correlations between the emission angles of the nascent CS2+ and S+ ions, following the explosion process. Our method will enable fs time-resolved structural imaging of weakly bound molecular complexes during conformational isomerization, including formation of exciplexes.

  11. Ameliorative effects of selenium and zinc

    African Journals Online (AJOL)

    Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. L Barkat, A Boumendjel, C Abdennour, MS Boulakoud, A El Feki, M Messarah ...

  12. Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

    International Nuclear Information System (INIS)

    Brzóska, Malgorzata M.; Rogalska, Joanna

    2013-01-01

    It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects from Cd-induced

  13. Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

    Energy Technology Data Exchange (ETDEWEB)

    Brzóska, Malgorzata M., E-mail: Malgorzata.Brzoska@umb.edu.pl; Rogalska, Joanna

    2013-10-01

    It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects from Cd-induced

  14. Strain mediated interaction of adatom dimers

    OpenAIRE

    Kappus, Wolfgang

    2013-01-01

    An earlier model for substrate strain mediated interactions between monomer adatoms is extended to the interaction of monomers with dimers and the interaction of dimers. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress caused by stretching their bond. Resulting interactions are strongly angle dependent and also reflect the elastic anisotropy of the substrate. The applicability of a continuum elast...

  15. Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

    Science.gov (United States)

    Onaolapo, Olakunle James; Ademakinwa, Olayemi Quyyom; Olalekan, Temitayo Opeyemi; Onaolapo, Adejoke Yetunde

    2017-09-01

    We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

  16. Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes.

    Science.gov (United States)

    Lee, Sook-Jeong; Koh, Jae-Young

    2010-10-26

    Zinc dyshomeostasis has been recognized as an important mechanism for cell death in acute brain injury. An increase in the level of free or histochemically reactive zinc in astrocytes and neurons is considered one of the major causes of death of these cells in ischemia and trauma. Although zinc dyshomeostasis can lead to cell death via diverse routes, the major pathway appears to involve oxidative stress.Recently, we found that a rise of zinc in autophagic vacuoles, including autolysosomes, is a prerequisite for lysosomal membrane permeabilization and cell death in cultured brain cells exposed to oxidative stress conditions. The source of zinc in this process is likely redox-sensitive zinc-binding proteins such as metallothioneins, which release zinc under oxidative conditions. Of the metallothioneins, metallothionein-3 is especially enriched in the central nervous system, but its physiologic role in this tissue is not well established. Like other metallothioneins, metallothionein-3 may function as metal detoxicant, but is also known to inhibit neurite outgrowth and, sometimes, promote neuronal death, likely by serving as a source of toxic zinc release. In addition, metallothionein-3 regulates lysosomal functions. In the absence of metallothionein-3, there are changes in lysosome-associated membrane protein-1 and -2, and reductions in certain lysosomal enzymes that result in decreased autophagic flux. This may have dual effects on cell survival. In acute oxidative injury, zinc dyshomeostasis and lysosomal membrane permeabilization are diminished in metallothionein-3 null cells, resulting in less cell death. But over the longer term, diminished lysosomal function may lead to the accumulation of abnormal proteins and cause cytotoxicity.The roles of zinc and metallothionein-3 in autophagy and/or lysosomal function have just begun to be investigated. In light of evidence that autophagy and lysosomes may play significant roles in the pathogenesis of various neurological

  17. Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes

    Directory of Open Access Journals (Sweden)

    Lee Sook-Jeong

    2010-10-01

    Full Text Available Abstract Zinc dyshomeostasis has been recognized as an important mechanism for cell death in acute brain injury. An increase in the level of free or histochemically reactive zinc in astrocytes and neurons is considered one of the major causes of death of these cells in ischemia and trauma. Although zinc dyshomeostasis can lead to cell death via diverse routes, the major pathway appears to involve oxidative stress. Recently, we found that a rise of zinc in autophagic vacuoles, including autolysosomes, is a prerequisite for lysosomal membrane permeabilization and cell death in cultured brain cells exposed to oxidative stress conditions. The source of zinc in this process is likely redox-sensitive zinc-binding proteins such as metallothioneins, which release zinc under oxidative conditions. Of the metallothioneins, metallothionein-3 is especially enriched in the central nervous system, but its physiologic role in this tissue is not well established. Like other metallothioneins, metallothionein-3 may function as metal detoxicant, but is also known to inhibit neurite outgrowth and, sometimes, promote neuronal death, likely by serving as a source of toxic zinc release. In addition, metallothionein-3 regulates lysosomal functions. In the absence of metallothionein-3, there are changes in lysosome-associated membrane protein-1 and -2, and reductions in certain lysosomal enzymes that result in decreased autophagic flux. This may have dual effects on cell survival. In acute oxidative injury, zinc dyshomeostasis and lysosomal membrane permeabilization are diminished in metallothionein-3 null cells, resulting in less cell death. But over the longer term, diminished lysosomal function may lead to the accumulation of abnormal proteins and cause cytotoxicity. The roles of zinc and metallothionein-3 in autophagy and/or lysosomal function have just begun to be investigated. In light of evidence that autophagy and lysosomes may play significant roles in the

  18. Formic acid dimers in a nitrogen matrix

    Science.gov (United States)

    Lopes, Susy; Fausto, Rui; Khriachtchev, Leonid

    2018-01-01

    Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. We benefit from the use of a nitrogen matrix where the lifetime of the higher-energy (cis) conformer is very long (˜11 h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large proportion of the cis conformer can be produced by vibrational excitation of the lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis-cis dimers are found in the experiments. The spectroscopic information on most of these dimers is enriched compared to the previous studies in an argon matrix. The cis-cis dimers of ordinary formic acid (without deuteration) are reported here for the first time. Several conformational processes are obtained using selective excitation by infrared light, some of them also for the first time. In particular, we report on the formation of cis-cis dimers upon vibrational excitation of trans-cis dimers. Tunneling decays of several dimers have been detected in the dark. The tunneling decay of cis-cis dimers of formic acid as well as the stabilization of cis units in cis-cis dimers is also observed for the first time.

  19. Highly toughened polypropylene/ethylene–propylene-diene monomer/zinc dimethacrylate ternary blends prepared via peroxide-induced dynamic vulcanization

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yukun, E-mail: cyk@scut.edu.cn [The Key Laboratory of Polymer Processing Engineering, Ministry of Education, South China University of Technology, Guangzhou 510640 (China); School of Mechanical and Automotive Engineering, South China University of Technology, Guangzhou 510640 (China); Xu, Chuanhui [College of Material Science and Engineering, South China University of Technology, Guangzhou 510640 (China); Cao, Liming [The Key Laboratory of Polymer Processing Engineering, Ministry of Education, South China University of Technology, Guangzhou 510640 (China); School of Mechanical and Automotive Engineering, South China University of Technology, Guangzhou 510640 (China); Cao, Xiaodong [College of Material Science and Engineering, South China University of Technology, Guangzhou 510640 (China)

    2013-02-15

    Polypropylene (PP)/ethylene–propylene-diene monomer (EPDM)/zinc dimethacrylate (ZDMA) blends with remarkable toughness and extensibility were successfully prepared via peroxide dynamical vulcanization. A unique structure with the EPDM particles surrounded by a transition zone containing numerous polymerized ZDMA (PZDMA) nano-particles was observed for the first time by using transmission electron microscopy (TEM) examination, which contributed to the dramatically increase of Izod impact strength. Dynamic mechanical analysis (DMA) confirmed that the possible PZDMA graft products resulted from peroxide dynamical vulcanization improved the compatibility between EPDM and PP phases. The specific morphology of the PP/EPDM/ZDMA blends indicated that ZDMA can lead to size reduction and good distribution uniformity of the crosslinked rubber particles and the increase of adhesion between PP matrix and EPDM phases during deformation. The synergic effect of the increase in the effective volume of the EPDM phase, the improved compatibility and adhesion between EPDM and PP phases and the deformation of those fine rubber particles is believed to result in the remarkable high toughness and extensibility of the PP/EPDM/ZDMA blends. Particularly for the PP/EPDM ratio of 70/30, the PP/EPDM/ZDMA (70/30/9, w/w/w) ternary blends with the Izod impact strength nearly 2 times higher than PP/EPDM (70/30, w/w) binary blends and 15–20 times higher than PP are achieved; besides, the elongation at break of PP/EPDM/ZDMA ternary blends is 4–5 times higher than that of PP/EPDM binary blends. - Highlights: ► ZDMA largely toughen peroxide dynamically vulcanized PP/EPDM blend. ► PZDMA graft products improved the compatibility and adhesion between EPDM and PP. ► Size reduction and good distribution uniformity of crosslinked rubber particles.

  20. Highly toughened polypropylene/ethylene–propylene-diene monomer/zinc dimethacrylate ternary blends prepared via peroxide-induced dynamic vulcanization

    International Nuclear Information System (INIS)

    Chen, Yukun; Xu, Chuanhui; Cao, Liming; Cao, Xiaodong

    2013-01-01

    Polypropylene (PP)/ethylene–propylene-diene monomer (EPDM)/zinc dimethacrylate (ZDMA) blends with remarkable toughness and extensibility were successfully prepared via peroxide dynamical vulcanization. A unique structure with the EPDM particles surrounded by a transition zone containing numerous polymerized ZDMA (PZDMA) nano-particles was observed for the first time by using transmission electron microscopy (TEM) examination, which contributed to the dramatically increase of Izod impact strength. Dynamic mechanical analysis (DMA) confirmed that the possible PZDMA graft products resulted from peroxide dynamical vulcanization improved the compatibility between EPDM and PP phases. The specific morphology of the PP/EPDM/ZDMA blends indicated that ZDMA can lead to size reduction and good distribution uniformity of the crosslinked rubber particles and the increase of adhesion between PP matrix and EPDM phases during deformation. The synergic effect of the increase in the effective volume of the EPDM phase, the improved compatibility and adhesion between EPDM and PP phases and the deformation of those fine rubber particles is believed to result in the remarkable high toughness and extensibility of the PP/EPDM/ZDMA blends. Particularly for the PP/EPDM ratio of 70/30, the PP/EPDM/ZDMA (70/30/9, w/w/w) ternary blends with the Izod impact strength nearly 2 times higher than PP/EPDM (70/30, w/w) binary blends and 15–20 times higher than PP are achieved; besides, the elongation at break of PP/EPDM/ZDMA ternary blends is 4–5 times higher than that of PP/EPDM binary blends. - Highlights: ► ZDMA largely toughen peroxide dynamically vulcanized PP/EPDM blend. ► PZDMA graft products improved the compatibility and adhesion between EPDM and PP. ► Size reduction and good distribution uniformity of crosslinked rubber particles

  1. Production of zinc pellets

    Science.gov (United States)

    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.

  2. Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles

    Science.gov (United States)

    2012-01-01

    Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID:22303956

  3. Designer interface peptide grafts target estrogen receptor alpha dimerization

    International Nuclear Information System (INIS)

    Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

    2016-01-01

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  4. Designer interface peptide grafts target estrogen receptor alpha dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

    2016-09-09

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  5. Hippocampus-like corticoneurogenesis induced by two isoforms of the BTB-zinc finger gene Zbtb20 in mice

    DEFF Research Database (Denmark)

    Nielsen, Jakob V; Nielsen, Flemming H; Ismail, Rola

    2007-01-01

    result in behavioral abnormalities suggestive of a deficient processing of visual and spatial memory cues in the cerebral cortex of adult Zbtb20 transgenic mice. Overall, our in vivo data suggest that Zbtb20 functions as a molecular switch for a pathway that induces invariant pyramidal neuron...

  6. Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.

    Science.gov (United States)

    Pati, Rashmirekha; Mehta, Ranjit Kumar; Mohanty, Soumitra; Padhi, Avinash; Sengupta, Mitali; Vaseeharan, Baskarlingam; Goswami, Chandan; Sonawane, Avinash

    2014-08-01

    Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis-BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis-GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus. Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections. This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Analysis of interfacial energy states in Au/pentacene/polyimide/indium-zinc-oxide diodes by electroluminescence spectroscopy and electric-field-induced optical second-harmonic generation measurement

    Science.gov (United States)

    Taguchi, Dai; Manaka, Takaaki; Iwamoto, Mitsumasa

    2016-03-01

    By using electroluminescence (EL) spectroscopy and electric-field-induced optical second-harmonic generation (EFISHG) measurement, we analyzed interfacial energy states in Au/pentacene/polyimide/indium-zinc-oxide (IZO) diodes, to characterize the pentacene/polyimide interface. Under positive voltage application to the Au electrode with reference to the IZO electrode, the EFISHG showed that holes are injected from Au electrode, and accumulate at the pentacene/polyimide interface with the surface charge density of Qs = 3.8 × 10-7 C/cm2. The EL spectra suggested that the accumulated holes are not merely located in the pentacene but they are transferred to the interface states of polyimide. These accumulated holes distribute with the interface state density greater than 1012 cm-2 eV-1 in the range E = 1.5-1.8 and 1.7-2.4 eV in pentacene and in polyimide, respectively, under assumption that accumulated holes govern recombination radiation. The EL-EFISHG measurement is helpful to characterize organic-organic layer interfaces in organic devices and provides a way to analyze interface energy states.

  8. Autoradiographic studies of the protein metabolism and histochemical demonstration of the zinc content of the brain in diabetic rats. 1. Streptozotocin-induced diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Gatzke, H D [Freie Univ. Berlin (Germany, F.R.); Wildmeister, W [Krankenhaus Kempen (Germany, F.R.). Innere Klinik

    1979-11-01

    Diabetes mellitus was induced in rats by application of streptozotocin: 40 mg/kg body weight streptozotocin produced a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin caused a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals received 308 MBq/animal /sup 3/H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of /sup 3/H-leucine in different areas of the rat brain were measured. The values of the control animals were compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the /sup 3/H-leucine values of the diabetic animals were considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the /sup 3/H-leucine values as well as the zinc content of diabetic animals decreased according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions was discussed.

  9. Analysis of current-voltage characteristics of Au/pentacene/fluorine polymer/indium zinc oxide diodes by electric-field-induced optical second-harmonic generation

    Energy Technology Data Exchange (ETDEWEB)

    Nishi, Shohei; Taguchi, Dai; Manaka, Takaaki; Iwamoto, Mitsumasa, E-mail: iwamoto@pe.titech.ac.jp [Department of Physical Electronics, Tokyo Institute of Technology, 2-12-1 S3-33, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan)

    2015-06-28

    By using electric-field-induced optical second-harmonic generation measurement coupled with the conventional current-voltage (I-V) measurement, we studied the carrier transport of organic double-layer diodes with a Au/pentacene/fluorine polymer (FP)/indium zinc oxide (IZO) structure. The rectifying I-V characteristics were converted into the I-E characteristics of the FP and pentacene layers. Results suggest a model in which Schottky-type electron injection from the IZO electrode to the FP layer governs the forward electrical conduction (V > 0), where the space charge electric field produced in the FP layer by accumulated holes at the pentacene/FP interface makes a significant contribution. On the other hand, Schottky-type injection by accumulated interface electrons from the pentacene layer to the FP layer governs the backward electrical conduction (V < 0). The electroluminescence generated from the pentacene layer in the region V > 0 verifies the electron transport across the FP layer, and supports the above suggested model.

  10. Analysis of current-voltage characteristics of Au/pentacene/fluorine polymer/indium zinc oxide diodes by electric-field-induced optical second-harmonic generation

    International Nuclear Information System (INIS)

    Nishi, Shohei; Taguchi, Dai; Manaka, Takaaki; Iwamoto, Mitsumasa

    2015-01-01

    By using electric-field-induced optical second-harmonic generation measurement coupled with the conventional current-voltage (I-V) measurement, we studied the carrier transport of organic double-layer diodes with a Au/pentacene/fluorine polymer (FP)/indium zinc oxide (IZO) structure. The rectifying I-V characteristics were converted into the I-E characteristics of the FP and pentacene layers. Results suggest a model in which Schottky-type electron injection from the IZO electrode to the FP layer governs the forward electrical conduction (V > 0), where the space charge electric field produced in the FP layer by accumulated holes at the pentacene/FP interface makes a significant contribution. On the other hand, Schottky-type injection by accumulated interface electrons from the pentacene layer to the FP layer governs the backward electrical conduction (V < 0). The electroluminescence generated from the pentacene layer in the region V > 0 verifies the electron transport across the FP layer, and supports the above suggested model

  11. Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs.

    Science.gov (United States)

    Wu, Wenting; Ichihara, Gaku; Hashimoto, Naozumi; Hasegawa, Yoshinori; Hayashi, Yasuhiko; Tada-Oikawa, Saeko; Suzuki, Yuka; Chang, Jie; Kato, Masashi; D'Alessandro-Gabazza, Corina N; Gabazza, Esteban C; Ichihara, Sahoko

    2014-12-30

    Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.

  12. Effect of zinc gluconate, sage oil on inflammatory patterns and hyperglycemia in zinc deficient diabetic rats.

    Science.gov (United States)

    Elseweidy, Mohamed M; Ali, Abdel-Moniem A; Elabidine, Nabila Zein; Mursey, Nada M

    2017-11-01

    The relationship between zinc homeostasis and pancreatic function had been established. In this study we aimed firstly to configure the inflammatory pattern and hyperglycemia in zinc deficient diabetic rats. Secondly to illustrate the effect of two selected agents namely Zinc gluconate and sage oil (Salvia Officinalis, family Lamiaceae). Rats were fed on Zinc deficient diet, deionized water for 28days along with Zinc level check up at intervals to achieve zinc deficient state then rats were rendered diabetic through receiving one dose of alloxan monohydrate (120mg/kg) body weight, classified later into 5 subgroups. Treatment with sage oil (0.042mg/kg IP) and Zinc gluconate orally (150mg/kg) body weight daily for 8 weeks significantly reduced serum glucose, C-reactive protein (CRP), Tumor necrosis factor alpha (TNF- α), interleukins-6 1 β, inflammatory8 (IFN ȣ), pancreatic 1L1-β along with an increase in serum Zinc and pancreatic Zinc transporter 8 (ZNT8). Histopathological results of pancreatic tissues showed a good correlation with the biochemical findings. Both sage oil and zinc gluconate induced an improvement in the glycemic and inflammatory states. This may be of value like the therapeutic agent for diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Chloroplast Preproteins Bind to the Dimer Interface of the Toc159 Receptor during Import1[OPEN

    Science.gov (United States)

    Chen, Lih-Jen; Yeh, Yi-Hung; Hsiao, Chwan-Deng

    2017-01-01

    Most chloroplast proteins are synthesized in the cytosol as higher molecular weight preproteins and imported via the translocons in the outer (TOC) and inner (TIC) envelope membranes of chloroplasts. Toc159 functions as a primary receptor and directly binds preproteins through its dimeric GTPase domain. As a first step toward a molecular understanding of how Toc159 mediates preprotein import, we mapped the preprotein-binding regions on the Toc159 GTPase domain (Toc159G) of pea (Pisum sativum) using cleavage by bound preproteins conjugated with the artificial protease FeBABE and cysteine-cysteine cross-linking. Our results show that residues at the dimer interface and the switch II region of Toc159G are in close proximity to preproteins. The mature portion of preproteins was observed preferentially at the dimer interface, whereas the transit peptide was found at both regions equally. Chloroplasts from transgenic plants expressing engineered Toc159 with a cysteine placed at the dimer interface showed increased cross-linking to bound preproteins. Our data suggest that, during preprotein import, the Toc159G dimer disengages and the dimer interface contacts translocating preproteins, which is consistent with a model in which conformational changes induced by dimer-monomer conversion in Toc159 play a direct role in facilitating preprotein import. PMID:28250068

  14. Molecular mechanics calculations on cobalt phthalocyanine dimers

    NARCIS (Netherlands)

    Heuts, J.P.A.; Schipper, E.T.W.M.; Piet, P.; German, A.L.

    1995-01-01

    In order to obtain insight into the structure of cobalt phthalocyanine dimers, molecular mechanics calculations were performed on dimeric cobalt phthalocyanine species. Molecular mechanics calculations are first presented on monomeric cobalt(II) phthalocyanine. Using the Tripos force field for the

  15. Mahler Measure, Eisenstein Series and Dimers

    NARCIS (Netherlands)

    Stienstra, J.

    2007-01-01

    This note reveals a mysterious link between the partition function of certain dimer models on 2-dimensional tori and the L-function of their spectral curves. It also relates the partition function in certain families of dimer models to Eisenstein series. http://www.arxiv.org/abs/math.NT/0502197

  16. Dietary phytate, zinc and hidden zinc deficiency.

    Science.gov (United States)

    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.

  17. Contribution to depth profiling by particle induced X-ray emission application to the study of zinc diffusion in AgZn alloy

    International Nuclear Information System (INIS)

    Frontier, J.P.

    1987-08-01

    A contribution of the study of the capacities of Particle Induced X-ray Emission (P.I.X.E.) for depth profiling, in the range of 1 to 10 micrometers and over, is presented here. It is shown that, in a non destructuve way, the concentration profile of a given element can be obtained, in principle, by deconvoluting the X-ray yields of this element, measured in a set of experiments in which the energy of the impinging protons, hence their range, is systematically varied. Direct deconvolution procedure, which leads to the inversion of an ill-conditionned matrix is unsuitable. So we generalized the iterative procedure previously used by Vegh to solve a similar problem. Alternatively we also used a fitting procedure of several parameters which gave us somewhat better than those of the iterative procedure. Both algorithms where applied to a set of X-ray yields induced by protons of energy between 0.45 to 2 MeV, corresponding to the first 6 micrometers of various depletion profiles of zinc in an initially homogeneous Ag-3 at % Zn annealed under vacuum. For investigation of deeper layers, a sectionning technique which consists in analysing thin film hydroxide targets by specific chemistry of tiny turning, was developped with success. Cross-reference of all the obtained profiles was made with electron microprobe determination on transverse section, and with the predictions of the theory of atomic diffusion. In addition, the possibilities of increasing the depth resolution by developping techniques either of controled sanding of the surface, or analysis of the sample is discussed [fr

  18. Statistical transmutation in doped quantum dimer models.

    Science.gov (United States)

    Lamas, C A; Ralko, A; Cabra, D C; Poilblanc, D; Pujol, P

    2012-07-06

    We prove a "statistical transmutation" symmetry of doped quantum dimer models on the square, triangular, and kagome lattices: the energy spectrum is invariant under a simultaneous change of statistics (i.e., bosonic into fermionic or vice versa) of the holes and of the signs of all the dimer resonance loops. This exact transformation enables us to define the duality equivalence between doped quantum dimer Hamiltonians and provides the analytic framework to analyze dynamical statistical transmutations. We investigate numerically the doping of the triangular quantum dimer model with special focus on the topological Z(2) dimer liquid. Doping leads to four (instead of two for the square lattice) inequivalent families of Hamiltonians. Competition between phase separation, superfluidity, supersolidity, and fermionic phases is investigated in the four families.

