Integration of biotic ligand models (BLM) and bioaccumulation kinetics into a mechanistic framework for metal uptake in aquatic organisms.

PubMed

Veltman, Karin; Huijbregts, Mark A J; Hendriks, A Jan

2010-07-01

Both biotic ligand models (BLM) and bioaccumulation models aim to quantify metal exposure based on mechanistic knowledge, but key factors included in the description of metal uptake differ between the two approaches. Here, we present a quantitative comparison of both approaches and show that BLM and bioaccumulation kinetics can be merged into a common mechanistic framework for metal uptake in aquatic organisms. Our results show that metal-specific absorption efficiencies calculated from BLM-parameters for freshwater fish are highly comparable, i.e. within a factor of 2.4 for silver, cadmium, copper, and zinc, to bioaccumulation-absorption efficiencies for predominantly marine fish. Conditional affinity constants are significantly related to the metal-specific covalent index. Additionally, the affinity constants of calcium, cadmium, copper, sodium, and zinc are significantly comparable across aquatic species, including molluscs, daphnids, and fish. This suggests that affinity constants can be estimated from the covalent index, and constants can be extrapolated across species. A new model is proposed that integrates the combined effect of metal chemodynamics, as speciation, competition, and ligand affinity, and species characteristics, as size, on metal uptake by aquatic organisms. An important direction for further research is the quantitative comparison of the proposed model with acute toxicity values for organisms belonging to different size classes.

Cooperative binding modes of Cu(II) in prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Chisnell, Robin; Lu, Wenchang; Bernholc, Jerry

2007-03-01

The misfolding of the prion protein, PrP, is responsible for a group of neurodegenerative diseases including mad cow disease and Creutzfeldt-Jakob disease. It is known that the PrP can efficiently bind copper ions; four high-affinity binding sites located in the octarepeat region of PrP are now well known. Recent experiments suggest that at low copper concentrations new binding modes, in which one copper ion is shared between two or more binding sites, are possible. Using our hybrid Thomas-Fermi/DFT computational scheme, which is well suited for simulations of biomolecules in solution, we investigate the geometries and energetics of two, three and four binding sites cooperatively binding one copper ion. These geometries are then used as inputs for classical molecular dynamics simulations. We find that copper binding affects the secondary structure of the PrP and that it stabilizes the unstructured (unfolded) part of the protein.

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

PubMed Central

2014-01-01

Background Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. Methods Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. Results Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of intracellular (IC) copper delivery via the copper chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which normalized SOD1 activity with consequent bolstering of anti-oxidant defenses. Furthermore, diabetes depressed levels of additional intracellular copper-transporting proteins, including antioxidant-protein-1 (ATOX1) and copper-transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1 (ATP7A). Conclusions Myocardial copper deficiency and defective cellular copper transport/trafficking are revealed as key molecular defects underlying LV impairment in diabetes, and TETA-mediated restoration of copper regulation provides a potential new class of therapeutic molecules for DCM. PMID:24927960

Copper(II) ions and the Alzheimer's amyloid-β peptide: Affinity and stoichiometry of binding

NASA Astrophysics Data System (ADS)

Tõugu, Vello; Friedemann, Merlin; Tiiman, Ann; Palumaa, Peep

2014-10-01

Deposition of amyloid beta (Aβ) peptides into amyloid plaques is the hallmark of Alzheimer's disease. According to the amyloid cascade hypothesis this deposition is an early event and primary cause of the disease, however, the mechanisms that cause this deposition remain elusive. An increasing amount of evidence shows that the interactions of biometals can contribute to the fibrillization and amyloid formation by amyloidogenic peptides. From different anions the copper ions deserve the most attention since it can contribute not only toamyloid formation but also to its toxicity due to the generation of ROS. In this thesis we focus on the affinity and stoichiometry of copper(II) binding to the Aβ molecule.

Combined copper/zinc attachment to prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Bernholc, Jerry

2013-03-01

Misfolding of prion protein (PrP) is responsible for diseases such as ``mad-cow disease'' in cattle and Creutzfeldt-Jacob in humans. Extensive experimental investigation has established that this protein strongly interacts with copper ions, and this ability has been linked to its still unknown function. Attachment of other metal ions (zinc, iron, manganese) have been demonstrated as well, but none of them could outcompete copper. Recent finding, however, indicates that at intermediate concentrations both copper and zinc ions can attach to the PrP at the octarepeat region, which contains high affinity metal binding sites. Based on this evidence, we have performed density functional theory simulations to investigate the combined Cu/Zn attachment. We consider all previously reported binding modes of copper at the octarepeat region and examine a possibility simultaneous Cu/Zn attachment. We find that this can indeed occur for only one of the known binding sites, when copper changes its coordination mode to allow for attachment of zinc ion. The implications of the simultaneous attachment on neural function remain to be explored.

Arabidopsis Copper Transport Protein COPT2 Participates in the Cross Talk between Iron Deficiency Responses and Low-Phosphate Signaling1[C][W

PubMed Central

Perea-García, Ana; Garcia-Molina, Antoni; Andrés-Colás, Nuria; Vera-Sirera, Francisco; Pérez-Amador, Miguel A.; Puig, Sergi; Peñarrubia, Lola

2013-01-01

Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes, including respiration, photosynthesis, and oxidative stress protection. In many eukaryotic organisms, including yeast (Saccharomyces cerevisiae) and mammals, copper and iron homeostases are highly interconnected; yet, such interdependence is not well established in higher plants. Here, we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis (Arabidopsis thaliana). COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 could play a dual role under iron deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation, possibly to minimize further iron consumption. Second, global expression analyses of copt2-1 versus wild-type Arabidopsis plants indicate that low-phosphate responses increase in the mutant. These results open up new biotechnological approaches to fight iron deficiency in crops. PMID:23487432

Calcium- and potassium-permeable plasma membrane transporters are activated by copper in Arabidopsis root tips: linking copper transport with cytosolic hydroxyl radical production.

PubMed

Rodrigo-Moreno, Ana; Andrés-Colás, Nuria; Poschenrieder, Charlotte; Gunsé, Benet; Peñarrubia, Lola; Shabala, Sergey

2013-04-01

Transition metals such as copper can interact with ascorbate or hydrogen peroxide to form highly reactive hydroxyl radicals (OH(•) ), with numerous implications to membrane transport activity and cell metabolism. So far, such interaction was described for extracellular (apoplastic) space but not cytosol. Here, a range of advanced electrophysiological and imaging techniques were applied to Arabidopsis thaliana plants differing in their copper-transport activity: Col-0, high-affinity copper transporter COPT1-overexpressing (C1(OE) ) seedlings, and T-DNA COPT1 insertion mutant (copt1). Low Cu concentrations (10 µm) stimulated a dose-dependent Gd(3+) and verapamil sensitive net Ca(2+) influx in the root apex but not in mature zone. C1(OE) also showed a fivefold higher Cu-induced K(+) efflux at the root tip level compared with Col-0, and a reduction in basal peroxide accumulation at the root tip after copper exposure. Copper caused membrane disruptions of the root apex in C1(OE) seedlings but not in copt1 plants; this damage was prevented by pretreatment with Gd(3+) . Our results suggest that copper transport into cytosol in root apex results in hydroxyl radical generation at the cytosolic side, with a consequent regulation of plasma membrane OH(•) -sensitive Ca(2+) and K(+) transport systems. © 2012 Blackwell Publishing Ltd.

Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2.

PubMed

Logeman, Brandon L; Wood, L Kent; Lee, Jaekwon; Thiele, Dennis J

2017-07-07

Copper is an essential element for proper organismal development and is involved in a range of processes, including oxidative phosphorylation, neuropeptide biogenesis, and connective tissue maturation. The copper transporter (Ctr) family of integral membrane proteins is ubiquitously found in eukaryotes and mediates the high-affinity transport of Cu + across both the plasma membrane and endomembranes. Although mammalian Ctr1 functions as a Cu + transporter for Cu acquisition and is essential for embryonic development, a homologous protein, Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary relationship to Ctr1 is unclear. Here we report a biochemical, genetic, and phylogenetic comparison of metazoan Ctr1 and Ctr2, suggesting that Ctr2 arose over 550 million years ago as a result of a gene duplication event followed by loss of Cu + transport activity. Using a random mutagenesis and growth selection approach, we identified amino acid substitutions in human and mouse Ctr2 proteins that support copper-dependent growth in yeast and enhance copper accumulation in Ctr1 -/- mouse embryonic fibroblasts. These mutations revert Ctr2 to a more ancestral Ctr1-like state while maintaining endogenous functions, such as stimulating Ctr1 cleavage. We suggest key structural aspects of metazoan Ctr1 and Ctr2 that discriminate between their biological roles, providing mechanistic insights into the evolutionary, biochemical, and functional relationships between these two related proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Selective and Sensitive Fluorescent Detection of Picric Acid by New Pyrene and Anthracene Based Copper Complexes.

PubMed

Reddy, Kumbam Lingeshwar; Kumar, Anabathula Manoj; Dhir, Abhimanew; Krishnan, Venkata

2016-11-01

New pyrene and anthracene based copper complexes 4 and 7 respectively were designed, synthesized and characterized. The fluorescence behaviour of both 4 and 7 were evaluated towards nitro aromatics and anions. Both 4 and 7 possess high selectivity for the detection of well-known explosive picric acid (PA) by showing maximum fluorescence affinity. Furthermore, complex 4 showed similar sensing efficiency towards PA at different pH ranges. It was also used for real world applications, as illustrated by the very fast detection of PA from soil samples observed directly by naked eye.

Cu-rGO subsurface layer creation on copper substrate and its resistance to oxidation

NASA Astrophysics Data System (ADS)

Pietrzak, Katarzyna; Strojny-Nędza, Agata; Olesińska, Wiesława; Bańkowska, Anna; Gładki, Andrzej

2017-11-01

On the basis of a specially designed experiment, this paper presents a model, which is an attempt to explain the mechanism of formatting and creating oxidation resistance of Cu-rGO subsurface layers. Practically zero chemical affinity of copper to carbon is a fundamental difficulty in creating composite structures of Cu-C, properties which are theoretically possible to estimate. In order to bind the thermally reduced graphene oxide with copper surface, the effect of structural rebuilding of the copper oxide, in the process of annealing in a nitrogen atmosphere, have been used. On intentionally oxidized and anoxic copper substrates the dispersed graphene oxide (GO) and thermally reduced graphene oxide (rGO) were loaded. Annealing processes after the binding effects of both graphene oxide forms to Cu substrates were tested. The methods for high-resolution electron microscopy were found subsurface rGO-Cu layer having a substantially greater resistance to oxidation than pure copper. The mechanism for the effective resistance to oxidation of the Cu-rGO has been presented in a hypothetical form.

Using Tryptophan Mutants To Probe the Structural and Functional Status of BsSCO, a Copper Binding, Cytochrome c Oxidase Assembly Protein from Bacillus subtilis.

PubMed

Hussain, Shina; Andrews, Diann; Hill, Bruce C

2017-12-05

The synthesis of cytochrome c oxidase protein from Bacillus subtilis (i.e., BsSCO) binds copper with picomolar affinity, which increases the protein's melting temperature (i.e., T M ) by 20 °C. Here two native tryptophans (i.e., W36 and W101) are identified as major contributors to BsSCO's structural form, and their contributions to the stability, intrinsic fluorescence, and copper binding properties of BsSCO are explored. Single mutations of tryptophan to phenylalanine decrease the T M by 10 °C and the folding free energy by 3-4 kcal/mol. A more severe change to alanine (i.e., W36A BsSCO) decreases the T M by 20 °C and the stability by 9 kcal/mol. However, these mutants bind copper with high affinity and assemble cytochrome c oxidase in vivo. Replacing phenylalanine at a position near (∼5 Å) the copper binding site with tryptophan (i.e., F42W) increases the T M of apo-BsSCO by 3 °C but diminishes the effect of copper binding. When both native tryptophans are changed to alanine, apo-BsSCO is unfolded in vitro and is not functional in cytochrome c oxidase assembly in vivo. A double-mutant of BsSCO in which W36A is combined with F42W exhibits a form of metastability. Apo-W36A/F42W BsSCO melts at 37 °C, which upon binding of copper shifts to 65 °C. B. subtilis expressing W36A/F42W BsSCO and grown at 37 °C does not assemble cytochrome c oxidase. However, when these cells are cooled to 25 °C, cytochrome c oxidase activity is recovered. Our results illustrate the subtle relationship between the structural stability and functional properties of BsSCO in the assembly of cytochrome c oxidase.

Identification of Two Conserved Residues Involved in Copper Release from Chloroplast PIB-1-ATPases*

PubMed Central

Sautron, Emeline; Giustini, Cécile; Dang, ThuyVan; Moyet, Lucas; Salvi, Daniel; Crouzy, Serge; Rolland, Norbert; Catty, Patrice; Seigneurin-Berny, Daphné

2016-01-01

Copper is an essential transition metal for living organisms. In the plant model Arabidopsis thaliana, half of the copper content is localized in the chloroplast, and as a cofactor of plastocyanin, copper is essential for photosynthesis. Within the chloroplast, copper delivery to plastocyanin involves two transporters of the PIB-1-ATPases subfamily: HMA6 at the chloroplast envelope and HMA8 in the thylakoid membranes. Both proteins are high affinity copper transporters but share distinct enzymatic properties. In the present work, the comparison of 140 sequences of PIB-1-ATPases revealed a conserved region unusually rich in histidine and cysteine residues in the TMA-L1 region of eukaryotic chloroplast copper ATPases. To evaluate the role of these residues, we mutated them in HMA6 and HMA8. Mutants of interest were selected from phenotypic tests in yeast and produced in Lactococcus lactis for further biochemical characterizations using phosphorylation assays from ATP and Pi. Combining functional and structural data, we highlight the importance of the cysteine and the first histidine of the CX3HX2H motif in the process of copper release from HMA6 and HMA8 and propose a copper pathway through the membrane domain of these transporters. Finally, our work suggests a more general role of the histidine residue in the transport of copper by PIB-1-ATPases. PMID:27493208

3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

NASA Astrophysics Data System (ADS)

Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

2014-02-01

Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

Mechanism of Selenium Loss in Copper Slag

NASA Astrophysics Data System (ADS)

Desai, Bhavin; Tathavadkar, Vilas; Basu, Somnath

2018-03-01

During smelting of copper sulfide concentrate, selenium is distributed between silica-saturated iron-silicate slag and copper-iron sulfide matte. The recovery coefficients of selenium between slag and matte were determined as a function of the initial concentration of selenium at 1523 K (1250 °C) under an inert atmosphere in a vertical tubular furnace. The initial concentration of selenium was varied by the addition of metallic selenium as well as selenium dioxide to the mixture of slag and matte. Analysis of the results indicated high affinity of selenium for matte. The apparent loss of selenium with the slag was attributed to the presence of selenium-enriched matte particles entrapped in the slag, rather than dissolved SeO2. The mechanisms proposed by previous investigators were discussed and also compared with the results of the present investigation.

Mechanism of Selenium Loss in Copper Slag

NASA Astrophysics Data System (ADS)

Desai, Bhavin; Tathavadkar, Vilas; Basu, Somnath

2018-06-01

During smelting of copper sulfide concentrate, selenium is distributed between silica-saturated iron-silicate slag and copper-iron sulfide matte. The recovery coefficients of selenium between slag and matte were determined as a function of the initial concentration of selenium at 1523 K (1250 °C) under an inert atmosphere in a vertical tubular furnace. The initial concentration of selenium was varied by the addition of metallic selenium as well as selenium dioxide to the mixture of slag and matte. Analysis of the results indicated high affinity of selenium for matte. The apparent loss of selenium with the slag was attributed to the presence of selenium-enriched matte particles entrapped in the slag, rather than dissolved SeO2. The mechanisms proposed by previous investigators were discussed and also compared with the results of the present investigation.

Decoration of silicon nanostructures with copper particles for simultaneous selective capture and mass spectrometry detection of His-tagged model peptide.

PubMed

Coffinier, Yannick; Kurylo, Ievgen; Drobecq, Hervé; Szunerits, Sabine; Melnyk, Oleg; Zaitsev, Vladimir N; Boukherroub, Rabah

2014-10-21

We present in this work a simple and fast preparation method of a new affinity surface-assisted laser/desorption ionization mass spectrometry (SALDI-MS) substrate based on silicon nanostructures decorated with copper particles. The silicon nanostructures were fabricated by the metal-assisted chemical etching (MACE) method. Then, superhydrophilic areas surrounded by superhydrophobic regions were formed through hydrosilylation reaction of 1-octadecene, followed by local degradation of the octadecyl layer. After that, copper particles were deposited in the hydrophilic areas by using the electroless method. We have demonstrated that these surfaces were able to perform high selective capture of model His-tag peptide even in a complex mixture such as serum solution. Then, the captured peptide was detected by mass spectrometry at a femtomolar level without the need of organic matrix.

Geochemical constraints on adakites of different origins and copper mineralization

USGS Publications Warehouse

Sun, W.-D.; Ling, M.-X.; Chung, S.-L.; Ding, X.; Yang, X.-Y.; Liang, H.-Y.; Fan, W.-M.; Goldfarb, R.; Yin, Q.-Z.

2012-01-01

The petrogenesis of adakites holds important clues to the formation of the continental crust and copper ?? gold porphyry mineralization. However, it remains highly debated as to whether adakites form by slab melting, by partial melting of the lower continental crust, or by fractional crystallization of normal arc magmas. Here, we show that to form adakitic signature, partial melting of a subducting oceanic slab would require high pressure at depths of >50 km, whereas partial melting of the lower continental crust would require the presence of plagioclase and thus shallower depths and additional water. These two types of adakites can be discriminated using geochemical indexes. Compiled data show that adakites from circum-Pacific regions, which have close affinity to subduction of young hot oceanic plate, can be clearly discriminated from adakites from the Dabie Mountains and the Tibetan Plateau, which have been attributed to partial melting of continental crust, in Sr/Y-versus-La/Yb diagram. Given that oceanic crust has copper concentrations about two times higher than those in the continental crust, whereas the high oxygen fugacity in the subduction environment promotes the release of copper during partial melting, slab melting provides the most efficient mechanism to concentrate copper and gold; slab melts would be more than two times greater in copper (and also gold) concentrations than lower continental crust melts and normal arc magmas. Thus, identification of slab melt adakites is important for predicting exploration targets for copper- and gold-porphyry ore deposits. This explains the close association of ridge subduction with large porphyry copper deposits because ridge subduction is the most favorable place for slab melting. ?? 2012 by The University of Chicago.

The Copper Active Site of CBM33 Polysaccharide Oxygenases

PubMed Central

2013-01-01

The capacity of metal-dependent fungal and bacterial polysaccharide oxygenases, termed GH61 and CBM33, respectively, to potentiate the enzymatic degradation of cellulose opens new possibilities for the conversion of recalcitrant biomass to biofuels. GH61s have already been shown to be unique metalloenzymes containing an active site with a mononuclear copper ion coordinated by two histidines, one of which is an unusual τ-N-methylated N-terminal histidine. We now report the structural and spectroscopic characterization of the corresponding copper CBM33 enzymes. CBM33 binds copper with high affinity at a mononuclear site, significantly stabilizing the enzyme. X-band EPR spectroscopy of Cu(II)-CBM33 shows a mononuclear type 2 copper site with the copper ion in a distorted axial coordination sphere, into which azide will coordinate as evidenced by the concomitant formation of a new absorption band in the UV/vis spectrum at 390 nm. The enzyme’s three-dimensional structure contains copper, which has been photoreduced to Cu(I) by the incident X-rays, confirmed by X-ray absorption/fluorescence studies of both aqueous solution and intact crystals of Cu-CBM33. The single copper(I) ion is ligated in a T-shaped configuration by three nitrogen atoms from two histidine side chains and the amino terminus, similar to the endogenous copper coordination geometry found in fungal GH61. PMID:23540833

Evaluating the Field Emission Characteristics of Aluminum for DC High Voltage Photo-Electron Guns

NASA Astrophysics Data System (ADS)

Taus, Rhys; Poelker, Matthew; Forman, Eric; Mamun, Abdullah

2014-03-01

High current photoguns require high power laser light, but only a small portion of the laser light illuminating the photocathode produces electron beam. Most of the laser light (~ 65%) simply serves to heat the photocathode, which leads to evaporation of the chemicals required to create the negative electron affinity condition necessary for photoemission. Photocathode cooling techniques have been employed to address this problem, but active cooling of the photocathode is complicated because the cooling apparatus must float at high voltage. This work evaluates the field emission characteristics of cathode electrodes manufactured from materials with high thermal conductivity: aluminum and copper. These electrodes could serve as effective heat sinks, to passively cool the photocathode that resides within such a structure. However, literature suggests ``soft'' materials like aluminum and copper are ill suited for photogun applications, due to excessive field emission when biased at high voltage. This work provides an evaluation of aluminum and copper electrodes inside a high voltage field emission test stand, before and after coating with titanium nitride (TiN), a coating that enhances surface hardness. National Science Foundation Award Number: 1062320 and the Department of Defence ASSURE program.

Copper metallothioneins.

PubMed

Calvo, Jenifer; Jung, Hunmin; Meloni, Gabriele

2017-04-01

Metallothioneins (MTs) are a class of low molecular weight and cysteine-rich metal binding proteins present in all the branches of the tree of life. MTs efficiently bind with high affinity several essential and toxic divalent and monovalent transition metals by forming characteristic polynuclear metal-thiolate clusters within their structure. MTs fulfil multiple biological functions related to their metal binding properties, with essential roles in both Zn(II) and Cu(I) homeostasis as well as metal detoxification. Depending on the organism considered, the primary sequence, and the specific physiological and metabolic status, Cu(I)-bound MT isoforms have been isolated, and their chemistry and biology characterized. Besides the recognized role in the biochemistry of divalent metals, it is becoming evident that unique biological functions in selectively controlling copper levels, its reactivity as well as copper-mediated biochemical processes have evolved in some members of the MT superfamily. Selected examples are reviewed to highlight the peculiar chemical properties and biological functions of copper MTs. © 2016 IUBMB Life, 69(4):236-245, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Electrocatalytic Production of C3-C4 Compounds by Conversion of CO2 on a Chloride-Induced Bi-Phasic Cu2O-Cu Catalyst.

PubMed

Lee, Seunghwa; Kim, Dahee; Lee, Jaeyoung

2015-12-01

Electrocatalytic conversion of carbon dioxide (CO2) has recently received considerable attention as one of the most feasible CO2 utilization techniques. In particular, copper and copper-derived catalysts have exhibited the ability to produce a number of organic molecules from CO2. Herein, we report a chloride (Cl)-induced bi-phasic cuprous oxide (Cu2O) and metallic copper (Cu) electrode (Cu2OCl) as an efficient catalyst for the formation of high-carbon organic molecules by CO2 conversion, and identify the origin of electroselectivity toward the formation of high-carbon organic compounds. The Cu2OCl electrocatalyst results in the preferential formation of multi-carbon fuels, including n-propanol and n-butane C3-C4 compounds. We propose that the remarkable electrocatalytic conversion behavior is due to the favorable affinity between the reaction intermediates and the catalytic surface. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism.

PubMed

Rehmani, Nida; Zafar, Atif; Arif, Hussain; Hadi, Sheikh Mumtaz; Wani, Altaf A

2017-04-01

Oxidative DNA damage has been implicated in the pathogenesis of neurological disorders, cancer and ageing. Owing to the established link between labile copper concentrations and neurological diseases, it is critical to explore the interactions of neurotransmitters and drug supplements with copper. Herein, we investigate the pro-oxidant DNA damage induced by the interaction of L-DOPA and dopamine (DA) with copper. The DNA binding affinity order of the compounds has been determined by in silico molecular docking. Agarose gel electrophoresis reveals that L-DOPA and DA are able to induce strand scission in plasmid pcDNA3.1 (+/-) in a copper dependent reaction. These metabolites also cause cellular DNA breakage in human lymphocytes by mobilizing endogenous copper, as assessed by comet assay. Further, L-DOPA and DA-mediated DNA breaks were detected by the appearance of post-DNA damage sensitive marker γH2AX in cancer cell lines accumulating high copper. Immunofluorescence demonstrated the co-localization of downstream repair factor 53BP1 at the damaged induced γH2AX foci in cancer cells. The present study corroborates and provides a mechanism to the hypothesis that suggests metal-mediated oxidation of catecholamines contributes to the pathogenesis of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of cell condition, pH, and temperature on lead, zinc, and copper sorption to Acidithiobacillus caldus strain BC13

DOE Office of Scientific and Technical Information (OSTI.GOV)

John E. Aston; William A. Apel; Brady D. Lee

2010-12-01

This study describes the effects of cell condition, pH, and temperature on lead, zinc, and copper sorption to Acidithiobacillus caldus strain BC13 with a Langmuir model. Copper exhibited the highest loading capacity, 4.76 ± 0.28 mmol g-1, to viable cells at pH 5.5. The highest kL (binding-site affinity) observed was 61.2 ± 3.0 L mmol-1 to dehydrated cells at pH 4.0. The pHs that maximized loading capacities and binding-site affinities were generally between 4.0 and 5.5, where the sum of free-proton and complexed-metal concentrations was near a minimum. Of additional importance, lead, zinc, and copper sorbed to viable cells atmore » pH values as low as 1.5. Previous studies with other acidithiobacilli did not measure viable-cell sorption below pH 4.0. In separate experiments, desorption studies showed that far less copper was recovered from viable cells than any other metal or cell condition, suggesting that uptake may play an important role in copper sorption by At. caldus strain BC13. To reflect an applied system, the sorption of metal mixtures was also studied. In these experiments, lead, zinc, and copper sorption from a tertiary mixture were 40.2 ± 4.3%, 28.7 ± 3.8%, and 91.3 ± 3.0%, respectively, of that sorbed in single-metal systems.« less

CopM is a novel copper-binding protein involved in copper resistance in Synechocystis sp. PCC 6803.

PubMed

Giner-Lamia, Joaquín; López-Maury, Luis; Florencio, Francisco J

2015-02-01

Copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803 comprises two operons, copMRS and copBAC, which are expressed in response to copper in the media. copBAC codes for a heavy-metal efflux-resistance nodulation and division (HME-RND) system, while copMRS codes for a protein of unknown function, CopM, and a two-component system CopRS, which controls the expression of these two operons. Here, we report that CopM is a periplasmic protein able to bind Cu(I) with high affinity (KD ~3 × 10(-16) ). Mutants lacking copM showed a sensitive copper phenotype similar to mutants affected in copB, but lower than mutants of the two-component system CopRS, suggesting that CopBAC and CopM constitute two independent resistance mechanisms. Moreover, constitutive expression of copM is able to partially suppress the copper sensitivity of the copR mutant strain, pointing out that CopM per se is able to confer copper resistance. Furthermore, constitutive expression of copM was able to reduce total cellular copper content of the copR mutant to the levels determined in the wild-type (WT) strain. Finally, CopM was localized not only in the periplasm but also in the extracellular space, suggesting that CopM can also prevent copper accumulation probably by direct copper binding outside the cell. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

CopM is a novel copper-binding protein involved in copper resistance in Synechocystis sp. PCC 6803

PubMed Central

Giner-Lamia, Joaquín; López-Maury, Luis; Florencio, Francisco J

2015-01-01

Copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803 comprises two operons, copMRS and copBAC, which are expressed in response to copper in the media. copBAC codes for a heavy-metal efflux–resistance nodulation and division (HME-RND) system, while copMRS codes for a protein of unknown function, CopM, and a two-component system CopRS, which controls the expression of these two operons. Here, we report that CopM is a periplasmic protein able to bind Cu(I) with high affinity (KD ∼3 × 10−16). Mutants lacking copM showed a sensitive copper phenotype similar to mutants affected in copB, but lower than mutants of the two-component system CopRS, suggesting that CopBAC and CopM constitute two independent resistance mechanisms. Moreover, constitutive expression of copM is able to partially suppress the copper sensitivity of the copR mutant strain, pointing out that CopM per se is able to confer copper resistance. Furthermore, constitutive expression of copM was able to reduce total cellular copper content of the copR mutant to the levels determined in the wild-type (WT) strain. Finally, CopM was localized not only in the periplasm but also in the extracellular space, suggesting that CopM can also prevent copper accumulation probably by direct copper binding outside the cell. PMID:25545960

Copper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy.

PubMed

Masaldan, Shashank; Clatworthy, Sharnel A S; Gamell, Cristina; Smith, Zoe M; Francis, Paul S; Denoyer, Delphine; Meggyesy, Peter M; Fontaine, Sharon La; Cater, Michael A

2018-06-01

Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs was accompanied by elevated levels of high-affinity copper uptake protein 1 (Ctr1), diminished levels of copper-transporting ATPase 1 (Atp7a) (copper export) and enhanced antioxidant defence reflected by elevated levels of glutathione (GSH), superoxide dismutase 1 (SOD1) and glutaredoxin 1 (Grx1). The levels of intracellular copper were further increased in senescent MEFs cultured in copper supplemented medium and in senescent Mottled Brindled (Mo br ) MEFs lacking functional Atp7a. Finally, we demonstrated that the restoration/preservation of autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment correlated with attenuation of copper accumulation in these cells despite a further decrease in Atp7a levels. This study for the first time establishes a link between Atp7a and the autophagic-lysosomal pathway, and a requirement for both to effect efficient copper export. Such a connection between cellular autophagy and copper homeostasis is significant, as both have emerged as important facets of age-associated degenerative disease. Copyright © 2018. Published by Elsevier B.V.

N,N',N"-tris(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane (Deofix) - a high-affinity, high-specificity chelator for first transition series metal cations with significant deodorant, antimicrobial, and antioxidant activity.

PubMed

Laden, Karl; Zaklad, Haim; Simhon, Elliot D; Klein, Joseph Y; Cyjon, Rosa L; Winchell, Harry S

2003-01-01

Deofix, N,N',N"-tris(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane, is a high-affinity, high-specificity chelator for first transition series cations such as iron, zinc, manganese, and copper. A 1% solution in 50% ethanol was found to be significantly better at reducing underarm malodor than a solution of 0.3% Triclosan in 50% ethanol. Compared to a 50% alcohol control, Deofix was found to produce a significant reduction in malodor for at least 48 hours. Deofix appears to work by reducing the concentration of first transition series metal ions below the levels needed for microbial cell reproduction and by inhibiting oxidative processes by interfering with catalytic formation of free radicals. Deofix has very low levels of toxicity when measured via a number of screening techniques.

Electronic structure probed with positronium: Theoretical viewpoint

NASA Astrophysics Data System (ADS)

Kuriplach, Jan; Barbiellini, Bernardo

2018-05-01

We inspect carefully how the positronium can be used to study the electronic structure of materials. Recent combined experimental and computational study [A.C.L. Jones et al., Phys. Rev. Lett. 117, 216402 (2016)] has shown that the positronium affinity can be used to benchmark the exchange-correlation approximations in copper. Here we investigate whether an improvement can be achieved by increasing the numerical precision of calculations and by employing the strongly constrained and appropriately normed (SCAN) scheme, and extend the study to other selected systems like aluminum and high entropy alloys. From the methodological viewpoint, the computations of the positronium affinity are further refined and an alternative way of determining the electron chemical potential using charged supercells is examined.

Characterization of calcineurin-dependent response element binding protein and its involvement in copper-metallothionein gene expression in Neurospora

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Kalari Satish; Ravi Kumar, B.; Siddavattam, Dayananda

2006-07-07

In continuation of our recent observations indicating the presence of a lone calcineurin-dependent response element (CDRE) in the -3730 bp upstream region of copper-induced metallothionein (CuMT) gene of Neurospora [K.S. Kumar, S. Dayananda, C. Subramanyam, Copper alone, but not oxidative stress, induces copper-metallothionein gene in Neurospora crassa, FEMS Microbiol. Lett. 242 (2005) 45-50], we isolated and characterized the CDRE-binding protein. The cloned upstream region of CuMT gene was used as the template to specifically amplify CDRE element, which was immobilized on CNBr-activated Sepharose 4B for use as the affinity matrix to purify the CDRE binding protein from nuclear extracts obtainedmore » from Neurospora cultures grown in presence of copper. Two-dimensional gel electrophoresis of the affinity purified protein revealed the presence of a single 17 kDa protein, which was identified and characterized by MALDI-TOF. Peptide mass finger printing of tryptic digests and analysis of the 17 kDa protein matched with the regulatory {beta}-subunit of calcineurin (Ca{sup 2+}-calmodulin dependent protein phosphatase). Parallel identification of nuclear localization signals in this protein by in silico analysis suggests a putative role for calcineurin in the regulation of CuMT gene expression.« less

Monolith-based immobilized metal affinity chromatography increases production efficiency for plasmid DNA purification.

PubMed

Shin, Min Jae; Tan, Lihan; Jeong, Min Ho; Kim, Ji-Heung; Choe, Woo-Seok

2011-08-05

Immobilized metal affinity monolith column as a new class of chromatographic support is shown to be superior to conventional particle-based column as plasmid DNA (pDNA) purification platform. By harnessing the affinity of endotoxin to copper ions in the solution, a majority of endotoxin (90%) was removed from the alkaline cell lysate using CuCl(2)-induced precipitation. RNA and remaining endotoxin were subsequently removed to below detection limit with minimal loss of pDNA using either monolith or particle-based column. Monolith column has the additional advantage of feed concentration and flowrate-independent dynamic binding capacity for RNA molecules, enabling purification process to be conducted at high feed RNA concentration and flowrate. The use of monolith column gives three fold increased productivity of pDNA as compared to particle-based column, providing a more rapid and economical platform for pDNA purification. Copyright © 2011 Elsevier B.V. All rights reserved.

Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in 64Cu PET Imaging for Alzheimer's Disease.

PubMed

Sharma, Anuj K; Schultz, Jason W; Prior, John T; Rath, Nigam P; Mirica, Liviu M

2017-11-20

Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, 11 C and 18 F, have short half-lives, and their usage is thus somewhat limited. By comparison, the 64 Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu 2+ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid β fibrillar aggregates. Determination of the protonation constants (pK a values) and stability constants (log β values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel 64 Cu PET imaging agents for Alzheimer's disease.

Growth of copper-benzene-1,3,5-tricarboxylate on boron nitride nanotubes and application of the composite in methane sensing

NASA Astrophysics Data System (ADS)

Xiang, Cuili; Chen, Ting; Zhang, Haitao; Zou, Yongjin; Chu, Hailiang; Zhang, Huanzhi; Xu, Fen; Sun, Lixian; Tang, Chengying

2017-12-01

A new composite material based on copper-benzene-1,3,5-tricarboxylate (Cu-BTC) deposited on boron nitride nanotubes (BNNTs) in a hydrothermal process were investigated for methane (CH4) sensing. The composite was characterized by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The Cu-BTC deposited on the BNNTs had an average grain size of 80 nm. The sensing performance of the as-grown product was studied for different concentrations of CH4 (20-200 ppm) at 150 °C. The results revealed that the Cu-BTC/BNNT composite exhibited high sensitivity and selectivity toward CH4. The good sensing performance of the composite was attributed to the high surface area and high affinity of Cu-BTC for CH4, which would allow the composite to act like a preconcentrator for CH4 gas sensing.

Towards a selective adsorbent for arsenate and selenite in the presence of phosphate: Assessment of adsorption efficiency, mechanism, and binary separation factors of the chitosan-copper complex.

PubMed

Yamani, Jamila S; Lounsbury, Amanda W; Zimmerman, Julie B

2016-01-01

The potential for a chitosan-copper polymer complex to select for the target contaminants in the presence of their respective competitive ions was evaluated by synthesizing chitosan-copper beads (CCB) for the treatment of (arsenate:phosphate), (selenite:phosphate), and (selenate:sulfate). Based on work by Rhazi et al., copper (II) binds to the amine moiety on the chitosan backbone as a monodentate complex (Type I) and as a bidentate complex crosslinking two polymer chains (Type II), depending on pH and copper loading. In general, the Type I complex exists alone; however, beyond threshold conditions of pH 5.5 during synthesis and a copper loading of 0.25 mol Cu(II)/mol chitosan monomer, the Type I and Type II complexes coexist. Subsequent chelation of this chitosan-copper ligand to oxyanions results in enhanced and selective adsorption of the target contaminants in complex matrices with high background ion concentrations. With differing affinities for arsenate, selenite, and phosphate, the Type I complex favors phosphate chelation while the Type II complex favors arsenate chelation due to electrostatic considerations and selenite chelation due to steric effects. No trend was exhibited for the selenate:sulfate system possibly due to the high Ksp of the corresponding copper salts. Binary separation factors, α12, were calculated for the arsenate-phosphate and selenite-phosphate systems, supporting the mechanistic hypothesis. While, further research is needed to develop a synthesis method for the independent formation of the Type II complexes to select for target contaminants in complex matrices, this work can provide initial steps in the development of a selective adsorbent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distinctive EPR signals provide an understanding of the affinity of bis-(3-hydroxy-4-pyridinonato) copper(II) complexes for hydrophobic environments.

PubMed

Rangel, Maria; Leite, Andreia; Silva, André M N; Moniz, Tânia; Nunes, Ana; Amorim, M João; Queirós, Carla; Cunha-Silva, Luís; Gameiro, Paula; Burgess, John

2014-07-07

In this work we report the synthesis and characterization of a set of 3-hydroxy-4-pyridinone copper(ii) complexes with variable lipophilicity. EPR spectroscopy was used to characterize the structure of copper(ii) complexes in solution, and as a tool to gain insight into solvent interactions. EPR spectra of solutions of the [CuL2] complexes recorded in different solvents reveal the presence of two copper species whose ratio depends on the nature of the solvent. Investigation of EPR spectra in the pure solvents methanol, dimethylsulfoxide, dichloromethane and their 50% (v/v) mixtures with toluene allowed the characterization of two types of copper signals (gzz = 2.30 and gzz = 2.26) whose spin-Hamiltonian parameters are consistent with solvated and non-solvated square-planar copper(ii) complexes. Regarding the potential biological application of ligands and complexes and to get insight into the partition properties in water-membrane interfaces, EPR spectra were also obtained in water-saturated octanol, an aqueous solution buffered at pH = 7.4 and liposome suspensions, for three compounds representative of different hydro-lipophilic balances. Analysis of the EPR spectra obtained in liposomes allowed establishment of the location of the complexes in the water and lipid phases. In view of the results of this work we put forward the use of EPR spectroscopy to assess the affinity of copper(ii) complexes for a hydrophobic environment and also to obtain indirect information about the lipophilicity of the ligands and similar EPR silent complexes.

On-demand oil-water separation via low-voltage wettability switching of core-shell structures on copper substrates

NASA Astrophysics Data System (ADS)

Kung, Chun Haow; Zahiri, Beniamin; Sow, Pradeep Kumar; Mérida, Walter

2018-06-01

A copper mesh with dendritic copper-oxide core-shell structure is prepared using an additive-free electrochemical deposition strategy for on-demand oil-water separation. Electrochemical manipulation of the oxidation state of the copper oxide shell phase results in opposite affinities towards water and oil. The copper mesh can be tuned to manifest both superhydrophobic and superoleophilic properties to enable oil-removal. Conversely, switching to superhydrophilic and underwater superoleophobic allows water-removal. These changes correspond to the application of small reduction voltages (<1.5 V) and subsequent air drying. In the oil-removal mode, heavy oil selectively passes through the mesh while water is retained; in water-removal mode, the mesh allows water to permeate but blocks light oil. The smart membrane achieved separation efficiencies higher than 98% for a series of oil-water mixtures. The separation efficiency remains high with less than 5% variation after 30 cycles of oil-water separation in both modes. The switchable wetting mechanism is demonstrated with the aid of microstructural and electrochemical analysis and based on the well-known Cassie-Baxter and Wenzel theories. The selective removal of water or oil from the oil-water mixtures is driven solely by gravity and yields high efficiency and recyclability. The potential applications for the relevant technologies include oil spills cleanup, fuel purification, and wastewater treatment.

Online immunocapture ICP-MS for the determination of the metalloprotein ceruloplasmin in human serum.

PubMed

Bernevic, Bogdan; El-Khatib, Ahmed H; Jakubowski, Norbert; Weller, Michael G

2018-04-02

The human copper-protein ceruloplasmin (Cp) is the major copper-containing protein in the human body. The accurate determination of Cp is mandatory for the reliable diagnosis of several diseases. However, the analysis of Cp has proven to be difficult. The aim of our work was a proof of concept for the determination of a metalloprotein-based on online immunocapture ICP-MS. The immuno-affinity step is responsible for the enrichment and isolation of the analyte from serum, whereas the compound-independent quantitation with ICP-MS delivers the sensitivity, precision, and large dynamic range. Off-line ELISA (enzyme-linked immunosorbent assay) was used in parallel to confirm the elution profile of the analyte with a structure-selective method. The total protein elution was observed with the 32 S mass trace. The ICP-MS signals were normalized on a 59 Co signal. The human copper-protein Cp could be selectively determined. This was shown with pure Cp and with a sample of human serum. The good correlation with off-line ELISA shows that Cp could be captured and eluted selectively from the anti-Cp affinity column and subsequently determined by the copper signal of ICP-MS.

Methanobactin and the Link between Copper and Bacterial Methane Oxidation

PubMed Central

Semrau, Jeremy D.; Murrell, J. Colin; Gallagher, Warren H.; Dennison, Christopher; Vuilleumier, Stéphane

2016-01-01

SUMMARY Methanobactins (mbs) are low-molecular-mass (<1,200 Da) copper-binding peptides, or chalkophores, produced by many methane-oxidizing bacteria (methanotrophs). These molecules exhibit similarities to certain iron-binding siderophores but are expressed and secreted in response to copper limitation. Structurally, mbs are characterized by a pair of heterocyclic rings with associated thioamide groups that form the copper coordination site. One of the rings is always an oxazolone and the second ring an oxazolone, an imidazolone, or a pyrazinedione moiety. The mb molecule originates from a peptide precursor that undergoes a series of posttranslational modifications, including (i) ring formation, (ii) cleavage of a leader peptide sequence, and (iii) in some cases, addition of a sulfate group. Functionally, mbs represent the extracellular component of a copper acquisition system. Consistent with this role in copper acquisition, mbs have a high affinity for copper ions. Following binding, mbs rapidly reduce Cu2+ to Cu1+. In addition to binding copper, mbs will bind most transition metals and near-transition metals and protect the host methanotroph as well as other bacteria from toxic metals. Several other physiological functions have been assigned to mbs, based primarily on their redox and metal-binding properties. In this review, we examine the current state of knowledge of this novel type of metal-binding peptide. We also explore its potential applications, how mbs may alter the bioavailability of multiple metals, and the many roles mbs may play in the physiology of methanotrophs. PMID:26984926

Selective Removal of Hemoglobin from Blood Using Hierarchical Copper Shells Anchored to Magnetic Nanoparticles

PubMed Central

Wang, Yaokun; Yan, Mingyang

2017-01-01

Hierarchical copper shells anchored on magnetic nanoparticles were designed and fabricated to selectively deplete hemoglobin from human blood by immobilized metal affinity chromatography. Briefly, CoFe2O4 nanoparticles coated with polyacrylic acid were first synthesized by a one-pot solvothermal method. Hierarchical copper shells were then deposited by immobilizing Cu2+ on nanoparticles and subsequently by reducing between the solid CoFe2O4@COOH and copper solution with NaBH4. The resulting nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, and vibrating sample magnetometry. The particles were also tested against purified bovine hemoglobin over a range of pH, contact time, and initial protein concentration. Hemoglobin adsorption followed pseudo-second-order kinetics and reached equilibrium in 90 min. Isothermal data also fit the Langmuir model well, with calculated maximum adsorption capacity 666 mg g−1. Due to the high density of Cu2+ on the shell, the nanoparticles efficiently and selectively deplete hemoglobin from human blood. Taken together, the results demonstrate that the particles with hierarchical copper shells effectively remove abundant, histidine-rich proteins, such as hemoglobin from human blood, and thereby minimize interference in diagnostic and other assays. PMID:28316987

Holographic study of conventional and negative Poisson's ratio metallic foams - Elasticity, yield and micro-deformation

NASA Technical Reports Server (NTRS)

Chen, C. P.; Lakes, R. S.

1991-01-01

An experimental study by holographic interferometry is reported of the following material properties of conventional and negative Poisson's ratio copper foams: Young's moduli, Poisson's ratios, yield strengths and characteristic lengths associated with inhomogeneous deformation. The Young's modulus and yield strength of the conventional copper foam were comparable to those predicted by microstructural modeling on the basis of cellular rib bending. The reentrant copper foam exhibited a negative Poisson's ratio, as indicated by the elliptical contour fringes on the specimen surface in the bending tests. Inhomogeneous, non-affine deformation was observed holographically in both foam materials.

Copper Ferrocyanide Functionalized Core-Shell Magnetic Silica Composites for the Selective Removal of Cesium Ions from Radioactive Liquid Waste.

PubMed

Lee, Hyun Kyu; Yang, Da Som; Oh, Wonzin; Choi, Sang-June

2016-06-01

The copper ferrocyanide functionalized core-shell magnetic silica composite (mag@silica-CuFC) was prepared and was found to be easily separated from aqueous solutions by using magnetic field. The synthesized mag@silica-CuFC composite has a high sorption ability of Cs owing to its strong affinity for Cs as well as the high surface area of the supports. Cs sorption on the mag@silica-CuFC composite quickly reached the sorption equilibrium after 2 h of contact time. The effect of the presence of salts with a high concentration of up to 3.5 wt% on the efficiency of Cs sorption onto the composites was also studied. The maximum sorption ability was found to be maintained in the presence of up to 3.5 wt% of NaCl in the solution. Considering these results, the mag@silica-CuFC composite has great potential for use as an effective sorbent for the selective removal of radioactive Cs ions.

Neurokinin B and serum albumin limit copper binding to mammalian gonadotropin releasing hormone.

PubMed

Gul, Ahmad Samir; Tran, Kevin K; Jones, Christopher E

2018-02-26

Gonadotropin releasing hormone (GnRH) triggers secretion of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary gland. GnRH is able to bind copper, and both in vitro and in vivo studies have suggested that the copper-GnRH complex is more potent at triggering gonadotropin release than GnRH alone. However, it remains unclear whether copper-GnRH is the active species in vivo. To explore this we have estimated the GnRH-copper affinity and have examined whether GnRH remains copper-bound in the presence of serum albumin and the neuropeptide neurokinin B, both copper-binding proteins that GnRH will encounter in vivo. We show that GnRH has a copper dissociation constant of ∼0.9 × 10 -9  M, however serum albumin and neurokinin B can extract metal from the copper-GnRH complex. It is therefore unlikely that a copper-GnRH complex will survive transit through the pituitary portal circulation and that any effect of copper must occur outside the bloodstream in the absence of neurokinin B. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular Characterization of CTR-type Copper Transporters in an Oceanic Diatom, Thalassiosira oceanica 1005

NASA Astrophysics Data System (ADS)

Kong, L.; Price, N. M.

2016-02-01

Copper is an essential micronutrient for phytoplankton growth because of its role as a redox cofactor in electron transfer proteins in photosynthesis and respiration, and a potentially limiting resource in parts of the open sea. Thalassiosira oceanica 1005 can grow at inorganic copper concentrations varying from 10 fmol/L to 10 nmol/L by regulating copper uptake across plasma membrane. Four putative CTR-type copper transporter genes (ToCTR1, ToCTR2, ToCTR3.1 and ToCTR3.2) were identified by BLASTP search against the T. oceanica genome. Predicted gene models were revised by assembled mRNA sequencing transcripts and updated gene models contained all conserved features of characterized CTR-type copper transporters. ToCTR3.1 and ToCTR3.2 may arise from one another by gene duplication as they shared a sequence similarity of 97.6% with a peptide insertion of 5 amino acids at N-terminus of ToCTR3.1. The expression of ToCTR1, ToCTR2 and ToCTR3.1/3.2 was upregulated in low copper concentrations, but only ToCTR3.1/3.2 showed a significant increase (2.5 fold) in copper-starved cells. Both ToCTR3.1 and ToCTR3.2 restored growth of a yeast double mutant, Saccharomyces cerevisiae ctr1Δctr3Δ, in copper deficient medium. GFP-fused ToCTR expression showed that some ToCTR3.1 localized to the plasma membrane but a large portion was retained in the endoplasmic reticulum. Inefficient targeting of ToCTR3.1 to the yeast outer membrane may explain poorer growth compared to the Saccharomyces native ScCTR1 transformant. Thus, diatom CTR genes encoding CTR-type copper transporters show high-affinity copper uptake and their regulation may enable diatoms to survive in ocean environments containing a wide range of copper concentrations.

Water Adsorption and Dissociation on Polycrystalline Copper Oxides: Effects of Environmental Contamination and Experimental Protocol

DOE PAGES

Trotochaud, Lena; Head, Ashley R.; Pletincx, Sven; ...

2017-11-02

We use ambient-pressure X-ray photoelectron spectroscopy (APXPS) to study chemical changes, including hydroxylation and water adsorption, at copper oxide surfaces from ultrahigh vacuum to ambient relative humidities of ~5%. Polycrystalline CuO and Cu 2O surfaces were prepared by selective oxidation of metallic copper foils. For both oxides, hydroxylation occurs readily, even at high-vacuum conditions. Hydroxylation on both oxides plateaus near ~0.01% relative humidity (RH) at a coverage of ~1 monolayer. In contrast to previous studies, neither oxide shows significant accumulation of molecular water; rather, both surfaces show a high affinity for adventitious carbon contaminants. Results of isobaric and isothermic experimentsmore » are compared, and the strengths and potential drawbacks of each method are discussed. We also provide critical evaluations of the effects of the hot filament of the ion pressure gauge on the reactivity of gas-phase species, the peak fitting procedure on the quantitative analysis of spectra, and rigorous accounting of carbon contamination on data analysis and interpretation. Lastly, this work underscores the importance of considering experimental design and data analysis protocols during APXPS experiments with water vapor in order to minimize misinterpretations arising from these factors.« less

Water Adsorption and Dissociation on Polycrystalline Copper Oxides: Effects of Environmental Contamination and Experimental Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trotochaud, Lena; Head, Ashley R.; Pletincx, Sven

We use ambient-pressure X-ray photoelectron spectroscopy (APXPS) to study chemical changes, including hydroxylation and water adsorption, at copper oxide surfaces from ultrahigh vacuum to ambient relative humidities of ~5%. Polycrystalline CuO and Cu 2O surfaces were prepared by selective oxidation of metallic copper foils. For both oxides, hydroxylation occurs readily, even at high-vacuum conditions. Hydroxylation on both oxides plateaus near ~0.01% relative humidity (RH) at a coverage of ~1 monolayer. In contrast to previous studies, neither oxide shows significant accumulation of molecular water; rather, both surfaces show a high affinity for adventitious carbon contaminants. Results of isobaric and isothermic experimentsmore » are compared, and the strengths and potential drawbacks of each method are discussed. We also provide critical evaluations of the effects of the hot filament of the ion pressure gauge on the reactivity of gas-phase species, the peak fitting procedure on the quantitative analysis of spectra, and rigorous accounting of carbon contamination on data analysis and interpretation. Lastly, this work underscores the importance of considering experimental design and data analysis protocols during APXPS experiments with water vapor in order to minimize misinterpretations arising from these factors.« less

Molecular Basis of the Bohr Effect in Arthropod Hemocyanin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirota, S.; Kawahara, T; Beltramini, M

2008-01-01

Flash photolysis and K-edge x-ray absorption spectroscopy (XAS) were used to investigate the functional and structural effects of pH on the oxygen affinity of three homologous arthropod hemocyanins (Hcs). Flash photolysis measurements showed that the well-characterized pH dependence of oxygen affinity (Bohr effect) is attributable to changes in the oxygen binding rate constant, kon, rather than changes in koff. In parallel, coordination geometry of copper in Hc was evaluated as a function of pH by XAS. It was found that the geometry of copper in the oxygenated protein is unchanged at all pH values investigated, while significant changes were observedmore » for the deoxygenated protein as a function of pH. The interpretation of these changes was based on previously described correlations between spectral lineshape and coordination geometry obtained for model compounds of known structure A pH-dependent change in the geometry of cuprous copper in the active site of deoxyHc, from pseudotetrahedral toward trigonal was assigned from the observed intensity dependence of the 1s ? 4pz transition in x-ray absorption near edge structure (XANES) spectra. The structural alteration correlated well with increase in oxygen affinity at alkaline pH determined in flash photolysis experiments. These results suggest that the oxygen binding rate in deoxyHc depends on the coordination geometry of Cu(I) and suggest a structural origin for the Bohr effect in arthropod Hcs.« less

The impact of tertiary wastewater treatment on copper and zinc complexation.

PubMed

Constantino, C; Gardner, M; Comber, S D W; Scrimshaw, M D; Ellor, B

2015-01-01

Tightening quality standards for European waters has seen a move towards enhanced wastewater treatment technologies such as granulated organic carbon treatment and ozonation. Although these technologies are likely to be successful in degrading certain micro-organic contaminants, these may also destroy compounds which would otherwise complex and render metals significantly less toxic. This study examined the impact of enhanced tertiary treatment on the capacity of organic compounds within sewage effluents to complex copper and zinc. The data show that granulated organic carbon treatment removes a dissolved organic carbon (DOC) fraction that is unimportant to complexation such that no detrimental impact on complexation or metal bioavailability is likely to occur from this treatment type. High concentrations of ozone (>1 mg O3/mg DOC) are, however, likely to impact the complexation capacity for copper although this is unlikely to be important at the concentrations of copper typically found in effluent discharges or in rivers. Ozone treatment did not affect zinc complexation capacity. The complexation profiles of the sewage effluents show these to contain a category of non-humic ligand that appears unaffected by tertiary treatment and which displays a high affinity for zinc, suggesting these may substantially reduce the bioavailability of zinc in effluent discharges. The implication is that traditional metal bioavailability assessment approaches such as the biotic ligand model may overestimate zinc bioavailability in sewage effluents and effluent-impacted waters.

Role of an archaeal PitA transporter in the copper and arsenic resistance of Metallosphaera sedula, an extreme thermoacidophile.

PubMed

McCarthy, Samuel; Ai, Chenbing; Wheaton, Garrett; Tevatia, Rahul; Eckrich, Valerie; Kelly, Robert; Blum, Paul

2014-10-01

Thermoacidophilic archaea, such as Metallosphaera sedula, are lithoautotrophs that occupy metal-rich environments. In previous studies, an M. sedula mutant lacking the primary copper efflux transporter, CopA, became copper sensitive. In contrast, the basis for supranormal copper resistance remained unclear in the spontaneous M. sedula mutant, CuR1. Here, transcriptomic analysis of copper-shocked cultures indicated that CuR1 had a unique regulatory response to metal challenge corresponding to the upregulation of 55 genes. Genome resequencing identified 17 confirmed mutations unique to CuR1 that were likely to change gene function. Of these, 12 mapped to genes with annotated function associated with transcription, metabolism, or transport. These mutations included 7 nonsynonymous substitutions, 4 insertions, and 1 deletion. One of the insertion mutations mapped to pseudogene Msed_1517 and extended its reading frame an additional 209 amino acids. The extended mutant allele was identified as a homolog of Pho4, a family of phosphate symporters that includes the bacterial PitA proteins. Orthologs of this allele were apparent in related extremely thermoacidophilic species, suggesting M. sedula naturally lacked this gene. Phosphate transport studies combined with physiologic analysis demonstrated M. sedula PitA was a low-affinity, high-velocity secondary transporter implicated in copper resistance and arsenate sensitivity. Genetic analysis demonstrated that spontaneous arsenate-resistant mutants derived from CuR1 all underwent mutation in pitA and nonselectively became copper sensitive. Taken together, these results point to archaeal PitA as a key requirement for the increased metal resistance of strain CuR1 and its accelerated capacity for copper bioleaching. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Role of an Archaeal PitA Transporter in the Copper and Arsenic Resistance of Metallosphaera sedula, an Extreme Thermoacidophile

PubMed Central

McCarthy, Samuel; Ai, Chenbing; Wheaton, Garrett; Tevatia, Rahul; Eckrich, Valerie; Kelly, Robert

2014-01-01

Thermoacidophilic archaea, such as Metallosphaera sedula, are lithoautotrophs that occupy metal-rich environments. In previous studies, an M. sedula mutant lacking the primary copper efflux transporter, CopA, became copper sensitive. In contrast, the basis for supranormal copper resistance remained unclear in the spontaneous M. sedula mutant, CuR1. Here, transcriptomic analysis of copper-shocked cultures indicated that CuR1 had a unique regulatory response to metal challenge corresponding to the upregulation of 55 genes. Genome resequencing identified 17 confirmed mutations unique to CuR1 that were likely to change gene function. Of these, 12 mapped to genes with annotated function associated with transcription, metabolism, or transport. These mutations included 7 nonsynonymous substitutions, 4 insertions, and 1 deletion. One of the insertion mutations mapped to pseudogene Msed_1517 and extended its reading frame an additional 209 amino acids. The extended mutant allele was identified as a homolog of Pho4, a family of phosphate symporters that includes the bacterial PitA proteins. Orthologs of this allele were apparent in related extremely thermoacidophilic species, suggesting M. sedula naturally lacked this gene. Phosphate transport studies combined with physiologic analysis demonstrated M. sedula PitA was a low-affinity, high-velocity secondary transporter implicated in copper resistance and arsenate sensitivity. Genetic analysis demonstrated that spontaneous arsenate-resistant mutants derived from CuR1 all underwent mutation in pitA and nonselectively became copper sensitive. Taken together, these results point to archaeal PitA as a key requirement for the increased metal resistance of strain CuR1 and its accelerated capacity for copper bioleaching. PMID:25092032

Copper(II)-based metal affinity chromatography for the isolation of the anticancer agent bleomycin from Streptomyces verticillus culture.

PubMed

Gu, Jiesi; Codd, Rachel

2012-10-01

The glycopeptide-based bleomycins are structurally complex natural products produced by Streptomyces verticillus used in combination therapy against testicular and other cancers. Bleomycin has a high affinity towards a range of transition metal ions with the 1:1 Fe(II) complex relevant to its mechanism of action in vivo and the 1:1 Cu(II) complex relevant to its production from culture. The affinity between Cu(II) and bleomycin was the underlying principle for using Cu(II)-based metal affinity chromatography in this work to selectively capture bleomycin from crude S. verticillus culture. A solution of standard bleomycin was retained at a binding capacity of 300 nmol mL(-1) on a 1-mL bed volume of Cu(II)-loaded iminodiacetate (IDA) resin at pH 9 via the formation of the heteroleptic immobilized complex [Cu(IDA)(bleomycin)]. Bleomycin was eluted from the resin at pH 5 as the metal-free ligand under conditions where pK(a) (IDA)

Surface functionalization of copper via oxidative graft polymerization of 2,2'-bithiophene and immobilization of silver nanoparticles for combating biocorrosion.

PubMed

Wan, Dong; Yuan, Shaojun; Neoh, K G; Kang, E T

2010-06-01

An environmentally benign approach to surface modification was developed to impart copper surface with enhanced resistance to corrosion, bacterial adhesion and biocorrosion. Oxidative graft polymerization of 2,2'-bithiophene from the copper surface with self-assembled 2,2'-bithiophene monolayer, and subsequent reduction of silver ions to silver nanoparticles (Ag NPs) on the surface, give rise to a homogeneous bithiophene polymer (PBT) film with densely coupled Ag NPs on the copper surface (Cu-g-PBT-Ag NP surface). The immobilized Ag NPs were found to significantly inhibit bacterial adhesion and enhance the antibacterial properties of the PBT modified copper surface. The corrosion inhibition performance of the functionalized copper substrates was evaluated by Tafel polarization curves and electrochemical impedance spectroscopy. Arising from the chemical affinity of thiols for the noble and coinage metals, the copper surface functionalized with both PBT brushes and Ag NPs also exhibits long-term stability, and is thus potentially useful for combating the combined problems of corrosion and biocorrosion in harsh marine and aquatic environments.

Holographic study of non-affine deformation in copper foam with a negative Poisson's ratio of -0.8

NASA Technical Reports Server (NTRS)

Chen, C. P.; Lakes, R. S.

1993-01-01

While conventional foams have positive Poisson's ratios (become smaller in cross-section when stretched and larger when compressed), foam materials have recently been defined which possess 'reentrant' cellular architectures; in these, inwardly-protruding cell ribs are responsible for negative Poisson's ratio behavior, yielding greater resilience than conventional foams. Double-exposure holographic interferometry is presently used to examine the microdeformation of a reentrant copper foam. Attention is given to the nonaffine (inhomogeneous) deformation of this foam.

Electron transfer between cytochrome. alpha. and copper A in cytochrome c oxidase: A perturbed equilibrium study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgan, J.E.; Li, P.M.; Jang, D.J.

1989-08-22

Intramolecular electron transfer in partially reduced cytochrome c oxidase has been studied by the perturbed equilibrium method. The authors have prepared a three-electron-reduced, CO-inhibited form of the enzyme in which cytochrome a and copper A are partially reduced and in an intramolecular redox equilibrium. When these samples were irradiated with a nitrogen laser to photodissociate the bound CO, changes in absorbance at 598 and 830 nm were observed which were consistent with a fast electron transfer from cytochrome a to copper A. The absorbance changes at 598 nm gave an apparent rate of 17,000 {plus minus} 2,000 s{sup {minus}1} (1more » {sigma}), at pH 7.0 and 25.5{degree}C. These changes were not observed in either the CO mixed-valence or the CO-inhibited fully reduced forms of the enzyme. The rate was fastest at about pH 8.0, falling off toward both lower and higher pHs. There was a small but clear temperature dependence. The process was also observed in the cytochrome c-cytochrome c oxidase high-affinity complex. The electron equilibration measured between cytochrome {alpha} and copper A is far faster than any rate measured or inferred previously for this process.« less

The role of siderophores in metal homeostasis of members of the genus Burkholderia.

PubMed

Mathew, Anugraha; Jenul, Christian; Carlier, Aurelien L; Eberl, Leo

2016-02-01

Although members of the genus Burkholderia can utilize a high-affinity iron uptake system to sustain growth under iron-limiting conditions, many strains also produce siderophores, suggesting that they may serve alternative functions. Here we demonstrate that the two Burkholderia siderophores pyochelin and ornibactin can protect the cells from metal toxicity and thus play an alternative role in metal homeostasis. We also demonstrate that metals such as copper and zinc induce the production of ornibactin. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Cu(I)/Cu(II) mixed-valence surface complexes of S-[(2-hydroxyamino)-2-oxoethyl]-N,N-dibutyldithiocarbamate: Hydrophobic mechanism to malachite flotation.

PubMed

Liu, Sheng; Zhong, Hong; Liu, Guangyi; Xu, Zhenghe

2018-02-15

Hydroxamate and sulfhydryl surfactants are effective collectors for flotation of copper minerals. The combination application of hydroxamate and sulfhydryl collectors has been proved to be an effective approach for improving the flotation recovery of non-sulfide copper minerals. A surfactant owing both hydroxamate and dithiocarbamate groups might exhibit strong affinity to non-sulfide copper minerals through double sites adsorption, rendering an enhanced hydrophobization to non-sulfide copper minerals flotation. The flotation performance of S-[(2-hydroxyamino)-2-oxoethyl]- N,N-dibutyldithiocarbamate (HABTC) to malachite, calcite and quartz were first evaluated through systematic micro-flotation experiments. HABTC's hydrophobic mechanism to malachite was further investigated and analyzed by zeta potential, Fourier transform infrared spectroscopy (FTIR), time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). The micro-flotation results demonstrated HABTC was an excellent collector for malachite flotation and exhibited favorable selectivity for flotation separation of malachite from quartz or calcite under pH 8.5-10.3. Zeta potential and FTIR implied that HABTC might bond with the surface copper atoms of malachite, with releasing the H + ions of its hydroxamate group into pulp. ToF-SIMS provided clear evidences that the Cu-hydroxamate and Cu-dithiocarbamate groups were formed on malachite surfaces after HABTC adsorption. XPS revealed that Cu(I)/Cu(II) mixed-valence surface complexes of HABTC anchored on malachite through formation of Cu(I)S and Cu(II)O bonds, accompanying with reduction of partial surface Cu(II) to Cu(I). The Cu(I)/Cu(II) mixed-valence double chelating character and "chair"-shape N,N-dibutyldithiocarbamate hydrophobic group, resulting in an enhanced affinity and hydrophobization of HABTC to malachite flotation. Copyright © 2017 Elsevier Inc. All rights reserved.

Elucidating the mechanism for the reduction of nitrite by copper nitrite reductase--a contribution from quantum chemical studies.

PubMed

De Marothy, S A; Blomberg, M R A; Siegbahn, P E M

2007-01-30

Density functional methods have been applied to investigate the properties of the active site of copper-containing nitrite reductases and possible reaction mechanisms for the enzyme catalysis. The results for a model of the active site indicate that a hydroxyl intermediate is not formed during the catalytic cycle, but rather a state with a protonated nitrite bound to the reduced copper. Electron affinity calculations indicate that reduction of the T2 copper site does not occur immediately after nitrite binding. Proton affinity calculations are indicative of substantial pK(a) differences between different states of the T2 site. The calculations further suggest that the reaction does not proceed until uptake of a second proton from the bulk solution. They also indicate that Asp-92 may play both a key role as a proton donor to the substrate, and a structural role in promoting catalysis. In the D92N mutant another base, presumably a nearby histidine (His-249) may take the role as the proton donor. On the basis of these model calculations and available experimental evidence, an ordered reaction mechanism for the reduction of nitrite is suggested. An investigation of the binding modes of the nitric oxide product and the nitrite substrate to the model site has also been made, indicating that nitric oxide prefers to bind in an end-on fashion to the reduced T2 site.

Immobilized metal ion affinity electrophoresis. A study with several model proteins containing histidine.

PubMed

Goubran-Botros, H; Nanak, E; Abdul Nour, J; Birkenmeir, G; Vijayalakshmi, M A

1992-04-24

Immobilized metal ion affinity electrophoresis (IMA-Elec) is one among the many methods derived from the immobilized metal ion affinity chromatography. Two approaches for incorporating the metal ligand, were studied. One was in the form of insoluble particulate material based on Sepharose 6B and the other in the form of soluble polymer based on polyethylene glycol (PEG) 5000. Both the polymers coupled with iminodiacetate and metallized with copper or zinc were used as ligands, incorporated into soluble agarose as the electrophoretic gel. Several histidine-containing model proteins were studied with both the systems and their metal binding strengths were determined as the dissociation constants, Kd. The results clearly demonstrated that the mechanism of protein recognition by immobilized copper or zinc via the accessible histidyl residues was maintained in the IMA-Elec system. Proteins with increasing numbers of histidine residues showed increasing binding strength (lower Kd values). While this basic mechanism was conserved, the supporting polymers (Sepharose 6B and the PEG 5000) showed significant differences in the metal binding to the protein. The polysaccharide Sepharose 6B enhanced the binding strength compared with PEG 5000. The optimum electrophoretic parameters were determined to be current intensities up to 20 mA and pH ca. 7.0. At pH greater than 8.0, a significant decrease in the affinity was observed, this decrease being greater with PEG 5000 than Sepharose 6B as supporting material.

The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences.

PubMed

Bossak, Karolina; Drew, Simon C; Stefaniak, Ewelina; Płonka, Dawid; Bonna, Arkadiusz; Bal, Wojciech

2018-05-01

Copper Transporter 1 (CTR1) is a homotrimeric membrane protein providing the main route of copper transport into eukaryotic cells from the extracellular milieu. Its N-terminal extracellular domain, rich in His and Met residues, is considered responsible for directing copper into the transmembrane channel. Most of vertebrate CTR1 proteins contain the His residue in position three from N-terminus, creating a well-known Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) site. CTR1 from humans, primates and many other species contains the Met-Asp-His (MDH) sequence, while some rodents including mouse have the Met-Asn-His (MNH) N-terminal sequence. CTR1 is thought to collect Cu(II) ions from blood copper transport proteins, including albumin, but previous reports indicated that the affinity of N-terminal peptide/domain of CTR1 is significantly lower than that of albumin, casting serious doubt on this aspect of CTR1 function. Using potentiometry and spectroscopic techniques we demonstrated that MDH-amide, a tripeptide model of human CTR1 N-terminus, binds Cu(II) with K of 1.3 × 10 13  M -1 at pH 7.4, ~13 times stronger than Human Serum Albumin (HSA), and MNH-amide is even stronger, K of 3.2 × 10 14  M -1 at pH 7.4. These results indicate that the N-terminus of CTR1 may serve as intermediate binding site during Cu(II) transfer from blood copper carriers to the transporter. MDH-amide, but not MNH-amide also forms a low abundance complex with non-ATCUN coordination involving the Met amine, His imidazole and Asp carboxylate. This species might assist Cu(II) relay down the peptide chain or its reduction to Cu(I), both steps necessary for the CTR1 function. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulation of copper and iron homeostasis by metal chelators: a possible chemotherapy for Alzheimer's disease.