  19. Directed diffusion of reconstituting dimers

    International Nuclear Information System (INIS)

    Barma, Mustansir; Grynberg, Marcelo D; Stinchcombe, Robin B

    2007-01-01

    We discuss the dynamical aspects of an asymmetric version of assisted diffusion of hard core particles on a ring studied by Menon et al (1997 J. Stat. Phys. 86 1237). The asymmetry brings in phenomena like kinematic waves and effects of the Kardar-Parisi-Zhang non-linearity, which combine with the feature of strongly broken ergodicity, a characteristic of the model. A central role is played by a single non-local invariant, the irreducible string, whose interplay with the driven motion of reconstituting dimers, arising from the assisted hopping, determines the asymptotic dynamics and scaling regimes. These are investigated both analytically and numerically through sector-dependent mappings to the asymmetric simple exclusion process

  20. Directed diffusion of reconstituting dimers

    Energy Technology Data Exchange (ETDEWEB)

    Barma, Mustansir [Department of Theoretical Physics, Tata Institute of Fundamental Research, Mumbai 400005 (India); Grynberg, Marcelo D [Departamento de Fisica, Universidad Nacional de La Plata (1900) La Plata (Argentina); Stinchcombe, Robin B [Isaac Newton Institute for Mathematical Sciences, 20 Clarkson Road, Cambridge CB3 0EH (United Kingdom)

    2007-02-14

    We discuss the dynamical aspects of an asymmetric version of assisted diffusion of hard core particles on a ring studied by Menon et al (1997 J. Stat. Phys. 86 1237). The asymmetry brings in phenomena like kinematic waves and effects of the Kardar-Parisi-Zhang non-linearity, which combine with the feature of strongly broken ergodicity, a characteristic of the model. A central role is played by a single non-local invariant, the irreducible string, whose interplay with the driven motion of reconstituting dimers, arising from the assisted hopping, determines the asymptotic dynamics and scaling regimes. These are investigated both analytically and numerically through sector-dependent mappings to the asymmetric simple exclusion process.

  1. BWR zinc addition Sourcebook

    International Nuclear Information System (INIS)

    Garcia, Susan E.; Giannelli, Joseph F.; Jarvis, Alfred J.

    2014-01-01

    Boiling Water Reactors (BWRs) have been injecting zinc into the primary coolant via the reactor feedwater system for over 25 years for the purpose of controlling primary system radiation fields. The BWR zinc injection process has evolved since the initial application at the Hope Creek Nuclear Station in 1986. Key transitions were from the original natural zinc oxide (NZO) to depleted zinc oxide (DZO), and from active zinc injection of a powdered zinc oxide slurry (pumped systems) to passive injection systems (zinc pellet beds). Zinc addition has continued through various chemistry regimes changes, from normal water chemistry (NWC) to hydrogen water chemistry (HWC) and HWC with noble metals (NobleChem™) for mitigation of intergranular stress corrosion cracking (IGSCC) of reactor internals and primary system piping. While past reports published by the Electric Power Research Institute (EPRI) document specific industry experience related to these topics, the Zinc Sourcebook was prepared to consolidate all of the experience gained over the past 25 years. The Zinc Sourcebook will benefit experienced BWR Chemistry, Operations, Radiation Protection and Engineering personnel as well as new people entering the nuclear power industry. While all North American BWRs implement feedwater zinc injection, a number of other BWRs do not inject zinc. This Sourcebook will also be a valuable resource to plants considering the benefits of zinc addition process implementation, and to gain insights on industry experience related to zinc process control and best practices. This paper presents some of the highlights from the Sourcebook. (author)

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

    Science.gov (United States)

    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.

  3. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Yuka; Tada-Oikawa, Saeko [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Ichihara, Gaku [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya (Japan); Yabata, Masayuki; Izuoka, Kiyora [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Suzuki, Masako; Sakai, Kiyoshi [Nagoya City Public Health Research Institute, Nagoya (Japan); Ichihara, Sahoko, E-mail: saho@gene.mie-u.ac.jp [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan)

    2014-07-01

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.

  4. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish

    International Nuclear Information System (INIS)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Li, Wei-Ye

    2016-01-01

    Highlights: • Zn and Cd induced some differences in oxidative damage in the liver of zebrafish. • Zn and Cd enhanced expression of Cu/Zn-SOD and CAT through Nrf2 pathway. • Zn and Cd did not affected protein levels of CAT. • Cd inhibited biological activities of Cu/Zn-SOD and CAT proteins. • Zn stimulated activity and protein levels of Cu/Zn-SOD. - Abstract: Based on the same toxic level of 0.6% LC_5_0 for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180 μg L"−"1) and Cd exposures (30 μg L"−"1) on growth, survival, histology, ultrastructure, and oxidative stress in the liver of zebrafish for 5 weeks. Growth performance and survival rate remained relatively constant under Zn stress, but was reduced under Cd exposure. Cd exposure also induced severe pyknotic nuclei, evident ultrastructure damage, and considerable lipid inclusions in the hepatocytes. However, these phenomena were not pronounced under Zn exposure. The negative effects caused by Cd may be explained by an increase in hepatic oxidative damage, as reflected by the enhanced levels of lipid peroxidation (LPO) and protein carbonylation (PC). The reduced activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) may result in the enhanced hepatic oxidative damage, though the mRNA and protein levels of both genes increased and remained unchanged respectively. On the contrary, Zn up-regulated the levels of mRNA, protein and activity of Cu/Zn-SOD, which may contribute to the decreased LPO levels. Nonetheless, the sharply up-regulated mRNA levels of CAT did not induce an increase in the protein and activity levels of CAT under Zn stress. Furthermore, transcription factor NF-E2-related factor 2 (Nrf2) expression parelleled with its target genes, suggesting that Nrf2 is required for the protracted induction of antioxidant genes. In conclusion, our data demonstrated that essential and non-essential metals induced some differences in oxidative damage

  5. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Yuan, Shuang-Shuang; Wu, Chang-Wen [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Li, Wei-Ye [Zhoushan fisheries research institute, Zhoushan 316022 (China)

    2016-08-15

    Highlights: • Zn and Cd induced some differences in oxidative damage in the liver of zebrafish. • Zn and Cd enhanced expression of Cu/Zn-SOD and CAT through Nrf2 pathway. • Zn and Cd did not affected protein levels of CAT. • Cd inhibited biological activities of Cu/Zn-SOD and CAT proteins. • Zn stimulated activity and protein levels of Cu/Zn-SOD. - Abstract: Based on the same toxic level of 0.6% LC{sub 50} for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180 μg L{sup −1}) and Cd exposures (30 μg L{sup −1}) on growth, survival, histology, ultrastructure, and oxidative stress in the liver of zebrafish for 5 weeks. Growth performance and survival rate remained relatively constant under Zn stress, but was reduced under Cd exposure. Cd exposure also induced severe pyknotic nuclei, evident ultrastructure damage, and considerable lipid inclusions in the hepatocytes. However, these phenomena were not pronounced under Zn exposure. The negative effects caused by Cd may be explained by an increase in hepatic oxidative damage, as reflected by the enhanced levels of lipid peroxidation (LPO) and protein carbonylation (PC). The reduced activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) may result in the enhanced hepatic oxidative damage, though the mRNA and protein levels of both genes increased and remained unchanged respectively. On the contrary, Zn up-regulated the levels of mRNA, protein and activity of Cu/Zn-SOD, which may contribute to the decreased LPO levels. Nonetheless, the sharply up-regulated mRNA levels of CAT did not induce an increase in the protein and activity levels of CAT under Zn stress. Furthermore, transcription factor NF-E2-related factor 2 (Nrf2) expression parelleled with its target genes, suggesting that Nrf2 is required for the protracted induction of antioxidant genes. In conclusion, our data demonstrated that essential and non-essential metals induced some differences in

  6. Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma.

    Science.gov (United States)

    Uharcek, P; Mlyncek, M; Ravinger, J

    2007-01-01

    Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.

  7. Magnetic field-induced cluster formation and variation of magneto-optical signals in zinc-substituted ferrofluids

    Energy Technology Data Exchange (ETDEWEB)

    Nair, S.S. [Department of Physics, Cochin University of Science and Technology, Cochin 682 022 (India)]. E-mail: swapna@cusat.ac.in; Rajesh, S. [Department of Physics, Cochin University of Science and Technology, Cochin 682 022 (India); Abraham, V.S. [School of Engineering and Sciences, International University of Bremen, 28759 (Germany); Anantharaman, M.R. [Department of Physics, Cochin University of Science and Technology, Cochin 682 022 (India)]. E-mail: mraiyer@yahoo.com; Nampoori, V.P.N. [International School of Photonics, Cochin University of Science and Technology, Cochin-22 (India)

    2006-10-15

    Fine magnetic particles (size{approx_equal}100 A) belonging to the series Zn {sub x} Fe{sub 1-} {sub x} Fe{sub 2}O{sub 4} were synthesized by cold co-precipitation methods and their structural properties were evaluated using X-ray diffraction. Magnetization studies have been carried out using vibrating sample magnetometry (VSM) showing near-zero loss loop characteristics. Ferrofluids were then prepared employing these fine magnetic powders using oleic acid as surfactant and kerosene as carrier liquid by modifying the usually reported synthesis technique in order to induce anisotropy and enhance the magneto-optical signals. Liquid thin films of these fluids were prepared and field-induced laser transmission through these films was studied. The transmitted light intensity decreases at the centre with applied magnetic field in a linear fashion when subjected to low magnetic fields and saturate at higher fields. This is in accordance with the saturation in cluster formation. The pattern exhibited by these films in the presence of different magnetic fields was observed with the help of a CCD camera and was recorded photographically.

  8. Soft solution synthesis and intense visible photoluminescence of lamellar zinc oxide hybrids

    International Nuclear Information System (INIS)

    Sağlam, Özge

    2013-01-01

    Graphical abstract: -- In this study, we demonstrate the synthesis of layered zinc oxide films intercalated with dodecyl sulphate ions by a simple soft solution process. The presence of potassium (K + ) and lithium (Li + ) ions in the precursor solution of layered zinc hydroxide resulted in lamellar hybrid zinc oxide films instead of layered zinc hydroxides. On the other hand, the addition of nickel phthalocyanine induces zinc hydroxide host layers which exhibit an intense blue emission. This is also promoted by K + and Li + ions

  9. Zinc at glutamatergic synapses.

    Science.gov (United States)

    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.

  10. Solution-dispersible Au nanocube dimers with greatly enhanced two-photon luminescence and SERS

    Science.gov (United States)

    Liu, Xiao-Li; Liang, Shan; Nan, Fan; Yang, Zhong-Jian; Yu, Xue-Feng; Zhou, Li; Hao, Zhong-Hua; Wang, Qu-Quan

    2013-05-01

    We report the synthesis of 43-nm diameter Au nanocube dimers by using Ag+ ions as competitive ligands to freeze l-cysteine-induced assembly process of the nanocubes to a desirable stage. Ascribed to the resonant interparticle coupling with an newly arising plasmon band at 710 nm and local field enhancement, the two-photon luminescence intensity of the Au nanocube dimers in solution was over 20 times stronger than that of the monomers in the wavelength range 555-620 nm. Furthermore, by coupling Raman tags onto the nanocube surface, a solution-based surface-enhanced Raman scattering (SERS) of the nanocube dimers had an enhancement factor of over 10 times compared to the isolated nanocubes. To sum up, with high stability in solution and attractive optical properties, the Au nanocube dimers have potential applications in in vivo bio-imaging and solution-based SERS.We report the synthesis of 43-nm diameter Au nanocube dimers by using Ag+ ions as competitive ligands to freeze l-cysteine-induced assembly process of the nanocubes to a desirable stage. Ascribed to the resonant interparticle coupling with an newly arising plasmon band at 710 nm and local field enhancement, the two-photon luminescence intensity of the Au nanocube dimers in solution was over 20 times stronger than that of the monomers in the wavelength range 555-620 nm. Furthermore, by coupling Raman tags onto the nanocube surface, a solution-based surface-enhanced Raman scattering (SERS) of the nanocube dimers had an enhancement factor of over 10 times compared to the isolated nanocubes. To sum up, with high stability in solution and attractive optical properties, the Au nanocube dimers have potential applications in in vivo bio-imaging and solution-based SERS. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr01170d

  11. Zinc oxide overdose

    Science.gov (United States)

    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 ...

  12. Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

    Directory of Open Access Journals (Sweden)

    John P. Collister

    2014-12-01

    Full Text Available The brain senses circulating levels of angiotensin II (AngII via circumventricular organs, such as the subfornical organ (SFO, and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD, an intracellular superoxide (O2·− scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·− in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD or control vector (AdEmpty were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min for ten days. Rats over-expressing CuZnSOD (n = 7 in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9. These results support the hypothesis that production of O2·− in the MnPO contributes to the development of chronic AngII-dependent hypertension.

  13. Modulation of microtubule assembly by the HIV-1 Tat protein is strongly dependent on zinc binding to Tat

    Directory of Open Access Journals (Sweden)

    Muller Sylviane

    2008-07-01

    Full Text Available Abstract Background During HIV-1 infection, the Tat protein plays a key role by transactivating the transcription of the HIV-1 proviral DNA. In addition, Tat induces apoptosis of non-infected T lymphocytes, leading to a massive loss of immune competence. This apoptosis is notably mediated by the interaction of Tat with microtubules, which are dynamic components essential for cell structure and division. Tat binds two Zn2+ ions through its conserved cysteine-rich region in vitro, but the role of zinc in the structure and properties of Tat is still controversial. Results To investigate the role of zinc, we first characterized Tat apo- and holo-forms by fluorescence correlation spectroscopy and time-resolved fluorescence spectroscopy. Both of the Tat forms are monomeric and poorly folded but differ by local conformational changes in the vicinity of the cysteine-rich region. The interaction of the two Tat forms with tubulin dimers and microtubules was monitored by analytical ultracentrifugation, turbidity measurements and electron microscopy. At 20°C, both of the Tat forms bind tubulin dimers, but only the holo-Tat was found to form discrete complexes. At 37°C, both forms promoted the nucleation and increased the elongation rates of tubulin assembly. However, only the holo-Tat increased the amount of microtubules, decreased the tubulin critical concentration, and stabilized the microtubules. In contrast, apo-Tat induced a large amount of tubulin aggregates. Conclusion Our data suggest that holo-Tat corresponds to the active form, responsible for the Tat-mediated apoptosis.

  14. Zinc and gastrointestinal disease

    Institute of Scientific and Technical Information of China (English)

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

    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.

  15. Construction and application of a zinc-specific biosensor for assessing the immobilization and bioavailability of zinc in different soils

    International Nuclear Information System (INIS)

    Liu Pulin; Huang Qiaoyun; Chen Wenli

    2012-01-01

    The inducibility and specificity of different czcRS operons in Pseudomonas putida X4 were studied by lacZ gene fusions. The data of β-glycosidase activity confirmed that the czcR3 promoter responded quantitatively to zinc. A zinc-specific biosensor, P. putida X4 (pczcR3GFP), was constructed by fusing a promoterless enhanced green fluorescent protein (egfp) gene with the czcR3 promoter in the chromosome of P. putida X4. In water extracts of four different soils amended with zinc, the reporter strain detected about 90% of the zinc content of the samples. Both the bioavailability assessment and the sequential extraction analysis demonstrated that the immobilization of zinc was highly dependent on the physico-chemical properties of soils. The results also showed that the lability of zinc decreased over time. It is concluded that the biosensor constitutes an alternative system for the convenient evaluation of zinc toxicity in the environment. - Highlights: ► A zinc-specific bacterial biosensor was developed. ► Four spiked soils were used to test the application of this biosensor. ► The bioavailable zinc in soil-water extracts decreased due to aging. ► The immobilization and speciation of zinc were highly dependent on the soil type. - The immobilization and bioavailability of zinc in soil were investigated as a function of soil type and aging by a newly constructed zinc-specific biosensor coupled with chemical analysis.

  16. Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.

    Science.gov (United States)

    Cho, Minsu; Hu, Guanggan; Caza, Mélissa; Horianopoulos, Linda C; Kronstad, James W; Jung, Won Hee

    2018-01-01

    Zinc is an important transition metal in all living organisms and is required for numerous biological processes. However, excess zinc can also be toxic to cells and cause cellular stress. In the model fungus Saccharomyces cerevisiae, a vacuolar zinc transporter, Zrc1, plays important roles in the storage and detoxification of excess intracellular zinc to protect the cell. In this study, we identified an ortholog of the S. cerevisiae ZRC1 gene in the human fungal pathogen Cryptococcus neoformans. Zrc1 was localized in the vacuolar membrane in C. neoformans, and a mutant lacking ZRC1 showed significant growth defects under high-zinc conditions. These results suggested a role for Zrc1 in zinc detoxification. However, contrary to our expectation, the expression of Zrc1 was induced in cells grown in zinc-limited conditions and decreased upon the addition of zinc. These expression patterns were similar to those of Zip1, the high-affinity zinc transporter in the plasma membrane of C. neoformans. Furthermore, we used the zrc1 mutant in a murine model of cryptococcosis to examine whether a mammalian host could inhibit the survival of C. neoformans using zinc toxicity. We found that the mutant showed no difference in virulence compared with the wildtype strain. This result suggests that Zrc1-mediated zinc detoxification is not required for the virulence of C. neoformans, and imply that zinc toxicity may not be an important aspect of the host immune response to the fungus.

  17. Correlative SEM SERS for quantitative analysis of dimer nanoparticles.

    Science.gov (United States)

    Timmermans, F J; Lenferink, A T M; van Wolferen, H A G M; Otto, C

    2016-11-14

    A Raman microscope integrated with a scanning electron microscope was used to investigate plasmonic structures by correlative SEM-SERS analysis. The integrated Raman-SEM microscope combines high-resolution electron microscopy information with SERS signal enhancement from selected nanostructures with adsorbed Raman reporter molecules. Correlative analysis is performed for dimers of two gold nanospheres. Dimers were selected on the basis of SEM images from multi aggregate samples. The effect of the orientation of the dimer with respect to the polarization state of the laser light and the effect of the particle gap size on the Raman signal intensity is observed. Additionally, calculations are performed to simulate the electric near field enhancement. These simulations are based on the morphologies observed by electron microscopy. In this way the experiments are compared with the enhancement factor calculated with near field simulations and are subsequently used to quantify the SERS enhancement factor. Large differences between experimentally observed and calculated enhancement factors are regularly detected, a phenomenon caused by nanoscale differences between the real and 'simplified' simulated structures. Quantitative SERS experiments reveal the structure induced enhancement factor, ranging from ∼200 to ∼20 000, averaged over the full nanostructure surface. The results demonstrate correlative Raman-SEM microscopy for the quantitative analysis of plasmonic particles and structures, thus enabling a new analytical method in the field of SERS and plasmonics.

  18. A Zinc Chelator TPEN Attenuates Airway Hyperresponsiveness Airway Inflammation in Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Satoru Fukuyama

    2011-01-01

    Conclusions: In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.

  19. Dynamic interplay between adhesive and lateral E-cadherin dimers

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Laur, Oscar Y; Troyanovsky, Regina B

    2002-01-01

    M. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime...

  20. The two-state dimer receptor model: a general model for receptor dimers.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2006-06-01

    Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

  1. The water dimer II: Theoretical investigations

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, Anamika; Xantheas, Sotiris S.; Saykally, Richard J.

    2018-03-29

    As the archetype of hydrogen bonding between water molecules, the water dimer has been extensively studied by both theory and experiment for nearly seven decades. In this article, we present a detailed chronological review of the theoretical advances using electronic structure methods pertaining to the structure, hydrogen bonding and vibrational spectroscopy of the water dimer as well as the role of its potential energy surface in the development of classical force fields to describe intermolecular interaction in clusters and liquid water.

  2. Light activation of the LOV protein vivid generates a rapidly exchanging dimer.

    Science.gov (United States)

    Zoltowski, Brian D; Crane, Brian R

    2008-07-08

    The fungal photoreceptor Vivid (VVD) plays an important role in the adaptation of blue-light responses in Neurospora crassa. VVD, an FAD-binding LOV (light, oxygen, voltage) protein, couples light-induced cysteinyl adduct formation at the flavin ring to conformational changes in the N-terminal cap (Ncap) of the VVD PAS domain. Size-exclusion chromatography (SEC), equilibrium ultracentrifugation, and static and dynamic light scattering show that these conformational changes generate a rapidly exchanging VVD dimer, with an expanded hydrodynamic radius. A three-residue N-terminal beta-turn that assumes two different conformations in a crystal structure of a VVD C71V variant is essential for light-state dimerization. Residue substitutions at a critical hinge between the Ncap and PAS core can inhibit or enhance dimerization, whereas a Tyr to Trp substitution at the Ncap-PAS interface stabilizes the light-state dimer. Cross-linking through engineered disulfides indicates that the light-state dimer differs considerably from the dark-state dimer found in VVD crystal structures. These results verify the role of Ncap conformational changes in gating the photic response of N. crassa and indicate that LOV-LOV homo- or heterodimerization may be a mechanism for regulating light-activated gene expression.

  3. Quantitation of pyrimidine dimers in DNA from UVB-irradiated alfalfa (Medicago sativa L.) seedlings

    International Nuclear Information System (INIS)

    Quaite, F.E.; Sutherland, B.M.; Sutherland, J.C.

    1991-01-01

    Depletion of stratospheric ozone will increase the solar ultraviolet radiation in the range from 290-320 nm (UVB) that reaches the surface of the earth, placing an increased UV burden on exposed organisms. One consequence of increased UVB may be decreased productivity of crop plants. A principal lesion caused by UV in DNA is the cyclobutyl pyrimidine dimer. We have adapted a method for measuring these dimers in nanogram quantities of non-radioactive DNA for use in UV-irradiated plants. We find that biologically relevant doses of broad band UVB radiation induce easily detectable frequencies of pyrimidine dimers in the DNA of irradiated alfalfa sprout leaves and that the dose response for dimer formation is linear up to doses of at least 690 J/m 2 . We also find easily measurable frequencies of dimers in the leaves of seedlings grown in glass filtered sunlight but not exposed to additional UVB, suggesting that significant number of dimers are formed in plants exposed to normal sunlight. 27 refs., 3 figs., 1 tab

  4. Adsorption of dimeric surfactants in lamellar silicates

    Energy Technology Data Exchange (ETDEWEB)

    Balcerzak, Mateusz; Pietralik, Zuzanna [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Domka, Ludwik [Department of Metalorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań (Poland); Skrzypczak, Andrzej [Institute of Chemical Technology, Poznań University of Technology, Berdychowo 4, 60-965 Poznań (Poland); Kozak, Maciej, E-mail: mkozak@amu.edu.pl [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

    2015-12-01

    Highlights: • The intercalation of dimeric surfactants changed the morphology of MMT samples. • XRD indicated structures formed by surfactant molecules in interlayer space. • The four-step thermal decomposition of dimeric surfactant, confirms intercalation. - Abstract: The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay – hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1′-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d{sub 001}) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH{sub 2} and CH{sub 3} groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

  5. Retroviral RNA Dimerization: From Structure to Functions

    Directory of Open Access Journals (Sweden)

    Noé Dubois

    2018-03-01

    Full Text Available The genome of the retroviruses is a dimer composed by two homologous copies of genomic RNA (gRNA molecules of positive polarity. The dimerization process allows two gRNA molecules to be non-covalently linked together through intermolecular base-pairing. This step is critical for the viral life cycle and is highly conserved among retroviruses with the exception of spumaretroviruses. Furthermore, packaging of two gRNA copies into viral particles presents an important evolutionary advantage for immune system evasion and drug resistance. Recent studies reported RNA switches models regulating not only gRNA dimerization, but also translation and packaging, and a spatio-temporal characterization of viral gRNA dimerization within cells are now at hand. This review summarizes our current understanding on the structural features of the dimerization signals for a variety of retroviruses (HIVs, MLV, RSV, BLV, MMTV, MPMV…, the mechanisms of RNA dimer formation and functional implications in the retroviral cycle.

  6. Zinc in human serum

    International Nuclear Information System (INIS)

    Kiilerich, S.

    1987-01-01

    The zinc ion is essential for the living organism. Many pathological conditions have been described as a consequence of zinc deficiency. As zinc constitutes less than 0.01 per cent of the body weight, it conventionally belongs to the group of trace elements. The method of atomic absorption spectrophotometry is used to measure the concentration of zinc in serum and urine from healthy persons. The assumptions of the method is discussed. The importance of proteinbinding, diet and the diurnal variation of serum zinc concentration is presented. Serum versus plasma zinc concentration is discussed. Reference serum zinc values from 104 normal subjects are given. Zinc in serum is almost entirely bound to proteins. A preliminary model for the estimation of the distribution of zinc between serum albumin and α 2 -macroglobulin is set up. This estimate has been examined by an ultracentrufugation method. The binding of zinc to a α 2 -macroglobulin in normal persons is appoximately 7 per cent, in patients with cirrhosis of the liver of alcoholic origin approximately 6 per cent, in patients with insulin dependent diabetes mellitus approximately 5 per cent, and in patients with chronic renal failure approximately 2 per cent. It is concluded, therefore, that for clinical purposes it is sufficient to use the concentration of total serum zinc corrected for the concentration of serum albumin. (author)

  7. Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells

    Energy Technology Data Exchange (ETDEWEB)

    Saquib, Quaiser; Al-Khedhairy, Abdulaziz A.; Ahmad, Javed; Siddiqui, Maqsood A.; Dwivedi, Sourabh; Khan, Shams T. [Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Musarrat, Javed, E-mail: musarratj1@yahoo.com [Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh 202002, U.P. (India)

    2013-12-01

    The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe{sub 2}O{sub 4}-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 μg/ml of ZnFe{sub 2}O{sub 4}-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48 h of ZnFe{sub 2}O{sub 4}-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT{sup 2} Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p < 0.01) population of ZnFe{sub 2}O{sub 4}-NPs (100 μg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe{sub 2}O{sub 4}-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe{sub 2}O{sub 4}-NPs induced cellular and genetic damage. - Highlights: • First report on the molecular toxicity of ZnFe{sub 2}O{sub 4}-NPs in cells of placental origin • WISH cells treated with ZnFe{sub 2}O{sub 4}-NPs exhibited cytoplasmic

  8. Pseudomonas aeruginosa Trent and zinc homeostasis.

    Science.gov (United States)

    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.

  9. Serum zinc levels in gestational diabetes

    Directory of Open Access Journals (Sweden)

    Rahimi Sharbaf F

    2008-12-01

    Full Text Available "nBackground: Maternal zinc deficiency during pregnancy has been related to adverse pregnancy outcomes. Most studies in which pregnant women have been supplemented with zinc to examine its effects on the outcome of the pregnancy have been carried out in industrialized countries and the results have been inconclusive. It has been shown that women with gestational diabetes (GDM have lower serum zinc levels than healthy pregnant women, and higher rates of macrosomia. Zinc is required for normal glucose metabolism, and strengthens the insulin-induced transportation of glucose into cells by its effect on the insulin signaling pathway. The purpose of this study was to assess the serum zinc levels of GDM patients and evaluate the effect of zinc supplementation. "nMethods: In the first stage of this prospective controlled study, we enrolled 70 women who were 24-28 weeks pregnant at the Prenatal Care Center of Mirza Kochak Khan Hospital, Tehran, Iran. The serum zinc level of each subject was determined. In the second stage, among these 70 subjects, the diabetics receiving insulin were divided into two groups, only one of which received a zinc supplement and the other group was the control group. Birth weight of neonates and insulin dosages were recorded. "nResults: The mean serum zinc level in the GDM group was lower than that of the control group (94.83 vs. 103.49mg/dl, respectively and the mean birth weight of neonates from the GDM women who received the zinc supplement was lower than that of the control group (3849g vs. 4136g. The rate of macrosomia was lower in the zinc supplemented group (20% vs. 53%. The mean of increase of insulin after receiving the zinc supplement was lower (8.4u vs. 13.53. "nConclusion: Maternal insulin resistance is associated with the accumulation of maternal fat tissue during early stages of pregnancy and greater fetoplacental nutrient availability in later stages, when 70% of fetal growth occurs, resulting in macrosomia. In

  10. Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6, and rad9 of Saccharomyces cerevisiae. [nicking

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics; Rochester Univ., N.Y. (USA). School of Medicine and Dentistry)

    1977-10-01

    The ability to remove ultraviolet-induced pyrimidine dimers was examined in four radiation-sensitive mutants of Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by either the T4 uv-endonuclease or an endonuclease activity found in crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad3 and rad4 mutants are shown to be defective in dimer excision whereas the rad6 and rad9 mutants are proficient in dimer excision.

  11. D-dimers (DD) in CVST.

    Science.gov (United States)

    Wang, Hui Fang; Pu, Chuan Qiang; Yin, Xi; Tian, Cheng Lin; Chen, Ting; Guo, Jun Hong; Shi, Qiang

    2017-06-01

    We were interested in further confirming whether D-dimers (DD) are indeed elevated in cerebral venous sinus thrombosis (CVST) as reported in those studies. CVST patients who had a plasma D-dimer test (139 cases) were included and divided into two groups: elevated D-dimer group (EDG) (>0.5 μg/mL; 65 cases) and normal D-dimer group (NDG) (≤0.5 μg/mL; 74 cases). The two groups were compared in terms of demographic data, clinical manifestation, laboratory and imaging data, using inferential statistical methods. The chi-squared and Fisher exact test showed that, compared to the NDG (74 cases), patients with elevated D-dimer levels were more likely to have a shorter symptom duration (SD) (30 ± 83.9 versus 90 ± 58.9 d, p = 0.003), more risk factors (75.4% versus 52.7%, p = 0.006), higher multiple venous sinus involvement (75.4% versus 59.5%, p = 0.037), increased fibrinogen (43.1% versus 18.9%, p = 0.037) and higher levels of blood glucose (18.3% versus 11%, p = 0.037). According to correlation analyses, D-dimer levels were positively correlated with number of venous sinuses involvement (NVS) (r = 0.321, p = 0.009) in the EDG. Multivariate logistic regression analysis showed that SD (OR, 0.025; 95% CI, 1.324-6.043; p = 0.000), NVS (OR, 1.573; 95% CI, 1.15-2.151; p = 0.005) and risk factors (OR, 3.321; 95% CI, 1.451-7.564; p = 0.004) were significantly different between the two groups. D-dimer is elevated in patients with acute/subacute CVST.

  12. Calix[4]arene supported clusters: a dimer of [Mn(III)Mn(II)] dimers

    DEFF Research Database (Denmark)

    Taylor, Stephanie M; McIntosh, Ruaraidh D; Beavers, Christine M

    2011-01-01

    Phosphinate ligands allow for the transformation of a calix[4]arene supported [Mn(III)(2)Mn(II)(2)] tetramer cluster motif into an unusual [Mn(III)Mn(II)](2) dimer of dimers; the clusters self-assemble in the crystal to form bi-layer arrays reminiscent of the typical packing of calixarene solvates....

  13. Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells

    Directory of Open Access Journals (Sweden)

    Kira G. Slepchenko

    2012-01-01

    Full Text Available Zinc (Zn2+ appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

  14. Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

    Science.gov (United States)

    Slepchenko, Kira G; Li, Yang V

    2012-01-01

    Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

  15. The role of nitrergic system in antidepressant effects of acute administration of zinc, magnesium and thiamine on progesterone induced postpartum depression in mice

    Directory of Open Access Journals (Sweden)

    Nikseresht S

    2010-08-01

    Full Text Available "nBackground: Postpartum depression is a mood disorder that has harmful effects on mothers, infants, family and relationships. Acute decrease of progesterone after delivery has been proposed as a cause for postpartum depression. This hormone can affect neurotransmitters' function. Zinc (Zn and magnesium (Mg as trace elements exert their antidepressant effects through neurotransmitter pathways. On the other hand, thiamin (Vit B1 deficiency leads to depression in animal models. The aim of this study was to evaluate effects of combination of zinc, magnesium and thiamine on postpartum depression and role of nitrergic system. "n"nMethods: One hundred ten female mice in five groups were used. Postpartum depression was conducted using progesterone injections. Combinations of Zinc chloride, magnesium chloride and thiamine HCL were administered 30 minutes before open field and forced swimming test (FST. In order to investigate role of nitrergic system, L-arginine and LNAME were administered. "n"nResults: All treatment groups spent less immobility time than the control group (p< 0.05. Combined administration of Zn+ Mg+ Vit B1 caused the most reduction in immobility time. Administration of L-NAME in Zn+ Mg+ Vit B1 group caused reduction in immobility time while administration of L-arginine caused increase in immobility time in the same group. "nConclusion: Zinc, magnesium and thiamine can improve depressive symptoms by nitrergic pathway. These elements as supplement compounds could be alternatives for antidepressants in postpartum period.

  16. Differences in pyrimidine dimer removal between rat skin cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Mullaart, E.; Lohman, P.H.; Vijg, J.

    1988-01-01

    Pyrimidine dimers, the most abundant type of DNA lesions induced by ultraviolet light (UV), are rapidly repaired in human skin fibroblasts in vitro. In the same cell type from rats, however, there is hardly any removal of such dimers. To investigate whether this low capacity of rat skin cells to repair lesions in their DNA is an inherent characteristic of this species or an artifact due to cell culturing, we measured the removal of UV-induced pyrimidine dimers from rat epidermal keratinocytes both in vitro and in vivo. Epidermal keratinocytes in vitro were unable to remove any dimers over the first 3 h after UV-irradiation, while only about 20% was removed during a repair period of 24 h. In this respect, these cells were not different from cultured rat fibroblasts. In contrast to the results obtained with keratinocytes in vitro, we observed a rapid repair of pyrimidine dimers in UV-irradiated keratinocytes in vivo over the first 3 h; this rapid repair phase was followed by a much slower repair phase between 3 and 24 h. These results are discussed in terms of the possibility that mammalian cells are able to switch from one DNA repair pathway to another

  17. Plasmonic nanospherical dimers for color pixels

    KAUST Repository

    Alrasheed, Salma

    2018-04-20

    Display technologies are evolving more toward higher resolution and miniaturization. Plasmonic color pixels can offer solutions to realize such technologies due to their sharp resonances and selective scattering and absorption at particular wavelengths. Metal nanosphere dimers are capable of supporting plasmon resonances that can be tuned to span the entire visible spectrum. In this article, we demonstrate numerically bright color pixels that are highly polarized and broadly tuned using periodic arrays of metal nanosphere dimers on a glass substrate. We show that it is possible to obtain RGB pixels in the reflection mode. The longitudinal plasmon resonance of nanosphere dimers along the axis of the dimer is the main contributor to the color of the pixel, while far-field diffractive coupling further enhances and tunes the plasmon resonance. The computational method used is the finite-difference time-domain method. The advantages of this approach include simplicity of the design, bright coloration, and highly polarized function. In addition, we show that it is possible to obtain different colors by varying the angle of incidence, the periodicity, the size of the dimer, the gap, and the substrate thickness.

  18. A High-Resolution Crystal Structure of a Psychrohalophilic α-Carbonic Anhydrase from Photobacterium profundum Reveals a Unique Dimer Interface.

    Directory of Open Access Journals (Sweden)

    Vijayakumar Somalinga

    Full Text Available Bacterial α-carbonic anhydrases (α-CA are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α-CA (PprCA reveals that the protein is a heterogeneous mix of monomers and dimers. Furthermore, an "in-gel" carbonic anhydrase activity assay, also known as protonography, revealed two distinct bands corresponding to monomeric and dimeric forms of PprCA that are catalytically active. The crystal structure of PprCA was determined in its native form and reveals a highly conserved "knot-topology" that is characteristic of α-CA's. Similar to other bacterial α-CA's, PprCA also crystallized as a dimer. Furthermore, dimer interface analysis revealed the presence of a chloride ion (Cl- in the interface which is unique to PprCA and has not been observed in any other α-CA's characterized so far. Molecular dynamics simulation and chloride ion occupancy analysis shows 100% occupancy for the Cl- ion in the dimer interface. Zinc coordinating triple histidine residues, substrate binding hydrophobic patch residues, and the hydrophilic proton wire residues are highly conserved in PprCA and are identical to other well-studied α-CA's.

  19. After oxidation, zinc nanoparticles lose their ability to enhance responses to odorants.

    Science.gov (United States)

    Hagerty, Samantha; Daniels, Yasmine; Singletary, Melissa; Pustovyy, Oleg; Globa, Ludmila; MacCrehan, William A; Muramoto, Shin; Stan, Gheorghe; Lau, June W; Morrison, Edward E; Sorokulova, Iryna; Vodyanoy, Vitaly

    2016-12-01

    Electrical responses of olfactory sensory neurons to odorants were examined in the presence of zinc nanoparticles of various sizes and degrees of oxidation. The zinc nanoparticles were prepared by the underwater electrical discharge method and analyzed by atomic force microscopy and X-ray photoelectron spectroscopy. Small (1.2 ± 0.3 nm) zinc nanoparticles significantly enhanced electrical responses of olfactory neurons to odorants. After oxidation, however, these small zinc nanoparticles were no longer capable of enhancing olfactory responses. Larger zinc oxide nanoparticles (15 nm and 70 nm) also did not modulate responses to odorants. Neither zinc nor zinc oxide nanoparticles produced olfactory responses when added without odorants. The enhancement of odorant responses by small zinc nanoparticles was explained by the creation of olfactory receptor dimers initiated by small zinc nanoparticles. The results of this work will clarify the mechanisms for the initial events in olfaction, as well as to provide new ways to alleviate anosmia related to the loss of olfactory receptors.

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

    Directory of Open Access Journals (Sweden)

    Travis J A Craddock

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ, intracellular neurofibrillary tangles (NFTs composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau, and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1 used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2 performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3 used metallomic imaging mass spectrometry (MIMS to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of

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

    Science.gov (United States)

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

    2012-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized

  2. Radiation chemistry of aromatic dimer radical cations

    International Nuclear Information System (INIS)

    Okamoto, Kazumasa; Tagawa, Seiichi

    2009-01-01

    π-π Interactions of aromatic molecules are paid attention much in many fields, especially biology, chemistry, and applied physics, represented as protein, DNA, electron donor-accepter complexes, charge transfers, and self assembly molecules. Aromatic molecules including benzene rings are the simplest case to study the π-π interactions. To interpret the charge resonance (CR) structure in the dimer radical cations, spectroscopic and ESR methods have been carried out. The spectroscopic study on the dimer radical ion of molecules with two chromophores would be profitable to identify the electronic and configurational properties. In this article, dynamics of the dimer radical cation of benzenes, polystyrenes, and resist polymers is described on the basis of direct observation of CR band by the nanosecond pulse radiolysis and low temperature γ-radiolysis methods. (author)

  3. Photoionization of helium dimers; Photoionisation von Heliumdimeren

    Energy Technology Data Exchange (ETDEWEB)

    Havermeier, Tilo

    2010-06-09

    The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

  4. Harman inhibits the removal of pyrimidine dimers from the DNA of human cells

    International Nuclear Information System (INIS)

    Castellani, A.; Setlow, R.B.

    1981-01-01

    Normal human fibroblasts were UV-irradiated and incubated for 6 hr with harman. The losses of sites, in the extracted DNA, sensitive to a UV specific endonuclease were determined as precision measures of the excision of UV-induced pyrimidine dimers. Harman inhibited excision, rising from approx. 30% inhibition at 200 μM to 75% inhibition at 500 μM

  5. Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in photolyase transgenic mice

    NARCIS (Netherlands)

    W. Schul; J. Jans (Judith); Y.M. Rijksen (Yvonne); K.H. Klemann; J. de Wit (Jan); O. Nikaido; S. Nakajima; A. Yasui (Akira); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); A.P.M. Eker (André)

    2002-01-01

    textabstractDuring evolution, placental mammals appear to have lost cyclobutane pyrimidine dimer (CPD) photolyase, an enzyme that efficiently removes UV-induced CPDs from DNA in a light-dependent manner. As a consequence, they have to rely solely on the more complex, and for this lesion less

  6. How Does Thymine DNA Survive Ultrafast Dimerization Damage?

    Directory of Open Access Journals (Sweden)

    Hongjuan Wang

    2016-12-01

    Full Text Available The photodimerization reaction between the two adjacent thymine bases within a single strand has been the subject of numerous studies due to its potential to induce DNA mutagenesis and possible tumorigenesis in human skin cells. It is well established that the cycloaddition photoreaction takes place on a picosecond time scale along barrierless or low barrier singlet/triplet pathways. However, the observed dimerization quantum yield in different thymine multimer is considerable lower than might be expected. A reasonable explanation is required to understand why thymine in DNA is able to survive ultrafast dimerization damage. In this work, accurate quantum calculations based on the combined CASPT2//CASSCF/AMBER method were conducted to map the excited state relaxation pathways of the thymine monomer in aqueous solution and of the thymine oligomer in DNA. A monomer-like decay pathway, induced by the twisting of the methyl group, is found to provide a bypass channel to ensure the photostability of thymine in single-stranded oligomers. This fast relaxation path is regulated by the conical intersection between the bright SCT(1ππ* state with the intra-base charge transfer character and the ground state to remove the excess excitation energy, thereby achieving the ground-state recovery with high efficiency.

  7. Photon Propagation through Linearly Active Dimers

    Directory of Open Access Journals (Sweden)

    José Delfino Huerta Morales

    2017-06-01

    Full Text Available We provide an analytic propagator for non-Hermitian dimers showing linear gain or losses in the quantum regime. In particular, we focus on experimentally feasible realizations of the PT -symmetric dimer and provide their mean photon number and second order two-point correlation. We study the propagation of vacuum, single photon spatially-separable, and two-photon spatially-entangled states. We show that each configuration produces a particular signature that might signal their possible uses as photon switches, semi-classical intensity-tunable sources, or spatially entangled sources to mention a few possible applications.

  8. On the asymptotics of dimers on tori

    OpenAIRE

    Kenyon, Richard W.; Sun, Nike; Wilson, David B.

    2013-01-01

    We study asymptotics of the dimer model on large toric graphs. Let $\\mathbb L$ be a weighted $\\mathbb{Z}^2$-periodic planar graph, and let $\\mathbb{Z}^2 E$ be a large-index sublattice of $\\mathbb{Z}^2$. For $\\mathbb L$ bipartite we show that the dimer partition function on the quotient $\\mathbb{L}/(\\mathbb{Z}^2 E)$ has the asymptotic expansion $\\exp[A f_0 + \\text{fsc} + o(1)]$, where $A$ is the area of $\\mathbb{L}/(\\mathbb{Z}^2 E)$, $f_0$ is the free energy density in the bulk, and $\\text{fsc...

  9. Chelators for investigating zinc metalloneurochemistry

    OpenAIRE

    Radford, Robert John; Lippard, Stephen J.

    2013-01-01

    The physiology and pathology of mobile zinc signaling has become an important topic in metalloneurochemistry. To study the action of mobile zinc effectively, specialized tools are required that probe the temporal and positional changes of zinc ions within live tissue and cells. In the present article we describe the design and implementation of selective zinc chelators as antagonists to interrogate the function of mobile zinc, with an emphasis on the pools of vesicular zinc in the terminals o...

  10. Unravelling Thiol’s Role in Directing Asymmetric Growth of Au Nanorod–Au Nanoparticle Dimers

    KAUST Repository

    Huang, Jianfeng

    2015-12-15

    Asymmetric nanocrystals have practical significance in nanotechnologies but present fundamental synthetic challenges. Thiol ligands have proven effective in breaking the symmetric growth of metallic nanocrystals but their exact roles in the synthesis remain elusive. Here, we synthesized an unprecedented Au nanorod-Au nanoparticle (AuNR-AuNP) dimer structure with the assistance of a thiol ligand. On the basis of our experimental observations, we unraveled for the first time that the thiol could cause an inhomogeneous distribution of surface strains on the seed crystals as well as a modulated reduction rate of metal precursors, which jointly induced the asymmetric growth of monometallic dimers. © 2015 American Chemical Society.

  11. Sigma- versus Pi-Dimerization Modes of Triangulene.

    Science.gov (United States)

    Mou, Zhongyu; Kertesz, Miklos

    2018-04-20

    We show that the diradicaloid triangulene, a graphene nano-flake molecule, can aggregate in a variety of dimerization modes. We found by density functional theory modeling a number of triangulene dimers including six doubly bonded σ-dimers in addition to the previously reported six pancake bonded π-dimer isomers. The σ-dimers display a wide range of stabilities: the interaction energy of the most stable σ-dimer is -25.17 kcal mol -1 . Besides the doubly bonded σ-dimers with closed shell ground states, we also found an open-shell singly σ-bonded diradicaloid dimer. We found an interesting isomerization route between a doubly bonded σ-dimer, a singly bonded σ-dimer with a low-lying triplet state and two π-bonded dimers with low-lying quintet states. Derivatives of triangulene, trioxo-triangulenes (TOTs) have been previously characterized experimentally. Here, we show the reasons why so far only the π-dimer but not the σ-dimer was experimentally observed for all TOTs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. High-performance characteristics of the bonded magnets produced from the Sm2 Fe17 Nx powder stabilized by photo-induced zinc metal coatings

    International Nuclear Information System (INIS)

    Machida, K.; Izumi, H.; Shiomi, A.; Iguchi, M.; Adachi, G.