PubMed

Robert, Anne; Liu, Yan; Nguyen, Michel; Meunier, Bernard

2015-05-19

With the increase of life expectancy of humans in more than two-thirds of the countries in the World, aging diseases are becoming the frontline health problems. Alzheimer's disease (AD) is now one of the major challenges in drug discovery, since, with the exception of memantine in 2003, all clinical trials with drug candidates failed over the past decade. If we consider that the loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions like copper linked to amyloids of different sizes, regulation of metal homeostasis is a key target. The difficulty for large copper-carrier proteins to directly extract copper ions from metalated amyloids might be considered as being at the origin of the rupture of the copper homeostasis regulation in AD brains. So, there is an urgent need for new specific metal chelators that should be able to regulate the homeostasis of metal ions, specially copper and iron, in AD brains. As a consequence of that concept, chelators promoting metal excretion from brain are not desired. One should favor ligands able to extract copper ions from sinks (amyloids being the major one) and to transfer these redox-active metal ions to copper-carrier proteins or copper-containing enzymes. Obviously, the affinity of these chelators for the metal ion should not be a sufficient criterion, but the metal specificity and the ability of the chelators to release the metal under specific biological conditions should be considered. Such an approach is still largely unexplored. The requirements for the chelators are very high (ability to cross the brain-blood barrier, lack of toxicity, etc.), few chemical series were proposed, and, among them, biochemical or biological data are scarce. As a matter of fact, the bioinorganic pharmacology of AD represents less than 1% of all articles dedicated to AD drug research. The major part of these articles deals with an old and rather toxic drug, clioquinol and related analogs, that do not efficiently extract copper from soluble amyloids. We have designed and developed new tetradendate ligands such as 21 and PA1637 based on bis(8-aminoquinolines) that are specific for copper chelation and are able to extract copper(II) from amyloids and then can release copper ion upon reduction with a biological reducing agent. These studies contribute to the understanding of the physicochemical properties of the tetradentate copper ligands compared with bidentate ligands like clioquinol. One of these copper ligands, PA1637, after selection with a nontransgenic mouse model that is able to efficiently monitor the loss of episodic memory, is currently under preclinical development.

Engineering Copper Carboxylate Functionalities on Water Stable Metal–Organic Frameworks for Enhancement of Ammonia Removal Capacities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joshi, Jayraj N.; Garcia-Gutierrez, Erika Y.; Moran, Colton M.

Functionalization of copper carboxylate groups on a series of UiO-66 metal organic framework (MOF) analogues and their corresponding impact on humid and dry ammonia adsorption behavior were studied. Relative locations of possible carboxylic acid binding sites for copper on the MOF analogues were varied on ligand and missing linker defect sites. Materials after copper incorporation exhibited increased water vapor and ammonia affinity during isothermal adsorption and breakthrough experiments, respectively. The introduction of copper markedly increased ammonia adsorption capacities for all adsorbents possessing carboxyl binding sites. In particular, the new MOF UiO-66-(COOCu)2 displayed the highest ammonia breakthrough capacities of 6.38 andmore » 6.84 mmol g–1 under dry and humid conditions, respectively, while retaining crystallinity and porosity. Relative carboxylic acid site locations were also found to impact sorbent stability, as missing linker defect functionalized materials degraded under humid conditions after copper incorporation. Postsynthetic metal insertion provides a method for adding sites that are analogous to open metal sites while maintaining good structural stability.« less

Aspartate aminotransferase is potently inhibited by copper complexes: Exploring copper complex-binding proteome.

PubMed

Jia, Yuqi; Lu, Liping; Yuan, Caixia; Feng, Sisi; Zhu, Miaoli

2017-05-01

Recent researches indicated that a copper complex-binding proteome that potently interacted with copper complexes and then influenced cellular metabolism might exist in organism. In order to explore the copper complex-binding proteome, a copper chelating ion-immobilized affinity chromatography (Cu-IMAC) column and mass spectrometry were used to separate and identify putative Cu-binding proteins in primary rat hepatocytes. A total of 97 putative Cu-binding proteins were isolated and identified. Five higher abundance proteins, aspartate aminotransferase (AST), malate dehydrogenase (MDH), catalase (CAT), calreticulin (CRT) and albumin (Alb) were further purified using a SP-, and (or) Q-Sepharose Fast Flow column. The interaction between the purified proteins and selected 11 copper complexes and CuCl 2 was investigated. The enzymes inhibition tests demonstrated that AST was potently inhibited by copper complexes while MDH and CAT were weakly inhibited. Schiff-based copper complexes 6 and 7 potently inhibited AST with the IC 50 value of 3.6 and 7.2μM, respectively and exhibited better selectivity over MDH and CAT. Fluorescence titration results showed the two complexes tightly bound to AST with binding constant of 3.89×10 6 and 3.73×10 6 M -1 , respectively and a stoichiometry ratio of 1:1. Copper complex 6 was able to enter into HepG2 cells and further inhibit intracellular AST activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Studies of Copper, Silver, and Gold Cluster Anions: Evidence of Electronic Shell Structure.

NASA Astrophysics Data System (ADS)

Pettiette, Claire Lynn

A new Ultraviolet Magnetic Time-of-Flight Photoelectron Spectrometer (MTOFPES) has been developed for the study of the electronic structure of clusters produced in a pulsed supersonic molecular beam. This is the first technique which has been successful in probing the valence electronic states of metal clusters. The ultraviolet photoelectron spectra of negative cluster ions of the noble metals have been taken at several different photon energies. These are presented along with the electron affinity and HOMO-LUMO gap measurements for Cu_6^- to Cu_ {41}^-, using 4.66 eV and 6.42 eV detachment energies; Ag_3^- to Ag_{21}^-, using 6.42 eV detachment energy; and Au_3^ - to Au_{21}^-, using 6.42 eV and 7.89 eV detachment energies. The spectra provide the first detailed probes of the s valence electrons of the noble metal clusters. In addition, the 6.42 eV and 7.89 eV spectra probe the first one to two electron volts of the molecular orbitals of the d valence electrons of copper and gold clusters. The electron affinity and HOMO-LUMO gap measurements of the noble metal clusters agree with the predictions of the ellipsoidal shell model for mono-valent metal clusters. In particular, cluster numbers 8, 20, and 40--which correspond to the spherical shell closings of this model--have low electron affinities and large HOMO-LUMO gaps. The spectra of the gold cluster ions indicate that the molecular orbital energies of the cluster valence electrons are more widely spaced for gold than for copper or silver. This is to be expected for the heavy atom clusters when relativistic effects are taken into account.

Copper binding to soil fulvic and humic acids: NICA-Donnan modeling and conditional affinity spectra.

PubMed

Xu, Jinling; Tan, Wenfeng; Xiong, Juan; Wang, Mingxia; Fang, Linchuan; Koopal, Luuk K

2016-07-01

Binding of Cu(II) to soil fulvic acid (JGFA), soil humic acids (JGHA, JLHA), and lignite-based humic acid (PAHA) was investigated through NICA-Donnan modeling and conditional affinity spectrum (CAS). It is to extend the knowledge of copper binding by soil humic substances (HS) both in respect of enlarging the database of metal ion binding to HS and obtaining a good insight into Cu binding to the functional groups of FA and HA by using the NICA-Donnan model to unravel the intrinsic and conditional affinity spectra. Results showed that Cu binding to HS increased with increasing pH and decreasing ionic strength. The amount of Cu bound to the HAs was larger than the amount bound to JGFA. Milne's generic parameters did not provide satisfactory predictions for the present soil HS samples, while material-specific NICA-Donnan model parameters described and predicted Cu binding to the HS well. Both the 'low' and 'high' concentration fitting procedures indicated a substantial bidentate structure of the Cu complexes with HS. By means of CAS underlying NICA isotherm, which was scarcely used, the nature of the binding at different solution conditions for a given sample and the differences in binding mode were illustrated. It was indicated that carboxylic group played an indispensable role in Cu binding to HS in that the carboxylic CAS had stronger conditional affinity than the phenolic distribution due to its large degree of proton dissociation. The fact was especially true for JGFA and JLHA which contain much larger amount of carboxylic groups, and the occupation of phenolic sites by Cu was negligible. Comparable amounts of carboxylic and phenolic groups on PAHA and JGHA, increased the occupation of phenolic type sites by Cu. The binding strength of PAHA-Cu and JGHA-Cu was stronger than that of JGFA-Cu and JLHA-Cu. The presence of phenolic groups increased the chance of forming more stable complexes, such as the salicylate-Cu or catechol-Cu type structures. Copyright © 2016. Published by Elsevier Inc.

Elucidation of the factors affecting the oxidative activity of Acremonium sp. HI-25 ascorbate oxidase by an electrochemical approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murata, Kenichi; Nakamura, Nobuhumi; Ohno, Hiroyuki

Steady-state kinetics of Acremonium sp. HI-25 ascorbate oxidase toward p-hydroquinone derivatives have been examined by using an electrochemical analysis based on the theory of steady-state bioelectrocatalysis. The electrochemical technique has enabled one to examine the influence of electronic and chemical properties of substrates on the activity. It was proven that the oxidative activity of ascorbate oxidase was dominated by the highly selective substrate-binding affinity based on electrostatic interaction beyond the one-electron redox potential difference between ascorbate oxidase's type 1 copper site and substrate.

The Lumenal Loop Met672–Pro707 of Copper-transporting ATPase ATP7A Binds Metals and Facilitates Copper Release from the Intramembrane Sites*

PubMed Central

Barry, Amanda N.; Otoikhian, Adenike; Bhatt, Sujata; Shinde, Ujwal; Tsivkovskii, Ruslan; Blackburn, Ninian J.; Lutsenko, Svetlana

2011-01-01

The copper-transporting ATPase ATP7A has an essential role in human physiology. ATP7A transfers the copper cofactor to metalloenzymes within the secretory pathway; inactivation of ATP7A results in an untreatable neurodegenerative disorder, Menkes disease. Presently, the mechanism of ATP7A-mediated copper release into the secretory pathway is not understood. We demonstrate that the characteristic His/Met-rich segment Met672–Pro707 (HM-loop) that connects the first two transmembrane segments of ATP7A is important for copper release. Mutations within this loop do not prevent the ability of ATP7A to form a phosphorylated intermediate during ATP hydrolysis but inhibit subsequent dephosphorylation, a step associated with copper release. The HM-loop inserted into a scaffold protein forms two structurally distinct binding sites and coordinates copper in a mixed His-Met environment with an ∼2:1 stoichiometry. Binding of either copper or silver, a Cu(I) analog, induces structural changes in the loop. Mutations of 4 Met residues to Ile or two His-His pairs to Ala-Gly decrease affinity for copper. Altogether, the data suggest a two-step process, where copper released from the transport sites binds to the first His(Met)2 site, triggering a structural change and binding to a second 2-coordinate His-His or His-Met site. We also show that copper binding within the HM-loop stabilizes Cu(I) and protects it from oxidation, which may further aid the transfer of copper from ATP7A to acceptor proteins. The mechanism of copper entry into the secretory pathway is discussed. PMID:21646353

Four-electron Reduction of Dioxygen by a Multicopper Oxidase, CueO, and Roles of Asp112 and Glu506 Located Adjacent to the Trinuclear Copper Center*S⃞

PubMed Central

Kataoka, Kunishige; Sugiyama, Ryosuke; Hirota, Shun; Inoue, Megumi; Urata, Kanae; Minagawa, Yoichi; Seo, Daisuke; Sakurai, Takeshi

2009-01-01

The mechanism of the four-electron reduction of dioxygen by a multicopper oxidase, CueO, was studied based on reactions of single and double mutants with Cys500, a type I copper ligand, and the noncoordinating Asp112 and Glu506, which form hydrogen bonds with the trinuclear copper center directly and indirectly via a water molecule. The reaction of C500S containing a vacant type I copper center produced intermediate I in an EPR-silent peroxide-bound form. The formation of intermediate I from C500S/D112N was restricted due to a reduction in the affinity of the trinuclear copper center for dioxygen. The state of intermediate I was realized to be the resting form of C500S/E506Q and C500S of the truncated mutant Δα5–7CueO, in which the 50 amino acids covering the substrate-binding site were removed. Reactions of the recombinant CueO and E506Q afforded intermediate II, a fully oxidized form different from the resting one, with a very broad EPR signal, g < 2, detectable only at cryogenic temperatures and unsaturated with high power microwaves. The lifetime of intermediate II was prolonged by the mutation at Glu506 involved in the donation of protons. The structure of intermediates I and II and the mechanism of the four-electron reduction of dioxygen driven by Asp112 and Glu506 are discussed. PMID:19297322

Petrogenesis of ore-bearing porphyry in non-subduction setting: a case study of the Eocene potassic intrusions in the western Yangtze Block

NASA Astrophysics Data System (ADS)

Liu, Zheng; Liao, Shi-Yong; Zhou, Qing; Zhang, Xin

2018-05-01

In the western Yangtze Block, abundant Eocene ( 38-34 Ma) potassic adakite-like intrusions and associated porphyry copper deposits are exposed in non-subduction setting, including Machangjing, Beiya, Binchuan, Habo and Tongchang intrusions. All these ore-bearing porphyries share many geochemical characteristics of adakite such as depletion in heavy rare earth elements (HREEs), enrichment in Sr and Ba, absence of negative Eu anomalies, high SiO2, Al2O3, Sr/Y, La/Yb and low Y, Yb contents. They also exhibit affinities of potassic rocks, e.g., alkali-rich, high K2O/Na2O ratios and enrichment in light rare earth elements (LREEs) and large ion lithophile elements (LILEs). Their Sr-Nd isotopic ratios are similar to coeval shoshonitic lamprophyres. Geochemical data indicate that they were probably produced by partial melting of newly underplated potassic rocks sourced from a modified and enriched lithospheric mantle. These underplated rocks have elevated oxygen fugacity, water and copper contents, with high metallogenic potential. We propose that all the studied potassic rocks were emplaced in a post-collisional setting, associated with the local removal of lithospheric mantle.

Assessing change in diet and biological affinity between the 4th and 3rd millennia cal BCE in the Portuguese Estremadura: a preliminary dental comparison of Feteira II and Bolores.

PubMed

Horwath, B C; Waterman, A J; Lillios, K T; Irish, J D

2014-04-01

Although the social and political changes accompanying the transition from the Neolithic through Copper Age, between the 4th and 3rd millennia cal BCE, in southwestern Iberia are reasonably well understood, much less is known about whether population movements and dietary changes accompanied these transformations. To address this question, human dental remains from the Middle through Late Neolithic site of Feteira II (3600-2900 cal BCE) and the Late Neolithic site of Bolores (2800-2600 cal BCE) in the Portuguese Estremadura were used to examine diet (microwear) and affinity (dental non-metrics). Microwear features were not found to be significantly different between Feteira II and Bolores, suggesting that the emergence of social complexity during this period did not result in large-scale changes in subsistence practices during the period of use at these sites. Using the Arizona State University Dental Anthropology System and supporting statistics, no significant difference between the samples from Feteira II and Bolores was observed, suggesting that no population replacement occurred between the Middle Neolithic and Late Neolithic/Copper Age. However, at Bolores there is some indication that there may have been demographic exchanges between southern Iberian and North African populations during the Late Neolithic/Copper Age. Copyright © 2013 Elsevier GmbH. All rights reserved.

Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hao; Zhang, Yikai; Zheng, Shanyuan

Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cellsmore » by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities of cisplatin.« less

Mechanisms of iron and copper-frataxin interactions.

PubMed

Han, T H L; Camadro, J M; Santos, R; Lesuisse, E; El Hage Chahine, J M; Ha-Duong, N T

2017-08-16

Frataxin is a mitochondrial protein whose deficiency is the cause of Friedreich's ataxia, a hereditary neurodegenerative disease. This protein plays a role in iron-sulfur cluster biosynthesis, protection against oxidative stress and iron metabolism. In an attempt to provide a better understanding of the role played by metals in its metabolic functions, the mechanisms of mitochondrial metal binding to frataxin in vitro have been investigated. A purified recombinant yeast frataxin homolog Yfh1 binds two Cu(ii) ions with a K d1 (Cu II ) of 1.3 × 10 -7 M and a K d2 (Cu II ) of 3.1 × 10 -4 M and a single Cu(i) ion with a higher affinity than for Cu(ii) (K d (Cu I ) = 3.2 × 10 -8 M). Mn(ii) forms two complexes with Yfh1 (K d1 (Mn II ) = 4.0 × 10 -8 M; K d2 (Mn II ) = 4.0 × 10 -7 M). Cu and Mn bind Yfh1 with higher affinities than Fe(ii). It is established for the first time that the mechanisms of the interaction of iron and copper with frataxin are comparable and involve three kinetic steps. The first step occurs in the 50-500 ms range and corresponds to a first metal uptake. This is followed by two other kinetic processes that are related to a second metal uptake and/or to a change in the conformation leading to thermodynamic equilibrium. Frataxin deficient Δyfh1 yeast cells exhibited a marked growth defect in the presence of exogenous Cu or Mn. Mitochondria from Δyfh1 strains also accumulated higher amounts of copper, suggesting a functional role of frataxin in vivo in copper homeostasis.

The water soluble peripherally tetra-substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines as new potential anticancer agents.

PubMed

Barut, Burak; Sofuoğlu, Ayşenur; Biyiklioglu, Zekeriya; Özel, Arzu

2016-09-28

In this study, [2-(2-morpholin-4-ylethoxy)ethoxy] group substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines 2-4 and their water soluble derivatives 2a, 3a and 4a were synthesized and the interactions of compounds 2a, 3a and 4a with CT-DNA and supercoiled pBR322 plasmid DNA were investigated. The results of binding experiments showed that these compounds were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 3a > 2a > 4a. DNA-photocleavage activities of compounds 2a, 3a and 4a were determined. These compounds cleaved supercoiled pBR322 plasmid DNA efficiently under irradiation at 650 nm for 2a and 4a, and at 750 nm for 3a. These compounds displayed remarkable inhibitory activities against topoisomerase I enzyme in a dose-dependent manner. All of these results suggest that these phthalocyanines might be suitable anticancer agents due to their strong binding affinities, significant cleavage activities and effective topoisomerase I inhibition.

Metal chelate affinity precipitation of RNA and purification of plasmid DNA

NASA Technical Reports Server (NTRS)

Balan, Sindhu; Murphy, Jason; Galaev, Igor; Kumar, Ashok; Fox, George E.; Mattiasson, Bo; Willson, Richard C.

2003-01-01

The affinity of metal chelates for amino acids, such as histidine, is widely used in purifying proteins, most notably through six-histidine 'tails'. We have found that metal affinity interactions can also be applied to separation of single-stranded nucleic acids through interactions involving exposed purines. Here we describe a metal affinity precipitation method to resolve RNA from linear and plasmid DNA. A copper-charged copolymer of N-isopropyl acrylamide (NIPAM) and vinyl imidazole (VI) is used to purify plasmid from an alkaline lysate of E. coli. The NIPAM units confer reversible solubility on the copolymer while the imidazole chelates metal ions in a manner accessible to interaction with soluble ligands. RNA was separated from the plasmid by precipitation along with the polymer in the presence of 800 mM NaCl. Bound RNA could be recovered by elution with imidazole and separated from copolymer by a second precipitation step. RNA binding showed a strong dependence on temperature and on the type of buffer used.

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

PubMed Central

Doñate, F; Juarez, J C; Burnett, M E; Manuia, M M; Guan, X; Shaw, D E; Smith, E L P; Timucin, C; Braunstein, M J; Batuman, O A; Mazar, A P

2008-01-01

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development. PMID:18253124

Glassy carbon electrode modified with polyanilne/ethylenediamine for detection of copper ions

NASA Astrophysics Data System (ADS)

Patil, Harshada K.; Deshmukh, Megha A.; Bodkhe, Gajanan A.; Shirsat, Mahendra D.

2018-05-01

Increasing water pollution is having high concern, since it creates the threats to all leaving organisms of existence. Industrial sewages have not only polluted the main stream lines of water, also the ground level water is having serious contaminations. Heavy metal ions are the pollutants which are not degradable and can be accumulated on living things ultimately the excess accumulation results into the serious concerns. Therefore, it is necessary to develop the sensors which can detect the heavy metal ions up to its maximum contamination limits. Conducting polymers are the materials which possess large application spectra. This investigation reports the electrochemically synthesized polyaniline (PANI) for modification of glassy carbon electrode (GCE). Ethylenediamine (EDA) - chelating ligand used for the modification of polyaniline so as to inculcate the selectivity toward copper ions Cu (II). The electrochemical cyclic voltammetry (CV) was used for the study of redox characteristics of PANI and influence of EDA modification. The result of CV has shown the reduced oxidation and reduction peak currents after modification indicating the domination of EDA. GCE modified with PANI/EDA was then employed for the detection of divalent copper ions and have shown the affinity toward Cu ions. The detection limit achieved was equal to 10mg/lit.

Mineralogical and Geochemical Study of Titanite Associated With Copper Mineralization in the Hopper Property, Yukon Territory, Canada

NASA Astrophysics Data System (ADS)

Blumenthal, V. H.; Linnen, R. L.

2009-05-01

Copper mineralization in central Yukon is well known, but the metallogeny of the Ruby Range batholith, west of the copper belt, is poorly understood. The Hopper property, situated in the south western part of the Yukon in the Yukon-Tanana terrane, contains copper mineralization hosted by granodiorite and quartz feldspar porphyry of cal-alkaline affinity. These rock units, interpreted to be part of the Ruby Range batholith, intruded metasediments of the Ashihik Metamorphic Suite rocks. Mafic dykes cross cut the intrusion followed by aplite dykes. Small occurrences of skarn also occur in the area and some of these contain copper mineralization. The copper mineralization at the Hopper property appears to have a porphyry-type affinity. However, it is associated with a shear zone and propylitic alteration unlike other typical copper porphyry-type deposits. This raises the question whether or not the mineralization is orthomagmatic in origin, i.e., whether or not this is a true porphyry system. The main zone of mineralization is 1 kilometer long and 0.5 kilometer wide. It is characterized by disseminated chalcopyrite and pyrite, which also occur along fractures. Molybdenite mineralization was found to be associated with slickensides. Alteration minerals associated with the copper mineralization are chlorite, epidote-clinozoisite, carbonate and titanite. Chlorite and epidote-clinozoisite are concentrated in the mineralized zone, whereas an earlier potassic alteration shows a weaker spatial correlation with the mineralization. The association of the mineralization with propylitic alteration leads us to believe the mineralization is shear related, although a deeper porphyritic system may be present at depth. Two populations of titanite at the Hopper property are recognized based on their shape, size and association with other minerals. The first population, defined by a length of 100 micrometers to 1 centimeter, euhedral boundaries, and planar contacts with other magmatic phases, is interpreted to be magmatic in origin. The second population is 10 to 500 micrometers long, anhedral and shows a close association with chlorite and chalcopyrite. This type of titanite is hydrothermal in origin. Preliminary electron microprobe analyses of titanite show the magmatic titanite grains have higher concentrations of Al, Fe, Nb, Ce, Zr and Mn, and lower concentrations of Ti and Ca compared to hydrothermal titanite grains. This corresponds with substitutions of Al, Fe, Nb, and Ce to Ti and substitutions of Ce, Zr to Ca. The association of titanite with propylitic alteration and its susceptibility to trace element substitutions make this an ideal test case to evaluate magmatic versus hydrothermal titanite.

Using two-dimensional correlation size exclusion chromatography (2D-CoSEC) to explore the size-dependent heterogeneity of humic substances for copper binding.

PubMed

Lee, Yun-Kyung; Hur, Jin

2017-08-01

Knowledge of the heterogeneous distribution of humic substances (HS) reactivities along a continuum of molecular weight (MW) is crucial for the systems where the HS MW is subject to change. In this study, two dimensional correlation spectroscopy combined with size exclusion chromatography (2D-CoSEC) was first utilized to obtain a continuous and heterogeneous presence of copper binding characteristics within bulk HS with respect to MW. HS solutions with varying copper concentrations were directly injected into a size exclusion chromatography (SEC) system with Tris-HCl buffer as a mobile phase. Several validation tests confirmed neither structural disruption of HS nor competition effect of the mobile phase used. Similar to batch systems, fluorescence quenching was observed in the chromatograms over a wide range of HS MW. 2D-CoSEC maps of a soil-derived HS (Elliot soil humic acid) showed the greater fluorescence quenching degrees with respect to the apparent MW on the order of 12500 Da > 10600 Da > 7000 Da > 15800 Da. The binding constants calculated based on modified Stern-Volmer equation were consistent with the 2D-CoSEC results. More heterogeneity of copper binding affinities within bulk HS was found for the soil-derived HS versus an aquatic HS. The traditional fluorescence quenching titration method using ultrafiltered HS size fractions failed to delineate detailed distribution of the copper binding characteristics, exhibiting a much shorter range of the binding constants than those obtained from the 2D-CoSEC. Our proposed technique demonstrated a great potential to describe metal binding characteristics of HS at high MW resolution, providing a clear picture of the size-dependent metal-HS interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of the Bridging Ligand in the Active Site of Tyrosinase.

PubMed

Zou, Congming; Huang, Wei; Zhao, Gaokun; Wan, Xiao; Hu, Xiaodong; Jin, Yan; Li, Junying; Liu, Junjun

2017-10-28

Tyrosinase is a type-3 copper enzyme that is widely distributed in plants, fungi, insects, and mammals. Developing high potent inhibitors against tyrosinase is of great interest in diverse fields including tobacco curing, food processing, bio-insecticides development, cosmetic development, and human healthcare-related research. In the crystal structure of Agaricus bisporus mushroom tyrosinase, there is an oxygen atom bridging the two copper ions in the active site. It is unclear whether the identity of this bridging oxygen is a water molecule or a hydroxide anion. In the present study, we theoretically determine the identity of this critical bridging oxygen by performing first-principles hybrid quantum mechanics/molecular mechanics/Poisson-Boltzmann-surface area (QM/MM-PBSA) calculations along with a thermodynamic cycle that aim to improve the accuracy. Our results show that the binding with water molecule is energy favored and the QM/MM-optimized structure is very close to the crystal structure, whereas the binding with hydroxide anions causes the increase of energy and significant structural changes of the active site, indicating that the identity of the bridging oxygen must be a water molecule rather than a hydroxide anion. The different binding behavior between water and hydroxide anions may explain why molecules with a carboxyl group or too many negative charges have lower inhibitory activity. In light of this, the design of high potent active inhibitors against tyrosinase should satisfy both the affinity to the copper ions and the charge neutrality of the entire molecule.

Investigation of metal ligand affinities of atom transfer radical polymerization catalysts with a quadrupole ion trap.

PubMed

di Lena, Fabio; Matyjaszewski, Krzysztof

2009-11-07

An electrospray ionization mass spectrometer equipped with a quadrupole ion trap as the mass analyzer provided a powerful tool for the investigation of metal ligand affinities of catalysts for atom transfer radical polymerization. It allowed, in particular, (i) the identification, in a library of ligands, of the most stable, and thus active, copper catalysts; (ii) the assessment of the effects of the reaction medium on the relative stabilities of the catalyst complexes; and (iii) the evaluation of the influence of the nature of the ligand on both the complex halogenophilicity and the metal-ligand stabilities in the gas-phase.

EFFECT OF HUMIC ACID ON UPTAKE AND TRANSFER OF COPPER FROM MICROBES TO CILIATES TO COPEPODS

EPA Science Inventory

This research is part of an ongoing project designed to determine the effect of humic acid on the uptake and transfer of metals by marine organisms at the lower end of the food chain. Binding affinities for Cu, Cd, Zn, and Cr to Suwannee River humic acid were determined at variou...

Cu2+ triggers reversible aggregation of a disordered His-rich dehydrin MpDhn12 from Musa paradisiaca.

PubMed

Mu, Peiqiang; Feng, Dongru; Su, Jianbin; Zhang, Yang; Dai, Jinran; Jin, Honglei; Liu, Bing; He, Yanming; Qi, Kangbiao; Wang, Hongbin; Wang, Jinfa

2011-11-01

Copper is an essential nutrient, but it is toxic in excess. Here, we cloned and characterized a His-rich low molecular weight dehydrin from Musa paradisiaca, MpDhn12. Analysis by circular dichroism (CD) spectra and a thermal stability assay showed that MpDhn12 is an intrinsically disordered protein, and immobilized-metal affinity chromatography (IMAC) analysis revealed that MpDhn12 can bind Cu(2+) both in vitro and in vivo. Interestingly, MpDhn12 aggregated under excess Cu(2+) conditions, and the aggregation was reversible and impaired by histidine modification with diethylpyrocarbonate (DEPC), while the disordered structure of another dehydrin ERD14 (as a control) was not changed. Furthermore, MpDhn12 could complement the copper-sensitive phenotype of yeast mutant Δsod1. These results together suggested that MpDhn12 may take part in buffering copper levels through chelation and formation of aggregates in excess Cu(2+) conditions. To the best of our knowledge, it is the first report that a dehydrin interchanged between disordered and aggregated state triggered by copper.

The Stoichiometry of Isoquercitrin Complex with Iron or Copper Is Highly Dependent on Experimental Conditions

PubMed Central

Tvrdý, Václav; Karlíčková, Jana; Migkos, Thomas; Mladěnka, Přemysl

2017-01-01

Interaction of flavonoids with transition metals can be partially responsible for their impact on humans. Stoichiometry of the iron/copper complex with a flavonoid glycoside isoquercitrin, a frequent component of food supplements, was assessed using competitive and non-competitive methods in four (patho)physiologically-relevant pH values (4.5. 5.5, 6.8, and 7.5). Isoquercitrin chelated all tested ions (Fe2+, Fe3+, Cu2+, and Cu+) but its affinity for Cu+ ions proved to be very low. In general, the chelation potency dropped with pH lowering. Metal complexes of 1:1 stoichiometry were mostly formed, however, they were not stable and the stoichiometry changed depending on conditions. Isoquercitrin was able to reduce both Cu2+ and Fe3+ ions at low ratios, but its reducing potential was diminished at higher ratios (isoquercitrin to metal) due to the metal chelation. In conclusion, this study emphasizes the need of using multiple different methods for the assessment of chelation potential in moderately-active metal chelators, like flavonoids. PMID:29084179

Covalent modifications of the amyloid beta peptide by hydroxynonenal: Effects on metal ion binding by monomers and insights into the fibril topology.

PubMed

Grasso, G; Komatsu, H; Axelsen, P H

2017-09-01

Amyloid β peptides (Aβ) and metal ions are associated with oxidative stress in Alzheimer's disease (AD). Oxidative stress, acting on ω-6 polyunsaturated fatty acyl chains, produces diverse products, including 4-hydroxy-2-nonenal (HNE), which can covalently modify the Aβ that helped to produce it. To examine possible feedback mechanisms involving Aβ, metal ions and HNE production, the effects of HNE modification and fibril formation on metal ion binding was investigated. Results indicate that copper(II) generally inhibits the modification of His side chains in Aβ by HNE, but that once modified, copper(II) still binds to Aβ with high affinity. Fibril formation protects only one of the three His residues in Aβ from HNE modification, and this protection is consistent with proposed models of fibril structure. These results provide insight into a network of biochemical reactions that may be operating as a consequence of oxidative stress in AD, or as part of the pathogenic process. Copyright © 2016. Published by Elsevier Inc.

Affinity and Efficacy of Copper Following an Algicide Exposure: Application of the Critical Burden Concept for Lyngbya wollei Control in Lay Lake, AL

NASA Astrophysics Data System (ADS)

Bishop, West M.; Willis, Ben E.; Horton, C. Todd

2015-04-01

Accurate predictions of nuisance algae responses to algicide exposures are needed to guide management decisions. Copper sorption and responses of Lyngbya wollei (Farlow ex Gomont) Speziale and Dyck were measured in the laboratory and two areas in Lay Lake (AL, USA) to treatments of Captain® XTR (SePRO Corporation; chelated copper algicide) and a sequential treatment of GreenClean® Liquid (BioSafe Systems, LLC; peroxygen algicide) combined with Hydrothol® 191 (United Phosphorus, Inc.; endothall algicide) followed by Captain XTR. Measured filament viability in laboratory exposures predicted Captain XTR alone could control L. wollei in Lay Lake, with 2 mg Cu/g algae EC75. This produced a targeted field treatment of 9.7 kg Cu/ha which was divided into three applications of 0.3 mg Cu/L as Captain XTR in the treatment areas. Laboratory and field experiments indicated treatments of Captain XTR alone and the combination treatment resulted in comparable copper sorption and responses of L. wollei. Copper adsorbed greater to L. wollei in laboratory experiments than in the treated areas of Lay Lake with comparable exposures (2 mg Cu/g L. wollei). However, responses and infused copper were similar and correlated in laboratory experiments and treated areas of Lay Lake indicating infused copper is critical for governing toxicity. Laboratory exposures as mg Cu/g algae accurately predicted the necessary algicide exposure required to attain the critical burden of infused copper and elicit desired responses of L. wollei in treated areas of Lay Lake.

Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme

NASA Astrophysics Data System (ADS)

Patwardhan, Anjali A.

The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized Cu(II) derivatives of the aminoglycosides, kanamycin A, tobramycin, neamine, kanamycin B, neomycin B, and paromomycin. The first three exhibit preferential and tight binding to Cu(II) as against neomycin B and kanamycin B and paromomycin. EPR of frozen solutions and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence co-reactants like hydrogen peroxide or ascorbic acid. Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific with C-4' H abstraction resulting in characteristic base propenal and nucleotide base products. Hydroxyl radicals generated are copper based and are generated in close proximity of the substrate. Hammerhead ribozymes are selectively hydrolyzed in the presence of divalent ions with Mg2+ being the metal ion of choice in vivo . Our studies with complex ions like cobalt hexaammine and fac-triamminetriaquochromium(III) establish outer sphere interactions of Mg2+ with the hammerhead in the catalytic site. There are two sets of sites, one structural and one catalytic. Complex ions in the catalytic site and divalent ions in the structural site result in a slow but active hammerhead ribozyme suggesting that the complex ions are not inhibitory, contrary to what was suggested previously.

Metal deposition by electroless plating on polydopamine functionalized micro- and nanoparticles.

PubMed

Mondin, Giovanni; Wisser, Florian M; Leifert, Annika; Mohamed-Noriega, Nasser; Grothe, Julia; Dörfler, Susanne; Kaskel, Stefan

2013-12-01

A novel approach for the fabrication of metal coated micro- and nanoparticles by functionalization with a thin polydopamine layer followed by electroless plating is reported. The particles are initially coated with polydopamine via self-polymerization. The resulting polydopamine coated particles have a surface rich in catechols and amino groups, resulting in a high affinity toward metal ions. Thus, they provide an effective platform for selective electroless metal deposition without further activation and sensitization steps. The combination of a polydopamine-based functionalization with electroless plating ensures a simple, scalable, and cost-effective metal coating strategy. Silver-plated tungsten carbide microparticles, copper-plated tungsten carbide microparticles, and copper-plated alumina nanoparticles were successfully fabricated, showing also the high versatility of the method, since the polymerization of dopamine leads to the formation of an adherent polydopamine layer on the surface of particles of any material and size. The metal coated particles produced with this process are particularly well suited for the production of metal matrix composites, since the metal coating increases the wettability of the particles by the metal, promoting their integration within the matrix. Such composite materials are used in a variety of applications including electrical contacts, components for the automotive industries, magnets, and electromagnetic interference shielding. Copyright © 2013 Elsevier Inc. All rights reserved.

Inhibition of heme biosynthesis prevents transcription of iron uptake genes in yeast.

PubMed

Crisp, Robert J; Pollington, Annette; Galea, Charles; Jaron, Shulamit; Yamaguchi-Iwai, Yuko; Kaplan, Jerry

2003-11-14

Yeast are capable of modifying their metabolism in response to environmental changes. We investigated the activity of the oxygen-dependent high-affinity iron uptake system of Saccharomyces cerevisiae under conditions of heme depletion. We found that the absence of heme, due to a deletion in the gene that encodes delta-aminolevulinic acid synthase (HEM1), resulted in decreased transcription of genes belonging to both the iron and copper regulons, but not the zinc regulon. Decreased transcription of the iron regulon was not due to decreased expression of the iron sensitive transcriptional activator Aft1p. Expression of the constitutively active allele AFT1-1up was unable to induce transcription of the high affinity iron uptake system in heme-depleted cells. We demonstrated that under heme-depleted conditions, Aft1p-GFP was able to cycle normally between the nucleus and cytosol in response to cytosolic iron. Despite the inability to induce transcription under low iron conditions, chromatin immunoprecipitation demonstrated that Aft1p binds to the FET3 promoter in the absence of heme. Finally, we provide evidence that under heme-depleted conditions, yeast are able to regulate mitochondrial iron uptake and do not accumulate pathologic iron concentrations, as is seen when iron-sulfur cluster synthesis is disrupted.

Differential affinity of BsSCO for Cu(II) and Cu(I) suggests a redox role in copper transfer to the Cu(A) center of cytochrome c oxidase.

PubMed

Hill, Bruce C; Andrews, Diann

2012-06-01

SCO (synthesis of cytochrome c oxidase) proteins are involved in the assembly of the respiratory chain enzyme cytochrome c oxidase acting to assist in the assembly of the Cu(A) center contained within subunit II of the oxidase complex. The Cu(A) center receives electrons from the reductive substrate ferrocytochrome c, and passes them on to the cytochrome a center. Cytochrome a feeds electrons to the oxygen reaction site composed of cytochrome a(3) and Cu(B). Cu(A) consists of two copper ions positioned within bonding distance and ligated by two histidine side chains, one methionine, a backbone carbonyl and two bridging cysteine residues. The complex structure and redox capacity of Cu(A) present a potential assembly challenge. SCO proteins are members of the thioredoxin family which led to the early suggestion of a disulfide exchange function for SCO in Cu(A) assembly, whereas the copper binding capacity of the Bacillus subtilis version of SCO (i.e., BsSCO) suggests a direct role for SCO proteins in copper transfer. We have characterized redox and copper exchange properties of apo- and metalated-BsSCO. The release of copper (II) from its complex with BsSCO is best achieved by reducing it to Cu(I). We propose a mechanism involving both disulfide and copper exchange between BsSCO and the apo-Cu(A) site. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. Copyright © 2011 Elsevier B.V. All rights reserved.

Interactions between copper(II) and DOM in the urban stormwater runoff: modeling and characterizations.

PubMed

Zhao, Chen; Wang, Chong-Chen; Li, Jun-Qi; Wang, Peng; Ou, Jia-Qi; Cui, Jing-Rui

2018-01-01

Dissolved organic matter (DOM) can strongly interact with both organic and inorganic contaminants to influence their transportation, transformation, bioavailability, toxicity and even their ultimate fate. Within this work, DOM was extracted from urban stormwater runoff samples collected from a regular sampling site of a typical residential area in Beijing, China. Copper(II) ions were selected as model to investigate the interactions between DOM and typical heavy metals. Both ultraviolet (UV) absorbance and fluorescence titration methods were introduced to determine the complex capacities (C L ) and conditional stability constants (log K M ) of bonding between DOM and copper (II) ions, which revealed that the values of C L were 85.62 and 87.23 μmol mg -1 and the log K M values were 5.37 and 5.48, respectively. The results suggested the successful complexation between DOM and copper(II) ions. Furthermore, morphology of the DOM binding to copper(II) ions was confirmed by both energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS), which can facilitate to clarify the corresponding mechanism. The Cu 2p 3/2 peak at 933.7 eV and the characteristic shake-up peaks of Cu-O were found in the XPS spectra, implying that copper(II) ions might coordinate with hydroxyl (aliphatic or phenolic) or carboxyl groups. With these profitable results, it can be concluded that DOM in urban stormwater runoff has a strong binding affinity with copper(II) ions, which may further lead to potentially significant influence on their migration and transformation.

Fate and transport with material response characterization of green sorption media for copper removal via adsorption process.

PubMed

Chang, Ni-Bin; Houmann, Cameron; Lin, Kuen-Song; Wanielista, Martin

2016-02-01

Green adsorption media with the inclusion of renewable and recycled materials can be applied as a stormwater best management practice for copper removal. A green adsorption media mixture composed of recycled tire chunk, expanded clay aggregate, and coconut coir was physicochemically evaluated for its potential use in an upflow media filter. A suite of tests were conducted on the media mixture and the individual media components including studies of particle size distribution, isotherms, column adsorption and reaction kinetics. Isotherm test results revealed that the coconut coir had the highest affinity for copper (q(max) = 71.1 mg g(-1)), and that adsorption was maximized at a pH of 7.0. The coconut coir also performed the best under dynamic conditions, having an equilibrium uptake of 1.63 mg g(-1). FE-SEM imaging found a strong correlation between the porosity of the micro pore structure and the adsorptive capacity. The use of the green adsorption media mixture in isolation or the coconut coir with an expanded clay filtration chamber could be an effective and reliable stormwater best management practice for copper removal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modelling of the acid-base properties of natural and synthetic adsorbent materials used for heavy metal removal from aqueous solutions.

PubMed

Pagnanelli, Francesca; Vegliò, Francesco; Toro, Luigi

2004-02-01

In this paper a comparison about kinetic behaviour, acid-base properties and copper removal capacities was carried out between two different adsorbent materials used for heavy metal removal from aqueous solutions: an aminodiacetic chelating resin as commercial product (Lewatit TP207) and a lyophilised bacterial biomass of Sphaerotilus natans. The acid-base properties of a S. natans cell suspension were well described by simplified mechanistic models without electrostatic corrections considering two kinds of weakly acidic active sites. In particular the introduction of two-peak distribution function for the proton affinity constants allows a better representation of the experimental data reproducing the site heterogeneity. A priori knowledge about resin functional groups (aminodiacetic groups) is the base for preliminary simulations of titration curve assuming a Donnan gel structure for the resin phase considered as a concentrated aqueous solution of aminodiacetic acid (ADA). Departures from experimental and simulated data can be interpreted by considering the heterogeneity of the functional groups and the effect of ionic concentration in the resin phase. Two-site continuous model describes adequately the experimental data. Moreover the values of apparent protonation constants (as adjustable parameters found by non-linear regression) are very near to the apparent constants evaluated by a Donnan model assuming the intrinsic constants in resin phase equal to the equilibrium constants in aqueous solution of ADA and considering the amphoteric nature of active sites for the evaluation of counter-ion concentration in the resin phase. Copper removal outlined the strong affinity of the active groups of the resin for this ion in solution compared to the S. natans biomass according to the complexation constants between aminodiacetic and mono-carboxylic groups and copper ions.

SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell.

PubMed

Feng, Chenzhe; Ma, Fang; Hu, Chunhong; Ma, Jin-An; Wang, Jingjing; Zhang, Yang; Wu, Fang; Hou, Tao; Jiang, Shun; Wang, Yapeng; Feng, Yeqian

2018-01-01

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.

Transcriptome Sequencing Identifies SPL7-Regulated Copper Acquisition Genes FRO4/FRO5 and the Copper Dependence of Iron Homeostasis in Arabidopsis[C][W

PubMed Central

Bernal, María; Casero, David; Singh, Vasantika; Wilson, Grandon T.; Grande, Arne; Yang, Huijun; Dodani, Sheel C.; Pellegrini, Matteo; Huijser, Peter; Connolly, Erin L.; Merchant, Sabeeha S.; Krämer, Ute

2012-01-01

The transition metal copper (Cu) is essential for all living organisms but is toxic when present in excess. To identify Cu deficiency responses comprehensively, we conducted genome-wide sequencing-based transcript profiling of Arabidopsis thaliana wild-type plants and of a mutant defective in the gene encoding SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7), which acts as a transcriptional regulator of Cu deficiency responses. In response to Cu deficiency, FERRIC REDUCTASE OXIDASE5 (FRO5) and FRO4 transcript levels increased strongly, in an SPL7-dependent manner. Biochemical assays and confocal imaging of a Cu-specific fluorophore showed that high-affinity root Cu uptake requires prior FRO5/FRO4-dependent Cu(II)-specific reduction to Cu(I) and SPL7 function. Plant iron (Fe) deficiency markers were activated in Cu-deficient media, in which reduced growth of the spl7 mutant was partially rescued by Fe supplementation. Cultivation in Cu-deficient media caused a defect in root-to-shoot Fe translocation, which was exacerbated in spl7 and associated with a lack of ferroxidase activity. This is consistent with a possible role for a multicopper oxidase in Arabidopsis Fe homeostasis, as previously described in yeast, humans, and green algae. These insights into root Cu uptake and the interaction between Cu and Fe homeostasis will advance plant nutrition, crop breeding, and biogeochemical research. PMID:22374396

Spectroscopic and TDDFT investigation on highly selective fluorogenic chemosensor and construction of molecular logic gates.

PubMed

Basheer, Sabeel M; Kumar, Saravana Loganathan Ashok; Kumar, Moorthy Saravana; Sreekanth, Anandaram

2017-03-01

1,5-Bis(2-fluorene)thiocarbohydrazone (FBTC) was designed and synthesized for selective sensing of fluoride and copper ions. The binding constants of FBTC towards fluoride and copper ions have been calculated using the Benesi-Hildebrand equation, and FBTC has more binding affinity towards copper ion than fluoride ion. The 1 H NMR and 13 C NMR titration studies strongly support the deprotonation was taken from the N-H protons followed by the formation of hydrogen bond via N-H … F. To understand the fluoride ion sensing mechanism, theoretical investigation had been carried out using the density functional theory and time-dependent density functional theory. The theoretical data well reproduced the experimental results. The deprotonation process has a moderate transition barrier (481.55kcal/mol). The calculated ΔE and ΔG values (-253.92 and -192.41kcal/mol respectively) suggest the feasibility of sensing process. The potential energy curves give the optimized structures of FBTC-F complex in the ground state and excited state, which states the proton transition occurs at the excited state. The excited state proton transition mechanism was further confirmed with natural bond orbital analysis. The reversibility of the sensor was monitored by the alternate addition of F - and Cu 2+ ions, which was explained with "Read-Erase-Write-Read" behaviour. The multi-ion detection of sensor used to construct the molecular logic gate, such as AND, OR, NOR and INHIBITION logic gates. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Cuprimine® and Syprine® for Decorporation of Radioisotopes of Cesium, Cobalt, Iridium, and Strontium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Creim, Jeffrey A.; Curry, Terry L.

2011-08-01

Cuprimine and Syprine are therapeutics approved by FDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally deposited copper. These oral therapeutics are based on respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl)-1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians increasingly are turning to Syprine as first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. The literature reports that these agents exhibit high affinity for a range of transition and f-metals and metalloids in vitro. Our previousmore » in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for cobalt-60 and polonium-210 (Levitskaia et al 2010a). Currently we are expanding these studies to evaluate in vivo decorporation efficacy of these drugs for several additional radionuclides. In this paper, we discuss results of this investigation using gamma-emitting radionuclides including cesium-137 (137Cs), cobalt-60 (60Co), iridium-192 (192Ir), and strontium-85 (85Sr). Short-term 48 hr pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potency using male Wistar-Han rats. In these studies, radionuclide solution was administered to animals by IV injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show highly effective decorporation of 60Co by DPA. DPA and Trien were modestly effective in decorporation 137Cs and 85Sr, respectively. Based on these promising findings, further studies to evaluate the dose-response pharmacokinetic profiles for decorporation are warranted.« less

One-pot preparation of silica-supported hybrid immobilized metal affinity adsorbent with macroporous surface based on surface imprinting coating technique combined with polysaccharide incorporated sol--gel process.

PubMed

Li, Feng; Li, Xue-Mei; Zhang, Shu-Sheng

2006-10-06

A simple and reliable one-pot approach using surface imprinting coating technique combined with polysaccharide incorporated sol-gel process was established to synthesize a new organic-inorganic hybrid matrix possessing macroporous surface and functional ligand. Using mesoporous silica gel being a support, immobilized metal affinity adsorbent with a macroporous shell/mesoporous core structure was obtained after metal ion loading. In the prepared matrix, covalently bonded coating and morphology manipulation on silica gel was achieved by using one-pot sol-gel process starting from an inorganic precursor, -glycidoxypropyltrimethoxysiloxane (GPTMS), and a functional biopolymer, chitosan (CS) at the atmosphere of imprinting polyethylene glycol (PEG). Self-hydrolysis of GPTMS, self-condensation, and co-condensation of silanol groups (Si-OH) from siloxane and silica gel surface, and in situ covalent cross-linking of CS created an orderly coating on silica gel surface. PEG extraction using hot ammonium hydroxide solution gave a chemically and mechanically stabilized pore structure and deactivated residual epoxy groups. The prepared matrix was characterized by using X-ray energy dispersion spectroscopy (EDX), scanning electron microscopy (SEM) and mercury intrusion porosimetry. The matrix possessed a high capacity for copper ion loading. Protein adsorption performance of the new immobilized metal affinity adsorbent was evaluated by batch adsorption and column chromatographic experiment using bovine serum albumin (BSA) as a simple model protein. Under the optimized coating conditions, the obtained macroporous surface resulted in a fast kinetics and high capability for protein adsorption, while the matrix non-charged with metal ions offered a low non-specific adsorption.

Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5'untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator.

PubMed

Bandyopadhyay, S; Huang, X; Cho, H; Greig, N H; Youdim, M B; Rogers, J T

2006-01-01

Iron closely regulates the expression of the Alzheimer's Amyloid Precursor Protein (APP) gene at the level of message translation by a pathway similar to iron control of the translation of the ferritin L- and H mRNAs by Iron-responsive Elements in their 5' untranslated regions (5'UTRs). Using transfection based assays in SH-SY5Y neuroblastoma cells we tested the relative efficiency by which iron, copper and zinc up-regulate IRE activity in the APP 5'UTR. Desferrioxamine (high affinity Fe3+ chelator), (ii) clioquinol (low affinity Fe/Cu/Zn chelator), (iii) piperazine-1 (oral Fe chelator), (iv) VK-28 (oral Fe chelator), were tested for their relative modulation of APP 5' UTR directed translation of a luciferase reporter gene. Iron chelation based therapeutic strategies for slowing the progression of Alzheimer's disease (and other neurological disorders that manifest iron imbalance) are discussed with regard to the relative neural toxic action of each chelator in SH-SY5Y cells and in H4 glioblastoma cells.

Development of two highly sensitive immunoassays for detection of copper ions and a suite of relevant immunochemicals.

PubMed

Zhao, Hongwei; Nan, Tiegui; Tan, Guiyu; Gao, Wei; Cao, Zhen; Sun, Shuo; Li, Zhaohu; Li, Qing X; Wang, Baomin

2011-09-19

Availability of highly sensitive assays for metal ions can help monitor and manage the environmental and food contamination. In the present study, a monoclonal antibody against Copper(II)-ethylenediaminetetraacetic acid was used to develop two sensitive ELISAs for Cu(II) analysis. Cobalt(II)-EDTA-BSA was the coating antigen in a heterologous indirect competitive ELISA (hicELISA), whereas Co(II)-EDTA-BSA-horseradish peroxidase (HRP) was the enzyme tracer in a heterologous direct competitive ELISA (hdcELISA). Both ELISAs were validated for detecting the content of Cu(II) in environmental waters. The ELISA data agreed well with those from graphite furnace atomic absorption spectroscopy. The methods of developing the Cu(II) hicELISA and hdcELISA are potentially applicable for developing ELISAs for other metals. The chelator-protein complexes such as EDTA-BSA and EDTA-BSA-HRP can form a suite of metal complexes having the consistent hapten density, location and orientation on the conjugates except the difference of the metal core, which can be used as ideal reagents to investigate the relationship between assay sensitivity and antibody affinities for the haptens and the analytes. The strategy of conjugating a haptenated protein directly with HRP can reduce the loss of HRP activity during the conjugation reaction and thus can be applicable for the development of ELISAs for small molecules. Copyright © 2011. Published by Elsevier B.V.

Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role

PubMed Central

Kettenbach, Kathrin; Reffert, Laura M.; Schieferstein, Hanno; Pektor, Stefanie; Eckert, Raphael; Miederer, Matthias; Rösch, Frank

2018-01-01

Within the last decade, several folate-based radiopharmaceuticals for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been evaluated; however, there is still a lack of suitable 18F-folates for clinical PET imaging. Herein, we report the synthesis and evaluation of two novel 18F-folates employing strain-promoted and copper-catalyzed click chemistry. Furthermore, the influence of both click-methods on lipophilicity and pharmacokinetics of the 18F-folates was investigated. 18F-Ala-folate and 18F-DBCO-folate were both stable in human serum albumin. In vitro studies proved their high affinity to the folate receptor (FR). The lipophilic character of the strain-promoted clicked 18F-DBCO-folate (logD = 0.6) contributed to a higher non-specific binding in cell internalization studies. In the following in vivo PET imaging studies, FR-positive tumors could not be visualized in a maximum intensity projection images. Compared with 18F-DBCO-folate, 18F-Ala-folate (logD = −1.4), synthesized by the copper-catalyzed click reaction, exhibited reduced lipophilicity, and as a result an improved in vivo performance and a clear-cut visualization of FR-positive tumors. In view of high radiochemical yield, radiochemical purity and favorable pharmacokinetics, 18F-Ala-folate is expected to be a promising candidate for FR-PET imaging. PMID:29562610

Pilot Study of 64Cu(I) for PET Imaging of Melanoma

DOE PAGES

Jiang, Lei; Tu, Yingfeng; Hu, Xiang; ...

2017-05-31

Currently, 64Cu(II) labeled tracers including 64CuCl 2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of 64Cu(I) for PET imaging. 64Cu(II) was reduced to 64Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively. Small animal PET and biodistribution studies were performed in both B16F10 and A375 tumor-bearing mice. Comparedmore » with 64Cu(II), 64Cu(I) exhibited higher cellular uptake by melanoma, which testified CTR1 specially influx of Cu(I). But, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. In addition, radiation absorbed doses for major tissues of human were calculated based on the mouse biodistribution. Radiodosimetry calculations for 64/67Cu(I) and 64/67Cu(II) were similar, which suggested that although melanoma were with high radiation absorbed doses, high radioactivity accumulation by liver and kidney should be noticed for the further application. Thus, 64Cu(I) should be further studied to evaluate it as a PET imaging radiotracer.« less

Pilot Study of 64Cu(I) for PET Imaging of Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Lei; Tu, Yingfeng; Hu, Xiang

Currently, 64Cu(II) labeled tracers including 64CuCl 2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of 64Cu(I) for PET imaging. 64Cu(II) was reduced to 64Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively. Small animal PET and biodistribution studies were performed in both B16F10 and A375 tumor-bearing mice. Comparedmore » with 64Cu(II), 64Cu(I) exhibited higher cellular uptake by melanoma, which testified CTR1 specially influx of Cu(I). But, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. In addition, radiation absorbed doses for major tissues of human were calculated based on the mouse biodistribution. Radiodosimetry calculations for 64/67Cu(I) and 64/67Cu(II) were similar, which suggested that although melanoma were with high radiation absorbed doses, high radioactivity accumulation by liver and kidney should be noticed for the further application. Thus, 64Cu(I) should be further studied to evaluate it as a PET imaging radiotracer.« less

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

PubMed Central

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-01-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides. PMID:2548206

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

PubMed

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

Advanced purification strategy for CueR, a cysteine containing copper(I) and DNA binding protein.

PubMed

Balogh, Ria K; Gyurcsik, Béla; Hunyadi-Gulyás, Éva; Christensen, Hans E M; Jancsó, Attila

2016-07-01

Metal ion regulation is essential for living organisms. In prokaryotes metal ion dependent transcriptional factors, the so-called metalloregulatory proteins play a fundamental role in controlling the concentration of metal ions. These proteins recognize metal ions with an outstanding selectivity. A detailed understanding of their function may be exploited in potential health, environmental and analytical applications. Members of the MerR protein family sense a broad range of mostly late transition and heavy metal ions through their cysteine thiolates. The air sensitivity of latter groups makes the expression and purification of such proteins challenging. Here we describe a method for the purification of the copper-regulatory CueR protein under optimized conditions. In order to avoid protein precipitation and/or eventual aggregation and to get rid of the co-purifying Escherichia coli elongation factor, our procedure consisted of four steps supplemented by DNA digestion. Subsequent anion exchange on Sepharose FF Q 16/10, affinity chromatography on Heparin FF 16/10, second anion exchange on Source 30 Q 16/13 and gel filtration on Superdex 75 26/60 resulted in large amounts of pure CueR protein without any affinity tag. Structure and functionality tests performed with mass spectrometry, circular dichroism spectroscopy and electrophoretic gel mobility shift assays approved the success of the purification procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

Insights into geometries, stabilities, electronic structures, reactivity descriptors, and magnetic properties of bimetallic Nim Cun-m (m = 1, 2; n = 3-13) clusters: Comparison with pure copper clusters.

PubMed

Singh, Raman K; Iwasa, Takeshi; Taketsugu, Tetsuya

2018-05-25

A long-range corrected density functional theory (LC-DFT) was applied to study the geometric structures, relative stabilities, electronic structures, reactivity descriptors and magnetic properties of the bimetallic NiCu n -1 and Ni 2 Cu n -2 (n = 3-13) clusters, obtained by doping one or two Ni atoms to the lowest energy structures of Cu n , followed by geometry optimizations. The optimized geometries revealed that the lowest energy structures of the NiCu n -1 and Ni 2 Cu n -2 clusters favor the Ni atom(s) situated at the most highly coordinated position of the host copper clusters. The averaged binding energy, the fragmentation energies and the second-order energy differences signified that the Ni doped clusters can continue to gain an energy during the growth process. The electronic structures revealed that the highest occupied molecular orbital and the lowest unoccupied molecular orbital energies of the LC-DFT are reliable and can be used to predict the vertical ionization potential and the vertical electron affinity of the systems. The reactivity descriptors such as the chemical potential, chemical hardness and electrophilic power, and the reactivity principle such as the minimum polarizability principle are operative for characterizing and rationalizing the electronic structures of these clusters. Moreover, doping of Ni atoms into the copper clusters carry most of the total spin magnetic moment. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Overcoming platinum drug resistance with copper-lowering agents.

PubMed

Chen, Helen H W; Kuo, Macus Tien

2013-10-01

Platinum (Pt)-based antitumor agents have been the mainstay of cancer chemotherapy for the last three decades. While multiple mechanisms are responsible for treatment failure, deficiency in drug transport is an important contributor. The human high-affinity copper (Cu) transporter-1 (hCtr1) can also transport Pt-based drugs including cisplatin (cDDP) and carboplatin. Reduced hCtr1 expression frequently occurs in cDDP-resistant cell lines and in cancer in patients who failed chemotherapy with these drugs. We previously demonstrated that Cu chelation induces the expression of transcription factor Sp1 which binds the promoters of Sp1 and hCtr1, thereby, up-regulating their expression, whereas Cu overload shuts down hCtr1 and Sp1 expression by dissociating Sp1 from their promoter promoters. Thus, mammalian Cu homeostasis is transcriptionally regulated within a loop consisting of Sp1, hCtr1, and Cu in a three-way mutually regulated manner. These findings suggest that it is feasible to module cDDP transport capacity through intervention of mammalian Cu homeostasis. Indeed, we found that cDDP resistance can be overcome by Cu-lowering agents through enhanced hCtr1 expression by up-regulation of Sp1 in cultured cells. This discovery provided a mechanistic basis for the ongoing clinical study using Cu chelator to overcome cDDP resistance in ovarian cancer chemotherapy. Preliminary study using copper chelator (trientine) for enhancing the treatment efficacy of carboplatin in 5 ovarian cancer patients showed encouraging results. This short review describes the perspectives of using Cu-lowering agents in overcoming Pt resistance in cancer chemotherapy.

Crystal structure of a four-copper laccase complexed with an arylamine: insights into substrate recognition and correlation with kinetics.

PubMed

Bertrand, Thomas; Jolivalt, Claude; Briozzo, Pierre; Caminade, Eliane; Joly, Nathalie; Madzak, Catherine; Mougin, Christian

2002-06-11

Laccases are multicopper oxidases that catalyze the oxidation of a wide range of phenols or arylamines, and their use in industrial oxidative processes is increasing. We purified from the white rot fungus Trametes versicolor a laccase that exists as five different isozymes, depending on glycosylation. The 2.4 A resolution structure of the most abundant isozyme of the glycosylated enzyme was solved. The four copper atoms are present, and it is the first crystal structure of a laccase in its active form. The crystallized enzyme binds 2,5-xylidine, which was used as a laccase inducer in the fungus culture. This arylamine is a very weak reducing substrate of the enzyme. The cavity enclosing 2,5-xylidine is rather wide, allowing the accommodation of substrates of various sizes. Several amino acid residues make hydrophobic interactions with the aromatic ring of the ligand. In addition, two charged or polar residues interact with its amino group. The first one is an histidine that also coordinates the copper that functions as the primary electron acceptor. The second is an aspartate conserved among fungal laccases. The purified enzyme can oxidize various hydroxylated compounds of the phenylurea family of herbicides that we synthesized. These phenolic substrates have better affinities at pH 5 than at pH 3, which could be related to the 2,5-xylidine binding by the aspartate. This is the first high-resolution structure of a multicopper oxidase complexed to a reducing substrate. It provides a model for engineering laccases that are either more efficient or with a wider substrate specificity.

The effects of silver ions on copper metabolism in rats.

PubMed

Ilyechova, E Yu; Saveliev, A N; Skvortsov, A N; Babich, P S; Zatulovskaia, Yu A; Pliss, M G; Korzhevskii, D E; Tsymbalenko, N V; Puchkova, L V

2014-10-01

The influence of short and prolonged diet containing silver ions (Ag-diet) on copper metabolism was studied. Two groups of animals were used: one group of adult rats received a Ag-diet for one month (Ag-A1) and another group received a Ag-diet for 6 months from birth (Ag-N6). In Ag-A1 rats, the Ag-diet caused a dramatic decrease of copper status indexes that was manifested as ceruloplasmin-associated copper deficiency. In Ag-N6 rats, copper status indexes decreased only 2-fold as compared to control rats. In rats of both groups, silver entered the bloodstream and accumulated in the liver. Silver was incorporated into ceruloplasmin (Cp), but not SOD1. In the liver, a prolonged Ag-diet caused a decrease of the expression level of genes, associated with copper metabolism. Comparative spectrophotometric analysis of partially purified Cp fractions has shown that Cp from Ag-N6 rats was closer to holo-Cp by specific enzymatic activities and tertiary structure than Cp from Ag-A1 rats. However, Cp of Ag-N6 differs from control holo-Cp and Cp of Ag-A1 in its affinity to DEAE-Sepharose and in its binding properties to lectins. In the bloodstream of Ag-N6, two Cp forms are present as shown in pulse-experiments on rats with the liver isolated from circulation. One of the Cp isoforms is of hepatic origin, and the other is of extrahepatic origin; the latter is characterized by a faster rate of secretion than hepatic Cp. These data allowed us to suggest that the disturbance of holo-Cp formation in the liver was compensated by induction of extrahepatic Cp synthesis. The possible biological importance of these effects is discussed.

Influence of carbon content on the copper-telluride phase formation and on the resistive switching behavior of carbon alloyed Cu-Te conductive bridge random access memory cells

NASA Astrophysics Data System (ADS)

Devulder, Wouter; Opsomer, Karl; Franquet, Alexis; Meersschaut, Johan; Belmonte, Attilio; Muller, Robert; De Schutter, Bob; Van Elshocht, Sven; Jurczak, Malgorzata; Goux, Ludovic; Detavernier, Christophe

2014-02-01

In this paper, we investigate the influence of the carbon content on the Cu-Te phase formation and on the resistive switching behavior in carbon alloyed Cu0.6Te0.4 based conductive bridge random access memory (CBRAM) cells. Carbon alloying of copper-tellurium inhibits the crystallization, while attractive switching behavior is preserved when using the material as Cu-supply layer in CBRAM cells. The phase formation is first investigated in a combinatorial way. With increasing carbon content, an enlargement of the temperature window in which the material stays amorphous was observed. Moreover, if crystalline phases are formed, subsequent phase transformations are inhibited. The electrical switching behavior of memory cells with different carbon contents is then investigated by implementing them in 580 μm diameter dot TiN/Cu0.6Te0.4-C/Al2O3/Si memory cells. Reliable switching behavior is observed for carbon contents up to 40 at. %, with a resistive window of more than 2 orders of magnitude, whereas for 50 at. % carbon, a higher current in the off state and only a small resistive window are present after repeated cycling. This degradation can be ascribed to the higher thermal and lower drift contribution to the reset operation due to a lower Cu affinity towards the supply layer, leading cycle-after-cycle to an increasing amount of Cu in the switching layer, which contributes to the current. The thermal diffusion of Cu into Al2O3 under annealing also gives an indication of the Cu affinity of the source layer. Time of flight secondary ion mass spectroscopy was used to investigate this migration depth in Al2O3 before and after annealing, showing a higher Cu, Te, and C migration for high carbon contents.

Effects of copper sulfate supplement on growth, tissue concentration, and ruminal solubilities of molybdenum and copper in sheep fed low and high molybdenum diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivan, M.; Veira, D.M.

1985-01-01

Each of four groups of six wethers were fed one of a low molybdenum, high molybdenum, high molybdenum plus copper sulfate, or high molybdenum plus copper sulfate corn silage-based diet for ad libitum intake for 221 days. Average daily gains and ratios of feed/gain were depressed for the high molybdenum diet as compared with the low molybdenum diet suggesting molybdenum toxicity in sheep fed the high molybdenum diet. This was alleviated partly by the copper sulfate supplement. The supplement also decreased solubility of both copper and molybdenum in the rumen but had no effect on copper concentration in blood plasma.more » Concentration of molybdenum was higher in both liver and kidney in sheep fed high-molybdenum diets as compared with low-molybdenum diets. Copper concentration was higher in kidneys of sheep fed high-molybdenum diets, but no difference was significant in liver copper between sheep fed diets high or low in molybdenum.« less

Copper tolerance in clones of Agrostis gigantea from a mine waste site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, G.D.; Courtin, G.M.; Rauser, W.E.

1977-04-15

A mine waste site from Sudbury, Ontario, contaminated with heavy metals is described. The dominant vegetative cover was formed by two grasses: Agrostis gigantea Roth. and Agrostis scabra Willd. Testing of 10 clones of A. gigantea from the roast bed and an adjoining area for copper tolerance showed that two clones collected from the roast bed were tolerant to increased copper levels. Copper tolerance was found in clones growing on soils with high copper contents and low pHs. The combination of high copper content and low pH brought about a high level of extractable copper within the soil. Soils withmore » equally high copper levels but higher pHs and therefore low extractable-copper levels did not support copper-tolerant clones.« less

Ferric reductase genes involved in high-affinity iron uptake are differentially regulated in yeast and hyphae of Candida albicans.

PubMed

Jeeves, Rose E; Mason, Robert P; Woodacre, Alexandra; Cashmore, Annette M

2011-09-01

The pathogenic yeast Candida albicans possesses a reductive iron uptake system which is active in iron-restricted conditions. The sequestration of iron by this mechanism initially requires the reduction of free iron to the soluble ferrous form, which is catalysed by ferric reductase proteins. Reduced iron is then taken up into the cell by a complex of a multicopper oxidase protein and an iron transport protein. Multicopper oxidase proteins require copper to function and so reductive iron and copper uptake are inextricably linked. It has previously been established that Fre10 is the major cell surface ferric reductase in C. albicans and that transcription of FRE10 is regulated in response to iron levels. We demonstrate here that Fre10 is also a cupric reductase and that Fre7 also makes a significant contribution to cell surface ferric and cupric reductase activity. It is also shown, for the first time, that transcription of FRE10 and FRE7 is lower in hyphae compared to yeast and that this leads to a corresponding decrease in cell surface ferric, but not cupric, reductase activity. This demonstrates that the regulation of two virulence determinants, the reductive iron uptake system and the morphological form of C. albicans, are linked. Copyright © 2011 John Wiley & Sons, Ltd.

Occupancy of a C2-C2 type 'zinc-finger' protein domain by copper. Direct observation by electrospray ionization mass spectrometry.

PubMed

Hutchens, T W; Allen, M H; Li, C M; Yip, T T

1992-09-07

The metal ion specificity of most 'zinc-finger' metal binding domains is unknown. The human estrogen receptor protein contains two different C2-C2 type 'zinc-finger' sequences within its DNA-binding domain (ERDBD). Copper inhibits the function of this protein by mechanisms which remain unclear. We have used electrospray ionization mass spectrometry to evaluate directly the 71-residue ERDBD (K180-M250) in the absence and presence of Cu(II) ions. The ERDBD showed a high affinity for Cu and was completely occupied with 4 Cu bound; each Cu ion was evidently bound to only two ligand residues (net loss of only 2 Da per bound Cu). The Cu binding stoichiometry was confirmed by atomic absorption. These results (i) provide the first direct physical evidence for the ability of the estrogen receptor DNA-binding domain to bind Cu and (ii) document a twofold difference in the Zn- and Cu-binding capacity. Differences in the ERDBD domain structure with bound Zn and Cu are predicted. Given the relative intracellular contents of Zn and Cu, our findings demonstrate the need to investigate further the Cu occupancy of this and other zinc-finger domains both in vitro and in vivo.

Potential phytoextraction and phytostabilization of perennial peanut on copper-contaminated vineyard soils and copper mining waste.

PubMed

Andreazza, Robson; Bortolon, Leandro; Pieniz, Simone; Giacometti, Marcelo; Roehrs, Dione D; Lambais, Mácio R; Camargo, Flávio A O

2011-12-01

This study sought to evaluate the potential of perennial peanut (Arachis pintoi) for copper phytoremediation in vineyard soils (Inceptisol and Mollisol) contaminated with copper and copper mining waste. Our results showed high phytomass production of perennial peanut in both vineyard soils. Macronutrient uptakes were not negatively affected by perennial peanut cultivated in all contaminated soils. Plants cultivated in Mollisol showed high copper concentrations in the roots and shoots of 475 and 52 mg kg(-1), respectively. Perennial peanut plants showed low translocation factor values for Cu, although these plants showed high bioaccumulation factor (BCF) for both vineyard soils, Inceptisol and Mollisol, with BCF values of 3.83 and 3.24, respectively, being characterized as a copper hyperaccumulator plant in these soils. Copper phytoextraction from Inceptisol soil was the highest for both roots and entire plant biomass, with more than 800 mg kg(-1) of copper in whole plant. The highest potential copper phytoextraction by perennial peanut was in Inceptisol soil with copper removal of 2,500 g ha(-1). Also, perennial peanut showed high potential for copper phytoremoval in copper mining waste and Mollisol with 1,700 and 1,500 g of copper per hectare, respectively. In addition, perennial peanuts characterized high potential for phytoextraction and phytostabilization of copper in vineyard soils and copper mining waste.