    1996-01-01

    Finely and uniformly ground powders of Sm 2 Fe 17 N x were stabilized by surface-coating with the zinc metal produced from Zn (C 2 H 5 ) 2 . The epoxy resin-bonded magnets produced from the Zn/Sm 2 Fe 17 N x composite powder provided high-performance permanent magnetic characteristics: (BH)max=∼ 176 kJm -3 . (author)

  13. Further studies on selective radioprotection by organic zinc salts and synergism of zinc aspartate with WR 2721

    International Nuclear Information System (INIS)

    Floersheim, G.L.; Bieri, A.

    1990-01-01

    Protection of the haematocrit and thrombocytes by small doses of the aminothiol radioprotector WR 2721 was markedly improved by the concomitant administration of small doses of zinc aspartate. Zinc aspartate was the only one of the tested zinc salts not inhibiting the regression induced by radiotherapy of human tumours grown as xenografts in immunosuppressed mice. This also applied to zinc aspartate with WR 2721. A dose of zinc aspartate which afforded synergistic haematological protection did not enhance the toxicity of WR 2721. The synergism of zinc aspartate with WR 2721 and the differential radioprotection of the combined protocol may make it possible in clinical cancer radiotherapy to obtain selective radioprotection at a lower toxicity giving an improved therapeutic ratio compared with WR 2721 alone. (author)

  14. Effect of Oral Zinc Sulphate in Preventionof Radiation Induced OropharyngealMucositis During and After Radiotherapyin Patients with Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadianpanah

    2010-04-01

    Full Text Available Introduction:Mucositis is a disturbing side effect of radiotherapy treatment forhead and neck cancer. To date, no effective modality for its prophylaxis and treatmenthas been found. We performed this study to evaluate the efficacy of oral zincsulphate in delaying the onset of oral and pharyngeal mucositis and decreasing theirseverity.Materials and Methods: Atotal of 58 patients who were treated for head andneck squamous cell carcinoma with radiotherapy or chemoradiotherapy wererandomly assigned to receive oral zinc sulphate (220 mg or an oral placebo 3 timesa day during their radiotherapy course. Total radiation dose was 6000 cGy to 7000cGy by conventional radiotherapy. Seventy nine percent of the patients also receivedconcurrent chemotherapy. Oral and pharyngeal mucositis were scored according toan RTOG protocol. Results:Time to onset of mucositis did not vary between the two groups.However, oral mucositis scores were less severe in the zinc group in weeks 4 to 6.The difference was statistically significant and the Pvalues for weeks 4, 5 and 6 were0.02, 0.007, and 0.012, respectively. Treatment interruptions in both groups were thesame (four cases each and all were due to dysphagia (pharyngeal mucositis.Conclusion:Our results suggest that zinc is effective in reducing the severity oforal mucositis but not pharyngeal mucositis. Treatment interruptions were morefrequently caused by pharyngeal mucositis which presented as dysphagia, rather thanoral pain that was a manifestation of oral mucositis.

  15. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

    Directory of Open Access Journals (Sweden)

    Diego M Presman

    2014-03-01

    Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

  16. Role of quaternary structure in muscle creatine kinase stability: tryptophan 210 is important for dimer cohesion.

    Science.gov (United States)

    Perraut, C; Clottes, E; Leydier, C; Vial, C; Marcillat, O

    1998-07-01

    A mutant of the dimeric rabbit muscle creatine kinase (MM-CK) in which tryptophan 210 was replaced has been studied to assess the role of this residue in dimer cohesion and the importance of the dimeric state for the native enzyme stability. Wild-type protein equilibrium unfolding induced by guanidine hydrochloride occurs through intermediate states with formation of a molten globule and a premolten globule. Unlike the wild-type enzyme, the mutant inactivates at lower denaturant concentration and the loss of enzymatic activity is accompanied by the dissociation of the dimer into two apparently compact monomers. However, the Stokes radius of the monomer increases with denaturant concentration as determined by size exclusion chromatography, indicating that, upon monomerization, the protein structure is destabilized. Binding of 8-anilinonaphthalene-1-sulfonate shows that the dissociated monomer exposes hydrophobic patches at its surface, suggesting that it could be a molten globule. At higher denaturant concentrations, both wild-type and mutant follow similar denaturation pathways with formation of a premolten globule around 1.5-M guanidine, indicating that tryptophan 210 does not contribute to a large extent to the monomer conformational stability, which may be ensured in the dimeric state through quaternary interactions.

  17. Structural insights into the intertwined dimer of fyn SH2.

    Science.gov (United States)

    Huculeci, Radu; Garcia-Pino, Abel; Buts, Lieven; Lenaerts, Tom; van Nuland, Nico

    2015-12-01

    Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. © 2015 The Protein Society.

  18. Synthesis and characterization of monomeric and dimeric ...

    African Journals Online (AJOL)

    The two complexes are isostructural, with the central metal atom lying on a crystallographic 2-fold axis. Both complexes are approximately octahedral, the coordination being provided by two trans pyridine nitrogen atoms and two cis amine nitrogen atoms from the oxime ligands, and by two cis chlorides. The dimeric ...

  19. The hyperfine spectrum of hydrogen dimers

    International Nuclear Information System (INIS)

    Verberne, J.F.C.

    1979-01-01

    The authors' aim was to obtain the level scheme for the hydrogen dimers and to investigate the angle dependent interactions by analyzing the zero magnetic field hyperfine spectrum of the ortho-ortho and ortho-para species. The results were tested by several recent semi-empirical and ab initio potentials. (Auth.)

  20. What factors control dimerization of coniferyl alcohol?

    Science.gov (United States)

    Carl J. Houtman

    1999-01-01

    Data suggest that the dimerization of coniferyl alcohol is not under thermodynamic control. In this study, molecular dynamics calculations were used to estimate the effect of the solvent environment. In water, the coniferyl alcohol radicals were forced to associate by the formation of a solvent cage. In glycerol, the solvent cage effect appeared to be absent. These...

  1. Surface compounds and the routes of formation of the reaction products in the interaction of propylene with zinc oxide

    Energy Technology Data Exchange (ETDEWEB)

    Davydov, A.A.; Yefremov, A.A.; Mikhalchenko, V.G.; Sokolovskii, V.D.

    1979-06-15

    Temperature programed desorption of propylene and allyl bromide from zinc oxide in the absence and presence of oxygen and an IR spectroscopic study of the adsorbed allyl bromide showed that propylene chemisorbed reversibly as a m-allyl species which may undergo dimerization at higher pressures or temperatures but does not form acrolein because the necessary electron transfer does not proceed on the n-type zinc oxide; that propylene also forms carbon dioxide and water via carbonate/carboxylate intermediates; and that the allyl bromide, which forms cations on the zinc oxide surface, is oxidized to acrolein.

  2. Determination of the Tetramer-Dimer Equilibrium Constant of Rabbit ...

    African Journals Online (AJOL)

    Hemoglobin is a tetrameric protein which is able to dissociate into dimers. The dimers can in turn dissociate into tetramers. It has been found that dimers are more reactive than tetramers. The difference in the reactivity of these two species has been used to determine the tetramerdimer dissociation constant of various ...

  3. Stochastic optimization-based study of dimerization kinetics

    Indian Academy of Sciences (India)

    To this end, we study dimerization kinetics of protein as a model system. We follow the dimerization kinetics using a stochastic simulation algorithm and ... optimization; dimerization kinetics; sensitivity analysis; stochastic simulation ... tion in large molecules and clusters, or the design ..... An unbiased strategy of allocating.

  4. CtBP1/BARS Gly172 → Glu mutant structure: Impairing NAD(H)-binding and dimerization

    International Nuclear Information System (INIS)

    Nardini, Marco; Valente, Carmen; Ricagno, Stefano; Luini, Alberto; Corda, Daniela; Bolognesi, Martino

    2009-01-01

    C-terminal binding proteins (CtBPs) are multi-functional proteins involved in nuclear transcriptional co-repression, Golgi membrane fission, and synaptic ribbon formation. Binding of NAD(H) to CtBPs promotes dimerization. CtBP dimers act as a scaffold for multimeric protein complex formation, thus bridging transcriptional repressors and their targets in the nucleus. Based on size-exclusion chromatography experiments and on the crystal structure of the NAD(H)-free G172E CtBP mutant, we show here that absence of NAD(H) induces flexibility/backbone conformational changes at the dimerization interface and at the CtBP interdomain region. The results presented shed first light on the correlation between NAD(H)-binding and functional CtBP dimerization.

  5. Immersion autometallography: histochemical in situ capturing of zinc ions in catalytic zinc-sulfur nanocrystals.

    Science.gov (United States)

    Danscher, Gorm; Stoltenberg, Meredin; Bruhn, Mikkel; Søndergaard, Chris; Jensen, Dorete

    2004-12-01

    In the mid-1980s, two versions of Timm's original immersion sulfide silver method were published. The authors used immersion of tissue in a sulfide solution as opposed to Timm, who used immersion of tissue blocks in hydrogen sulfide-bubbled alcohol. The autometallography staining resulting from the "sulfide only immersion" was not particularly impressive, but the significance of this return to an old approach became obvious when Wenzel and co-workers presented their approach in connection with introduction by the Palmiter group of zinc transporter 3 (ZnT3). The Wenzel/Palmiter pictures are the first high-resolution, high-quality pictures taken from tissues in which free and loosely bound zinc ions have been captured in zinc-sulfur nanocrystals by immersion. The trick was to place formalin-fixed blocks of mouse brains in a solution containing 3% glutaraldehyde and 0.1% sodium sulfide, ingredients used for transcardial perfusion in the zinc-specific NeoTimm method. That the NeoTimm technique results in silver enhancement of zinc-sulfur nanocrystals has been proved by proton-induced X-ray multielement analyses (PIXE) and in vivo chelation with diethyldithiocarbamate (DEDTC). The aims of the present study were (a) to make the immersion-based capturing of zinc ions in zinc-sulfur nanocrystals work directly on sections and slices of fixed brain tissue, (b) to work out protocols that ensure zinc specificity and optimal quality of the staining, (c) to apply "immersion autometallography" (iZnSAMG) to other tissues that contain zinc-enriched (ZEN) cells, and (d) to make the immersion approach work on unfixed fresh tissue.

  6. Structures of DNA containing psoralen crosslink and thymine dimer

    International Nuclear Information System (INIS)

    Kim, S.H.; Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.

    1985-01-01

    UV irradiation by itself or in conjunction with other chemicals can cause covalent damages to DNA in living cells. To overcome the detrimental effect of DNA damage, cells developed a repair mechanism by which damaged DNA is repaired. In the absence of such repair, cell malfunction or cell death can occur. Two most studied radiation-induced DNA damage are thymine dimer formation by UV irradiation and psoralen crosslink by combination of psoralens and UV: In the former, two adjacent thymine bases on a strand of DNA are fused by forming cyclobutane ring, and in the latter, one pyrimidine on one DNA strand is crosslinked to another pyrimidine on the other strand via a psoralen. The authors' objective is to deduce the structure of DNA segment which contains a psoralen crosslink or a thymine dimer using the combination of results of X-ray crystallographic studies, molecular model building, and energy minimization. These structural features may be important for understanding the biological effects of such damages and for the recognition by the repair enzymes

  7. Changes in the Spectral Features of Zinc Phthalocyanine Induced by Nitrogen Dioxide Gas in Solution and in Solid Polymer Nanofiber Media.

    Science.gov (United States)

    Zugle, Ruphino; Tetteh, Samuel

    2017-03-01

    The changes in the spectral features of zinc phthalocyanine in the visible domain as a result of its interaction with nitrogen dioxide gas were assessed in this work. This was done both in solution and when the phthalocyanine was incorporated into a solid polystyrene polymer nanofiber matrix. The spectral changes were found to be spontaneous and marked in both cases suggesting a rapid response criterion for the detection of the gas. In particular, the functionalised nano-fabric material could serve as a practical fire alarm system as it rapidly detects the nitrogen dioxide gas generated during burning.

  8. Pyrimidine dimer formation and repair in human skin

    International Nuclear Information System (INIS)

    Sutherland, B.M.; Harber, L.C.; Kochevar, I.E.

    1980-01-01

    Cyclobutyl pyrimidine dimers have been detected in the DNA of human skin following in vivo irradiation with suberythermal doses of ultraviolet (UV) radiation from FS-20 sun lamp fluorescent tubes. Dimers were assayed by treatment of extracted DNA with Micrococus luteus UV-specific endonuclease, alkaline agarose electrophoresis, and ethidum bromide staining. This technique, in contrast to conventional dimer assays, can be used with nonradioactive DNA and is optimal at low UV light doses. These data suggest that some dimer disappearance by excision repair occurs within 20 min of UV irradiation and that photoreactivation of dimers can make a contribution to the total repair process

  9. Structures and energetics of lithium adatom and its dimer on graphene–a DFT study

    International Nuclear Information System (INIS)

    Kaur, Gagandeep; Gupta, Shuchi; Dharamvir, Keya

    2015-01-01

    Highlights: • For single Li adatom adsorption on graphene, it prefers H-site followed by B-site. • By the examination of the calculated cohesive energies, it is possible to conclude that both Li/Li 2 binds strongly to graphene which corroborate previous results. • The calculations showed that the interaction between Li and graphene has minimal effects on the electronic states of the graphene sheet, in agreement with previous calculations. • Charge transfer (0.338e)upon adsorption also induces significant electric dipole moments and affect total magnetic moment at B-site and T-site. • For the Li dimer adsorption, we found that horizontal orientation is favored over the vertical. • Adsorption of lithium dimer to the HH-site alters graphene sheet only by small amount ∼0.0022 Å–0.0034 Å. • The methodology demonstrated in this paper maybe applied to larger lithium clusters on graphene sheet. - Abstract: We performed a systematic density functional theory (DFT) study of the adsorption of Lithium adatom and its dimer on graphene using SIESTA package [1], in the generalized gradient approximation (GGA). The adsorption energy, geometry, charge transfer and density of states of adatom/dimer-graphene system are calculated. The calculations showed that the interaction between Li adatom and graphene is strong (∼1.07 eV) and it prefers to adsorb on H-site. Further calculations of both horizontally and vertically aligned dimers show that the adsorption is also weak for the latter orientation. The preferred orientation of each dimer was found to be parallel to graphene sheet with the two atoms of the dimer occupying adjacent H-sites on the graphene. Significant charge transfer (∼0.388e) from Li adatom to graphene will induce electric dipole moments in the adatom/graphene system. We also calculated DOS for the stable Li -graphene system. The Fermi energy is seen to lie above the Dirac point inside the conduction band indicating that appreciable electrons

  10. Zinc phosphate conversion coatings

    Science.gov (United States)

    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.

  11. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.

    Science.gov (United States)

    de Queiroz, Camila A A; Fonseca, Said Gonçalves C; Frota, Priscila B; Figueiredo, Italo L; Aragão, Karoline S; Magalhães, Carlos Emanuel C; de Carvalho, Cibele B M; Lima, Aldo Ângelo M; Ribeiro, Ronaldo A; Guerrant, Richard L; Moore, Sean R; Oriá, Reinaldo B

    2014-08-05

    WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc's anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.

  12. Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14, and MMS19

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L; Prakash, S

    1979-01-01

    The ability to remove ultraviolet (uv)-induced pyrimidine dimers from the nuclear DNA of yeast was examined in two radiation-sensitive (rad) mutants and one methyl methanesulfonate-sensitive (mms) mutant of the yeast Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by an endonuclease activity prepared from crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad7, rad14, and mms19 mutants were found to be defective in their ability to remove uv-induced dimers from nuclear DNA. All three mutants belong to the same episatic group as the other mutants involved in excision-repair. All three mutants show enhanced uv-induced mutations. The rad 14 mutant also shows epistatic interactions with genes in the other two uv repair pathways.

  13. Effect of molybdenum on the severity of toxicity symptoms in flax induced by an excess of either manganese, zinc, copper, nickel or cobalt in the nutrient solution

    Energy Technology Data Exchange (ETDEWEB)

    Millikan, C R

    1947-01-01

    The addition of molybdenum to solutions containing an excess of either manganese, zinc, copper, nickel or cobalt respectively, resulted in decreases in the severity of iron deficiency symptoms which normally occurred when flax was grown in solutions containing the same concentrations of any of these elements, but without molybdenum. The efficacy of molybdenum in this regard increased with increasing concentration up to 25 parts per million. However, concentrations of 0.5 to 2 parts per million of molybdenum had little effect on the severity of iron deficiency symptoms at the concentrations of heavy metals used. Molybdenum 5, 10 or 25 parts per million also retarded the date of appearance and reduced the severity of lower leaf necrosis which is another characteristic symptom of the presence of excess manganese (25 to 100 parts per million) in the nutrient solution. It is concluded that an essential function of molybdenum is intimately associated with the regulation of the deleterious effect of manganese, zinc, copper, nickel or cobalt on the physiological availability of iron to the plant. 46 references, 3 figures.

  14. Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains

    International Nuclear Information System (INIS)

    Vallee, B.L.; Auld, D.S.; Coleman, J.E.

    1991-01-01

    The authors recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a zinc cluster akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is ∼3.5 angstrom. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is ∼13 angstrom, and in this instance, a zinc twist is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native zinc fingers, structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent

  15. Fibrillar dimer formation of islet amyloid polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Chi-cheng [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); de Pablo, Juan J. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-05-08

    Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  16. An introduction to the dimer model

    International Nuclear Information System (INIS)

    Kenyon, R.

    2004-01-01

    A perfect matching of a graph is a subset of edges which covers every vertex exactly once, that is, for every vertex there is exactly one edge in the set with that vertex as endpoint. The dimer model is the study of the set of perfect matchings of a (possibly infinite) graph. The most well-known example is when the graph is Z 2 , for which perfect matchings are equivalent (via a simple duality) to domino tilings, that is, tilings of the plane with 2 x 1 and 1 x 2 rectangles. In the first three sections we study domino tilings of the plane and of finite polygonal regions, or equivalently, perfect matchings on Z 2 and subgraphs of Z 2 . In the last two sections we study the FK-percolation model and the dimer model on a more general family of planar graphs

  17. Revisiting the Optical PT-Symmetric Dimer

    Directory of Open Access Journals (Sweden)

    José Delfino Huerta Morales

    2016-08-01

    Full Text Available Optics has proved a fertile ground for the experimental simulation of quantum mechanics. Most recently, optical realizations of PT -symmetric quantum mechanics have been shown, both theoretically and experimentally, opening the door to international efforts aiming at the design of practical optical devices exploiting this symmetry. Here, we focus on the optical PT -symmetric dimer, a two-waveguide coupler where the materials show symmetric effective gain and loss, and provide a review of the linear and nonlinear optical realizations from a symmetry-based point of view. We go beyond a simple review of the literature and show that the dimer is just the smallest of a class of planar N-waveguide couplers that are the optical realization of the Lorentz group in 2 + 1 dimensions. Furthermore, we provide a formulation to describe light propagation through waveguide couplers described by non-Hermitian mode coupling matrices based on a non-Hermitian generalization of the Ehrenfest theorem.

  18. Palmitoylated APP Forms Dimers, Cleaved by BACE1.

    Directory of Open Access Journals (Sweden)

    Raja Bhattacharyya

    Full Text Available A major rate-limiting step for Aβ generation and deposition in Alzheimer's disease brains is BACE1-mediated cleavage (β-cleavage of the amyloid precursor protein (APP. We previously reported that APP undergoes palmitoylation at two cysteine residues (Cys186 and Cys187 in the E1-ectodomain. 8-10% of total APP is palmitoylated in vitro and in vivo. Palmitoylated APP (palAPP shows greater preference for β-cleavage than total APP in detergent resistant lipid rafts. Protein palmitoylation is known to promote protein dimerization. Since dimerization of APP at its E1-ectodomain results in elevated BACE1-mediated cleavage of APP, we have now investigated whether palmitoylation of APP affects its dimerization and whether this leads to elevated β-cleavage of the protein. Here we report that over 90% of palAPP is dimerized while only ~20% of total APP forms dimers. PalAPP-dimers are predominantly cis-oriented while total APP dimerizes in both cis- and trans-orientation. PalAPP forms dimers 4.5-times more efficiently than total APP. Overexpression of the palmitoylating enzymes DHHC7 and DHHC21 that increase palAPP levels and Aβ release, also increased APP dimerization in cells. Conversely, inhibition of APP palmitoylation by pharmacological inhibitors reduced APP-dimerization in coimmunoprecipitation and FLIM/FRET assays. Finally, in vitro BACE1-activity assays demonstrate that palmitoylation-dependent dimerization of APP promotes β-cleavage of APP in lipid-rich detergent resistant cell membranes (DRMs, when compared to total APP. Most importantly, generation of sAPPβ-sAPPβ dimers is dependent on APP-palmitoylation while total sAPPβ generation is not. Since BACE1 shows preference for palAPP dimers over total APP, palAPP dimers may serve as novel targets for effective β-cleavage inhibitors of APP as opposed to BACE1 inhibitors.

  19. Zinc in diet

    Science.gov (United States)

    ... Effects Symptoms of zinc deficiency include: Frequent infections Hypogonadism in males Loss of hair Poor appetite Problems with the ... any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should ...

  20. ttm-1 encodes CDF transporters that excrete zinc from intestinal cells of C. elegans and act in a parallel negative feedback circuit that promotes homeostasis.

    Directory of Open Access Journals (Sweden)

    Hyun Cheol Roh

    2013-05-01

    Full Text Available Zinc is an essential metal involved in a wide range of biological processes, and aberrant zinc metabolism is implicated in human diseases. The gastrointestinal tract of animals is a critical site of zinc metabolism that is responsible for dietary zinc uptake and distribution to the body. However, the role of the gastrointestinal tract in zinc excretion remains unclear. Zinc transporters are key regulators of zinc metabolism that mediate the movement of zinc ions across membranes. Here, we identified a comprehensive list of 14 predicted Cation Diffusion Facilitator (CDF family zinc transporters in Caenorhabditis elegans and demonstrated that zinc is excreted from intestinal cells by one of these CDF proteins, TTM-1B. The ttm-1 locus encodes two transcripts, ttm-1a and ttm-1b, that use different transcription start sites. ttm-1b expression was induced by high levels of zinc specifically in intestinal cells, whereas ttm-1a was not induced by zinc. TTM-1B was localized to the apical plasma membrane of intestinal cells, and analyses of loss-of-function mutant animals indicated that TTM-1B promotes zinc excretion into the intestinal lumen. Zinc excretion mediated by TTM-1B contributes to zinc detoxification. These observations indicate that ttm-1 is a component of a negative feedback circuit, since high levels of cytoplasmic zinc increase ttm-1b transcript levels and TTM-1B protein functions to reduce the level of cytoplasmic zinc. We showed that TTM-1 isoforms function in tandem with CDF-2, which is also induced by high levels of cytoplasmic zinc and reduces cytoplasmic zinc levels by sequestering zinc in lysosome-related organelles. These findings define a parallel negative feedback circuit that promotes zinc homeostasis and advance the understanding of the physiological roles of the gastrointestinal tract in zinc metabolism in animals.

  1. Oxidation of NAD dimers by horseradish peroxidase.

    OpenAIRE

    Avigliano, L; Carelli, V; Casini, A; Finazzi-Agrò, A; Liberatore, F

    1985-01-01

    Horseradish peroxidase catalyses the oxidation of NAD dimers, (NAD)2, to NAD+ in accordance with a reaction that is pH-dependent and requires 1 mol of O2 per 2 mol of (NAD)2. Horseradish peroxidase also catalyses the peroxidation of (NAD)2 to NAD+. In contrast, bacterial NADH peroxidase does not catalyse the peroxidation or the oxidation of (NAD)2. A free-radical mechanism is proposed for both horseradish-peroxidase-catalysed oxidation and peroxidation of (NAD)2.

  2. On the dimerization of linear polymers

    International Nuclear Information System (INIS)

    Aragao Carvalho, C. de.

    1988-08-01

    We use the continuum limit of the Su-Schrieffer-Heeger model for linear polymers to construct its effective potential (Gibbs free energy) both at zero and finite temperature. We study both trans and cis-polymers. Our results show that, depending on a renormalization condition to be extracted from experiment, there are several possibilities for the minima of the dimerized ground state of cis-polymers. All calculations are done in the one-loop approximation. (author). 16 refs, 3 figs

  3. Entanglement in a Dimerized Antiferromagnetic Heisenberg Chain

    OpenAIRE

    Hao, Xiang; Zhu, Shiqun

    2008-01-01

    The entanglement properties in an antiferromagnetic dimerized Heisenberg spin-1/2 chain are investigated. The entanglement gap, which is the difference between the ground-state energy and the minimal energy that any separable state can attain, is calculated to detect the entanglement. It is found that the entanglement gap can be increased by varying the alternation parameter. Through thermal energy, the witness of the entanglement can determine a characteristic temperature below that an entan...

  4. Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

    International Nuclear Information System (INIS)

    Chen, W.; Barthelman, M.; Martinez, J.; Alberts, D.; Gensler, H.L.

    1997-01-01

    Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

  5. Comparative studies on the correlation between pyrimidine dimer formation and tyrosinase activity in Cloudman S91 melanoma cells after ultraviolet-irradiation

    International Nuclear Information System (INIS)

    Niggli, H.J.

    1990-01-01

    The authors compared the induction of pyrimidine dimer densities after UV-irradiation in mouse melanoma cells before and after treatment with cholera toxin. Treatment with cholera toxin stimulated tyrosinase activity up to 50-fold, leading to a marked, visually apparent increase in cellular melanin concentrations. Results indicate that de novo melanin pigmentation induced via the c-AMP pathway is not involved in protection against UV-induced thymine-containing pyrimidine dimers. In separate experiments, irradiation of toxin-treated and untreated mouse melanoma cells with UVC or UVB light produced a 20-30% lower dimer density compared to irradiated human skin fibroblasts. This finding suggests that melanin has some protection properties against UV-induced pyrimidine dimers, although the exact defense mechanism seems highly complex. (author)

  6. Repair of pyrimidine dimers in nuclear and mitochondrial DNA of yeast irradiated with low doses of ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics

    1975-01-01

    The repair of damage induced by ultraviolet light has been examined in both the nuclear and mitochondrial DNA of the yeast Saccharomyces cerevisiae. The sensitive assay used in this study is based on the capacity of the bacteriophage T4 u.v. endonuclease to produce single-strand breaks in DNA that contains pyrimidine dimers, thus permitting the use of low fluences (doses) of u.v. The results demonstrate that virtually all of the dimers induced in the nuclear DNA of a repair-proficient strain (RAD+) are removed following dark incubation for four hours in growth medium. In contrast, the dimers induced in mitochondrial DNA by the same u.v. fluence are retained under the same conditions. In the excision-deficient mutant, rad1-2, no evidence was obtained for removal of pyrimidine dimers from nuclear DNA. Photoreactivation of both RAD + and rad1-2 cultures resulted in decreases of dimers from both nuclear and mitochondrial DNA. It is concluded that an excision-repair mechanism operates on nuclear but not mitochondrial DNA in repair-proficient yeast, and that the rad1-2 mutant is defective in this process.

  7. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R

    2000-01-01

    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...

  8. Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

    Science.gov (United States)

    Wolf, G; Schmidt, W

    1983-01-01

    A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

  9. Interfacial Chemistry-Induced Modulation of Schottky Barrier Heights: In Situ Measurements of the Pt-Amorphous Indium Gallium Zinc Oxide Interface Using X-ray Photoelectron Spectroscopy.

    Science.gov (United States)

    Flynn, Brendan T; Oleksak, Richard P; Thevuthasan, Suntharampillai; Herman, Gregory S

    2018-01-31

    A method to understand the role of interfacial chemistry on the modulation of Schottky barrier heights for platinum and amorphous indium gallium zinc oxide (a-IGZO) interfaces is demonstrated through thermal processing and background ambient pressure control. In situ X-ray photoelectron spectroscopy was used to characterize the interfacial chemistries that modulate barrier heights in this system. The primary changes were a significant chemical reduction of indium, from In 3+ to In 0 , that occurs during deposition of Pt on to the a-IGZO surface in ultrahigh vacuum. Postannealing and controlling the background ambient O 2 pressure allows further tuning of the reduction of indium and the corresponding Schottky barrier heights from 0.17 to 0.77 eV. Understanding the detailed interfacial chemistries at Pt/a-IGZO interfaces may allow for improved electronic device performance, including Schottky diodes, memristors, and metal-semiconductor field-effect transistors.

  10. Peptides Interfering 3A Protein Dimerization Decrease FMDV Multiplication.

    Directory of Open Access Journals (Sweden)

    Mónica González-Magaldi

    Full Text Available Nonstructural protein 3A is involved in relevant functions in foot-and-mouth disease virus (FMDV replication. FMDV 3A can form homodimers and preservation of the two hydrophobic α-helices (α1 and α2 that stabilize the dimer interface is essential for virus replication. In this work, small peptides mimicking residues involved in the dimer interface were used to interfere with dimerization and thus gain insight on its biological function. The dimer interface peptides α1, α2 and that spanning the two hydrophobic α-helices, α12, impaired in vitro dimer formation of a peptide containing the two α-helices, this effect being higher with peptide α12. To assess the effect of dimer inhibition in cultured cells, the interfering peptides were N-terminally fused to a heptaarginine (R7 sequence to favor their intracellular translocation. Thus, when fused to R7, interference peptides (100 μM were able to inhibit dimerization of transiently expressed 3A, the higher inhibitions being found with peptides α1 and α12. The 3A dimerization impairment exerted by the peptides correlated with significant, specific reductions in the viral yield recovered from peptide-treated FMDV infected cells. In this case, α2 was the only peptide producing significant reductions at concentrations lower than 100 μM. Thus, dimer interface peptides constitute a tool to understand the structure-function relationship of this viral protein and point to 3A dimerization as a potential antiviral target.

  11. The bioavailability of four zinc oxide sources and zinc sulphate in broiler chickens

    OpenAIRE

    Veldkamp, T.; Diepen, van, J.T.M.; Bikker, P.

    2014-01-01

    Zinc is an essential trace element for all farm animal species. It is commonly included in animal diets as zinc oxide, zinc sulphate or organically bound zinc. Umicore Zinc Chemicals developed zinc oxide products with different mean particle sizes. Umicore Zinc Chemicals requested Wageningen UR Livestock Research to determine the bioavailability of four zinc oxide sources and zinc sulphate in broiler chickens. A precise estimate of the bioavailability of zinc sources is required both for fulf...

  12. Erythrocyte metallothionein as an index of zinc status in humans

    International Nuclear Information System (INIS)

    Grider, A.; Bailey, L.B.; Cousins, R.J.

    1990-01-01

    Metallothionein concentrations in erythrocyte lysates derived from human subjects were measured by an ELISA procedure. IgG obtained from serum of sheep injected with human metallothionein 1 was used in this competitive assay. Subjects were fed a semipurified zinc-deficient diet for an 8-day depletion period after 3 days of acclimation. Fasting plasma zinc concentrations were reduced ∼7%. Metallothionein in the erythrocyte lysates was significantly decreased to 59% of the initial level by the end of the depletion period. Supplementation of these depleted subjects with zinc did not increase erythrocyte metallothionein levels within 24 hr. Daily supplementation of control subjects with zinc increased erythrocyte metallothionein to a 7-fold maximum within 7 days. These levels were reduced by 61% within 14 days after zinc supplementation was terminated. Incubation of rat [ 35 S]metallothionein with human erythrocyte lysate showed a time-dependent increase in 35 S soluble in 20% trichloroacetic acid, indicating degradation of the labeled protein, presumably via protease activity in the lysate. It is proposed that zinc supplementation induces erythrocyte metallothionein during erythropoiesis and that low zinc intake decreases synthesis and/or accelerates degradation of the protein in reticulocytes/erythrocytes. Metallothionein levels in erythrocytes may provide a useful index upon which to assess zinc status in humans

  13. Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents

    Science.gov (United States)

    Goldberg, Burt; Bona, Constantin

    2011-01-01

    Abstract The interactions of the T cell receptor (TCR) with cognate MHC-peptide and co-stimulatory molecules expressed at surface of antigen presenting cells (APC) leads to activation or tolerance of T cells. The development of molecular biological tools allowed for the preparation of soluble MHC-peptide molecules as surrogate for the APC. A decade ago a monomeric class II MHC molecule in which the peptide was covalently linked to β-chain of class II molecule was generated. This type of molecule had a low-binding affinity and did not cause the multimerization of TCR. The requirement of multimerization of TCR led to development of a new class of reagents, chimeric peptides covalently linked to MHC that was dimerized via Fc fragment of an immunoglobulin and linked to 3′ end of the β-chain of MHC class II molecule. These soluble dimerized MHC-peptide chimeric molecules display high affinity for the TCR and caused multimerization of TCR without processing by an APC. Because dimeric molecules are devoid of co-stimulatory molecules interacting with CD28, a second signal, they induce anergy rather the activation of T cells. In this review, we compare the human and murine dimerized MHC class II-peptides and their effect on CD4+ T cells, particularly the generation of T regulatory cells, which make these chimeric molecules an appealing approach for the treatment of autoimmune diseases. PMID:21435177

  14. Dimeric Structure of the Blue Light Sensor Protein Photozipper in the Active State.

    Science.gov (United States)

    Ozeki, Kohei; Tsukuno, Hiroyuki; Nagashima, Hiroki; Hisatomi, Osamu; Mino, Hiroyuki

    2018-02-06

    The light oxygen voltage-sensing (LOV) domain plays a crucial role in blue light (BL) sensing in plants and microorganisms. LOV domains are usually associated with the effector domains and regulate the activities of effector domains in a BL-dependent manner. Photozipper (PZ) is monomeric in the dark state. BL induces reversible dimerization of PZ and subsequently increases its affinity for the target DNA sequence. In this study, we report the analyses of PZ by pulsed electron-electron double resonance (PELDOR). The neutral flavin radical was formed by BL illumination in the presence of dithiothreitol in the LOV-C254S (without the bZIP domain) and PZ-C254S mutants, where the cysteine residue responsible for adduct formation was replaced with serine. The magnetic dipole interactions of 3 MHz between the neutral radicals were detected in both LOV-C254S and PZ-C254S, indicating that these mutants are dimeric in the radical state. The PELDOR simulation showed that the distance between the radical pair is close to that estimated from the dimeric crystal structure in the "light state" [Heintz, U., and Schlichting, I. (2016) eLife 5, e11860], suggesting that in the radical state, LOV domains in PZ-C254S form a dimer similar to that of LOV-C254S, which lacks the bZIP domain.

  15. Zinc-induced modification of the dynamical magnetic susceptibility in the superconducting state of YBa{sub 2}Cu{sub 3}O{sub 6+}{sub {ital x}} as revealed by inelastic neutron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Sidis, Y.; Bourges, P.; Hennion, B. [Laboratoire Leon Brillouin, CEA-CNRS, Centre dEtudes de Saclay, 91191 Gif-sur-Yvette (France); Regnault, L.P. [Centre dEtudes Nucleaires de Grenoble, Departement de Recherche Fondamentale sur la Matiere Condensee, Service de Physique Statistique, Magnetisme et Supraconductivite, Groupe Magnetisme et Diffraction Neutronique, 85 X, 38041 Grenoble cedex (France); Villeneuve, R.; Collin, G. [Laboratoire Leon Brillouin, CEA-CNRS, Centre dEtudes de Saclay, 91191 Gif-sur-Yvette (France); Marucco, J.F. [Laboratoire des Composes Non-Stoechiometriques, CNRS URA 446, Batiment 415, Universite Paris Sud centre dOrsay, Orsay (France)

    1996-03-01

    Inelastic-neutron-scattering measurements have been performed to determine the imaginary part of the dynamical susceptibility, {chi}{double_prime}({ital Q},{omega}), of a YBa{sub 2}(Cu{sub 1{minus}{ital y}}Zn{sub {ital y}}){sub 3}O{sub 6.97} sample exhibiting a superconducting transition at {ital T}{sub {ital c}}=69 K. Zinc substitution induces striking modifications of the energy dependence of {chi}{double_prime}({ital Q},{omega}) but magnetic fluctuations remain peaked at the antiferromagnetic wave vector, {ital Q}{sub AF}, at all investigated energies. In the superconducting state of the zinc-free compound, {chi}{double_prime}({ital Q},{omega}) is restricted to a narrow energy range, {h_bar}{omega}=33{endash}47 meV, displaying a {ital spin} {ital gap} at {ital E}{sub {ital G}}=33 meV and a resonant enhancement at {ital E}{sub {tau}}=39 meV, both features vanishing upon heating up above {ital T}{sub {ital c}}. In the {ital y}=0.02 substituted sample in the superconducting state, there is still an energy band in the range 32{endash}47 meV but no clear resonance, and a signal is now observed in the low energy range, though the line shape of {chi}{double_prime}({ital Q},{omega}) indicates some reminiscence of the spin gap of the pure compound. {copyright} {ital 1996 The American Physical Society.}

  16. Influence of extracellular zinc on M1 microglial activation.

    Science.gov (United States)

    Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

    2017-02-27

    Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

  17. Protective effects of zinc acetate toward the toxicity of nickelous acetate in rats

    International Nuclear Information System (INIS)

    Waalkes, M.P.; Kasprzak, K.S.; Ohshima, M.; Poirier, L.A.

    1985-01-01

    This study was designed to determine the effects of zinc pretreatment on the acute toxicity of nickel. Male Fischer rats received either nickel alone (i.p.), zinc alone (s.c.), zinc plus nickel, or saline (i.p. and s.c.; controls). Zinc pretreatment significantly increased the 14-day survival of nickel-related rats. Zinc did not, however, prevent the reduction in weight gain over 2 weeks seen with nickel treatment. Histopathologically, at 120 h following nickel exposure, kidneys in the group receiving nickel alone generally showed moderate nephropathy (multifocal proximal tubule degeneration with necrosis) while in the zinc plus nickel group the nephropathy was generally mild. Zinc pretreatment had no apparent effect on the pharmacokinetics of nickel over 24 h as assessed by urinary excretion, blood levels or organ distribution. Zinc pretreatment also did not alter the subcellular distribution of renal nickel 6 h after nickel exposure. Enhanced synthesis of metallothionein did not appear to play a critical role in the reduction of nickel toxicity, since renal concentrations of this metalbuilding protein, although elevated compared to control, were not different in rats receiving zinc and nickel or zinc alone. Zinc pretreatment did, however, have marked effect on nickel-induced hyperglycemia, reducing both the duration and severity of elevated blood glucose levels. Results of the study show that zinc can prevent some of the toxic effects of nickel and that the mechanism of this action does not appear to involve either metalothionein or alterations in the pharmacokinetics of nickel. (author)

  18. Relationship between maternal serum zinc, cord blood zinc and ...

    African Journals Online (AJOL)

    Background: Adequate in utero supply of zinc is essential for optimal fetal growth because of the role of zinc in cellular division, growth and differentiation. Low maternal serum zinc has been reported to be associated with low birth weight and the later is associated with increased morbidity and mortality in newborns.

  19. The study and microstructure analysis of zinc and zinc oxide

    Czech Academy of Sciences Publication Activity Database

    Luptáková, Natália; Pešlová, F.; Kliber, J.

    2015-01-01

    Roč. 54, č. 1 (2015), s. 43-46 ISSN 0543-5846 Grant - others:KEGA(SK) KEGA 007 TnUAD-4/2013 Institutional support: RVO:68081723 Keywords : zinc * production of zinc oxide * microstructure * chemical composition * zinc slag Subject RIV: JG - Metal lurgy Impact factor: 0.959, year: 2014

  20. Dimerization in the Grb7 Protein

    OpenAIRE

    Peterson, Tabitha A.; Benallie, Renee L.; Bradford, Andrew M.; Pias, Sally C.; Yazzie, Jaron.; Lor, Siamee N.; Haulsee, Zachary M.; Park, Chad K.; Johnson, Dennis L.; Rohrschneider, Larry R.; Spuches, Anne.; Lyons, Barbara A.

    2012-01-01

    In previous studies, we showed that the tyrosine phosphorylation state of growth factor receptor–bound protein 7 (Grb7) affects its ability to bind to the transcription regulator FHL2 and the cortactin-interacting protein, human HS-1-associated protein-1. Here, we present results describing the importance of dimerization in the Grb7–Src homology 2 (SH2) domain in terms of its structural integrity and the ability to bind phosphorylated tyrosine peptide ligands. A tyrosine phosphorylation-mimic...

  1. Dimeric assembly of enterocyte brush border enzymes

    DEFF Research Database (Denmark)

    Danielsen, E M

    1994-01-01

    The noncovalent, dimeric assembly of small intestinal brush border enzymes was studied by sedimentation analysis in density gradients of extracts of pulse-labeled pig jejunal mucosal explants. Like aminopeptidase N (EC 3.4.11.2), sucrase-isomaltase (EC 3.2.1.48-10), aminopeptidase A (EC 3...... appearance of the liposome-reconstituted enzyme [Norén et al. (1986) J. Biol. Chem. 261, 12306-12309], showing only the inner, membrane-anchored domains of the monomers to be in close contact with one another while the outer domains are far apart. In contrast to the other brush border enzymes studied...

  2. Dimer pair correlations on the brick lattice

    International Nuclear Information System (INIS)

    Yokoi, C.S.O.; Nagle, J.F.; Sulinas, S.R.

    1986-01-01

    Using exact methods, pair-correlation functions are studied in the dimer model defined on a brick lattice. At long distances these functions exhibit strongly anisotropic algebraic decay and, near criticality, the length scales diverge differently in the two principal directions. The critical exponents are v /sub x/ =1/2 and v /sub y/ =1. These results are in agreement with deductions drawn from recent exact finite-size scaling calculations. We also interpret our results in the light of domain wall theories of commensurate-incommensurate transitions, and in particular we study the relation of the present model to the discrete version of the Pokrovsky-Talapov model introduced by Villain

  3. Water-Based Assembly and Purification of Plasmon-Coupled Gold Nanoparticle Dimers and Trimers

    Directory of Open Access Journals (Sweden)

    Sébastien Bidault

    2012-01-01

    Full Text Available We describe a simple one-pot water-based scheme to produce gold nanoparticle groupings with short interparticle spacings. This approach combines a cross-linking molecule and a hydrophilic passivation layer to control the level of induced aggregation. Suspensions of dimers and trimers are readily obtained using a single electrophoretic purification step. The final interparticle spacings allow efficient coupling of the particle plasmon modes as verified in extinction spectroscopy.

  4. Formation of covalent di-tyrosine dimers in recombinant α-synuclein

    DEFF Research Database (Denmark)

    van Maarschalkerweerd, A; Pedersen, MN; Peterson, H

    2015-01-01

    in standard recombinant protein preparations, induced without extrinsic oxidative or nitrative agents. The dimers exhibit no secondary structure but advanced SAXS studies reveal an increased structural definition, resulting in a more hydrophobic micro-environment than the highly disordered monomer......Parkinson's disease is associated with fibril deposition in the diseased brain. Misfolding events of the intrinsically disordered synaptic protein α-synuclein are suggested to lead to the formation of transient oligomeric and cytotoxic species. The etiology of Parkinson's disease is further...

  5. Tunneling anisotropic magnetoresistance via molecular π orbitals of Pb dimers

    Science.gov (United States)

    Schöneberg, Johannes; Ferriani, Paolo; Heinze, Stefan; Weismann, Alexander; Berndt, Richard

    2018-01-01

    Pb dimers on a ferromagnetic surface are shown to exhibit large tunneling anisotropic magnetoresistance (TAMR) due to molecular π orbitals. Dimers oriented differently with respect to the magnetization directions of a ferromagnetic Fe double layer on W(110) were made with a scanning tunneling microscope. Depending on the dimer orientations, TAMR is absent or as large as 20% at the Fermi level. General arguments and first-principles calculations show that mixing of molecular orbitals due to spin-orbit coupling, which leads to TAMR, is maximal when the magnetization is oriented parallel to the dimer axis.

  6. Zinc biofortification of cereals

    DEFF Research Database (Denmark)

    Palmgren, Michael; Clemens, Stephan; Williams, Lorraine E.

    2008-01-01

    The goal of biofortification is to develop plants that have an increased content of bioavailable nutrients in their edible parts. Cereals serve as the main staple food for a large proportion of the world population but have the shortcoming, from a nutrition perspective, of being low in zinc...... and other essential nutrients. Major bottlenecks in plant biofortification appear to be the root-shoot barrier and - in cereals - the process of grain filling. New findings demonstrate that the root-shoot distribution of zinc is controlled mainly by heavy metal transporting P1B-ATPases and the metal...... tolerance protein (MTP) family. A greater understanding of zinc transport is important to improve crop quality and also to help alleviate accumulation of any toxic metals....

  7. Interplay of histidine residues of the Alzheimer’s disease Aβ peptide governs its Zn-induced oligomerization

    Science.gov (United States)

    Istrate, Andrey N.; Kozin, Sergey A.; Zhokhov, Sergey S.; Mantsyzov, Alexey B.; Kechko, Olga I.; Pastore, Annalisa; Makarov, Alexander A.; Polshakov, Vladimir I.

    2016-02-01

    Conformational changes of Aβ peptide result in its transformation from native monomeric state to the toxic soluble dimers, oligomers and insoluble aggregates that are hallmarks of Alzheimer’s disease (AD). Interactions of zinc ions with Aβ are mediated by the N-terminal Aβ1-16 domain and appear to play a key role in AD progression. There is a range of results indicating that these interactions trigger the Aβ plaque formation. We have determined structure and functional characteristics of the metal binding domains derived from several Aβ variants and found that their zinc-induced oligomerization is governed by conformational changes in the minimal zinc binding site 6HDSGYEVHH14. The residue H6 and segment 11EVHH14, which are part of this site are crucial for formation of the two zinc-mediated interaction interfaces in Aβ. These structural determinants can be considered as promising targets for rational design of the AD-modifying drugs aimed at blocking pathological Aβ aggregation.