Occupancy of the Zinc-binding Site by Transition Metals Decreases the Substrate Affinity of the Human Dopamine Transporter by an Allosteric Mechanism*

PubMed Central

Li, Yang; Mayer, Felix P.; Hasenhuetl, Peter S.; Burtscher, Verena; Schicker, Klaus; Sitte, Harald H.; Freissmuth, Michael; Sandtner, Walter

2017-01-01

The human dopamine transporter (DAT) has a tetrahedral Zn2+-binding site. Zn2+-binding sites are also recognized by other first-row transition metals. Excessive accumulation of manganese or of copper can lead to parkinsonism because of dopamine deficiency. Accordingly, we examined the effect of Mn2+, Co2+, Ni2+, and Cu2+ on transport-associated currents through DAT and DAT-H193K, a mutant with a disrupted Zn2+-binding site. All transition metals except Mn2+ modulated the transport cycle of wild-type DAT with affinities in the low micromolar range. In this concentration range, they were devoid of any action on DAT-H193K. The active transition metals reduced the affinity of DAT for dopamine. The affinity shift was most pronounced for Cu2+, followed by Ni2+ and Zn2+ (= Co2+). The extent of the affinity shift and the reciprocal effect of substrate on metal affinity accounted for the different modes of action: Ni2+ and Cu2+ uniformly stimulated and inhibited, respectively, the substrate-induced steady-state currents through DAT. In contrast, Zn2+ elicited biphasic effects on transport, i.e. stimulation at 1 μm and inhibition at 10 μm. A kinetic model that posited preferential binding of transition metal ions to the outward-facing apo state of DAT and a reciprocal interaction of dopamine and transition metals recapitulated all experimental findings. Allosteric activation of DAT via the Zn2+-binding site may be of interest to restore transport in loss-of-function mutants. PMID:28096460

Selective Capture of Cesium and Thallium from Natural Waters and Simulated Wastes with Copper Ferrocyanide Functionalized Mesoporous Silica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sangvanich, Thanapon; Sukwarotwat, Vichaya; Wiacek, Robert J.

2010-10-15

Copper(II) ferrocyanide immobilized inside mesoporous silica MCM-41 supports (Cu-FC-EDA-SAMMSTM) has been evaluated against iron(III) hexacyanoferrate(II) (insoluble Prussian blue) for the sorption of cesium (Cs+) and thallium (Tl+) from natural waters and simulated wastes. The affinities (in term of distribution coefficients, Kd) of both sorbents for Cs and Tl were measured as a function of solution pH, competing cations, and matrices. For the entire pH studied (pH 0.1 to 7.3), Cu-FC-EDA-SAMMS had higher affinities for Cs and Tl (one to two orders of magnitude higher Kd) than Prussian blue and was less negatively impacted by the solution pH, competing cations, andmore » matrices. The adsorption isotherms and kinetics of the two sorbents for Cs and/or Tl were also determined in seawater and simulated acid and alkaline wastes. SAMMS outperformed Prussian blue in terms of maximum adsorption capacity (e.g., 21.7 versus 2.6 mg Cs/g in acid waste stimulant, pH 1.1), and rate (e.g., over 95 wt% of Cs was removed after 2 minutes with SAMMS, while only 75 wt% was removed with Prussian blue). The lower affinity, capacity, and rate of Cs and Tl sorption on Prussian blue than those on Cu-FC-EDA-SAMMS were attributed to the molecular pore sizes, which restrict mass transport, and the insoluble Cs abducts of the Prussian blue, which restrict the ability of neighboring binding sites to further bind Cs ions. On the other hand, the large pores of SAMMS not only enable faster diffusion and faster binding chemistry, but they also allow isolation of binding sites so that one Cs binding event does not impact further Cs binding. In addition, iron (Fe) dissolved from insoluble Prussian blue over 10-fold of that from Cu-FC-EDA-SAMMS after 24 hours of contact time, indicating poorer material stability of Prussian blue.« less

Efficient synthesis of a fluorine-18 labeled biotin derivative.

PubMed

Claesener, Michael; Breyholz, Hans-Jörg; Hermann, Sven; Faust, Andreas; Wagner, Stefan; Schober, Otmar; Schäfers, Michael; Kopka, Klaus

2012-11-01

The natural occurring vitamin biotin, also known as vitamin H or vitamin B(7), plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10(-15)M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [(18)F]4 for a potential application in positron emission tomography (PET). Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [(18)F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined. Compound [(18)F]4 was obtained from precursor compound 3 with an average specific activity of 16GBq/μmol within 45min and a radiochemical yield of 45±5% (decay corrected). [(18)F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [(18)F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination. An efficient synthesis for [(18)F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [(18)F]4. Copyright © 2012 Elsevier Inc. All rights reserved.

Immunotoxicological and biochemical effects of aflatoxins in rats prevented by Tunisian montmorillonite with reference to HSCAS.

PubMed

Abbès, Samir; Ben Salah-Abbès, Jalila; Abdel-Wahhab, Mosaad A; Ouslati, Ridha

2010-09-01

Previously we reported that hydrated sodium calcium aluminosilicate (HSCAS) and Tunisian Montmorillonite (TM) had an ability to sorb aflatoxins with a high affinity. Addition of these compounds to feedstuffs contaminated with aflatoxins has shown protective effects against the development of aflatoxicosis in farm and laboratory animals. The objective of the current study was to compare the efficiency of HSCAS and the TM in respect to the protection against immunotoxicological effects of aflatoxins in rats. Animals fed an aflatoxin-contaminated diet (2.5 mg/kg diet) showed a significant decrease in all hematological parameters, cholesterol, triglycerides, cholinesterase, total protein, albumin, zinc and copper concentrations. Such feeding significantly increased createnine, bilirubin, urea nitrogen, alkaline phosphatase and transaminases concentrations. The immunological results showed a significant decrease in lymphocytes of the total white blood cells, immunoglobulin profile (Ig G and Ig A), T-cells sub-types (CD3(+), CD4(+) and CD8(+)), NK and pro-inflammatory cytokines (TNFalpha and IL-1beta) typical of aflatoxicosis. Both HSCAS and TM at the level of 5 g/kg contaminated diet resulted in a significant improvement in all immunological parameters-in lymphocyte, immunoglobulin profile, T-cells sub-types and pro-inflammatory cytokines as well as the mineral status and the biochemical parameters. The deleterious effects of aflatoxin could be overcome or, at least, diminished by the addition of sorbents. Moreover, both tested sorbents by themselves had no toxic effects and bind aflatoxin with high affinity.

Generating a Metal-responsive Transcriptional Regulator to Test What Confers Metal Sensing in Cells*

PubMed Central

Osman, Deenah; Piergentili, Cecilia; Chen, Junjun; Chakrabarti, Buddhapriya; Foster, Andrew W.; Lurie-Luke, Elena; Huggins, Thomas G.; Robinson, Nigel J.

2015-01-01

FrmR from Salmonella enterica serovar typhimurium (a CsoR/RcnR-like transcriptional de-repressor) is shown to repress the frmRA operator-promoter, and repression is alleviated by formaldehyde but not manganese, iron, cobalt, nickel, copper, or Zn(II) within cells. In contrast, repression by a mutant FrmRE64H (which gains an RcnR metal ligand) is alleviated by cobalt and Zn(II). Unexpectedly, FrmR was found to already bind Co(II), Zn(II), and Cu(I), and moreover metals, as well as formaldehyde, trigger an allosteric response that weakens DNA affinity. However, the sensory metal sites of the cells' endogenous metal sensors (RcnR, ZntR, Zur, and CueR) are all tighter than FrmR for their cognate metals. Furthermore, the endogenous metal sensors are shown to out-compete FrmR. The metal-sensing FrmRE64H mutant has tighter metal affinities than FrmR by approximately 1 order of magnitude. Gain of cobalt sensing by FrmRE64H remains enigmatic because the cobalt affinity of FrmRE64H is substantially weaker than that of the endogenous cobalt sensor. Cobalt sensing requires glutathione, which may assist cobalt access, conferring a kinetic advantage. For Zn(II), the metal affinity of FrmRE64H approaches the metal affinities of cognate Zn(II) sensors. Counter-intuitively, the allosteric coupling free energy for Zn(II) is smaller in metal-sensing FrmRE64H compared with nonsensing FrmR. By determining the copies of FrmR and FrmRE64H tetramers per cell, then estimating promoter occupancy as a function of intracellular Zn(II) concentration, we show how a modest tightening of Zn(II) affinity, plus weakened DNA affinity of the apoprotein, conspires to make the relative properties of FrmRE64H (compared with ZntR and Zur) sufficient to sense Zn(II) inside cells. PMID:26109070

A Mini HIP HOP Assay Uncovers a Central Role for Copper and Zinc in the Antifungal Mode of Action of Allicin.

PubMed

Prescott, Thomas A K; Panaretou, Barry

2017-05-10

Garlic contains the organosulfur compound allicin which exhibits potent antifungal activity. Here we demonstrate the use of a highly simplified yeast chemical genetic screen to characterize its mode of action. By screening 24 validated yeast gene deletion "signature" strains for which hypersensitivity is characteristic for common antifungal modes of action, yeast lacking the high affinity Cu 2+ transporter Ctr1 was found to be hypersensitive to allicin. Focusing on transition metal related genes identified two more hypersensitive strains lacking the Cu 2+ and Zn 2+ transcription factors Mac1 and Zap1. Hypersensitivity in these strains was reversed by the addition of Cu 2+ and Zn 2+ ions, respectively. The results suggest the antifungal activity of allicin is mediated through restricted Cu 2+ and Zn 2+ uptake or inhibition of Cu 2+ and Zn 2+ metalloproteins. As certain antimicrobial modes of action are much more common than others, the approach taken here provides a useful way to identify them early on.

Methane and Trichloroethylene Degradation by Methylosinus trichosporium OB3b Expressing Particulate Methane Monooxygenase

PubMed Central

Lontoh, Sonny; Semrau, Jeremy D.

1998-01-01

Whole-cell assays of methane and trichloroethylene (TCE) consumption have been performed on Methylosinus trichosporium OB3b expressing particulate methane monooxygenase (pMMO). From these assays it is apparent that varying the growth concentration of copper causes a change in the kinetics of methane and TCE degradation. For M. trichosporium OB3b, increasing the copper growth concentration from 2.5 to 20 μM caused the maximal degradation rate of methane (Vmax) to decrease from 300 to 82 nmol of methane/min/mg of protein. The methane concentration at half the maximal degradation rate (Ks) also decreased from 62 to 8.3 μM. The pseudo-first-order rate constant for methane, Vmax/Ks, doubled from 4.9 × 10−3 to 9.9 × 10−3 liters/min/mg of protein, however, as the growth concentration of copper increased from 2.5 to 20 μM. TCE degradation by M. trichosporium OB3b was also examined with varying copper and formate concentrations. M. trichosporium OB3b grown with 2.5 μM copper was unable to degrade TCE in both the absence and presence of an exogenous source of reducing equivalents in the form of formate. Cells grown with 20 μM copper, however, were able to degrade TCE regardless of whether formate was provided. Without formate the Vmax for TCE was 2.5 nmol/min/mg of protein, while providing formate increased the Vmax to 4.1 nmol/min/mg of protein. The affinity for TCE also increased with increasing copper, as seen by a change in Ks from 36 to 7.9 μM. Vmax/Ks for TCE degradation by pMMO also increased from 6.9 × 10−5 to 5.2 × 10−4 liters/min/mg of protein with the addition of formate. From these whole-cell studies it is apparent that the amount of copper available is critical in determining the oxidation of substrates in methanotrophs that are expressing only pMMO. PMID:16349516

Characterization of the three different states of the cholecystokinin (CCK) receptor in pancreatic acini.

PubMed

Talkad, V D; Patto, R J; Metz, D C; Turner, R J; Fortune, K P; Bhat, S T; Gardner, J D

1994-10-20

By measuring binding of [125I]CCK-8 and [3H]L-364,718 to rat pancreatic acini we demonstrated directly that the pancreatic CCK receptor can exist in three different affinity states with respect to CCK--high affinity, low affinity and very low affinity. Binding of [125I]CCK-8 reflects interaction of the tracer with the high and low affinity states, whereas binding of [3H]L-364,718 reflects interaction of the tracer with the low and very low affinity states. Treating acini with carbachol abolished the high affinity state of the CCK receptor and converted approximately 25% of the low affinity receptors to the very low affinity state. Carbachol treatment was particularly useful in establishing the values of Kd for the high and low affinity states for different CCK receptor agonists and antagonists. Of the various CCK receptor agonists tested, CCK-8 had the highest affinity for the high affinity state (Kd approximately 1 nM), whereas CCK-JMV-180 had the highest affinity for the low (Kd 7 nM) and very low affinity (Kd 200 nM) states. Gastrin and de(SO4)CCK-8 had affinities for the high and low affinity states of the receptor that were 100- to 400-fold less than those of CCK-8 but had affinities for the very low affinity state that were only 3- to 10-fold less than that of CCK-8. CCK receptor antagonists showed several patterns in interacting with the different states of the CCK receptor. L-364,718 had the same affinity for each state of the CCK receptor. CR1409 and Bt2cGMP each had similar affinities for the high and low affinity states and lower affinity for the very low affinity state. L-365,260 and CCK-JMV-179 had the highest affinity for the low affinity state and lower affinities for the high and very low affinity states. Different CCK receptor agonists caused the same maximal stimulation of amylase secretion but showed different degrees of amplification in terms of the relationship between their abilities to stimulate amylase secretion and their abilities to occupy the low affinity state of the CCK receptor. When amplification was expressed quantitatively as the value of Kd for the low affinity state divided by the corresponding EC50 for stimulating amylase secretion the values were CCK-8 (1000), de(SO)CCK-8 (1500), gastrin (100) and CCK-JMV-180 (Menozzi, D., Vinayek, R., Jensen, R.T. and Gardner, J.D. (1991) J. Biol. Chem. 266, 10385-1091).(ABSTRACT TRUNCATED AT 400 WORDS)

Recovery of copper and cyanide from waste cyanide solutions using emulsion liquid membrane with LIX 7950 as the carrier.

PubMed

Xie, Feng; Wang, Wei

2017-08-01

The feasibility of using emulsion liquid membranes (ELMs) with the guanidine extractant LIX 7950 as the mobile carrier for detoxifying copper-containing waste cyanide solutions has been determined. Relatively stable ELMs can be maintained under suitable stirring speed during mixing ELMs and the external solution. Effective extraction of copper cyanides by ELMs only occurs at pH below 11. High copper concentration in the external phase and high volume ratio of the external phase to ELMs result in high transport rates of copper and cyanide. High molar ratio of cyanide to copper tends to suppress copper extraction. The presence of thiocyanate ion significantly depresses the transport of copper and cyanide through the membrane while the thiosulfate ion produces less impact on copper removal by ELMs. Zinc and nickel cyanides can also be effectively extracted by ELMs. More than 90% copper and cyanide can be effectively removed from alkaline cyanide solutions by ELMs under suitable experimental conditions, indicating the effectiveness of using the designed ELM for recovering copper and cyanide from waste cyanide solutions.

Regional setting and characteristics of the Neoproterozoic Wadi Hamama Zn-Cu-Ag-Au prospect: evidence for an intra-oceanic island arc-hosted volcanogenic hydrothermal system

NASA Astrophysics Data System (ADS)

Abd El-Rahman, Yasser; Surour, Adel A.; El-Manawi, Abdel Hamid W.; El-Dougdoug, Abdel-Monem A.; Omar, Sayed

2015-04-01

The Wadi Hamama area is a volcanogenic Zn-Cu-Au-Ag prospect. It is hosted by a Neoproterozoic bimodal-mafic sequence, which comprises basalt, dacite and rhyolite along with volcaniclastic rocks. The rocks have a low-K tholeiitic affinity and are enriched in large ion lithophile elements over high field strength elements, which indicated their formation in an intra-oceanic island arc tectonic setting. The area was intruded by a tonalite-trondhjemite body, which has an intra-oceanic island arc affinity and later by diorite, which has a cordilleran-margin geochemical affinity. These rock units were intruded by post-tectonic granite dykes, which have a within-plate geochemical signature. There is a quartz-carbonate horizon extending along the contact between the basalt and the volcaniclastic rocks, mainly banded and lapilli tuffs. This horizon is of exhalative origin and is underlain by a mushroom-shaped alteration zone extending from the horizon down to the massive basalt. The footwall alteration is characterized by a silica-rich core surrounded by a thick chlorite sheath. Both the quartz-carbonate horizon and the footwall-altered rocks enclose historical trenches and pits. Sulfide-rich core samples are enriched in Zn, relative to Cu, and in Ag, which indicates the low-temperature nature of the hydrothermal system. The prospect was affected by supergene processes, which led to the widespread occurrence of secondary copper minerals and gold enrichment relative to the leached base metals, especially Zn. The prospect formed through a limited rifting of an intra-oceanic island arc which resulted in the formation of a small-scale volcanogenic Zn-Cu-Ag-Au prospect.

Copper induces vasorelaxation and antagonizes noradrenaline-induced vasoconstriction in rat mesenteric artery.

PubMed

Wang, Yu-Chun; Hu, Chao-Wei; Liu, Ming-Yu; Jiang, Hong-Chao; Huo, Rong; Dong, De-Li

2013-01-01

Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA) and high K(+) induced vasoconstriction. The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME). Copper did not blunt high K(+)-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K(+)-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC) antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv) significantly decreased blood pressure of rabbits and NA or DTC injection (iv) did not rescue the copper-induced hypotension and animal death. Copper blunted NA but not high K(+)-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO), but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms. © 2013 S. Karger AG, Basel.

High frequency lateral flow affinity assay using superparamagnetic nanoparticles

NASA Astrophysics Data System (ADS)

Lago-Cachón, D.; Rivas, M.; Martínez-García, J. C.; Oliveira-Rodríguez, M.; Blanco-López, M. C.; García, J. A.

2017-02-01

Lateral flow assay is one of the simplest and most extended techniques in medical diagnosis for point-of-care testing. Although it has been traditionally a positive/negative test, some work has been lately done to add quantitative abilities to lateral flow assay. One of the most successful strategies involves magnetic beads and magnetic sensors. Recently, a new technique of superparamagnetic nanoparticle detection has been reported, based on the increase of the impedance induced by the nanoparticles on a RF-current carrying copper conductor. This method requires no external magnetic field, which reduces the system complexity. In this work, nitrocellulose membranes have been installed on the sensor, and impedance measurements have been carried out during the sample diffusion by capillarity along the membrane. The impedance of the sensor changes because of the presence of magnetic nanoparticles. The results prove the potentiality of the method for point-of-care testing of biochemical substances and nanoparticle capillarity flow studies.

Sovereign Challenge Conference (6th). Borders & Security: Similarities, Differences and Shared Affinities. Held in El Paso, Texas on November 7-10, 2010

DTIC Science & Technology

2010-11-01

protection and to isolate threats in order to survive and develop. The cell model implies osmosis , allowing flows to take place across the borders and the...relationships to new levels, much as cell phone technology replaces the laying of copper wire for traditional telephone service. Whole-of-Government/Whole...in urban, rural, and remote environments. This practical experience with the men and women of the U.S. Border Patrol animated many of the concepts

Physiology and biochemistry of a lignin degrading bacterium Erwinia sp. Cu 3614

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajan, J.S.

1992-01-01

Previous researchers have reported the isolation of a diphenylether cleaving organism, Erwinia sp., using an enrichment medium containing lignin. A copper and dinitrophenol resistant mutant of this organism, Erwinia sp. Cu3614, has also been reported. To assess the effect of copper on the growth and biochemistry of this organism, continuous cultivation was used employing an apparently optimized medium containing ethanol as carbon source. Upon increasing the concentration of copper sulfate in the medium from 5 [mu]g/ml to 10 [mu]g/ml increases in maximum specific growth rate and growth yield were seen. Also decrease in the values for doubling time and themore » coefficient for maintenance energy were seen. At higher levels of copper sulfate a [open quotes]non competitive[close quotes] inhibition of growth was seen as indicated by the values calculated for substrate affinity constant, and inhibition constant. To assess this organism's ligninolytic ability, an assay for residual lignin was developed. The assay measured a reaction between diazotized sulfanilic acid and lignin in alkaline solution by spectrophotometric monitoring of the resulting adduct. Use of this technique indicated that Erwinia sp. Cu3614 could degrade up to 80% of lignin in batch cultures. Further evidence about the ligninolytic ability of this organism was provided by examination of electron micrographs of lignocellulosic substrates incubated with cell suspensions. An assay for monitoring diphenylether cleaving abilities was also developed using resazurin, a redox dye. In vivo assays with cells obtained from continuous culture studies indicated a linear relationship between the rates of reaction with resazurin and the amount of copper associated with cells. In vitro assays, employing cell free extracts and resazurin, were used to obtain a fraction enriched in diphenylether cleaving activity by a heat treatment procedure.« less

Adsorption of Cu2+ to biomass ash and its modified product.

PubMed

Xu, Lei; Cui, Hongbiao; Zheng, Xuebo; Liang, Jiani; Xing, Xiangyu; Yao, Lunguang; Chen, Zhaojin; Zhou, Jing

2017-04-01

Ash produced by biomass power plants has great potential for the removal of heavy metal ions from aqueous solution. The pollution of toxic heavy metals to water is a worldwide environmental problem. Discharges containing copper, in particular, are strictly controlled because the excessive copper can cause serious harm to the environment and human health. This work aims to investigate the adsorption characteristics of copper ions in aqueous solution by biomass ash and the modified products, and to evaluate their potential application in water pollution control. The biomass ash was modified with a mesoporous siliceous material and functionalized with 3-aminopropyltriethoxysilane. The surface properties of the biomass ash and the new matrix were studied to evaluate their adsorption property for Cu 2+ ions at different pHs, initial metal concentrations and the thermodynamic and kinetic were studied. The chemical and morphological properties of this modified material are analyzed; the specific surface area of the modified biomass ash was nine times that of the initial ash. Both of the two materials showed a strong affinity for Cu 2+ , and the Langmuir model could best represent the adsorption characteristics of Cu 2+ on the two kinds of materials. The adsorption capacity of copper on the material increased with the increase of pH and pH 6 was the optimum pH. Thermodynamic analysis results showed that the adsorption of Cu 2+ was spontaneous and endothermic in nature. The adsorptions of Cu 2+ onto the modified biomass ash followed pseudo-second-order kinetics.

Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications.

PubMed

David, Tomáš; Kubíček, Vojtěch; Gutten, Ondrej; Lubal, Přemysl; Kotek, Jan; Pietzsch, Hans-Jürgen; Rulíšek, Lubomír; Hermann, Petr

2015-12-21

Cyclam derivatives bearing one geminal bis(phosphinic acid), -CH2PO2HCH2PO2H2 (H2L(1)), or phosphinic-phosphonic acid, -CH2PO2HCH2PO3H2 (H3L(2)), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions (log KCuL = 25.8 and 27.7 for H2L(1) and H3L(2), respectively). Kinetic study revealed an unusual three-step complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu(2+) bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH ≈5, 25 °C, Cu:L = 1:1, cM ≈ 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL(2))] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L(2) compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L(1) and H3L(2) with (64)Cu was fast and efficient, even at room temperature, giving specific activities of around 70 GBq of (64)Cu per 1 μmol of the ligand (pH 6.2, 10 min, ca. 90 equiv of the ligand). These specific activities were much higher than those of H3nota and H4dota complexes prepared under identical conditions. The rare combination of simple ligand synthesis, very fast copper(II) complex formation, high thermodynamic stability, kinetic inertness, efficient radiolabeling, and expected low bone tissue affinity makes such ligands suitably predisposed to serve as chelators of copper radioisotopes in nuclear medicine.

Internal electron transfer between hemes and Cu(II) bound at cysteine beta93 promotes methemoglobin reduction by carbon monoxide.

PubMed

Bonaventura, C; Godette, G; Tesh, S; Holm, D E; Bonaventura, J; Crumbliss, A L; Pearce, L L; Peterson, J

1999-02-26

Previous studies showed that CO/H2O oxidation provides electrons to drive the reduction of oxidized hemoglobin (metHb). We report here that Cu(II) addition accelerates the rate of metHb beta chain reduction by CO by a factor of about 1000. A mechanism whereby electron transfer occurs via an internal pathway coupling CO/H2O oxidation to Fe(III) and Cu(II) reduction is suggested by the observation that the copper-induced rate enhancement is inhibited by blocking Cys-beta93 with N-ethylmaleimide. Furthermore, this internal electron-transfer pathway is more readily established at low Cu(II) concentrations in Hb Deer Lodge (beta2His --> Arg) and other species lacking His-beta2 than in Hb A0. This difference is consistent with preferential binding of Cu(II) in Hb A0 to a high affinity site involving His-beta2, which is ineffective in promoting electron exchange between Cu(II) and the beta heme iron. Effective electron transfer is thus affected by Hb type but is not governed by the R left arrow over right arrow T conformational equilibrium. The beta hemes in Cu(II)-metHb are reduced under CO at rates close to those observed for cytochrome c oxidase, where heme and copper are present together in the oxygen-binding site and where internal electron transfer also occurs.

First insights on the molybdenum-copper Bled M'Dena complex (Eglab massif, Algeria)

NASA Astrophysics Data System (ADS)

Lagraa, Karima; Salvi, Stefano; Béziat, Didier; Debat, Pierre; Kolli, Omar

2017-03-01

Molybdenum-Copper showings in the Eglab massif (eastern part of the Reguibat rise of Algeria), are found in quartz-monzodiorite and granodiorite of the Bled M'Dena complex, a Paleoproterozoic circular structure of ∼5 km in diameter, comprising volcanic and intrusive suites. The latter consist of quartz-diorite, quartz-monzodiorite and granodiorite with a metaluminous normative composition. They display an "adakitic character" with moderate light rare-earth element (LREE) enrichment, minor Eu anomalies, high Sr/Y ratio and low Yb concentration, suggestive of a hydrous, arc magma of volcanic-arc affinity. The mineralization occurs mostly in quartz + molybdenite + chalcopyrite stockwork veins marked by widespread propylitic alteration along the selvages. Molybdenite and chalcopyrite are commonly associated with calcite, which precipitated at relatively late stages of the hydrothermal alteration. Fluid inclusions related to the mineralization stage, range from aqueous to aqueous-carbonic to solid bearing. The latter inclusions have the highest homogenization temperature (up to ∼400 °C), are salt saturated, and commonly contain molybdenite and/or chalcopyrite crystals. The petrology and geochemistry of the host rocks, the style of the hydrothermal alteration, the ore mineral associations, and the characteristics of the fluid inclusions, are all coherent in indicating that the Bled M'Dena represents a Paleoproterozoic porphyry style Mo mineralization, which is far unreported in the African continent.

Phototherapeutic spectrum expansion through synergistic effect of mesoporous silica trio-nanohybrids against antibiotic-resistant gram-negative bacterium.

PubMed

Kuthati, Yaswanth; Kankala, Ranjith Kumar; Busa, Prabhakar; Lin, Shi-Xiang; Deng, Jin-Pei; Mou, Chung-Yuan; Lee, Chia-Hung

2017-04-01

The extensive impact of antibiotic resistance has led to the exploration of new anti-bacterial modalities. We designed copper impregnated mesoporous silica nanoparticles (Cu-MSN) with immobilizing silver nanoparticles (SNPs) to apply photodynamic inactivation (PDI) of antibiotic-resistant E. coli. SNPs were decorated over the Cu-MSN surfaces by coordination of silver ions on diamine-functionalized Cu-MSN and further reduced to silver nanoparticles with formalin. We demonstrate that silver is capable of sensitizing the gram-negative bacteria E. coli to a gram-positive specific phototherapeutic agent in vitro; thereby expanding curcumin's phototherapeutic spectrum. The mesoporous structure of Cu-MSN remains intact after the exterior decoration with silver nanoparticles and subsequent curcumin loading through an enhanced effect from copper metal-curcumin affinity interaction. The synthesis, as well as successful assembly of the functional nanomaterials, was confirmed by various physical characterization techniques. Curcumin is capable of producing high amounts of reactive oxygen species (ROS) under light irradiation, which can further improve the silver ion release kinetics for antibacterial activity. In addition, the positive charged modified surfaces of Cu-MSN facilitate antimicrobial response through electrostatic attractions towards negatively charged bacterial cell membranes. The antibacterial action of the synthesized nanocomposites can be activated through a synergistic mechanism of energy transfer of the absorbed light from SNP to curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

Hemoglobin and Myoglobin as Reducing Agents in Biological Systems. Redox Reactions of Globins with Copper and Iron Salts and Complexes.

PubMed

Postnikova, G B; Shekhovtsova, E A

2016-12-01

In addition to reversible O2 binding, respiratory proteins of the globin family, hemoglobin (Hb) and myoglobin (Mb), participate in redox reactions with various metal complexes, including biologically significant ones, such as those of copper and iron. HbO 2 and MbO 2 are present in cells in large amounts and, as redox agents, can contribute to maintaining cell redox state and resisting oxidative stress. Divalent copper complexes with high redox potentials (E 0 , 200-600 mV) and high stability constants, such as [Cu(phen) 2 ] 2+ , [Cu(dmphen) 2 ] 2+ , and CuDTA oxidize ferrous heme proteins by the simple outer-sphere electron transfer mechanism through overlapping π-orbitals of the heme and the copper complex. Weaker oxidants, such as Cu2+, CuEDTA, CuNTA, CuCit, CuATP, and CuHis (E 0 ≤ 100-150 mV) react with HbO 2 and MbO 2 through preliminary binding to the protein with substitution of the metal ligands with protein groups and subsequent intramolecular electron transfer in the complex (the site-specific outer-sphere electron transfer mechanism). Oxidation of HbO 2 and MbO 2 by potassium ferricyanide and Fe(3) complexes with NTA, EDTA, CDTA, ATP, 2,3-DPG, citrate, and pyrophosphate PP i proceeds mainly through the simple outer-sphere electron transfer mechanism via the exposed heme edge. According to Marcus theory, the rate of this reaction correlates with the difference in redox potentials of the reagents and their self-exchange rates. For charged reagents, the reaction may be preceded by their nonspecific binding to the protein due to electrostatic interactions. The reactions of LbO 2 with carboxylate Fe complexes, unlike its reactions with ferricyanide, occur via the site-specific outer-sphere electron transfer mechanism, even though the same reagents oxidize structurally similar MbO 2 and cytochrome b 5 via the simple outer-sphere electron transfer mechanism. Of particular biological interest is HbO 2 and MbO 2 transformation into met-forms in the presence of small amounts of metal ions or complexes (catalysis), which, until recently, had been demonstrated only for copper compounds with intermediate redox potentials. The main contribution to the reaction rate comes from copper binding to the "inner" histidines, His97 (0.66 nm from the heme) that forms a hydrogen bond with the heme propionate COO - group, and the distal His64. The affinity of both histidines for copper is much lower than that of the surface histidines residues, and they are inaccessible for modification with chemical reagents. However, it was found recently that the high-potential Fe(3) complex, potassium ferricyanide (400 mV), at a 5 to 20% of molar protein concentration can be an efficient catalyst of MbO 2 oxidation into metMb. The catalytic process includes binding of ferrocyanide anion in the region of the His119 residue due to the presence there of a large positive local electrostatic potential and existence of a "pocket" formed by Lys16, Ala19, Asp20, and Arg118 that is sufficient to accommodate [Fe(CN) 6 ] 4- . Fast, proton-assisted reoxidation of the bound ferrocyanide by oxygen (which is required for completion of the catalytic cycle), unlike slow [Fe(CN) 6 ] 4- oxidation in solution, is provided by the optimal location of neighboring protonated His113 and His116, as it occurs in the enzyme active site.

Optimizing the performance of catalytic traps for hydrocarbon abatement during the cold-start of a gasoline engine.

PubMed

Puértolas, B; Navlani-García, M; García, T; Navarro, M V; Lozano-Castelló, D; Cazorla-Amorós, D

2014-08-30

A key target to reduce current hydrocarbon emissions from vehicular exhaust is to improve their abatement under cold-start conditions. Herein, we demonstrate the potential of factorial analysis to design a highly efficient catalytic trap. The impact of the synthesis conditions on the preparation of copper-loaded ZSM-5 is clearly revealed by XRD, N2 sorption, FTIR, NH3-TPD, SEM and TEM. A high concentration of copper nitrate precursor in the synthesis improves the removal of hydrocarbons, providing both strong adsorption sites for hydrocarbon retention at low temperature and copper oxide nanoparticles for full hydrocarbon catalytic combustion at high temperature. The use of copper acetate precursor leads to a more homogeneous dispersion of copper oxide nanoparticles also providing enough catalytic sites for the total oxidation of hydrocarbons released from the adsorption sites, although lower copper loadings are achieved. Thus, synthesis conditions leading to high copper loadings jointly with highly dispersed copper oxide nanoparticles would result in an exceptional catalytic trap able to reach superior hydrocarbon abatement under highly demanding operational conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Initial stage corrosion of nanocrystalline copper particles and thin films

NASA Astrophysics Data System (ADS)

Tao, Weimin

1997-12-01

Corrosion behavior is an important issue in nanocrystalline materials research and development. A very fine grain size is expected to have significant effects on the corrosion resistance of these novel materials. However, both the macroscopic corrosion properties and the corresponding structure evolution during corrosion have not been fully studied. Under such circumstances, conducting fundamental research in this area is important and necessary. In this study, high purity nanocrystalline and coarse-grained copper were selected as our sample material, sodium nitrite aqueous solution at room temperature and air at a high temperature were employed as corrosive environments. The weight loss testing and electrochemical methods were used to obtain the macroscopic corrosion properties, whereas the high resolution transmission electron microscope was employed for the structure analysis. The weight loss tests indicate that the corrosion rate of nanocrystalline copper is about 5 times higher than that of coarse-grained copper at the initial stage of corrosion. The electrochemical measurements show that the corrosion potential of the nanocrystalline copper has a 230 mV negative shift in comparison with that of the coarse-grained copper. The nanocrystalline copper also exhibits a significantly higher exchange current density than the coarse-grained copper. High resolution TEM revealed that the surface structure changes at the initial stage of corrosion. It was found that the first copper oxide layer formed on the surface of nanocrystalline copper thin film contains a large density of high angle grain boundaries, whereas that formed on the surface of coarse-grained copper shows highly oriented oxide nuclei and appears to show a strong tendency for forming low angle grain boundaries. A correlation between the macroscopic corrosion properties and the structure characteristics is proposed for the nanocrystalline copper based on the concept of the "apparent" exchange current density associated with mass transport of ions in the oxide layer. A hypothesis is developed that the high corrosion rate of the nanocrystalline copper is closely associated with the structure of the copper oxide layer. Therefore, a high "apparent" exchange current density for the nanocrystalline copper is associated with the high angle grain boundary structure in the initial oxide layer. Additional structure analysis was also carried out: (a) High resolution TEM imaging has provided a cross sectional view of the epitaxial interface between nanocrystalline copper and copper (I) oxide and explicitly discloses the presence of interface defects such as misfit dislocations. Based on this observation, a mechanism was proposed to explain the Cu/Cusb2O interface misfit accommodation. This appears to be the first time this interface has been directly examined. (b) A nanocrystalline analogue to a cross-section of Gwathmey's copper single crystal sphere was revealed by high resolution TEM imaging. A partially oxidized nanocrystalline copper particle is used to examine the variation of the Cu/Cusb2O orientation relationship with respect to changes in surface orientation. A new orientation relationship, Cu (011) //Cusb2O (11), ˜ Cu(011)//Cusb2O(111), was found for the oxidation of nanocrystalline copper.

Phytostabilization potential of evening primrose (Oenothera glazioviana) for copper-contaminated sites.

PubMed

Guo, Pan; Wang, Ting; Liu, Yanli; Xia, Yan; Wang, Guiping; Shen, Zhenguo; Chen, Yahua

2014-01-01

A field investigation, field experiment, and hydroponic experiment were conducted to evaluate feasibility of using Oenothera glazioviana for phytostabilization of copper-contaminated soil. In semiarid mine tailings in Tongling, Anhui, China, O. glazioviana, a copper excluder, was a dominant species in the community, with a low bioaccumulation factor, the lowest copper translocation factor, and the lowest copper content in seed (8 mg kg(-1)). When O. glazioviana was planted in copper-polluted farmland soil in Nanjing, Jiangsu, China, its growth and development improved and the level of γ-linolenic acid in seeds reached 17.1%, compared with 8.73% in mine tailings. A hydroponic study showed that O. glazioviana had high tolerance to copper, low upward transportation capacity of copper, and a high γ-linolenic acid content. Therefore, it has great potential for the phytostabilization of copper-contaminated soils and a high commercial value without risk to human health.

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

PubMed

Wang, F; Jiao, P; Qi, M; Frezza, M; Dou, Q P; Yan, B

2010-01-01

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

A novel colorimetric method based on copper nanoclusters with intrinsic peroxidase-like for detecting xanthine in serum samples

NASA Astrophysics Data System (ADS)

Yan, Zhengyu; Niu, Qianqian; Mou, Mingyao; Wu, Yi; Liu, Xiaoxuan; Liao, Shenghua

2017-07-01

A facile strategy for detecting xanthine in serum samples by copper nanocluster (CuNCs) with high intrinsic peroxidase-like activity was reported. Firstly, a simple, mild and time-saving method for preparing CuNCs was developed, in which dithiothreitol (DTT) and bovine serum albumin (BSA) were used as reductant and stabilizer, respectively. The as-prepared CuNCs exhibited a fluorescence emission at 590 nm with a quantum yield (QY) of approximately 5.29%, the fluorescence intensity of the as-prepared CuNCs exhibited no considerable change when stored under ambient condition with the lifetime is 1.75 μs. Moreover, the as-prepared CuNCs exhibited high intrinsic peroxidase-like activity with lower K m ( K m = 8.90 × 10-6 mol L-1) for H2O2, which indicated that CuNCs have a higher affinity for H2O2. Compared with natural enzyme, the as-synthesized CuNCs are more catalytic stable over a wide range of pH (4.0 13.0) and temperature (4 80 °C). Finally, an indirect method for sensing xanthine was established because xanthine oxidase can catalyse the oxidation of xanthine to produce H2O2. Xanthine could be detected as low as 3.8 × 10-7 mol L-1 with a linear range from 5.0 × 10-7 to 1.0 × 10-4 mol L-1. These results proved that the proposed method is sensitive and accurate and could be successfully applied to the determination of xanthine in the serum sample with satisfaction.

Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

NASA Technical Reports Server (NTRS)

Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

1999-01-01

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

Cloning and functional characterization of the high-affinity K+ transporter HAK1 of pepper.

PubMed

Martínez-Cordero, M Angeles; Martínez, Vicente; Rubio, Francisco

2004-10-01

High-affinity K+ uptake in plants plays a crucial role in K+ nutrition and different systems have been postulated to contribute to the high-affinity K+ uptake. The results presented here with pepper (Capsicum annum) demonstrate that a HAK1-type transporter greatly contributes to the high-affinity K+ uptake observed in roots. Pepper plants starved of K+ for 3 d showed high-affinity K+ uptake (Km of 6 microM K+) that was very sensitive to NH and their roots expressed a high-affinity K+ transporter, CaHAK1, which clusters in group I of the KT/HAK/KUP family of transporters. When expressed in yeast ( Saccharomyces cerevisiae ), CaHAK1 mediated high-affinity K+ and Rb+ uptake with Km values of 3.3 and 1.9 microM, respectively. Rb+ uptake was competitively inhibited by micromolar concentrations of NH and Cs+, and by millimolar concentrations of Na+.

Developing radiopure copper alloys for high strength low background applications

NASA Astrophysics Data System (ADS)

Suriano, A. M.; Howard, S. M.; Christofferson, C. D.; Arnquist, I. J.; Hoppe, E. W.

2018-01-01

High purity copper continues to play an important role for ultra-low-background detectors. Measurements of rare nuclear decays, e.g. neutrinoless double-beta decay, and searches for dark matter can require construction materials that have high thermal and electrical conductivity with bulk radiopurity less than one micro-Becquerel per kilogram. However, experiments currently using components constructed of radiopure electroformed copper struggle with design of structural and mechanical parts due to the physical properties of pure copper. A higher strength material which possesses many of the favorable attributes of copper yet remains radiopure is desired. A number of copper alloying candidates which may provide improved mechanical performance and adequate radiopurity were considered. Development of an electrodeposited copper-chrome alloy from additive-free electrolyte systems is discussed. The resulting material is shown to possess high strength and meets the aforementioned radiopurity goals.

Evaluating the corrosiveness of southern pine treated with several wood preservatives using electrochemical techniques

Treesearch

Samuel L. Zelinka; Douglas R. Rammer; Donald S. Stone

2009-01-01

Chromated copper arsenate (CCA), the most widely used wood preservative of the past 50 years, has been replaced for most uses with alkaline-copper systems such as alkaline copper quaternary (ACQ), copper azole (CuAz) and micronized copper quaternary (MCQ). Preliminary research using high-temperature, high-humidity environments have shown that some of these wood...

Dietary fructose but not starch is responsible for hyperlipidemia associated with copper deficiency in rats: effect of high-fat diet.

PubMed

Fields, M; Lewis, C G

1999-02-01

To test the hypothesis that copper deficiency in rats may be hyperlipidemic only when the diets consumed contain nutrients which contribute to blood lipids such as fructose and high fat. Weanling male Sprague Dawley rats were fed diets which contained either starch or fructose as their sole carbohydrate source. The diets were either inadequate (0.6 microg Cu/g) or adequate (6.0 microg Cu/g) in copper and contained either high (300 g/kg) or low (60 g/kg) fat. At the end of the 4th week the rats were killed. Livers were analyzed for copper content. Plasma was analyzed for cholesterol and triglyceride concentrations. High-fat diet did not increase blood lipids in rats fed a copper-deficient diet containing starch. In contrast, the combination of high-fat diet with fructose increased blood triglycerides and fructose with copper deficiency resulted in a significant increases in blood cholesterol. Hyperlipidemia of copper deficiency in rats is dependent on synergistic effects between dietary fructose and copper deficiency and fructose and amount of dietary fat. Hyperlipidemia does not develop if starch is the main source of dietary carbohydrate in a copper-deficient diet even if a high-fat diet is fed.

Cytoplasmic CopZ-Like Protein and Periplasmic Rusticyanin and AcoP Proteins as Possible Copper Resistance Determinants in Acidithiobacillus ferrooxidans ATCC 23270

PubMed Central

Navarro, Claudio A.; von Bernath, Diego; Martínez-Bussenius, Cristóbal; Castillo, Rodrigo A.

2015-01-01

Acidophilic organisms, such as Acidithiobacillus ferrooxidans, possess high-level resistance to copper and other metals. A. ferrooxidans contains canonical copper resistance determinants present in other bacteria, such as CopA ATPases and RND efflux pumps, but these components do not entirely explain its high metal tolerance. The aim of this study was to find other possible copper resistance determinants in this bacterium. Transcriptional expression of A. ferrooxidans genes coding for a cytoplasmic CopZ-like copper-binding chaperone and the periplasmic copper-binding proteins rusticyanin and AcoP, which form part of an iron-oxidizing supercomplex, was found to increase when the microorganism was grown in the presence of copper. All of these proteins conferred more resistance to copper when expressed heterologously in a copper-sensitive Escherichia coli strain. This effect was absent when site-directed-mutation mutants of these proteins with altered copper-binding sites were used in this metal sensitivity assay. These results strongly suggest that the three copper-binding proteins analyzed here are copper resistance determinants in this extremophile and contribute to the high-level metal resistance of this industrially important biomining bacterium. PMID:26637599

Role of the constant region domain in the structural diversity of human antibody light chains.

PubMed

Hifumi, Emi; Taguchi, Hiroaki; Kato, Ryuichi; Uda, Taizo

2017-04-01

Issues regarding the structural diversity (heterogeneity) of an antibody molecule have been the subject of discussion along with the development of antibody drugs. Research on heterogeneity has been extensive in recent years, but no clear solution has been reached. Heterogeneity is also observed in catalytic antibody κ light chains (CLs). In this study, we investigated how the constant region domain of CLs concerns structural diversity because it is a simple and good example for elucidating heterogeneity. By means of cation-exchange chromatography, SDS-PAGE, and 2-dimensional electrophoresis for the CL, multimolecular forms consisting of different electrical charges and molecular sizes coexisted in the solution, resulting in the similar heterogeneity of the full length of CLs. The addition of copper ion could cause the multimolecular forms to change to monomolecular forms. Copper ion contributed greatly to the enrichment of the dimer form of CL and the homogenization of the differently charged CLs. Two molecules of the CL protein bound one copper ion. The binding affinity of the ion was 48.0 μM -1 Several divalent metal ions were examined, but only zinc showed a similar effect.-Hifumi, E., Taguchi, H., Kato, R., Uda, T. Role of the constant region domain in the structural diversity of human antibody light chains. © FASEB.

Copper and nitrophenol pollutants removal by Na-montmorillonite/alginate microcapsules.

PubMed

Ely, Abdellahi; Baudu, Michel; Basly, Jean-Philippe; Kankou, Mohamed Ould Sid'Ahmed Ould

2009-11-15

The use of renewable bioresources allows the development of low cost adsorbents that are versatile. In the present paper, the affinity and the removal capacity of montmorillonite/alginate microcapsules for a hydrophobic organic pollutant (4-nitrophenol) and an inorganic pollutant (copper) were evaluated. The physicochemical processes through sorption and kinetic experiments under different ratios of montmorillonite vs. alginate and initial contaminant concentrations were investigated. The total weight loss and diameter decrease during the drying process were 90-96% and 64%, respectively. A significant decrease in beads diameter, related to water elimination, has been observed during the first 24h. Structural modifications that occur during the drying process were evaluated using thermal analysis. From correlation coefficients, the second-order equation depicts properly the adsorption of copper by the microbeads adsorption capacity increases to saturation with time; 3 and 6h were needed to reach equilibrium on wet and dry mixed microcapsules. The pseudo-second order model properly depicts the adsorption process of 4-NP onto Na-mont and (Na-mont/SA) mixed microcapsules but failed to reproduce the data observed for the alginate beads. Isotherms data were fitted with good correlation using the Langmuir model; alginate and montmorillonite adsorption capacities (q(m)/wet beads) agree with those obtained by various studies.

Direct patterning of highly-conductive graphene@copper composites using copper naphthenate as a resist for graphene device applications.

PubMed

Bi, Kaixi; Xiang, Quan; Chen, Yiqin; Shi, Huimin; Li, Zhiqin; Lin, Jun; Zhang, Yongzhe; Wan, Qiang; Zhang, Guanhua; Qin, Shiqiao; Zhang, Xueao; Duan, Huigao

2017-11-09

We report an electron-beam lithography process to directly fabricate graphene@copper composite patterns without involving metal deposition, lift-off and etching processes using copper naphthenate as a high-resolution negative-tone resist. As a commonly used industrial painting product, copper naphthenate is extremely cheap with a long shelf time but demonstrates an unexpected patterning resolution better than 10 nm. With appropriate annealing under a hydrogen atmosphere, the produced graphene@copper composite patterns show high conductivity of ∼400 S cm -1 . X-ray diffraction, conformal Raman spectroscopy and X-ray photoelectron spectroscopy were used to analyze the chemical composition of the final patterns. With the properties of high resolution and high conductivity, the patterned graphene@copper composites could be used as conductive pads and interconnects for graphene electronic devices with ohmic contacts. Compared to common fabrication processes involving metal evaporation and lift-off steps, this pattern-transfer-free fabrication process using copper naphthenate resist is direct and simple but allows comparable device performance in practical device applications.

High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

PubMed Central

Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R.; Collins, James F.

2016-01-01

Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

Identification and partial characterization of a low affinity metal-binding site in the light chain of tetanus toxin.

PubMed

Wright, J F; Pernollet, M; Reboul, A; Aude, C; Colomb, M G

1992-05-05

Tetanus toxin was shown to contain a metal-binding site for zinc and copper. Equilibrium dialysis binding experiments using 65Zn indicated an association constant of 9-15 microM, with one zinc-binding site/toxin molecule. The zinc-binding site was localized to the toxin light chain as determined by binding of 65Zn to the light chain but not to the heavy chain after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transfer to Immobilon membranes. Copper was an efficient inhibitor of 65Zn binding to tetanus toxin and caused two peptide bond cleavages in the toxin light chain in the presence of ascorbate. These metal-catalyzed oxidative cleavages were inhibited by the presence of zinc. Partial characterization of metal-catalyzed oxidative modifications of a peptide based on a putative metal-binding site (HELIH) in the toxin light chain was used to map the metal-binding site in the protein.

CHL1 is a dual-affinity nitrate transporter of Arabidopsis involved in multiple phases of nitrate uptake.

PubMed Central

Liu, K H; Huang, C Y; Tsay, Y F

1999-01-01

Higher plants have both high- and low-affinity nitrate uptake systems. These systems are generally thought to be genetically distinct. Here, we demonstrate that a well-known low-affinity nitrate uptake mutant of Arabidopsis, chl1, is also defective in high-affinity nitrate uptake. Two to 3 hr after nitrate induction, uptake activities of various chl1 mutants at 250 microM nitrate (a high-affinity concentration) were only 18 to 30% of those of wild-type plants. In these mutants, both the inducible phase and the constitutive phase of high-affinity nitrate uptake activities were reduced, with the inducible phase being severely reduced. Expressing a CHL1 cDNA driven by the cauliflower mosaic virus 35S promoter in a transgenic chl1 plant effectively recovered the defect in high-affinity uptake for the constitutive phase but not for the induced phase, which is consistent with the constitutive level of CHL1 expression in the transgenic plant. Kinetic analysis of nitrate uptake by CHL1-injected Xenopus oocytes displayed a biphasic pattern with a Michaelis-Menten Km value of approximately 50 microM for the high-affinity phase and approximately 4 mM for the low-affinity phase. These results indicate that in addition to being a low-affinity nitrate transporter, as previously recognized, CHL1 is also involved in both the inducible and constitutive phases of high-affinity nitrate uptake in Arabidopsis. PMID:10330471

Exploring high-affinity binding properties of octamer peptides by principal component analysis of tetramer peptides.

PubMed

Kume, Akiko; Kawai, Shun; Kato, Ryuji; Iwata, Shinmei; Shimizu, Kazunori; Honda, Hiroyuki

2017-02-01

To investigate the binding properties of a peptide sequence, we conducted principal component analysis (PCA) of the physicochemical features of a tetramer peptide library comprised of 512 peptides, and the variables were reduced to two principal components. We selected IL-2 and IgG as model proteins and the binding affinity to these proteins was assayed using the 512 peptides mentioned above. PCA of binding affinity data showed that 16 and 18 variables were suitable for localizing IL-2 and IgG high-affinity binding peptides, respectively, into a restricted region of the PCA plot. We then investigated whether the binding affinity of octamer peptide libraries could be predicted using the identified region in the tetramer PCA. The results show that octamer high-affinity binding peptides were also concentrated in the tetramer high-affinity binding region of both IL-2 and IgG. The average fluorescence intensity of high-affinity binding peptides was 3.3- and 2.1-fold higher than that of low-affinity binding peptides for IL-2 and IgG, respectively. We conclude that PCA may be used to identify octamer peptides with high- or low-affinity binding properties from data from a tetramer peptide library. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Evaluation of copper resistant bacteria from vineyard soils and mining waste for copper biosorption

PubMed Central

Andreazza, R.; Pieniz, S.; Okeke, B.C.; Camargo, F.A.O

2011-01-01

Vineyard soils are frequently polluted with high concentrations of copper due application of copper sulfate in order to control fungal diseases. Bioremediation is an efficient process for the treatment of contaminated sites. Efficient copper sorption bacteria can be used for bioremoval of copper from contaminated sites. In this study, a total of 106 copper resistant bacteria were examined for resistance to copper toxicity and biosorption of copper. Eighty isolates (45 from vineyard Mollisol, 35 from Inceptisol) were obtained from EMBRAPA (Empresa Brasileira de Pesquisa Agropecuária) experimental station, Bento Gonçalves, RS, Brazil (29°09′53.92″S and 51°31′39.40″W) and 26 were obtained from copper mining waste from Caçapava do Sul, RS, Brazil (30°29′43.48″S and 53′32′37.87W). Based on resistance to copper toxicity and biosorption, 15 isolates were identified by 16S rRNA gene sequencing. Maximal copper resistance and biosorption at high copper concentration were observed with isolate N2 which removed 80 mg L−1 in 24 h. Contrarily isolate N11 (Bacillus pumilus) displayed the highest specific copper biosorption (121.82 mg/L/OD unit in 24 h). GenBank MEGABLAST analysis revealed that isolate N2 is 99% similar to Staphylococcus pasteuri. Results indicate that several of our isolates have potential use for bioremediation treatment of vineyards soils and mining waste contaminated with high copper concentration. PMID:24031606

Effect of Minor Titanium Addition on Copper/Diamond Composites Prepared by Hot Forging

NASA Astrophysics Data System (ADS)

Yang, Fei; Sun, Wei; Singh, Ajit; Bolzoni, Leandro

2018-03-01

Copper/diamond composites have great potential to lead the next generation of advanced heat sink materials for use in high-power electronic devices and high-density integrated circuits because of their potential excellent properties of high thermal conductivity and close thermal expansion to the chip materials (e.g., Si, InP, GaAs). However, the poor wettability between copper and diamond presents a challenge for synthesizing copper/diamond composites with effective metallurgical bonding and satisfied thermal performance. In this article, copper/diamond composites were successfully prepared by hot forging of elemental copper and artificial diamond powders with small amounts (0 vol.%, 3 vol.% and 5 vol.%) of titanium additives. Microstructure observation and mechanical tests showed that adding minor titanium additions in the copper/diamond composite resulted in fewer cracks in the composites' microstructure and significantly improved the bonding between the copper and diamond. The strongest bonding strength was achieved for the copper/diamond composite with 3 vol.% titanium addition, and the possible reasons were discussed.

Electrodeposition of Copper onto Polypyrrole Films: Application to Proton Reduction

NASA Astrophysics Data System (ADS)

Chikouche, Imene; Sahari, Ali; Zouaoui, Ahmed; Zegadi, Ameur

2016-09-01

In this paper, we have electrodeposited copper on polypyrrole surface. Results show that at high applied cathodic potential (>-1.8V), copper electrodeposition occurs with difficulties. The amount of electrodeposited copper is low (1.32%) and it is limited by the low polypyrrole conductivity. At this potential, poor conductivity is caused by its insulating state. However, at an applied cathodic potential of -1.2V, the polypyrrole exhibits a relatively high conductivity and copper particles are electrodeposited with large amounts (12.44%) on polypyrrole/silicon system. At high applied cathodic potential, the SEM images show clearly dispersed grains of copper, but polypyrrole surface is less occupied. At an applied cathodic potential of -1.2V, the SEM image shows that polypyrrole surface is homogenously more occupied with copper. After copper deposition, the Cu/PPy/Si system is used to catalyze the hydrogen reaction. It was found that, once the deposited copper is present with considerable amounts, the proton reduction occurs easily. As for the polypyrrole conductivity, it was found that electrodeposited copper onto PPy/Si surface affect the total conductivity.

Formation of Copper Catalysts for CO 2 Reduction with High Ethylene/Methane Product Ratio Investigated with In Situ X-ray Absorption Spectroscopy

DOE PAGES

Eilert, André; Roberts, F. Sloan; Friebel, Daniel; ...

2016-04-04

Nanostructured copper cathodes are among the most efficient and selective catalysts to date for making multicarbon products from the electrochemical carbon dioxide reduction reaction (CO 2RR). We report an in situ X-ray absorption spectroscopy investigation of the formation of a copper nanocube CO 2RR catalyst with high activity that highly favors ethylene over methane production. The results show that the precursor for the copper nanocube formation is copper(I)-oxide, not copper(I)-chloride as previously assumed. A second route to an electrochemically similar material via a copper(II)–carbonate/hydroxide is also reported. In conclusion, this study highlights the importance of using oxidized copper precursors formore » constructing selective CO 2 reduction catalysts and shows the precursor oxidation state does not affect the electrocatalyst selectivity toward ethylene formation.« less

ELEMENTAL MERCURY IN COPPER, SILVER, AND GOLD ORES: AN UNEXPECTED CONTRIBUTION TO LAKE SUPERIOR SEDIMENTS WITH GLOBAL IMPLICATIONS

EPA Science Inventory

Mercury and copper inventories are low in central Lake Superior and increase markedly towards the Keweenaw Peninsula...where copper, mercury, and silver inventories are elevated and highly correlated. High copper, silver, and mercury inventories can be traced back to shoreline st...

Cytoplasmic CopZ-Like Protein and Periplasmic Rusticyanin and AcoP Proteins as Possible Copper Resistance Determinants in Acidithiobacillus ferrooxidans ATCC 23270.

PubMed

Navarro, Claudio A; von Bernath, Diego; Martínez-Bussenius, Cristóbal; Castillo, Rodrigo A; Jerez, Carlos A

2016-02-15

Acidophilic organisms, such as Acidithiobacillus ferrooxidans, possess high-level resistance to copper and other metals. A. ferrooxidans contains canonical copper resistance determinants present in other bacteria, such as CopA ATPases and RND efflux pumps, but these components do not entirely explain its high metal tolerance. The aim of this study was to find other possible copper resistance determinants in this bacterium. Transcriptional expression of A. ferrooxidans genes coding for a cytoplasmic CopZ-like copper-binding chaperone and the periplasmic copper-binding proteins rusticyanin and AcoP, which form part of an iron-oxidizing supercomplex, was found to increase when the microorganism was grown in the presence of copper. All of these proteins conferred more resistance to copper when expressed heterologously in a copper-sensitive Escherichia coli strain. This effect was absent when site-directed-mutation mutants of these proteins with altered copper-binding sites were used in this metal sensitivity assay. These results strongly suggest that the three copper-binding proteins analyzed here are copper resistance determinants in this extremophile and contribute to the high-level metal resistance of this industrially important biomining bacterium. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Covalent attachment of Arc repressor subunits by a peptide linker enhances affinity for operator DNA.

PubMed

Robinson, C R; Sauer, R T

1996-01-09

By designing a recombinant gene containing tandem copies of the arc coding sequence with intervening DNA encoding the linker sequence GGGSGGGTGGGSGGG, the two subunits of the P22 Are repressor dimer have been covalently linked to form a single-chain protein called Arc-L1-Arc. The 15-residue linker joins the C-terminus of one monomer to the N-terminus of the second, a distance of approximately 45 A in the Arc-operator cocrystal structure. Arc-L1-Arc is expressed at high levels in Escherichia coli, with no evidence of degradation or proteolytic clipping of the linker, and is more active than wild-type Arc in repression assays. The purified Arc-L1-Arc protein has the molecular weight expected for the designed protein and unfolds cooperatively, reversibly, and with no concentration dependence in thermal-denaturation studies. Arc-L1-Arc protects operator DNA in a manner indistinguishable from that of wild-type Arc in DNase I and copper-phenanthroline footprinting studies, but the covalent attachment of the two monomers results in enhanced affinity for operator DNA. Arc-L1-Arc binds operator DNA half-maximally at a concentration of 1.7 pM, compared with the wild-type value of 185 pM, and also binds DNA fragments containing the left or right operator half-sites more tightly than wild type. Because wild-type Arc is monomeric at sub-nanomolar concentrations and must dimerize before binding to the operator, it was anticipated that Arc-L1-Arc would exhibit a lower half-maximal binding concentration. However, even when the change from a monomeric to a dimeric species is taken into account, the affinity of Arc-L1-Arc for operator and half-operator DNA is greater than the wild-type affinity. This tighter binding appears to result from slower dissociation, as Arc-L1-Arc DNA complexes with full or half-site operators dissociate at rates 5-10 times slower than the corresponding Arc--DNA complexes. Hence, the activity of the designed Arc-L1-Arc protein is substantially increased relative to wild-type Arc in a variety of assays.

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il; Shoshani-Dror, Dana; Guillemin, Claire

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy.more » Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and oxidative stress of liver.« less

Liver mitochondrial dysfunction and electron transport chain defect induced by high dietary copper in broilers.

PubMed

Yang, Fan; Cao, Huabin; Su, Rongsheng; Guo, Jianying; Li, Chengmei; Pan, Jiaqiang; Tang, Zhaoxin

2017-09-01

Copper is an important trace mineral in the diet of poultry due to its biological activity. However, limited information is available concerning the effects of high copper on mitochondrial dysfunction. In this study, 72 broilers were used to investigate the effects of high dietary copper on liver mitochondrial dysfunction and electron transport chain defect. Birds were fed with different concentrations [11, 110, 220, and 330 mg of copper/kg dry matter (DM)] of copper from tribasic copper chloride (TBCC). The experiment lasted for 60 d. Liver tissues on d 60 were subjected to histopathological observation. Additionally, liver mitochondrial function was recorded on d 12, 36, and 60. Moreover, a site-specific defect in the electron transport chain in liver mitochondria was also identified by using various chemical inhibitors of mitochondrial respiration. The results showed different degrees of degeneration, mitochondrial swelling, and high-density electrons in hepatocytes. In addition, the respiratory control ratio (RCR) and oxidative phosphorylation rate (OPR) in liver mitochondria increased at first and then decreased in high-dose groups. Moreover, hydrogen peroxide (H2O2) generation velocity in treated groups was higher than that in control group, which were magnified by inhibiting electron transport at Complex IV. The results indicated that high dietary copper could decline liver mitochondrial function in broilers. The presence of a site-specific defect at Complex IV in liver mitochondria may be responsible for liver mitochondrial dysfunction caused by high dietary copper. © 2017 Poultry Science Association Inc.

Charge-transfer photodissociation of adsorbed molecules via electron image states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, E. T.

The 248 and 193 nm photodissociations of submonolayer quantities of CH{sub 3}Br and CH{sub 3}I adsorbed on thin layers of n-hexane indicate that the dissociation is caused by dissociative electron attachment from subvacuum level photoelectrons created in the copper substrate. The characteristics of this photodissociation-translation energy distributions and coverage dependences show that the dissociation is mediated by an image potential state which temporarily traps the photoelectrons near the n-hexane-vacuum interface, and then the charge transfers from this image state to the affinity level of a coadsorbed halomethane which then dissociates.

Quantitative analysis of rat brain alpha 2-receptors discriminated by [3H]clonidine and [3H]rauwolscine.

PubMed

Asakura, M; Tsukamoto, T; Imafuku, J; Matsui, H; Ino, M; Hasegawa, K

1984-10-30

Quantitative analysis of direct ligand binding of both [3H]clonidine and [3H]rauwolscine to the rat cerebral cortex alpha 2-receptors indicates the existence of two affinity states of the same receptor populations. In the presence of Mn2+, the high affinity state of [3H]clonidine binding was increased, whereas the high affinity state of [3H]rauwolscine binding was reduced. By contrast, GTP in micromolar ranges caused a decrease of the agonist high affinity state and an increase of the antagonist high affinity state. The total receptor sites and the respective separate affinities for both radioligands were approximately equal to their control values under all conditions, indicating that Mn2+ and GTP modulate the proportion of the two affinity states of the receptor. These results can be incorporated into a two-step, ternary complex model involving a guanine nucleotide binding protein (N protein) for the agonist and antagonist interaction with the alpha 2-receptor. Furthermore, the effects of GTP on the interaction of both ligands with the two affinity states can be mimicked by EDTA. It is suggested that divalent cations induce the formation of the receptor-N protein binary complex showing high affinity for agonists and low affinity for antagonists.

Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs.

PubMed

Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedahl; Haugaard, Anne Stæhr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardóttir, Sara Björk; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E; Clausen, Rasmus Prætorius; Harpsøe, Kasper; Wellendorph, Petrine; Frølund, Bente

2017-11-09

γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K i ) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.

Development of a highly sensitive MIP based-QCM nanosensor for selective determination of cholic acid level in body fluids.

PubMed

Gültekin, Aytaç; Karanfil, Gamze; Sönmezoğlu, Savaş; Say, Rıdvan

2014-09-01

Determination of cholic acid is very important and necessary in body fluids due to its both pharmaceutical and clinical significance. In this study, a quartz crystal microbalance (QCM) nanosensor, which is imprinted cholic acid, has been developed for the assignation of cholic acid. The cholic acid selective memories have been generated on QCM electrode surface by using molecularly imprinted polymer (MIP) based on methacryloylamidohistidine-copper (II) (MAH-Cu(II)) pre-organized monomer. The cholic acid imprinted nanosensor was characterized by atomic force microscopy (AFM) and then analytical performance of the cholic acid imprinted QCM nanosensor was studied. The detection limit was found to be 0.0065μM with linear range of 0.01-1,000 μM. Moreover, the high value of Langmuir constant (b) (7.3*10(5)) obtained by Langmuir graph showed that the cholic acid imprinted nanosensor had quite strong binding sites affinity. At the last step of this procedure, cholic acid levels in body fluids were determined by the prepared imprinted QCM nanosensor. Copyright © 2014 Elsevier B.V. All rights reserved.

Highly Conductive and Reliable Copper-Filled Isotropically Conductive Adhesives Using Organic Acids for Oxidation Prevention

NASA Astrophysics Data System (ADS)

Chen, Wenjun; Deng, Dunying; Cheng, Yuanrong; Xiao, Fei

2015-07-01

The easy oxidation of copper is one critical obstacle to high-performance copper-filled isotropically conductive adhesives (ICAs). In this paper, a facile method to prepare highly reliable, highly conductive, and low-cost ICAs is reported. The copper fillers were treated by organic acids for oxidation prevention. Compared with ICA filled with untreated copper flakes, the ICA filled with copper flakes treated by different organic acids exhibited much lower bulk resistivity. The lowest bulk resistivity achieved was 4.5 × 10-5 Ω cm, which is comparable to that of commercially available Ag-filled ICA. After 500 h of 85°C/85% relative humidity (RH) aging, the treated ICAs showed quite stable bulk resistivity and relatively stable contact resistance. Through analyzing the results of x-ray diffraction, x-ray photoelectron spectroscopy, and thermogravimetric analysis, we found that, with the assistance of organic acids, the treated copper flakes exhibited resistance to oxidation, thus guaranteeing good performance.

Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

PubMed Central

Orcutt, Kelly Davis; Slusarczyk, Adrian L; Cieslewicz, Maryelise; Ruiz-Yi, Benjamin; Bhushan, Kumar R; Frangioni, John V; Wittrup, K Dane

2014-01-01

Introduction In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to DOTA chelates for use in PRIT applications. Methods We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), reformatted as a single chain variable fragment (scFv). Results Modeling predicts that for high antigen density and saturating bsAb dose, a hapten binding affinity of 100 picomolar (pM) is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nanomolar (nM) to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2 ± 1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen (CEA), pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions We have engineered a versatile, high-affinity DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals. PMID:21315278

SOLVING COPPER CORROSION PROBLEMS WHILE MAINTAINING LEAD CONTROL IN A HIGH ALKALINITY WATER USING ORTHOPHOSPHATE

EPA Science Inventory

Lead and Copper Rule sampling in 1992 uncovered high copper levels in many homes in the Indian Hill Water Works, Ohio (IHWW) water system. The 90th percentile copper and lead levels were 1.63 mg/L and 0.012 mg/L, respectively. IHWW supplies water to several suburban communities t...

Genetic identification of a gene involved in constitutive, high-affinity nitrate transport in higher plants.

PubMed Central

Wang, R; Crawford, N M

1996-01-01

Two mutations have been found in a gene (NRT2) of Arabidopsis thaliana that specifically impair constitutive, high-affinity nitrate uptake. These mutants were selected for resistance to 0.1 mM chlorate in the absence of nitrate. Progency from one of the backcrossed mutants showed no constitutive uptake of nitrate below 0.5 mM at pH 7.0 in liquid culture (that is, within 30 min of initial exposure to nitrate). All other uptake activities measured (high-affinity phosphate and sulfate uptake, inducible high-affinity nitrate uptake, and constitutive low-affinity nitrate uptake) were present or nearly normal in the backcrossed mutant. Electrophysiological analysis of individual root cells showed that the nrt2 mutant showed little response to 0.25 mM of nitrate, whereas NRT2 wild-type cells showed an initial depolarization followed by recovery. At 10 mM of nitrate both the mutant and wild-type cells displayed similar, strong electrical responses. These results indicate that NRT2 is a critical and perhaps necessary gene for constitutive, high-affinity nitrate uptake in Arabidopsis, but not for inducible, high-affinity nor constitutive, low-affinity nitrate uptake. Thus, these systems are genetically distinct. PMID:8799195

Spatial investigation of the elemental distribution in Wilson's disease liver after d-penicillamine treatment by LA-ICP-MS.

PubMed

Hachmöller, Oliver; Zibert, Andree; Zischka, Hans; Sperling, Michael; Groba, Sara Reinartz; Grünewald, Inga; Wardelmann, Eva; Schmidt, Hartmut H-J; Karst, Uwe

2017-12-01

At present, the copper chelator d-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10μm) laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method was applied. Untreated LPP -/- rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA-ICP-MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

High-strength braze joints between copper and steel

NASA Technical Reports Server (NTRS)

Kuhn, R. F.

1967-01-01

High-strength braze joints between copper and steel are produced by plating the faying surface of the copper with a layer of gold. This reduces porosity in the braze area and strengthens the resultant joint.

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

PubMed Central

Williams, Caitlin L.; Neu, Heather M.; Gilbreath, Jeremy J.; Michel, Sarah L. J.; Zurawski, Daniel V.