  8. Cationic polyelectrolyte induced separation of some inorganic contaminants and their mixture (zirconium silicate, kaolin, K-feldspar, zinc oxide) as well as of the paraffin oil from water.

    Science.gov (United States)

    Ghimici, Luminita

    2016-03-15

    The flocculation efficiency of a cationic polyelectrolyte with quaternary ammonium salt groups in the backbone, namely PCA5 was evaluated on zirconium silicate (kreutzonit), kaolin, K- feldspar and zinc oxide (ZnO) suspensions prepared either with each pollutant or with their mixture. The effect of several parameters such as settling time, polymer dose and the pollutant type on the separation efficacy was evaluated and followed by optical density and zeta potential measurements. Except for ZnO, the interactions between PCA5 and suspended particles led to low residual turbidity values (around 4% for kreutzonit, 5% for kaolin and 8% for K-feldspar) as well as to the reduction of flocs settling time (from 1200 min to 30 min and 120 min in case of kaolinit and K-feldspar, respectively), that meant a high efficiency in their separation. The negative value of the zeta potential and flocs size measurements, at the optimum polymer dose, point to contribution from charge patch mechanism for the particles flocculation. A good efficiency of PCA5 in separation of paraffin oil (a minimum residual turbidity of 9.8%) has been also found. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Sprayed zinc oxide films: Ultra-violet light-induced reversible surface wettability and platinum-sensitization-assisted improved liquefied petroleum gas response.

    Science.gov (United States)

    Nakate, Umesh T; Patil, Pramila; Bulakhe, R N; Lokhande, C D; Kale, Sangeeta N; Naushad, Mu; Mane, Rajaram S

    2016-10-15

    We report the rapid (superhydrophobic to superhydrophilic) transition property and improvement in the liquefied petroleum gas (LPG) sensing response of zinc oxide (ZnO) nanorods (NRs) on UV-irradiation and platinum (Pt) surface sensitization, respectively. The morphological evolution of ZnO NRs is evidenced from the field emission scanning electron microscope and atomic force microscope digital images and for the structural elucidation X-ray diffraction pattern is used. Elemental survey mapping is obtained from energy dispersive X-ray analysis spectrum. The optical properties have been studied by UV-Visible and photoluminescence spectroscopy measurements. The rapid (120sec) conversion of superhydrophobic (154°) ZnO NRs film to superhydrophilic (7°) is obtained under UV light illumination and the superhydrophobicity is regained by storing sample in dark. The mechanism for switching wettability behavior of ZnO NRs has thoroughly been discussed. In second phase, Pt-sensitized ZnO NRs film has demonstrated considerable gas sensitivity at 260ppm concentration of LPG. At 623K operating temperature, the maximum LPG response of 58% and the response time of 49sec for 1040ppm LPG concentration of Pt- sensitized ZnO NRs film are obtained. This higher LPG response of Pt-sensitized ZnO NRs film over pristine is primarily due to electronic effect and catalytic effect (spill-over effect) caused by an additional of Pt on ZnO NRs film surface. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Identification of ‘safe harbor’ loci in indica rice genome by harnessing the property of zinc-finger nucleases to induce DNA damage and repair.

    Directory of Open Access Journals (Sweden)

    Christian eCantos

    2014-06-01

    Full Text Available Zinc-finger nucleases (ZFNs have proved to be successful tools for targeted genome manipulation in several organisms. Their main property is the induction of double-strand breaks (DSBs at specific sites, which are further repaired through homologous recombination (HR or non-homologous end joining (NHEJ. However, for the appropriate integration of genes at specific chromosomal locations, proper sites for gene integration need to be identified. These regions, hereby named safe harbor loci, must be localized in non-coding regions and possess high gene expression. In the present study, three different ZFN constructs (pZFN1, pZFN2, pZFN3, harboring β-glucuronidase (GUS as a reporter gene, were used to identify safe harbor loci regions on rice chromosomes. The constructs were delivered into IR64 rice by using an improved Agrobacterium-mediated transformation protocol, based on the use of immature embryos. Gene expression was measured by histochemical GUS activity and the flanking regions were determined through thermal-asymmetric interlaced polymerase chain reaction (TAIL PCR. Following sequencing, 28 regions were identified as putative sites for safe integration, but only one was localized in a non-coding region and it also possessed high GUS expression. These findings have significant applicability to create crops with new and valuable traits, since the site can be subsequently used to stably introduce one or more genes in a targeted manner.

  11. Method development for the determination of calcium, copper, magnesium, manganese, iron, potassium, phosphorus and zinc in different types of breads by microwave induced plasma-atomic emission spectrometry.

    Science.gov (United States)

    Ozbek, Nil; Akman, Suleyman

    2016-06-01

    A novel method was developed for the determination of calcium, magnesium, potassium, iron, copper, zinc, and manganese and phosphorous in various kinds of breads samples sold in Turkey by microwave plasma-atomic emission spectrometry (MIP-AES). Breads were dried at 100 °C for one day, ground thoroughly and then digested using nitric acid/hydrogen per oxide (3:1). The analytes in certified reference wheat flour and maize flour samples were determined in the uncertainty limits of the certified values as well as the analytes added to the mixture of ground bread and acid mixture prior to digestion were recovered quantitatively (>90%). Therefore, all determinations were made by linear calibration technique using aqueous standards. The LOD values for Ca, Cu, Fe, K, Mg, Mn, P and Zn were 13.1, 0.28, 4.47, 118, 1.10, 0.41, 7550 and 3.00 ng mL(-1), respectively. No spectral interference was detected at the working wavelengths of the analytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Quantitative determination of cyclobutane thymine dimers in DNA by stable isotope-dilution mass spectrometry

    International Nuclear Information System (INIS)

    Podmore, I.D.; Cooke, M.S.; Herbert, K.E.; Lunec, J.

    1996-01-01

    In order to understand the role of UV-induced DNA lesions in biological processes such as mutagenesis and carcinogenesis, it is essential to detect and quantify DNA damage in cells. In this paper we present a novel and both highly selective and sensitive assay using capillary gas chromatography (GC) combined with mass spectrometry (MS) for the detection and accurate quantitation of a major product of UV-induced DNA damage (cis-syb cyclobutadithymine). Quantitation of the cyclobutane thymine dimer was achieved by the use of an internal standard in the form of a stable 2 H-labeled analogue. Both isotopically labeled and nonlabeled dimers were prepared directly from their corresponding monomers. Each was identified as their trimethylsilyl ether derivative by GC-MS. Calibration plots were obtained for known quantities of both nonlabeled and analyte and internal standard. Quantitation of cis-syn cyclobutadithymine was demonstrated in DNA exposed to UVC radiation over a dose range of 0 3500 J m -2 . Under the conditions used, the limit of detection was found to be 20-50 fmol on column (equivalent to 0.002-0.005 nmol dimer per mg DNA). The results of the present study indicate that capillary GC-MS is an ideally suited technique for selective and sensitive quantification of cis-syn cyclobutadithymine in DNA and hence UV-induced DNA damage. (author)

  13. Photovoltaic cells employing zinc phosphide

    Science.gov (United States)

    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.

  14. Environmental risk limits for zinc

    NARCIS (Netherlands)

    Bodar CWM; SEC

    2007-01-01

    Environmental Riks Limits (ERLs) were derived for zinc. ERLs serve as advisory values to set environmental quality standards in the Netherlands. The ERLs for zinc closely follow the outcomes of earlier discussions on zinc within the Water Framework Directive and EC Regulation 793/93. The ERLs

  15. Environmental risk limits for zinc

    NARCIS (Netherlands)

    Bodar CWM; SEC

    2007-01-01

    Environmental Riks Limits (ERLs) were derived for zinc. ERLs serve as advisory values to set environmental quality standards in the Netherlands. The ERLs for zinc closely follow the outcomes of earlier discussions on zinc within the Water Framework Directive and EC Regulation 793/93. The ERLs refer

  16. The bioavailability of four zinc oxide sources and zinc sulphate in broiler chickens

    NARCIS (Netherlands)

    Veldkamp, T.; Diepen, van J.T.M.; Bikker, P.

    2014-01-01

    Zinc is an essential trace element for all farm animal species. It is commonly included in animal diets as zinc oxide, zinc sulphate or organically bound zinc. Umicore Zinc Chemicals developed zinc oxide products with different mean particle sizes. Umicore Zinc Chemicals requested Wageningen UR

  17. Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

    KAUST Repository

    Liang, Yu; Huimei Hong, Felicia; Ganesan, Pugalenthi; Jiang, Sizun; Jauch, Ralf; Stanton, Lawrence W.; Kolatkar, Prasanna R.

    2012-01-01

    Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

  18. Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

    KAUST Repository

    Liang, Yu

    2012-06-26

    Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

  19. Fibrillar dimer formation of islet amyloid polypeptides

    Directory of Open Access Journals (Sweden)

    Chi-cheng Chiu

    2015-09-01

    Full Text Available Amyloid deposits of human islet amyloid polypeptide (hIAPP, a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  20. Dimerization of translationally controlled tumor protein is essential for its cytokine-like activity.

    Directory of Open Access Journals (Sweden)

    Miyoung Kim

    Full Text Available BACKGROUND: Translationally Controlled Tumor Protein (TCTP found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF. Human recombinant HRF (HrHRF has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn. METHODS AND FINDINGS: We found that only NH(2-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP. Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS: Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development.

  1. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    International Nuclear Information System (INIS)

    Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

    2014-01-01

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools

  2. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  3. Changes in lead and zinc lability during weathering-induced acidification of desert mine tailings: Coupling chemical and micro-scale analyses

    International Nuclear Information System (INIS)

    Hayes, Sarah M.; White, Scott A.; Thompson, Thomas L.; Maier, Raina M.; Chorover, Jon

    2009-01-01

    Desert mine tailings may accumulate toxic metals in the near surface centimeters because of low water through-flux rates. Along with other constraints, metal toxicity precludes natural plant colonization even over decadal time scales. Since unconsolidated particles can be subjected to transport by wind and water erosion, potentially resulting in direct human and ecosystem exposure, there is a need to know how the lability and form of metals change in the tailings weathering environment. A combination of chemical extractions, X-ray diffraction, micro-X-ray fluorescence spectroscopy, and micro-Raman spectroscopy were employed to study Pb and Zn contamination in surficial arid mine tailings from the Arizona Klondyke State Superfund Site. Initial site characterization indicated a wide range in pH (2.5-8.0) in the surficial tailings pile. Ligand-promoted (DTPA) extractions, used to assess plant-available metal pools, showed decreasing available Zn and Mn with progressive tailings acidification. Aluminum shows the inverse trend, and Pb and Fe show more complex pH dependence. Since the tailings derive from a common source and parent mineralogy, it is presumed that variations in pH and 'bio-available' metal concentrations result from associated variation in particle-scale geochemistry. Four sub-samples, ranging in pH from 2.6 to 5.4, were subjected to further characterization to elucidate micro-scale controls on metal mobility. With acidification, total Pb (ranging from 5 to 13 g kg -1 ) was increasingly associated with Fe and S in plumbojarosite aggregates. For Zn, both total (0.4-6 g kg -1 ) and labile fractions decreased with decreasing pH. Zinc was found to be primarily associated with the secondary Mn phases manjiroite and chalcophanite. The results suggest that progressive tailings acidification diminishes the overall lability of the total Pb and Zn pools.

  4. Zinc in multiple sclerosis

    DEFF Research Database (Denmark)

    Bredholt, Mikkel; Fredriksen, Jette Lautrup

    2016-01-01

    In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS...

  5. The polar 2e/12c bond in phenalenyl-azaphenalenyl hetero-dimers: Stronger stacking interaction and fascinating interlayer charge transfer

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Rong-Lin; Li, Zhi-Ru, E-mail: hlxu@nenu.edu.cn, E-mail: lzr@jlu.edu.cn [Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China); Xu, Hong-Liang, E-mail: hlxu@nenu.edu.cn, E-mail: lzr@jlu.edu.cn [Institute of Functional Material Chemistry, Faculty of Chemistry, Northeast Normal University, Changchun, Jilin 130024 (China)

    2016-08-07

    An increasing number of chemists have focused on the two-electron/multicenter bond (2e/mc) that was first introduced to interpret the bonding mechanism of radical dimers. Herein, we report the polar two-electron/twelve center (2e/12c) bonding character in a series of phenalenyl-azaphenalenyl radical hetero-dimers. Interestingly, the bonding energy of weaker polar hetero-dimer (P-TAP) is dominated by the overlap of the two different singly occupied molecular orbital of radicals, while that of stronger polar hetero-dimer (P-HAP) is dominated by the electrostatic attraction. Results show that the difference between the electronegativity of the monomers plays a prominent role in the essential attribution of the polar 2e/12c bond. Correspondingly, a stronger stacking interaction in the hetero-dimer could be effectively achieved by increasing the difference of nitrogen atoms number between the monomers. It is worthy of note that an interesting interlayer charge transfer character is induced in the polar hetero-dimers, which is dependent on the difference between the electronegativity of the monomers. It is our expectation that the new knowledge about the bonding nature of radical hetero-dimers might provide important information for designing radical based functional materials with various applications.

  6. Protective effect of zinc against ischemic neuronal injury in a middle cerebral artery occlusion model.

    Science.gov (United States)

    Kitamura, Youji; Iida, Yasuhiko; Abe, Jun; Ueda, Masashi; Mifune, Masaki; Kasuya, Fumiyo; Ohta, Masayuki; Igarashi, Kazuo; Saito, Yutaka; Saji, Hideo

    2006-02-01

    In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 microM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 microM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury.

  7. Excitonic Behavior of Rhodamine Dimers: A Single-Molecule Study

    NARCIS (Netherlands)

    Hernando Campos, J.; van der Schaaf, Martijn; van Dijk, E.M.H.P.; Sauer, Markus; Garcia Parajo, M.F.; van Hulst, N.F.

    2003-01-01

    The optical behavior of a dimer of tetramethylrhodamine-5-isothiocyanate has been investigated by means of single-molecule measurements. Bulk absorption and fluorescence spectra show the existence of two populations of the dimer molecule that exhibit distinct excitonic interactions (strong and weak

  8. Two Populations Mean-Field Monomer-Dimer Model

    Science.gov (United States)

    Alberici, Diego; Mingione, Emanuele

    2018-04-01

    A two populations mean-field monomer-dimer model including both hard-core and attractive interactions between dimers is considered. The pressure density in the thermodynamic limit is proved to satisfy a variational principle. A detailed analysis is made in the limit of one population is much smaller than the other and a ferromagnetic mean-field phase transition is found.

  9. On the diffusion and self-trapping of surface dimers

    Science.gov (United States)

    Kappus, W.

    1982-03-01

    The theory of elastic interactions between surface atoms which are caused by substrate strains is applied to the interaction of dimers on the (211) surface of tungsten. From the comparison of theoretical and experimental interactions which were derived from the diffusion behaviour of dimers, conclusions are drawn on the nature of the adatom-substrate bond.

  10. Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

    KAUST Repository

    Han, Yu; Huang, Jianfeng; Zhu, Yihan

    2016-01-01

    and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near

  11. Exact Solution of a Generalized Nonlinear Schrodinger Equation Dimer

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Maniadis, P.; Tsironis, G.P.

    1998-01-01

    We present exact solutions for a nonlinear dimer system defined throught a discrete nonlinear Schrodinger equation that contains also an integrable Ablowitz-Ladik term. The solutions are obtained throught a transformation that maps the dimer into a double Sine-Gordon like ordinary nonlinear...... differential equation....

  12. Zinc bioavailability in the chick

    International Nuclear Information System (INIS)

    Hempe, J.M.

    1987-01-01

    Methods for assessing zinc bioavailability were evaluated in the chick. A low-zinc chick diet was developed using rehydrated, spray-dried egg white autoclaved at 121 C for 30 min as the primary protein source. The relative bioavailability of zinc from soy flour and beef was determined by whole-body retention of extrinsic 65 Zn, and in slope ratio assays for growth rate and tissue zinc. Compared to zinc carbonate added to an egg white-based diet, all methods gave similar estimates of approximately 100% zinc bioavailability for beef but estimates for soy flour varied widely. The slope ratio assay for growth rate gave the best estimate of zinc bioavailability for soy flour. True absorption, as measured by percent isotope retention from extrinsically labeled soy flour, was 47%

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

    Science.gov (United States)

    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

  14. Dimers at Ge/Si(001) surfaces: Ge coverage dependent quenching, reactivation of flip-flop motion, and interaction with dimer vacancy lines

    International Nuclear Information System (INIS)

    Hirayama, H.; Mizuno, H.; Yoshida, R.

    2002-01-01

    We studied Ge coverage (θ Ge ) dependent quenching, reactivation of the flip-flop motion, and interaction with dimer vacancy lines (DVLs) of dimers on Ge/Si(001) surfaces using a scanning tunneling microscope (STM) combined with a molecular beam epitaxy apparatus. Deposition of ∼0.3 ML (monolayer) Ge quenched the flip-flop motion, making all dimers asymmetric. Further deposition introduced DVLs at θ Ge ≥∼0.5 ML, and symmetric dimer domains appeared again locally at θ≥1.5 ML. High-resolution STM images indicated that asymmetric dimer rows always invert their phase in alternation with buckled dimer's up-end at the DVLs. Low-temperature STM images indicated that the symmetric dimer domains were due to flip-flopping of asymmetric dimers activated by large θ Ge at room temperature. The symmetric dimer domains extended along the dimer rows over the DVLs due to the phase correlation

  15. Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingers

    Directory of Open Access Journals (Sweden)

    Muriaux Delphine

    2007-08-01

    Full Text Available Abstract Background The HIV-1 nucleocapsid protein (NC is formed of two CCHC zinc fingers flanked by highly basic regions. HIV-1 NC plays key roles in virus structure and replication via its nucleic acid binding and chaperoning properties. In fact, NC controls proviral DNA synthesis by reverse transcriptase (RT, gRNA dimerization and packaging, and virion assembly. Results We previously reported a role for the first NC zinc finger in virion structure and replication 1. To investigate the role of both NC zinc fingers in intracellular Gag trafficking, and in virion assembly, we generated series of NC zinc fingers mutations. Results show that all Zinc finger mutations have a negative impact on virion biogenesis and maturation and rendered defective the mutant viruses. The NC zinc finger mutations caused an intracellular accumulation of Gag, which was found either diffuse in the cytoplasm or at the plasma membrane but not associated with endosomal membranes as for wild type Gag. Evidences are also provided showing that the intracellular interactions between NC-mutated Gag and the gRNA were impaired. Conclusion These results show that Gag oligomerization mediated by gRNA-NC interactions is required for correct Gag trafficking, and assembly in HIV-1 producing cells and the release of infectious viruses.

  16. Ultrafast deactivation processes in the 2-aminopyridine dimer and the adenine-thymine base pair: Similarities and differences

    International Nuclear Information System (INIS)

    Ai Yuejie; Zhang Feng; Cui Ganglong; Fang Weihai; Luo Yi

    2010-01-01

    2-aminopyridine dimer has frequently been used as a model system for studying photochemistry of DNA base pairs. We examine here the relevance of 2-aminopyridine dimer for a Watson-Crick adenine-thymine base pair by studying UV-light induced photodynamics along two main hydrogen bridges after the excitation to the localized 1 ππ* excited-state. The respective two-dimensional potential-energy surfaces have been determined by time-dependent density functional theory with Coulomb-attenuated hybrid exchange-correlation functional (CAM-B3LYP). Different mechanistic aspects of the deactivation pathway have been analyzed and compared in detail for both systems, while the related reaction rates have also be obtained from Monte Carlo kinetic simulations. The limitations of the 2-aminopyridine dimer as a model system for the adenine-thymine base pair are discussed.

  17. Atom-dimer scattering in a heteronuclear mixture with a finite intraspecies scattering length

    Science.gov (United States)

    Gao, Chao; Zhang, Peng

    2018-04-01

    We study the three-body problem of two ultracold identical bosonic atoms (denoted by B ) and one extra atom (denoted by X ), where the scattering length aB X between each bosonic atom and atom X is resonantly large and positive. We calculate the scattering length aad between one bosonic atom and the shallow dimer formed by the other bosonic atom and atom X , and investigate the effect induced by the interaction between the two bosonic atoms. We find that even if this interaction is weak (i.e., the corresponding scattering length aB B is of the same order of the van der Waals length rvdW or even smaller), it can still induce a significant effect for the atom-dimer scattering length aad. Explicitly, an atom-dimer scattering resonance can always occur when the value of aB B varies in the region with | aB B|≲ rvdW . As a result, both the sign and the absolute value of aad, as well as the behavior of the aad-aB X function, depends sensitively on the exact value of aB B. Our results show that, for a good quantitative theory, the intraspecies interaction is required to be taken into account for this heteronuclear system, even if this interaction is weak.

  18. Hair Zinc Level Analysis and Correlative Micronutrients in Children Presenting with Malnutrition and Poor Growth

    OpenAIRE

    Han, Tae Hwan; Lee, Jin; Kim, Yong Joo

    2016-01-01

    Purpose Zinc deficiency can induce serious clinical problems in the gastrointestinal (GI) system and immune system and can affect growth and development. It is more severe in younger patients. Chronic zinc deficiency is reflected more precisely in hair than in serum. We studied hair zinc levels and other hair and serum micronutrients in chronic malnourished children to identify which micronutrients are affected or correlated with the other ones. Methods Hair mineral analyses were performed in...

  19. Dualism of Sensitivity and Selectivity of Porphyrin Dimers in Electroanalysis.

    Science.gov (United States)

    Lisak, Grzegorz; Tamaki, Takashi; Ogawa, Takuji

    2017-04-04

    This work uncovers the application of porphyrin dimers for the use in electroanalysis, such as potentiometric determination of ions. It also puts in question a current perception of an occurrence of the super-Nernstian response, as a result of the possible dimerization of single porphyrins within an ion-selective membrane. To study that, four various porphyrin dimers were used as ionophores, namely, freebase-freebase, Zn-Zn, Zn-freebase, and freebase-Zn. Since the Zn-freebase and freebase-Zn porphyrin dimers carried both anion- and cation-sensitive porphyrin units, their application in ISEs was utilized in both anion- and cation-sensitive sensors. With respect to the lipophilic salt added, both porphyrins dimers were found anion- and cation-sensitive. This allowed using a single molecule as novel type of versatile ionophore (anion- and cation-selective), simply by varying the membrane composition. All anion-sensitive sensors were perchlorate-sensitive, while the cation-selective sensors were silver-sensitive. The selectivity of the sensors depended primarily on the porphyrin dimers in the ion-selective membrane. Furthermore, the selectivity of cation-sensitive dimer based sensors was found significantly superior to the ones measured for the single porphyrin unit based sensors (precursors of the porphyrin dimers). Thus, the dimerization of single porphyrins may actually be a factor to increase or modulate porphyrin selectivity. Moreover, in the case of cation-sensitive sensors, the selectivity vastly depended on the order of porphyrin units in the dimer. This opens a new approach of regulating and adjusting sensitivity and selectivity of the sensor through the application of complex porphyrin systems with more than one porphyrin units with mix sensitive porphyrins.