2016-01-01

ABSTRACT Acinetobacter baumannii is an important emerging pathogen that is capable of causing many types of severe infection, especially in immunocompromised hosts. Since A. baumannii can rapidly acquire antibiotic resistance genes, many infections are on the verge of being untreatable, and novel therapies are desperately needed. To investigate the potential utility of copper-based antibacterial strategies against Acinetobacter infections, we characterized copper resistance in a panel of recent clinical A. baumannii isolates. Exposure to increasing concentrations of copper in liquid culture and on solid surfaces resulted in dose-dependent and strain-dependent effects; levels of copper resistance varied broadly across isolates, possibly resulting from identified genotypic variation among strains. Examination of the growth-phase-dependent effect of copper on A. baumannii revealed that resistance to copper increased dramatically in stationary phase. Moreover, A. baumannii biofilms were more resistant to copper than planktonic cells but were still susceptible to copper toxicity. Exposure of bacteria to subinhibitory concentrations of copper allowed them to better adapt to and grow in high concentrations of copper; this copper tolerance response is likely achieved via increased expression of copper resistance mechanisms. Indeed, genomic analysis revealed numerous putative copper resistance proteins that share amino acid homology to known proteins in Escherichia coli and Pseudomonas aeruginosa. Transcriptional analysis revealed significant upregulation of these putative copper resistance genes following brief copper exposure. Future characterization of copper resistance mechanisms may aid in the search for novel antibiotics against Acinetobacter and other highly antibiotic-resistant pathogens. IMPORTANCE Acinetobacter baumannii causes many types of severe nosocomial infections; unfortunately, some isolates have acquired resistance to almost every available antibiotic, and treatment options are incredibly limited. Copper is an essential nutrient but becomes toxic at high concentrations. The inherent antimicrobial properties of copper give it potential for use in novel therapeutics against drug-resistant pathogens. We show that A. baumannii clinical isolates are sensitive to copper in vitro, both in liquid and on solid metal surfaces. Since bacterial resistance to copper is mediated though mechanisms of efflux and detoxification, we identified genes encoding putative copper-related proteins in A. baumannii and showed that expression of some of these genes is regulated by the copper concentration. We propose that the antimicrobial effects of copper may be beneficial in the development of future therapeutics that target multidrug-resistant bacteria. PMID:27520808

Fate and transport of copper-based crop protectants in plasticulture runoff and the impact of sedimentation as a best management practice.

PubMed

Gallagher, D L; Johnston, K M; Dietrich, A M

2001-08-01

The fate and distribution of copper-based crop protectants, applied to plasticulture tomato fields to protect against disease, were investigated in a greenhouse-scale simulation of farming conditions in a coastal environment. Following rainfall, 99% of the applied copper was found to remain on the fields sorbed to the soil and plants; most of the soil-bound copper was found sorbed to the top 2.5 cm of soil between the plasticulture rows. Of the copper leaving the agricultural fields, 82% was found in the runoff with the majority, 74%. sorbed to the suspended solids. The remaining copper, 18%, leached through the soil and entered the groundwater with 10% in the dissolved phase and 8% sorbed to suspended solids. Although only 1% copper was found to leave the field, this was sufficient to cause high copper concentrations (average 2102+/-433 microg/L total copper and 189+/-139 microg/L dissolved copper) in the runoff. Copper concentrations in groundwater samples were also high (average 312+/-198 microg/L total copper and 216+/-99 microg/L dissolved copper). Sedimentation, a best management practice for reducing copper loadings. was found to reduce the total copper concentrations in runoff by 90% to a concentration of 245+/-127 microg/L; however, dissolved copper concentrations remained stable, averaging 139+/-55 microg/L. Total copper concentrations were significantly reduced by the effective removal of suspended solids with sorbed copper.

Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1.

PubMed

Juarez, Jose C; Betancourt, Oscar; Pirie-Shepherd, Steven R; Guan, Xiaojun; Price, Melissa L; Shaw, David E; Mazar, Andrew P; Doñate, Fernando

2006-08-15

A second-generation tetrathiomolybdate analogue (ATN-224; choline tetrathiomolybdate), which selectively binds copper with high affinity, is currently completing two phase I clinical trials in patients with advanced solid and advanced hematologic malignancies. However, there is very little information about the mechanism of action of ATN-224 at the molecular level. The effects of ATN-224 on endothelial and tumor cell growth were evaluated in cell culture experiments in vitro. The antiangiogenic activity of ATN-224 was investigated using the Matrigel plug model of angiogenesis. ATN-224 inhibits superoxide dismutase 1 (SOD1) in tumor and endothelial cells. The inhibition of SOD1 leads to inhibition of endothelial cell proliferation in vitro and attenuation of angiogenesis in vivo. The inhibition of SOD1 activity in endothelial cells is dose and time dependent and leads to an increase in the steady-state levels of superoxide anions, resulting in the inhibition of extracellular signal-regulated kinase phosphorylation without apparent induction of apoptosis. In contrast, the inhibition of SOD1 in tumor cells leads to the induction of apoptosis. The effects of ATN-224 on endothelial and tumor cells could be substantially reversed using Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, a catalytic small-molecule SOD mimetic. These data provide a distinct molecular target for the activity of ATN-224 and provide validation for SOD1 as a target for the inhibition of angiogenesis and tumor growth.

Point mutation increases a form of the NK1 receptor with high affinity for neurokinin A and B and septide

PubMed Central

Ciucci, Alessandra; Palma, Carla; Manzini, Stefano; Werge, Thomas M

1998-01-01

The binding modalities of substance P and neurokinin A on the wild type and Gly166 to-Cys mutant NK1 receptors expressed on CHO cells were investigated in homologous and heterologous binding experiments using both radiolabelled substance P and neurokinin A.On the wild type NK1 receptor NKA displaces radiolabelled substance P with very low apparent affinity, despite its high-affinity binding constant (determined in homologous binding experiments). The Gly166 to-Cys substitution in the NK1 tachykinin receptor greatly enhances the apparent affinity of neurokinin A in competition for radiolabelled substance P, but it does not change the binding constant of neurokinin A. The mutation, thereby, eliminates the discrepancy between the low apparent affinity and the high binding constant of neurokinin A.On the wild type receptor the binding capacity of neurokinin A is significantly smaller than that of substance P. In contrast, the two tachykinins bind to approximately the same number of sites on the mutant receptor.Simultaneous mass action law analysis of binding data in which multiple radioligands were employed in parallel demonstrated that a one-site model was unable to accommodate all the experimental data, whereas a two-site model provided a dramatically better description.These two receptor-sites display equally high affinity for substance P, while neurokinin A strongly discriminates between a high and a low affinity component. The binding affinities of neurokinin A are not affected by the mutation, which instead specifically alters the distribution between receptor sites in favour of a high affinity neurokinin A binding form.The low apparent affinity and binding capacity of neurokinin A on the wild type receptor results from neurokinin A binding with high affinity only to a fraction of the sites labelled by substance P. The mutation increases the proportion of this site, and consequently enhances the apparent affinity and binding capacity of neurokinin A.The binding modalities of septide-like ligands (i.e. neurokinin B, SP(6-11), SP-methyl ester) are affected similarly to neurokinin A and are better resolved into two sites. The mutation leaves the affinity of these ligands for the two receptor forms unchanged, but increases the fraction of high-affinity sites. On the other hand, the binding of non-peptide and peptide antagonists (SR140.333 and FK888) behaved similarly to substance P with a single high affinity site that is unaffected by the mutation.These findings may suggest that the NK1 receptor exists in two different forms with similar affinity for substance P and NK1 antagonists, but with a high and a low affinity for neurokinin A and septide-like ligands. Hence, the Gly166 in the NK1 receptor would seem to control the distribution between a pan-reactive form and a substance P-selective form of the receptor. PMID:9786514

Improved Tumor Targeting and Longer Retention Time of NIR Fluorescent Probes Using Bioorthogonal Chemistry.

PubMed

Zhang, Xianghan; Wang, Bo; Zhao, Na; Tian, Zuhong; Dai, Yunpeng; Nie, Yongzhan; Tian, Jie; Wang, Zhongliang; Chen, Xiaoyuan

2017-01-01

The traditional labeling method for targeted NIR fluorescence probes requires directly covalent-bonded conjugation of targeting domains and fluorophores in vitro . Although this strategy works well, it is not sufficient for detecting or treating cancers in vivo , due to steric hindrance effects that relatively large fluorophore molecules exert on the configurations and physiological functions of specific targeting domains. The copper-free, "click-chemistry"-assisted assembly of small molecules in living systems may enhance tumor accumulation of fluorescence probes by improving the binding affinities of the targeting factors. Here, we employed a vascular homing peptide, GEBP11, as a targeting factor for gastric tumors, and we demonstrate its effectiveness for in vivo imaging via click-chemistry-mediated conjugation with fluorescence molecules in tumor xenograft mouse models. This strategy showed higher binding affinities than those of the traditional conjugation method, and our results showed that the tumor accumulation of click-chemistry-mediated probes are 11-fold higher than that of directly labeled probes. The tracking life was prolonged by 12-fold, and uptake of the probes into the kidney was reduced by 6.5-fold. For lesion tumors of different sizes, click-chemistry-mediated probes can achieve sufficient signal-to-background ratios (3.5-5) for in vivo detection, and with diagnostic sensitivity approximately 3.5 times that of traditional labeling probes. The click-chemistry-assisted detection strategy utilizes the advantages of "small molecule" probes while not perturbing their physiological functions; this enables tumor detection with high sensitivity and specific selectivity.

Hydrostatic extrusion of Cu-Ag melt spun ribbon

DOEpatents

Hill, M.A.; Bingert, J.F.; Bingert, S.A.; Thoma, D.J.

1998-09-08

The present invention provides a method of producing high-strength and high-conductance copper and silver materials comprising the steps of combining a predetermined ratio of the copper with the silver to produce a composite material, and melt spinning the composite material to produce a ribbon of copper and silver. The ribbon of copper and silver is heated in a hydrogen atmosphere, and thereafter die pressed into a slug. The slug then is placed into a high-purity copper vessel and the vessel is sealed with an electron beam. The vessel and slug then are extruded into wire form using a cold hydrostatic extrusion process. 5 figs.

Hydrostatic extrusion of Cu-Ag melt spun ribbon

DOEpatents

Hill, Mary Ann; Bingert, John F.; Bingert, Sherri A.; Thoma, Dan J.

1998-01-01

The present invention provides a method of producing high-strength and high-conductance copper and silver materials comprising the steps of combining a predetermined ratio of the copper with the silver to produce a composite material, and melt spinning the composite material to produce a ribbon of copper and silver. The ribbon of copper and silver is heated in a hydrogen atmosphere, and thereafter die pressed into a slug. The slug then is placed into a high-purity copper vessel and the vessel is sealed with an electron beam. The vessel and slug then are extruded into wire form using a cold hydrostatic extrusion process.

Metal stabilization of collagen and de novo designed mimetic peptides

PubMed Central

Parmar, Avanish S.; Xu, Fei; Pike, Douglas H.; Belure, Sandeep V.; Hasan, Nida F.; Drzewiecki, Kathryn E.; Shreiber, David I.; Nanda, Vikas

2017-01-01

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix. PMID:26225466

Contrasting Granite Metallogeny through the Zircon Record: A Case Study from Myanmar.

PubMed

Gardiner, Nicholas J; Hawkesworth, Chris J; Robb, Laurence J; Whitehouse, Martin J; Roberts, Nick M W; Kirkland, Christopher L; Evans, Noreen J

2017-04-07

Granitoid-hosted mineral deposits are major global sources of a number of economically important metals. The fundamental controls on magma metal fertility are tectonic setting, the nature of source rocks, and magma differentiation. A clearer understanding of these petrogenetic processes has been forged through the accessory mineral zircon, which has considerable potential in metallogenic studies. We present an integrated zircon isotope (U-Pb, Lu-Hf, O) and trace element dataset from the paired Cu-Au (copper) and Sn-W (tin) magmatic belts in Myanmar. Copper arc zircons have juvenile εHf (+7.6 to +11.5) and mantle-like δ 18 O (5.2-5.5‰), whereas tin belt zircons have low εHf (-7 to -13) and heavier δ 18 O (6.2-7.7‰). Variations in zircon Hf and U/Yb reaffirm that tin belt magmas contain greater crustal contributions than copper arc rocks. Links between whole-rock Rb/Sr and zircon Eu/Eu* highlight that the latter can monitor magma fractionation in these systems. Zircon Ce/Ce* and Eu/Eu* are sensitive to redox and fractionation respectively, and here are used to evaluate zircon sensitivity to the metallogenic affinity of their host rock. Critical contents of Sn in granitic magmas, which may be required for the development of economic tin deposits, are marked by zircon Eu/Eu* values of ca. ≤0.08.

Metal Stabilization of Collagen and de Novo Designed Mimetic Peptides.

PubMed

Parmar, Avanish S; Xu, Fei; Pike, Douglas H; Belure, Sandeep V; Hasan, Nida F; Drzewiecki, Kathryn E; Shreiber, David I; Nanda, Vikas

2015-08-18

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo- and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal-specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix.

Copper and Antibiotics: Discovery, Modes of Action, and Opportunities for Medicinal Applications.

PubMed

Dalecki, Alex G; Crawford, Cameron L; Wolschendorf, Frank

2017-01-01

Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects. This weakness is actively exploited by phagocytes, which utilize a copper burst to destroy pathogens. Though administration of free copper is an unreasonable therapeutic antimicrobial itself, due to insufficient selectivity between host and pathogen, small-molecule ligands may provide an opportunity for therapeutic mimicry of the immune system. By modulating cellular entry, complex stability, resistance evasion, and target selectivity, ligand/metal coordination complexes can synergistically result in high levels of antibacterial activity. Several established therapeutic drugs, such as disulfiram and pyrithione, display remarkable copper-dependent inhibitory activity. These findings have led to development of new drug discovery techniques, using copper ions as the focal point. High-throughput screens for copper-dependent inhibitors against Mycobacterium tuberculosis and Staphylococcus aureus uncovered several new compounds, including a new class of inhibitors, the NNSNs. In this review, we highlight the microbial biology of copper, its antibacterial activities, and mechanisms to discover new inhibitors that synergize with copper. © 2017 Elsevier Ltd. All rights reserved.

Underwater explosive compaction-sintering of tungsten-copper coating on a copper surface

NASA Astrophysics Data System (ADS)

Chen, Xiang; Li, Xiaojie; Yan, Honghao; Wang, Xiaohong; Chen, Saiwei

2018-01-01

This study investigated underwater explosive compaction-sintering for coating a high-density tungsten-copper composite on a copper surface. First, 50% W-50% Cu tungsten-copper composite powder was prepared by mechanical alloying. The composite powder was pre-compacted and sintered by hydrogen. Underwater explosive compaction was carried out. Finally, a high-density tungsten-copper coating was obtained by diffusion sintering of the specimen after explosive compaction. A simulation of the underwater explosive compaction process showed that the peak value of the pressure in the coating was between 3.0 and 4.8 GPa. The hardness values of the tungsten-copper layer and the copper substrate were in the range of 87-133 and 49 HV, respectively. The bonding strength between the coating and the substrate was approximately 100-105 MPa.

Role of plastic deformation in wear of copper and copper - 10-percent-aluminum alloy in cryogenic fuels

NASA Technical Reports Server (NTRS)

Bill, R. C.; Wisander, D. W.

1973-01-01

High-purity copper specimens and a copper-aluminum (10%) alloy specimen were subjected to sliding against Type 440 C in cryogenic fuel environments. It was found that virtually all wear occurred by the plastic deformation of a recrystallized layer extending to about 10 micrometers below the wear scar surface of the copper or copper alloy. The wear debris was in the form of a layered structure adhering to the exit region of the wear scar. Measurements on the high purity copper specimens indicated that the wear rate was proportional to the applied load and to the sliding velocity squared. A physical model of the wear process is proposed to account for these observations.

Magmatic context of Bou Skour copper deposit (Eastern Anti-Atlas, Morocco): Petrogrography, geochemistry and alterations

NASA Astrophysics Data System (ADS)

EL Azmi, Daoud; Aissa, M.; Ouguir, H.; Mahdoudi, M. L.; El Azmi, M.; Ouadjo, A.; Zouhair, M.

2014-09-01

The Bou Skour copper deposit is located in the western part of the Saghro massif (Eastern Anti-Atlas), about 50 km East of the city of Ouarzazate. It is subdivided into several areas that are, from North to South: “Panthère”, “Chaigne”, “Anne Marie”, “Chapeau de fer” and “Patte d'Oie”. The latter is economically the most important and is the object of this study. The “Patte d'Oie” district consists mainly of extrusive and intrusive igneous rocks. The extrusive rocks are represented by andesites spatially associated with pyroclastic terms (ignimbrites and pyroclastic breccias). This volcanic unit is intruded by a pink granite pluton and a I-type granodiorite with equigranular texture (Bou Skour granodiorite) showing to the border a microgranular facies (microgranodiorite). All these magmatic formations are intersected by rhyolitic dykes (NNE-SSW) and doleritic dykes (WNW-ESE to NW-SE). The granodiorite and andesite have undergone a polyphase hydrothermal alteration: (i) potassic alteration, (ii) phyllitic alteration, (iii) silicification, (iv) argillic alteration and (v) propylitic alteration. The analysis of geochemical data of granodiorite, granite, andesite and dolerite confirmed: (i) their petrographic natures, (ii) the medium-K calc-alkaline affiliation of andesite and granodiorite, which would have been set up into an active geotectonic environment, probably of island arc or collision, during the Pan-African orogeny, (iii) The high-K calc-alkaline character of granite indicating a post-collision development during the Pan-African orogeny and (iv) The alkaline affinity of the dolerite which is linked to an extensive post-orogenic setting (post-Pan-African). The copper mineralization of “Patte d'Oie” area is hosted, exclusively, in the andesitic and granodioritic facies. It is represented, essentially, by chalcopyrite and bornite minerals and is, probably, related to a porphyry system (disseminated and stockwork mineralization) remobilized late, in Hercynian structures (vein mineralization).

Impact of copper ligand mutations on a cupredoxin with a green copper center.

PubMed

Roger, Magali; Sciara, Giuliano; Biaso, Frédéric; Lojou, Elisabeth; Wang, Xie; Bauzan, Marielle; Giudici-Orticoni, Marie-Thérèse; Vila, Alejandro J; Ilbert, Marianne

2017-05-01

Mononuclear cupredoxins contain a type 1 copper center with a trigonal or tetragonal geometry usually maintained by four ligands, a cystein, two histidines and a methionine. The recent discovery of new members of this family with unusual properties demonstrates, however, the versatility of this class of proteins. Changes in their ligand set lead to drastic variation in their metal site geometry and in the resulting spectroscopic and redox features. In our work, we report the identification of the copper ligands in the recently discovered cupredoxin AcoP. We show that even though AcoP possesses a classical copper ligand set, it has a highly perturbed copper center. In depth studies of mutant's properties suggest a high degree of constraint existing in the copper center of the wild type protein and even the addition of exogenous ligands does not lead to the reconstitution of the initial copper center. Not only the chemical nature of the axial ligand but also constraints brought by its covalent binding to the protein backbone might be critical to maintain a green copper site with high redox potential. This work illustrates the importance of experimentally dissecting the molecular diversity of cupredoxins to determine the molecular determinants responsible for their copper center geometry and redox potential. Copyright © 2017 Elsevier B.V. All rights reserved.

Characteristics of coated copper wire specimens using high frequency ultrasonic complex vibration welding equipments.

PubMed

Tsujino, J; Ihara, S; Harada, Y; Kasahara, K; Sakamaki, N

2004-04-01

Welding characteristic of thin coated copper wires were studied using 40, 60, 100 kHz ultrasonic complex vibration welding equipments with elliptical to circular vibration locus. The complex vibration systems consisted of a longitudinal-torsional vibration converter and a driving longitudinal vibration system. Polyurethane coated copper wires of 0.036 mm outer diameter and copper plates of 0.3 mm thickness and the other dimension wires were used as welding specimens. The copper wire part is completely welded on the copper substrate and the insulated coating material is driven from welded area to outsides of the wire specimens by high frequency complex vibration.

Copper-Exchanged Zeolite L Traps Oxygen

NASA Technical Reports Server (NTRS)

Sharma, Pramod K.; Seshan, Panchalam K.

1991-01-01

Brief series of simple chemical treatments found to enhance ability of zeolite to remove oxygen from mixture of gases. Thermally stable up to 700 degrees C and has high specific surface area which provides high capacity for adsorption of gases. To increase ability to adsorb oxygen selectively, copper added by ion exchange, and copper-exchanged zeolite reduced with hydrogen. As result, copper dispersed atomically on inner surfaces of zeolite, making it highly reactive to oxygen, even at room temperature. Reactivity to oxygen even greater at higher temperatures.

Microstructure and Mechanical Properties of High Copper HSLA-100 Steel in 2-inch Plate Form

DTIC Science & Technology

1992-06-01

2. HSLA-100 Steel Continuous Cooling Transformation Diagram [Ref. 13:p. 262] One of the most desirable characteristics of the low -carbon, copper ...none V mild v.strong v. strong V. strong moderate The use of copper as an alloying element in low carbon HSLA steel has resulted in the following...HY-130 steel . In research presently being done, it has been determined that the high copper alloy has a highly dislocated martensitic /bainitic

Circulation of copper in the biotic compartments of a freshwater dammed reservoir.

PubMed

Vinot, I; Pihan, J C

2005-01-01

This study concerns a chronic copper release in an aquatic ecosystem: Mirgenbach reservoir; which is characterized by high salinity, conductivity and hardness, a eutrophic state and a high temperature. To study the bioavailability of copper in the biotic compartments, the sampling covered the entire food chain (phyto- and zooplankton, macroalgae, aquatic plants, crustaceans, mollusks, and fish). Of the organisms present, the filter feeder Dreissena polymorpha, the detritivorous Bithynia tentaculata and Orconectes limosus were most contaminated by copper. The level of copper found in fish was the lowest. Body copper concentrations recorded in the present study show large variability between species even in some that are closely related. In most cases, however, the metal handling strategy, feeding habits, morphology and ecology can, at least partially, explain the metal content recorded. Pollution factors have been used to assess the state of contamination of the food chain. This study showed finally that the copper in the lake is bioavailable and bioaccumulated by organisms up to high levels and some effects of long-term toxicity of copper on benthic community and planktonic biomass were pointed out.

Effects of an aged copper contamination on distribution of earthworms, reproduction and cocoon hatchability.

PubMed

Mirmonsef, Hassan; Hornum, Hanne D; Jensen, John; Holmstrup, Martin

2017-01-01

Contaminated soil is a problem throughout the industrialized world, and a significant proportion of these sites are polluted with heavy metals such as copper. Ecological risk assessment of contaminated sites requires ecotoxicological studies with spiked soils as well as in-situ ecological observations. Here, we report laboratory and field assessment of copper toxicity for earthworms at a Danish site (Hygum) exclusively contaminated with an increasing gradient in copper from background to highly toxic levels (>1000mgkg -1 dry soil). More specifically, we report effects on field populations, body contents of copper, hatching of earthworm cocoons and reproduction of the common species Aporrectodea tuberculata. Abundance of earthworms and cocoons decreased significantly from about 400-150m -2 along the gradient as the soil copper concentration increased from ca. 50 to ca. 1000mgkg -1 . At lower concentrations, the population was dominated by endogeic species, whereas at high concentrations the population was dominated by epigeic species. At high copper contents the internal concentration of copper was in the range 100-160mgkg -1 dry tissue. Despite the high internal copper contents, hatchability of field collected cocoons was not impaired in any species. The EC50 reproduction value of A. tuberculata was about 220mg copper kg -1 dry soil in the first two exposure periods, but nearly doubled in the third period suggesting that an acclimation response had occurred. Also in the laboratory reproduction test, cocoon hatchability was not reduced, but rather slightly stimulated by copper. Based on these results we discuss the possibility that acute exposure in laboratory experiments is more detrimental than exposure in a field situation, perhaps because increased tolerance may be acquired through natural selection and genetic adaptation through increased use of defense mechanisms such as metallothioneins. Further, we discuss that the rather high tissue copper level of earthworms from the Hygum site may have smaller effects in these free-ranging worms than it would have in acute-exposure laboratory tests because the copper is more efficiently sequestered and detoxified in the field situation where populations have been exposed for many generations. Copyright © 2016 Elsevier Inc. All rights reserved.

Melanin-Based Coatings as Lead-Binding Agents

PubMed Central

Sono, Karin; Lye, Diane; Moore, Christine A.; Boyd, W. Christopher; Gorlin, Thomas A.; Belitsky, Jason M.

2012-01-01

Interactions between metal ions and different forms of melanin play significant roles in melanin biochemistry. The binding properties of natural melanin and related synthetic materials can be exploited for nonbiological applications, potentially including water purification. A method for investigating metal ion-melanin interactions on solid support is described, with lead as the initial target. 2.5 cm discs of the hydrophobic polymer PVDF were coated with synthetic eumelanin from the tyrosinase-catalyzed polymerization of L-dopa, and with melanin extracted from human hair. Lead (Pb2+) binding was quantified by atomic absorption spectroscopy (flame mode), and the data was well fit by the Langmuir model. Langmuir affinities ranged from 3.4 · 103 to 2.2 · 104 M−1. At the maximum capacity observed, the synthetic eumelanin coating bound ~9% of its mass in lead. Binding of copper (Cu2+), zinc (Zn2+), and cadmium (Cd2+) to the synthetic-eumelanin-coated discs was also investigated. Under the conditions tested, the Langmuir affinities for Zn2+, Cd2+, and Cu2+ were 35%, 53%, and 77%, respectively, of the Langmuir affinity for Pb2+. The synthetic-eumelanin-coated discs have a slightly higher capacity for Cu2+ on a per mole basis than for Pb2+, and lower capacities for Cd2+ and Zn2+. The system described can be used to address biological questions and potentially be applied toward melanin-based water purification. PMID:22611345

Comments on “Arc magmatism and subduction history beneath the Zagros Mountains, Iran: A new report of adakites and geodynamic consequences” by J. Omrani, P. Agard, H. Whitechurch, M. Bennoit, G. Prouteau, L. Jolivet

NASA Astrophysics Data System (ADS)

Aftabi, Alijan; Atapour, Habibeh

2009-12-01

Based on the imprecise geochemical data for 62 samples from Qom, Anar and Baft regions in central Iranian magmatic arc Omrani et al. (Omrani, J., Agard, P., Witechurch, H., Benoit, M., Prouteau, G., Jolivet, L., 2008. Arc magmatism and subduction history beneath the Zagsros Mountains, Iran: A new report of adakites and geodynamic consequences. Lithos 106, 380-398.), suggested that all studied magmatic rocks display the geochemical affinity of subduction-related calc-alkalic rock suites. Here, we demonstrate that the incorrect altered and variable geochemical data (e.g., Al 2O 3, Sr, Y, Ni, Cr, SiO 2, Na 2O, La/Yb and Th/Ce), show that most of the samples actually display calc-alkaline, shoshonitic and calc-alkalic-adakitic affinities. Furthermore, as a result of alteration, rock samples of similar age (e.g., Qom) indicate both adakitic and non-adakitic compositional signatures, which is misleading. On the basis of more than 400 previously published geochemical analyses, we suggest that, after eliminating the false geochemical signatures, the calc-alkaline and adakitic affinities of the central Iranian magmatic arc are due to flat subduction and might be related to a second phase of Miocene- Pliocene porphyry copper mineralization, which is a considerable exploration target and thus merits further investigation.

IgG1 memory B cells keep the memory of IgE responses.

PubMed

He, Jin-Shu; Subramaniam, Sharrada; Narang, Vipin; Srinivasan, Kandhadayar; Saunders, Sean P; Carbajo, Daniel; Wen-Shan, Tsao; Hidayah Hamadee, Nur; Lum, Josephine; Lee, Andrea; Chen, Jinmiao; Poidinger, Michael; Zolezzi, Francesca; Lafaille, Juan J; Curotto de Lafaille, Maria A

2017-09-21

The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80 + CD73 + and CD80 - CD73 - , contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE. Furthermore, repertoire analysis indicates that high affinity IgE and IgG1 plasma cells differentiate from rare CD80 + CD73 + high affinity memory clones without undergoing further mutagenesis. By identifying the cellular origin of high affinity IgE and the clonal selection of high affinity memory B cells into the plasma cell fate, our findings provide fundamental insights into the pathogenesis of allergies, and on the mechanisms of antibody production in memory B cell responses.IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.

The trade-off of availability and growth inhibition through copper for the production of copper-dependent enzymes by Pichia pastoris.

PubMed

Balakumaran, Palanisamy Athiyaman; Förster, Jan; Zimmermann, Martin; Charumathi, Jayachandran; Schmitz, Andreas; Czarnotta, Eik; Lehnen, Mathias; Sudarsan, Suresh; Ebert, Birgitta E; Blank, Lars Mathias; Meenakshisundaram, Sankaranarayanan

2016-02-20

Copper is an essential chemical element for life as it is a part of prosthetic groups of enzymes including super oxide dismutase and cytochrome c oxidase; however, it is also toxic at high concentrations. Here, we present the trade-off of copper availability and growth inhibition of a common host used for copper-dependent protein production, Pichia pastoris. At copper concentrations ranging from 0.1 mM (6.35 mg/L) to 2 mM (127 mg/L), growth rates of 0.25 h(-1) to 0.16 h(-1) were observed with copper uptake of as high as 20 mgcopper/gCDW. The intracellular copper content was estimated by subtracting the copper adsorbed on the cell wall from the total copper concentration in the biomass. Higher copper concentrations led to stronger cell growth retardation and, at 10 mM (635 mg/L) and above, to growth inhibition. To test the determined copper concentration range for optimal recombinant protein production, a laccase gene from Aspergillus clavatus [EMBL: EAW07265.1] was cloned under the control of the constitutive glyceraldehyde-3-phosphate (GAP) dehydrogenase promoter for expression in P. pastoris. Notably, in the presence of copper, laccase expression improved the specific growth rate of P. pastoris. Although copper concentrations of 0.1 mM and 0.2 mM augmented laccase expression 4 times up to 3 U/mL compared to the control (0.75 U/mL), while higher copper concentrations resulted in reduced laccase production. An intracellular copper content between 1 and 2 mgcopper/gCDW was sufficient for increased laccase activity. The physiology of the yeast could be excluded as a reason for the stop of laccase production at moderate copper concentrations as no flux redistribution could be observed by (13)C-metabolic flux analysis. Copper and its pivotal role to sustain cellular functions is noteworthy. However, knowledge on its cellular accumulation, availability and distribution for recombinant protein production is limited. This study attempts to address one such challenge, which revealed the fact that intracellular copper accumulation influenced laccase production and should be considered for high protein expression of copper-dependent enzymes when using P. pastoris. The results are discussed in the context of P. pastoris as a general host for copper -dependent enzyme production.

High temperature, low-cycle fatigue of copper-base alloys in argon. Part 1: Preliminary results for 12 alloys at 1000 F (538 C)

NASA Technical Reports Server (NTRS)

Conway, J. B.; Stentz, R. H.; Berling, J. T.

1973-01-01

Short-term tensile evaluations at room temperature and 538 C and low-cycle fatigue evaluations at 538 C are presented for the following materials: Zirconium copper-annealed, Zirconium copper-1/4 hard, Zirconium copper-1/2 hard, Tellurium copper-1/2 hard, Chromium copper-SA and aged, OFHC copper-hard, OFHC copper-1/4 hard, OFHC copper-annealed, Silver-as drawn, Zr-Cr-Mg copper-SA, CW and aged, Electroformed copper-30-35 ksi, and Co-Be-Zr- copper-SA, aged. A total of 50 tensile tests and 76 low-cycle fatigue tests were performed using a strain rate of 0.2 percent per second.

Inter-residue coupling contributes to high-affinity subtype-selective binding of α-bungarotoxin to nicotinic receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sine, Steven M.; Huang, Sun; Li, Shu-Xing

2013-09-01

The crystal structure of a pentameric α7 ligand-binding domain chimaera with bound α-btx (α-bungarotoxin) showed that of the five conserved aromatic residues in α7, only Tyr 184 in loop C of the ligand-binding site was required for high-affinity binding. To determine whether the contribution of Tyr 184 depends on local residues, we generated mutations in an α7/5HT 3A (5-hydroxytryptamine type 3A) receptor chimaera, individually and in pairs, and measured 125I-labelled α-btx binding. The results show that mutations of individual residues near Tyr 184 do not affect α-btx affinity, but pairwise mutations decrease affinity in an energetically coupled manner. Kinetic measurementsmore » show that the affinity decreases arise through increases in the α-btx dissociation rate with little change in the association rate. Replacing loop C in α7 with loop C from the α-btx-insensitive α2 or α3 subunits abolishes high-affinity α-btx binding, but preserves acetylcholine-elicited single channel currents. However, in both the α2 and α3 construct, mutating either residue that flanks Tyr 184 to its α7 counterpart restores high-affinity α-btx binding. Analogously, in α7, mutating both residues that flank Tyr 184 to the α2 or α3 counterparts abolishes high-affinity α-btx binding. Thus interaction between Tyr 184 and local residues contributes to high-affinity subtype-selective α-btx binding.« less

High adherence copper plating process

DOEpatents

Nignardot, Henry

1993-01-01

A process for applying copper to a substrate of aluminum or steel by electrodeposition and for preparing an aluminum or steel substrate for electrodeposition of copper. Practice of the invention provides good adhesion of the copper layer to the substrate.

[Interaction of human factor X with thromboplastin].

PubMed

Kiselev, S V; Zubairov, D M; Timarbaev, V N

2003-01-01

The binding of 125I-labeled human factor X to native and papaine-treated tissue tromboplastin in the presence of CaCl2 or EDTA was studied. The Scatchard analysis suggests the existence of high (Kd=l,8 x10(-9) M) and low affinity binding sites on the thromboplastin surface. The removal of Ca2+ reduced affinity of factor X to the high affinity sites. This was accompanied by some increase of their number. Proteolysis by papaine decreased affinity of high affinity sites and caused the increase of their number in the presence of Ca2+. In the absence of Ca2+ the affinity remained unchanged, but the number of sites decreased. At low concentrations of factor X positive cooperativity for high affinity binding sites was observed. It did not depend on the presence of Ca2+. The results indirectly confirm the role of hydrophobic interactons in Ca2+ dependent binding of factor X to thromboplastin and the fact that heterogeneity of this binding is determined by mesophase structure of the thromboplastin phospholipids.

Enhanced Requirement for TNFR2 in Graft Rejection Mediated by Low Affinity Memory CD8+ T Cells During Heterologous Immunity

PubMed Central

Krummey, Scott M.; Chen, Ching-Wen; Guasch, Sara A.; Liu, Danya; Wagener, Maylene; Larsen, Christian P; Ford, Mandy L.

2016-01-01

The affinity of a T cell receptor (TCR) binding to peptide:MHC profoundly impacts the phenotype and function of effector and memory cell differentiation. Little is known about the effect of low affinity priming on memory cell generation and function, which is particularly important in heterologous immunity, when microbe-specific T cells cross-react with allogeneic antigen and mediate graft rejection. We found that low affinity primed memory CD8+ T cells produced high levels of TNF ex vivo in response to heterologous rechallenge compared to high affinity primed memory T cells. Low affinity secondary effectors significantly upregulated TNFR2 on the cell surface and contained a higher frequency of TNFR2hi proliferating cells. Low affinity primed secondary effectors concurrently downregulated TNF production. Importantly, blockade of TNFR2 attenuated graft rejection in low but not high affinity primed animals. These data establish a functional connection between TNF signaling and TCR priming affinity and have implications for the immunomodulation of pathogenic T cell responses during transplantation. PMID:27481849

Multiphase separation of copper nanowires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Fang; Lan, Pui Ching; Olson, Tammy

Here, this communication reports a new method to purify copper nanowires with nearly 100% yield from undesired copper nanoparticle side-products formed during batch processes of copper nanowire synthesis. Also, this simple separation method can yield large quantities of long, uniform, high-purity copper nanowires to meet the requirements of nanoelectronics applications as well as provide an avenue for purifying copper nanowires in the industrial scale synthesis of copper nanowires, a key step for commercialization and application of nanowires.

Multiphase separation of copper nanowires

DOE PAGES

Qian, Fang; Lan, Pui Ching; Olson, Tammy; ...

2016-09-01

Here, this communication reports a new method to purify copper nanowires with nearly 100% yield from undesired copper nanoparticle side-products formed during batch processes of copper nanowire synthesis. Also, this simple separation method can yield large quantities of long, uniform, high-purity copper nanowires to meet the requirements of nanoelectronics applications as well as provide an avenue for purifying copper nanowires in the industrial scale synthesis of copper nanowires, a key step for commercialization and application of nanowires.

Low-cost optical fabrication of flexible copper electrode via laser-induced reductive sintering and adhesive transfer

NASA Astrophysics Data System (ADS)

Back, Seunghyun; Kang, Bongchul

2018-02-01

Fabricating copper electrodes on heat-sensitive polymer films in air is highly challenging owing to the need of expensive copper nanoparticles, rapid oxidation of precursor during sintering, and limitation of sintering temperature to prevent the thermal damage of the polymer film. A laser-induced hybrid process of reductive sintering and adhesive transfer is demonstrated to cost-effectively fabricate copper electrode on a polyethylene film with a thermal resistance below 100 °C. A laser-induced reductive sintering process directly fabricates a high-conductive copper electrode onto a glass donor from copper oxide nanoparticle solution via photo-thermochemical reduction and agglomeration of copper oxide nanoparticles. The sintered copper patterns were transferred in parallel to a heat-sensitive polyethylene film through self-selective surface adhesion of the film, which was generated by the selective laser absorption of the copper pattern. The method reported here could become one of the most important manufacturing technologies for fabricating low-cost wearable and disposable electronics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eilert, André; Roberts, F. Sloan; Friebel, Daniel

Nanostructured copper cathodes are among the most efficient and selective catalysts to date for making multicarbon products from the electrochemical carbon dioxide reduction reaction (CO 2RR). We report an in situ X-ray absorption spectroscopy investigation of the formation of a copper nanocube CO 2RR catalyst with high activity that highly favors ethylene over methane production. The results show that the precursor for the copper nanocube formation is copper(I)-oxide, not copper(I)-chloride as previously assumed. A second route to an electrochemically similar material via a copper(II)–carbonate/hydroxide is also reported. In conclusion, this study highlights the importance of using oxidized copper precursors formore » constructing selective CO 2 reduction catalysts and shows the precursor oxidation state does not affect the electrocatalyst selectivity toward ethylene formation.« less

High catalytic activity of oriented 2.0.0 copper(I) oxide grown on graphene film

PubMed Central

Primo, Ana; Esteve-Adell, Ivan; Blandez, Juan F.; Dhakshinamoorthy, Amarajothi; Álvaro, Mercedes; Candu, Natalia; Coman, Simona M.; Parvulescu, Vasile I.; García, Hermenegildo

2015-01-01

Metal oxide nanoparticles supported on graphene exhibit high catalytic activity for oxidation, reduction and coupling reactions. Here we show that pyrolysis at 900 °C under inert atmosphere of copper(II) nitrate embedded in chitosan films affords 1.1.1 facet-oriented copper nanoplatelets supported on few-layered graphene. Oriented (1.1.1) copper nanoplatelets on graphene undergo spontaneous oxidation to render oriented (2.0.0) copper(I) oxide nanoplatelets on few-layered graphene. These films containing oriented copper(I) oxide exhibit as catalyst turnover numbers that can be three orders of magnitude higher for the Ullmann-type coupling, dehydrogenative coupling of dimethylphenylsilane with n-butanol and C–N cross-coupling than those of analogous unoriented graphene-supported copper(I) oxide nanoplatelets. PMID:26509224

New precursors and chemistry for the growth of transition metal films by atomic layer deposition

NASA Astrophysics Data System (ADS)

Knisley, Thomas Joseph

The advancing complexity of advanced microelectronic devices is placing rigorous demands on currently used PVD and CVD deposition techniques. The ALD deposition method is proposed to meet the film thickness and conformality constraints needed by the semiconductor industry in future manufacturing processes. Unfortunately, there is a limited number of chemical precursors available that have high thermal stability, reactivity, and vapor pressure suitable for ALD film growth to occur. These properties collectively contribute to the lack of suitable transition metal precursors available for use in ALD. In this thesis, we report the discovery of a series of novel transition metal diazadienate precursors that promising properties deemed suitable for ALD. The volatility and thermal stability of the new transition metal diazadienyl compounds were studied by preparative sublimation and capillary tube melting point/decomposition experiments. Thermogravimetric analyses (TGA) demonstrate precursor residues of less than 4% at 500 °C. In addition, sublimation data, melting points, and decomposition temperatures for all complexes are presented. The manganese diazadienyl complex has the highest decomposition temperature of the series of complexes produced (325 °C). During preparative sublimations, the product recoveries of all transition metal diazadienyl complexes were greater than 92.0% with nonvolatile residues of less than 7.0%. This is an excellent indication that these complexes may be suitable candidates as metal precursors for ALD. Nickel nitride (NixN) films have been studied as an intermediate material for the formation of both nickel metal and nickel silicide using chemical vapor deposition. Herein, we describe the ALD growth of nickel nitride thin films from bis(1,4-di-tert-butyl-1,3-diazabutadiene) nickel(II) (Ni(tBu2DAD)2) and 1,1-dimethylhydrazine. An ALD window for the deposition of nickel nitride films on 500 nm thermal SiO2 substrates was observed between 225 and 240 °C with a constant growth rate of 0.70 Å/cycle. X-Ray photoelectron spectroscopy (XPS) showed all expected ionizations with carbon concentrations below the detection limit after argon ion sputtering. Due to preferential nitrogen sputtering in XPS, Rutherford backscattering spectrometry (RBS) and nuclear reaction analysis (NRA) were performed and subsequently revealed Ni:N ratios between 2-4 for films deposited within the ALD window. AFM measurements revealed a RMS roughness value of 10.8 nm on an as-deposited film at 225°C. All as-deposited films were amorphous as determined by X-ray diffraction. Copper is the primary interconnect material in microelectronics devices, due to its high conductivity and low affinity towards electromigration. With transistor gate lengths scheduled to reach 14 nm by 2014, there are severe demands upon the current film growth techniques used in device fabrication. The ALD film growth method is ideally suited for future microelectronics manufacturing, since it inherently provides highly conformal thin films, even in high aspect ratio nanoscale features, and allows sub-nanometer control over film thicknesses. In Chapter 4, we describe the atomic layer deposition of high purity, low resistivity copper metal thin films using a three precursor sequence entailing Cu(dmap)2, formic acid, and hydrazine. In this process, Cu(dmap) 2 is unreactive towards hydrazine but is transformed to copper(II) formate, which is then readily reduced to copper metal by subsequent hydrazine exposure. The present work therefore addresses a central problem with the ALD growth of metal thin films: low reactivity of metal precursors toward common reducing agents. A constant growth rate of 0.47-0.50 Å/cycle upon prime grade Si(100) was observed at substrate temperatures between 100 and 170 °C. Compositional analyses (XPS and TOF-ERDA) revealed copper films with low levels of carbon, oxygen, nitrogen, and hydrogen. Powder X-ray diffraction spectra of all films showed polycrystalline copper. The resistivities of films grown between 100 and 140 °C ranged between 9.6 and 16.4 μΩ·cm, demonstrating the growth of high purity, low resistivity copper films. An AFM measurement revealed a RMS roughness value of 3.5 nm on an as-deposited 50 nm Cu film at 120 °C.

"Twin copper source" growth of metal-organic framework membrane: Cu(3)(BTC)(2) with high permeability and selectivity for recycling H(2).

PubMed

Guo, Hailing; Zhu, Guangshan; Hewitt, Ian J; Qiu, Shilun

2009-02-11

In this communication, the copper net supported Cu(3)(BTC)(2) membranes have been successfully synthesized by means of a "twin copper source" technique. Separation studies on gaseous mixtures (H(2)/CO(2), H(2)/CH(4), and H(2)/N(2)) using the membrane revealed that the membrane possesses high permeability and selectivity for H(2) over CO(2), N(2), and CH(4). Compared with the conventional zeolite membranes, the copper net supported Cu(3)(BTC)(2) membrane exhibited high permeation flux in gas separation. Such highly efficient copper net supported Cu(3)(BTC)(2) membranes could be used to separate, recycle, and reuse H(2) exhausted from steam reforming natural gas.

Culture-dependent and independent studies of microbial diversity in highly copper-contaminated Chilean marine sediments.

PubMed

Besaury, Ludovic; Marty, Florence; Buquet, Sylvaine; Mesnage, Valérie; Muyzer, Gerard; Quillet, Laurent

2013-02-01

Cultivation and molecular-based approaches were used to study microbial diversity in two Chilean marine sediments contaminated with high (835 ppm) and very high concentrations of copper (1,533 ppm). The diversity of cultivable bacteria resistant to copper was studied at oxic and anoxic conditions, focusing on sulfate-, thiosulfate-, and iron-reducing bacteria. For both sediments, the cultivable bacteria isolated at oxic conditions were mostly affiliated to the genus Bacillus, while at anoxic conditions the majority of the cultivable bacteria found were closely related to members of the genera Desulfovibrio, Sphingomonas, and Virgibacillus. Copper resistance was between 100 and 400 ppm, with the exception of a strain affiliated to members of the genus Desulfuromonas, which was resistant up to 1,000 ppm of copper. In parallel, cloning and sequencing of 16S rRNA was performed to study the total bacterial diversity in the sediments. A weak correlation was observed between the isolated strains and the 16S rRNA operational taxonomic units detected. The presence of copper resistance genes (copA, cusA, and pcoA) was tested for all the strains isolated; only copA was detected in a few isolates, suggesting that other copper resistance mechanisms could be used by the bacteria in those highly copper-contaminated sediments.

Reactivity of food phenols with iron and copper ions: binding, dioxygen activation and oxidation mechanisms.

PubMed

Nkhili, Ezzohra; Loonis, Michèle; Mihai, Simona; El Hajji, Hakima; Dangles, Olivier

2014-06-01

In this work, the affinity of common dietary phenols (gallic acid, caffeic acid, catechin, and rutin) for iron and copper ions was quantitatively investigated in neutral phosphate buffer as well as the reactivity of the complexes toward dioxygen. Contrasting behaviors were observed: because of the competing phosphate ions, Fe(III) binding is much slower than Fe(II) binding, which is rapidly followed by autoxidation of Fe(II) into Fe(III). With both ions, O2 consumption and H2O2 production are modest and the phenolic ligands are only slowly oxidized. By contrast, metal-phenol binding is fast with both Cu(I) and Cu(II). With Cu(I), O2 consumption and H2O2 production are very significant and the phenolic ligands are rapidly oxidized into a complex mixture of oligomers. The corresponding mechanism with Cu(II) is hampered by the preliminary rate-determining step of Cu(II) reduction by the phenols. The consequences of these findings for the stability and antioxidant activity of plant phenols are discussed.

Liquid/Liquid Interfacial Synthesis of a Click Nanosheet.

PubMed

Rapakousiou, Amalia; Sakamoto, Ryota; Shiotsuki, Ryo; Matsuoka, Ryota; Nakajima, Ukyo; Pal, Tigmansu; Shimada, Rintaro; Hossain, Amran; Masunaga, Hiroyasu; Horike, Satoshi; Kitagawa, Yasutaka; Sasaki, Sono; Kato, Kenichi; Ozawa, Takeaki; Astruc, Didier; Nishihara, Hiroshi

2017-06-22

A liquid/liquid interfacial synthesis is employed, for the first time, to synthesize a covalent two-dimensional polymer nanosheet. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) between a three-way terminal alkyne and azide at a water/dichloromethane interface generates a 1,2,3-triazole-linked nanosheet. The resultant nanosheet, with a flat and smooth texture, has a maximum domain size of 20 μm and minimum thickness of 5.3 nm. The starting monomers in the organic phase and the copper catalyst in the aqueous phase can only meet at the liquid/liquid interface as a two-dimensional reaction space; this allows them to form the two-dimensional polymer. The robust triazole linkage generated by irreversible covalent-bond formation allows the nanosheet to resist hydrolysis under both acidic and alkaline conditions, and to endure pyrolysis up to more than 300 °C. The coordination ability of the triazolyl group enables the nanosheet to act as a reservoir for metal ions, with an affinity order of Pd 2+ >Au 3+ >Cu 2+ . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermodynamic Bounds on the Ultra- and Infra-affinity of Hsp70 for Its Substrates

NASA Astrophysics Data System (ADS)

Nguyen, Basile; Hartich, David; Seifert, Udo; Rios, Paolo De Los

2017-07-01

The 70 kDa Heat Shock Proteins Hsp70 have several essential functions in living systems, such as protecting cells against protein aggregation, assisting protein folding, remodeling protein complexes and driving the translocation into organelles. These functions require high affinity for non-specific amino-acid sequences that are ubiquitous in proteins. It has been recently shown that this high affinity, called ultra-affinity, depends on a process driven out of equilibrium by ATP hydrolysis. Here we establish the thermodynamic bounds for ultra-affinity, and further show that the same reaction scheme can in principle be used both to strengthen and to weaken affinities (leading in this case to infra-affinity). We show that cofactors are essential to achieve affinity beyond the equilibrium range. Finally, biological implications are discussed.

α-Conotoxin dendrimers have enhanced potency and selectivity for homomeric nicotinic acetylcholine receptors.

PubMed

Wan, Jingjing; Huang, Johnny X; Vetter, Irina; Mobli, Mehdi; Lawson, Joshua; Tae, Han-Shen; Abraham, Nikita; Paul, Blessy; Cooper, Matthew A; Adams, David J; Lewis, Richard J; Alewood, Paul F

2015-03-11

Covalently attached peptide dendrimers can enhance binding affinity and functional activity. Homogenous di- and tetravalent dendrimers incorporating the α7-nicotinic receptor blocker α-conotoxin ImI (α-ImI) with polyethylene glycol spacers were designed and synthesized via a copper-catalyzed azide-alkyne cycloaddition of azide-modified α-ImI to an alkyne-modified polylysine dendron. NMR and CD structural analysis confirmed that each α-ImI moiety in the dendrimers had the same 3D structure as native α-ImI. The binding of the α-ImI dendrimers to binding protein Ac-AChBP was measured by surface plasmon resonance and revealed enhanced affinity. Quantitative electrophysiology showed that α-ImI dendrimers had ∼100-fold enhanced potency at hα7 nAChRs (IC50 = 4 nM) compared to native α-ImI (IC50 = 440 nM). In contrast, no significant potency enhancement was observed at heteromeric hα3β2 and hα9α10 nAChRs. These findings indicate that multimeric ligands can significantly enhance conotoxin potency and selectivity at homomeric nicotinic ion channels.

Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process.

PubMed

Cano, María Emilia; Varela, Oscar; García-Moreno, María Isabel; García Fernández, José Manuel; Kovensky, José; Uhrig, María Laura

2017-04-18

The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from l-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent β-N-galactopyranosylamides was obtained and fully characterized. The binding affinities of the ligands towards the model lectin PNA were measured by the enzyme-linked lectin assay (ELLA). The IC 50 values were significantly higher than that of galactose but the presence of hydroxyl groups in the aglycone chain improved lectin recognition. Docking and molecular dynamics experiments were in accordance with the hypothesis that a hydroxyl group properly disposed in the linker could mimic the Glc O3 in the recognition process. On the other hand, divalent presentation of the ligands led to lectin affinity enhancements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Complex electronic waste treatment - An effective process to selectively recover copper with solutions containing different ammonium salts.

PubMed

Sun, Z H I; Xiao, Y; Sietsma, J; Agterhuis, H; Yang, Y

2016-11-01

Recovery of valuable metals from electronic waste has been highlighted by the EU directives. The difficulties for recycling are induced by the high complexity of such waste. In this research, copper could be selectively recovered using an ammonia-based process, from industrially processed information and communication technology (ICT) waste with high complexity. A detailed understanding on the role of ammonium salt was focused during both stages of leaching copper into a solution and the subsequent step for copper recovery from the solution. By comparing the reactivity of the leaching solution with different ammonium salts, their physiochemical behaviour as well as the leaching efficiency could be identified. The copper recovery rate could reach 95% with ammonium carbonate as the leaching salt. In the stage of copper recovery from the solution, electrodeposition was introduced without an additional solvent extraction step and the electrochemical behaviour of the solution was figured out. With a careful control of the electrodeposition conditions, the current efficiency could be improved to be 80-90% depending on the ammonia salts and high purity copper (99.9wt.%). This research provides basis for improving the recyclability and efficiency of copper recovery from such electronic waste and the whole process design for copper recycling. Copyright © 2016 Elsevier Ltd. All rights reserved.

A study of the uptake of chloroquine in malaria-infected erythrocytes. High and low affinity uptake and the influence of glucose and its analogues.

PubMed

Diribe, C O; Warhurst, D C

1985-09-01

A study of concentration- and substrate-dependence of chloroquine uptake has been carried out on mouse erythrocytes infected with the chloroquine-sensitive NK65 and the chloroquine-resistant RC strains of Plasmodium berghei. The presence of drug binding sites of high and low affinity in such strains of P. berghei was confirmed. High affinity uptake sites in cells parasitized with chloroquine-sensitive and chloroquine-resistant parasites have similar characteristics, but in the sensitive strain the major component of chloroquine-uptake is at high affinity and dependent on the availability of ATP whilst in the resistant strain the major component of uptake is at low affinity and independent of energy. An absolute increase in the quantity of the low affinity site in erythrocytes parasitized with chloroquine-resistant P. berghei was noted, which may be related to an increase in quantity of parasite membrane.

Rapid Separation of Copper Phase and Iron-Rich Phase From Copper Slag at Low Temperature in a Super-Gravity Field

NASA Astrophysics Data System (ADS)

Lan, Xi; Gao, Jintao; Huang, Zili; Guo, Zhancheng

2018-03-01

A novel approach for quickly separating a metal copper phase and iron-rich phase from copper slag at low temperature is proposed based on a super-gravity method. The morphology and mineral evolution of the copper slag with increasing temperature were studied using in situ high-temperature confocal laser scanning microscopy and ex situ scanning electron microscopy and X-ray diffraction methods. Fe3O4 particles dispersed among the copper slag were transformed into FeO by adding an appropriate amount of carbon as a reducing agent, forming the slag melt with SiO2 at low temperature and assisting separation of the copper phase from the slag. Consequently, in a super-gravity field, the metallic copper and copper matte were concentrated as the copper phase along the super-gravity direction, whereas the iron-rich slag migrated in the opposite direction and was quickly separated from the copper phase. Increasing the gravity coefficient (G) significantly enhanced the separation efficiency. After super-gravity separation at G = 1000 and 1473 K (1200 °C) for 3 minutes, the mass fraction of Cu in the separated copper phase reached 86.11 wt pct, while that in the separated iron-rich phase was reduced to 0.105 wt pct. The recovery ratio of Cu in the copper phase was as high as up to 97.47 pct.

Rapid Separation of Copper Phase and Iron-Rich Phase From Copper Slag at Low Temperature in a Super-Gravity Field

NASA Astrophysics Data System (ADS)

Lan, Xi; Gao, Jintao; Huang, Zili; Guo, Zhancheng

2018-06-01

A novel approach for quickly separating a metal copper phase and iron-rich phase from copper slag at low temperature is proposed based on a super-gravity method. The morphology and mineral evolution of the copper slag with increasing temperature were studied using in situ high-temperature confocal laser scanning microscopy and ex situ scanning electron microscopy and X-ray diffraction methods. Fe3O4 particles dispersed among the copper slag were transformed into FeO by adding an appropriate amount of carbon as a reducing agent, forming the slag melt with SiO2 at low temperature and assisting separation of the copper phase from the slag. Consequently, in a super-gravity field, the metallic copper and copper matte were concentrated as the copper phase along the super-gravity direction, whereas the iron-rich slag migrated in the opposite direction and was quickly separated from the copper phase. Increasing the gravity coefficient (G) significantly enhanced the separation efficiency. After super-gravity separation at G = 1000 and 1473 K (1200 °C) for 3 minutes, the mass fraction of Cu in the separated copper phase reached 86.11 wt pct, while that in the separated iron-rich phase was reduced to 0.105 wt pct. The recovery ratio of Cu in the copper phase was as high as up to 97.47 pct.

Disproportionation for growing copper nanowires and their controlled self-assembly facilitated by ligand exchange.

PubMed

Ye, Enyi; Zhang, Shuang-Yuan; Liu, Shuhua; Han, Ming-Yong

2011-03-07

The coating makes the wire bundle: High-quality free-standing copper nanowires have been successfully produced by disproportionation of Cu(+) in oleylamine. This provides an effective way to prepare high-quality copper nanowires, but also enriches synthetic routes to other nanostructures. These copper nanowires can self-assemble by surface ligand exchange of oleylamine with trioctylphosphine. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Commercial Products from Copper Wire-Drawing Waste

NASA Astrophysics Data System (ADS)

Ayala, J.; Fernández, B.

2014-06-01

Copper powder and copper sulfate pentahydrate were obtained from copper wire-drawing scale. The hydrometallurgical recycling process proposed in this article yields a high-purity copper powder and analytical grade copper sulfate pentahydrate. In the first stage of this process, the copper is dissolved in sulfuric acid media via dismutation of the scale. In the second stage, copper sulfate pentahydrate is precipitated using ethanol. Effects such as pH, reaction times, stirring speed, initial copper concentration, and ethanol/solution volume ratio were studied during the precipitation from solution reaction. The proposed method is technically straightforward and provides efficient recovery of Cu from wire-drawing scale.

Copper emissions from a high volume air sampler

NASA Technical Reports Server (NTRS)

King, R. B.; Toma, J.

1975-01-01

High volume air samplers (hi vols) are described which utilize a brush-type electric motor to power the fans used for pulling air through the filter. Anomalously high copper values were attributed to removal of copper from the commutator into the air stream due to arcing of the brushes and recirculation through the filter. Duplicate hi vols were set up under three operating conditions: (1) unmodified; (2) gasketed to prevent internal recirculation; and (3) gasketed and provided with a pipe to transport the motor exhaust some 20 feet away. The results of 5 days' operation demonstrate that hi vols can suddenly start emitting increased amounts of copper with no discernible operational indication, and that recirculation and capture on the filter can take place. Copper levels found with hi vols whose exhaust was discharged at a distance downwind were among the lowest found, and apparently provides a satisfactory solution to copper contamination.

Laser-Assisted Reduction of Highly Conductive Circuits Based on Copper Nitrate for Flexible Printed Sensors

NASA Astrophysics Data System (ADS)

Bai, Shi; Zhang, Shigang; Zhou, Weiping; Ma, Delong; Ma, Ying; Joshi, Pooran; Hu, Anming

2017-10-01

Stretchable electronic sensing devices are defining the path toward wearable electronics. High-performance flexible strain sensors attached on clothing or human skin are required for potential applications in the entertainment, health monitoring, and medical care sectors. In this work, conducting copper electrodes were fabricated on polydimethylsiloxane as sensitive stretchable microsensors by integrating laser direct writing and transfer printing approaches. The copper electrode was reduced from copper salt using laser writing rather than the general approach of printing with pre-synthesized copper or copper oxide nanoparticles. An electrical resistivity of 96 μΩ cm was achieved on 40-μm-thick Cu electrodes on flexible substrates. The motion sensing functionality successfully demonstrated a high sensitivity and mechanical robustness. This in situ fabrication method leads to a path toward electronic devices on flexible substrates.[Figure not available: see fulltext.

Thermal conductivity and thermal expansion of graphite fiber/copper matrix composites

NASA Technical Reports Server (NTRS)

Ellis, David L.; Mcdanels, David L.

1991-01-01

The high specific conductivity of graphite fiber/copper matrix (Gr/Cu) composites offers great potential for high heat flux structures operating at elevated temperatures. To determine the feasibility of applying Gr/Cu composites to high heat flux structures, composite plates were fabricated using unidirectional and cross-plied pitch-based P100 graphite fibers in a pure copper matrix. Thermal conductivity of the composites was measured from room temperature to 1073 K, and thermal expansion was measured from room temperature to 1050 K. The longitudinal thermal conductivity, parallel to the fiber direction, was comparable to pure copper. The transverse thermal conductivity, normal to the fiber direction, was less than that of pure copper and decreased with increasing fiber content. The longitudinal thermal expansion decreased with increasing fiber content. The transverse thermal expansion was greater than pure copper and nearly independent of fiber content.

Thermal conductivity and thermal expansion of graphite fiber-reinforced copper matrix composites

NASA Technical Reports Server (NTRS)

Ellis, David L.; Mcdanels, David L.

1993-01-01

The high specific conductivity of graphite fiber/copper matrix (Gr/Cu) composites offers great potential for high heat flux structures operating at elevated temperatures. To determine the feasibility of applying Gr/Cu composites to high heat flux structures, composite plates were fabricated using unidirectional and cross-plied pitch-based P100 graphite fibers in a pure copper matrix. Thermal conductivity of the composites was measured from room temperature to 1073 K, and thermal expansion was measured from room temperature to 1050 K. The longitudinal thermal conductivity, parallel to the fiber direction, was comparable to pure copper. The transverse thermal conductivity, normal to the fiber direction, was less than that of pure copper and decreased with increasing fiber content. The longitudinal thermal expansion decreased with increasing fiber content. The transverse thermal expansion was greater than pure copper and nearly independent of fiber content.

Electrical wire explosion process of copper/silver hybrid nano-particle ink and its sintering via flash white light to achieve high electrical conductivity.

PubMed

Chung, Wan-Ho; Hwang, Yeon-Taek; Lee, Seung-Hyun; Kim, Hak-Sung

2016-05-20

In this work, combined silver/copper nanoparticles were fabricated by the electrical explosion of a metal wire. In this method, a high electrical current passes through the metal wire with a high voltage. Consequently, the metal wire evaporates and metal nanoparticles are formed. The diameters of the silver and copper nanoparticles were controlled by changing the voltage conditions. The fabricated silver and copper nano-inks were printed on a flexible polyimide (PI) substrate and sintered at room temperature via a flash light process, using a xenon lamp and varying the light energy. The microstructures of the sintered silver and copper films were observed using a scanning electron microscope (SEM) and a transmission electron microscope (TEM). To investigate the crystal phases of the flash-light-sintered silver and copper films, x-ray diffraction (XRD) was performed. The absorption wavelengths of the silver and copper nano-inks were measured using ultraviolet-visible spectroscopy (UV-vis). Furthermore, the resistivity of the sintered silver and copper films was measured using the four-point probe method and an alpha step. As a result, the fabricated Cu/Ag film shows a high electrical conductivity (4.06 μΩcm), which is comparable to the resistivity of bulk copper (1.68 μΩcm). In addition, the fabricated Cu/Ag nanoparticle film shows superior oxidation stability compared to the Cu nanoparticle film.

The effect of natural and anthropogenic factors on sorption of copper in chernozem

NASA Astrophysics Data System (ADS)

Bauer, Tatiana; Minkina, Tatiana; Mandzhieva, Saglara; Pinskii, David; Linnik, Vitaly; Sushkova, Svetlana

2016-04-01

The aim of this work was to study the effect of the attendant anions and particle-size distribution on the adsorption of copper by ordinary chernozem. Solutions of HM nitrates, acetates, chlorides, and sulfates were used to study the effect of the chemical composition of added copper salts on the adsorption of copper by an ordinary chernozem. Samples of the soil sieved through a 1-mm sieve in the natural ionic form and soil fraction with different particle size (clay - the particle with size < 1μm and physical clay < 10 μm) were treated with solutions of the corresponding copper salts at a soil : solution ratio of 1:10. The concentrations of the initial copper solutions were 0.02, 0.05, 0.08, 0.1, 0.3, 0.5, and 1.0 mM/L. The range of Cu2+ concentrations in the studied system covers different geochemical situations corresponding to the actual levels of soil contamination with the metal under study. The suspensions were shaken for 1 h, left to stand for 24 h, and then filtered. The contents of the HM in the filtrates were determined by atomic absorption spectrometry (AAS). The contents of the adsorbed copper cations were calculated from the difference between the metal concentrations in the initial and equilibrium solutions. The isotherms of copper adsorption from the metal nitrate, chloride, and sulfate solutions have near linear shapes and, hence, can be satisfactorily described by a Henry or Freundlich equation: Cads = KH •Ceq.(1) Cads = KF •Ceqn,(2) where Cadsis the content of the adsorbed cations, mM/kg soil;Ceq is the concentration of copper in the equilibrium solution, mM/L; KH and KF denote the Henry and Freundlich adsorption coefficients, respectively, kg/L. The isotherm of Cu2+ adsorption by ordinary chernozem from acetate solutions is described by the Langmuir equation: Cads = C∞ÊLC / (1 + ÊLC), (3) where Cadsis the content of the adsorbed cations, mM/kg soil;C∞ is the maximum adsorption of the HM, mM/kg soil; ÊL is the affinity constant, L/mM; C is the concentration of the HM in the equilibrium solution, mM/L. According to the values of KH, the binding strength of the copper cations adsorbed from different salt solutions decreases in the series: Cu(Ac)2(1880,5± 76,2) > CuCl2(1442,8±113,5) > Cu(NO3)2(911,4 ± 31,1) >> CuSO4(165,3 ± 12,9). Thus, copper is most strongly adsorbed from the acetate solution and least strongly from the sulfate solution. The adsorption of copper by clay and physical clay fractions from the ordinary chernozem was of limited character and followed the (3) equation. In the particle-size fractions separated from the soils, the concentrations of copper decreased with the decreasing particle size. The values of ÊL and C∞characterizing the HM adsorption by the chernozem and its particle-size fractions formed the following sequence: clay (80,20±20,29 and 28,45±0,46 > physical clay (58,20±14,54 and 22,15±1,22) > entire soil (38,80±12,33 and 17,58±3,038). This work was supported by the Russian Ministry of Education and Science, project no. 5.885.2014/K, Russian Foundation for Basic Research, projects no. 14-05-00586 À

High adherence copper plating process

DOEpatents

Nignardot, H.

1993-09-21

A process is described for applying copper to a substrate of aluminum or steel by electrodeposition and for preparing the surface of an aluminum or steel substrate for the electrodeposition of copper. Practice of the invention provides good adhesion of the copper layer to either substrate.

Is a high serum copper concentration a risk factor for implantation failure?

PubMed

Matsubayashi, Hidehiko; Kitaya, Kotaro; Yamaguchi, Kohei; Nishiyama, Rie; Takaya, Yukiko; Ishikawa, Tomomoto

2017-08-10

Copper-containing contraceptive devices may deposit copper ions in the endometrium, resulting in implantation failure. The deposition of copper ions in many organs has been reported in patients with untreated Wilson's disease. Since these patients sometimes exhibit subfertility and/or early pregnancy loss, copper ions were also considered to accumulate in the uterine endometrium. Wilson's disease patients treated with zinc successfully delivered babies because zinc interfered with the absorption of copper from the gastrointestinal tract. These findings led to the hypothesis that infertile patients with high serum copper concentrations may have implantation failure due to the excess accumulation of copper ions. The relationship between implantation (pregnancy) rates and serum copper concentrations has not yet been examined. The Japanese government recently stated that actual copper intake was higher among Japanese than needed. Therefore, the aim of the present study was to investigate whether serum copper concentrations are related to the implantation (pregnancy) rates of human embryos in vivo. We included 269 patients (age <40 years old) who underwent vitrifying and warming single embryo transfer with a hormone replacement cycle using good blastocysts (3BB or more with Gardner's classification). Serum hCG, copper, and zinc concentrations were measured 16 days after the first date of progesterone replacement. We compared 96 women who were pregnant without miscarriage at 10 weeks of gestation (group P) and 173 women who were not pregnant (group NP). No significant differences were observed in age or BMI between the groups. Copper concentrations were significantly higher in group NP (average 193.2 μg/dL) than in group P (average 178.1 μg/dL). According to the area under the curve (AUC) on the receiver operating characteristic curve for the prediction of clinical pregnancy rates, the Cu/Zn ratio (AUC 0.64, 95% CI 0.54-0.71) was a better predictor than copper or zinc. When we set the cut-off as 1.59/1.60 for the Cu/Zn ratio, sensitivity, specificity, the positive predictive value, and negative predictive value were 0.98, 0.29, 0.71, and 0.88, respectively. Our single-center retrospective study suggests that high serum copper concentrations (high Cu/Zn ratio) are a risk factor for implantation failure.

Control of New Copper Corrosion in High-Alkalinity Drinking Water using Orthophosphate - article

EPA Science Inventory

Research and field experience have shown that high-alkalinity waters can be associated with elevated copper levels in drinking water. The objective of this study was to document the application of orthophosphate to the distribution system of a building with a copper problem asso...

Copper Complexation Screen Reveals Compounds with Potent Antibiotic Properties against Methicillin-Resistant Staphylococcus aureus

PubMed Central

Haeili, Mehri; Moore, Casey; Davis, Christopher J. C.; Cochran, James B.; Shah, Santosh; Shrestha, Tej B.; Zhang, Yaofang; Bossmann, Stefan H.; Benjamin, William H.

2014-01-01

Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant Staphylococcus aureus (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface. PMID:24752262

The role of CH/π interactions in the high affinity binding of streptavidin and biotin.

PubMed

Ozawa, Motoyasu; Ozawa, Tomonaga; Nishio, Motohiro; Ueda, Kazuyoshi

2017-08-01

The streptavidin-biotin complex has an extraordinarily high affinity (Ka: 10 15 mol -1 ) and contains one of the strongest non-covalent interactions known. This strong interaction is widely used in biological tools, including for affinity tags, detection, and immobilization of proteins. Although hydrogen bond networks and hydrophobic interactions have been proposed to explain this high affinity, the reasons for it remain poorly understood. Inspired by the deceased affinity of biotin observed for point mutations of streptavidin at tryptophan residues, we hypothesized that a CH/π interaction may also contribute to the strong interaction between streptavidin and biotin. CH/π interactions were explored and analyzed at the biotin-binding site and at the interface of the subunits by the fragment molecular orbital method (FMO) and extended applications: PIEDA and FMO4. The results show that CH/π interactions are involved in the high affinity for biotin at the binding site of streptavidin. We further suggest that the involvement of CH/π interactions at the subunit interfaces and an extended CH/π network play more critical roles in determining the high affinity, rather than involvement at the binding site. Copyright © 2017 Elsevier Inc. All rights reserved.

Radioactivity at the Copper Creek copper lode prospect, Eagle district, east-central Alaska

USGS Publications Warehouse

Wedow, Helmuth; Tolbert, Gene Edward

1952-01-01

Investigation of radioactivity anomalies at the Copper Creek copper lode prospect, Eagle district, east-central Alaska, during 1949 disclosed that the radioactivity is associated with copper mineralization in highly metamorphosed sedimentary rocks. These rocks are a roof pendant in the Mesozoic "Charley River" batholith. The radioactivity is probably all due to uranium associated with bornite and malachite.

Unraveling the Amycolatopsis tucumanensis copper-resistome.

PubMed

Dávila Costa, José Sebastián; Kothe, Erika; Abate, Carlos Mauricio; Amoroso, María Julia

2012-10-01

Heavy metal pollution is widespread causing serious ecological problems in many parts of the world; especially in developing countries where a budget for remediation technology is not affordable. Therefore, screening for microbes with high accumulation capacities and studying their stable resistance characteristics is advisable to define cost-effective any remediation strategies. Herein, the copper-resistome of the novel copper-resistant strain Amycolatopsis tucumanensis was studied using several approaches. Two dimensional gel electrophoresis revealed that proteins of the central metabolism, energy production, transcriptional regulators, two-component system, antioxidants and protective metabolites increased their abundance upon copper-stress conditions. Transcriptome analysis revealed that in presence of copper, superoxide dismutase, alkyl hydroperoxide reductase and mycothiol reductase genes were markedly induced in expression. The oxidative damage of protein and lipid from A. tucumanensis was negligible compared with that observed in the copper-sensitive strain Amycolatopsis eurytherma. Thus, we provide evidence that A. tucumamensis shows a high adaptation towards copper, the sum of which is proposed as the copper-resistome. This adaptation allows the strain to accumulate copper and survive this stress; besides, it constitutes the first report in which the copper-resistome of a strain of the genus Amycolatopsis with bioremediation potential has been evaluated.

Fabrication of high wettability gradient on copper substrate

NASA Astrophysics Data System (ADS)

Huang, Ding-Jun; Leu, Tzong-Shyng

2013-09-01

Copper is one of the most widely used materials in condensation heat transfer. Recently there has been great interest in improving the condensation heat transfer efficiency through copper surface modification. In this study, we describe the fabrication processes of how copper surfaces were modified to be superhydrophilic (CA ≤ 10°) and superhydrophobic (CA > 150°) by means of H2O2 immersion and fluorination with Teflon. The wettability gradient of copper surfaces with contact angles (CA) changing from superhydrophilic to superhydrophobic are also demonstrated. Unlike previous studies on gradient surfaces in which the wettability gradient is controlled either non-precisely or entirely uncontrolled, in this study, the contact angles along wettability gradient copper surfaces vary with a precisely designed gradient. It is demonstrated that a high wettability gradient copper surface can be successfully fabricated using photolithography to define the area ratios between superhydrophilic and superhydrophobic patterns within a short distance. The fabricated wettability gradient of copper surfaces is expected to be able to enhance the condensation heat transfer efficiency.

Copper Corrosion and Biocorrosion Events in Premise Plumbing

PubMed Central

Fischer, Diego A.; Alsina, Marco A.; Pastén, Pablo A.

2017-01-01

Corrosion of copper pipes may release high amounts of copper into the water, exceeding the maximum concentration of copper for drinking water standards. Typically, the events with the highest release of copper into drinking water are related to the presence of biofilms. This article reviews this phenomenon, focusing on copper ingestion and its health impacts, the physicochemical mechanisms and the microbial involvement on copper release, the techniques used to describe and understand this phenomenon, and the hydrodynamic effects. A conceptual model is proposed and the mathematical models are reviewed. PMID:28872628

Copper Corrosion and Biocorrosion Events in Premise Plumbing.

PubMed

Vargas, Ignacio T; Fischer, Diego A; Alsina, Marco A; Pavissich, Juan P; Pastén, Pablo A; Pizarro, Gonzalo E

2017-09-05

Corrosion of copper pipes may release high amounts of copper into the water, exceeding the maximum concentration of copper for drinking water standards. Typically, the events with the highest release of copper into drinking water are related to the presence of biofilms. This article reviews this phenomenon, focusing on copper ingestion and its health impacts, the physicochemical mechanisms and the microbial involvement on copper release, the techniques used to describe and understand this phenomenon, and the hydrodynamic effects. A conceptual model is proposed and the mathematical models are reviewed.

Dynamic Shock Compression of Copper to Multi-Megabar Pressure

NASA Astrophysics Data System (ADS)

Haill, T. A.; Furnish, M. D.; Twyeffort, L. L.; Arrington, C. L.; Lemke, R. W.; Knudson, M. D.; Davis, J.-P.

2015-11-01

Copper is an important material for a variety of shock and high energy density applications and experiments. Copper is used as a standard reference material to determine the EOS properties of other materials. The high conductivity of copper makes it useful as an MHD driver layer in high current dynamic materials experiments on Sandia National Laboratories Z machine. Composite aluminum/copper flyer plates increase the dwell time in plate impact experiments by taking advantage of the slower wave speeds in copper. This presentation reports on recent efforts to reinstate a composite Al/Cu flyer capability on Z and to extend the range of equation-of-state shock compression data through the use of hyper-velocity composite flyers and symmetric planar impact with copper targets. We will present results from multi-dimensional ALEGRA MHD simulations, as well as experimental designs and methods of composite flyer fabrication. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Company, for the U.S. DOE's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Atomic layer deposition of copper thin film and feasibility of deposition on inner walls of waveguides

NASA Astrophysics Data System (ADS)

Yuqing, XIONG; Hengjiao, GAO; Ni, REN; Zhongwei, LIU

2018-03-01

Copper thin films were deposited by plasma-enhanced atomic layer deposition at low temperature, using copper(I)-N,N‧-di-sec-butylacetamidinate as a precursor and hydrogen as a reductive gas. The influence of temperature, plasma power, mode of plasma, and pulse time, on the deposition rate of copper thin film, the purity of the film and the step coverage were studied. The feasibility of copper film deposition on the inner wall of a carbon fibre reinforced plastic waveguide with high aspect ratio was also studied. The morphology and composition of the thin film were studied by atomic force microscopy and x-ray photoelectron spectroscopy, respectively. The square resistance of the thin film was also tested by a four-probe technique. On the basis of on-line diagnosis, a growth mechanism of copper thin film was put forward, and it was considered that surface functional group played an important role in the process of nucleation and in determining the properties of thin films. A high density of plasma and high free-radical content were helpful for the deposition of copper thin films.

Use of Electrodeposition for Sample Preparation and Rejection Rate Prediction for Assay of Electroformed Ultra High Purity Copper for 232Th and 238U Prior to Inductively Coupled Plasma Mass Spectrometry (ICP/MS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoppe, Eric W.; Aalseth, Craig E.; Brodzinski, Ronald L.

The search for neutrinoless double beta decay in 76Ge has driven the need for ultra-low background Ge detectors shielded by electroformed copper of ultra-high radiopurity (<0.1µBq/kg). Although electrodeposition processes are almost sophisticated enough to produce copper of this purity, to date there are no methods sensitive enough to assay it. Inductively-coupled plasma mass spectrometry (ICP/MS) can detect thorium and uranium at femtogram levels, but in the past, this assay has been hindered by high copper concentrations in the sample. Electrodeposition of copper samples removes copper from the solution while selectively concentrating thorium and uranium contaminants to be assayed by ICP/MS.more » Spiking 232Th and 238U into the plating bath simulates low purity copper and allows for the calculation of the electrochemical rejection rate of thorium and uranium in the electroplating system. This rejection value will help to model plating bath chemistry.« less

[Role of hemoglobin affinity to oxygen in adaptation to hypoxemia].

PubMed

Kwasiborski, Przemysław Jerzy; Kowalczyk, Paweł; Zieliński, Jakub; Przybylski, Jacek; Cwetsch, Andrzej

2010-04-01

One of the basic mechanisms of adapting to hypoxemia is a decrease in the affinity of hemoglobin for oxygen. This process occurs mainly due to the increased synthesis of 2,3-diphosphoglycerate (2,3-DPG) in the erythrocytes, as well as through the Bohr effect. Hemoglobin with decreased affinity for oxygen increases the oxygenation of tissues, because it gives up oxygen more easily during microcirculation. In foetal circulation, however, at a partial oxygen pressure (pO2) of 25 mmHg in the umbilical vein, the oxygen carrier is type F hemoglobin which has a high oxygen affinity. The commonly accepted role for hemoglobin F is limited to facilitating diffusion through the placenta. Is fetal life the only moment when haemoglobin F is useful? THE AIM OF STUDY was to create a mathematical model, which would answer the question at what conditions an increase, rather than a decrease, in haemoglobin oxygen affinity is of benefit to the body. Using the kinetics of dissociation of oxygen from hemoglobin described by the Hill equation as the basis for further discussion, we created a mathematical model describing the pO2 value in the microcirculatory system and its dependence on arterial blood pO2. The calculations were performed for hemoglobin with low oxygen affinity (adult type) and high-affinity hemoglobin (fetal type). The modelling took into account both physiological and pathological ranges of acid-base equilibrium and tissue oxygen extraction parameters. It was shown that for the physiological range of acid-base equilibrium and the resting level of tissue oxygen extraction parameters, with an arterial blood pO2 of 26.8 mmHg, the higher-affinity hemoglobin becomes the more effective oxygen carrier. It was also demonstrated that the arterial blood pO2, below which the high-affinity hemoglobin becomes the more effective carrier, is dependent on blood pH and the difference between the arterial and venous oxygen saturation levels. Simulations performed for the pathological states showed that acidosis and increased tissue oxygen demand lead to a broadened arterial blood pO2 range, in which the high-affinity hemoglobin is more efficient. Contrary to the widely held view that the only response to hypoxemia is a decrease in haemoglobin oxygen affinity, it was shown that under extreme hypoxemic conditions, an increased haemoglobin oxygen affinity improves the oxygenation of tissues. It was also shown that the dominance of hemoglobin with a high oxygen affinity rapidly exceeds hemoglobin with low oxygen affinity in the case of acidosis with its accompanying high tissue oxygen extraction. In cases of extreme disruptions of the acid-base equilibrium, the dominance of high-oxygen-affinity hemoglobin spans over the entire possible range of pO2 in arterial blood.

Affinity proteomics to study endogenous protein complexes: Pointers, pitfalls, preferences and perspectives

PubMed Central

LaCava, John; Molloy, Kelly R.; Taylor, Martin S.; Domanski, Michal; Chait, Brian T.; Rout, Michael P.

2015-01-01

Dissecting and studying cellular systems requires the ability to specifically isolate distinct proteins along with the co-assembled constituents of their associated complexes. Affinity capture techniques leverage high affinity, high specificity reagents to target and capture proteins of interest along with specifically associated proteins from cell extracts. Affinity capture coupled to mass spectrometry (MS)-based proteomic analyses has enabled the isolation and characterization of a wide range of endogenous protein complexes. Here, we outline effective procedures for the affinity capture of protein complexes, highlighting best practices and common pitfalls. PMID:25757543

Geochemical prospecting for copper and nickel in the Wulgai and Tor Tangi areas southeast of Hindubagh, Quetta Division, Pakistan

USGS Publications Warehouse

Stanin, S. Anthony; Wahid, M.A.; Khan, Shamsher

1975-01-01

Showings of magnetite, copper, and possible nickel mineralization in the Hindubagh chromite mining district are near Wulgai and Tor Tangi. Several hundred samples of clastic material from dry streambeds in these areas were sieved for the minus-80-mesh fraction and analyzed for copper using 2, 2'-biquinoline and for nickel using alpha-furildioxime. The copper threshold is 75 ppm, and the nickel threshold is 400 ppm. A geochemical map has been prepared that shows nine areas of anomalously high copper and six areas of high nickel. The nickel anomalies may represent secondary dispersion patterns derived from the erosion of nickeliferous ultramafic rocks of the Hindubagh intrusive complex. Copper showings in and near four of the anomalous copper areas indicate that detailed geological investigation and detailed geochemical sampling of rocks, soil, and unconsolidated clastic material are required to determine the source of the anomalies.

Antioxidant Properties of Pterocarpans through Their Copper(II) Coordination Ability. A DFT Study in Vacuo and in Aqueous Solution

NASA Astrophysics Data System (ADS)

Alagona, Giuliano; Ghio, Caterina

2009-10-01

The antioxidant activity of 3,9-dimethoxy-4-prenylpterocarpan (bitucarpin A) and 3,9-dihydroxy-4,8-diprenylpterocarpan (erybraedin C) is supposed to be related to their copper coordination ability. Therefore several complexes with Cu2+ of low-energy conformers of these two prenylated pterocarpans, whose conformational landscape was the subject of a prior B3LYP/6-31G* study (Alagona, Ghio, Monti Phys. Chem. Chem. Phys. 2004, 6, 2849), have been taken into account at the same computational level, with the metal ion described by effective core potentials in the LanL2DZ valence basis set. Their metal ion affinity (MIA) values have been determined and compared with the results obtained earlier with the same methods for the preferred binding sites of plicatin B, a prenylchalcone that can exist in E and Z configurations as well as in tautomeric forms. The stability order of the metalated species at the various coordination sites strongly depends on their position and nature. The spin density of the cation upon ligand coordination becomes vanishingly small, whereas the ligand spin density approaches 1. Thus the ligand is oxidized to a radical cation (Ligand•+), while Cu(II) is reduced to Cu(I). A very favorable MIA is obtained in vacuo when Cu2+ is chelated between the prenyl and O lone pair moieties for both pterocarpans (MIA = 370 and 380 kcal/mol for bitucarpin A and erybraedin C, respectively). High affinity values are found also when the cation is sequestered within the two end groups (prenyl π density and D ring) in the Ot configuration (MIA = 371 and 373 kcal/mol for bitucarpin A and erybraedin C, respectively). In aqueous solution, the solvent effect dampens the free energy differences and reduces the MIA especially when the ion is remarkably exposed to the solvent. Conversely, when Cu2+ is sequestered, the MIA decrease in solution is limited (MIA = 327 and 360 kcal/mol for bitucarpin A and erybraedin C, respectively). The solvent effect is significantly larger in plicatin B, where the MIA is lowered by 80 to 140 kcal/mol, probably because (a) the screening ability of the substituted phenolic ring is lower and (b) the positive charge on the ligand is less efficiently delocalized than in the four fused ring system of pterocarpans.

Characterization and mechanism of copper biosorption by a highly copper-resistant fungal strain isolated from copper-polluted acidic orchard soil.

PubMed

Tu, Chen; Liu, Ying; Wei, Jing; Li, Lianzhen; Scheckel, Kirk G; Luo, Yongming

2018-06-22

In this paper, a highly copper-resistant fungal strain NT-1 was characterized by morphological, physiological, biochemical, and molecular biological techniques. Physiological response to Cu(II) stress, effects of environmental factors on Cu(II) biosorption, as well as mechanisms of Cu(II) biosorption by strain NT-1 were also investigated in this study. The results showed that NT-1 belonged to the genus Gibberella, which exhibited high tolerance to both acidic conditions and Cu(II) contamination in the environment. High concentrations of copper stress inhibited the growth of NT-1 to various degrees, leading to the decreases in mycelial biomass and colony diameter, as well as changes in morphology. Under optimal conditions (initial copper concentration: 200 mg L -1 , temperature 28 °C, pH 5.0, and inoculum dose 10%), the maximum copper removal percentage from solution through culture of strain NT-1 within 5 days reached up to 45.5%. The biosorption of Cu(II) by NT-1 conformed to quasi-second-order kinetics and Langmuir isothermal adsorption model and was confirmed to be a monolayer adsorption process dominated by surface adsorption. The binding of NT-1 to Cu(II) was mainly achieved by forming polydentate complexes with carboxylate and amide group through covalent interactions and forming Cu-nitrogen-containing heterocyclic complexes via Cu(II)-π interaction. The results of this study provide a new fungal resource and key parameters influencing growth and copper removal capacity of the strain for developing an effective bioremediation strategy for copper-contaminated acidic orchard soils.

A demonstration of the antimicrobial effectiveness of various copper surfaces

PubMed Central

2013-01-01

Background Bacterial contamination on touch surfaces results in increased risk of infection. In the last few decades, work has been done on the antimicrobial properties of copper and its alloys against a range of micro-organisms threatening public health in food processing, healthcare and air conditioning applications; however, an optimum copper method of surface deposition and mass structure has not been identified. Results A proof-of-concept study of the disinfection effectiveness of three copper surfaces was performed. The surfaces were produced by the deposition of copper using three methods of thermal spray, namely, plasma spray, wire arc spray and cold spray The surfaces were then inoculated with meticillin-resistant Staphylococcus aureus (MRSA). After a two hour exposure to the surfaces, the surviving MRSA were assayed and the results compared. The differences in the copper depositions produced by the three thermal spray methods were examined in order to explain the mechanism that causes the observed differences in MRSA killing efficiencies. The cold spray deposition method was significantly more effective than the other methods. It was determined that work hardening caused by the high velocity particle impacts created by the cold spray technique results in a copper microstructure that enhances ionic diffusion, and copper ions are principally responsible for antimicrobial activity. Conclusions This test showed significant microbiologic differences between coatings produced by different spray techniques and demonstrates the importance of the copper application technique. The cold spray technique shows superior anti-microbial effectiveness caused by the high impact velocity imparted to the sprayed particles which results in high dislocation density and high ionic diffusivity. PMID:23537176

High Surface-Enhanced Raman Scattering (SERS) Amplification Factor Obtained with Silver Printed Circuit Boards and the Influence of Phenolic Resins for the Characterization of the Pesticide Thiram.

PubMed

Silva de Almeida, Francylaine; Bussler, Larissa; Marcio Lima, Sandro; Fiorucci, Antonio Rogério; da Cunha Andrade, Luis Humberto

2016-07-01

In this work, low-cost substrates with rough silver surfaces were prepared from commercial copper foil-covered phenolic board (CPB) and an aqueous solution of AgNO3, and were used for surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) measurements. A maximum SERS amplification factor of 1.2 × 10(7) was obtained for Rhodamine 6G (R6G), and use of the CPB resulted in a detection limit for Thiram pesticide of 0.5 µmol L(-1) The minimum detection level was limited by residual traces of phenolic groups that originated from the substrate resin, which became solubilized in the aqueous Ag(+) solution. It was found that the bands corresponding to the impurities had less influence in the Thiram analysis, which could be explained by the high affinity of sulfur for Ag surfaces. The influence of impurities in the SERS analyses therefore depended on the linkage between the rough silver surface and the analyte. The findings demonstrated the ease and effectiveness of using CPB to prepare a nanostructured surface for SERS. © The Author(s) 2016.

HIGH-AFFINITY T CELL RECEPTOR DIFFERENTIATES COGNATE PEPTIDE-MHC AND ALTERED PEPTIDE LIGANDS WITH DISTINCT KINETICS AND THERMODYNAMICS

PubMed Central

Persaud, Stephen P.; Donermeyer, David L.; Weber, K. Scott; Kranz, David M.; Allen, Paul M.

2010-01-01

Interactions between the T cell receptor and cognate peptide-MHC are crucial initiating events in the adaptive immune response. These binding events are highly specific yet occur with micromolar affinity. Even weaker interactions between TCR and self-pMHC complexes play critical regulatory roles in T cell development, maintenance and coagonist activity. Due to their low affinity, the kinetics and thermodynamics of such weak interactions are difficult to study. In this work, we used M15, a high-affinity TCR engineered from the 3.L2 TCR system, to study the binding properties, thermodynamics, and specificity of two altered peptide ligands (APLs). Our affinity measurements of the high-affinity TCR support the view that the wild type TCR binds these APLs in the millimolar affinity range, and hence very low affinities can still elicit biological functions. Finally, single methylene differences among the APLs gave rise to strikingly different binding thermodynamics. These minor changes in the pMHC antigen were associated with significant and unpredictable changes in both the entropy and enthalpy of the reaction. As the identical TCR was analyzed with several structurally similar ligands, the distinct thermodynamic binding profiles provide a mechanistic perspective on how exquisite antigen specificity is achieved by the T cell receptor. PMID:20334923

Let's get specific: the relationship between specificity and affinity.

PubMed

Eaton, B E; Gold, L; Zichi, D A

1995-10-01

The factors that lead to high-affinity binding are a good fit between the surfaces of the two molecules in their ground state and charge complementarity. Exactly the same factors give high specificity for a target. We argue that selection for high-affinity binding automatically leads to highly specific binding. This principle can be used to simplify screening approaches aimed at generating useful drugs.

Increased mercury emissions from modern dental amalgams.

PubMed

Bengtsson, Ulf G; Hylander, Lars D

2017-04-01

All types of dental amalgams contain mercury, which partly is emitted as mercury vapor. All types of dental amalgams corrode after being placed in the oral cavity. Modern high copper amalgams exhibit two new traits of increased instability. Firstly, when subjected to wear/polishing, droplets rich in mercury are formed on the surface, showing that mercury is not being strongly bonded to the base or alloy metals. Secondly, high copper amalgams emit substantially larger amounts of mercury vapor than the low copper amalgams used before the 1970s. High copper amalgams has been developed with focus on mechanical strength and corrosion resistance, but has been sub-optimized in other aspects, resulting in increased instability and higher emission of mercury vapor. This has not been presented to policy makers and scientists. Both low and high copper amalgams undergo a transformation process for several years after placement, resulting in a substantial reduction in mercury content, but there exist no limit for maximum allowed emission of mercury from dental amalgams. These modern high copper amalgams are nowadays totally dominating the European, US and other markets, resulting in significant emissions of mercury, not considered when judging their suitability for dental restoration.

ESI-MS measurements for the equilibrium constants of copper(II)-insulin complexes.

PubMed

Gülfen, Mustafa; Özdemir, Abdil; Lin, Jung-Lee; Chen, Chung-Hsuan

2018-06-01

Trace elements regulate many biological reactions in the body. Copper(II) is known as one of trace elements and capable of binding to proteins. Insulin is a blood glucose-lowering peptide hormone and it is secreted by the pancreatic β-cells. In this study, Cu(II)-insulin complexes were investigated by using ESI-MS method. Insulin molecule gives ESI-MS peaks at +4, +5, +6 and +7 charged states. Cu(II)-insulin complexes can be monitored and quantified on the ESI-MS spectra as the shifted peaks according to insulin peaks. The solutions of Cu(II)-insulin complexes at different pHs and mole ratios of Cu(II) ions to insulin molecule were measured on the ESI-MS. The highest complex formation ratio for Cu(II)-insulin were found at pH 7. The multiple bindings of Cu(II) ions to insulin molecule was observed. The formation equilibrium constants of Cu(II)-insulin complexes were calculated as Kf 1 : 3.34 × 10 4 , Kf 2 : 2.99 × 10 4 , Kf 3 : 7.00 × 10 3 and Kf 4 :2.86 × 10 3 . The specific binding property of Cu(II) ions was controlled by using different spray ion sources including electrospray and nano-electrospray. The binding property of Cu(II) also investigated by MS/MS fragmentation. It was concluded from the ESI-MS measurements that Cu(II) ion has a high affinity to insulin molecules to form stable complexes. Copyright © 2018 Elsevier B.V. All rights reserved.

Interaction Between ABA Signaling and Copper Homeostasis in Arabidopsis thaliana.

PubMed

Carrió-Seguí, Àngela; Romero, Paco; Sanz, Amparo; Peñarrubia, Lola

2016-07-01

ABA is involved in plant responses to non-optimal environmental conditions, including nutrient availability. Since copper (Cu) is a very important micronutrient, unraveling how ABA affects Cu uptake and distribution is relevant to ensure adequate Cu nutrition in plants subjected to stress conditions. Inversely, knowledge about how the plant nutritional status can interfere with ABA biosynthesis and signaling mechanisms is necessary to optimize stress tolerance in horticultural crops. Here the reciprocal influence between ABA and Cu content was addressed by using knockout mutants and overexpressing transgenic plants of high affinity plasma membrane Cu transporters (pmCOPT) with altered Cu uptake. Exogenous ABA inhibited pmCOPT expression and drastically modified COPT2-driven localization in roots. ABA regulated SPL7, the main transcription factor responsive for Cu deficiency responses, and subsequently affected expression of its targets. ABA biosynthesis (aba2) and signaling (hab1-1 abi1-2) mutants differentially responded to ABA according to Cu levels. Alteration of Cu homeostasis in the pmCOPT mutants affected ABA biosynthesis, transport and signaling as genes such as NCED3, WRKY40, HY5 and ABI5 were differentially modulated by Cu status, and also in the pmCOPT and ABA mutants. Altered Cu uptake resulted in modified plant sensitivity to salt-mediated increases in endogenous ABA. The overall results provide evidence for reciprocal cross-talk between Cu status and ABA metabolism and signaling. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A novel cyanide ion sensing approach based on Raman scattering for the detection of environmental cyanides.

PubMed

Yan, Fei; Gopal Reddy, C V; Zhang, Yan; Vo-Dinh, Tuan

2010-09-01

This paper describes a direct optical approach based on Raman scattering for selective and sensitive detection of cyanide ions in aqueous environment without requiring time-consuming sample pretreatment and the formation of hydrogen cyanide. Due to the strong affinity between copper (I) and cyanide ion, evaporated copper (I) iodide (CuI) thin films are shown to be excellent substrates for selective recognition of free cyanide ions in aqueous matrices. The amount of cyanide ion retained by the copper (I) in the CuI thin films reflects its actual concentration in tested samples, and the subsequent Raman measurements of the substrate are shown to be capable of detecting toxic cyanide content at levels under international drinking water standard and environmental regulatory concentrations. Measurements obtained from the same batch of evaporated CuI thin films (approximately 100-nm thickness) show excellent linearity over a variety of cyanide concentrations ranging from 1.5 microM to 0.15 mM. This detection method offers the advantage of selectively detecting cyanides causing a health hazard while avoiding detection of other common interfering anions such as Cl-, Br-, PO4(3-), SO4(2-), NO2-, S2- and SCN-. Coupled with portable Raman systems that are commercially available, our detection approach will provide on-site monitoring capability with little sample preparation or instrument supervision, which will greatly expedite the assessment of potential environmental cyanide risks. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Copper-boosting compounds: a novel concept for antimycobacterial drug discovery.

PubMed

Speer, Alexander; Shrestha, Tej B; Bossmann, Stefan H; Basaraba, Randall J; Harber, Gregory J; Michalek, Suzanne M; Niederweis, Michael; Kutsch, Olaf; Wolschendorf, Frank

2013-02-01

We and others recently identified copper resistance as important for virulence of Mycobacterium tuberculosis. Here, we introduce a high-throughput screening assay for agents that induce a copper hypersensitivity phenotype in M. tuberculosis and demonstrate that such copper-boosting compounds are effective against replicating and nonreplicating M. tuberculosis strains.

Casting copper to tungsten for high-power arc lamp cathodes

NASA Technical Reports Server (NTRS)

Will, H. A.

1974-01-01

Voids forming at interface when copper is cast onto tungsten can be eliminated by adding wetting agent during casting process. Small amount of copper and nickel are cast onto thoriated tungsten insert, insert is recast with more copper to form electrode. Good thermal conductance results in long-lived cathode.

Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus.

PubMed

Haeili, Mehri; Moore, Casey; Davis, Christopher J C; Cochran, James B; Shah, Santosh; Shrestha, Tej B; Zhang, Yaofang; Bossmann, Stefan H; Benjamin, William H; Kutsch, Olaf; Wolschendorf, Frank

2014-07-01

Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant Staphylococcus aureus (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Unmasking of CD22 Co-receptor on Germinal Center B-cells Occurs by Alternative Mechanisms in Mouse and Man*

PubMed Central

Macauley, Matthew S.; Kawasaki, Norihito; Peng, Wenjie; Wang, Shui-Hua; He, Yuan; Arlian, Britni M.; McBride, Ryan; Kannagi, Reiji; Khoo, Kay-Hooi; Paulson, James C.

2015-01-01

CD22 is an inhibitory B-cell co-receptor whose function is modulated by sialic acid (Sia)-bearing glycan ligands. Glycan remodeling in the germinal center (GC) alters CD22 ligands, with as yet no ascribed biological consequence. Here, we show in both mice and humans that loss of high affinity ligands on GC B-cells unmasks the binding site of CD22 relative to naive and memory B-cells, promoting recognition of trans ligands. The conserved modulation of CD22 ligands on GC B-cells is striking because high affinity glycan ligands of CD22 are species-specific. In both species, the high affinity ligand is based on the sequence Siaα2–6Galβ1–4GlcNAc, which terminates N-glycans. The human ligand has N-acetylneuraminic acid (Neu5Ac) as the sialic acid, and the high affinity ligand on naive B-cells contains 6-O-sulfate on the GlcNAc. On human GC B-cells, this sulfate modification is lost, giving rise to lower affinity CD22 ligands. Ligands of CD22 on naive murine B-cells do not contain the 6-O-sulfate modification. Instead, the high affinity ligand for mouse CD22 has N-glycolylneuraminic acid (Neu5Gc) as the sialic acid, which is replaced on GC B-cells with Neu5Ac. Human naive and memory B-cells express sulfated glycans as high affinity CD22 ligands, which are lost on GC B-cells. In mice, Neu5Gc-containing glycans serve as high affinity CD22 ligands that are replaced by Neu5Ac-containing glycans on GC B-cells. Our results demonstrate that loss of high affinity CD22 ligands on GC B-cells occurs in both mice and humans through alternative mechanisms, unmasking CD22 relative to naive and memory B-cells. PMID:26507663

Unmasking of CD22 Co-receptor on Germinal Center B-cells Occurs by Alternative Mechanisms in Mouse and Man.

PubMed

Macauley, Matthew S; Kawasaki, Norihito; Peng, Wenjie; Wang, Shui-Hua; He, Yuan; Arlian, Britni M; McBride, Ryan; Kannagi, Reiji; Khoo, Kay-Hooi; Paulson, James C

2015-12-11

CD22 is an inhibitory B-cell co-receptor whose function is modulated by sialic acid (Sia)-bearing glycan ligands. Glycan remodeling in the germinal center (GC) alters CD22 ligands, with as yet no ascribed biological consequence. Here, we show in both mice and humans that loss of high affinity ligands on GC B-cells unmasks the binding site of CD22 relative to naive and memory B-cells, promoting recognition of trans ligands. The conserved modulation of CD22 ligands on GC B-cells is striking because high affinity glycan ligands of CD22 are species-specific. In both species, the high affinity ligand is based on the sequence Siaα2-6Galβ1-4GlcNAc, which terminates N-glycans. The human ligand has N-acetylneuraminic acid (Neu5Ac) as the sialic acid, and the high affinity ligand on naive B-cells contains 6-O-sulfate on the GlcNAc. On human GC B-cells, this sulfate modification is lost, giving rise to lower affinity CD22 ligands. Ligands of CD22 on naive murine B-cells do not contain the 6-O-sulfate modification. Instead, the high affinity ligand for mouse CD22 has N-glycolylneuraminic acid (Neu5Gc) as the sialic acid, which is replaced on GC B-cells with Neu5Ac. Human naive and memory B-cells express sulfated glycans as high affinity CD22 ligands, which are lost on GC B-cells. In mice, Neu5Gc-containing glycans serve as high affinity CD22 ligands that are replaced by Neu5Ac-containing glycans on GC B-cells. Our results demonstrate that loss of high affinity CD22 ligands on GC B-cells occurs in both mice and humans through alternative mechanisms, unmasking CD22 relative to naive and memory B-cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential effects of ethanol and other inducers of drug metabolism on the two forms of hamster liver microsomal aniline hydroxylase.

PubMed

McCoy, G D

1980-03-01

The aniline hydroxylase activity of microsomes isolated from hamster liver can be differentiated kinetically into high affinity (low K(m), form I) and low affinity (high K(m), form II) forms. Microsomes isolated from uninduced animals contain slightly more form I activity. The activity of the low affinity form (form II) is preferentially enhanced by Aroclor or 3-methylcholanthrene treatment, while phenobarbital treatment increases the activity of both forms. Chronic ethanol consumption results in enhancement of only the high affinity form (form I).

Effect of copper on the performance and bacterial communities of activated sludge using Illumina MiSeq platforms.

PubMed

Sun, Fu-Lin; Fan, Lei-Lei; Xie, Guang-Jian

2016-08-01

The anaerobic-anoxic-aerobic (A2O) process is a highly efficient sewage treatment method, which uses complex bacterial communities. However, the effect of copper on this process and the bacterial communities involved remains unknown. In this study, a systematic investigation of the effect of persistent exposure of copper in the A2O wastewater treatment system was performed. An A2O device was designed to examine the effect of copper on the removal efficiency and microbial community compositions of activated sludge that was continuously treated with 10, 20, and 40 mg L(-1) copper, respectively. Surprisingly, a decrease in chemical oxygen demand (COD) and ammonia nitrogen (NH4N) removal efficiency was observed, and the toxicity of high copper concentration was significantly greater at 7d than at 1d. Proteobacteria, Bacteroidetes, Acidobacteria, Chlorobi, and Nitrospirae were the dominant bacterial taxa in the A2O system, and significant changes in microbial community were observed during the exposure period. Most of the dominant bacterial groups were easily susceptible to copper toxicity and diversely changed at different copper concentrations. However, not all the bacterial taxa were inhibited by copper treatment. At high copper concentration, many bacterial species were stimulated and their abundance increased. Cluster analysis and principal coordinate analysis (PCoA) based on operational taxonomic units (OTUs) revealed clear differences in the bacterial communities among the samples. These findings indicated that copper severely affected the performance and key microbial populations in the A2O system as well as disturbed the stability of the bacterial communities in the system, thus decreasing the removal efficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

A comprehensive device modelling of perovskite solar cell with inorganic copper iodide as hole transport material

NASA Astrophysics Data System (ADS)

Zulqarnain Haider, Syed; Anwar, Hafeez; Wang, Mingqing

2018-03-01

Hole transport material (HTM) plays an important role in the efficiency and stability of perovskite solar cells (PSCs). Spiro-MeOTAD, the commonly used HTM, is costly and can be easily degraded by heat and moisture, thus offering hindrance to commercialize PSCs. There is dire need to find an alternate inorganic and stable HTM to exploit PSCs with their maximum capability. In this paper, a comprehensive device simulation is used to study various possible parameters that can influence the performance of perovskite solar cell with CuI as HTM. These include the effect of doping density, defect density and thickness of absorber layer, along with the influence of diffusion length of carriers as well as electron affinity of electron transport layer (ETM) and HTM on the performance of PSCs. In addition, hole mobility and doping density of HTM is also investigated. CuI is a p-type inorganic material with low cost and relatively high stability. It is found that concentration of dopant in absorber layer and HTM, the electron affinity of HTM and ETM affect the performance of solar cell minutely, while cell performance improves greatly with the reduction of defect density. Upon optimization of parameters, power conversion efficiency for this device is found to be 21.32%. The result shows that lead-based PSC with CuI as HTM is an efficient system. Enhancing the stability and reduction of defect density are critical factors for future research. These factors can be improved by better fabrication process and proper encapsulation of solar cell.

Characteristics of the Copper,Zinc Superoxide Dismutase of a Hadal Sea Cucumber (Paelopatides sp.) from the Mariana Trench.

PubMed

Li, Yanan; Kong, Xue; Chen, Jiawei; Liu, Helu; Zhang, Haibin

2018-05-18

Superoxide dismutases (SODs) are among the most important antioxidant enzymes and show great potential in preventing adverse effects during therapeutic trials. In the present study, cloning, expression, and characterization of a novel Cu,Zn superoxide dismutase (Ps-Cu,Zn-SOD) from a hadal sea cucumber ( Paelopatides sp.) were reported. Phylogenetic analysis showed that Ps-Cu,Zn-SOD belonged to a class of intracellular SOD. Its K m and V max were 0.0258 ± 0.0048 mM and 925.1816 ± 28.0430 units/mg, respectively. The low K m value of this enzyme represents a high substrate affinity and can adapt to the low metabolic rate of deep sea organisms. The enzyme functioned from 0 °C to 80 °C with an optimal temperature of 40 °C. Moreover, the enzyme activity was maintained up to 87.12% at 5 °C. The enzyme was active at pH 4 to 12 with an optimal pH of 8.5. Furthermore, Ps-Cu,Zn-SOD tolerated high concentration of urea and GuHCl, resisted hydrolysis by proteases, and maintained stability at high pressure. All these features demonstrated that the deep sea Ps-Cu,Zn-SOD is a potential candidate for application to the biopharmaceutical field.

Purine uptake in Plasmodium: transport versus metabolism.

PubMed

Kirk, Kiaran; Howitt, Susan M; Bröer, Stefan; Saliba, Kevin J; Downie, Megan J

2009-06-01

In a recent paper, Quashie et al. have proposed that purine uptake into the intraerythrocytic malaria parasite involves four different plasma membrane transporters - two high affinity and two low affinity. They equate one of the two high-affinity transporters with PfNT1, a transporter reported previously to be a low-affinity system. Here, we offer an alternative interpretation of their data, suggesting that the conclusions drawn by Quashie et al. take insufficient account of metabolism.

Host-Guest Complexes with Protein-Ligand-Like Affinities: Computational Analysis and Design

PubMed Central

Moghaddam, Sarvin; Inoue, Yoshihisa

2009-01-01

It has recently been discovered that guests combining a nonpolar core with cationic substituents bind cucurbit[7]uril (CB[7]) in water with ultra-high affinities. The present study uses the Mining Minima algorithm to study the physics of these extraordinary associations and to computationally test a new series of CB[7] ligands designed to bind with similarly high affinity. The calculations reproduce key experimental observations regarding the affinities of ferrocene-based guests with CB[7] and β-cyclodextrin and provide a coherent view of the roles of electrostatics and configurational entropy as determinants of affinity in these systems. The newly designed series of compounds is based on a bicyclo[2.2.2]octane core, which is similar in size and polarity to the ferrocene core of the existing series. Mining Minima predicts that these new compounds will, like the ferrocenes, bind CB[7] with extremely high affinities. PMID:19133781

Structural Insights into the Affinity of Cel7A Carbohydrate-binding Module for Lignin*

PubMed Central

Strobel, Kathryn L.; Pfeiffer, Katherine A.; Blanch, Harvey W.; Clark, Douglas S.

2015-01-01

The high cost of hydrolytic enzymes impedes the commercial production of lignocellulosic biofuels. High enzyme loadings are required in part due to their non-productive adsorption to lignin, a major component of biomass. Despite numerous studies documenting cellulase adsorption to lignin, few attempts have been made to engineer enzymes to reduce lignin binding. In this work, we used alanine-scanning mutagenesis to elucidate the structural basis for the lignin affinity of Trichoderma reesei Cel7A carbohydrate binding module (CBM). T. reesei Cel7A CBM mutants were produced with a Talaromyces emersonii Cel7A catalytic domain and screened for their binding to cellulose and lignin. Mutation of aromatic and polar residues on the planar face of the CBM greatly decreased binding to both cellulose and lignin, supporting the hypothesis that the cellulose-binding face is also responsible for lignin affinity. Cellulose and lignin affinity of the 31 mutants were highly correlated, although several mutants displayed selective reductions in lignin or cellulose affinity. Four mutants with increased cellulose selectivity (Q2A, H4A, V18A, and P30A) did not exhibit improved hydrolysis of cellulose in the presence of lignin. Further reduction in lignin affinity while maintaining a high level of cellulose affinity is thus necessary to generate an enzyme with improved hydrolysis capability. This work provides insights into the structural underpinnings of lignin affinity, identifies residues amenable to mutation without compromising cellulose affinity, and informs engineering strategies for family one CBMs. PMID:26209638

Solvent polarity effect on quality of n-octadecanethiol self-assembled monolayers on copper and oxidized copper

NASA Astrophysics Data System (ADS)

Zhang, Yaozhong; Zhou, Jun; Zhang, Xiaoli; Hu, Jun; Gao, Han

2014-11-01

This article reports the effect of solvent polarity on the formation of n-octadecanethiol self-assembled monolayers (C18SH-SAMs) on pure copper surface and oxidized copper surface. The quality of SAMs prepared in different solvents (n-hexane, toluene, trichloroethylene, chloroform, acetone, acetonitrile, ethanol) was monitored by EIS, RAIRS and XPS. The results indicated that C18SH-SAMs formed in these solvents were in good barrier properties on pure copper surface and the structures of monolayers formed in high polarity solvents were more compact and orderly than that formed in low polarity solvents. For comparison, C18SH adsorbed on the surface of oxidized copper in these solvents were studied and the results indicated that C18SH could be adsorbed on oxidized copper surface after the reduction of copper oxide layer by thiols. Compared with high polarity solvents, a limited reduction process of oxidized copper by thiols led to the incompletely formation of monolayers in low polarity solvents. This can be interpreted that the generated water on solid-liquid interface and a smaller reaction force restrict the continuous reduction reaction in low polarity solvents

High-affinity K+ uptake in pepper plants.

PubMed

Martínez-Cordero, M Angeles; Martínez, Vicente; Rubio, Francisco

2005-06-01

High-affinity K+ uptake is an essential process for plant nutrition under K+-limiting conditions. The results presented here demonstrate that pepper (Capsicum annuum) plants grown in the absence of NH4+ and starved of K+ show an NH4+-sensitive high-affinity K+ uptake that allows plant roots to deplete external K+ to values below 1 microM. When plants are grown in the presence of NH4+, high-affinity K+ uptake is not inhibited by NH4+. Although NH4+-grown plants deplete external K+ below 1 microM in the absence of NH4+, when 1 mM NH4+ is present they do not deplete external K+ below 10 microM. A K+ transporter of the HAK family, CaHAK1, is very likely mediating the NH4+-sensitive component of the high-affinity K+ uptake in pepper roots. CaHAK1 is strongly induced in the roots that show the NH4+-sensitive high-affinity K+ uptake and its induction is reduced in K+-starved plants grown in the presence of NH4+. The NH4+-insensitive K+ uptake may be mediated by an AKT1-like K+ channel.

High l-Trp affinity of indoleamine 2,3-dioxygenase 1 is attributed to two residues located in the distal heme pocket.

PubMed

Yuasa, Hajime J

2016-10-01

Indoleamine 2, 3-dioxygenase (IDO) catalyzes the oxidative cleavage of the pyrrole ring of l-Trp to generate N-formyl-kynurenine. Two IDO genes, IDO1 and IDO2, are found in vertebrates. Mammalian IDO1s are high-affinity, l-Trp-degrading enzymes, whereas IDO2s generally have a relatively low affinity. It has been suggested that the distal-Ser (corresponding to Ser167 of human IDO1) was crucial for improvement in the affinity for l-Trp but this idea was insufficient to explain the high affinity shown by mammalian IDO1. In this study, the amino acid sequences of vertebrate ancestral IDO1 and ancestral IDO2 were inferred, and bacterially expressed ancestral IDOs were characterized. Although the amino acid sequences of the enzymes shared high identity (86%) with each other, they showed distinct enzymatic properties. In analyses of a series of ancestral IDO1/IDO2 chimeric enzymes and their variants, the distal-Tyr (corresponding to Tyr126 of human IDO1) was detected as another and was probably the most crucial residue for high l-Trp affinity. The two amino acid substitutions (distal-Ser to Thr and distal-Tyr to His) drastically decreased the l-Trp affinity and catalytic efficiency of IDO1s. Conversely, two substitutions (distal-Thr to Ser and distal-His to Tyr) were sufficient to bestow IDO1-like high affinity on ancestral and chicken IDO2. © 2016 Federation of European Biochemical Societies.

High fructose feeding induces copper deficiency in Sprague-Dawley rats: A novel mechanism for obesity related fatty liver

USDA-ARS?s Scientific Manuscript database

Dietary copper deficiency is associated with a variety of manifestations of the metabolic syndrome, including hyperlipidemia and fatty liver. Fructose feeding has been reported to exacerbate complications of copper deficiency. In this study, we investigated whether copper deficiency plays a role in ...

Insights into the mechanism of copper-tolerance in Fibroporia radiculosa: The biosynthesis of oxalate

Treesearch

Katie Jenkins; Carol A. Clausen; Frederick Green; Susan V. Diehl

2015-01-01

Copper is currently used as the key component in wood preservatives despite the known tolerance of many brown-rot Basidiomycetes. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate when exposed to copper. To gain insight into the mechanism of oxalate production, four F. radiculosa...

Flexible transparent conducting hybrid film using a surface-embedded copper nanowire network: a highly oxidation-resistant copper nanowire electrode for flexible optoelectronics.

PubMed

Im, Hyeon-Gyun; Jung, Soo-Ho; Jin, Jungho; Lee, Dasom; Lee, Jaemin; Lee, Daewon; Lee, Jung-Yong; Kim, Il-Doo; Bae, Byeong-Soo

2014-10-28

We report a flexible high-performance conducting film using an embedded copper nanowire transparent conducting electrode; this material can be used as a transparent electrode platform for typical flexible optoelectronic devices. The monolithic composite structure of our transparent conducting film enables simultaneously an outstanding oxidation stability of the copper nanowire network (14 d at 80 °C), an exceptionally smooth surface topography (R(rms) < 2 nm), and an excellent opto-electrical performances (Rsh = 25 Ω sq(-1) and T = 82%). A flexible organic light emitting diode device is fabricated on the transparent conducting film to demonstrate its potential as a flexible copper nanowire electrode platform.

Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides.

PubMed

Li, Hsin-Yi; Chen, Chien-Yuan; Cheng, Hui-Ting; Chu, Yen-Ho

2016-10-13

Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5- a ]pyridine, a number of bicyclic triazolium ionic liquids 1 - 3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1 , 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides.

Low-macroscopic field emission properties of wide bandgap copper aluminium oxide nanoparticles for low-power panel applications.

PubMed

Banerjee, Arghya Narayan; Joo, Sang W

2011-09-07

Field emission properties of CuAlO(2) nanoparticles are reported for the first time, with a low turn-on field of approximately 2 V µm(-1) and field enhancement factor around 230. The field emission process follows the standard Fowler-Nordheim tunnelling of cold electron emission. The emission mechanism is found to be a combination of low electron affinity, internal nanostructure and large field enhancement at the low-dimensional emitter tips of the nanoparticles. The field emission properties are comparable to the conventional carbon-based field emitters, and thus can become alternative candidate for field emission devices for low-power panel applications.

Low-macroscopic field emission properties of wide bandgap copper aluminium oxide nanoparticles for low-power panel applications

NASA Astrophysics Data System (ADS)

Narayan Banerjee, Arghya; Joo, Sang W.

2011-09-01

Field emission properties of CuAlO2 nanoparticles are reported for the first time, with a low turn-on field of approximately 2 V µm - 1 and field enhancement factor around 230. The field emission process follows the standard Fowler-Nordheim tunnelling of cold electron emission. The emission mechanism is found to be a combination of low electron affinity, internal nanostructure and large field enhancement at the low-dimensional emitter tips of the nanoparticles. The field emission properties are comparable to the conventional carbon-based field emitters, and thus can become alternative candidate for field emission devices for low-power panel applications.

Communication between the N and C Termini Is Required for Copper-stimulated Ser/Thr Phosphorylation of Cu(I)-ATPase (ATP7B)*

PubMed Central

Braiterman, Lelita T.; Gupta, Arnab; Chaerkady, Raghothama; Cole, Robert N.; Hubbard, Ann L.

2015-01-01

The Wilson disease protein ATP7B exhibits copper-dependent trafficking. In high copper, ATP7B exits the trans-Golgi network and moves to the apical domain of hepatocytes where it facilitates elimination of excess copper through the bile. Copper levels also affect ATP7B phosphorylation. ATP7B is basally phosphorylated in low copper and becomes more phosphorylated (“hyperphosphorylated”) in elevated copper. The functional significance of hyperphosphorylation remains unclear. We showed that hyperphosphorylation occurs even when ATP7B is restricted to the trans-Golgi network. We performed comprehensive phosphoproteomics of ATP7B in low versus high copper, which revealed that 24 Ser/Thr residues in ATP7B could be phosphorylated, and only four of these were copper-responsive. Most of the phosphorylated sites were found in the N- and C-terminal cytoplasmic domains. Using truncation and mutagenesis, we showed that inactivation or elimination of all six N-terminal metal binding domains did not block copper-dependent, reversible, apical trafficking but did block hyperphosphorylation in hepatic cells. We showed that nine of 15 Ser/Thr residues in the C-terminal domain were phosphorylated. Inactivation of 13 C-terminal phosphorylation sites reduced basal phosphorylation and eliminated hyperphosphorylation, suggesting that copper binding at the N terminus propagates to the ATP7B C-terminal region. C-terminal mutants with either inactivating or phosphomimetic substitutions showed little effect upon copper-stimulated trafficking, indicating that trafficking does not depend on phosphorylation at these sites. Thus, our studies revealed that copper-dependent conformational changes in the N-terminal region lead to hyperphosphorylation at C-terminal sites, which seem not to affect trafficking and may instead fine-tune copper sequestration. PMID:25666620

Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahy, N.; Woolkalis, M.; Thermos, K.

1988-08-01

The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog (125I)CGP 23996. (125I)CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was tomore » a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity (125I)CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of (125I)CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect (125I)CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with (125I) CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to (125I)CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors.« less

Effects of a copper-tolerant grass (Agrostis capillaris) on the ecosystem of a copper-contaminated arable soil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boon, G.T.; Bouwman, L.A.; Bloem, J.

1998-10-01

To test how a dysfunctioning ecosystem of a severely metal-polluted soil responds to renewed plant growth, a pot experiment was conducted with soil from an experimental arable field with pH and copper gradients imposed 13 years ago. In this experiment, four pH/copper combinations from this field were either planted with a pH- and copper-resistant grass cultivar or remained fallow. During a 10-week period, the dynamics of the microbial activity and of the abundances of bacteria, protozoa. and nematodes were measured, as were the dynamics of several chemical soil parameters. After 13 years of copper, which had resulted in severely reducedmore » crop growth, no effects were observed on bacterial numbers, respiration, or protozoan numbers, but bacterial growth was strongly reduced in the low pH plots, and even more so in low pH plots enriched with copper. Of the organisms, only nematodes were negatively affected under conditions of high copper load at low pH. In these plots, numbers belonging to all feeding categories were strongly reduced. Planting of a copper-tolerant grass variety, Agrostis capillaris L. var. Parys Mountain, resulted within 10 weeks in faster bacterial growth and more protozoa and bacterivorous nematodes in comparison with fallow controls; these effects were markedly strongest in the acidic, copper-enriched soils. During incubation, fungivorous nematodes increased in all treatments, in fallow and in planted pots and in the pots with high-copper, low-pH soil. The results of this experiment suggest that introduction of plant growth is one of the major causes of increased biological activity in acidic contaminated soils. Planting such soils with metal-tolerant plant species can reestablish the necessary food base to support soil organism growth, and this can lead to numerous positive effects, reversing the loss of soil functions due to the high copper levels under acidic conditions.« less

Laboratory evolution of copper tolerant yeast strains

PubMed Central

2012-01-01

Background Yeast strains endowed with robustness towards copper and/or enriched in intracellular Cu might find application in biotechnology processes, among others in the production of functional foods. Moreover, they can contribute to the study of human diseases related to impairments of copper metabolism. In this study, we investigated the molecular and physiological factors that confer copper tolerance to strains of baker's yeasts. Results We characterized the effects elicited in natural strains of Candida humilis and Saccharomyces cerevisiae by the exposure to copper in the culture broth. We observed that, whereas the growth of Saccharomyces cells was inhibited already at low Cu concentration, C. humilis was naturally robust and tolerated up to 1 g · L-1 CuSO4 in the medium. This resistant strain accumulated over 7 mg of Cu per gram of biomass and escaped severe oxidative stress thanks to high constitutive levels of superoxide dismutase and catalase. Both yeasts were then "evolved" to obtain hyper-resistant cells able to proliferate in high copper medium. While in S. cerevisiae the evolution of robustness towards Cu was paralleled by the increase of antioxidative enzymes, these same activities decreased in evolved hyper-resistant Candida cells. We also characterized in some detail changes in the profile of copper binding proteins, that appeared to be modified by evolution but, again, in a different way in the two yeasts. Conclusions Following evolution, both Candida and Saccharomyces cells were able to proliferate up to 2.5 g · L-1 CuSO4 and to accumulate high amounts of intracellular copper. The comparison of yeasts differing in their robustness, allowed highlighting physiological and molecular determinants of natural and acquired copper tolerance. We observed that different mechanisms contribute to confer metal tolerance: the control of copper uptake, changes in the levels of enzymes involved in oxidative stress response and changes in the copper-binding proteome. However, copper elicits different physiological and molecular reactions in yeasts with different backgrounds. PMID:22214286

Cytomegalovirus-Specific CD8+ T-Cells With Different T-Cell Receptor Affinities Segregate T-Cell Phenotypes and Correlate With Chronic Graft-Versus-Host Disease in Patients Post-Hematopoietic Stem Cell Transplantation

PubMed Central

Poiret, Thomas; Axelsson-Robertson, Rebecca; Remberger, Mats; Luo, Xiao-Hua; Rao, Martin; Nagchowdhury, Anurupa; Von Landenberg, Anna; Ernberg, Ingemar; Ringden, Olle; Maeurer, Markus

2018-01-01

Virus-specific T-cell responses are crucial to control cytomegalovirus (CMV) infections/reactivation in immunocompromised individuals. Adoptive cellular therapy with CMV-specific T-cells has become a viable treatment option. High-affinity anti-viral cellular immune responses are associated with improved long-term immune protection against CMV infection. To date, the characterization of high-affinity T-cell responses against CMV has not been achieved in blood from patients after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, the purpose of this study was to describe and analyze the phenotype and clinical impact of different CMV-specific CD8+ cytotoxic T-lymphocytes (CMV-CTL) classes based on their T-cell receptor (TCR) affinity. T-cells isolated from 23 patients during the first year following HSCT were tested for the expression of memory markers, programmed cell death 1 (PD-1), as well as TCR affinity, using three different HLA-A*02:01 CMVNLVPMVATV-Pp65 tetramers (wild-type, a245v and q226a mutants). High-affinity CMV-CTL defined by q226a tetramer binding, exhibited a higher frequency in CD8+ T-cells in the first month post-HSCT and exhibited an effector memory phenotype associated with strong PD-1 expression as compared to the medium- and low-affinity CMV-CTLs. High-affinity CMV-CTL was found at higher proportion in patients with chronic graft-versus-host disease (p < 0.001). This study provides a first insight into the detailed TCR affinities of CMV-CTL. This may be useful in order to improve current immunotherapy protocols using isolation of viral-specific T-cell populations based on their TCR affinity. PMID:29692783

Removal of sulfur and nitrogen containing pollutants from discharge gases

DOEpatents

Joubert, James I.

1986-01-01

Oxides of sulfur and of nitrogen are removed from waste gases by reaction with an unsupported copper oxide powder to form copper sulfate. The resulting copper sulfate is dissolved in water to effect separation from insoluble mineral ash and dried to form solid copper sulfate pentahydrate. This solid sulfate is thermally decomposed to finely divided copper oxide powder with high specific surface area. The copper oxide powder is recycled into contact with the waste gases requiring cleanup. A reducing gas can be introduced to convert the oxide of nitrogen pollutants to nitrogen.

Textured carbon surfaces on copper by sputtering

NASA Technical Reports Server (NTRS)

Curren, A. N. (Inventor); Jensen, K. A. (Inventor); Roman, R. F. (Inventor)

1986-01-01

A very thin layer of highly textured carbon is applied to a copper surface by a triode sputtering process. A carbon target and a copper substrate are simultaneously exposed to an argon plasma in a vacuum chamber. The resulting carbon surface is characterized by a dense, random array of needle like spires or peaks which extend perpendicularly from the copper surface. The coated copper is especially useful for electrode plates in multistage depressed collectors.

The impact of aging wine in high and low oxygen conditions on the fractionation of Cu and Fe in Chardonnay wine.

PubMed

Kontoudakis, Nikolaos; Guo, Anque; Scollary, Geoffrey R; Clark, Andrew C

2017-08-15

Solid-phase extraction has previously been used to fractionate copper and iron into hydrophobic, cationic and residual forms. This study showed the change in fractionated copper and iron in Chardonnay wines with 1-year of bottle aging under variable oxygen and protein concentrations. Wines containing protein in low oxygen conditions induced a decrease (20-50%) in total copper and increased the proportion of the hydrophobic copper fraction, associated with copper(I) sulfide. In contrast, protein stabilised wines showed a lower proportion of the hydrophobic copper fraction after 1-year of aging. In oxidative storage conditions, the total iron decreased by 60% when at high concentration, and the concentration of the residual fraction of both copper and iron increased. The results show that oxidative storage increases the most oxidative catalytic form of the metal, whilst changes during reductive storage depend on the extent of protein stabilisation of the wine. Copyright © 2017 Elsevier Ltd. All rights reserved.

pMHC affinity controls duration of CD8+ T cell–DC interactions and imprints timing of effector differentiation versus expansion

PubMed Central

Sharpe, James; Zehn, Dietmar; Kreutzfeldt, Mario

2016-01-01

During adaptive immune responses, CD8+ T cells with low TCR affinities are released early into the circulation before high-affinity clones become dominant at later time points. How functional avidity maturation is orchestrated in lymphoid tissue and how low-affinity cells contribute to host protection remains unclear. In this study, we used intravital imaging of reactive lymph nodes (LNs) to show that T cells rapidly attached to dendritic cells irrespective of TCR affinity, whereas one day later, the duration of these stable interactions ceased progressively with lowering peptide major histocompatibility complex (pMHC) affinity. This correlated inversely BATF (basic leucine zipper transcription factor, ATF-like) and IRF4 (interferon-regulated factor 4) induction and timing of effector differentiation, as low affinity–primed T cells acquired cytotoxic activity earlier than high affinity–primed ones. After activation, low-affinity effector CD8+ T cells accumulated at efferent lymphatic vessels for egress, whereas high affinity–stimulated CD8+ T cells moved to interfollicular regions in a CXCR3-dependent manner for sustained pMHC stimulation and prolonged expansion. The early release of low-affinity effector T cells led to rapid target cell elimination outside reactive LNs. Our data provide a model for affinity-dependent spatiotemporal orchestration of CD8+ T cell activation inside LNs leading to functional avidity maturation and uncover a role for low-affinity effector T cells during early microbial containment. PMID:27799622

Extracellular and circulating redox- and metalloregulated eRNA and eRNP: copper ion-structured RNA cytokines (angiotropin ribokines) and bioaptamer targets imparting RNA chaperone and novel biofunctions to S100-EF-hand and disease-associated proteins.

PubMed

Wissler, Josef H

2004-06-01

Bioassays for cellular differentiation and tissue morphogenesis were used to design methods for isolation of bioactive redox- and metalloregulated nucleic acids and copper ion complexes with proteins from extracellular, circulating, wound, and supernatant fluids of cultured cells. In extracellular biospheres, diversities of nucleic acids were found to be secreted by cells upon activation. They may reflect nucleic acid biolibraries with molecular imprints of cellular history. After removal of protein components, eRNA prototypes exuded by activated cells were sequenced. They are small, endogenous, highly modified and edited, redox- and metalloregulated 5'-end phosphorylated extracellular eRNA (approximately 2-200 bases) with cellular, enzymic, and bioaptamer functions. Fenton-type OH* radical redox reactions may form modified nucleotides in RNA as wobbles eRNA per se, or as copper ion-complex with protein (e.g., S100A12-EF-hand protein, angiotropin-related protein, calgranulin-C, hippocampal neurite differentiation factor) are shown to be bioactive in vivo and in vitro as cytokines (ribokines) and as nonmitogenic angiomorphogens for endothelial cell differentiation in the formation of organoid supracellular capillary structures. As bioaptamers, copper ion-structured eRNA imparts novel biofunctions to proteins that they do not have on their own. The origin of extracellular RNA and intermediate precursors (up to 500 bases) was traced to intracellular parent nucleic acids. Intermediate precursors with and without partial homology were found. This suggests that bioaptamers are not directly retranslatable gene products. Metalloregulated eRNA bioaptamer function was investigated by domains (e.g. 5'...CUG...3' hairpin loop) for folding, bioactivity, and binding of protein with copper, calcium, and alkali metal ion affinity. Vice versa, metalloregulated nucleic acid-binding domains (K3H, R3H) in proteins were identified. Interaction of protein and eRNA docking potentials were visualized by 3D-rapid prototyping of accurate molecular image models based on crystallographic or NMR data. For S100A12-homologous proteins, receptor- and metalloregulated RNA chaperone-shaped protein assemblies were investigated. They suggest insight into signaling cascades as to how eRNA transmits its cytokine (ribokine) bioinformation from the extracellular RNA biosphere into cells. Proteomics of the extracellular RNA biosphere demonstrate the presence of nucleic acid-binding domain homologies in defense-, aging-, and disease-associated neuronal and other proteins as targets for RNA orphans. By structural relationships found to transmissible processes, proteinaceous transfer ("infectivity") and feedback of bioinformation beyond the central dogma of molecular biology are considered in terms of metalloregulated RNA bioaptamer function, nucleic acid-binding domains, and protein conformation.

Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics.

PubMed

Seeman, P; Ko, F; Tallerico, T

2005-09-01

Although phencyclidine and ketamine are used to model a hypoglutamate theory of schizophrenia, their selectivity for NMDA receptors has been questioned. To determine the affinities of phencyclidine, ketamine, dizocilpine and LSD for the functional high-affinity state of the dopamine D2 receptor, D2High, their dissociation constants (Ki) were obtained on [3H]domperidone binding to human cloned dopamine D2 receptors. Phencyclidine had a high affinity for D2High with a Ki of 2.7 nM, in contrast to its low affinity for the NMDA receptor, with a Ki of 313 nM, as labeled by [3H]dizocilpine on rat striatal tissue. Ketamine also had a high affinity for D2High with a Ki of 55 nM, an affinity higher than its 3100 nM Ki for the NMDA sites. Dizocilpine had a Ki of 0.3 nM at D2High, but a Kd of 1.8 nM at the NMDA receptor. LSD had a Ki of 2 nM at D2High. Because the psychotomimetics had higher potency at D2High than at the NMDA site, the psychotomimetic action of these drugs must have a major contribution from D2 agonism. Because these drugs have a combined action on both dopamine receptors and NMDA receptors, these drugs, when given in vivo, test a combined hyperdopamine and hypoglutamate theory of psychosis.

Metals in Metal Salts: A Copper Mirror Demonstration

ERIC Educational Resources Information Center

Pike, Robert D.

2010-01-01

A simple lecture demonstration is described to show the latent presence of metal atoms in a metal salt. Copper(II) formate tetrahydrate is heated in a round-bottom flask forming a high-quality copper mirror.

High rate copper and energy recovery in microbial fuel cells

PubMed Central

Rodenas Motos, Pau; ter Heijne, Annemiek; van der Weijden, Renata; Saakes, Michel; Buisman, Cees J. N.; Sleutels, Tom H. J. A.

2015-01-01

Bioelectrochemical systems (BESs) are a novel, promising technology for the recovery of metals. The prerequisite for upscaling from laboratory to industrial size is that high current and high power densities can be produced. In this study we report the recovery of copper from a copper sulfate stream (2 g L-1 Cu2+) using a laboratory scale BES at high rate. To achieve this, we used a novel cell configuration to reduce the internal voltage losses of the system. At the anode, electroactive microorganisms produce electrons at the surface of an electrode, which generates a stable cell voltage of 485 mV when combined with a cathode where copper is reduced. In this system, a maximum current density of 23 A m-2 in combination with a power density of 5.5 W m-2 was produced. XRD analysis confirmed 99% purity in copper of copper deposited onto cathode surface. Analysis of voltage losses showed that at the highest current, most voltage losses occurred at the cathode, and membrane, while anode losses had the lowest contribution to the total voltage loss. These results encourage further development of BESs for bioelectrochemical metal recovery. PMID:26150802

Rupture testing for the quality control of electrodeposited copper interconnections in high-speed, high-density circuits

NASA Technical Reports Server (NTRS)

Zakraysek, Louis

1987-01-01

Printed Wiring Multilayer Board (PWMLB) structures for high speed, high density circuits are prone to failure due to the microcracking of electrolytic copper interconnections. The failure can occur in the foil that makes up the inner layer traces or in the plated through holes (PTH) deposit that forms the layer to layer interconnections. It is shown that there are some distinctive differences in the quality of Type E copper and that these differences can be detected before its use in a PWMLB. It is suggested that the strength of some Type E copper can be very low when the material is hot and that it is the use of this poor quality material in a PWMLB that results in PTH and inner layer microcracking. Since the PWMLB failure in question are induced by a thermal stress, and since the poorer grades of Type E materials used in these structures are susceptible to premature failure under thermal stress, the use of elevated temperature rupture and creep rupture testing is proposed as a means for screening copper foil, or its PTH equivalent, in order to eliminate the problem of Type E copper microcracking in advanced PWMLBs.

Identification and properties of steroid-binding proteins in nesting Chelonia mydas plasma.

PubMed

Ikonomopoulou, M P; Bradley, A J; Whittier, J M; Ibrahim, K

2006-11-01

We report for the first time the presence of a sex steroid-binding protein in the plasma of green sea turtles Chelonia mydas, which provides an insight into reproductive status. A high affinity, low capacity sex hormone steroid-binding protein was identified in nesting C. mydas and its thermal profile was established. In nesting C. mydas testosterone and oestradiol bind at 4 degrees C with high affinity (K (a) = 1.49 +/- 0.09 x 10(9) M(-1); 0.17 +/- 0.02 x 10(7) M(-1)) and low binding capacity (B (max) = 3.24 +/- 0.84 x 10(-5) M; 0.33 +/- 0.06 x 10(-4) M). The binding affinity and capacity of testosterone at 23 and 36 degrees C, respectively were similar to those determined at 4 degrees C. However, oestradiol showed no binding activity at 36 degrees C. With competition studies we showed that oestradiol and oestrone do not compete for binding sites. Furthermore, in nesting C. mydas plasma no high-affinity binding was observed for adrenocortical steroids (cortisol and corticosterone) and progesterone. Our results indicate that in nesting C. mydas plasma temperature has a minimal effect on the high-affinity binding of testosterone to sex steroid-binding protein, however, the high affinity binding of oestradiol to sex steroid-binding protein is abolished at a hypothetically high (36 degrees C) sea/ambient/body temperature. This suggests that at high core body temperatures most of the oestradiol becomes biologically available to the tissues rather than remaining bound to a high-affinity carrier.

High mortality rates occur in copper deficient rats exposed to a normally nonlethal endotoxin treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiSilvestro, R.; Joseph, E.; Yang, F.L.

Endotoxin hepatotoxicity is proposed to occur by processes which could be retarded by 3 copper enzymes: ceruloplasmin, Cu-Zn superoxide dismutase (SOD), and extracellular (EC) SOD. Weanling rats fed low copper for 40 days showed low activity levels of these enzymes, and a very high mortality rate 20 h after endotoxin injection. No rats fed adequate copper died from this treatment. In addition, serum transaminase activities, indicators of liver damage, were elevated by 3 h to a greater extent in the deficient rats than in the adequates. The high susceptibility to endotoxemia in the deficient rats was not associated with lowmore » hepatic glutathione, high liver malondialedhyde, nor restricted metallothionein induction 3 h after endotoxin injection. Endotoxin reduced serum EC SOD activities in adequate and deficient rats, but final values were lower in the latter. Studies on roles of specific copper enzymes in resistance to endotoxemia are currently underway.« less

Suppression of copper thin film loss during graphene synthesis.

PubMed

Lee, Alvin L; Tao, Li; Akinwande, Deji

2015-01-28

Thin metal films can be used to catalyze the growth of nanomaterials in place of the bulk metal, while greatly reducing the amount of material used. A big drawback of copper thin films (0.5-1.5 μm thick) is that, under high temperature/vacuum synthesis, the mass loss of films severely reduces the process time due to discontinuities in the metal film, thereby limiting the time scale for controlling metal grain and film growth. In this work, we have developed a facile method, namely "covered growth" to extend the time copper thin films can be exposed to high temperature/vacuum environment for graphene synthesis. The key to preventing severe mass loss of copper film during the high temperature chemical vapor deposition (CVD) process is to have a cover piece on top of the growth substrate. This new "covered growth" method enables the high-temperature annealing of the copper film upward of 4 h with minimal mass loss, while increasing copper film grain and graphene domain size. Graphene was then successfully grown on the capped copper film with subsequent transfer for device fabrication. Device characterization indicated equivalent physical, chemical, and electrical properties to conventional CVD graphene. Our "covered growth" provides a convenient and effective solution to the mass loss issue of thin films that serve as catalysts for a variety of 2D material syntheses.

The Application of Orthophosphate to Reduce Elevated Copper Levels in a New Building with High DIC Water

EPA Science Inventory

Public water utilities in the United States are required to meet the 1991 Lead and Copper Rule action level of 1.3 mg/L for copper I drinking water. The effect of water chemistry on Cu(II) solubility has been studied, and drawing upon conclusions from this research , new copper ...

Evaluating the Mechanism of Oxalate Synthesis of Fibroporia Radiculosa Isolates Adapting to Copper-Tolerance

Treesearch

Katie Marie Jenkins

2012-01-01

Despite the drawbacks associated with tolerant organisms, copper is still used as the key component in current wood preservatives. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate in response to copper. The biosynthesis of oxalate has been connected to specific enzymes in the glyoxylate and...

Effects of Copper Pollution on the Phenolic Compound Content, Color, and Antioxidant Activity of Wine.

PubMed

Sun, Xiangyu; Ma, Tingting; Han, Luyang; Huang, Weidong; Zhan, Jicheng

2017-05-03

The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, and the antioxidant activity values of the wine also increased. When the copper concentration reached the lowest level of the medium copper range (9.6~16 mg/L), most of the indices also improved. When the copper concentrations reached the latter part of the medium copper range (19.2 and 22.4 mg/L), many of the tested indices began to decrease. Furthermore, when the copper concentration reached the high ranges (32, 64, and 96 mg/L), the polyphenol content, CIELAB color parameters, and antioxidant activity of wine were substantially decreased, indicating the need to control increasing copper content in grape must.

The competitive advantage of a dual-transporter system.