  20. Unusual dimeric tetrahydroxanthone derivatives from Aspergillus lentulus and the determination of their axial chiralities

    Science.gov (United States)

    Li, Tian-Xiao; Yang, Ming-Hua; Wang, Ying; Wang, Xiao-Bing; Luo, Jun; Luo, Jian-Guang; Kong, Ling-Yi

    2016-12-01

    The research on secondary metabolites of Aspergillus lentulus afforded eight unusual heterodimeric tetrahydroxanthone derivatives, lentulins A-H (2-9), along with the known compound neosartorin (1). Compounds 1-6 exhibited potent antimicrobial activities especially against methicillin-resistant Staphylococci. Their absolute configurations, particularly the axial chiralities, were unambiguously demonstrated by a combination of electronic circular dichroism (ECD), Rh2(OCOCF3)4-induced ECD experiments, modified Mosher methods, and chemical conversions. Interestingly, compounds 1-4 were the first samples of atropisomers within the dimeric tetrahydroxanthone class. Further investigation of the relationships between their axial chiralities and ECD Cotton effects led to the proposal of a specific CD Exciton Chirality rule to determine the axial chiralities in dimeric tetrahydroxanthones and their derivatives.

  1. Removal of pyrimidine dimers from Saccharomyces cerevisiae nuclear DNA under nongrowth conditions as detected by a sensitive, enzymatic assay

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, R J [Tennessee Univ., Oak Ridge (USA). Graduate School of Biomedical Sciences

    1978-04-01

    A sensitive and quantitative procedure for the detection of pyrimidine dimers in yeast nuclear DNA is described. The assay employs dimer-specific, endonuclease activities from Micrococcus luteus together with DNA sedimentation through calibrated, alkaline sucrose gradients to detect endonuclease-induced, single-strand breaks. Breaks were induced in a dose-dependent manner from 0 to 80 J m/sup -2/ at 254 nm and in numbers equivalent to the numbers of dimers induced by similar doses. Endonuclease-sensitive sites in the wild-type, haploid strain S288C, after irradiation with 5 J m/sup -2/ (254 nm), were removed in less than 5 min when cells were incuba ted in buffer (pH 7.0) at 28/sup 0/C. After irra diation with dos es from 30 to 100 J m/sup -2/ site removal in S288C required longer postirradiation incubations and was about 90% complete. In a radiation-sensitive strain carrying the mutant allele rad 4-3 the number of endonuclease-sensitive sites remained constant for 6 h after irradiation with 5 J m/sup -2/. The retention of sites in this strain indicates that it is defective in the excision of pyrimidine dimers. (Auth.

  2. In situ detection of estrogen receptor dimers in breast carcinoma cells in archival materials using proximity ligation assay (PLA).

    Science.gov (United States)

    Iwabuchi, Erina; Miki, Yasuhiro; Ono, Katsuhiko; Onodera, Yoshiaki; Suzuki, Takashi; Hirakawa, Hisashi; Ishida, Takanori; Ohuchi, Noriaki; Sasano, Hironobu

    2017-01-01

    Estrogen receptor (ER) is required for carcinoma cell proliferation in the great majority of breast cancer and also functions as a dimer. ER dimeric proteins have been largely identified by BRET/FRET analyses but their in situ visualization have not yet been reported. Recently, in situ Proximity Ligation Assay (PLA) has been developed as the methods detecting protein interactions in situ. Therefore, in this study we firstly demonstrated the dimerization of ERα in breast carcinoma cell lines and tissues using PLA. The human breast carcinoma cell lines MCF-7, T-47D and MDA-MB-231 were used in this study. Cells were treated with ER agonist or antagonist and fixed in 4% PFA, and ER dimers were subsequently detected using PLA. The evaluation of ER dimers in breast carcinoma cell lines were quantified by measuring the area of dots localized in the nuclei using image analysis. We also firstly demonstrated the visualization of ER dimer patterns in 10% formalin-fixed paraffin-embedded tissues of breast cancer using PLA technique. Estradiol (E2) administration induced ERα homodimers in the nuclei of MCF-7 and T-47D but not in ER-negative MDA-MB-231. 4-OH tamoxifen also induced ERα homodimers but the subcellular localization of these ERα homodimers was predominant in cytoplasm instead of the nuclei induced by E2 treatment. ICI182,780 treatment did decrease the number of formation of ERα homodimers in MCF-7. In breast cancer patients, ERα PLA score was significantly correlated positively with ERα- or PgR (progesterone receptor) immunohistochemical scores and inversely with Ki-67-labeling index, respectively. We also demonstrated the ERα/β heterodimer as well as ERα homodimers in both breast carcinoma cell lines and surgical pathology specimens. In summary, we did firstly succeed in the visualization of ER dimeric proteins using PLA method. The evaluation of ER dimer patterns could provide pivotal information as to the prediction of response to endocrine therapy of

  3. Dimerization of eosin on nanostructured gold surfaces: Size regime dependence of the small metallic particles

    Science.gov (United States)

    Ghosh, Sujit Kumar; Pal, Anjali; Nath, Sudip; Kundu, Subrata; Panigrahi, Sudipa; Pal, Tarasankar

    2005-08-01

    Gold nanoparticles of variable sizes have been exploited to study their influence on the absorption and emission spectral characteristics of eosin, a fluorescent dye. It has been found that smaller particles of gold stimulate J-aggregation of eosin on the surface of metal particles whereas larger particles cannot induce any kind of aggregation amongst the dye molecules. The size regime dependence of the gold nanoparticles has been attributed to the intercluster interactions induced by the dye molecules for smaller gold nanoparticles and consequently, close packing of the dye molecules around the gold surface engenders intermolecular interactions amongst the dye molecules leading to dimerization.

  4. Tunneling dynamics of double proton transfer in formic acid and benzoic acid dimers

    Science.gov (United States)

    Smedarchina, Zorka; Fernández-Ramos, Antonio; Siebrand, Willem

    2005-04-01

    Direct dynamics calculations based on instanton techniques are reported of tunneling splittings due to double proton transfer in formic and benzoic acid dimers. The results are used to assign the observed splittings to levels for which the authors of the high-resolution spectra could not provide a definitive assignment. In both cases the splitting is shown to be due mainly to the zero-point level rather than to the vibrationally or electronically excited level whose spectrum was investigated. This leads to zero-point splittings of 375MHz for (DCOOH)2 and 1107MHz for the benzoic acid dimer. Thus, contrary to earlier calculations, it is found that the splitting is considerably larger in the benzoic than in the formic acid dimer. The calculations are extended to solid benzoic acid where the asymmetry of the proton-transfer potential induced by the crystal can be overcome by suitable doping. This has allowed direct measurement of the interactions responsible for double proton transfer, which were found to be much larger than those in the isolated dimer. To account for this observation both static and dynamic effects of the crystal forces on the intradimer hydrogen bonds are included in the calculations. The same methodology, extended to higher temperatures, is used to calculate rate constants for HH, HD, and DD transfers in neat benzoic acid crystals. The results are in good agreement with reported experimental rate constants measured by NMR relaxometry and, if allowance is made for small structural changes induced by doping, with the transfer matrix elements observed in doped crystals. Hence the method used allows a unified description of tunneling splittings in the gas phase and in doped crystals as well as of transfer rates in neat crystals.

  5. Interaction Between Yeasts and Zinc

    Science.gov (United States)

    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

  6. Zinc coordination is required for and regulates transcription activation by Epstein-Barr nuclear antigen 1.

    Directory of Open Access Journals (Sweden)

    Siddhesh Aras

    2009-06-01

    Full Text Available Epstein-Barr Nuclear Antigen 1 (EBNA1 is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO(2. Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO(2 and redox potential.

  7. A moonlighting function of Mycobacterium smegmatis Ku in zinc homeostasis?

    Science.gov (United States)

    Kushwaha, Ambuj K; Deochand, Dinesh K; Grove, Anne

    2015-02-01

    Ku protein participates in DNA double-strand break repair via the nonhomologous end-joining pathway. The three-dimensional structure of eukaryotic Ku reveals a central core consisting of a β-barrel domain and pillar and bridge regions that combine to form a ring-like structure that encircles DNA. Homologs of Ku are encoded by a subset of bacterial species, and they are predicted to conserve this core domain. In addition, the bridge region of Ku from some bacteria is predicted from homology modeling and sequence analyses to contain a conventional HxxC and CxxC (where x is any residue) zinc-binding motif. These potential zinc-binding sites have either deteriorated or been entirely lost in Ku from other organisms. Using an in vitro metal binding assay, we show that Mycobacterium smegmatis Ku binds two zinc ions. Zinc binding modestly stabilizes the Ku protein (by ∼3°C) and prevents cysteine oxidation, but it has little effect on DNA binding. In vivo, zinc induces significant upregulation of the gene encoding Ku (∼sixfold) as well as a divergently oriented gene encoding a predicted zinc-dependent MarR family transcription factor. Notably, overexpression of Ku confers zinc tolerance on Escherichia coli. We speculate that zinc-binding sites in Ku proteins from M. smegmatis and other mycobacterial species have been evolutionarily retained to provide protection against zinc toxicity without compromising the function of Ku in DNA double-strand break repair. © 2014 The Protein Society.

  8. Autoregulatory Feedback Mechanism of P38MAPK/Caspase-8 in Photodynamic Therapy-Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy Phthalocyanine Zinc-Induced Apoptosis of Human Hepatocellular Carcinoma Bel-7402 Cells

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2014-01-01

    Full Text Available Photodynamic therapy (PDT is a novel and promising antitumor treatment. Our previous study showed that hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy phthalocyanine zinc- (TαPcZn- mediated PDT (TαPcZn-PDT inhibits the proliferation of human hepatocellular carcinoma Bel-7402 cells by triggering apoptosis and arresting cell cycle. However, mechanisms of TαPcZn-PDT-induced apoptosis of Bel-7402 cells have not been fully clarified. In the present study, therefore, effect of TαPcZn-PDT on apoptosis, P38MAPK, p-P38MAPK, Caspase-8, Caspase-3, Bcl-2, Bid, Cytochrome c, and mitochondria membrane potential in Bel-7402 cells without or with P38MAPK inhibitor SB203580 or Caspase-8 inhibitor Ac-IEFD-CHO was investigated by haematoxylin and eosin (HE staining assay, flow cytometry analysis of annexin V-FITC/propidium iodide (PI double staining cells and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1, and immunoblot assay. We found that TαPcZn-PDT resulted in apoptosis induction, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. In contrast, SB203580 or Ac-IEFD-CHO attenuated induction of apoptosis, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. Taken together, we conclude that Caspase-3, Bcl-2, Bid, and mitochondria are involved in autoregulatory feedback of P38MAPK/Caspase-8 during TαPcZn-PDT-induced apoptosis of Bel-7402 cells.

  9. Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly (ADP-ribose) polymerase-1

    OpenAIRE

    Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G.; Liu, Ke Jian

    2013-01-01

    Arsenic enhances genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic co-carcinogenesis, and DNA repair proteins such as poly (ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlyi...

  10. Does the oral zinc tolerance test measure zinc absorption

    Energy Technology Data Exchange (ETDEWEB)

    Valberg, L.S.; Flanagan, P.R.; Brennan, J.; Chamberlain, M.J.

    1985-01-01

    Increases in plasma zinc concentration were compared with radiozinc absorption after oral test doses. Ten healthy, fasting subjects were each given 385 mumol zinc chloride (25 mg Zn) labelled with 0.5 muCi /sup 65/ZnCl/sub 2/ and a non-absorbed marker, /sup 51/CrCl/sub 3/, dissolved in 100 ml of water; another 10 persons were given 354 mumol zinc chloride and 125 g of minced turkey containing 31 mumol zinc also labelled with /sup 65/Zn and /sup 51/Cr. Measurements were made of plasma zinc concentration at hourly intervals for 5 hours, radiozinc absorption by stool counting of unabsorbed radioactivity 12-36 hours later, and radiozinc retention by whole body counting at 7 days. The mean percentage of radiozinc absorbed and retained in the body from the two test meals was found to be identical (42%). In contrast the increased area under the plasma zinc curve up to 5 hours after the turkey meal, 28 +/- 9 mumol/L (mean +/- SD) was significantly less than that for zinc chloride alone, 47 +/- 15 mumol/L, p less than 0.005. Despite this difference, a good correlation was found between the area under the plasma zinc curve and /sup 65/Zn absorption in individual subjects after each meal. The discrepancy between the results of zinc absorption derived from the plasma zinc curve and /sup 65/Zn absorption for the liquid and solid test meals was most likely explained by binding of zinc to food and delayed gastric emptying of the solid meal. With a test meal of turkey meat at least this dampened the plasma appearance of zinc but did not affect its overall absorption.

  11. Does the oral zinc tolerance test measure zinc absorption

    International Nuclear Information System (INIS)

    Valberg, L.S.; Flanagan, P.R.; Brennan, J.; Chamberlain, M.J.

    1985-01-01

    Increases in plasma zinc concentration were compared with radiozinc absorption after oral test doses. Ten healthy, fasting subjects were each given 385 mumol zinc chloride (25 mg Zn) labelled with 0.5 muCi 65 ZnCl 2 and a non-absorbed marker, 51 CrCl 3 , dissolved in 100 ml of water; another 10 persons were given 354 mumol zinc chloride and 125 g of minced turkey containing 31 mumol zinc also labelled with 65 Zn and 51 Cr. Measurements were made of plasma zinc concentration at hourly intervals for 5 hours, radiozinc absorption by stool counting of unabsorbed radioactivity 12-36 hours later, and radiozinc retention by whole body counting at 7 days. The mean percentage of radiozinc absorbed and retained in the body from the two test meals was found to be identical (42%). In contrast the increased area under the plasma zinc curve up to 5 hours after the turkey meal, 28 +/- 9 mumol/L (mean +/- SD) was significantly less than that for zinc chloride alone, 47 +/- 15 mumol/L, p less than 0.005. Despite this difference, a good correlation was found between the area under the plasma zinc curve and 65 Zn absorption in individual subjects after each meal. The discrepancy between the results of zinc absorption derived from the plasma zinc curve and 65 Zn absorption for the liquid and solid test meals was most likely explained by binding of zinc to food and delayed gastric emptying of the solid meal. With a test meal of turkey meat at least this dampened the plasma appearance of zinc but did not affect its overall absorption

  12. Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

    KAUST Repository

    Han, Yu

    2016-03-31

    The fabrication of asymmetric monometallic nanocrystals with novel properties for plasmonics, nanophotonics and nanoelectronics. Asymmetric monometallic plasmonic nanocrystals are of both fundamental synthetic challenge and practical significance. In an example, a thiol-ligand mediated growth strategy that enables the synthesis of unprecedented Au Nanorod-Au Nanoparticle (AuNR-AuNP) dimers from pre-synthesized AuNR seeds. Using high-resolution electron microscopy and tomography, crystal structure and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near infrared regions (300 - 1300 nm). This unexpected property makes the AuNR-AuNP dimer example useful for many nanophotonic applications. In two experiments, the dimer example was tested as a surface- enhanced Raman scattering (SERS) substrate and a solar light harvester for photothermal conversion, in comparison with the mixture of AuNR and AuNP. In the SERS experiment, the dimer example showed an enhancement factor about 10 times higher than that of the mixture, when the excitation wavelength (660 nm) was off the two surface plasmon resonance (SPR) bands of the mixture. In the photothermal conversion experiment under simulated sunlight illumination, the dimer example exhibited an energy conversion efficiency about 1.4 times as high as that of the mixture.

  13. Role of cyclobutane dimers in UV-denaturation of DNA

    International Nuclear Information System (INIS)

    Zavil'gel'skij, G.B.; Zuev, A.V.

    1978-01-01

    UV irradiation of double-stranded DNA produces local denatured regions. The evidence presented indicates that these single-stranded regions arise from photoproducts other than pyrimidine dimers. The irradiation of T2 DNA at 8x10 4 erg/mm 2 (254 nm) produces 6-8% thymine dimers, amd Tsub(mel) drops by 12-14 deg C, accompanied by a significant broadening of the transition profile. The kinetics of denatured region formation and lowering Tsub(mel) corresponds to that of formation of crosslinkages and differs markedly from the kinetics of formation of cyclobutane pyrimidine dimers. Treatment of UV-irradiated DNA with light in the presence of yeast photoreactivating enzyme monomerizes almost all thymine dimers but does not change the Tsub(mel). Local denatured regions are detected in UV-irradiated DNA and are absent from AcPhM-sensibilized DNA, which contains 20-25% thymine dimers, as determined by the accridine orange fluorescence technique. S1 nuclease from Aspergillis oryzae produces single-strand breaks in UV-irradiated DNA of phage PM2 but is not active on AcPhM-treated PM2 DNA, which contains about 50 thymine dimers. It is supposed that the formation of a cyclobutane dimer only weakens the hydrogen bonds in the AT base pair rather than breaks them. Local denatured regions are thought to arise from the accumulation in UV-irradiated DNA (254 nm) of the sufficient number of photoproducts with impaired ability to base pairing

  14. Quantum dissipative dynamics and decoherence of dimers on helium droplets

    International Nuclear Information System (INIS)

    Schlesinger, Martin

    2011-01-01

    In this thesis, quantum dynamical simulations are performed in order to describe the vibrational motion of diatomic molecules in a highly quantum environment, so-called helium droplets. We aim to reproduce and explain experimental findings which were obtained from dimers on helium droplets. Nanometer-sized helium droplets contain several thousands of 4 He atoms. They serve as a host for embedded atoms or molecules and provide an ultracold ''refrigerator'' for them. Spectroscopy of molecules in or on these droplets reveals information on both the molecule and the helium environment. The droplets are known to be in the superfluid He II phase. Superfluidity in nanoscale systems is a steadily growing field of research. Spectra obtained from full quantum simulations for the unperturbed dimer show deviations from measurements with dimers on helium droplets. These deviations result from the influence of the helium environment on the dimer dynamics. In this work, a well-established quantum optical master equation is used in order to describe the dimer dynamics effectively. The master equation allows to describe damping fully quantum mechanically. By employing that equation in the quantum dynamical simulation, one can study the role of dissipation and decoherence in dimers on helium droplets. The effective description allows to explain experiments with Rb 2 dimers on helium droplets. Here, we identify vibrational damping and associated decoherence as the main explanation for the experimental results. The relation between decoherence and dissipation in Morse-like systems at zero temperature is studied in more detail. The dissipative model is also used to investigate experiments with K 2 dimers on helium droplets. However, by comparing numerical simulations with experimental data, one finds that further mechanisms are active. Here, a good agreement is obtained through accounting for rapid desorption of dimers. We find that decoherence occurs in the electronic manifold of the

  15. Inducing indel mutation in the SOX6 gene by zinc finger nuclease for gamma reactivation: An approach towards gene therapy of beta thalassemia.

    Science.gov (United States)

    Modares Sadeghi, Mehran; Shariati, Laleh; Hejazi, Zahra; Shahbazi, Mansoureh; Tabatabaiefar, Mohammad Amin; Khanahmad, Hossein

    2018-03-01

    β-thalassemia is a common autosomal recessive disorder characterized by a deficiency in the synthesis of β-chains. Evidences show that increased HbF levels improve the symptoms in patients with β-thalassemia or sickle cell anemia. In this study, ZFN technology was applied to induce a mutation in the binding domain region of SOX6 to reactivate γ-globin expression. The sequences coding for ZFP arrays were designed and sub cloned in TDH plus as a transfer vector. The ZFN expression was confirmed using Western blot analysis. In the next step, using the site-directed mutagenesis strategy through the overlap PCR, a missense mutation (D64V) was induced in the catalytic domain of the integrase gene in the packaging plasmid and verified using DNA sequencing. Then, the integrase minus lentivirus containing ZFN cassette was packaged. Transduction of K562 cells with this virus was performed. Mutation detection assay was performed. The indel percentage of the cells transducted with lenti virus containing ZFN was 31%. After 5 days of erythroid differentiation with 15 μg/mL cisplatin, the levels of γ-globin mRNA were sixfold in the cells treated with ZFN compared to untreated cells. In the meantime, the measurement of HbF expression levels was carried out using hemoglobin electrophoresis and showed the same results. Integrase minus lentivirus can provide a useful tool for efficient transient gene expression and helps avoid disadvantages of gene targeting using the native virus. The ZFN strategy applied here to induce indel on SOX6 gene in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with β-thalassemia. © 2017 Wiley Periodicals, Inc.

  16. Covalent α-synuclein dimers: chemico-physical and aggregation properties.

    Directory of Open Access Journals (Sweden)

    Micaela Pivato

    Full Text Available The aggregation of α-synuclein into amyloid fibrils constitutes a key step in the onset of Parkinson's disease. Amyloid fibrils of α-synuclein are the major component of Lewy bodies, histological hallmarks of the disease. Little is known about the mechanism of aggregation of α-synuclein. During this process, α-synuclein forms transient intermediates that are considered to be toxic species. The dimerization of α-synuclein could represent a rate-limiting step in the aggregation of the protein. Here, we analyzed four covalent dimers of α-synuclein, obtained by covalent link of the N-terms, C-terms, tandem cloning of two sequences and tandem juxtaposition in one protein of the 1-104 and 29-140 sequences. Their biophysical properties in solution were determined by CD, FT-IR and NMR spectroscopies. SDS-induced folding was also studied. The fibrils formation was analyzed by ThT and polarization fluorescence assays. Their morphology was investigated by TEM and AFM-based quantitative morphometric analysis. All dimers were found to be devoid of ordered secondary structure under physiological conditions and undergo α-helical transition upon interaction with SDS. All protein species are able to form amyloid-like fibrils. The reciprocal orientation of the α-synuclein monomers in the dimeric constructs affects the kinetics of the aggregation process and a scale of relative amyloidogenic propensity was determined. Structural investigations by FT IR spectroscopy, and proteolytic mapping of the fibril core did not evidence remarkable difference among the species, whereas morphological analyses showed that fibrils formed by dimers display a lower and diversified level of organization in comparison with α-synuclein fibrils. This study demonstrates that although α-synuclein dimerization does not imply the acquisition of a preferred conformation by the participating monomers, it can strongly affect the aggregation properties of the molecules. The results

  17. Subsurface dimerization in III-V semiconductor (001) surfaces

    DEFF Research Database (Denmark)

    Kumpf, C.; Marks, L.D.; Ellis, D.