PubMed

Levy, Sagi; Kafri, Moshe; Carmi, Miri; Barkai, Naama

2011-12-09

Cells use transporters of different affinities to regulate nutrient influx. When nutrients are depleted, low-affinity transporters are replaced by high-affinity ones. High-affinity transporters are helpful when concentrations of nutrients are low, but the advantage of reducing their abundance when nutrients are abundant is less clear. When we eliminated such reduced production of the Saccharomyces cerevisiae high-affinity transporters for phosphate and zinc, the elapsed time from the initiation of the starvation program until the lack of nutrients limited growth was shortened, and recovery from starvation was delayed. The latter phenotype was rescued by constitutive activation of the starvation program. Dual-transporter systems appear to prolong preparation for starvation and to facilitate subsequent recovery, which may optimize sensing of nutrient depletion by integrating internal and external information about nutrient availability.

SLC31 (CTR) Family of Copper Transporters in Health and Disease

PubMed Central

Kim, Heejeong; Wu, Xiaobin; Lee, Jaekwon

2012-01-01

Copper is a vital mineral for many organisms, yet it is highly toxic as demonstrated by serious health concerns associated with its deficiency or excess accumulation. The SLC31 (CTR) family of copper transporters is a major gateway of copper acquisition in eukaryotes, ranging from yeast to humans. Characterization of the function, modes of action, and regulation of CTR and other molecular factors that functionally cooperate with CTR for copper transport, compartmentalization, incorporation into cuproproteins, and detoxification has revealed that organisms have evolved fascinating mechanisms for tight control of copper metabolism. This research progress further indicates the significance of copper in health and disease and opens avenues for therapeutic control of copper bioavailability and its metabolic pathways. PMID:23506889

A HIGH-LEVEL CALCULATION OF THE PROTON AFFINITY OF DIBORANE

EPA Science Inventory

The experimental proton affinity of diborane (B2H6) is based on an unstable species, B2H,+, 4 which has been observed only at low temperatures. The present work calculates the proton 5 affinity of diborane using the Gaussian-3 method and other high-level compound ab initio 6 met...

Graphite fiber/copper matrix composites for space power heat pipe fin applications

NASA Astrophysics Data System (ADS)

McDanels, David L.; Baker, Karl W.; Ellis, David L.

1991-01-01

High specific thermal conductivity (thermal conductivity divided by density) is a major design criterion for minimizing system mass for space power systems. For nuclear source power systems, graphite fiber reinforced copper matrix (Gr/Cu) composites offer good potential as a radiator fin material operating at service temperatures above 500 K. Specific thermal conductivity in the longitudinal direction is better than beryllium and almost twice that of copper. The high specific thermal conductivity of Gr/Cu offers the potential of reducing radiator mass by as much as 30 percent. Gr/Cu composites also offer the designer a range of available properties for various missions and applications. The properties of Gr/Cu are highly anisotropic. Longitudinal elastic modulus is comparable to beryllium and about three times that of copper. Thermal expansion in the longitudinal direction is near zero, while it exceeds that of copper in the transverse direction.

Facile and green synthesis of highly stable L-cysteine functionalized copper nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Nikhil; Upadhyay, Lata Sheo Bachan

2016-11-01

A simple eco-friendly method for L-cysteine capped copper nanoparticles (CCNPs) synthesis in aqueous solution has been developed. Glucose and L-cysteine were used as reducing agent and capping/functionalizing agent, respectively. Different parameters such as capping agent concentration, pH, reaction temperature, and reducing agent concentration were optimized during the synthesis. The L-cysteine capped copper nanoparticle were characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, Particle size and zeta potential analyser, and high resolution transmission electron microscopy. Spherical shaped cysteine functionalized/capped copper nanoparticles with an average size of 40 nm were found to be highly stable at room temperature (RT) for a period of 1 month

Heteroleptic Copper(I)-Based Complexes for Photocatalysis: Combinatorial Assembly, Discovery, and Optimization.

PubMed

Minozzi, Clémentine; Caron, Antoine; Grenier-Petel, Jean-Christophe; Santandrea, Jeffrey; Collins, Shawn K

2018-05-04

A library of 50 copper-based complexes derived from bisphosphines and diamines was prepared and evaluated in three mechanistically distinct photocatalytic reactions. In all cases, a copper-based catalyst was identified to afford high yields, where new heteroleptic complexes derived from the bisphosphine BINAP displayed high efficiency across all reaction types. Importantly, the evaluation of the library of copper complexes revealed that even when photophysical data is available, it is not always possible to predict which catalyst structure will be efficient or inefficient in a given process, emphasizing the advantages for catalyst structures with high modularity and structural variability. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

PubMed

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

Detection of ovomucoid-specific low-affinity IgE in infants and its relationship to eczema.

PubMed

Kawamoto, Norio; Kamemura, Norio; Kido, Hiroshi; Fukao, Toshiyuki

2017-06-01

Allergen-specific low-affinity IgE was previously detected in cord blood by a highly sensitive densely carboxylated protein (DCP) chip, but not by ImmunoCAP. Here, we investigated the presence of low-affinity IgE during the early life of infants and observed its relationship with eczema. We conducted a birth cohort study, collecting sera at birth and 6 and 14 months of age (n = 110). We monitored the ovomucoid (OM)- and egg white (EW)-specific IgE (sIgE) by ImmunoCAP or DCP chip and analyzed the antigen affinity of sIgE by binding inhibition assays in the presence or absence of a mild chaotropic agent, diethyl amine (DEA). The low- and high-affinity OM-sIgEs and sensitization risk factors were analyzed by a multivariate logistic analysis. The OM-sIgE measured by DCP chip significantly correlated with that measured by ImmunoCAP, but some samples assessed as OM-sIgE positive by DCP chip were considered OM-sIgE negative by ImmunoCAP. Binding inhibition analysis after DEA treatment was performed for participants judged as OM-sIgE positive by DCP chip at 14 M. The group assessed as negative for OM- and EW-sIgE by ImmunoCAP at 6 and 14 months showed a larger binding inhibition curve shift after DEA treatment than did the group assessed as positive at these times, indicating the presence of low-affinity sIgE antibodies at 14 months. The logistic regression analysis found that persistent eczema from 6 to 14 months is a significant risk factor for developing high-affinity, but not low-affinity, sIgE. Human infant peripheral blood contains allergen-specific low-affinity sIgE. Persistent eczema is related to the development of high-affinity, but not low-affinity, IgE. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Laser synthesis of a copper-single-walled carbon nanotube nanocomposite via molecular-level mixing and non-equilibrium solidification

NASA Astrophysics Data System (ADS)

Tu, Jay F.; Rajule, Nilesh; Molian, Pal; Liu, Yi

2016-12-01

A copper-single-walled carbon nanotube (Cu-SWCNT) metal nanocomposite could be an ideal material if it can substantially improve the strength of copper while preserving the metal’s excellent thermal and electrical properties. However, synthesis of such a nanocomposite is highly challenging, because copper and SWCNTs do not form intermetallic compounds and are insoluble; as a result, there are serious issues regarding wettability and fine dispersion of SWCNTs within the copper matrix. In this paper we present a novel wet process, called the laser surface implantation process (LSI), to synthesize Cu-SWCNT nanocomposites by mixing SWCNTs into molten copper. The LSI process includes drilling several microholes on a copper substrate, filling the microholes with SWCNTs suspended in solution, and melting the copper substrate to create a micro-well of molten copper. The molten copper advances radially outward to engulf the microholes with pre-deposited SWCNTs to form the Cu-SWCNT implant upon solidification. Rapid and non-equilibrium solidification is achieved due to copper’s excellent heat conductivity, so that SWCNTs are locked in position within the copper matrix without agglomerating into large clusters. This wet process is very different from the typical dry processes used in powder metallurgy. Very high hardness improvement, up to 527% over pure copper, was achieved, confirmed by micro-indentation tests, with only a 0.23% SWCNT volume fraction. The nanostructure of the nanocomposite was characterized by TEM imaging, energy-dispersive x-ray spectroscopy mapping and spectroscopy measurements. The SWCNTs were found to be finely dispersed within the copper matrix with cluster sizes in the range of nanometers, achieving the goal of molecular-level mixing.

Analysis of copper contamination in transformer insulating material with nanosecond- and femtosecond-laser-induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Aparna, N.; Vasa, N. J.; Sarathi, R.

2018-06-01

This work examines the oil-impregnated pressboard insulation of high-voltage power transformers, for the determination of copper contamination. Nanosecond- and femtosecond-laser-induced breakdown spectroscopy revealed atomic copper lines and molecular copper monoxide bands due to copper sulphide diffusion. X-ray diffraction studies also indicated the presence of CuO emission. Elemental and molecular mapping compared transformer insulating material ageing in different media—air, N2, He and vacuum.

Molecular dynamic simulations of the high-speed copper nanoparticles collision with the aluminum surface

NASA Astrophysics Data System (ADS)

Pogorelko, V. V.; Mayer, A. E.

2016-11-01

With the use of the molecular dynamic simulations, we investigated the effect of the high-speed (500 m/s, 1000 m/s) copper nanoparticle impact on the mechanical properties of an aluminum surface. Dislocation analysis shows that a large number of dislocations are formed in the impact area; the total length of dislocations is determined not only by the speed and size of the incoming copper nanoparticle (kinetic energy of the nanoparticle), but by a temperature of the system as well. The dislocations occupy the whole area of the aluminum single crystal at high kinetic energy of the nanoparticle. With the decrease of the nanoparticle kinetic energy, the dislocation structures are formed in the near-surface layer; formation of the dislocation loops takes place. Temperature rise of the system (aluminum substrate + nanoparticle) reduces the total dislocation length in the single crystal of aluminum; there is deeper penetration of the copper atoms in the aluminum at high temperatures. Average energy of the nanoparticles and room temperature of the system are optimal for production of high-quality layers of copper on the aluminum surface.

A horizontally gene transferred copper resistance locus confers hyper‐resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages

PubMed Central

Purves, Joanne; Thomas, Jamie; Riboldi, Gustavo P.; Zapotoczna, Marta; Tarrant, Emma; Andrew, Peter W.; Londoño, Alejandra; Planet, Paul J.; Geoghegan, Joan A.; Waldron, Kevin J.

2018-01-01

Summary Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA‐MRSA) USA300, confers copper hyper‐resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in emerging pathogenic isolates. Our data show that CopX, a putative P1B‐3‐ATPase efflux transporter, and CopL, a novel lipoprotein, confer copper hyper‐resistance compared to typical S. aureus strains. The copXL genes form an operon that is tightly repressed in low copper environments by the copper regulator CsoR. Significantly, CopX and CopL are important for S. aureus USA300 intracellular survival within macrophages. Therefore, the emergence of new S. aureus clones with the copXL locus has significant implications for public health because these genes confer increased resistance to antibacterial copper toxicity, enhancing bacterial fitness by altering S. aureus interaction with innate immunity. PMID:29521441

Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth

PubMed Central

Vittorio, Orazio; Brandl, Miriam; Cirillo, Giuseppe; Kimpton, Kathleen; Hinde, Elizabeth; Gaus, Katharina; Yee, Eugene; Kumar, Naresh; Duong, Hien; Fleming, Claudia; Haber, Michelle; Norris, Murray; Boyer, Cyrille; Kavallaris, Maria

2016-01-01

Neuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti-cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran-Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran-Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth. PMID:27374085

Templated synthesis of copper(II) azacyclam complexes using urea as a locking fragment and their metal-enhanced binding tendencies towards anions.

PubMed

Boiocchi, Massimo; Fabbrizzi, Luigi; Garolfi, Mauro; Licchelli, Maurizio; Mosca, Lorenzo; Zanini, Cristina

2009-10-26

Copper(II) azacyclam complexes 3(2+) and 4(2+) were obtained through a metal-templated procedure involving the pertinent open-chain tetramine, formaldehyde and a phenylurea derivative as a locking fragment. Both metal complexes can establish interactions with anions through the metal centre and the amide NH group. Equilibrium studies in DMSO by a spectrophotometric titration technique were carried out to assess the affinity of 3(2+) and 4(2+) towards anions. While the NH group of an amide model compound and the metal centre of the plain Cu(II)(azacyclam)(2+) complex do not interact at all with anions, 3(2+) and 4(2+) establish strong interactions with oxo anions, profiting from a pronounced cooperative effect. In particular, 1) they form stable 1:1 and 1:2 complexes with H(2)PO(4) (-) ions in a stepwise mode with both hydrogen-bonding and metal-ligand interactions, and 2) in the presence of CH(3)COO(-), they undergo deprotonation of the amido NH group and thus profit from axial coordination of the partially negatively charged carbonyl oxygen atom in a scorpionate binding mode.

Azide–Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination

PubMed Central

Mann, Victor R.; Powers, Alexander S.; Tilley, Drew C.; Sack, Jon T.; Cohen, Bruce E.

2018-01-01

Functionalization of nanocrystals is essential for their practical application, but synthesis on nanocrystal surfaces is limited by incompatibilities with certain key reagents. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is among the most useful methods for ligating molecules to surfaces, but has been largely useless for semiconductor quantum dots (QDs) because Cu+ ions quickly and irreversibly quench QD fluorescence. To discover non-quenching synthetic conditions for Cu-catalyzed click reactions on QD surfaces, we developed a combinatorial fluorescence assay to screen >2000 reaction conditions to maximize cycloaddition efficiency while minimizing QD quenching. We identify conditions for complete coupling without significant quenching, which are compatible with common QD polymer surfaces and various azide/alkyne pairs. Based on insight from the combinatorial screen and mechanistic studies of Cu coordination and quenching, we find that superstoichiometric concentrations of Cu can promote full coupling if accompanied by ligands that selectively compete the Cu from the QD surface but allow it to remain catalytically active. Applied to the conjugation of a K+ channel-specific peptidyl toxin to CdSe/ZnS QDs, we synthesize unquenched QD conjugates and image their specific and voltage-dependent affinity for K+ channels in live cells. PMID:29608274

Heavy metal-binding proteins from metal-stimulated bacteria as a novel adsorbent for metal removal technology.

PubMed

Sano, D; Myojo, K; Omura, T

2006-01-01

Water pollution with toxic heavy metals is of growing concern because heavy metals could bring about serious problems for not only ecosystems in the water environment but also human health. Some metal removal technologies have been in practical use, but much energy and troublesome treatments for chemical wastes are required to operate these conventional technologies. In this study, heavy metal-binding proteins (HMBPs) were obtained from metal-stimulated activated sludge culture with affinity chromatography using copper ion as a ligand. Two-dimensional electrophoresis revealed that a number of proteins in activated sludge culture were recovered as HMBPs for copper ion. N-termini of five HMBPs were determined, and two of them were found to be newly discovered proteins for which no amino acid sequences in protein databases were retrieved at more than 80% identities. Metal-coordinating amino acids occupied 38% of residues in one of the N-terminal sequences of the newly discovered HMBPs. Since these HMBPs were expected to be stable under conditions of water and wastewater treatments, it would be possible to utilize HMBPs as novel adsorbents for heavy metal removal if mass volume of HMBPs can be obtained with protein cloning techniques.

Selective Capture of Cesium and Thallium from Natural Waters and Simulated Wastes with Copper Ferrocyanide Functionalized Mesoporous Silica

PubMed Central

Sangvanich, Thanapon; Sukwarotwat, Vichaya; Wiacek, Robert J.; Grudzien, Rafal M.; Fryxell, Glen E.; Addleman, R. Shane; Timchalk, Charles; Yantasee, Wassana

2010-01-01

Copper(II) ferrocyanide on mesoporous silica (FC-Cu-EDA-SAMMS™) has been evaluated against iron(III) hexacyanoferrate(II) (insoluble Prussian Blue) for removing cesium (Cs+) and thallium (Tl+) from natural waters and simulated acidic and alkaline wastes. From pH 0.1 – 7.3, FC-Cu-EDA-SAMMS had greater affinities for Cs and Tl and was less affected by the solution pH, competing cations, and matrices. SAMMS also outperformed Prussian Blue in terms of adsorption capacities (e.g., 21.7 versus 2.6 mg Cs/g in acidic waste stimulant (pH 1.1), 28.3 versus 5.8 mg Tl/g in seawater), and rate (e.g., over 95 wt% of Cs was removed from seawater after 2 min with SAMMS, while only 75 wt% was removed with Prussian Blue). SAMMS also had higher stability (e.g., 2.5 to 13-fold less Fe dissolved from 2 to 24 hr of contact time). In addition to environmental applications, SAMMS has great potential to be used as orally administered drug for limiting the absorption of radioactive Cs and toxic Tl in gastrointestinal tract. PMID:20594644

Genotoxicity of mercury used in chromosome aberration tests.

PubMed

Akiyama, M; Oshima, H; Nakamura, M

2001-01-01

The purpose of this study was to investigate the genotoxic effects of Hg released from dental amalgams. The chromosome aberration test was conducted using original extracts and their diluted solutions of conventional type amalgam and high copper amalgam. The concentrations of Hg, Cu and Ag in the original extract of high copper amalgam were 17.64, 7.97 and 43.90 microM, respectively. Those in the original extract of conventional type amalgam were 20.63, 7.87 and 14.79 microM, respectively. 10 and 30 microM Hg(2+) were also used for comparison. The frequency of chromosome aberrations was below 5% with 0 microM Hg(2+) and with a triple dilution of high copper amalgam extract, containing 5.88 microM Hg, 14.63 microM Cu and 2.65 microM Ag. However, 9.5% of the cells showed chromosome aberrations with a quadruple dilution of conventional type amalgam, containing 5.15 microM Hg, 3.69 microM Cu and 1.96 microM Ag. The amount of Hg in the quadruple dilution of conventional type amalgam was less than that in the triple dilution of high copper amalgam extract and 10 microM Hg(2+). A concentration of 30 microM Hg(2+) caused 34.5% of the cells to show chromosome aberrations while with a two-thirds dilution of high copper amalgam extract, containing 11.76 microM Hg, 29.26 microM Cu and 5.31 microM Ag, 58.5% of the cells showed chromosome aberrations. A two-thirds dilution of high copper amalgam extract induced more chromosome aberrations than 30 microM Hg(2+), although the amount of Hg was less than 30 microM Hg(2+). A triple dilution of conventional type amalgam extract, original extracts of conventional type amalgam and high copper amalgam and 100 microM Hg(2+) were induced few metaphases. It was revealed that the conventional type amalgam induced chromosome aberrations with quadruple dilution where cell viability was about 80% and that the high copper amalgam induced a high level of chromosome aberrations with the two-thirds dilution. The effects of low level Hg on humans are not clear.

Investigation of electroforming techniques. [fabrication of regeneratively cooled thrust chambers

NASA Technical Reports Server (NTRS)

Malone, G. A.

1975-01-01

Copper and nickel electroforming was examined for the purpose of establishing the necessary processes and procedures for repeatable, successful fabrication of the outer structures of regeneratively cooled thrust chambers. The selection of electrolytes for copper and nickel deposition is described. The development studies performed to refine and complete the processes necessary for successful chamber shell fabrication and the testing employed to verify the applicability of the processes and procedures to small scale hardware are described. Specifications were developed to afford a guideline for the electroforming of high quality outer shells on regeneratively cooled thrust chamber liners. Test results indicated repeatable mechanical properties could be produced in copper deposits from the copper sulfate electrolyte with periodic current reversal and in nickel deposits from the sulfamate solution. Use of inert, removable channel fillers and the conductivizing of such is described. Techniques (verified by test) which produce high integrity bonds to copper and copper alloy liners are discussed.

Modeling of copper sorption onto GFH and design of full-scale GFH adsorbers.

PubMed

Steiner, Michele; Pronk, Wouter; Boller, Markus A

2006-03-01

During rain events, copper wash-off occurring from copper roofs results in environmental hazards. In this study, columns filled with granulated ferric hydroxide (GFH) were used to treat copper-containing roof runoff. It was shown that copper could be removed to a high extent. A model was developed to describe this removal process. The model was based on the Two Region Model (TRM), extended with an additional diffusion zone. The extended model was able to describe the copper removal in long-term experiments (up to 125 days) with variable flow rates reflecting realistic runoff events. The four parameters of the model were estimated based on data gained with specific column experiments according to maximum sensitivity for each parameter. After model validation, the parameter set was used for the design of full-scale adsorbers. These full-scale adsorbers show high removal rates during extended periods of time.

The Beaker phenomenon and the genomic transformation of northwest Europe.

PubMed

Olalde, Iñigo; Brace, Selina; Allentoft, Morten E; Armit, Ian; Kristiansen, Kristian; Booth, Thomas; Rohland, Nadin; Mallick, Swapan; Szécsényi-Nagy, Anna; Mittnik, Alissa; Altena, Eveline; Lipson, Mark; Lazaridis, Iosif; Harper, Thomas K; Patterson, Nick; Broomandkhoshbacht, Nasreen; Diekmann, Yoan; Faltyskova, Zuzana; Fernandes, Daniel; Ferry, Matthew; Harney, Eadaoin; de Knijff, Peter; Michel, Megan; Oppenheimer, Jonas; Stewardson, Kristin; Barclay, Alistair; Alt, Kurt Werner; Liesau, Corina; Ríos, Patricia; Blasco, Concepción; Miguel, Jorge Vega; García, Roberto Menduiña; Fernández, Azucena Avilés; Bánffy, Eszter; Bernabò-Brea, Maria; Billoin, David; Bonsall, Clive; Bonsall, Laura; Allen, Tim; Büster, Lindsey; Carver, Sophie; Navarro, Laura Castells; Craig, Oliver E; Cook, Gordon T; Cunliffe, Barry; Denaire, Anthony; Dinwiddy, Kirsten Egging; Dodwell, Natasha; Ernée, Michal; Evans, Christopher; Kuchařík, Milan; Farré, Joan Francès; Fowler, Chris; Gazenbeek, Michiel; Pena, Rafael Garrido; Haber-Uriarte, María; Haduch, Elżbieta; Hey, Gill; Jowett, Nick; Knowles, Timothy; Massy, Ken; Pfrengle, Saskia; Lefranc, Philippe; Lemercier, Olivier; Lefebvre, Arnaud; Martínez, César Heras; Olmo, Virginia Galera; Ramírez, Ana Bastida; Maurandi, Joaquín Lomba; Majó, Tona; McKinley, Jacqueline I; McSweeney, Kathleen; Mende, Balázs Gusztáv; Modi, Alessandra; Kulcsár, Gabriella; Kiss, Viktória; Czene, András; Patay, Róbert; Endrődi, Anna; Köhler, Kitti; Hajdu, Tamás; Szeniczey, Tamás; Dani, János; Bernert, Zsolt; Hoole, Maya; Cheronet, Olivia; Keating, Denise; Velemínský, Petr; Dobeš, Miroslav; Candilio, Francesca; Brown, Fraser; Fernández, Raúl Flores; Herrero-Corral, Ana-Mercedes; Tusa, Sebastiano; Carnieri, Emiliano; Lentini, Luigi; Valenti, Antonella; Zanini, Alessandro; Waddington, Clive; Delibes, Germán; Guerra-Doce, Elisa; Neil, Benjamin; Brittain, Marcus; Luke, Mike; Mortimer, Richard; Desideri, Jocelyne; Besse, Marie; Brücken, Günter; Furmanek, Mirosław; Hałuszko, Agata; Mackiewicz, Maksym; Rapiński, Artur; Leach, Stephany; Soriano, Ignacio; Lillios, Katina T; Cardoso, João Luís; Pearson, Michael Parker; Włodarczak, Piotr; Price, T Douglas; Prieto, Pilar; Rey, Pierre-Jérôme; Risch, Roberto; Rojo Guerra, Manuel A; Schmitt, Aurore; Serralongue, Joël; Silva, Ana Maria; Smrčka, Václav; Vergnaud, Luc; Zilhão, João; Caramelli, David; Higham, Thomas; Thomas, Mark G; Kennett, Douglas J; Fokkens, Harry; Heyd, Volker; Sheridan, Alison; Sjögren, Karl-Göran; Stockhammer, Philipp W; Krause, Johannes; Pinhasi, Ron; Haak, Wolfgang; Barnes, Ian; Lalueza-Fox, Carles; Reich, David

2018-03-08

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

The effect of copper doping on martensite shear stress in porous TiNi(Mo,Fe,Cu) alloys

NASA Astrophysics Data System (ADS)

Khodorenko, V. N.; Kaftaranova, M. I.; Gunther, V. E.

2015-03-01

The properties of alloys based on porous nickel-titanium (TiNi) with copper additives have been studied. It is established that the copper doping of porous TiNi(Mo,Fe,Cu) alloys fabricated by the method of self-propagating high-temperature synthesis leads to a significant decrease in the martensite shear stress (below 30 MPa). Low values of the martensite shear stress (σmin) in copper-doped TiNi-based alloys allows medical implants of complex shapes to be manufactured for various purposes, including oral surgery. The optimum concentration of copper additives (within 3-6 at %) has been determined that ensures high performance characteristics of TiNi-based porous alloys for medical implants.

The structure of molten CuCl: Reverse Monte Carlo modeling with high-energy X-ray diffraction data and molecular dynamics of a polarizable ion model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alcaraz, Olga; Trullàs, Joaquim, E-mail: quim.trullas@upc.edu; Tahara, Shuta

2016-09-07

The results of the structural properties of molten copper chloride are reported from high-energy X-ray diffraction measurements, reverse Monte Carlo modeling method, and molecular dynamics simulations using a polarizable ion model. The simulated X-ray structure factor reproduces all trends observed experimentally, in particular the shoulder at around 1 Å{sup −1} related to intermediate range ordering, as well as the partial copper-copper correlations from the reverse Monte Carlo modeling, which cannot be reproduced by using a simple rigid ion model. It is shown that the shoulder comes from intermediate range copper-copper correlations caused by the polarized chlorides.

Dynamic compression of copper to over 450 GPa: A high-pressure standard

DOE PAGES

Kraus, R. G.; Davis, J. -P.; Seagle, C. T.; ...

2016-04-12

We obtained an absolute stress-density path for shocklessly compressed copper to over 450 GPa. A magnetic pressure drive is temporally tailored to generate shockless compression waves through over 2.5-mm-thick copper samples. Furthermore, the free-surface velocity data is analyzed for Lagrangian sound velocity using the iterative Lagrangian analysis (ILA) technique, which relies upon the method of characteristics. We correct for the effects of strength and plastic work heating to determine an isentropic compression path. By assuming a Debye model for the heat capacity, we can further correct the isentrope to an isotherm. Finally, our determination of the isentrope and isotherm ofmore » copper represents a highly accurate pressure standard for copper to over 450 GPa.« less

Cryogenic properties of dispersion strengthened copper for high magnetic fields

NASA Astrophysics Data System (ADS)

Toplosky, V. J.; Han, K.; Walsh, R. P.; Swenson, C. A.

2014-01-01

Cold deformed copper matrix composite conductors, developed for use in the 100 tesla multi-shot pulsed magnet at the National High Magnetic Field Laboratory (NHMFL), have been characterized. The conductors are alumina strengthened copper which is fabricated by cold drawing that introduces high dislocation densities and high internal stresses. Both alumina particles and high density of dislocations provide us with high tensile strength and fatigue endurance. The conductors also have high electrical conductivities because alumina has limited solubility in Cu and dislocations have little scattering effect on conduction electrons. Such a combination of high strength and high conductivity makes it an excellent candidate over other resistive magnet materials. Thus, characterization is carried out by tensile testing and fully reversible fatigue testing. In tensile tests, the material exceeds the design criteria parameters. In the fatigue tests, both the load and displacement were measured and used to control the amplitude of the tests to simulate the various loading conditions in the pulsed magnet which is operated at 77 K in a non-destructive mode. In order to properly simulate the pulsed magnet operation, strain-controlled tests were more suitable than load controlled tests. For the dispersion strengthened coppers, the strengthening mechanism of the aluminum oxide provided better tensile and fatigue properties over convention copper.

Cleaning and passivation of copper surfaces to remove surface radioactivity and prevent oxide formation

NASA Astrophysics Data System (ADS)

Hoppe, E. W.; Seifert, A.; Aalseth, C. E.; Bachelor, P. P.; Day, A. R.; Edwards, D. J.; Hossbach, T. W.; Litke, K. E.; McIntyre, J. I.; Miley, H. S.; Schulte, S. M.; Smart, J. E.; Warren, G. A.

2007-08-01

High-purity copper is an attractive material for constructing ultra-low-background radiation measurement devices. Many low-background experiments using high-purity copper have indicated surface contamination emerges as the dominant background. Radon daughters plate out on exposed surfaces, leaving a residual 210Pb background that is difficult to avoid. Dust is also a problem; even under cleanroom conditions, the amount of U and Th deposited on surfaces can represent the largest remaining background. To control these backgrounds, a copper cleaning chemistry has been developed. Designed to replace an effective, but overly aggressive concentrated nitric acid etch, this peroxide-based solution allows for a more controlled cleaning of surfaces. The acidified hydrogen peroxide solution will generally target the Cu +/Cu 2+ species which are the predominant surface participants, leaving the bulk of copper metal intact. This preserves the critical tolerances of parts and eliminates significant waste disposal issues. Accompanying passivation chemistry has also been developed that protects copper surfaces from oxidation. Using a high-activity polonium surface spike, the most difficult-to-remove daughter isotope of radon, the performance of these methods are quantified.

Characterization of two ammonia-oxidizing bacteria isolated from reactors operated with low dissolved oxygen concentrations.

PubMed

Park, H-D; Noguera, D R

2007-05-01

To obtain ammonia-oxidizing bacterial (AOB) strains inhabiting low dissolved oxygen (DO) environments and to characterize them to better understand their function and ecology. Using a serial dilution method, two AOB strains (ML1 and NL7) were isolated from chemostat reactors operated with low DO concentrations (0.12-0.24 mg l(-1)). Phylogenetically, strains ML1 and NL7 are affiliated to AOB within the Nitrosomonas europaea and Nitrosomonas oligotropha lineages, respectively. Kinetically, strain ML1 had high affinity for oxygen (0.24 +/- 0.13 mg l(-1)) and low affinity for ammonia (1.62 +/- 0.97 mg N l(-1)), while strain NL7 had high affinity for ammonia (0.48 +/- 0.35 mg l(-1)), but a surprisingly low affinity for oxygen (1.22 +/- 0.43 mg l(-1)). A co-culture experiment was used to iteratively estimate decay constants for both strains. The results indicated that AOB without high affinity for oxygen may have other mechanisms to persist in low DO environments, with high affinity for ammonia being important. This study provides a method to determine AOB growth kinetic parameters without assuming or neglecting decay constant. And, this is the first report on oxygen affinity constant of a N. oligotropha strain.

Pharmacological and gene regulation properties point to the SlHAK5 K+ transporter as a system for high-affinity Cs+ uptake in tomato plants.

PubMed

Ródenas, Reyes; Nieves-Cordones, Manuel; Rivero, Rosa M; Martinez, Vicente; Rubio, Francisco

2018-04-01

Potassium (K + ) and cesium (Cs + ) are chemically similar but while K + is an essential nutrient, Cs + can be toxic for living organisms, plants included. Two different situations could lead to problems derived from the presence of Cs + in agricultural systems: (1) presence of Cs + at high concentrations that could produce toxic effects on plants, (2) presence of micromolar concentrations of radiocesium, which can be accumulated in the plant and affect animal and human health through the food chain. While K + uptake has been well described in tomato plants, information on molecular mechanisms involved in Cs + accumulation in this species is absent. Here, we show that in tomato plants, high concentrations of Cs + produce deficiency of K + but do not induce high-affinity K + uptake or the gene encoding the high-affinity K + transporter SlHAK5. At these concentrations, Cs + uptake takes place through a Ca 2+ -sensitive pathway, probably a non-selective cation channel. At micromolar concentrations, Cs + is accumulated by a high-affinity uptake system upregulated in K + -starved plants. This high-affinity Cs + uptake shares features with high-affinity K + uptake. It is sensitive to NH 4 + and insensitive to Ba 2+ and Ca 2+ and its presence parallels the pattern of SlHAK5 expression. Moreover, blockers of reactive oxygen species and ethylene action repress SlHAK5 and negatively regulate both high-affinity K + and Cs + uptake. Thus, we propose that SlHAK5 contributes to Cs + uptake from micromolar concentrations in tomato plants and can constitute a pathway for radiocesium transfer from contaminated areas to the food chain. © 2017 Scandinavian Plant Physiology Society.

CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis

PubMed Central

Marcus, Sarah A.; Sidiropoulos, Sarah W.; Steinberg, Howard; Talaat, Adel M.

2016-01-01

Mycobacterium tuberculosis, a pathogen infecting one third of the world population, faces numerous challenges within the host, including high levels of copper. We have previously shown that M. tuberculosis CsoR is a copper inducible transcriptional regulator. Here we examined the hypothesis that csoR is necessary for maintaining copper homeostasis and surviving under various stress conditions. With an unmarked csoR knockout strain, we were able to characterize the role of csoR in M. tuberculosis as it faced copper and host stress. Growth under high levels of copper demonstrated that M. tuberculosis survives copper stress significantly better in the absence of csoR. Yet under minimal levels of copper, differential expression analysis revealed that the loss of csoR results in a cell wide hypoxia-type stress response with the induction of the DosR regulon. Despite the stress placed on M. tuberculosis by the loss of csoR, survival of the knockout strain was increased compared to wild type during the early chronic stages of mouse infection, suggesting that csoR could play an active role in modulating M. tuberculosis fitness within the host. Overall, analysis of CsoR provided an increased understanding of the M. tuberculosis copper response with implications for other intracellular pathogens harboring CsoR. PMID:26999439

Incorporation of Tin on copper clad laminate to increase the interface adhesion for signal loss reduction of high-frequency PCB lamination

NASA Astrophysics Data System (ADS)

Wang, Chong; Wen, Na; Zhou, Guoyun; Wang, Shouxu; He, Wei; Su, Xinhong; Hu, Yongsuan

2017-11-01

A novel method of improving the adhesion between copper and prepreg in high frequency PCB was proposed and studied in this work. This process which aimed to decrease the IEP (isoelectric point) of the copper to obtain higher adhesion, was achieved by depositing a thin tin layer with lower IEP on copper. It was characterized by scanning electron microscopy (SEM), 3D microscope, peel strength test, X-Ray thickness test, grazing incidence X-ray diffraction (GXRD), X-ray photoelectron spectroscopy (XPS), Agilent vector network analyzer (VNA), which confirmed its excellent adhesion performance and outstanding electrical properties in high-frequency signal transmission compared with traditional brown oxide method. Moreover, the mechanism of achieving high adhesion for this method was also investigated.

Fabricating and strengthening the carbon nanotube/copper composite fibers with high strength and high electrical conductivity

NASA Astrophysics Data System (ADS)

Han, Baoshuai; Guo, Enyu; Xue, Xiang; Zhao, Zhiyong; Li, Tiejun; Xu, Yanjin; Luo, Liangshun; Hou, Hongliang

2018-05-01

Combining the excellent properties of carbon nanotube (CNT) and copper, CNT/Cu composite fibers were fabricated by physical vapor deposition (PVD) and rolling treatment. Dense and continuous copper film (∼2 μm) was coated on the surface of the CNT fibers by PVD, and rolling treatment was adopt to strengthen the CNT/Cu composite fibers. After the rolling treatment, the defects between the Cu grains and the CNT bundles were eliminated, and the structure of both the copper film and the core CNT fibers were optimized. The rolled CNT/Cu composite fibers possess high tensile effective strength (1.01 ± 0.13 GPa) and high electrical conductivity ((2.6 ± 0.3) × 107 S/m), and thus, this material may become a promising wire material.

[Compressive and bend strength of experimental admixed high copper alloys].

PubMed

Sourai, P; Paximada, H; Lagouvardos, P; Douvitsas, G

1988-01-01

Mixed alloys for dental amalgams have been used mainly in the form of admixed alloys, where eutectic spheres are blend with conventional flakes. In the present study the compressive strength, bend strength and microstructure of two high-copper alloys (Tytin, Ana-2000) is compared with three experimental alloys prepared of the two high copper by mixing them in proportions of 3:1, 1:1 and 1:3 by weight. The results revealed that experimental alloys inherited high early and final strength values without any significant change in their microstructure.

Textured carbon on copper: A novel surface with extremely low secondary electron emission characteristics

NASA Technical Reports Server (NTRS)

Curren, A. N.; Jensen, K. A.

1985-01-01

Experimentally determined values of true secondary electron emission and relative values of reflected primary electron yield for a range of primary electron beam energies and beam impingement angles are presented for a series of novel textured carbon surfaces on copper substrates. (All copper surfaces used in this study were oxygen-free, high-conductivity grade). The purpose of this investigation is to provide information necessary to develop high-efficiency multistage depressed collectors (MDC's) for microwave amplifier traveling-wave tubes (TWT's) for communications and aircraft applications. To attain the highest TWT signal quality and overall efficiency, the MDC electrode surface must have low secondary electron emission characteristics. While copper is the material most commonly used for MDC electrodes, it exhibits relatively high levels of secondary electron emission unless its surface is treated for emission control. The textured carbon surface on copper substrate described in this report is a particularly promising candidate for the MDC electrode application. Samples of textured carbon surfaces on copper substrates typical of three different levels of treatment are prepared and tested for this study. The materials are tested at primary electron beam energies of 200 to 2000 eV and at direct (0 deg) to near-grazing (85 deg) beam impingement angles. True secondary electron emission and relative reflected primary electron yield characteristics of the textured surfaces are compared with each other and with those of untreated copper. All the textured carbon surfaces on copper substrate tested exhibited sharply lower secondary electron emission characteristics than those of an untreated copper surface.

Talitrid amphipods (Crustacea) as biomonitors for copper and zinc

NASA Astrophysics Data System (ADS)

Rainbow, P. S.; Moore, P. G.; Watson, D.

1989-06-01

Data are presented on the copper and zinc concentrations of four talitrid amphipod species (standard dry weight 10 mg), i.e. Orchestia gammarellus (Pallas), O. mediterranea Costa, Talitrus saltator Montagu and Talorchestia deshayesii (Audouin), from 31 sites in S.W. Scotland, N. Wales and S.W. England. More limited data are also presented for cadmium in O. gammarellus (three sites) and T. deshayesii (one site). In S.W. Scotland, copper concentrations were raised significantly in O. gammarellus from Whithorn and Auchencairn (Solway) and Loch Long and Holy Loch (Clyde). In S.W. England, copper concentrations were highest at Restronguet Creek, Torpoint and Gannel (Cornwall). Samples of O. gammarellus from Islay (inner Hebrides) taken adjacent to the effluent outfalls of local whisky distilleries fell into two groups based on copper concentrations (presumably derived from copper stills), the higher copper levels deriving from the more productive distilleries. High copper levels were found in T. saltator and Tal. deshayesii from Dulas Bay (Wales). Zinc levels in O. gammarellus were high in Holy Loch and Auchencairn (Scotland), Gannel and Torpoint (England) but extremely elevated (as was Zn in O. mediterranea) at Restronguet Creek. Zinc was also high in T. saltator from Dulas Bay (Wales), but not in Tal. deshayesii. Cadmium levels in O. gammarellus from Kilve (Bristol Channel) were much raised. These differences (a) conform with expectations of elevated bioavailability of these metals from well researched areas (S.W. England & N. Wales), and (b) identify hitherto unappreciated areas of enrichment in S.W. Scotland. Orchestia gammarellus is put forward as a suitable biomonitor for copper and zinc in British coastal waters.

Distribution of trace metals in surface seawater and zooplankton of the Bay of Bengal, off Rushikulya estuary, East Coast of India.

PubMed

Srichandan, Suchismita; Panigrahy, R C; Baliarsingh, S K; Rao B, Srinivasa; Pati, Premalata; Sahu, Biraja K; Sahu, K C

2016-10-15

Concentrations of trace metals such as iron (Fe), copper (Cu), zinc (Zn), cobalt (Co), nickel (Ni), manganese (Mn), lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), vanadium (V), and selenium (Se) were determined in seawater and zooplankton from the surface waters off Rushikulya estuary, north-western Bay of Bengal. During the study period, the concentration of trace metals in seawater and zooplankton showed significant spatio-temporal variation. Cu and Co levels in seawater mostly remained non-detectable. Other elements were found at higher concentrations and exhibited marked variations. The rank order distribution of trace metals in terms of their average concentration in seawater was observed as Fe>Ni>Mn>Pb>As>Zn>Cr>V>Se>Cd while in zooplankton it was Fe>Mn>Cd>As>Pb>Ni>Cr>Zn>V>Se. The bioaccumulation factor (BAF) of Fe was highest followed by Zn and the lowest value was observed with Ni. Results of correlation analysis discerned positive affinity and good relationship among the majority of the trace metals, both in seawater and zooplankton suggesting their strong affinity and coexistence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes

PubMed Central

Gordon, Lily D.; Fang, Zhong; Holder, Robert C.; Reid, Sean D.

2015-01-01

ABSTRACT Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. IMPORTANCE Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. PMID:26013489

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes.

PubMed

Young, Christie A; Gordon, Lily D; Fang, Zhong; Holder, Robert C; Reid, Sean D

2015-08-01

Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Mechanical properties and microstructure of copper alloys and copper alloy-stainless steel laminates for fusion reactor high heat flux applications

NASA Astrophysics Data System (ADS)

Leedy, Kevin Daniel

A select group of copper alloys and bonded copper alloy-stainless steel panels are under consideration for heat sink applications in first wall and divertor structures of a planned thermonuclear fusion reactor. Because these materials must retain high strengths and withstand high heat fluxes, their material properties and microstructures must be well understood. Candidate copper alloys include precipitate strengthened CuNiBe and CuCrZr and dispersion strengthened Cu-Alsb2Osb3 (CuAl25). In this study, uniaxial mechanical fatigue tests were conducted on bulk copper alloy materials at temperatures up to 500sp°C in air and vacuum environments. Based on standardized mechanical properties measurement techniques, a series of tests were also implemented to characterize copper alloy-316L stainless steel joints produced by hot isostatic pressing or by explosive bonding. The correlation between mechanical properties and the microstructure of fatigued copper alloys and the interface of copper alloy-stainless steel laminates was examined. Commercial grades of these alloys were used to maintain a degree of standardization in the materials testing. The commercial alloys used were OMG Americas Glidcop CuAl25 and CuAl15; Brush Wellman Hycon 3HP and Trefimetaux CuNiBe; and Kabelmetal Elbrodur and Trefimetaux CuCrZr. CuAl25 and CuNiBe alloys possessed the best combination of fatigue resistance and microstructural stability. The CuAl25 alloy showed only minimal microstructural changes following fatigue while the CuNiBe alloy consistently exhibited the highest fatigue strength. Transmission electron microscopy observations revealed that small matrix grain sizes and high densities of submicron strengthening phases promoted homogeneous slip deformation in the copper alloys. Thus, highly organized fatigue dislocation structure formation, as commonly found in oxygen-free high conductivity Cu, was inhibited. A solid plate of CuAl25 alloy hot isostatically pressed to a 316L stainless steel plate showed the best overall mechanical properties of the studied bi-metallic bonded panels. Bond properties were nominally inferior to constituent bulk material properties and fracture toughness values, in particular, were quite low for all bonded laminates. Delamination near the copper alloy-stainless steel interface was the dominate failure mode in the bi-metallic panels. The joining processes caused microstructural alterations in the bond interfacial regions including: microporosity, new precipitate formation, existing precipitate morphology changes and interdiffusion of constituent elements.

Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts.

PubMed

Yañez, Fernando; Chianella, Iva; Piletsky, Sergey A; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2010-02-05

This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow (1 mL min(-1)) of 0.2 mM sodium cholate solution. Copyright 2009 Elsevier B.V. All rights reserved.

Preparation of graphite dispersed copper composite with intruding graphite particles in copper plate

NASA Astrophysics Data System (ADS)

Noor, Abdul Muizz Mohd; Ishikawa, Yoshikazu; Yokoyama, Seiji

2017-01-01

In this study, it was attempted that copper-graphite composite was prepared locally on the surface of a copper plate with using a spot welding machine. Experiments were carried out with changing the compressive load, the repetition number of the compression and the electrical current in order to study the effect of them on carbon content and Vickers hardness on the copper plate surface. When the graphite was pushed into copper plate only with the compressive load, the composite was mainly hardened by the work hardening. The Vickers hardness increased linearly with an increase in the carbon content. When an electrical current was energized through the composite at the compression, the copper around the graphite particles were heated to the temperature above approximately 2100 K and melted. The graphite particles partially or entirely dissolved into the melt. The graphite particles were precipitated from the melt under solidification. In addition, this high temperature caused the improvement of wetting of copper to graphite. This high temperature caused the annealing, and reduced the Vickers hardness. Even in this case, the Vickers hardness increased with an increase in the carbon content. This resulted from the dispersion hardening.

Forensic discrimination of copper wire using trace element concentrations.

PubMed

Dettman, Joshua R; Cassabaum, Alyssa A; Saunders, Christopher P; Snyder, Deanna L; Buscaglia, JoAnn

2014-08-19

Copper may be recovered as evidence in high-profile cases such as thefts and improvised explosive device incidents; comparison of copper samples from the crime scene and those associated with the subject of an investigation can provide probative associative evidence and investigative support. A solution-based inductively coupled plasma mass spectrometry method for measuring trace element concentrations in high-purity copper was developed using standard reference materials. The method was evaluated for its ability to use trace element profiles to statistically discriminate between copper samples considering the precision of the measurement and manufacturing processes. The discriminating power was estimated by comparing samples chosen on the basis of the copper refining and production process to represent the within-source (samples expected to be similar) and between-source (samples expected to be different) variability using multivariate parametric- and empirical-based data simulation models with bootstrap resampling. If the false exclusion rate is set to 5%, >90% of the copper samples can be correctly determined to originate from different sources using a parametric-based model and >87% with an empirical-based approach. These results demonstrate the potential utility of the developed method for the comparison of copper samples encountered as forensic evidence.

Copper wire theft and high voltage electrical burns

PubMed Central

Francis, Eamon C; Shelley, Odhran P

2014-01-01

High voltage electrical burns are uncommon. However in the midst of our economic recession we are noticing an increasing number of these injuries. Copper wire is a valuable commodity with physical properties as an excellent conductor of electricity making it both ubiquitous in society and prized on the black market. We present two consecutive cases referred to the National Burns Unit who sustained life threatening injuries from the alleged theft of high voltage copper wire and its omnipresence on an international scale. PMID:25356371

Copper wire theft and high voltage electrical burns.

PubMed

Francis, Eamon C; Shelley, Odhran P

2014-01-01

High voltage electrical burns are uncommon. However in the midst of our economic recession we are noticing an increasing number of these injuries. Copper wire is a valuable commodity with physical properties as an excellent conductor of electricity making it both ubiquitous in society and prized on the black market. We present two consecutive cases referred to the National Burns Unit who sustained life threatening injuries from the alleged theft of high voltage copper wire and its omnipresence on an international scale.

High-Valent Organometallic Copper and Palladium in Catalysis

PubMed Central

Hickman, Amanda J.; Sanford, Melanie S.

2015-01-01

Preface Copper and palladium catalysts are critically important for numerous commercial chemical processes. Improvements in the activity, selectivity, and scope of these catalysts have the potential to dramatically reduce the environmental impact and increase the sustainability of chemical reactions. One rapidly emerging strategy to achieve these goals is to exploit “high-valent” copper and palladium intermediates in catalysis. This review describes exciting recent advances involving both the fundamental chemistry and the applications of these high-valent metal complexes in numerous synthetically useful catalytic transformations. PMID:22498623

Dioxins reformation and destruction in secondary copper smelting fly ash under ball milling

PubMed Central

Cagnetta, Giovanni; Hassan, Mohammed Mansour; Huang, Jun; Yu, Gang; Weber, Roland

2016-01-01

Secondary copper recovery is attracting increasing interest because of the growth of copper containing waste including e-waste. The pyrometallurgical treatment in smelters is widely utilized, but it is known to produce waste fluxes containing a number of toxic pollutants due to the large amount of copper involved, which catalyses the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (“dioxins”). Dioxins are generated in secondary copper smelters on fly ash as their major source, resulting in highly contaminated residues. In order to assess the toxicity of this waste, an analysis of dioxin-like compounds was carried out. High levels were detected (79,090 ng TEQ kg−1) in the ash, above the Basel Convention low POPs content (15,000 ng TEQ kg−1) highlighting the hazardousness of this waste. Experimental tests of high energy ball milling with calcium oxide and silica were executed to assess its effectiveness to detoxify such fly ash. Mechanochemical treatment obtained 76% dioxins reduction in 4 h, but longer milling time induced a partial de novo formation of dioxins catalysed by copper. Nevertheless, after 12 h treatment the dioxin content was substantially decreased (85% reduction) and the copper, thanks to the phenomena of incorporation and amorphization that occur during milling, was almost inactivated. PMID:26975802

Dioxins reformation and destruction in secondary copper smelting fly ash under ball milling

NASA Astrophysics Data System (ADS)

Cagnetta, Giovanni; Hassan, Mohammed Mansour; Huang, Jun; Yu, Gang; Weber, Roland

2016-03-01

Secondary copper recovery is attracting increasing interest because of the growth of copper containing waste including e-waste. The pyrometallurgical treatment in smelters is widely utilized, but it is known to produce waste fluxes containing a number of toxic pollutants due to the large amount of copper involved, which catalyses the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (“dioxins”). Dioxins are generated in secondary copper smelters on fly ash as their major source, resulting in highly contaminated residues. In order to assess the toxicity of this waste, an analysis of dioxin-like compounds was carried out. High levels were detected (79,090 ng TEQ kg-1) in the ash, above the Basel Convention low POPs content (15,000 ng TEQ kg-1) highlighting the hazardousness of this waste. Experimental tests of high energy ball milling with calcium oxide and silica were executed to assess its effectiveness to detoxify such fly ash. Mechanochemical treatment obtained 76% dioxins reduction in 4 h, but longer milling time induced a partial de novo formation of dioxins catalysed by copper. Nevertheless, after 12 h treatment the dioxin content was substantially decreased (85% reduction) and the copper, thanks to the phenomena of incorporation and amorphization that occur during milling, was almost inactivated.

Occupation of low-affinity cholecystokinin (CCK) receptors by CCK activates signal transduction and stimulates amylase secretion in pancreatic acinar cells.

PubMed

Vinayek, R; Patto, R J; Menozzi, D; Gregory, J; Mrozinski, J E; Jensen, R T; Gardner, J D

1993-03-10

Based on the effects of monensin on binding of 125I-CCK-8 and its lack of effect on CCK-8-stimulated amylase secretion we previously proposed that pancreatic acinar cells possess three classes of CCK receptors: high-affinity receptors, low-affinity receptors and very low-affinity receptors [1]. In the present study we treated pancreatic acini with carbachol to induce a complete loss of high-affinity CCK receptors and then examined the action of CCK-8 on inositol trisphosphate IP3(1,4,5), cytosolic calcium and amylase secretion in an effort to confirm and extend our previous hypothesis. We found that first incubating pancreatic acini with 10 mM carbachol decreased binding of 125I-CCK-8 measured during a second incubation by causing a complete loss of high-affinity CCK receptors with no change in the low-affinity CCK receptors. Carbachol treatment of acini, however, did not alter the action of CCK-8 on IP3(1,4,5), cytosolic calcium or amylase secretion or the action of CCK-JMV-180 on amylase secretion or on the supramaximal inhibition of amylase secretion caused by CCK-8. The present findings support our previous hypothesis that pancreatic acinar cells possess three classes of CCK receptors and suggest that high-affinity CCK receptors do not mediate the action of CCK-8 on enzyme secretion, that low-affinity CCK receptors may mediate the action of CCK on cytosolic calcium that does not involve IP3(1,4,5) and produce the upstroke of the dose-response curve for CCK-8-stimulated amylase secretion and that very low-affinity CCK receptors mediate the actions of CCK on IP3(1,4,5) and cytosolic calcium and produce the downstroke of the dose-response curve for CCK-8-stimulated amylase secretion. Moreover, CCK-JMV-180 is a full agonist for stimulating amylase secretion by acting at low-affinity CCK receptors and is an antagonist at very low-affinity CCK receptors.

Characterization of Lactobacillus brevis L62 strain, highly tolerant to copper ions.

PubMed

Mrvčić, Jasna; Butorac, Ana; Solić, Ema; Stanzer, Damir; Bačun-Družina, Višnja; Cindrić, Mario; Stehlik-Tomas, Vesna

2013-01-01

Lactic acid bacteria (LAB) as starter culture in food industry must be suitable for large-scale industrial production and possess the ability to survive in unfavorable processes and storage conditions. Approaches taken to address these problems include the selection of stress-resistant strains. In food industry, LAB are often exposed to metal ions induced stress. The interactions between LAB and metal ions are very poorly investigated. Because of that, the influence of non-toxic, toxic and antioxidant metal ions (Zn, Cu, and Mn) on growth, acid production, metal ions binding capacity of wild and adapted species of Leuconostoc mesenteroides L3, Lactobacillus brevis L62 and Lactobacillus plantarum L73 were investigated. The proteomic approach was applied to clarify how the LAB cells, especially the adapted ones, protect themselves and tolerate high concentrations of toxic metal ions. Results have shown that Zn and Mn addition into MRS medium in the investigated concentrations did not have effect on the bacterial growth and acid production, while copper ions were highly toxic, especially in static conditions. Leuc. mesenteroides L3 was the most efficient in Zn binding processes among the chosen LAB species, while L. plantarum L73 accumulated the highest concentration of Mn. L. brevis L62 was the most copper resistant species. Adaptation had a positive effect on growth and acid production of all species in the presence of copper. However, the adapted species incorporated less metal ions than the wild species. The exception was adapted L. brevis L62 that accumulated high concentration of copper ions in static conditions. The obtained results showed that L. brevis L62 is highly tolerant to copper ions, which allows its use as starter culture in fermentative processes in media with high concentration of copper ions.

Comparison of human papillomavirus infection and cervical cytology in women using copper-containing and levonorgestrel-containing intrauterine devices.

PubMed

Lekovich, Jovana P; Amrane, Selma; Pangasa, Misha; Pereira, Nigel; Frey, Melissa K; Varrey, Aneesha; Holcomb, Kevin

2015-05-01

To investigate whether there is a difference in cervical cytology and high-risk human papillomavirus (HPV) infection clearance between levonorgestrel- and copper-containing intrauterine device (IUD) users. The electronic medical record system was searched by the appropriate procedural code for IUD insertion for all patients undergoing IUD placement during the study period (January 31, 2005 to January 31, 2012). Patients who received treatment for cervical dysplasia, had their IUDs removed, or conceived during the study period were excluded. High-risk HPV and cervical cytology results immediately preceding and after IUD placement were obtained. One hundred fifty patients had a copper-containing and 152 patients a levonorgestrel-containing IUD placed. The groups were comparable in terms of age, body mass index, duration of follow-up, and percentage of smokers. Sixty-six patients were high-risk HPV-positive before IUD insertion (30 in copper compared with 36 in the levonorgestrel IUD group, P=.4), and the groups had similar follow-up times (364.1±26.3 compared with 357.2±29.7 days, respectively, between the IUD placement and a repeat Pap test with high-risk HPV cotesting, P=.2). Of those, 21 (70%; 95% confidence interval [CI] 53.6-86.4%) cleared the infection after copper-containing IUD placement compared with 15 (42%; 95% CI 25.6-57.8%) in the levonorgestrel group (P=.04). There were only two (1.7%) new high-risk HPV infections in the copper compared with eight (6.9%) in the levonorgestrel group (P=.056). Our data suggest that levonorgestrel-containing IUD could be associated with decreased high-risk HPV infection clearance and possibly increased acquisition compared with the copper-containing IUD. II.

Advantages and challenges of increased antimicrobial copper use and copper mining.

PubMed

Elguindi, Jutta; Hao, Xiuli; Lin, Yanbing; Alwathnani, Hend A; Wei, Gehong; Rensing, Christopher

2011-07-01

Copper is a highly utilized metal for electrical, automotive, household objects, and more recently as an effective antimicrobial surface. Copper-containing solutions applied to fruits and vegetables can prevent bacterial and fungal infections. Bacteria, such as Salmonellae and Cronobacter sakazakii, often found in food contamination, are rapidly killed on contact with copper alloys. The antimicrobial effectiveness of copper alloys in the healthcare environment against bacteria causing hospital-acquired infections such as methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli O157:H7, and Clostridium difficile has been described recently. The use of copper and copper-containing materials will continue to expand and may lead to an increase in copper mining and production. However, the copper mining and manufacturing industry and the consumer do not necessarily enjoy a favorable relationship. Open pit mining, copper mine tailings, leaching products, and deposits of toxic metals in the environment often raises concerns and sometimes public outrage. In addition, consumers may fear that copper alloys utilized as antimicrobial surfaces in food production will lead to copper toxicity in humans. Therefore, there is a need to mitigate some of the negative effects of increased copper use and copper mining. More thermo-tolerant, copper ion-resistant microorganisms could improve copper leaching and lessen copper groundwater contamination. Copper ion-resistant bacteria associated with plants might be useful in biostabilization and phytoremediation of copper-contaminated environments. In this review, recent progress in microbiological and biotechnological aspects of microorganisms in contact with copper will be presented and discussed, exploring their role in the improvement for the industries involved as well as providing better environmental outcomes.

High-Affinity Recombinant Antibody Fragments (Fabs) Can Be Applied in Peptide Enrichment Immuno-MRM Assays

PubMed Central

2015-01-01

High-affinity antibodies binding to linear peptides in solution are a prerequisite for performing immuno-MRM, an emerging technology for protein quantitation with high precision and specificity using peptide immunoaffinity enrichment coupled to stable isotope dilution and targeted mass spectrometry. Recombinant antibodies can be generated from appropriate libraries in high-throughput in an automated laboratory and thus may offer advantages over conventional monoclonal antibodies. However, recombinant antibodies are typically obtained as fragments (Fab or scFv) expressed from E. coli, and it is not known whether these antibody formats are compatible with the established protocols and whether the affinities necessary for immunocapture of small linear peptides can be achieved with this technology. Hence, we performed a feasibility study to ask: (a) whether it is feasible to isolate high-affinity Fabs to small linear antigens and (b) whether it is feasible to incorporate antibody fragments into robust, quantitative immuno-MRM assays. We describe successful isolation of high-affinity Fab fragments against short (tryptic) peptides from a human combinatorial Fab library. We analytically characterize three immuno-MRM assays using recombinant Fabs, full-length IgGs constructed from these Fabs, or traditional monoclonals. We show that the antibody fragments show similar performance compared with traditional mouse- or rabbit-derived monoclonal antibodies. The data establish feasibility of isolating and incorporating high-affinity Fabs into peptide immuno-MRM assays. PMID:24568200

High-affinity recombinant antibody fragments (Fabs) can be applied in peptide enrichment immuno-MRM assays.

PubMed

Whiteaker, Jeffrey R; Zhao, Lei; Frisch, Christian; Ylera, Francisco; Harth, Stefan; Knappik, Achim; Paulovich, Amanda G

2014-04-04

High-affinity antibodies binding to linear peptides in solution are a prerequisite for performing immuno-MRM, an emerging technology for protein quantitation with high precision and specificity using peptide immunoaffinity enrichment coupled to stable isotope dilution and targeted mass spectrometry. Recombinant antibodies can be generated from appropriate libraries in high-throughput in an automated laboratory and thus may offer advantages over conventional monoclonal antibodies. However, recombinant antibodies are typically obtained as fragments (Fab or scFv) expressed from E. coli, and it is not known whether these antibody formats are compatible with the established protocols and whether the affinities necessary for immunocapture of small linear peptides can be achieved with this technology. Hence, we performed a feasibility study to ask: (a) whether it is feasible to isolate high-affinity Fabs to small linear antigens and (b) whether it is feasible to incorporate antibody fragments into robust, quantitative immuno-MRM assays. We describe successful isolation of high-affinity Fab fragments against short (tryptic) peptides from a human combinatorial Fab library. We analytically characterize three immuno-MRM assays using recombinant Fabs, full-length IgGs constructed from these Fabs, or traditional monoclonals. We show that the antibody fragments show similar performance compared with traditional mouse- or rabbit-derived monoclonal antibodies. The data establish feasibility of isolating and incorporating high-affinity Fabs into peptide immuno-MRM assays.

A Fluorescent Protein Scaffold for Presenting Structurally Constrained Peptides Provides an Effective Screening System to Identify High Affinity Target-Binding Peptides

PubMed Central

Kadonosono, Tetsuya; Yabe, Etsuri; Furuta, Tadaomi; Yamano, Akihiro; Tsubaki, Takuya; Sekine, Takuya; Kuchimaru, Takahiro; Sakurai, Minoru; Kizaka-Kondoh, Shinae

2014-01-01

Peptides that have high affinity for target molecules on the surface of cancer cells are crucial for the development of targeted cancer therapies. However, unstructured peptides often fail to bind their target molecules with high affinity. To efficiently identify high-affinity target-binding peptides, we have constructed a fluorescent protein scaffold, designated gFPS, in which structurally constrained peptides are integrated at residues K131–L137 of superfolder green fluorescent protein. Molecular dynamics simulation supported the suitability of this site for presentation of exogenous peptides with a constrained structure. gFPS can present 4 to 12 exogenous amino acids without a loss of fluorescence. When gFPSs presenting human epidermal growth factor receptor type 2 (HER2)-targeting peptides were added to the culture medium of HER2-expressing cells, we could easily identify the peptides with high HER2-affinity and -specificity based on gFPS fluorescence. In addition, gFPS could be expressed on the yeast cell surface and applied for a high-throughput screening. These results demonstrate that gFPS has the potential to serve as a powerful tool to improve screening of structurally constrained peptides that have a high target affinity, and suggest that it could expedite the one-step identification of clinically applicable cancer cell-binding peptides. PMID:25084350

Bohr effect and temperature sensitivity of hemoglobins from highland and lowland deer mice.

PubMed

Jensen, Birgitte; Storz, Jay F; Fago, Angela

2016-05-01

An important means of physiological adaptation to environmental hypoxia is an increased oxygen (O2) affinity of the hemoglobin (Hb) that can help secure high O2 saturation of arterial blood. However, the trade-off associated with a high Hb-O2 affinity is that it can compromise O2 unloading in the systemic capillaries. High-altitude deer mice (Peromyscus maniculatus) have evolved an increased Hb-O2 affinity relative to lowland conspecifics, but it is not known whether they have also evolved compensatory mechanisms to facilitate O2 unloading to respiring tissues. Here we investigate the effects of pH (Bohr effect) and temperature on the O2-affinity of high- and low-altitude deer mouse Hb variants, as these properties can potentially facilitate O2 unloading to metabolizing tissues. Our experiments revealed that Bohr factors for the high- and low-altitude Hb variants are very similar in spite of the differences in O2-affinity. The Bohr factors of deer mouse Hbs are also comparable to those of other mammalian Hbs. In contrast, the high- and low-altitude variants of deer mouse Hb exhibited similarly low temperature sensitivities that were independent of red blood cell anionic cofactors, suggesting an appreciable endothermic allosteric transition upon oxygenation. In conclusion, high-altitude deer mice have evolved an adaptive increase in Hb-O2 affinity, but this is not associated with compensatory changes in sensitivity to changes in pH or temperature. Instead, it appears that the elevated Hb-O2 affinity in high-altitude deer mice is compensated by an associated increase in the tissue diffusion capacity of O2 (via increased muscle capillarization), which promotes O2 unloading. Copyright © 2016 Elsevier Inc. All rights reserved.

Copper tolerance and copper accumulation of herbaceous plants colonizing inactive California copper mines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruckeberg, A.L.; Wu, L.

1992-06-01

Herbaceous plant species colonizing four copper mine waste sites in northern California were investigated for copper tolerance and copper accumulation. Copper tolerance was found in plant species colonizing soils with high concentrations of soil copper. Seven of the eight plant species tested were found at more than one copper mine. The mines are geographically isolated, which makes dispersal of seeds from one mine to another unlikely. Tolerance has probably evolved independently at each site. The nontolerant field control population of Vulpia microstachya displays significantly higher tolerance to copper at all copper concentration levels tested than the nontolerant Vulpia myrous population,more » and the degree of copper tolerance attained by V. microstachya at the two copper mines was much greater than that found in V. myrous. It suggests that even in these two closely related species, the innate tolerance in their nontolerant populations may reflect their potential for evolution of copper tolerance and their ability to initially colonize copper mine waste sites. The shoot tissue of the copper mine plants of Arenaria douglasii, Bromous mollis, and V. microstachya accumulated less copper than those plants of the same species from the field control sites when the two were grown in identical conditions in nutrient solution containing copper. The root tissue of these mine plants contain more copper than the roots of the nonmine plants. This result suggests that exclusion of copper from the shoots, in part by immobilization in the roots, may be a feature of copper tolerance. No difference in the tissue copper concentration was detected between tolerant and nontolerant plants of Lotus purshianus, Lupinus bicolor, and Trifolium pratense even though the root tissue had more copper than the leaves.« less

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites

PubMed Central

Vogensen, Stine B.; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H.F.; Clausen, Rasmus P.

2013-01-01

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Direct Measurement of Equilibrium Constants for High-Affinity Hemoglobins

PubMed Central

Kundu, Suman; Premer, Scott A.; Hoy, Julie A.; Trent, James T.; Hargrove, Mark S.

2003-01-01

The biological functions of heme proteins are linked to their rate and affinity constants for ligand binding. Kinetic experiments are commonly used to measure equilibrium constants for traditional hemoglobins comprised of pentacoordinate ligand binding sites and simple bimolecular reaction schemes. However, kinetic methods do not always yield reliable equilibrium constants with more complex hemoglobins for which reaction mechanisms are not clearly understood. Furthermore, even where reaction mechanisms are clearly understood, it is very difficult to directly measure equilibrium constants for oxygen and carbon monoxide binding to high-affinity (KD ≪ 1 μM) hemoglobins. This work presents a method for direct measurement of equilibrium constants for high-affinity hemoglobins that utilizes a competition for ligands between the "target" protein and an array of "scavenger" hemoglobins with known affinities. This method is described for oxygen and carbon monoxide binding to two hexacoordinate hemoglobins: rice nonsymbiotic hemoglobin and Synechocystis hemoglobin. Our results demonstrate that although these proteins have different mechanisms for ligand binding, their affinities for oxygen and carbon monoxide are similar. Their large affinity constants for oxygen, 285 and ∼100 μM−1 respectively, indicate that they are not capable of facilitating oxygen transport. PMID:12770899

Direct Measurement of T Cell Receptor Affinity and Sequence from Naïve Anti-Viral T Cells

PubMed Central

Zhang, Shuqi; Parker, Patricia; Ma, Keyue; He, Chenfeng; Shi, Qian; Cui, Zhonghao; Williams, Chad; Wendel, Ben S.; Meriwether, Amanda; Salazar, Mary A.; Jiang, Ning

2016-01-01

T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCR). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. Here, we introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8+ T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high affinity T cells compared to young individuals, demonstrating an age-related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications. PMID:27252176

Molecular Mediators Governing Iron-Copper Interactions

PubMed Central

Gulec, Sukru; Collins, James F.

2015-01-01

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

DNA sequence determinants controlling affinity, stability and shape of DNA complexes bound by the nucleoid protein Fis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, Stephen P.; Stella, Stefano; Cascio, Duilio

The abundant Fis nucleoid protein selectively binds poorly related DNA sequences with high affinities to regulate diverse DNA reactions. Fis binds DNA primarily through DNA backbone contacts and selects target sites by reading conformational properties of DNA sequences, most prominently intrinsic minor groove widths. High-affinity binding requires Fis-stabilized DNA conformational changes that vary depending on DNA sequence. In order to better understand the molecular basis for high affinity site recognition, we analyzed the effects of DNA sequence within and flanking the core Fis binding site on binding affinity and DNA structure. X-ray crystal structures of Fis-DNA complexes containing variable sequencesmore » in the noncontacted center of the binding site or variations within the major groove interfaces show that the DNA can adapt to the Fis dimer surface asymmetrically. We show that the presence and position of pyrimidine-purine base steps within the major groove interfaces affect both local DNA bending and minor groove compression to modulate affinities and lifetimes of Fis-DNA complexes. Sequences flanking the core binding site also modulate complex affinities, lifetimes, and the degree of local and global Fis-induced DNA bending. In particular, a G immediately upstream of the 15 bp core sequence inhibits binding and bending, and A-tracts within the flanking base pairs increase both complex lifetimes and global DNA curvatures. Taken together, our observations support a revised DNA motif specifying high-affinity Fis binding and highlight the range of conformations that Fis-bound DNA can adopt. Lastly, the affinities and DNA conformations of individual Fis-DNA complexes are likely to be tailored to their context-specific biological functions.« less

DNA sequence determinants controlling affinity, stability and shape of DNA complexes bound by the nucleoid protein Fis

DOE PAGES

Hancock, Stephen P.; Stella, Stefano; Cascio, Duilio; ...

2016-03-09

The abundant Fis nucleoid protein selectively binds poorly related DNA sequences with high affinities to regulate diverse DNA reactions. Fis binds DNA primarily through DNA backbone contacts and selects target sites by reading conformational properties of DNA sequences, most prominently intrinsic minor groove widths. High-affinity binding requires Fis-stabilized DNA conformational changes that vary depending on DNA sequence. In order to better understand the molecular basis for high affinity site recognition, we analyzed the effects of DNA sequence within and flanking the core Fis binding site on binding affinity and DNA structure. X-ray crystal structures of Fis-DNA complexes containing variable sequencesmore » in the noncontacted center of the binding site or variations within the major groove interfaces show that the DNA can adapt to the Fis dimer surface asymmetrically. We show that the presence and position of pyrimidine-purine base steps within the major groove interfaces affect both local DNA bending and minor groove compression to modulate affinities and lifetimes of Fis-DNA complexes. Sequences flanking the core binding site also modulate complex affinities, lifetimes, and the degree of local and global Fis-induced DNA bending. In particular, a G immediately upstream of the 15 bp core sequence inhibits binding and bending, and A-tracts within the flanking base pairs increase both complex lifetimes and global DNA curvatures. Taken together, our observations support a revised DNA motif specifying high-affinity Fis binding and highlight the range of conformations that Fis-bound DNA can adopt. Lastly, the affinities and DNA conformations of individual Fis-DNA complexes are likely to be tailored to their context-specific biological functions.« less

One hundred fold increase in current carrying capacity in a carbon nanotube–copper composite

PubMed Central

Subramaniam, Chandramouli; Yamada, Takeo; Kobashi, Kazufumi; Sekiguchi, Atsuko; Futaba, Don N.; Yumura, Motoo; Hata, Kenji

2013-01-01

Increased portability, versatility and ubiquity of electronics devices are a result of their progressive miniaturization, requiring current flow through narrow channels. Present-day devices operate close to the maximum current-carrying-capacity (that is, ampacity) of conductors (such as copper and gold), leading to decreased lifetime and performance, creating demand for new conductors with higher ampacity. Ampacity represents the maximum current-carrying capacity of the object that depends both on the structure and material. Here we report a carbon nanotube–copper composite exhibiting similar conductivity (2.3–4.7 × 105 S cm−1) as copper (5.8 × 105 S cm−1), but with a 100-times higher ampacity (6 × 108 A cm−2). Vacuum experiments demonstrate that carbon nanotubes suppress the primary failure pathways in copper as observed by the increased copper diffusion activation energy (∼2.0 eV) in carbon nanotube–copper composite, explaining its higher ampacity. This is the only material with both high conductivity and high ampacity, making it uniquely suited for applications in microscale electronics and inverters. PMID:23877359

Degradation of graphene coated copper in simulated proton exchange membrane fuel cell environment: Electrochemical impedance spectroscopy study

NASA Astrophysics Data System (ADS)

Ren, Y. J.; Anisur, M. R.; Qiu, W.; He, J. J.; Al-Saadi, S.; Singh Raman, R. K.

2017-09-01

Metallic materials are most suitable for bipolar plates of proton exchange membrane fuel cell (PEMFC) because they possess the required mechanical strength, durability, gas impermeability, acceptable cost and are suitable for mass production. However, metallic bipolar plates are prone to corrosion or they can passivate under PEMFC environment and interrupt the fuel cell operation. Therefore, it is highly attractive to develop corrosion resistance coating that is also highly conductive. Graphene fits these criteria. Graphene coating is developed on copper by chemical vapor deposition (CVD) with an aim to improving corrosion resistance of copper under PEMFC condition. The Raman Spectroscopy shows the graphene coating to be multilayered. The electrochemical degradation of graphene coated copper is investigated by electrochemical impedance spectroscopy (EIS) in 0.5 M H2SO4 solution at room temperature. After exposure to the electrolyte for up to 720 h, the charge transfer resistance (Rt) of the graphene coated copper is ∼3 times greater than that of the bare copper, indicating graphene coatings could improve the corrosion resistance of copper bipolar plates.

One hundred fold increase in current carrying capacity in a carbon nanotube-copper composite

NASA Astrophysics Data System (ADS)

Subramaniam, Chandramouli; Yamada, Takeo; Kobashi, Kazufumi; Sekiguchi, Atsuko; Futaba, Don N.; Yumura, Motoo; Hata, Kenji

2013-07-01

Increased portability, versatility and ubiquity of electronics devices are a result of their progressive miniaturization, requiring current flow through narrow channels. Present-day devices operate close to the maximum current-carrying-capacity (that is, ampacity) of conductors (such as copper and gold), leading to decreased lifetime and performance, creating demand for new conductors with higher ampacity. Ampacity represents the maximum current-carrying capacity of the object that depends both on the structure and material. Here we report a carbon nanotube-copper composite exhibiting similar conductivity (2.3-4.7 × 105Scm-1) as copper (5.8 × 105Scm-1), but with a 100-times higher ampacity (6 × 108Acm-2). Vacuum experiments demonstrate that carbon nanotubes suppress the primary failure pathways in copper as observed by the increased copper diffusion activation energy (~2.0eV) in carbon nanotube-copper composite, explaining its higher ampacity. This is the only material with both high conductivity and high ampacity, making it uniquely suited for applications in microscale electronics and inverters.

Improved Electroformed Structural Copper and Copper Alloys

NASA Technical Reports Server (NTRS)

Malone, G. A.; Hudson, W.; Babcock, B.; Edwards, R.

1998-01-01

Electroforming offers a superior means for fabricating internally cooled heat exchangers and structures subjected to thermal environments. Copper is deposited from many such applications because of the good thermal conductivity. It suffers from mediocre yield strength as a structural material and loses mechanical strength at intermediate temperatures. Mechanical properties similar to those of electroformed nickel are desired. Phase 1 examined innovative means to improve deposited copper structural performance. Yield strengths as high as 483 MPa (70 ksi) were obtained with useful ductility while retaining a high level of purity essential to good thermal conductivity. Phase 2 represents a program to explore new additive combinations in copper electrolytes to produce a more fine, equiaxed grain which can be thermally stabilized by other techniques such as alloying in modest degrees and dispersion strengthening. Evaluation of new technology - such as the codeposition of fullerness (diamond-like) particles were made to enhance thermal conductivity in low alloys. A test fire quality tube-bundle engine was fabricated using these copper property improvement concepts to show the superiority of the new coppers and fabrications methods over competitive technologies such as brazing and plasma deposition.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma

PubMed Central

Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-01-01

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies. PMID:29507693

How Does Boiling in the Earth's Crust Influence Metal Speciation and Transport?

NASA Astrophysics Data System (ADS)

Kam, K.; Lemke, K.

2014-12-01

The presence of large quantities of precious metals, such as gold and copper, near the Earth's surface (upper crust) is commonly attributed to transport in aqueous solution and precipitation upon variations in temperature and pressure. As a consequence, gold exploration is closely linked to solution chemistry, i.e. hydrothermal processes involving aqueous fluids with densities of around unity. However, as crustal fluids buoyantly ascend, boiling produces a coexisting low-density aqueous liquid with fundamentally different physical and chemical properties, and a, most importantly, a high affinity for coinage metals (Heinrich et al., Econ Geol., 1992, 87, 1566). From recent experimental studies of Au (Hurtig and Williams-Jones, 2014, Geochim. Cosmochim. Acta,, 127, 304), we know that metal speciation in this low-density phase differs fundamentally from that observed in bulk solution, clearly, with important implications for Au, and metal speciation in general, transport and ore concentrations processes (these processes would also be operable in industrial geothermal plants given the quite special solvent properties of steam). In brief, this study focuses on the speciation of select metal halides in bulk solution as well as in water vapor, and is driven by our need to understand the solvent properties of around 2.0x109 cubic kilometers of free water (or 2,500 times as much water as stored in all lakes and rivers) present in the Earth's crust. The scope of this study has particular applications in the geothermal and oil industries, as both deal with high temperature low-density aqueous fluids. Understanding how metal halide species behave upon boiling can also provide insight into how metals, such as copper and silver, coat turbine equipment and steam piping in geothermal plants, ultimately rendering these components inoperable. This study will also provide preliminary results from mass spectrometric experiments of transition metal halides, and will be augmented with results from molecular simulations of metal halides that are aimed at characterizing the nature (i.e. relativistic structures and energies) of metal clusters in water vapor.

Environmental concentrations of copper, chromium, and arsenic released from a chromated-copper-arsenate-(CCA-C-) treated wetland boardwalk

Treesearch

Stan T. Lebow; Daniel Foster

2005-01-01

A study was conducted to evaluate environmental accumulation and mobility of total copper, chromium, and arsenic adjacent to a chromated-copper-arsenate-(CCA-C-) treated wetland boardwalk. The study was considered a severe test because it included a large volume of treated wood in a site with high annual rainfall. Soil and sediment samples were collected before...

CCS and SOD1 mRNA are reduced after copper supplementation in peripheral mononuclear cells of individuals with high serum ceruloplasmin concentration.

PubMed

Suazo, Miriam; Olivares, Felipe; Mendez, Marco A; Pulgar, Rodrigo; Prohaska, Joseph R; Arredondo, Miguel; Pizarro, Fernando; Olivares, Manuel; Araya, Magdalena; González, Mauricio

2008-04-01

The limits of copper homeostatic regulation in humans are not known, making it difficult to define the milder effects of early copper excess. Furthermore, a robust assay to facilitate the detection of early stages of copper excess is needed. To address these issues, we assessed changes in relative mRNA abundance of methallothionein 2A (MT2A), prion (PrP), amyloid precursor-like protein 2 (APLP2), Cu/Zn superoxide dismutase (SOD1) and its copper chaperone (CCS) in peripheral mononuclear cells (PMNCs) from healthy adults representing the 5% highest and lowest extremes in the distribution curve of serum ceruloplasmin (Cp) concentrations of 800 individuals. The intracellular Cu content was also determined. PMNCs were isolated from individuals before and after exposure to a single daily dose of 10 mg Cu (as CuSO(4)) for 2 months. Results showed that although there were fluctuations in serum Cp values of the samples assessed before copper exposure, no significant differences were observed in cell copper content or in the relative abundance of MT2A, PrP and APLP2 transcripts in PMNCs. Also, these values were not modified after copper supplementation. However, CCS and SOD1 mRNA levels were reduced in PMNCs after copper supplementation in the individuals with the high Cp values, suggesting that they should be further explored as biomarkers of moderate copper overload in humans.

[Copper intake and blood levels as risk factors for atheromatous disease].

PubMed

Albala, C; Salazar, G; Vío, F; Araya, F; Feuerhacke, W; Olivares, S; Alvarez, G

1997-08-01

Copper is part of antioxidant enzymes and could have a cardiovascular protective effect. A higher cardiovascular risk has been associated with high as well as low plasma copper levels. To search for differences in copper intake and plasma levels between patients with coronary artery or cerebrovascular diseases and normal subjects. Zinc and copper intake, plasma levels and serum lipid levels were measured in 20 patients with cerebrovascular disease, 20 patients with an acute myocardial infarction and 40 subjects hospitalized for elective surgery, that served as controls. Copper and zinc intake was below recommended allowances in all subjects. Serum zinc and copper levels did not differ in the three study groups. In patients with myocardial infarction a weak correlation was found between serum copper and total cholesterol (r = 0.24; p < 0.05) and LDL cholesterol (r = 0.31; p < 0.05). No differences in copper levels were found in subjects with atherosclerosis and controls. The correlation between serum copper and cholesterol deserves further investigation.

Existence of three subtypes of bradykinin B2 receptors in guinea pig.

PubMed

Seguin, L; Widdowson, P S; Giesen-Crouse, E

1992-12-01

We describe the binding of [3H]bradykinin to homogenates of guinea pig brain, lung, and ileum. Analysis of [3H]bradykinin binding kinetics in guinea pig brain, lung, and ileum suggests the existence of two binding sites in each tissue. The finding of two binding sites for [3H]bradykinin in ileum, lung, and brain was further supported by Scatchard analysis of equilibrium binding in each tissue. [3H]Bradykinin binds to a high-affinity site in brain, lung, and ileum (KD = 70-200 pM), which constitutes approximately 20% of the bradykinin binding, and to a second, lower-affinity site (0.63-0.95 nM), which constitutes the remaining 80% of binding. Displacement studies with various bradykinin analogues led us to subdivide the high- and lower-affinity sites in each tissue and to suggest the existence of three subtypes of B2 receptors in the guinea pig, which we classify as B2a, B2b, and B2c. Binding of [3H]bradykinin is largely to a B2b receptor subtype, which constitutes the majority of binding in brain, lung, and ileum and represents the lower-affinity site in our binding studies. Receptor subtype B2c constitutes approximately 20% of binding sites in the brain and lung and is equivalent to the high-affinity site in brain and lung. We suggest that a third subtype of B2 receptor (high-affinity site in ileum), B2a, is found only in the ileum. All three subtypes of B2 receptors display a high affinity for bradykinin, whereas they show different affinities for various bradykinin analogues displaying agonist or antagonist activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice

PubMed Central

Liu, Xiaojun; Jiang, Shuguang; Fang, Chongyun; Yang, Shiyu; Olalere, Devvora; Pequignot, Edward C.; Cogdill, Alexandria P.; Li, Na; Ramones, Melissa; Granda, Brian; Zhou, Li; Loew, Andreas; Young, Regina M.; June, Carl H.; Zhao, Yangbing

2015-01-01

Target-mediated toxicity is a major limitation in the development of chimeric antigen T cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues which express it at physiologic levels. A CAR-expressing T cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. PMID:26330166

[Progresses in screening active compounds from herbal medicine by affinity chromatography].

PubMed

Feng, Ying-shu; Tong, Shan-shan; Xu, Xi-ming; Yu, Jiang-nan

2015-03-01

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.

Haemolymph from Mytilus galloprovincialis: Response to copper and temperature challenges studied by (1)H-NMR metabonomics.

PubMed

Digilio, Giuseppe; Sforzini, Susanna; Cassino, Claudio; Robotti, Elisa; Oliveri, Caterina; Marengo, Emilio; Musso, Davide; Osella, Domenico; Viarengo, Aldo

2016-01-01

Numerous studies on molluscs have been carried out to clarify the physiological roles of haemolymph serum proteins and haemocytes. However, little is known about the presence and functional role of the serum metabolites. In this study, Nuclear Magnetic Resonance (NMR) was used to assess whether changes of the metabolic profile of Mytilus galloprovincialis haemolymph may reflect alterations of the physiological status of the organisms due to environmental stressors, namely copper and temperature. Mussel haemolymph was taken from the posterior adductor muscle after a 4-day exposure to ambient (16 °C) or high temperature (24 °C) and in the absence or presence (5 μg/L, 20 μg/L, or 40 μg/L) of sublethal copper (Cu(2+)). The total glutathione (GSH) concentration in the haemolymph of both control and treated mussels was minimal, indicating the absence of significant contaminations by muscle intracellular metabolites due to the sampling procedure. In the (1)H-NMR spectrum of haemolymph, 27 metabolites were identified unambiguously. The separate and combined effects of exposure to copper and temperature on the haemolymph metabolic profile were assessed by Principal Component Analysis (PCA) and Ranking-PCA multivariate analysis. Changes of the metabolomic profile due to copper exposure at 16 °C became detectable at a dose of 20 μg/L copper. Alanine, lysine, serine, glutamine, glycogen, glucose and protein aliphatics played a major role in the classification of the metabolic changes according to the level of copper exposition. High temperature (24 °C) and high copper levels caused a coherent increase of a common set of metabolites (mostly glucose, serine, and lysine), indicating that the metabolic impairment due to high temperature is enforced by the presence of copper. Overall, the results demonstrate that, as for human blood plasma, the analysis of haemolymph metabolites represents a promising tool for the diagnosis of pollutant-induced stress syndrome in marine mussels. Copyright © 2016 Elsevier Inc. All rights reserved.

Cloning, heterologous expression, and in situ characterization of the first high affinity nucleobase transporter from a protozoan.

PubMed

Burchmore, Richard J S; Wallace, Lynsey J M; Candlish, Denise; Al-Salabi, Mohammed I; Beal, Paul R; Barrett, Michael P; Baldwin, Stephen A; de Koning, Harry P

2003-06-27

While multiple nucleoside transporters, some of which can also transport nucleobases, have been cloned in recent years from many different organisms, no sequence information is available for the high affinity, nucleobase-selective transporters of metazoa, parazoa, or protozoa. We have identified a gene, TbNBT1, from Trypanosoma brucei brucei that encodes a 435-residue protein of the equilibrative nucleoside transporter superfamily. The gene was expressed in both the procyclic and bloodstream forms of the organism. Expression of TbNBT1 in a Saccharomyces cerevisiae strain lacking an endogenous purine transporter allowed growth on adenine as sole purine source and introduced a high affinity transport activity for adenine and hypoxanthine, with Km values of 2.1 +/- 0.6 and 0.66 +/- 0.22 microm, respectively, as well as high affinity for xanthine, guanine, guanosine, and allopurinol and moderate affinity for inosine. A transporter with an indistinguishable kinetic profile was identified in T. b. brucei procyclics and designated H4. RNA interference of TbNBT1 in procyclics reduced cognate mRNA levels by approximately 80% and H4 transport activity by approximately 90%. Expression of TbNBT1 in Xenopus oocytes further confirmed that this gene encodes the first high affinity nucleobase transporter from protozoa or animals to be identified at the molecular level.

Copper thiobis(alkylphenols) and antioxidant compositions thereof

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braid, M.

1980-09-30

Novel copper thiobis(alkylphenol-phenolate) complexes are effective antioxidant additives for various organic media such as oils of lubricating viscosity and plastics. Additionally these novel copper organo-sulfur compounds are highly useful as energy quenchers and antisludging agents in a variety of organic substrates.

Studies on copper-yttria nanocomposites: high-energy ball milling versus chemical reduction method.

PubMed

Joshi, P B; Rehani, Bharati; Naik, Palak; Patel, Swati; Khanna, P K

2012-03-01

Oxide dispersion-strengthened copper-base composites are widely used for applications demanding high tensile strength, high hardness along with good electrical and thermal conductivity. Oxides of metals like aluminium, cerium, yttrium and zirconium are often used for this purpose as fine and uniformly distributed dispersoid particles in soft and ductile copper matrix. Such composites find applications as electrical contacts, resistance-welding tips, lead wires, continuous casting moulds, etc. In this investigation an attempt has been made to produce copper-yttria nanocomposites using two different morphologies of copper powder and two different processing routes namely, high-energy milling and in-situ chemical reduction. The synthesized powders were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) for their phase identification and morphological study. The nanocomposite powders in each case were subsequently processed to obtain bulk solids by classical powder metallurgy route of press-sinter-repress. The resultant bulk solid compacts were subjected to property evaluation. The study revealed that the properties of Cu-Y2O3 nanocomposites depend on the processing route used and in turn on the resultant powder morphology.

Bean peptides have higher in silico binding affinities than ezetimibe for the N-terminal domain of cholesterol receptor Niemann-Pick C1 Like-1.

PubMed

Real Hernandez, Luis M; Gonzalez de Mejia, Elvira

2017-04-01

Niemann-Pick C1 like-1 (NPC1L1) mediates cholesterol absorption at the apical membrane of enterocytes through a yet unknown mechanism. Bean, pea, and lentil proteins are naturally hydrolyzed during digestion to produce peptides. The potential for pulse peptides to have high binding affinities for NPC1L1 has not been determined. In this study , in silico binding affinities and interactions were determined between the N-terminal domain of NPC1L1 and 14 pulse peptides (5≥ amino acids) derived through pepsin-pancreatin digestion. Peptides were docked in triplicate to the N-terminal domain using docking program AutoDock Vina, and results were compared to those of ezetimibe, a prescribed NPC1L1 inhibitor. Three black bean peptides (-7.2 to -7.0kcal/mol) and the cowpea bean dipeptide Lys-Asp (-7.0kcal/mol) had higher binding affinities than ezetimibe (-6.6kcal/mol) for the N-terminal domain of NPC1L1. Lentil and pea peptides studied did not have high binding affinities. The common bean peptide Tyr-Ala-Ala-Ala-Thr (-7.2kcal/mol), which can be produced from black or navy bean proteins, had the highest binding affinity. Ezetimibe and peptides with high binding affinities for the N-terminal domain are expected to interact at different locations of the N-terminal domain. All high affinity black bean peptides are expected to have van der Waals interactions with SER130, PHE136, and LEU236 and a conventional hydrogen bond with GLU238 of NPC1L1. Due to their high affinity for the N-terminal domain of NPC1L1, black and cowpea bean peptides produced in the digestive track have the potential to disrupt interactions between NPC1L1 and membrane proteins that lead to cholesterol absorption. Copyright © 2017 Elsevier Inc. All rights reserved.

Copper: a metal for the ages

USGS Publications Warehouse

Doebrich, Jeff

2009-01-01

Copper was one of the first metals ever extracted and used by humans, and it has made vital contributions to sustaining and improving society since the dawn of civilization. Copper was first used in coins and ornaments starting about 8000 B.C., and at about 5500 B.C., copper tools helped civilization emerge from the Stone Age. The discovery that copper alloyed with tin produces bronze marked the beginning of the Bronze Age at about 3000 B.C. Copper is easily stretched, molded, and shaped; is resistant to corrosion; and conducts heat and electricity efficiently. As a result, copper was important to early humans and continues to be a material of choice for a variety of domestic, industrial, and high-technology applications today.

Selection of High-Affinity Peptidic Serine Protease Inhibitors with Increased Binding Entropy from a Back-Flip Library of Peptide-Protease Fusions.

PubMed

Sørensen, Hans Peter; Xu, Peng; Jiang, Longguang; Kromann-Hansen, Tobias; Jensen, Knud J; Huang, Mingdong; Andreasen, Peter A

2015-09-25

We have developed a new concept for designing peptidic protein modulators, by recombinantly fusing the peptidic modulator, with randomized residues, directly to the target protein via a linker and screening for internal modulation of the activity of the protein. We tested the feasibility of the concept by fusing a 10-residue-long, disulfide-bond-constrained inhibitory peptide, randomized in selected positions, to the catalytic domain of the serine protease murine urokinase-type plasminogen activator. High-affinity inhibitory peptide variants were identified as those that conferred to the fusion protease the lowest activity for substrate hydrolysis. The usefulness of the strategy was demonstrated by the selection of peptidic inhibitors of murine urokinase-type plasminogen activator with a low nanomolar affinity. The high affinity could not have been predicted by rational considerations, as the high affinity was associated with a loss of polar interactions and an increased binding entropy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

PubMed Central

Hebbel, R P; Eaton, J W; Kronenberg, R S; Zanjani, E D; Moore, L G; Berger, E M

1978-01-01

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude. PMID:29054

c-Type Cytochrome Assembly Is a Key Target of Copper Toxicity within the Bacterial Periplasm

PubMed Central

Durand, Anne; Azzouzi, Asma; Bourbon, Marie-Line; Steunou, Anne-Soisig; Liotenberg, Sylviane; Maeshima, Akinori; Astier, Chantal; Argentini, Manuela; Saito, Shingo

2015-01-01

ABSTRACT In the absence of a tight control of copper entrance into cells, bacteria have evolved different systems to control copper concentration within the cytoplasm and the periplasm. Central to these systems, the Cu+ ATPase CopA plays a major role in copper tolerance and translocates copper from the cytoplasm to the periplasm. The fate of copper in the periplasm varies among species. Copper can be sequestered, oxidized, or released outside the cells. Here we describe the identification of CopI, a periplasmic protein present in many proteobacteria, and show its requirement for copper tolerance in Rubrivivax gelatinosus. The ΔcopI mutant is more susceptible to copper than the Cu+ ATPase copA mutant. CopI is induced by copper, localized in the periplasm and could bind copper. Interestingly, copper affects cytochrome c membrane complexes (cbb3 oxidase and photosystem) in both ΔcopI and copA-null mutants, but the causes are different. In the copA mutant, heme and chlorophyll synthesis are affected, whereas in ΔcopI mutant, the decrease is a consequence of impaired cytochrome c assembly. This impact on c-type cytochromes would contribute also to the copper toxicity in the periplasm of the wild-type cells when they are exposed to high copper concentrations. PMID:26396241

Genome Data Mining and Soil Survey for the Novel Group 5 [NiFe]-Hydrogenase To Explore the Diversity and Ecological Importance of Presumptive High-Affinity H2-Oxidizing Bacteria ▿†

PubMed Central

Constant, Philippe; Chowdhury, Soumitra Paul; Hesse, Laura; Pratscher, Jennifer; Conrad, Ralf

2011-01-01

Streptomyces soil isolates exhibiting the unique ability to oxidize atmospheric H2 possess genes specifying a putative high-affinity [NiFe]-hydrogenase. This study was undertaken to explore the taxonomic diversity and the ecological importance of this novel functional group. We propose to designate the genes encoding the small and large subunits of the putative high-affinity hydrogenase hhyS and hhyL, respectively. Genome data mining revealed that the hhyL gene is unevenly distributed in the phyla Actinobacteria, Proteobacteria, Chloroflexi, and Acidobacteria. The hhyL gene sequences comprised a phylogenetically distinct group, namely, the group 5 [NiFe]-hydrogenase genes. The presumptive high-affinity H2-oxidizing bacteria constituting group 5 were shown to possess a hydrogenase gene cluster, including the genes encoding auxiliary and structural components of the enzyme and four additional open reading frames (ORFs) of unknown function. A soil survey confirmed that both high-affinity H2 oxidation activity and the hhyL gene are ubiquitous. A quantitative PCR assay revealed that soil contained 106 to 108 hhyL gene copies g (dry weight)−1. Assuming one hhyL gene copy per genome, the abundance of presumptive high-affinity H2-oxidizing bacteria was higher than the maximal population size for which maintenance energy requirements would be fully supplied through the H2 oxidation activity measured in soil. Our data indicate that the abundance of the hhyL gene should not be taken as a reliable proxy for the uptake of atmospheric H2 by soil, because high-affinity H2 oxidation is a facultatively mixotrophic metabolism, and microorganisms harboring a nonfunctional group 5 [NiFe]-hydrogenase may occur. PMID:21742924

Diversity and Evolutionary History of Iron Metabolism Genes in Diatoms

PubMed Central

Groussman, Ryan D.; Parker, Micaela S.; Armbrust, E. Virginia

2015-01-01

Ferroproteins arose early in Earth’s history, prior to the emergence of oxygenic photosynthesis and the subsequent reduction of bioavailable iron. Today, iron availability limits primary productivity in about 30% of the world’s oceans. Diatoms, responsible for nearly half of oceanic primary production, have evolved molecular strategies for coping with variable iron concentrations. Our understanding of the evolutionary breadth of these strategies has been restricted by the limited number of species for which molecular sequence data is available. To uncover the diversity of strategies marine diatoms employ to meet cellular iron demands, we analyzed 367 newly released marine microbial eukaryotic transcriptomes, which include 47 diatom species. We focused on genes encoding proteins previously identified as having a role in iron management: iron uptake (high-affinity ferric reductase, multi-copper oxidase, and Fe(III) permease); iron storage (ferritin); iron-induced protein substitutions (flavodoxin/ferredoxin, and plastocyanin/cytochrome c6) and defense against reactive oxygen species (superoxide dismutases). Homologs encoding the high-affinity iron uptake system components were detected across the four diatom Classes suggesting an ancient origin for this pathway. Ferritin transcripts were also detected in all Classes, revealing a more widespread utilization of ferritin throughout diatoms than previously recognized. Flavodoxin and plastocyanin transcripts indicate possible alternative redox metal strategies. Predicted localization signals for ferredoxin identify multiple examples of gene transfer from the plastid to the nuclear genome. Transcripts encoding four superoxide dismutase metalloforms were detected, including a putative nickel-coordinating isozyme. Taken together, our results suggest that the majority of iron metabolism genes in diatoms appear to be vertically inherited with functional diversity achieved via possible neofunctionalization of paralogs. This refined view of iron use strategies in diatoms elucidates the history of these adaptations, and provides potential molecular markers for determining the iron nutritional status of different diatom species in environmental samples. PMID:26052941

Oxidation-assisted graphene heteroepitaxy on copper foil.

PubMed

Reckinger, Nicolas; Tang, Xiaohui; Joucken, Frédéric; Lajaunie, Luc; Arenal, Raul; Dubois, Emmanuel; Hackens, Benoît; Henrard, Luc; Colomer, Jean-François

2016-11-10

We propose an innovative, easy-to-implement approach to synthesize aligned large-area single-crystalline graphene flakes by chemical vapor deposition on copper foil. This method doubly takes advantage of residual oxygen present in the gas phase. First, by slightly oxidizing the copper surface, we induce grain boundary pinning in copper and, in consequence, the freezing of the thermal recrystallization process. Subsequent reduction of copper under hydrogen suddenly unlocks the delayed reconstruction, favoring the growth of centimeter-sized copper (111) grains through the mechanism of abnormal grain growth. Second, the oxidation of the copper surface also drastically reduces the nucleation density of graphene. This oxidation/reduction sequence leads to the synthesis of aligned millimeter-sized monolayer graphene domains in epitaxial registry with copper (111). The as-grown graphene flakes are demonstrated to be both single-crystalline and of high quality.

Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2)[S

PubMed Central

Lionarons, Daniël A.; Boyer, James L.; Cai, Shi-Ying

2012-01-01

The apical Na+-dependent bile salt transporter (ASBT/SLC10A2) is essential for maintaining the enterohepatic circulation of bile salts. It is not known when Slc10a2 evolved as a bile salt transporter or how it adapted to substantial changes in bile salt structure during evolution. We characterized ASBT orthologs from two primitive vertebrates, the lamprey that utilizes early 5α-bile alcohols and the skate that utilizes structurally different 5β-bile alcohols, and compared substrate specificity with ASBT from humans who utilize modern 5β-bile acids. Everted gut sacs of skate but not the more primitive lamprey transported 3H-taurocholic acid (TCA), a modern 5β-bile acid. However, molecular cloning identified ASBT orthologs from both species. Cell-based assays using recombinant ASBT/Asbt's indicate that lamprey Asbt has high affinity for 5α-bile alcohols, low affinity for 5β-bile alcohols, and lacks affinity for TCA, whereas skate Asbt showed high affinity for 5α- and 5β-bile alcohols but low affinity for TCA. In contrast, human ASBT demonstrated high affinity for all three bile salt types. These findings suggest that ASBT evolved from the earliest vertebrates by gaining affinity for modern bile salts while retaining affinity for older bile salts. Also, our results indicate that the bile salt enterohepatic circulation is conserved throughout vertebrate evolution. PMID:22669917

Overlap of copper and iron uptake systems in mitochondria in Saccharomyces cerevisiae

PubMed Central

Wang, Jing; Gammon, Micah G.; Maynard, Margaret K.; White, Olivia L.; Cobine, Jai A.; Mahone, Wilkerson K.

2016-01-01

In Saccharomyces cerevisiae, the mitochondrial carrier family protein Pic2 imports copper into the matrix. Deletion of PIC2 causes defects in mitochondrial copper uptake and copper-dependent growth phenotypes owing to decreased cytochrome c oxidase activity. However, copper import is not completely eliminated in this mutant, so alternative transport systems must exist. Deletion of MRS3, a component of the iron import machinery, also causes a copper-dependent growth defect on non-fermentable carbon. Deletion of both PIC2 and MRS3 led to a more severe respiratory growth defect than either individual mutant. In addition, MRS3 expressed from a high copy number vector was able to suppress the oxygen consumption and copper uptake defects of a strain lacking PIC2. When expressed in Lactococcus lactis, Mrs3 mediated copper and iron import. Finally, a PIC2 and MRS3 double mutant prevented the copper-dependent activation of a heterologously expressed copper sensor in the mitochondrial intermembrane space. Taken together, these data support a role for the iron transporter Mrs3 in copper import into the mitochondrial matrix. PMID:26763345

Copper Alloy For High-Temperature Uses

NASA Technical Reports Server (NTRS)

Dreshfield, Robert L.; Ellis, David L.; Michal, Gary

1994-01-01

Alloy of Cu/8Cr/4Nb (numbers indicate parts by atom percent) improved over older high-temperature copper-based alloys in that it offers enhanced high temperature strength, resistance to creep, and ductility while retaining most of thermal conductivity of pure copper; in addition, alloy does not become embrittled upon exposure to hydrogen at temperatures as high as 705 degrees C. Designed for use in presence of high heat fluxes and active cooling; for example, in heat exchangers in advanced aircraft and spacecraft engines, and other high-temperature applications in which there is need for such material. High conductivity and hardness of alloy exploited in welding electrodes and in high-voltage and high-current switches and other applications in which wear poses design problem.

Fabrication of gas turbine water-cooled composite nozzle and bucket hardware employing plasma spray process

DOEpatents

Schilke, Peter W.; Muth, Myron C.; Schilling, William F.; Rairden, III, John R.

1983-01-01

In the method for fabrication of water-cooled composite nozzle and bucket hardware for high temperature gas turbines, a high thermal conductivity copper alloy is applied, employing a high velocity/low pressure (HV/LP) plasma arc spraying process, to an assembly comprising a structural framework of copper alloy or a nickel-based super alloy, or combination of the two, and overlying cooling tubes. The copper alloy is plamsa sprayed to a coating thickness sufficient to completely cover the cooling tubes, and to allow for machining back of the copper alloy to create a smooth surface having a thickness of from 0.010 inch (0.254 mm) to 0.150 inch (3.18 mm) or more. The layer of copper applied by the plasma spraying has no continuous porosity, and advantageously may readily be employed to sustain a pressure differential during hot isostatic pressing (HIP) bonding of the overall structure to enhance bonding by solid state diffusion between the component parts of the structure.

Iron and copper release in drinking-water distribution systems.

PubMed

Shi, Baoyou; Taylor, James S

2007-09-01

A large-scale pilot study was carried out to evaluate the impacts of changes in water source and treatment process on iron and copper release in water distribution systems. Finished surface waters, groundwaters, and desalinated waters were produced with seven different treatment systems and supplied to 18 pipe distribution systems (PDSs). The major water treatment processes included lime softening, ferric sulfate coagulation, reverse osmosis, nanofiltration, and integrated membrane systems. PDSs were constructed from PVC, lined cast iron, unlined cast iron, and galvanized pipes. Copper pipe loops were set up for corrosion monitoring. Results showed that surface water after ferric sulfate coagulation had low alkalinity and high sulfates, and consequently caused the highest iron release. Finished groundwater treated by conventional method produced the lowest iron release but the highest copper release. The iron release of desalinated water was relatively high because of the water's high chloride level and low alkalinity. Both iron and copper release behaviors were influenced by temperature.

Microstructural change in electroformed copper liners of shaped charges upon plastic deformation at ultra-high strain rate

NASA Astrophysics Data System (ADS)

Tian, W. H.; Hu, S. L.; Fan, A. L.; Wang, Z.

2002-01-01

Transmission electron microscopy (TEM) observations were carried out for examining the as-formed and post-deformed microstructures in a variety of electroformed copper liners of shaped charges. The deformation was carried out at an ultra-high strain rate. Specifically, the electron backscattering Kikuchi pattern (EBSP) technique was utilized to examine the micro-texture of these materials. TEM observations revealed that these electroformed copper liners of shaped charges have a grain size of about 1-3 mum, EBSP analysis demonstrated that the as-grown copper liners of shaped charges exhibit a l 10) fiber micro-texture which is parallel to the normal direction of the surface of the liners of shaped charges. Having undergone plastic deformation at ultra-high strain rate (10(7) s(-1)), the specimens which were recovered from the copper slugs were found to have grain size of the same order as that before deformation. EBSP analysis revealed that the (110) fiber texture existed in the as-formed copper liners disappears in the course of deformation. TEM examination results indicate that dynamic recovery and recrystallization play a significant role in this deformation process.

Cleaning and passivation of copper surfaces to remove surface radioactivity and prevent oxide formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoppe, Eric W.; Seifert, Allen; Aalseth, Craig E.

High-purity copper is an attractive material for constructing ultra-low-background radiation measurement devices. Many low-background experiments using high-purity copper have indicated surface contamination emerges as the dominant background. Radon daughters plate out on exposed surfaces, leaving a residual 210Pb background that is difficult to avoid. Dust is also a problem; even under cleanroom conditions, the amount of U and Th deposited on surfaces can represent the largest remaining background. To control these backgrounds, a copper cleaning chemistry has been developed. Designed to replace an effective, but overly aggressive concentrated nitric acid etch, this peroxide-based solution allows for a more controlled cleaningmore » of surfaces. The acidified hydrogen peroxide solution will generally target the Cu+/Cu2+ species which are the predominant surface participants, leaving the bulk of copper metal intact. This preserves the critical tolerances of parts and eliminates significant waste disposal issues. Accompanying passivation chemistry has also been developed that protects copper surfaces from oxidation. Using a high-activity polonium surface spike, the most difficult-to-remove daughter isotope of radon, the performance of these methods are quantified. © 2001 Elsevier Science. All rights reserved« less

Comparative Investigation of Copper Tolerance and Identification of Putative Tolerance Related Genes in Tardigrades

PubMed Central

Hygum, Thomas L.; Fobian, Dannie; Kamilari, Maria; Jørgensen, Aslak; Schiøtt, Morten; Grosell, Martin; Møbjerg, Nadja

2017-01-01

Tardigrades are microscopic aquatic animals renowned for their tolerance toward extreme environmental conditions. The current study is the first to investigate their tolerance toward heavy metals and we present a novel tardigrade toxicant tolerance assay based on activity assessments as a measure of survival. Specifically, we compare tolerance toward copper in four species representing different evolutionary lineages, habitats and adaptation strategies, i.e., a marine heterotardigrade, Echiniscoides sigismundi, a limno-terrestrial heterotardigrade, Echiniscus testudo, a limno-terrestrial eutardigrade, Ramazzottius oberhaeuseri, and a marine eutardigrade, Halobiotus crispae. The latter was sampled at a time of year, when the population is predominantly represented by aberrant P1 cysts, while the other species were in normal active states prior to exposure. Based on volume measurements and a general relation between body mass and copper tolerance, expected tardigrade EC50 values were estimated at 0.5–2 μg l−1. Following 24 h of exposure, tolerance was high with no apparent link to lineage or habitat. EC50s (95% CI), 24 h after exposure, were estimated at 178 (168–186) and 310 (295–328) μg l−1, respectively, for E. sigismundi and R. oberhaeuseri, whereas E. testudo and H. crispae were less affected. Highest tolerance was observed in H. crispae with a mean ± s.e.m. activity of 77 ± 2% (n = 3) 24 h after removal from ~3 mg l−1 copper, suggesting that tardigrade cysts have increased tolerance toward toxicants. In order to identify putative tolerance related genes, an E. sigismundi transcriptome was searched for key enzymes involved in osmoregulation, antioxidant defense and copper metabolism. We found high expression of Na/K ATPase and carbonic anhydrase, known targets for copper. Our transcriptome, furthermore, revealed high expression of antioxidant enzymes, copper transporters, ATOX1, and a Cu-ATPase. In summary, our results indicate that tardigrades express well-known key osmoregulatory enzymes, supporting the hypothesis that copper inhibits sodium turnover as demonstrated for other aquatic organisms. Tardigrades, nevertheless, have high tolerance toward the toxicant, which is likely linked to high expression of antioxidant enzymes and an ability to enter dormant states. Tardigrades, furthermore, seem to have a well-developed battery of cuproproteins involved in copper homeostasis, providing basis for active copper sequestering and excretion. PMID:28293195

Comparative Investigation of Copper Tolerance and Identification of Putative Tolerance Related Genes in Tardigrades.

PubMed

Hygum, Thomas L; Fobian, Dannie; Kamilari, Maria; Jørgensen, Aslak; Schiøtt, Morten; Grosell, Martin; Møbjerg, Nadja

2017-01-01

Tardigrades are microscopic aquatic animals renowned for their tolerance toward extreme environmental conditions. The current study is the first to investigate their tolerance toward heavy metals and we present a novel tardigrade toxicant tolerance assay based on activity assessments as a measure of survival. Specifically, we compare tolerance toward copper in four species representing different evolutionary lineages, habitats and adaptation strategies, i.e., a marine heterotardigrade, Echiniscoides sigismundi , a limno-terrestrial heterotardigrade, Echiniscus testudo , a limno-terrestrial eutardigrade, Ramazzottius oberhaeuseri , and a marine eutardigrade, Halobiotus crispae . The latter was sampled at a time of year, when the population is predominantly represented by aberrant P1 cysts, while the other species were in normal active states prior to exposure. Based on volume measurements and a general relation between body mass and copper tolerance, expected tardigrade EC50 values were estimated at 0.5-2 μg l -1 . Following 24 h of exposure, tolerance was high with no apparent link to lineage or habitat. EC50s (95% CI), 24 h after exposure, were estimated at 178 (168-186) and 310 (295-328) μg l -1 , respectively, for E. sigismundi and R. oberhaeuseri , whereas E. testudo and H. crispae were less affected. Highest tolerance was observed in H. crispae with a mean ± s.e.m . activity of 77 ± 2% ( n = 3) 24 h after removal from ~3 mg l -1 copper, suggesting that tardigrade cysts have increased tolerance toward toxicants. In order to identify putative tolerance related genes, an E. sigismundi transcriptome was searched for key enzymes involved in osmoregulation, antioxidant defense and copper metabolism. We found high expression of Na/K ATPase and carbonic anhydrase, known targets for copper. Our transcriptome, furthermore, revealed high expression of antioxidant enzymes, copper transporters, ATOX1, and a Cu-ATPase. In summary, our results indicate that tardigrades express well-known key osmoregulatory enzymes, supporting the hypothesis that copper inhibits sodium turnover as demonstrated for other aquatic organisms. Tardigrades, nevertheless, have high tolerance toward the toxicant, which is likely linked to high expression of antioxidant enzymes and an ability to enter dormant states. Tardigrades, furthermore, seem to have a well-developed battery of cuproproteins involved in copper homeostasis, providing basis for active copper sequestering and excretion.

Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

PubMed Central

2016-01-01

ABSTRACT In air-breathing vertebrates at high altitude, fine-tuned adjustments in hemoglobin (Hb)–O2 affinity provide an energetically efficient means of mitigating the effects of arterial hypoxemia. However, it is not always clear whether an increased or decreased Hb–O2 affinity should be expected to improve tissue O2 delivery under different degrees of hypoxia, due to the inherent trade-off between arterial O2 loading and peripheral O2 unloading. Theoretical results indicate that the optimal Hb–O2 affinity varies as a non-linear function of environmental O2 availability, and the threshold elevation at which an increased Hb–O2 affinity becomes advantageous depends on the magnitude of diffusion limitation (the extent to which O2 equilibration at the blood–gas interface is limited by the kinetics of O2 exchange). This body of theory provides a framework for interpreting the possible adaptive significance of evolved changes in Hb–O2 affinity in vertebrates that have colonized high-altitude environments. To evaluate the evidence for an empirical generalization and to test theoretical predictions, I synthesized comparative data in a phylogenetic framework to assess the strength of the relationship between Hb–O2 affinity and native elevation in mammals and birds. Evidence for a general trend in mammals is equivocal, but there is a remarkably strong positive relationship between Hb–O2 affinity and native elevation in birds. Evolved changes in Hb function in high-altitude birds provide one of the most compelling examples of convergent biochemical adaptation in vertebrates. PMID:27802149

Hemoglobin-oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

PubMed

Storz, Jay F

2016-10-15

In air-breathing vertebrates at high altitude, fine-tuned adjustments in hemoglobin (Hb)-O 2 affinity provide an energetically efficient means of mitigating the effects of arterial hypoxemia. However, it is not always clear whether an increased or decreased Hb-O 2 affinity should be expected to improve tissue O 2 delivery under different degrees of hypoxia, due to the inherent trade-off between arterial O 2 loading and peripheral O 2 unloading. Theoretical results indicate that the optimal Hb-O 2 affinity varies as a non-linear function of environmental O 2 availability, and the threshold elevation at which an increased Hb-O 2 affinity becomes advantageous depends on the magnitude of diffusion limitation (the extent to which O 2 equilibration at the blood-gas interface is limited by the kinetics of O 2 exchange). This body of theory provides a framework for interpreting the possible adaptive significance of evolved changes in Hb-O 2 affinity in vertebrates that have colonized high-altitude environments. To evaluate the evidence for an empirical generalization and to test theoretical predictions, I synthesized comparative data in a phylogenetic framework to assess the strength of the relationship between Hb-O 2 affinity and native elevation in mammals and birds. Evidence for a general trend in mammals is equivocal, but there is a remarkably strong positive relationship between Hb-O 2 affinity and native elevation in birds. Evolved changes in Hb function in high-altitude birds provide one of the most compelling examples of convergent biochemical adaptation in vertebrates. © 2016. Published by The Company of Biologists Ltd.

Specificity of cell–cell adhesion by classical cadherins: Critical role for low-affinity dimerization through β-strand swapping

PubMed Central

Chen, Chien Peter; Posy, Shoshana; Ben-Shaul, Avinoam; Shapiro, Lawrence; Honig, Barry H.

2005-01-01

Cadherins constitute a family of cell-surface proteins that mediate intercellular adhesion through the association of protomers presented from juxtaposed cells. Differential cadherin expression leads to highly specific intercellular interactions in vivo. This cell–cell specificity is difficult to understand at the molecular level because individual cadherins within a given subfamily are highly similar to each other both in sequence and structure, and they dimerize with remarkably low binding affinities. Here, we provide a molecular model that accounts for these apparently contradictory observations. The model is based in part on the fact that cadherins bind to one another by “swapping” the N-terminal β-strands of their adhesive domains. An inherent feature of strand swapping (or, more generally, the domain swapping phenomenon) is that “closed” monomeric conformations act as competitive inhibitors of dimer formation, thus lowering affinities even when the dimer interface has the characteristics of high-affinity complexes. The model describes quantitatively how small affinity differences between low-affinity cadherin dimers are amplified by multiple cadherin interactions to establish large specificity effects at the cellular level. It is shown that cellular specificity would not be observed if cadherins bound with high affinities, thus emphasizing the crucial role of strand swapping in cell–cell adhesion. Numerical estimates demonstrate that the strength of cellular adhesion is extremely sensitive to the concentration of cadherins expressed at the cell surface. We suggest that the domain swapping mechanism is used by a variety of cell-adhesion proteins and that related mechanisms to control affinity and specificity are exploited in other systems. PMID:15937105

DNA aptamers for the detection of Haemophilus influenzae type b by cell SELEX.

PubMed

Bitaraf, F S; Rasooli, I; Mousavi Gargari, S L

2016-03-01

Haemophilus influenzae type b (Hib) causes acute bacterial meningitis (ABM) in children, with a mortality rate of about 3-6 % of the affected patients. ABM can lead to death during a period of hours to several days and, hence, rapid and early detection of the infection is crucial. Aptamers, the short single-stranded DNA or RNA with high affinity to target molecules, are selected by a high-flux screening technique known as in vitro screening and systematic evolution of ligands by exponential enrichment technology (SELEX). In this study, whole-cell SELEX was applied for the selection of target-specific aptamers with high affinity to Hib. ssDNA aptamers prepared by lambda exonuclease were incubated with the target cells (Hib). The aptameric binding rate to Hib was characterized for binding affinity after seven SELEX rounds by flow cytometry. The aptamers with higher binding affinity were cloned. Four of 68 aptamer clones were selected for sequencing. The dissociation constant (Kd) of the high-affinity aptamer clones 45 and 63 were 47.10 and 28.46 pM, respectively. These aptamers did not bind to other bacterial species, including the seven meningitis-causing bacteria. They showed distinct affinity to various H. influenzae strains only. These aptamers showed the highest affinity to Hib and the lowest affinity to H. influenzae type c and to other meningitis-causing bacteria. Clone 63 could detect Hib in patients' cerebrospinal fluid (CSF) samples at 60 colony-forming units (CFU)/mL. The results indicate applicability of the aptamers for rapid and early detection of infections brought about by Hib.

Differences between high-affinity forskolin binding sites in dopamine-riche and other regions of rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poat, J.A.; Cripps, H.E.; Iversen, L.L.

1988-05-01

Forskolin labelled with (/sup 3/H) bound to high- and low-affinity sites in the rat brain. The high-affinity site was discretely located, with highest densities in the striatum, nucleus accumbens, olfactory tubercule, substantia nigra, hippocampus, and the molecular layers of the cerebellum. This site did not correlate well with the distribution of adenylate cyclase. The high-affinity striatal binding site may be associated with a stimulatory guanine nucleotide-binding protein. Thus, the number of sites was increased by the addition of Mg/sup 2 +/ and guanylyl imidodiphosphate. Cholera toxin stereotaxically injected into rat striatum increased the number of binding sites, and no furthermore » increase was noted following the subsequent addition of guanyl nucleotide. High-affinity forskolin binding sites in non-dopamine-rich brain areas (hippocampus and cerebullum) were modulated in a qualitatively different manner by guanyl nucleotides. In these areas the number of binding sites was significantly reduced by the addition of guanyl nucleotide. These results suggest that forskolin may have a potential role in identifying different functional/structural guanine nucleotide-binding proteins.« less

Characteristics and antimicrobial activity of copper-based materials

NASA Astrophysics Data System (ADS)

Li, Bowen

In this study, copper vermiculite was synthesized, and the characteristics, antimicrobial effects, and chemical stability of copper vermiculite were investigated. Two types of copper vermiculite materials, micron-sized copper vermiculite (MCV) and exfoliated copper vermiculite (MECV), are selected for this research. Since most of the functional fillers used in industry products, such as plastics, paints, rubbers, papers, and textiles prefer micron-scaled particles, micron-sized copper vermiculite was prepared by jet-milling vermiculite. Meanwhile, since the exfoliated vermiculite has very unique properties, such as high porosity, specific surface area, high aspect ratio of laminates, and low density, and has been extensively utilized as a functional additives, exfoliated copper vermiculite also was synthesized and investigated. The antibacterial efficiency of copper vermiculite was qualitatively evaluated by the diffusion methods (both liquid diffusion and solid diffusion) against the most common pathogenic species: Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Klebsiella pneumoniae (K. pneumoniae). The result showed that the release velocity of copper from copper vermiculite is very slow. However, copper vermiculite clearly has excellent antibacterial efficiency to S. aureus, K. pneumoniae and E. coli. The strongest antibacterial ability of copper vermiculite is its action on S. aureus. The antibacterial efficiency of copper vermiculite was also quantitatively evaluated by determining the reduction rate (death rate) of E. coli versus various levels of copper vermiculite. 10 ppm of copper vermiculite in solution is sufficient to reduce the cell population of E. coli, while the untreated vermiculite had no antibacterial activity. The slow release of copper revealed that the antimicrobial effect of copper vermiculite was due to the strong interactions between copper ions and bacteria cells. Exfoliated copper vermiculite has even stronger antibacterial activity than copper vermiculite against E. coli. With 200 ppm exfoliated copper vermiculite in bacteria suspension (4.68 ppm of metal copper), the reduction of viable bacteria are 99.8% at 1 hour, and >99.9% at 2 hours. With 10 ppm exfoliated copper vermiculite in bacteria dilution (0.234 ppm of copper atoms), the reduction of viable E. coli reached 98.7% at 1 hour, and >95.6% at 2 hours. Molds have the potential to cause health problems, such as allergic reactions, irritations, and mycotoxins, and damage to buildings, historic relics, properties, etc. Since copper has better antifungal property, an initial antifungal activity of copper vermiculite was evaluated in this study. Fat-free milk was used to develop molds in the test samples by saturated samples. Incubated at 36°C for 48 hours, all of the surfaces of untreated control samples, including micron-sized vermiculite, exfoliated vermiculite, bentonite, and kaolin, have been covered by thick mold layers. However, there were no mold showed on copper vermiculite and exfoliated copper vermiculite. Even after the incubation was lasted for 10 days, copper vermiculite and exfoliated copper vermiculite did not show any mold on the surface. These results exhibited copper vermiculite has excellent antifungal activities against mold. Stability of copper ions in copper vermiculite was measured by aqueous leaching process. Copper vermiculite and exfoliated copper vermiculite were put into distilled water in a ratio of 2.0g/100ml, and then implemented leaching processes by continuously shaking (leaching) and statically storing (soaking) for desired periods of time, respectively. According to the analytic result by inductively coupled plasma spectroscopy (ICP), the major metals released were copper, magnesium, iron, silicon, and aluminum. The release rate of copper depends on the environmental conditions. Under the dynamic leaching condition, all the major elements had shown linear leaching rates, and slowly increases along with the leaching time. Copper concentration in 1 hour leached solutions had sufficient concentration to inhibit E. coli in aqueous solution. Lasting for 1 month, 1 gram of copper vermiculite only released 185mug of copper. At this velocity, 11.5 years are required to completely exhaust the copper atoms from copper vermiculite. A soaking process provided a lower release rate than leaching process. Comparably, exfoliated copper vermiculite had lower copper concentration, stronger antimicrobial effect, but faster release rate than copper vermiculite, due to their different structure characteristics. (Abstract shortened by UMI.)

Effects of aluminum and copper chill on mechanical properties and microstructures of Cu-Zn-Al alloys with sand casting

NASA Astrophysics Data System (ADS)

Ardhyananta, Hosta; Wibisono, Alvian Toto; Ramadhani, Mavindra; Widyastuti, Farid, Muhammad; Gumilang, Muhammad Shena

2018-04-01

Cu-Zn-Al alloy is one type of brass, which has high strength and high corrosion resistant. It has been applied on ship propellers and marine equipment. In this research, the addition of aluminum (Al) with variation of 1, 2, 3, 4% aluminum to know the effect on mechanical properties and micro structure at casting process using a copper chill and without copper chill. This alloy is melted using furnace in 1100°C without holding. Then, the molten metal is poured into the mold with copper chill and without copper chill. The speciment of Cu-Zn-Al alloy were chracterized by using Optical Emission Spectroscopy (OES), Metallography Test, X-Ray Diffraction (XRD), Hardness Test of Rockwell B and Charpy Impact Test. The result is the addition of aluminum and the use of copper chill on the molds can reduce the grain size, increases the value of hardness and impact.

Estimating Dermal Transfer of Copper Particles from the ...

EPA Pesticide Factsheets

Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1 year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5 mg m-2) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1 month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was

Design and physical features of inductive coaxial copper vapor lasers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batenin, V. M.; Kazaryan, M. A.; Karpukhin, V. T.

A physical model of a copper vapor laser pumped by a pulse-periodic inductive (electrodeless) discharge is considered. The feasibility of efficient laser pumping by an inductive discharge and reaching high output parameters comparable to those of conventional copper vapor lasers pumped by a longitudinal electrode discharge is demonstrated. The design and physical features of an inductive copper vapor laser with an annular working volume are discussed.

Casting copper to tungsten for high power arc lamp cathodes

NASA Technical Reports Server (NTRS)

Will, H. A.

1973-01-01

A method for making 400-kW arc lamp cathodes is described. The cathodes are made by casting a 1.75-in. diameter copper body onto a thoriated tungsten insert. The addition of 0.5-percent nickel to the copper prevents voids from forming at the copper-tungsten interface. Cathodes made by this process have withstood more than 110 hours of operation in a 400-kW arc lamp.

The Chemistry of Ultra-Radiopure Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miley, Harry S.; Aalseth, Craig E.; Day, Anthony R.

Ultra-pure materials are needed for the construction of the next generation of ultra-low level radiation detectors. These detectors are used for environmental research as well as rare nuclear decay experiments, e.g. probing the effective mass and character of the neutrino. Unfortunately, radioactive isotopes are found in most construction materials, either primordial isotopes, activation/spallation products from cosmic-ray exposure, or surface deposition of dust or radon progeny. Copper is an ideal candidate material for these applications. High-purity copper is commercially available and, when even greater radiopurity is needed, additional electrochemical purification can be combined with the final construction step, resulting in “electroformed”more » copper of extreme purity. Copper also offers desirable thermal, mechanical, and electrical properties. To bridge the gap between commercially-available high purity copper and the most stringent requirements of next-generation low-background experiments, a method of additional chemical purification is being developed based on well-known copper electrochemistry. This method is complemented with the co-development of surface cleaning techniques and more sensitive assay for both surface and bulk contamination. Developments in the electroplating of copper, surface cleaning, assay of U and Th in the bulk copper, and residual surface contamination will be discussed relative to goals of less than 1 microBq/kg Th.« less

SELMAP - SELEX affinity landscape MAPping of transcription factor binding sites using integrated microfluidics

PubMed Central

Chen, Dana; Orenstein, Yaron; Golodnitsky, Rada; Pellach, Michal; Avrahami, Dorit; Wachtel, Chaim; Ovadia-Shochat, Avital; Shir-Shapira, Hila; Kedmi, Adi; Juven-Gershon, Tamar; Shamir, Ron; Gerber, Doron

2016-01-01

Transcription factors (TFs) alter gene expression in response to changes in the environment through sequence-specific interactions with the DNA. These interactions are best portrayed as a landscape of TF binding affinities. Current methods to study sequence-specific binding preferences suffer from limited dynamic range, sequence bias, lack of specificity and limited throughput. We have developed a microfluidic-based device for SELEX Affinity Landscape MAPping (SELMAP) of TF binding, which allows high-throughput measurement of 16 proteins in parallel. We used it to measure the relative affinities of Pho4, AtERF2 and Btd full-length proteins to millions of different DNA binding sites, and detected both high and low-affinity interactions in equilibrium conditions, generating a comprehensive landscape of the relative TF affinities to all possible DNA 6-mers, and even DNA10-mers with increased sequencing depth. Low quantities of both the TFs and DNA oligomers were sufficient for obtaining high-quality results, significantly reducing experimental costs. SELMAP allows in-depth screening of hundreds of TFs, and provides a means for better understanding of the regulatory processes that govern gene expression. PMID:27628341

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis.

PubMed

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

PubMed Central

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration. PMID:23986700

High-temperature sorbent method for removal of sulfur-containing gases from gaseous mixtures

DOEpatents

Young, J.E.; Jalan, V.M.

1982-07-07

A copper oxide-zinc oxide mixture is used as a sorbent for removing hydrogen sulfide and other sulfur containing gases at high temperatures from a gaseous fuel mixture. This high-temperature sorbent is especially useful for preparing fuel gases for high temperature fuel cells. The copper oxide is initially reduced in a preconditioning step to elemental copper and is present in a highly dispersed state throughout the zinc oxide which serves as a support as well as adding to the sulfur sorbtion capacity. The spent sorbent is regenerated by high-temperature treatment with an air fuel, air steam mixture followed by hydrogen reduction to remove and recover the sulfur.

High-temperature sorbent method for removal of sulfur containing gases from gaseous mixtures

DOEpatents

Young, J.E.; Jalan, V.M.

1984-06-19

A copper oxide-zinc oxide mixture is used as a sorbent for removing hydrogen sulfide and other sulfur containing gases at high temperatures from a gaseous fuel mixture. This high-temperature sorbent is especially useful for preparing fuel gases for high temperature fuel cells. The copper oxide is initially reduced in a preconditioning step to elemental copper and is present in a highly dispersed state throughout the zinc oxide which serves as a support as well as adding to the sulfur sorption capacity. The spent sorbent is regenerated by high-temperature treatment with an air fuel, air steam mixture followed by hydrogen reduction to remove and recover the sulfur.

High-temperature sorbent method for removal of sulfur containing gases from gaseous mixtures

DOEpatents

Young, John E.; Jalan, Vinod M.

1984-01-01

A copper oxide-zinc oxide mixture is used as a sorbent for removing hydrogen sulfide and other sulfur containing gases at high temperatures from a gaseous fuel mixture. This high-temperature sorbent is especially useful for preparing fuel gases for high temperature fuel cells. The copper oxide is initially reduced in a preconditioning step to elemental copper and is present in a highly dispersed state throughout the zinc oxide which serves as a support as well as adding to the sulfur sorption capacity. The spent sorbent is regenerated by high-temperature treatment with an air fuel, air steam mixture followed by hydrogen reduction to remove and recover the sulfur.

Selective ion exchange governed by the Irving-Williams series in K2Zn3[Fe(CN)6]2 nanoparticles: toward a designer prodrug for Wilson's disease.

PubMed

Kandanapitiye, Murthi S; Wang, Fan Jennifer; Valley, Benjamin; Gunathilake, Chamila; Jaroniec, Mietek; Huang, Songping D

2015-02-16

The principle of the Irving-Williams series is applied to the design of a novel prodrug based on K2Zn3[Fe(CN)6]2 nanoparticles (ZnPB NPs) for Wilson's disease (WD), a rare but fatal genetic disorder characterized by the accumulation of excess copper in the liver and other vital organs. The predetermined ion-exchange reaction rather than chelation between ZnPB NPs and copper ions leads to high selectivity of such NPs for copper in the presence of the other endogenous metal ions. Furthermore, ZnPB NPs are highly water-dispersible and noncytotoxic and can be readily internalized by cells to target intracellular copper ions for selective copper detoxification, suggesting their potential application as a new-generation treatment for WD.

Towards an all-copper redox flow battery based on a copper-containing ionic liquid.

PubMed

Schaltin, Stijn; Li, Yun; Brooks, Neil R; Sniekers, Jeroen; Vankelecom, Ivo F J; Binnemans, Koen; Fransaer, Jan

2016-01-07

The first redox flow battery (RFB), based on the all-copper liquid metal salt [Cu(MeCN)4][Tf2N], is presented. Liquid metal salts (LMS) are a new type of ionic liquid that functions both as solvent and electrolyte. Non-aqueous electrolytes have advantages over water-based solutions, such as a larger electrochemical window and large thermal stability. The proof-of-concept is given that LMSs can be used as the electrolyte in RFBs. The main advantage of [Cu(MeCN)4][Tf2N] is the high copper concentration, and thus high charge and energy densities of 300 kC l(-1) and 75 W h l(-1) respectively, since the copper(i) ions form an integral part of the electrolyte. A Coulombic efficiency up to 85% could be reached.

Cover crops influence soil microorganisms and phytoextraction of copper from a moderately contaminated vineyard.

PubMed

Mackie, K A; Schmidt, H P; Müller, T; Kandeler, E

2014-12-01

We investigated the ability of summer (Avena sativa [oat], Trifolium incarnatum [crimson clover], Chenopodium [goosefoot]) and winter (Vicia villosa [hairy vetch], Secale Cereale L. [Rye], Brassica napus L. partim [rape]) cover crops, including a mixed species treatment, to extract copper from an organic vineyard soil in situ and the microbial communities that may support it. Clover had the highest copper content (14.3mgCukg(-1) DM). However, it was the amount of total biomass production that determined which species was most effective at overall copper removal per hectare. The winter crop rye produced significantly higher amounts of biomass (3532kgDMha(-1)) and, therefore, removed significantly higher amounts of copper (14,920mgCuha(-1)), despite less accumulation of copper in plant shoots. The maximum annual removal rate, a summation of best performing summer and winter crops, would be 0.033kgCuha(-1)y(-1). Due to this low annual extraction efficiency, which is less than the 6kgCuha(-1)y(-1) permitted for application, phytoextraction cannot be recommended as a general method of copper extraction from vineyards. Copper concentration did not influence aboveground or belowground properties, as indicated by sampling at two distances from the grapevine row with different soil copper concentrations. Soil microorganisms may have become tolerant to the copper levels at this site. Microbial biomass and soil enzyme activities (arylsulfatase and phosphatase) were instead driven by seasonal fluxes of resource pools. Gram+ bacteria were associated with high soil moisture, while fungi seemed to be driven by extractable carbon, which was linked to high plant biomass. There was no microbial group associated with the increased phytoextraction of copper. Moreover, treatment did not influence the abundance, activity or community structure of soil microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

The influence of salinity on copper accumulation and its toxic effects in estuarine animals with differing osmoregulatory strategies.

PubMed

Lee, Jacqueline A; Marsden, Islay D; Glover, Chris N

2010-08-01

Copper is an important ionoregulatory toxicant in freshwater, but its effects in marine and brackish water systems are less well characterised. The effect of salinity on short-term copper accumulation and sublethal toxicity in two estuarine animals was investigated. The osmoregulating crab Hemigrapsus crenulatus accumulated copper in a concentration-dependent, but salinity-independent manner. Branchial copper accumulation correlated positively with branchial sodium accumulation. Sublethal effects of copper were most prevalent in 125% seawater, with a significant increase in haemolymph chloride noted after 96h at exposure levels of 510 microg Cu(II) L(-1). The osmoconforming gastropod, Scutus breviculus, was highly sensitive to copper exposure, a characteristic recognised previously in related species. Toxicity, as determined by a behavioural index, was present at all salinities and was positively correlated with branchial copper accumulation. At 100% seawater, increased branchial sodium accumulation, decreased haemolymph chloride and decreased haemolymph osmolarity were observed after 48h exposure to 221 microg Cu(II) L(-1), suggesting a mechanism of toxicity related to ionoregulation. However, these effects were likely secondary to a general effect on gill barrier function, and possibly mediated by mucus secretion. Significant impacts of copper on haemocyanin were also noted in both animals, highlighting a potentially novel mechanism of copper toxicity to animals utilising this respiratory pigment. Overall these findings indicate that physiology, as opposed to water chemistry, exerts the greatest influence over copper toxicity. An understanding of the physiological limits of marine and estuarine organisms may be critical for calibration of predictive models of metal toxicity in waters of high and fluctuating salinities. Copyright 2010 Elsevier B.V. All rights reserved.

Infinite-range Heisenberg model and high-temperature superconductivity

NASA Astrophysics Data System (ADS)

Tahir-Kheli, Jamil; Goddard, William A., III

1993-11-01

A strongly coupled variational wave function, the doublet spin-projected Néel state (DSPN), is proposed for oxygen holes in three-band models of high-temperature superconductors. This wave function has the three-spin system of the oxygen hole plus the two neighboring copper atoms coupled in a spin-1/2 doublet. The copper spins in the neighborhood of a hole are in an eigenstate of the infinite-range Heisenberg antiferromagnet (SPN state). The doublet three-spin magnetic polaron or hopping polaron (HP) is stabilized by the hopping terms tσ and tτ, rather than by the copper-oxygen antiferromagnetic coupling Jpd. Although, the HP has a large projection onto the Emery (Dg) polaron, a non-negligible amount of doublet-u (Du) character is required for optimal hopping stabilization. This is due to Jdd, the copper-copper antiferromagnetic coupling. For the copper spins near an oxygen hole, the copper-copper antiferromagnetic coupling can be considered to be almost infinite ranged, since the copper-spin-correlation length in the superconducting phase (0.06-0.25 holes per in-plane copper) is approximately equal to the mean separation of the holes (between 2 and 4 lattice spacings). The general DSPN wave function is constructed for the motion of a single quasiparticle in an antiferromagnetic background. The SPN state allows simple calculations of various couplings of the oxygen hole with the copper spins. The energy minimum is found at symmetry (π/2,π/2) and the bandwidth scales with Jdd. These results are in agreement with exact computations on a lattice. The coupling of the quasiparticles leads to an attraction of holes and its magnitude is estimated.

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein in vitro

PubMed Central

Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-01-01

SUMMARY High-density lipoproteins (HDL) prevent atherosclerosis by removing cholesterol from macrophages and by exerting anti-oxidant and anti-inflammatory effects. Oxidation is thought to impair HDL functions, yet certain oxidative modifications may be advantageous; thus, mild oxidation reportedly enhances cell cholesterol uptake by HDL whereas extensive oxidation impairs it. To elucidate the underlying energetic and structural basis, we analyzed the effects of copper and hypochlorite (that preferentially oxidize lipids and proteins, respectively) on thermal stability of plasma spherical HDL. Circular dichroism, light scattering, calorimetry, gel electrophoresis and electron microscopy showed that mild oxidation destabilizes HDL and accelerates protein dissociation and lipoprotein fusion, while extensive oxidation inhibits these reactions; this inhibition correlates with massive protein cross-linking and lipolysis. We propose that mild oxidation lowers kinetic barriers for HDL remodeling due to diminished apolipoprotein affinity for lipids resulting from oxidation of methionine and aromatic residues in apolipoproteins A-I and A-II followed by protein cross-linking into dimers and/or trimers. In contrast, advanced oxidation inhibits protein dissociation and HDL fusion due to lipid re-distribution from core to surface upon lipolysis and to massive protein cross-linking. Our results help reconcile the apparent controversy in the studies of oxidized HDL and suggest that mild oxidation may benefit HDL functions. PMID:18190928

Sorption of Cu and Zn in low organic matter-soils as influenced by soil properties and by the degree of soil weathering.

PubMed

Antoniadis, V; Golia, E E

2015-11-01

Copper and Zn sorption and desorption, among other factors, depend on soil pH, but in soils with different degree of weathering the role of other soil properties (e.g., oxides content and the level of their crystallinity) has not been thoroughly examined. We conducted batch sorption and desorption tests using 21 low-organic C soils that belonged to the soil orders of Entisols, newly developed soils, Inceptisols, and Alfisols, the most weathered soils. Zinc sorption was lower than that of Cu, and its desorption faster, confirming that it is a highly mobile metal. Alfisols had the weaker affinity for metals, due to the lower soil pH typical of this soil order, but also due to the low reactivity colloids they contained. Correlation analyses showed that Fe oxides in Alfisols increased metal release from soils, while they decreased metal desorption from Entisols. We conclude that in low organic matter-content soils, where the protective role of organic colloids is not to be expected, high soil pH alone is not sufficient to protect against metal contamination, but the degree of soil weathering is also important, due to the dominant role of other mineral phases (here, Fe oxides). Copyright © 2015 Elsevier Ltd. All rights reserved.

IS COPPER REQUIRED FOR EASTERN OYSTER SETTING AND METAMORPHOSIS?

EPA Science Inventory

Recent field research with eastern oysters demonstrated higher defense activities, including hemocyte numbers, locomotion and bactericidal ability, associated with locations exhibiting relatively high contamination. Copper and zinc, found in high concentrations in tissues of oyst...

The copper intrauterine device for emergency contraception: an opportunity to provide the optimal emergency contraception method and transition to highly effective contraception.

PubMed

Dermish, Amna I; Turok, David K

2013-07-01

Worldwide, 40% of all pregnancies are unintended. Widespread, over-the-counter availability of oral emergency contraception (EC) has not reduced unintended pregnancy rates. The EC visit presents an opportunity to initiate a highly effective method of contraception in a population at high risk of unintended pregnancy who are actively seeking to avoid pregnancy. The copper intrauterine device (IUD), the most effective method of EC, continues to provide contraception as effective as sterilization for up to 12 years, and it should be offered as the first-line method of EC wherever possible. Increased demand for and supply of the copper IUD for EC may have an important role in reducing rates of unintended pregnancy. The EC visit should include access to the copper IUD as optimal care but should ideally include access to all highly effective methods of contraception.

Composite material having high thermal conductivity and process for fabricating same

DOEpatents

Colella, N.J.; Davidson, H.L.; Kerns, J.A.; Makowiecki, D.M.

1998-07-21

A process is disclosed for fabricating a composite material such as that having high thermal conductivity and having specific application as a heat sink or heat spreader for high density integrated circuits. The composite material produced by this process has a thermal conductivity between that of diamond and copper, and basically consists of coated diamond particles dispersed in a high conductivity metal, such as copper. The composite material can be fabricated in small or relatively large sizes using inexpensive materials. The process basically consists, for example, of sputter coating diamond powder with several elements, including a carbide forming element and a brazeable material, compacting them into a porous body, and infiltrating the porous body with a suitable braze material, such as copper-silver alloy, thereby producing a dense diamond-copper composite material with a thermal conductivity comparable to synthetic diamond films at a fraction of the cost. 7 figs.