    2001-01-01

    We present the atomic structure of the c(8 X 2) reconstructions of InSb-, InAs-, and GaAs-(001) surfaces as determined by surface x-ray diffraction using direct methods. Contrary to common belief, group III dimers are not prominent on the surface, instead subsurface dimerization of group m atoms ...... takes place in the second bilayer, accompanied by a major rearrangement of the surface atoms above the dimers to form linear arrays. By varying the occupancies of four surface sites the (001)-c(8 X 2) reconstructions of III-V semiconductors can be described in a unified model....

  18. Dimeric Surfactants: Promising Ingredients of Cosmetics and Toiletries

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    2013-11-01

    Full Text Available Surfactants are an essential ingredient for cosmetic, toiletries and personal care products for enhancing their performance. Dimeric surfactants demonstrate superiority compared to conventional surfactants in all areas of application. Dimeric surfactants are extremely promising for utilization in various cosmetic formulations viz. shampoo, lotions, creams, conditioners etc. These surfactants possess extremely unique surface properties viz. lower surface tension, unique micellization, low critical micelle concentration (CMC and antimicrobial activity, higher solubilization etc. Dimerics enhance the performances of cosmetics in an extraordinary manner and provide eco-friendly preparations for human epidermis.

  19. Self-Assembling Multifunctional Peptide Dimers for Gene Delivery Systems

    Directory of Open Access Journals (Sweden)

    Kitae Ryu

    2015-01-01

    Full Text Available Self-assembling multifunctional peptide was designed for gene delivery systems. The multifunctional peptide (MP consists of cellular penetrating peptide moiety (R8, matrix metalloproteinase-2 (MMP-2 specific sequence (GPLGV, pH-responsive moiety (H5, and hydrophobic moiety (palmitic acid (CR8GPLGVH5-Pal. MP was oxidized to form multifunctional peptide dimer (MPD by DMSO oxidation of thiols in terminal cysteine residues. MPD could condense pDNA successfully at a weight ratio of 5. MPD itself could self-assemble into submicron micelle particles via hydrophobic interaction, of which critical micelle concentration is about 0.01 mM. MPD showed concentration-dependent but low cytotoxicity in comparison with PEI25k. MPD polyplexes showed low transfection efficiency in HEK293 cells expressing low level of MMP-2 but high transfection efficiency in A549 and C2C12 cells expressing high level of MMP-2, meaning the enhanced transfection efficiency probably due to MMP-induced structural change of polyplexes. Bafilomycin A1-treated transfection results suggest that the transfection of MPD is mediated via endosomal escape by endosome buffering ability. These results show the potential of MPD for MMP-2 targeted gene delivery systems due to its multifunctionality.

  20. Kinase activation through dimerization by human SH2-B.

    Science.gov (United States)

    Nishi, Masahiro; Werner, Eric D; Oh, Byung-Chul; Frantz, J Daniel; Dhe-Paganon, Sirano; Hansen, Lone; Lee, Jongsoon; Shoelson, Steven E

    2005-04-01

    The isoforms of SH2-B, APS, and Lnk form a family of signaling proteins that have been described as activators, mediators, or inhibitors of cytokine and growth factor signaling. We now show that the three alternatively spliced isoforms of human SH2-B readily homodimerize in yeast two-hybrid and cellular transfections assays, and this is mediated specifically by a unique domain in its amino terminus. Consistent with previous reports, we further show that the SH2 domains of SH2-B and APS bind JAK2 at Tyr813. These findings suggested a model in which two molecules of SH2-B or APS homodimerize with their SH2 domains bound to two JAK2 molecules, creating heterotetrameric JAK2-(SH2-B)2-JAK2 or JAK2-(APS)2-JAK2 complexes. We further show that APS and SH2-B isoforms heterodimerize. At lower levels of SH2-B or APS expression, dimerization approximates two JAK2 molecules to induce transactivation. At higher relative concentrations of SH2-B or APS, kinase activation is blocked. SH2-B or APS homodimerization and SH2-B/APS heterodimerization thus provide direct mechanisms for activating and inhibiting JAK2 and other kinases from the inside of the cell and for potentiating or attenuating cytokine and growth factor receptor signaling when ligands are present.

  1. Photoluminescence light-up detection of zinc ion and imaging in living cells based on the aggregation induced emission enhancement of glutathione-capped copper nanoclusters.

    Science.gov (United States)

    Lin, Liyun; Hu, Yuefang; Zhang, Liangliang; Huang, Yong; Zhao, Shulin

    2017-08-15

    In this work, we prepared glutathione (GSH)-capped copper nanoclusters (Cu NCs) with red emission by simply adjusting the pH of GSH/Cu 2+ mixture at room temperature. A photoluminescence light-up method for detecting Zn 2+ was then developed based on the aggregation induced emission enhancement of GSH-capped Cu NCs. Zn 2+ could trigger the aggregation of Cu NCs, inducing the enhancement of luminescence and the increase of absolute quantum yield from 1.3% to 6.2%. GSH-capped Cu NCs and the formed aggregates were characterized, and the possible mechanism was also discussed. The prepared GSH-capped Cu NCs exhibited a fast response towards Zn 2+ and a wider detection range from 4.68 to 2240μM. The detection limit (1.17μM) is much lower than that of the World Health Organization permitted in drinking water. Furthermore, taking advantages of the low cytotoxicity, large Stokes shift, red emission and light-up detection mode, we explored the use of the prepared GSH-capped Cu NCs in the imaging of Zn 2+ in living cells. The developed luminescence light-up nanoprobe may hold the potentials for Zn 2+ -related drinking water safety and biological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Acclimation-induced changes in toxicity and induction of metallothionein-like proteins in the fathead minnow following sublethal exposure to cobalt, silver, and zinc

    International Nuclear Information System (INIS)

    Hobson, J.F.

    1986-01-01

    Increases in tolerance and resistance to metal toxicity by aquatic organisms have been linked to elevated levels of low-molecular-weight metal-binding proteins (e.g., metallothioneins). Acclimation-induced changes in toxic response and the concentration of metallothionein-like proteins (MTP) were studied in laboratory populations of the fathead minnow, Pimephales promelas, following sublethal exposure to Co, Ag, and Zn. Following 7 and 14 days of sublethal exposure, tolerance and resistance, as measured by acute toxicity values, were altered in a dose dependent fashion. Acute toxicity values returned to control levels after 21 days of continuous exposure. Tolerance and resistance of Co- and Zn-acclimated animals were depressed after a 7-day post-acclimation period in control water. Tolerance and resistance of Ag-acclimated animals were temporarily enhanced after 7 days post-acclimation and returned to control levels after 14 days. Accumulation of Co, Ag, and Zn measured as wholebody residues appeared to be regulated in 4 of 6 exposure regimes with residues reaching stable levels after 7 to 14 days of exposure. MTP was induced by exposure to 1.8 mg Zn/L and 0.01 mg Ag/L, however, no sustained (i.e., post 21 days) tolerance or resistance were observed at these dose levels indicating that these two biological responses may not be directly related

  3. Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Anna W.; Satyshur, Kenneth A.; Morales, Neydis Moreno; Forest, Katrina T. (UW)

    2016-02-01

    ABSTRACT

    Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRRmon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.

  4. Observation by flow 1H NMR and dimerization kinetics and products of reactive ortho-quinodimethanes and benzocyclobutadiene

    International Nuclear Information System (INIS)

    Fischer, D.

    1990-01-01

    The reactive o-quinodimethanes, 1,2-dimethylene-1,2-dihydronaphthalene (9) and o-xylylene (1) were observed by flow 1 H NMR spectroscopy at room temperature. The 1 H NMR spectrum of 9 was obtained in the absence of precursor and dimers. However, the 1 H NMR spectrum of the more reactive 1, generated in a similar manner from [o-((trimethylsilyl)methyl)benzyl]trimethylammonium iodide (5.) could be obtained only in the presence of its stable [4 + 2] and [4 + 4] dimers. The dimerization kinetics of 3-methyl- (5'), 3,6-dimethyl- (11), 3-isopropyl- (12), and 3,6-diisoproply-1,2-xylylene (13) in acetonitrile (CH 3 CN) were studied by stopped-flow UV-visible spectroscopy. Fluoride ion induced 1,2-elimination from 2-elimination from 2-trimethylsilylbenzocyclobutenyl-1 mesylate (26) was used to generate the reactive molecule benzocyclobutadiene (1') in CD 3 CN, which was observed by flow 1 H NMR spectroscopy at room temperature. The 1 H NMR spectrum (in CD 3 CN) of 1,2-dimethylene-1,2-dihydrothiophene (1 double-prime), obtained by fluoride ion induced 1,4-elimination from 3-(trimethylammoniummethyl)-2-(trimethylsilylmethyl)thiophene iodine was observed by flow 1 H NMR spectroscopy at room temperature. The dimerization rate of 1 double-prime in CH 3 CN, generated in the same manner, was measured by UV-visible spectroscopy. 166 refs., 7 figs., 7 tabs

  5. Conformational stability of the epidermal growth factor (EGF) receptor as influenced by glycosylation, dimerization and EGF hormone binding.

    Science.gov (United States)

    Taylor, Eric S; Pol-Fachin, Laercio; Lins, Roberto D; Lower, Steven K

    2017-04-01

    The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand [epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described. Molecular dynamics simulations were performed to characterize the conformational preferences of the monomeric and dimeric forms of the EGFR extracellular domain upon binding to EGF in the presence and absence of N-glycan moieties. Structural stability analyses revealed that EGF provides the most conformational stability to EGFR, followed by glycosylation and dimerization, respectively. The findings also support that EGF-EGFR binding takes place through a large-scale induced-fitting mechanism. Proteins 2017; 85:561-570. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Innovative uses for zinc in dermatology.

    Science.gov (United States)

    Bae, Yoon Soo; Hill, Nikki D; Bibi, Yuval; Dreiher, Jacob; Cohen, Arnon D

    2010-07-01

    Severe zinc deficiency states, such as acrodermatitis enteropathica, are associated with a variety of skin manifestations, such as perioral, acral, and perineal dermatitis. These syndromes can be reversed with systemic zinc repletion. In addition to skin pathologies that are clearly zinc-dependent, many dermatologic conditions (eg, dandruff, acne, and diaper rash) have been associated and treated with zinc. Success rates for treatment with zinc vary greatly depending on the disease, mode of administration, and precise zinc preparation used. With the exception of systemic zinc deficiency states, there is little evidence that convincingly demonstrates the efficacy of zinc as a reliable first-line treatment for most dermatologic conditions. However, zinc may be considered as an adjunctive treatment modality. Further research is needed to establish the indications for zinc treatment in dermatology, optimal mode of zinc delivery, and best type of zinc compound to be used. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Zinc absorption in experimental osmotic diarrhea: effect of long-chain fatty acids.

    Science.gov (United States)

    Lee, S Y; Wapnir, R A

    1993-03-01

    The effect of free fatty acids on zinc absorption was studied in a rat model of chronic osmotic diarrhea induced with magnesium citrate and phenolphthalein. In vivo rates of zinc removal from the lumen and analysis of tissue for zinc uptake and metallothionein alterations were monitored. One mmol/L stearate enhanced zinc absorption in rats with or without diarrhea, from 207 +/- 22 and 353 +/- 13 pmol/min x cm to 676 +/- 34 and 610 +/- 26 pmol/min x cm, respectively. Palmitate was only effective in normal rats. Zinc absorption inversely correlated with mucosal zinc content in the perfused intestinal segments, in both type of rats. Hepatic metallothionein was enhanced by zinc and even more by oleate plus zinc in both groups; kidney metallothionein in animals with diarrhea was normalized by either oleate or zinc. The data support previous reports on the effect of long-chain fatty acids on the enhancement of zinc absorption: saturation and a longer chain appear to be positive factors. A membrane modification role of long-chain fatty acids could have nutritional implications in the formulation of special diets.

  8. Inhibition of presynaptic activity by zinc released from mossy fiber terminals during tetanic stimulation.

    Science.gov (United States)

    Minami, Akira; Sakurada, Naomi; Fuke, Sayuri; Kikuchi, Kazuya; Nagano, Tetsuo; Oku, Naoto; Takeda, Atsushi

    2006-01-01

    Zinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the mossy fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from mossy fibers is immediately retaken up by mossy fibers. When mossy fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in mossy fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced mossy fiber long-term potentiation, was also enhanced in mossy fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from mossy fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.

  9. Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers

    Science.gov (United States)

    Baburajendran, Nithya; Jauch, Ralf; Tan, Clara Yueh Zhen; Narasimhan, Kamesh; Kolatkar, Prasanna R.

    2011-01-01

    Smad proteins form multimeric complexes consisting of the ‘common partner’ Smad4 and receptor regulated R-Smads on clustered DNA binding sites. Deciphering how pathway specific Smad complexes multimerize on DNA to regulate gene expression is critical for a better understanding of the cis-regulatory logic of TGF-β and BMP signaling. To this end, we solved the crystal structure of the dimeric Smad4 MH1 domain bound to a palindromic Smad binding element. Surprisingly, the Smad4 MH1 forms a constitutive dimer on the SBE DNA without exhibiting any direct protein–protein interactions suggesting a DNA mediated indirect readout mechanism. However, the R-Smads Smad1, Smad2 and Smad3 homodimerize with substantially decreased efficiency despite pronounced structural similarities to Smad4. Therefore, intricate variations in the DNA structure induced by different Smads and/or variant energetic profiles likely contribute to their propensity to dimerize on DNA. Indeed, competitive binding assays revealed that the Smad4/R-Smad heterodimers predominate under equilibrium conditions while R-Smad homodimers are least favored. Together, we present the structural basis for DNA recognition by Smad4 and demonstrate that Smad4 constitutively homo- and heterodimerizes on DNA in contrast to its R-Smad partner proteins by a mechanism independent of direct protein contacts. PMID:21724602

  10. Explicit correlation treatment of the potential energy surface of CO{sub 2} dimer

    Energy Technology Data Exchange (ETDEWEB)

    Kalugina, Yulia N., E-mail: kalugina@phys.tsu.ru [Tomsk State University, 36 Lenin Ave., Tomsk 634050 (Russian Federation); Buryak, Ilya A. [Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences, Moscow (Russian Federation); Chemistry Department, Lomonosov Moscow State University, Moscow (Russian Federation); Ajili, Yosra [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 Bd Descartes, 77454 Marne-La-Vallée (France); Laboratoire de Spectroscopie Atomique, Moléculaire et Applications - LSAMA Université de Tunis El Manar (Tunisia); Vigasin, Andrei A. [Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences, Moscow (Russian Federation); Jaidane, Nejm Eddine [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications - LSAMA Université de Tunis El Manar (Tunisia); Hochlaf, Majdi [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 Bd Descartes, 77454 Marne-La-Vallée (France)

    2014-06-21

    We present an extensive study of the four-dimensional potential energy surface (4D-PES) of the carbon dioxide dimer, (CO{sub 2}){sub 2}. This PES is developed over the set of intermolecular coordinates. The electronic computations are carried out at the explicitly correlated coupled cluster method with single, double, and perturbative triple excitations [CCSD(T)-F12] level of theory in connection with the augmented correlation-consistent aug-cc-pVTZ basis set. An analytic representation of the 4D-PES is derived. Our extensive calculations confirm that “Slipped Parallel” is the most stable form and that the T-shaped structure corresponds to a transition state. Later on, this PES is employed for the calculations of the vibrational energy levels of the dimer. Moreover, the temperature dependence of the dimer second virial coefficient and of the first spectral moment of rototranslational collision-induced absorption spectrum is derived. For both quantities, a good agreement is found between our values and the experimental data for a wide range of temperatures. This attests to the high quality of our PES. Generally, our PES and results can be used for modeling CO{sub 2} supercritical fluidity and examination of its role in planetary atmospheres. It can be also incorporated into dynamical computations of CO{sub 2} capture and sequestration. This allows deep understanding, at the microscopic level, of these processes.

  11. DFT Study of dimers of dimethyl sulfoxide in gas phase

    Directory of Open Access Journals (Sweden)

    Reza Fazaeli

    2014-10-01

    Full Text Available Density functional (DFT calculations at M05-2x/aug-cc-pVDZ level were used to analyze the interactions between dimethyl sulfoxide (DMSO dimers. The structures obtained have been ana-lyzed with the Atoms in Molecules (AIMs and Natural Bond Orbital (NBO methodologies. Four minima were located on the potential energy surface of the dimers. Three types of interac-tions are observed, CH•••O, CH•••S hydrogen bonds and orthogonal interaction between the lone pair of the oxygen with the electron-deficient region of the sulfur atom. Stabilization energies of dimers including BSSE and ZPE are in the range 27–40 kJmol-1. The most stable conformers of dimers at DFT level is cyclic structure with antiparallel orientation of S=O groups pairing with three C–H∙∙∙O and a S∙∙∙O interactions.

  12. 21 CFR 176.120 - Alkyl ketene dimers.

    Science.gov (United States)

    2010-04-01

    ..., processing, preparing, treating, packaging, transporting, or holding food, subject to the provisions of this... paperboard. (c) The alkyl ketene dimers may be used in the form of an aqueous emulsion which may contain...

  13. Family C 7TM receptor dimerization and activation

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Sheikh, Søren P; Hansen, Jakob Lerche

    2006-01-01

    The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug...... to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.......-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational...

  14. Perturbation of the dimer interface of triosephosphate isomerase and its effect on Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Vanesa Olivares-Illana

    2007-10-01

    Full Text Available Chagas disease affects around 18 million people in the American continent. Unfortunately, there is no satisfactory treatment for the disease. The drugs currently used are not specific and exert serious toxic effects. Thus, there is an urgent need for drugs that are effective. Looking for molecules to eliminate the parasite, we have targeted a central enzyme of the glycolytic pathway: triosephosphate isomerase (TIM. The homodimeric enzyme is catalytically active only as a dimer. Because there are significant differences in the interface of the enzymes from the parasite and humans, we searched for small molecules that specifically disrupt contact between the two subunits of the enzyme from Trypanosoma cruzi but not those of TIM from Homo sapiens (HTIM, and tested if they kill the parasite.Dithiodianiline (DTDA at nanomolar concentrations completely inactivates recombinant TIM of T. cruzi (TcTIM. It also inactivated HTIM, but at concentrations around 400 times higher. DTDA was also tested on four TcTIM mutants with each of its four cysteines replaced with either valine or alanine. The sensitivity of the mutants to DTDA was markedly similar to that of the wild type. The crystal structure of the TcTIM soaked in DTDA at 2.15 A resolution, and the data on the mutants showed that inactivation resulted from alterations of the dimer interface. DTDA also prevented the growth of Escherichia coli cells transformed with TcTIM, had no effect on normal E. coli, and also killed T. cruzi epimastigotes in culture.By targeting on the dimer interface of oligomeric enzymes from parasites, it is possible to discover small molecules that selectively thwart the life of the parasite. Also, the conformational changes that DTDA induces in the dimer interface of the trypanosomal enzyme are unique and identify a region of the interface that could be targeted for drug discovery.

  15. Evidence for a zinc/proton antiporter in rat brain.

    Science.gov (United States)

    Colvin, R A; Davis, N; Nipper, R W; Carter, P A

    2000-05-01

    The data presented in this paper are consistent with the existence of a plasma membrane zinc/proton antiport activity in rat brain. Experiments were performed using purified plasma membrane vesicles isolated from whole rat brain. Incubating vesicles in the presence of various concentrations of 65Zn2+ resulted in a rapid accumulation of 65Zn2+. Hill plot analysis demonstrated a lack of cooperativity in zinc activation of 65Zn2+ uptake. Zinc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or CO2+. Calcium (1 mM) was less effective at inhibiting 65Zn2+ uptake and Mg2+ and Mn2+ had no effect. The initial rate of vesicular 65Zn2+ uptake was inhibited by increasing extravesicular H+ concentration. Vesicles preloaded with 65Zn2+ could be induced to release 65Zn2+ by increasing extravesicular H+ or addition of 1 mM nonradioactive Zn2+. Hill plot analysis showed a lack of cooperativity in H+ activation of 65Zn2+ release. Based on the Hill analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange and Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribute to the reuptake of zinc to replenish presynaptic vesicle stores after stimulation.

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

    Science.gov (United States)

    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.

  17. Uptake and partitioning of zinc in Lemnaceae.

    Science.gov (United States)

    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.

  18. Detection of zinc translocation into apical dendrite of CA1 pyramidal neuron after electrical stimulation.

    Science.gov (United States)

    Suh, Sang Won

    2009-02-15

    Translocation of the endogenous cation zinc from presynaptic terminals to postsynaptic neurons after brain insult has been implicated as a potential neurotoxic event. Several studies have previously demonstrated that a brief electrical stimulation is sufficient to induce the translocation of zinc from presynaptic vesicles into the cytoplasm (soma) of postsynaptic neurons. In the present work I have extended those findings in three ways: (i) providing evidence that zinc translocation occurs into apical dendrites, (ii) presenting data that there is an apparent translocation into apical dendrites when only a zinc-containing synaptic input is stimulated, and (iii) presenting data that there is no zinc translocation into apical dendrite of ZnT3 KO mice following electrical stimulation. Hippocampal slices were preloaded with the "trappable" zinc fluorescent probe, Newport Green. After washout, a single apical dendrite in the stratum radiatum of hippocampal CA1 area was selected and focused on. Burst stimulation (100Hz, 500microA, 0.2ms, monopolar) was delivered to either the adjacent Schaffer-collateral inputs (zinc-containing) or to the adjacent temporo-ammonic inputs (zinc-free) to the CA1 dendrites. Stimulation of the Schaffer collaterals increased the dendritic fluorescence, which was blocked by TTX, low-Ca medium, or the extracellular zinc chelator, CaEDTA. Stimulation of the temporo-ammonic pathway caused no significant rise in the fluorescence. Genetic depletion of vesicular zinc by ZnT3 KO showed no stimulation-induced apical dendrite zinc rise. The present study provides evidence that synaptically released zinc translocates into postsynaptic neurons through the apical dendrites of CA1 pyramidal neurons during physiological synaptic activity.

  19. Inhibitory zinc-enriched terminals in mouse spinal cord

    DEFF Research Database (Denmark)

    Danscher, G; Jo, S M; Varea, E

    2001-01-01

    The ultrastructural localization of zinc transporter-3, glutamate decarboxylase and zinc ions in zinc-enriched terminals in the mouse spinal cord was studied by zinc transporter-3 and glutamate decarboxylase immunohistochemistry and zinc selenium autometallography, respectively.The distribution...

  20. Multi-element analysis of the rat hippocampus by proton induced x-ray emission spectroscopy (phosphorus, sulfur, chlorine, potassium, calcium, iron, zinc, copper, lead, bromine, and rubidium)

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, K.; Danscher, G.

    1979-01-22

    A technique for multi-element analysis of brain tissue by proton induced x-ray emission spectroscopy (PIXE) is described and data from anal