An evaluation of a lathe-cut high-copper amalgam alloy.

PubMed

Knibbs, P J; Plant, C G; Shovelton, D S; Jones, P A

1987-09-01

Modification of an amalgam alloy may give rise to improved physical properties. The physical properties of a newly formulated, single-composition lathe-cut amalgam alloy were studied and found to be superior to those of a conventional lathe-cut amalgam alloy. However, such modification in formulation may result in changes in the clinical handling properties of the material. The high-copper amalgam alloy was assessed by a panel of general practitioners who found that the general handling properties of the material were similar to those of conventional lathe-cut amalgam alloys. The longer term performance of the high-copper alloy was assessed by means of a blind, controlled clinical trial carried out by two operators. A 1-year assessment of the resulting restorations and tooth replicas could not distinguish between the high-copper alloy and a conventional alloy. The two alloys had both given good clinical results.

Process for fabricating composite material having high thermal conductivity

DOEpatents

Colella, Nicholas J.; Davidson, Howard L.; Kerns, John A.; Makowiecki, Daniel M.

2001-01-01

A process for fabricating a composite material such as that having high thermal conductivity and having specific application as a heat sink or heat spreader for high density integrated circuits. The composite material produced by this process has a thermal conductivity between that of diamond and copper, and basically consists of coated diamond particles dispersed in a high conductivity metal, such as copper. The composite material can be fabricated in small or relatively large sizes using inexpensive materials. The process basically consists, for example, of sputter coating diamond powder with several elements, including a carbide forming element and a brazeable material, compacting them into a porous body, and infiltrating the porous body with a suitable braze material, such as copper-silver alloy, thereby producing a dense diamond-copper composite material with a thermal conductivity comparable to synthetic diamond films at a fraction of the cost.

Composite material having high thermal conductivity and process for fabricating same

DOEpatents

Colella, Nicholas J.; Davidson, Howard L.; Kerns, John A.; Makowiecki, Daniel M.

1998-01-01

A process for fabricating a composite material such as that having high thermal conductivity and having specific application as a heat sink or heat spreader for high density integrated circuits. The composite material produced by this process has a thermal conductivity between that of diamond and copper, and basically consists of coated diamond particles dispersed in a high conductivity metal, such as copper. The composite material can be fabricated in small or relatively large sizes using inexpensive materials. The process basically consists, for example, of sputter coating diamond powder with several elements, including a carbide forming element and a brazeable material, compacting them into a porous body, and infiltrating the porous body with a suitable braze material, such as copper-silver alloy, thereby producing a dense diamond-copper composite material with a thermal conductivity comparable to synthetic diamond films at a fraction of the cost.

Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sloan, J.W.

1984-01-01

These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) havemore » been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.« less

SOLVING A COPPER CORROSION PROBLEM WITH ORTHOPHOSPHATE: INDIAN HILL, OHIO CASE STUDY

EPA Science Inventory

Many small and medium-sized water systems have troublt complying with the copper Action Level (of the Lead and Copper Rule), sometimes concurrently with meeting the lead Action level. The problem is especially troubling and widespread with ground water supplies having high alkali...

A molecular recognizing system of serotonin in rat fetal axonal growth cones: uptake and high affinity binding.

PubMed

Mercado, R; Hernández, J

1992-09-18

Axonal growth cone particles (AGCP) isolated from prenatal and postnatal rat brain had different high-affinity 5-HT uptake characteristics. In postnatal AGCP the uptake behaves as in the adult rat brain, while in the prenatal AGCP the uptake characteristics seem to be in a transitional stage. Also in prenatal AGCP we observed specific, high-affinity 5-HT binding sites. These results support the idea of an important role for 5-HT during axogenesis.

Synthesis and superconductivity of highly underdoped HgBa2CuO4+δ

NASA Astrophysics Data System (ADS)

Edwards, P. P.; Gameson, I.; Fletcher, A.; Peacock, G. B.

1998-05-01

The highest transition temperature superconductors are found within the complex homologous series HgBa2Can-1CunO2n+2+δ (n=1-7), with the third member, HgBa2Ca2Cu3O8+δ possessing the record-high transition temperature (Tc) of 135 K at room pressure. The first member of this family, HgBa2CuO4+δ having a Tc of up to 97 K, displays the highest transition temperature for any analogous compounds with a single copper-layer. The chemical reaction for the formation of this material is intrinsically complex due to the natural high volatility of mercury-bearing compounds; chemical synthesis has been postulated to proceed via a solid-vapour reaction. With this in mind, we have developed a mixed solid/vapour phase synthesis for HgBa2CuO4+δ using what one might term a `remote' source of mercury, in this case elemental Hg itself. Interestingly, because of the zero oxidation state of elemental mercury in the reagent mixture, the synthesis reaction proceeds under reducing conditions. By this route, a highly underdoped state (Tc<=35 K) of the superconducting phase HgBa2CuO4+δ is readily obtained. This level of underdoping is extremely difficult to achieve by more conventional synthetic routes. We comment on the unusually high oxygen affinity of the resulting underdoped compound, in relation to other cuprate superconductors, and the implied mobility of oxygen defects within the crystal structure.

Copper pollution decreases the resistance of soil microbial community to subsequent dry-rewetting disturbance.

PubMed

Li, Jing; Wang, Jun-Tao; Hu, Hang-Wei; Ma, Yi-Bing; Zhang, Li-Mei; He, Ji-Zheng

2016-01-01

Dry-rewetting (DW) disturbance frequently occurs in soils due to rainfall and irrigation, and the frequency of DW cycles might exert significant influences on soil microbial communities and their mediated functions. However, how microorganisms respond to DW alternations in soils with a history of heavy metal pollution remains largely unknown. Here, soil laboratory microcosms were constructed to explore the impacts of ten DW cycles on the soil microbial communities in two contrasting soils (fluvo-aquic soil and red soil) under three copper concentrations (zero, medium and high). Results showed that the fluctuations of substrate induced respiration (SIR) decreased with repeated cycles of DW alternation. Furthermore, the resistance values of substrate induced respiration (RS-SIR) were highest in non-copper-stressed (zero) soils. Structural equation model (SEM) analysis ascertained that the shifts of bacterial communities determined the changes of RS-SIR in both soils. The rate of bacterial community variance was significantly lower in non-copper-stressed soil compared to the other two copper-stressed (medium and high) soils, which might lead to the higher RS-SIR in the fluvo-aquic soil. As for the red soil, the substantial increase of the dominant group WPS-2 after DW disturbance might result in the low RS-SIR in the high copper-stressed soil. Moreover, in both soils, the bacterial diversity was highest in non-copper-stressed soils. Our results revealed that initial copper stress could decrease the resistance of soil microbial community structure and function to subsequent DW disturbance. Copyright © 2015. Published by Elsevier B.V.

Surfactant-free Colloidal Particles with Specific Binding Affinity

PubMed Central

2017-01-01

Colloidal particles with specific binding affinity are essential for in vivo and in vitro biosensing, targeted drug delivery, and micrometer-scale self-assembly. Key to these techniques are surface functionalizations that provide high affinities to specific target molecules. For stabilization in physiological environments, current particle coating methods rely on adsorbed surfactants. However, spontaneous desorption of these surfactants typically has an undesirable influence on lipid membranes. To address this issue and create particles for targeting molecules in lipid membranes, we present here a surfactant-free coating method that combines high binding affinity with stability at physiological conditions. After activating charge-stabilized polystyrene microparticles with EDC/Sulfo-NHS, we first coat the particles with a specific protein and subsequently covalently attach a dense layer of poly(ethyelene) glycol. This polymer layer provides colloidal stability at physiological conditions as well as antiadhesive properties, while the protein coating provides the specific affinity to the targeted molecule. We show that NeutrAvidin-functionalized particles bind specifically to biotinylated membranes and that Concanavalin A-functionalized particles bind specifically to the glycocortex of Dictyostelium discoideum cells. The affinity of the particles changes with protein density, which can be tuned during the coating procedure. The generic and surfactant-free coating method reported here transfers the high affinity and specificity of a protein onto colloidal polystyrene microparticles. PMID:28847149

Copper localization, elemental content, and thallus colour in the copper hyperaccumulator lichen Lecanora sierrae from California

USGS Publications Warehouse

Purvis, O.W.; Bennett, J.P.; Spratt, J.

2011-01-01

An unusual dark blue-green lichen, Lecanora sierrae, was discovered over 30 years ago by Czehura near copper mines in the Lights Creek District, Plumas County, Northern California. Using atomic absorption spectroscopy, Czehura found that dark green lichen samples from Warren Canyon contained 4% Cu in ash and suggested that its colour was due to copper accumulation in the cortex. The present study addressed the hypothesis that the green colour in similar material we sampled from Warren Canyon in 2008, is caused by copper localization in the thallus. Optical microscopy and electron microprobe analysis of specimens of L. sierrae confirmed that copper localization took place in the cortex. Elemental analyses of L. sierrae and three other species from the same localities showed high enrichments of copper and selenium, suggesting that copper selenates or selenites might occur in these lichens and be responsible for the unusual colour. Copyright ?? 2011 British Lichen Society.

Copper localization, elemental content, and thallus colour in the copper hyperaccumulator lichen Lecanora sierra from California

USGS Publications Warehouse

Purvis, O.W.; Bennett, J.P.; Spratt, J.

2011-01-01

An unusual dark blue-green lichen, Lecanora sierrae, was discovered over 30 years ago by Czehura near copper mines in the Lights Creek District, Plumas County, Northern California. Using atomic absorption spectroscopy, Czehura found that dark green lichen samples from Warren Canyon contained 4% Cu in ash and suggested that its colour was due to copper accumulation in the cortex. The present study addressed the hypothesis that the green colour in similar material we sampled from Warren Canyon in 2008, is caused by copper localization in the thallus. Optical microscopy and electron microprobe analysis of specimens of L. sierrae confirmed that copper localization took place in the cortex. Elemental analyses of L. sierrae and three other species from the same localities showed high enrichments of copper and selenium, suggesting that copper selenates or selenites might occur in these lichens and be responsible for the unusual colour.

Effect of copper treatment on the composition and function of the bacterial community in the sponge Haliclona cymaeformis.

PubMed

Tian, Ren-Mao; Wang, Yong; Bougouffa, Salim; Gao, Zhao-Ming; Cai, Lin; Zhang, Wei-Peng; Bajic, Vladimir; Qian, Pei-Yuan

2014-11-04

Marine sponges are the most primitive metazoan and host symbiotic microorganisms. They are crucial components of the marine ecological system and play an essential role in pelagic processes. Copper pollution is currently a widespread problem and poses a threat to marine organisms. Here, we examined the effects of copper treatment on the composition of the sponge-associated bacterial community and the genetic features that facilitate the survival of enriched bacteria under copper stress. The 16S rRNA gene sequencing results showed that the sponge Haliclona cymaeformis harbored symbiotic sulfur-oxidizing Ectothiorhodospiraceae and photosynthetic Cyanobacteria as dominant species. However, these autotrophic bacteria decreased substantially after treatment with a high copper concentration, which enriched for a heterotrophic-bacterium-dominated community. Metagenomic comparison revealed a varied profile of functional genes and enriched functions, including bacterial motility and chemotaxis, extracellular polysaccharide and capsule synthesis, virulence-associated genes, and genes involved in cell signaling and regulation, suggesting short-period mechanisms of the enriched bacterial community for surviving copper stress in the microenvironment of the sponge. Microscopic observation and comparison revealed dynamic bacterial aggregation within the matrix and lysis of sponge cells. The bacteriophage community was also enriched, and the complete genome of a dominant phage was determined, implying that a lytic phage cycle was stimulated by the high copper concentration. This study demonstrated a copper-induced shift in the composition of functional genes of the sponge-associated bacterial community, revealing the selective effect of copper treatment on the functions of the bacterial community in the microenvironment of the sponge. This study determined the bacterial community structure of the common sponge Haliclona cymaeformis and examined the effect of copper treatment on the community structure and functional gene composition, revealing that copper treatment had a selective effect on the functions of the bacterial community in the sponge. These findings suggest that copper pollution has an ecological impact on the sponge symbiont. The analysis showed that the untreated sponges hosted symbiotic autotrophic bacteria as dominant species, and the high-concentration copper treatment enriched for a heterotrophic bacterial community with enrichment for genes important for bacterial motility, supplementary cellular components, signaling and regulation, and virulence. Microscopic observation showed obvious bacterial aggregation and a reduction of sponge cell numbers in treated sponges, which suggested the formation of aggregates to reduce the copper concentration. The enrichment for functions of directional bacterial movement and supplementary cellular components and the formation of bacterial aggregates and phage enrichment are novel findings in sponge studies. Copyright © 2014 Tian et al.

Interaction of Ochratoxin A and Its Thermal Degradation Product 2'R-Ochratoxin A with Human Serum Albumin.

PubMed

Sueck, Franziska; Poór, Miklós; Faisal, Zelma; Gertzen, Christoph G W; Cramer, Benedikt; Lemli, Beáta; Kunsági-Máté, Sándor; Gohlke, Holger; Humpf, Hans-Ulrich

2018-06-22

Ochratoxin A (OTA) is a toxic secondary metabolite produced by several fungal species of the genus Penicillium and Aspergillus . 2′ R -Ochratoxin A (2′ R -OTA) is a thermal isomerization product of OTA formed during food processing at high temperatures. Both compounds are detectable in human blood in concentrations between 0.02 and 0.41 µg/L with 2′ R -OTA being only detectable in the blood of coffee drinkers. Humans have approximately a fifty-fold higher exposure through food consumption to OTA than to 2′ R -OTA. In human blood, however, the differences between the concentrations of the two compounds is, on average, only a factor of two. To understand these unexpectedly high 2′ R -OTA concentrations found in human blood, the affinity of this compound to the most abundant protein in human blood the human serum albumin (HSA) was studied and compared to that of OTA, which has a well-known high binding affinity. Using fluorescence spectroscopy, equilibrium dialysis, circular dichroism (CD), high performance affinity chromatography (HPAC), and molecular modelling experiments, the affinities of OTA and 2′ R -OTA to HSA were determined and compared with each other. For the affinity of HSA towards OTA, a log K of 7.0⁻7.6 was calculated, while for its thermally produced isomer 2′ R -OTA, a lower, but still high, log K of 6.2⁻6.4 was determined. The data of all experiments showed consistently that OTA has a higher affinity to HSA than 2′ R -OTA. Thus, differences in the affinity to HSA cannot explain the relatively high levels of 2′ R -OTA found in human blood samples.

XAFS Study of the Ferro- and Antiferromagnetic Binuclear Copper(II) Complexes of Azomethine Based Tridentate Ligands

NASA Astrophysics Data System (ADS)

Vlasenko, Valery G.; Vasilchenko, Igor S.; Pirog, Irina V.; Shestakova, Tatiana E.; Uraev, Ali I.; Burlov, Anatolii S.; Garnovskii, Alexander D.

2007-02-01

Binuclear copper complexes are known to be models for metalloenzymes containing copper active sites, and some of them are of considerable interest due to their magnetic and charge transfer properties. The reactions of the complex formation of bibasic tridentate heterocyclic imines with copper acetate leads to two types of chelates with mono deprotonated ligands and with totally deprotonated ligands. Cu K-edge EXAFS has been applied to determine the local structure around the metal center in copper(II) azomethine complexes with five tridentate ligands: 1-(salycilideneimino)- or 1-(2-tosylaminobenzilideneimino)-2-amino(oxo, thio)benzimidazoles. It has been found that some of the chelates studied are bridged binuclear copper complexes, and others are mononuclear complexes. The copper-copper interatomic distances in the bridged binuclear copper complexes were found to be 2.85-3.01 Å. Variable temperature magnetic susceptibility data indicate the presence of both ferromagnetic and antiferromagnetic interactions within the dimer, the former is dominating at low temperatures and the latter at high temperatures.

Biogenic copper oxide nanoparticles synthesis using Tabernaemontana divaricate leaf extract and its antibacterial activity against urinary tract pathogen

NASA Astrophysics Data System (ADS)

Sivaraj, Rajeshwari; Rahman, Pattanathu K. S. M.; Rajiv, P.; Salam, Hasna Abdul; Venckatesh, R.

2014-12-01

This investigation explains the biosynthesis and characterization of copper oxide nanoparticles from an Indian medicinal plant by an eco-friendly method. The main objective of this study is to synthesize copper oxide nanoparticles from Tabernaemontana divaricate leaves through a green chemistry approach. Highly stable, spherical copper oxide nanoparticles were synthesized by using 50% concentration of Tabernaemontana leaf extract. Formation of copper oxide nanoparticles have been characterized by UV-Vis absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX) and transmission electron microscopy (TEM) analysis. All the analyses revealed that copper oxide nanoparticles were 48 ± 4 nm in size. Functional groups and chemical composition of copper oxide were also confirmed. Antimicrobial activity of biogenic copper oxide nanoparticles were investigated and maximum zone of inhibition was found in 50 μg/ml copper oxide nanoparticles against urinary tract pathogen (Escherichia coli).

Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers.

PubMed

Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

2013-11-15

Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. To produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (<5% yield). However, they were an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as the background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 μM in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity.

Construction of a high efficiency copper adsorption bacterial system via peptide display and its application on copper dye polluted wastewater.

PubMed

Maruthamuthu, Murali Kannan; Nadarajan, Saravanan Prabhu; Ganesh, Irisappan; Ravikumar, Sambandam; Yun, Hyungdon; Yoo, Ik-Keun; Hong, Soon Ho

2015-11-01

For the construction of an efficient copper waste treatment system, a cell surface display strategy was employed. The copper adsorption ability of recombinant bacterial strains displaying three different copper binding peptides were evaluated in LB Luria-Bertani medium (LB), artificial wastewater, and copper phthalocyanine containing textile dye industry wastewater samples. Structural characteristics of the three peptides were also analyzed by similarity-based structure modeling. The best binding peptide was chosen for the construction of a dimeric peptide display and the adsorption ability of the monomeric and dimeric peptide displayed strains were compared. The dimeric peptide displayed strain showed superior copper adsorption in all three tested conditions (LB, artificial wastewater, and textile dye industry wastewater). When the strains were exposed to copper phthalocyanine dye polluted wastewater, the dimeric peptide display [543.27 µmol/g DCW dry cell weight (DCW)] showed higher adsorption of copper when compared with the monomeric strains (243.53 µmol/g DCW).

Military Jet Fuels, 1944-1987

DTIC Science & Technology

1987-11-01

first high density, synthetic hydrocarbon missile fuel. Developed by the US Navy, RJ-4 was used in the mid-1960s in the ramjet-powered Tales missile...High Density Synthetic Hydrocarbon Type. Grades 7P-9 and JP-10, covers two fuels currently in use in the Air Launched Cruise Missile (ALCM). JP-9...revealed that a significant quantity of copper was in the fuel, carried over from a copper- sweetening process. The copper was chelated by the metal

FAST TRACK COMMUNICATION High rate straining of tantalum and copper

NASA Astrophysics Data System (ADS)

Armstrong, R. W.; Zerilli, F. J.

2010-12-01

High strain rate measurements reported recently for several tantalum and copper crystal/polycrystal materials are shown to follow dislocation mechanics-based constitutive relations, first at lower strain rates, for dislocation velocity control of the imposed plastic deformations and, then at higher rates, transitioning to nano-scale dislocation generation control by twinning or slip. For copper, there is the possibility of added-on slip dislocation displacements to be accounted for from the newly generated dislocations.

A novel recovery method of copper from waste printed circuit boards by supercritical methanol process: Preparation of ultrafine copper materials.

PubMed

Xiu, Fu-Rong; Weng, Huiwei; Qi, Yingying; Yu, Gending; Zhang, Zhigang; Zhang, Fu-Shen; Chen, Mengjun

2017-02-01

In this study, supercritical methanol (SCM) process was successfully used for the preparation of ultrafine copper materials from waste printed circuit boards (PCBs) after nitric acid pretreatment. Waste PCBs were pretreated twice in nitric acid. Sn and Pb were recovered by the first nitric acid pretreatment. The leach liquor with a high concentration of copper ions after the second nitric acid leaching was subjected to SCM process. The mixture of Cu and Cu 2 O with poor uniformity of particle size was formed due to the effect of ferric iron contained in the leach liquor of waste PCBs, while more uniform and spherical Cu particles with high monodispersity and smaller size could be prepared after the removal of Fe. The size of Cu particles increased obviously with the decline of SCM temperature, and particles became highly aggregated when the reaction temperature decreased to 300°C. The size of Cu particles decreased markedly with the decrease of initial concentration of copper ion in the leach liquor of waste PCBs. It is believed that the process developed in this study is simple and practical for the preparation of ultrafine copper materials from waste PCBs with the aim of recycling these waste resources as a high value-added product. Copyright © 2016 Elsevier Ltd. All rights reserved.

Absolute measurement of the Hugoniot and sound velocity of liquid copper at multimegabar pressures

DOE PAGES

McCoy, Chad August; Knudson, Marcus David; Root, Seth

2017-11-13

Measurement of the Hugoniot and sound velocity provides information on the bulk modulus and Grüneisen parameter of a material at extreme conditions. The capability to launch multilayered (copper/aluminum) flyer plates at velocities in excess of 20 km/s with the Sandia Z accelerator has enabled high-precision sound-velocity measurements at previously inaccessible pressures. For these experiments, the sound velocity of the copper flyer must be accurately known in the multi-Mbar regime. Here we describe the development of copper as an absolutely calibrated sound-velocity standard for high-precision measurements at pressures in excess of 400 GPa. Using multilayered flyer plates, we performed absolute measurementsmore » of the Hugoniot and sound velocity of copper for pressures from 500 to 1200 GPa. These measurements enabled the determination of the Grüneisen parameter for dense liquid copper, clearly showing a density dependence above the melt transition. As a result, combined with earlier data at lower pressures, these results constrain the sound velocity as a function of pressure, enabling the use of copper as a Hugoniot and sound-velocity standard for pressures up to 1200 GPa.« less

Absolute measurement of the Hugoniot and sound velocity of liquid copper at multimegabar pressures

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCoy, Chad August; Knudson, Marcus David; Root, Seth

Measurement of the Hugoniot and sound velocity provides information on the bulk modulus and Grüneisen parameter of a material at extreme conditions. The capability to launch multilayered (copper/aluminum) flyer plates at velocities in excess of 20 km/s with the Sandia Z accelerator has enabled high-precision sound-velocity measurements at previously inaccessible pressures. For these experiments, the sound velocity of the copper flyer must be accurately known in the multi-Mbar regime. Here we describe the development of copper as an absolutely calibrated sound-velocity standard for high-precision measurements at pressures in excess of 400 GPa. Using multilayered flyer plates, we performed absolute measurementsmore » of the Hugoniot and sound velocity of copper for pressures from 500 to 1200 GPa. These measurements enabled the determination of the Grüneisen parameter for dense liquid copper, clearly showing a density dependence above the melt transition. As a result, combined with earlier data at lower pressures, these results constrain the sound velocity as a function of pressure, enabling the use of copper as a Hugoniot and sound-velocity standard for pressures up to 1200 GPa.« less

Porphyry copper enrichment linked to excess aluminium in plagioclase

NASA Astrophysics Data System (ADS)

Williamson, B. J.; Herrington, R. J.; Morris, A.

2016-03-01

Porphyry copper deposits provide around 75%, 50% and 20% of world copper, molybdenum and gold, respectively. The deposits are mainly centred on calc-alkaline porphyry magmatic systems in subduction zone settings. Although calc-alkaline magmas are relatively common, large porphyry copper deposits are extremely rare and increasingly difficult to discover. Here, we compile existing geochemical data for magmatic plagioclase, a dominant mineral in calc-alkaline rocks, from fertile (porphyry-associated) and barren magmatic systems worldwide, barren examples having no associated porphyry deposit. We show that plagioclase from fertile systems is distinct in containing `excess’ aluminium. This signature is clearly demonstrated in a case study carried out on plagioclase from the fertile La Paloma and Los Sulfatos copper porphyry systems in Chile. Further, the presence of concentric zones of high excess aluminium suggests its incorporation as a result of magmatic processes. As excess aluminium has been linked to high melt water contents, the concentric zones may record injections of hydrous fluid or fluid-rich melts into the sub-porphyry magma chamber. We propose that excess aluminium may exclude copper from plagioclase, so enriching the remaining melts. Furthermore, this chemical signature can be used as an exploration indicator for copper porphyry deposits.

Assessment of the Bioaccessibility of Micronized Copper Wood on Simulated Stomach Fluid

EPA Pesticide Factsheets

The widespread use of copper-treated lumber has increased the potential for human exposure. Moreover, there is a lack of information on the fate and behavior of copper-treated wood particles following oral ingestion. In this study, the in vitro bioaccessibility of copper from copper-treated wood dust in simulated stomach fluid and DI water was determined. Three copper-treated wood products, liquid alkali copper quaternary and two micronized copper quarternary from different manufacturers, were incubated in the extraction media then fractionated by centrifugation and filtration through 0.45 ?m and 10 kDa filters. The copper concentrations from isolated fractions were measured using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). Total amounts of copper from each wood product were also determined using microwave-assisted acid digestion of dried wood samples and quantification using ICP-OES. The percent in vitro bioaccessible copper was between 83 and 90 % for all treated wood types. However, the percent of copper released in DI water was between 14 and 25 % for all wood products. This data suggests that copper is highly bioaccessible at low pH and may pose a potential human exposure risk upon ingestion. This dataset is associated with the following publication:Santiago-Rodrigues, L., J.L. Griggs, K. Bradham , C. Nelson , T. Luxton , W. Platten , and K. Rogers. Assessment of the bioaccessibility of micronized copper wood in synthetic stomach flu

CNC Machining Of The Complex Copper Electrodes

NASA Astrophysics Data System (ADS)

Popan, Ioan Alexandru; Balc, Nicolae; Popan, Alina

2015-07-01

This paper presents the machining process of the complex copper electrodes. Machining of the complex shapes in copper is difficult because this material is soft and sticky. This research presents the main steps for processing those copper electrodes at a high dimensional accuracy and a good surface quality. Special tooling solutions are required for this machining process and optimal process parameters have been found for the accurate CNC equipment, using smart CAD/CAM software.

Metabolism of ethylbenzene by human liver microsomes and recombinant human cytochrome P450s (CYP).

PubMed

Sams, Craig; Loizou, George D; Cocker, John; Lennard, Martin S

2004-03-07

The enzyme kinetics of the initial hydroxylation of ethylbenzene to form 1-phenylethanol were determined in human liver microsomes. The individual cytochrome P450 (CYP) forms catalysing this reaction were identified using selective inhibitors and recombinant preparations of hepatic CYPs. Production of 1-phenylethanol in hepatic microsomes exhibited biphasic kinetics with a high affinity, low Km, component (mean Km = 8 microM; V(max) = 689 pmol/min/mg protein; n = 6 livers) and a low affinity, high Km, component (Km = 391 microM; V(max) = 3039 pmol/min/mg protein; n = 6). The high-affinity component was inhibited 79%-95% (mean 86%) by diethyldithiocarbamate, and recombinant CYP2E1 was shown to metabolise ethylbenzene with low Km (35 microM), but also low (max) (7 pmol/min/pmol P450), indicating that this isoform catalysed the high-affinity component. Recombinant CYP1A2 and CYP2B6 exhibited high V(max) (88 and 71 pmol/min/pmol P450, respectively) and high Km (502 and 219 microM, respectively), suggesting their involvement in catalysing the low-affinity component. This study has demonstrated that CYP2E1 is the major enzyme responsible for high-affinity side chain hydroxylation of ethylbenzene in human liver microsomes. Activity of this enzyme in the population is highly variable due to induction or inhibition by physiological factors, chemicals in the diet or some pharmaceuticals. This variability can be incorporated into the risk assessment process to improve the setting of occupational exposure limits and guidance values for biological monitoring.

Binding of Copper and Silver to Single-Site Variants of Peptidylglycine Monooxygenase Reveals the Structure and Chemistry of the Individual Metal Centers

PubMed Central

2015-01-01

Peptidylglycine monooxygenase (PHM) catalyzes the final step in the biosynthesis of amidated peptides that serve as important signaling molecules in numerous endocrine pathways. The catalytic mechanism has attracted much attention because of a number of unique attributes, including the presence of a pair of uncoupled copper centers separated by 11 Å (termed CuH and CuM), an unusual Cu(I)SMet interaction at the oxygen binding M-site, and the postulated Cu(II)–superoxo intermediate. Understanding the mechanism requires determining the catalytic roles of the individual copper centers and how they change during catalysis, a task made more difficult by the overlapping spectral signals from each copper center in the wild-type (WT) protein. To aid in this effort, we constructed and characterized two PHM variants that bound metal at only one site. The H242A variant bound copper at the H-center, while the H107AH108A double mutant bound copper at the M-center; both mutants were devoid of catalytic activity. Oxidized Cu(II) forms showed electron paramagnetic resonance and extended X-ray absorption fine structure (EXAFS) spectra consistent with their previously determined Cu(II)His3O and Cu(II)His2O2 ligand sets for the H- and M-centers, respectively. Cu(I) forms, on the other hand, showed unique chemistry. The M-center bound two histidines and a methionine at all pHs, while the H-center was two-coordinate at neutral pH but coordinated a new methionine S ligand at low pH. Fourier transform infrared studies confirmed and extended previous assignments of CO binding and showed unambiguously that the 2092 cm–1 absorbing species observed in the WT and many variant forms is an M-site Cu(I)–CO adduct. Silver binding was also investigated. When H107AH108A and M109I (a WT analogue with both sites intact) were incubated with excess AgNO3, each variant bound a single Ag(I) ion, from which it was inferred that Ag(I) binds selectively at the M-center with little or no affinity for the H-center. EXAFS at the Ag K-edge established a strong degree of similarity between the ligand sets of Cu and Ag bound at the M-center. These studies validate previous spectral assignments and provide new insights into the detailed chemistry of each metal site. PMID:24471980

High-Speed Lateral Flow Strategy for a Fast Biosensing with an Improved Selectivity and Binding Affinity.

PubMed

Cho, Dong Guk; Yoo, Haneul; Lee, Haein; Choi, Yeol Kyo; Lee, Minju; Ahn, Dong June; Hong, Seunghun

2018-05-10

We report a high-speed lateral flow strategy for a fast biosensing with an improved selectivity and binding affinity even under harsh conditions. In this strategy, biosensors were fixed at a location away from the center of a round shape disk, and the disk was rotated to create the lateral flow of a target solution on the biosensors during the sensing measurements. Experimental results using the strategy showed high reaction speeds, high binding affinity, and low nonspecific adsorptions of target molecules to biosensors. Furthermore, binding affinity between target molecules and sensing molecules was enhanced even in harsh conditions such as low pH and low ionic strength conditions. These results show that the strategy can improve the performance of conventional biosensors by generating high-speed lateral flows on a biosensor surface. Therefore, our strategy can be utilized as a simple but powerful tool for versatile bio and medical applications.

Incorporation of copper nanoparticles into paper for point-of-use water purification

PubMed Central

Smith, James A.

2014-01-01

As a cost-effective alternative to silver nanoparticles, we have investigated the use of copper nanoparticles in paper filters for point-of-use water purification. This work reports an environmentally benign method for the direct in situ preparation of copper nanoparticles (CuNPs) in paper by reducing sorbed copper ions with ascorbic acid. Copper nanoparticles were quickly formed in less than 10 minutes and were well distributed on the paper fiber surfaces. Paper sheets were characterized by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, and atomic absorption spectroscopy. Antibacterial activity of the CuNP sheets was assessed for by passing Escherichia coli bacteria suspensions through the papers. The effluent was analyzed for viable bacteria and copper release. The CuNP papers with higher copper content showed a high bacteria reduction of log 8.8 for E. coli. The paper sheets containing copper nanoparticles were effective in inactivating the test bacteria as they passed through the paper. The copper levels released in the effluent water were below the recommended limit for copper in drinking water (1 ppm). PMID:25014431

High affinity ligands from in vitro selection: Complex targets

PubMed Central

Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry

1998-01-01

Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188

Haemoglobin Pierre-Benite--a high affinity variant associated with relative polycythaemia.

PubMed

Beard, M E; Potter, H C; Spearing, R L; Brennan, S O

2001-12-01

This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This mutation is associated with increased oxygen affinity and polycythaemia. No instability was found and there was no charge shift detected by cellulose acetate electrophoresis at pH 8.3. The mutation was however, clearly indicated by electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta chain with a 14 Da decrease in mass. Blood volume studies documented a relative rather than a true polycythaemia and this finding has been reported in at least two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This finding led to delay in diagnosis because high oxygen affinity variants are conventionally considered to cause a true polycythaemia.

Copper slag as a catalyst for mercury oxidation in coal combustion flue gas.

PubMed

Li, Hailong; Zhang, Weilin; Wang, Jun; Yang, Zequn; Li, Liqing; Shih, Kaimin

2018-04-01

Copper slag is a byproduct of the pyrometallurgical smelting of copper concentrate. It was used in this study to catalyze elemental mercury (Hg 0 ) oxidation in simulated coal combustion flue gas. The copper slag exhibited excellent catalytic performance in Hg 0 oxidation at temperatures between 200 °C and 300 °C. At the most optimal temperature of 250 °C, a Hg 0 oxidation efficiency of 93.8% was achieved under simulated coal combustion flue gas with both a high Hg 0 concentration and a high gas hourly space velocity of 128,000 h -1 . Hydrogen chloride (HCl) was the flue gas component responsible for Hg 0 oxidation over the copper slag. The transition metal oxides, including iron oxides and copper oxide in the copper slag, exhibited significant catalytic activities in the surface-mediated oxidation of Hg 0 in the presence of HCl. It is proposed that the Hg 0 oxidation over the copper slag followed the Langmuir-Hinshelwood mechanism whereby reactive chlorine species that originated from HCl reacted with the physically adsorbed Hg 0 to form oxidized mercury. This study demonstrated the possibility of reusing copper slag as a catalyst for Hg 0 oxidation and revealed the mechanisms involved in the process and the key factors in the performance. This knowledge has fundamental importance in simultaneously reducing industrial waste and controlling mercury emissions from coal-fired power plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accumulation and hyperaccumulation of copper in plants

NASA Astrophysics Data System (ADS)

Adam, V.; Trnkova, L.; Huska, D.; Babula, P.; Kizek, R.

2009-04-01

Copper is natural component of our environment. Flow of copper(II) ions in the environment depends on solubility of compounds containing this metal. Mobile ion coming from soil and rocks due to volcanic activity, rains and others are then distributed to water. Bio-availability of copper is substantially lower than its concentration in the aquatic environment. Copper present in the water reacts with other compounds and creates a complex, not available for organisms. The availability of copper varies depending on the environment, but moving around within the range from 5 to 25 % of total copper. Thus copper is stored in the sediments and the rest is transported to the seas and oceans. It is common knowledge that copper is essential element for most living organisms. For this reason this element is actively accumulated in the tissues. The total quantity of copper in soil ranges from 2 to 250 mg / kg, the average concentration is 30 mg / kg. Certain activities related to agriculture (the use of fungicides), possibly with the metallurgical industry and mining, tend to increase the total quantity of copper in the soil. This amount of copper in the soil is a problem particularly for agricultural production of food. The lack of copper causes a decrease in revenue and reduction in quality of production. In Europe, shows the low level of copper in total 18 million hectares of farmland. To remedy this adverse situation is the increasing use of copper fertilizers in agricultural soils. It is known that copper compounds are used in plant protection against various illnesses and pests. Mining of minerals is for the development of human society a key economic activity. An important site where the copper is mined in the Slovakia is nearby Smolníka. Due to long time mining in his area (more than 700 years) there are places with extremely high concentrations of various metals including copper. Besides copper, there are also detected iron, zinc and arsenic. Various plant species have adapted on such stress. The aim of this study is to investigate the behaviour of copper in plants and to assess its potential effect on the surrounding environment. To detect copper in biological samples electrochemical methods were employed particularly differential pulse voltammetry (DPV). Copper gave signals at 0.02 V measured by DPV. The obtained calibration dependence was linear (R2 = 0.995). Further, this method was utilized for determination of copper in real soil samples obtained from previously mentioned heavy-metal-polluted mining area. The content varied within range from tens to hundreds of mg of copper per kg of the soil. Moreover, we focused on investigation of copper influence on seedlings of Norway spruce. The seedlings were treated with copper (0, 0.1, 10 and 100 mM) for four weeks. We observed anatomical-morphological changes and other biochemical parameters in plants. We determined that seedlings synthesized more than 48 % protective thiols (glutathione and phytochelatins) compared to control ones. We investigated copper distribution in plant tissues by diphenylcarbazide staining. We found out that copper is highly accumulated in parenchymal stalk cells. In needles, change in auto-fluorescence of parenchymal cells of mesoderm similarly to endodermis cells. Besides, we analyzed samples of plants from the polluted area (spruce, pin, birch). The data obtained well correlated with previously mentioned. Acknowledgement The work on this experiment was supported by grant: INCHEMBIOL MSM0021622412.

Yeast Starter as a Biotechnological Tool for Reducing Copper Content in Wine

PubMed Central

Capece, Angela; Romaniello, Rossana; Scrano, Laura; Siesto, Gabriella; Romano, Patrizia

2018-01-01

Copper is widely used in agriculture as a traditional fungicide in organic farming to control downy mildew on grapes, consequently it is possible to find this metal during all stages of the vinification process. Low amounts of copper play a key role on the function of key cell enzymes, whereas excess quantities can exert amount-dependent cytotoxicity, resulting in general cellular damage. Nowadays the excessive copper ions in wines is removed by addition of adsorbents, but these additives can influence the sensory characteristics of wine, as well as detrimental to the health of consumers. It is well known that high concentrations of Cu2+ can be toxic to yeasts, inhibiting growth and activity, causing sluggish fermentation and reducing alcohol production. In this study, 47 S. cerevisiae strains were tested for copper tolerance by two different tests, growth on copper added medium and fermentative activity in copper added grape must. The results obtained by the two different tests were comparable and the high strain variability found was used to select four wild strains, possessing this characteristic at the highest (PP1-13 and A20) and the lowest level (MPR2-24 and A13). The selected strains were tested in synthetic and natural grape must fermentation for ability to reduce copper content in wine. The determination of copper content in wines and yeast cells revealed that at the lowest copper residual in wine corresponded the highest content in yeast cells, indicating a strong strain ability to reduce the copper content in wine. This effect was inversely correlated with strain copper resistance and the most powerful strain in copper reduction was the most sensitive strain, MPR2-24. This wild strain was finally tested as starter culture in cellar pilot scale fermentation in comparison to a commercial starter, confirming the behavior exhibited at lab scale. The use of this wild strain to complete the alcoholic fermentation and remove the copper from wine represents a biotechnological sustainable approach, as alternative to the chemical-physical methods, ensuring at the same time a completed alcoholic fermentation and organoleptic quality of wine. PMID:29375502

Specificity and Affinity Quantification of Flexible Recognition from Underlying Energy Landscape Topography

PubMed Central

Chu, Xiakun; Wang, Jin

2014-01-01

Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less) flexibility leads to weaker (stronger) coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition. PMID:25144525

Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.

PubMed

Chu, Xiakun; Wang, Jin

2014-08-01

Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less) flexibility leads to weaker (stronger) coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition.

Guanine nucleotide regulatory protein co-purifies with the D/sub 2/-dopamine receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senogles, S.E.; Caron, M.G.

1986-05-01

The D/sub 2/-dopamine receptor from bovine anterior pituitary was purified approx.1000 fold by affinity chromatography on CMOS-Sepharose. Reconstitution of the affinity-purified receptor into phospholipid vesicles revealed the presence of high and low affinity agonist sites as detected by N-n-propylnorapomorphine (NPA) competition experiments with /sup 3/H-spiperone. High affinity agonist binding could be converted to the low affinity form by guanine nucleotides, indicating the presence of an endogenous guanine nucleotide binding protein (N protein) in the affinity-purified D/sub 2/ receptor preparations. Furthermore, this preparation contained an agonist-sensitive GTPase activity which was stimulated 2-3 fold over basal by 10 ..mu..M NPA. /sup 35/S-GTP..gamma..Smore » binding to these preparations revealed a stoichiometry of 0.4-0.7 mole N protein/mole receptor, suggesting the N protein may be specifically coupled with the purified D/sub 2/-dopamine receptor and not present as a contaminant. Pertussis toxin treatment of the affinity purified receptor preparations prevented high affinity agonist binding, as well as agonist stimulation of the GTPase activity, presumably by inactivating the associated N protein. Pertussis toxin lead to the ADP-ribosylation of a protein of 39-40K on SDS-PAGE. These findings indicate that an endogenous N protein, N/sub i/ or N/sub o/, co-purifies with the D/sub 2/-dopamine receptor which may reflect a precoupling of this receptor with an N protein within the membranes.« less

Molecular Basis of Autophagic Cell Death in Prostate Cancer

DTIC Science & Technology

2009-03-01

lipid-binding proteinwith high affinity for phosphatidic acid (PA) and cardiolipin (CL). Previously, it has been shown that PA directly interacted...lyceride), PI (phosphatidylinositol), DAG (diacylglycerol), PI4P (PtdIns(4)P), PA ( phosphatidic acid ), PI4,5P2 (PtdIns(4,5)P2), PS (phosphatidylserine...with high affinity for phosphatidic acid and cardiolipin and less affinity for various phosphoinositides. Functional genomics analysis identified 5

Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif.

PubMed

Seet, Bruce T; Berry, Donna M; Maltzman, Jonathan S; Shabason, Jacob; Raina, Monica; Koretzky, Gary A; McGlade, C Jane; Pawson, Tony

2007-02-07

The relationship between the binding affinity and specificity of modular interaction domains is potentially important in determining biological signaling responses. In signaling from the T-cell receptor (TCR), the Gads C-terminal SH3 domain binds a core RxxK sequence motif in the SLP-76 scaffold. We show that residues surrounding this motif are largely optimized for binding the Gads C-SH3 domain resulting in a high-affinity interaction (K(D)=8-20 nM) that is essential for efficient TCR signaling in Jurkat T cells, since Gads-mediated signaling declines with decreasing affinity. Furthermore, the SLP-76 RxxK motif has evolved a very high specificity for the Gads C-SH3 domain. However, TCR signaling in Jurkat cells is tolerant of potential SLP-76 crossreactivity, provided that very high-affinity binding to the Gads C-SH3 domain is maintained. These data provide a quantitative argument that the affinity of the Gads C-SH3 domain for SLP-76 is physiologically important and suggest that the integrity of TCR signaling in vivo is sustained both by strong selection of SLP-76 for the Gads C-SH3 domain and by a capacity to buffer intrinsic crossreactivity.

Direct ROS scavenging activity of CueP from Salmonella enterica serovar Typhimurium.

PubMed

Yoon, Bo-Young; Yeom, Ji-Hyun; Kim, Jin-Sik; Um, Si-Hyeon; Jo, Inseong; Lee, Kangseok; Kim, Yong-Hak; Ha, Nam-Chul

2014-02-01

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an intracellular pathogen that has evolved to survive in the phagosome of macrophages. The periplasmic copper-binding protein CueP was initially known to confer copper resistance to S. Typhimurium. Crystal structure and biochemical studies on CueP revealed a putative copper binding site surrounded by the conserved cysteine and histidine residues. A recent study reported that CueP supplies copper ions to periplasmic Cu, Zn-superoxide dismutase (SodCII) at a low copper concentration and thus enables the sustained SodCII activity in the periplasm. In this study, we investigated the role of CueP in copper resistance at a high copper concentration. We observed that the survival of a cueP-deleted strain of Salmonella in macrophage phagosome was significantly reduced. Subsequent biochemical experiments revealed that CueP specifically mediates the reduction of copper ion using electrons released during the formation of the disulfide bond. We observed that the copper ion-mediated Fenton reaction in the presence of hydrogen peroxide was blocked by CueP. This study provides insight into how CueP confers copper resistance to S. Typhimurium in copper-rich environments such as the phagosome of macrophages.

Selective LPCVD growth of graphene on patterned copper and its growth mechanism

NASA Astrophysics Data System (ADS)

Zhang, M.; Huang, B.-C.; Wang, Y.; Woo, J. C. S.

2016-12-01

Copper-catalyzed graphene low-pressure chemical-vapor deposition (LPCVD) growth has been regarded as a viable solution towards its integration to CMOS technology, and the wafer-bonding method provides a reliable alternative for transferring the selective graphene grown on a patterned metal film for IC manufacturing. In this paper, selective LPCVD graphene growth using patterned copper dots has been studied. The Raman spectra of grown films have demonstrated large dependence on the growth conditions. To explain the results, the growth mechanisms based on surface adsorption and copper-vapor-assisted growth are investigated by the comparison between the blanket copper films with/without the additional copper source. The copper vapor density is found to be critical for high-quality graphene growth. In addition, the copper-vapor-assisted growth is also evidenced by the carbon deposition on the SiO2 substrate of the patterned-copper-dot sample and chamber wall during graphene growth. This growth mechanism explains the correlation between the growth condition and Raman spectrum for films on copper dots. The study on the copper-catalyzed selective graphene growth on the hard substrate paves the way for the synthesis and integration of the 2D material in VLSI.

Effects of copper supplement on growth and viability of strains used as starters and adjunct cultures for Emmental cheese manufacture.

PubMed

Rodríguez, L Mato; Alatossava, T

2008-10-01

To determine the effects of supplemented copper (Cu2+) on growth and viability of strains used as starters and adjunct cultures for Emmental cheese manufacture. Thirteen strains belonging to Lactobacillus delbrueckii, Lactobacillus helveticus, Lactobacillus rhamnosus, Streptococcus thermophilus or Propionibacterium freudenreichii species were exposed to various copper concentrations in the proper growth medium at relevant growth temperatures, and the effects of supplemented copper on bacterial growth and cell viability were determined by optical density and pH measurements, also by platings. Among the species considered, L. delbrueckii was the most copper resistant and S. thermophilus the most sensitive to copper. Anaerobic conditions increased this sensitivity significantly. There was also a considerable amount of variation in copper resistance at strain level. Copper resistance is both a species- and strain-dependent property and may reflect variability in copper-binding capacities by cell wall components among species and strains. In addition, the chemical state of copper may be involved. This study revealed that copper resistance is a highly variable property among starter and adjunct strains, and this variability should be considered when strains are selected for Emmental cheese manufacture.

The measurement of the stacking fault energy in copper, nickel and copper-nickel alloys

NASA Technical Reports Server (NTRS)

Leighly, H. P., Jr.

1982-01-01

The relationship of hydrogen solubility and the hydrogen embrittlement of high strength, high performance face centered cubic alloys to the stacking fault energy of the alloys was investigated. The stacking fault energy is inversely related to the distance between the two partial dislocations which are formed by the dissociation of a perfect dislocation. The two partial dislocations define a stacking fault in the crystal which offers a region for hydrogen segregation. The distance between the partial dislocations is measured by weak beam, dark field transmission electron microscopy. The stacking fault energy is calculated. Pure copper, pure nickel and copper-nickel single crystals are used to determine the stacking fault energy.

Single-site trinuclear copper oxygen clusters in mordenite for selective conversion of methane to methanol.

PubMed

Grundner, Sebastian; Markovits, Monica A C; Li, Guanna; Tromp, Moniek; Pidko, Evgeny A; Hensen, Emiel J M; Jentys, Andreas; Sanchez-Sanchez, Maricruz; Lercher, Johannes A

2015-06-25

Copper-exchanged zeolites with mordenite structure mimic the nuclearity and reactivity of active sites in particulate methane monooxygenase, which are enzymes able to selectively oxidize methane to methanol. Here we show that the mordenite micropores provide a perfect confined environment for the highly selective stabilization of trinuclear copper-oxo clusters that exhibit a high reactivity towards activation of carbon-hydrogen bonds in methane and its subsequent transformation to methanol. The similarity with the enzymatic systems is also implied from the similarity of the reversible rearrangements of the trinuclear clusters occurring during the selective transformations of methane along the reaction path towards methanol, in both the enzyme system and copper-exchanged mordenite.

Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors.

PubMed

Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C; Munson, P J; Rodbard, D

1979-12-01

Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions.

Hb Potomac (101 Glu replaced by Asp): speculations on placental oxygen transport in carriers of high-affinity hemoglobins.

PubMed

Charache, S; Jacobson, R; Brimhall, B; Murphy, E A; Hathaway, P; Winslow, R; Jones, R; Rath, C; Simkovich, J

1978-02-01

Blood from a woman with unexplained erythrocytosis had increased oxygen affinity, but no abnormality could be detected by electrophoresis or chromatography of her hemolysate. Separation of the tryptic peptides of her beta chains disclosed two half-sized peaks in the regions of beta T-11. The faster of these was abnormal, with the structure beta 101 Glu replaced by Asp. The new hemoglobin was called "Potomac." Three of the proband's four surviving siblings and both of her children were carriers. Differences in the ratio of carrier: normal children born to male of female carriers of 23 other high-affinity hemoglobins were not significant. The high proportion of carriers in this kindred was probably due to chance alone, and not because high maternal oxygen affinity interfered with oxygen transport to fetuses with normal hemoglobin.

Biomarker Candidates of Chlamydophila pneumoniae Proteins and Protein Fragments Identified by Affinity-Proteomics Using FTICR-MS and LC-MS/MS

NASA Astrophysics Data System (ADS)

Susnea, Iuliana; Bunk, Sebastian; Wendel, Albrecht; Hermann, Corinna; Przybylski, Michael

2011-04-01

We report here an affinity-proteomics approach that combines 2D-gel electrophoresis and immunoblotting with high performance mass spectrometry to the identification of both full length protein antigens and antigenic fragments of Chlamydophila pneumoniae (C. pneumoniae). The present affinity-mass spectrometry approach effectively utilized high resolution FTICR mass spectrometry and LC-tandem-MS for protein identification, and enabled the identification of several new highly antigenic C. pneumoniae proteins that were not hitherto reported or previously detected only in other Chlamydia species, such as Chlamydia trachomatis. Moreover, high resolution affinity-MS provided the identification of several neo-antigenic protein fragments containing N- and C-terminal, and central domains such as fragments of the membrane protein Pmp21 and the secreted chlamydial proteasome-like factor (Cpaf), representing specific biomarker candidates.

Lesion-induced plasticity of high affinity choline uptake in the developing rat fascia dentata.

PubMed

Nadler, J V; Shelton, D L; Cotman, C W

1979-03-23

After removal of the perforant path input to the rat fascia dentata at the age of 11 days, cholinergic septohippocampal fibers invade the denervated area. We have examined the effect of this lesion on hemicholinium-sensitive, high affinity choline uptake and its coupling to acetylcholine synthesis, specific properties of the septohippocampal input. Removal of the ipsilateral perforant path fibers increased the velocity of high affinity choline uptake by dentate particulate preparations, usually within 1 day. Studies conducted 5--104 days after operation showed a consistent 50--65% elevation in the molecular (denervated) layer. In contrast, the choline uptake rate in the granular layer eventually decreased slightly. Calculation of choline uptake rates independently of protein (per whole region) revealed that fasciae dentatae from operated and control sides accumulated choline at approximately equal rates, but on the operated side a greater percentage was transported by structures from the molecular layer and a lesser percentage by those from the granular layer. The rate of acetylcholine synthesis from exogenous choline increased to the same extent as high affinity choline uptake from 3 days after operation onwards. The changes in high affinity choline uptake and acetylcholine synthesis coincided spatially and temporally with the reactive growth of septohippocampal fibers. Our results support the view that a perforant path lesion during development permanently alters the distribution of functional septohippocampal boutons in the fascia dentata. Acetylcholine synthesis is regulated to the same extent by high affinity choline uptake in the anomalous boutons as in normally located boutons.

A putative role for the plasma membrane potential in the control of the expression of the gene encoding the tomato high-affinity potassium transporter HAK5.

PubMed

Nieves-Cordones, Manuel; Miller, Anthony J; Alemán, Fernando; Martínez, Vicente; Rubio, Francisco

2008-12-01

A chimeric CaHAK1-LeHAK5 transporter with only 15 amino acids of CaHAK1 in the N-terminus mediates high-affinity K(+) uptake in yeast cells. Kinetic and expression analyses strongly suggest that LeHAK5 mediates a significant proportion of the high-affinity K(+) uptake shown by K(+)-starved tomato (Solanum lycopersicum) plants. The development of high-affinity K(+) uptake, putatively mediated by LeHAK5, was correlated with increased LeHAK5 mRNA levels and a more negative electrical potential difference across the plasma membrane of root epidermal and cortical cells. However, this increase in high-affinity K(+) uptake was not correlated with the root K(+) content. Thus, (i) growth conditions that result in a hyperpolarized root plasma membrane potential, such as K(+) starvation or growth in the presence of NH(4) (+), but which do not decrease the K(+) content, lead to increased LeHAK5 expression; (ii) the presence of NaCl in the growth solution, which prevents the hyperpolarization induced by K(+) starvation, also prevents LeHAK5 expression. Moreover, once the gene is induced, depolarization of the plasma membrane potential then produces a decrease in the LeHAK5 mRNA. On the basis of these results, we propose that the plant membrane electrical potential plays a role in the regulation of the expression of this gene encoding a high-affinity K(+) transporter.

Studies on copper alloys containing chromium on the copper side phase diagram

NASA Technical Reports Server (NTRS)

Doi, T.

1984-01-01

Specimens were prepared from vacuum melted alloys of high purity vacuum melted copper and electrolytic chromium. The liquidus and eutectic point were determined by thermal analysis. The eutectic temperature is 1974.8 F and its composition is 1.28 wt% of chromium. The determination of solid solubility of chromium in copper was made by microscopic observation and electrical resistivity measurement. The solubility of chromium in solid copper is 0.6 wt% at 1050 F, 0.4 wt% at 1000 F, 0.25 wt% at 950 F, 0.17 wt% at 900 F, and 0.30 wt% at 840 F.

Self-reduction of a copper complex MOD ink for inkjet printing conductive patterns on plastics.

PubMed

Farraj, Yousef; Grouchko, Michael; Magdassi, Shlomo

2015-01-31

Highly conductive copper patterns on low-cost flexible substrates are obtained by inkjet printing a metal complex based ink. Upon heating the ink, the soluble complex, which is composed of copper formate and 2-amino-2-methyl-1-propanol, decomposes under nitrogen at 140 °C and is converted to pure metallic copper. The decomposition process of the complex is investigated and a suggested mechanism is presented. The ink is stable in air for prolonged periods, with no sedimentation or oxidation problems, which are usually encountered in copper nanoparticle based inks.

Cloning, Characterization and Expression Pattern Analysis of a Cytosolic Copper/Zinc Superoxide Dismutase (SaCSD1) in a Highly Salt Tolerant Mangrove (Sonneratia alba)

PubMed Central

Yang, Enze; Yi, Shanze; Bai, Fang; Niu, Dewei; Zhong, Junjie; Wu, Qiuhong; Chen, Shufang; Zhou, Renchao; Wang, Feng

2015-01-01

Mangroves are critical marine resources for their remarkable ability to tolerate seawater. Antioxidant enzymes play an especially significant role in eliminating reactive oxygen species and conferring abiotic stress tolerance. In this study, a cytosolic copper/zinc superoxide dismutase (SaCSD1) cDNA of Sonneratia alba, a mangrove species with high salt tolerance, was successfully cloned and then expressed in Escherichia coli Rosetta-gami (designated as SaCSD1). SaCSD1 comprised a complete open reading frame (ORF) of 459 bp which encoded a protein of 152 amino acids. Its mature protein is predicted to be 15.32 kDa and the deduced isoelectric point is 5.78. SaCSD1 has high sequence similarity (85%–90%) with the superoxide dismutase (CSD) of some other plant species. SaCSD1 was expressed with 30.6% yield regarding total protein content after being introduced into the pET-15b (Sma I) vector for expression in Rosetta-gami and being induced with IPTG. After affinity chromatography on Ni-NTA, recombinant SaCSD1 was obtained with 3.2-fold purification and a specific activity of 2200 U/mg. SaCSD1 showed good activity as well as stability in the ranges of pH between 3 and 7 and temperature between 25 and 55 °C. The activity of recombinant SaCSD1 was stable in 0.25 M NaCl, Dimethyl Sulphoxide (DMSO), glycerol, and chloroform, and was reduced to a great extent in β-mercaptoethanol, sodium dodecyl sulfate (SDS), H2O2, and phenol. Moreover, the SaCSD1 protein was very susceptive to pepsin digestion. Real-time Quantitative Polymerase Chain Reaction (PCR) assay demonstrated that SaCSD1 was expressed in leaf, stem, flower, and fruit organs, with the highest expression in fruits. Under 0.25 M and 0.5 M salt stress, the expression of SaCSD1 was down-regulated in roots, but up-regulated in leaves. PMID:26703583

Superconducting Cable Termination

DOEpatents

Sinha, Uday K.; Tolbert, Jerry

2005-08-30

Disclosed is a termination that connects high temperature superconducting (HTS) cable immersed in pressurized liquid nitrogen to high voltage and neutral (shield) external bushings at ambient temperature and pressure. The termination consists of a splice between the HTS power (inner) and shield (outer) conductors and concentric copper pipes which are the conductors in the termination. There is also a transition from the dielectric tape insulator used in the HTS cable to the insulators used between and around the copper pipe conductors in the termination. At the warm end of the termination the copper pipes are connected via copper braided straps to the conventional warm external bushings which have low thermal stresses. This termination allows for a natural temperature gradient in the copper pipe conductors inside the termination which enables the controlled flashing of the pressurized liquid coolant (nitrogen) to the gaseous state. Thus the entire termination is near the coolant supply pressure and the high voltage and shield cold bushings, a highly stressed component used in most HTS cables, are eliminated. A sliding seal allows for cable contraction as it is cooled from room temperature to ˜72-82 K. Seals, static vacuum, and multi-layer superinsulation minimize radial heat leak to the environment.

Novel preparation of highly photocatalytically active copper chromite nanostructured material via a simple hydrothermal route

PubMed Central

Beshkar, Farshad; Zinatloo-Ajabshir, Sahar; Bagheri, Samira; Salavati-Niasari, Masoud

2017-01-01

Highly photocatalytically active copper chromite nanostructured material were prepared via a novel simple hydrothermal reaction between [Cu(en)2(H2O)2]Cl2 and [Cr(en)3]Cl3.3H2O at low temperature, without adding any pH regulator or external capping agent. The as-synthesized nanostructured copper chromite was analyzed by transmission electron microscopy (TEM), UV–vis diffuse reflectance spectroscopy, energy dispersive X-ray microanalysis (EDX), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. Results of the morphological investigation of the as-synthesized products illustrate that the shape and size of the copper chromite depended on the surfactant sort, reaction duration and temperature. Moreover, the photocatalytic behavior of as-obtained copper chromite was evaluated by photodegradation of acid blue 92 (anionic dye) as water pollutant. PMID:28582420

Dealloying of gold–copper alloy nanowires: From hillocks to ring-shaped nanopores

PubMed Central

Chauvin, Adrien; Delacôte, Cyril; Boujtita, Mohammed; Angleraud, Benoit; Ding, Junjun; Choi, Chang-Hwan; Tessier, Pierre-Yves

2016-01-01

Summary We report on a novel fabrication approach of metal nanowires with complex surface. Taking advantage of nodular growth triggered by the presence of surface defects created intentionally on the substrate as well as the high tilt angle between the magnetron source axis and the normal to the substrate, metal nanowires containing hillocks emerging out of the surface can be created. The approach is demonstrated for several metals and alloys including gold, copper, silver, gold–copper and gold–silver. We demonstrate that applying an electrochemical dealloying process to the gold–copper alloy nanowire arrays allows for transforming the hillocks into ring-like shaped nanopores. The resulting porous gold nanowires exhibit a very high roughness and high specific surface making of them a promising candidate for the development of SERS-based sensors. PMID:27826510

Leaching behavior and chemical stability of copper butyl xanthate complex under acidic conditions.

PubMed

Chang, Yi Kuo; Chang, Juu En; Chiang, Li Choung

2003-08-01

Although xanthate addition can be used for treating copper-containing wastewater, a better understanding of the leaching toxicity and the stability characteristics of the copper xanthate complexes formed is essential. This work was undertaken to evaluate the leaching behavior of copper xanthate complex precipitates by means of toxicity characteristics leaching procedure (TCLP) and semi-dynamic leaching test (SDLT) using 1 N acetic acid solution as the leachant. Also, the chemical stability of the copper xanthate complex during extraction has been examined with the studying of variation of chemical structure using UV-vis, Fourier transform infrared and X-ray photoelectron spectroscopies (XPS). Both TCLP and SDLT results showed that a negligible amount of copper ion was leached out from the copper xanthate complex precipitate, indicating that the complex exhibited a high degree of copper leaching stability under acidic conditions. Nevertheless, chemical structure of the copper xanthate complex precipitate varied during the leaching tests. XPS data suggested that the copper xanthate complex initially contained both cupric and cuprous xanthate, but the unstable cupric xanthate change to the cuprous form after acid extraction, indicating the cuprous xanthate to be the final stabilizing structure. Despite that, the changes of chemical structure did not induce the rapid leaching of copper from the copper xanthate complex.

Urinary Copper Elevation in a Mouse Model of Wilson's Disease Is a Regulated Process to Specifically Decrease the Hepatic Copper Load

PubMed Central

Gray, Lawrence W.; Peng, Fangyu; Molloy, Shannon A.; Pendyala, Venkata S.; Muchenditsi, Abigael; Muzik, Otto; Lee, Jaekwon; Kaplan, Jack H.; Lutsenko, Svetlana

2012-01-01

Body copper homeostasis is regulated by the liver, which removes excess copper via bile. In Wilson's disease (WD), this function is disrupted due to inactivation of the copper transporter ATP7B resulting in hepatic copper overload. High urinary copper is a diagnostic feature of WD linked to liver malfunction; the mechanism behind urinary copper elevation is not fully understood. Using Positron Emission Tomography-Computed Tomography (PET-CT) imaging of live Atp7b−/− mice at different stages of disease, a longitudinal metal analysis, and characterization of copper-binding molecules, we show that urinary copper elevation is a specific regulatory process mediated by distinct molecules. PET-CT and atomic absorption spectroscopy directly demonstrate an age-dependent decrease in the capacity of Atp7b−/− livers to accumulate copper, concomitant with an increase in urinary copper. This reciprocal relationship is specific for copper, indicating that cell necrosis is not the primary cause for the initial phase of metal elevation in the urine. Instead, the urinary copper increase is associated with the down-regulation of the copper-transporter Ctr1 in the liver and appearance of a 2 kDa Small Copper Carrier, SCC, in the urine. SCC is also elevated in the urine of the liver-specific Ctr1 −/− knockouts, which have normal ATP7B function, suggesting that SCC is a normal metabolite carrying copper in the serum. In agreement with this hypothesis, partially purified SCC-Cu competes with free copper for uptake by Ctr1. Thus, hepatic down-regulation of Ctr1 allows switching to an SCC-mediated removal of copper via kidney when liver function is impaired. These results demonstrate that the body regulates copper export through more than one mechanism; better understanding of urinary copper excretion may contribute to an improved diagnosis and monitoring of WD. PMID:22802922

Analysis of Protein Interactions with Picomolar Binding Affinity by Fluorescence-Detected Sedimentation Velocity

PubMed Central

2014-01-01

The study of high-affinity protein interactions with equilibrium dissociation constants (KD) in the picomolar range is of significant interest in many fields, but the characterization of stoichiometry and free energy of such high-affinity binding can be far from trivial. Analytical ultracentrifugation has long been considered a gold standard in the study of protein interactions but is typically applied to systems with micromolar KD. Here we present a new approach for the study of high-affinity interactions using fluorescence detected sedimentation velocity analytical ultracentrifugation (FDS-SV). Taking full advantage of the large data sets in FDS-SV by direct boundary modeling with sedimentation coefficient distributions c(s), we demonstrate detection and hydrodynamic resolution of protein complexes at low picomolar concentrations. We show how this permits the characterization of the antibody–antigen interactions with low picomolar binding constants, 2 orders of magnitude lower than previously achieved. The strongly size-dependent separation and quantitation by concentration, size, and shape of free and complex species in free solution by FDS-SV has significant potential for studying high-affinity multistep and multicomponent protein assemblies. PMID:24552356

ECL-IAA and ECL-GADA Can Identify High-Risk Single Autoantibody-Positive Relatives in the TrialNet Pathway to Prevention Study.

PubMed

Steck, Andrea K; Fouts, Alexandra; Miao, Dongmei; Zhao, Zhiyuan; Dong, Fran; Sosenko, Jay; Gottlieb, Peter; Rewers, Marian J; Yu, Liping

2016-07-01

Relatives with single positive islet autoantibodies have a much lower risk of progression to diabetes than those with multiple autoantibodies. TrialNet subjects positive for single autoantibody to insulin (mIAA) (n = 50) or single autoantibody to glutamic acid decarboxylase (GADA) (n = 50) were analyzed using new electrochemiluminescence (ECL) assays (ECL-IAA and ECL-GADA, respectively) at their initial visit and longitudinally over time. Affinity assays were performed on a subset of single autoantibody-positive subjects at initial and most recent visits. After a mean follow-up of 5.3 years, 20 subjects developed type 1 diabetes. Among either single GADA or single mIAA subjects, those who were positive in the ECL assay showed higher affinity at the initial visit, and affinity results stayed consistent over time. No converting events from low to high or high to low affinity were seen over time. Confirmed positivity for ECL is associated with high affinity and can help staging of risk for type 1 diabetes in single autoantibody-positive subjects.

High-affinity RNA aptamers to C-reactive protein (CRP): newly developed pre-elution methods for aptamer selection

NASA Astrophysics Data System (ADS)

Orito, N.; Umekage, S.; Sato, K.; Kawauchi, S.; Tanaka, H.; Sakai, E.; Tanaka, T.; Kikuchi, Y.

2012-03-01

We have developed a modified SELEX (systematic evolution of ligands by exponential enrichment) method to obtain RNA aptamers with high affinity to C-reactive protein (CRP). CRP is a clinical biomarker present in plasma, the level of which increases in response to infections and noninfectious inflammation. The CRP level is also an important prognostic indicator in patients with several syndromes. At present, CRP content in blood is measured immunochemically using antibodies. To develop a more sensitive method using RNA aptamers, we have attempted to obtain high-affinity RNA aptamers to CRP. We succeeded in obtaining an RNA aptamer with high affinity to CRP using a CRP-immobilized Sepharose column and pre-elution procedure. Pre-elution is a method that removes the weak binding portion from a selected RNA population by washing for a short time with buffer containing CRP. By surface plasmon-resonance (SPR) analysis, the affinity constant of this aptamer for CRP was calculated to be KD = 2.25×10-9 (M). The secondary structure, contact sites with CRP protein, and application of this aptamer will be described.

High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

PubMed

Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D; Azuma, Takachika

2015-12-01

During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanical and electrical properties of laminates for high performance printed wiring boards

NASA Astrophysics Data System (ADS)

Guiles, Chester L.

The physical and electrical properties of laminate boards intended for high-performance applications are reviewed with particular reference to the coefficient of thermal expansion, dielectric constant, and characteristic impedance. It is shown, in particular, that the electrical properties can be tailored to some extent by using various conbinations of basic board materials, such as copper foil, fiberglass fabric, glass fabric, epoxy resin, polyimide resin, aluminum sheet, Kevlar and quartz fabrics, copper-invar-copper, and alumina-ceramic.

A model for predicting high-temperature fatigue failure of a W/Cu composite

NASA Technical Reports Server (NTRS)

Verrilli, M. J.; Kim, Y.-S.; Gabb, T. P.

1991-01-01

The material studied, a tungsten-fiber-reinforced, copper-matrix composite, is a candidate material for rocket nozzle liner applications. It was shown that at high temperatures, fatigue cracks initiate and propagate inside the copper matrix through a process of initiation, growth, and coalescence of grain boundary cavities. The ductile tungsten fibers neck and rupture locally after the surrounding matrix fails, and complete failure of the composite then ensues. A simple fatigue life prediction model is presented for the tungsten/copper composite system.

Controlling Fundamentals in High-Energy High-Rate Pulsed Power Materials Processing of Powdered Tungsten, Titanium Aluminides, and Copper-Graphite Composites

DTIC Science & Technology

1990-10-01

phase systems such as tungsten; plastic flow of a minor low -temperature phase in a two phase non-interacting system such as tungsten- copper ; and...consolidation heat treatment. The de- the wetting of graphite by copper or during consolidation by this tech- tailed phase transformation evolution other...The driving potential for this solid state phase transformation is the free surface energy associated with the total powder particle surface area in the

Global response of Acidithiobacillus ferrooxidans ATCC 53993 to high concentrations of copper: A quantitative proteomics approach.

PubMed

Martínez-Bussenius, Cristóbal; Navarro, Claudio A; Orellana, Luis; Paradela, Alberto; Jerez, Carlos A

2016-08-11

Acidithiobacillus ferrooxidans is used in industrial bioleaching of minerals to extract valuable metals. A. ferrooxidans strain ATCC 53993 is much more resistant to copper than other strains of this microorganism and it has been proposed that genes present in an exclusive genomic island (GI) of this strain would contribute to its extreme copper tolerance. ICPL (isotope-coded protein labeling) quantitative proteomics was used to study in detail the response of this bacterium to copper. A high overexpression of RND efflux systems and CusF copper chaperones, both present in the genome and the GI of strain ATCC 53993 was found. Also, changes in the levels of the respiratory system proteins such as AcoP and Rus copper binding proteins and several proteins with other predicted functions suggest that numerous metabolic changes are apparently involved in controlling the effects of the toxic metal on this acidophile. Using quantitative proteomics we overview the adaptation mechanisms that biomining acidophiles use to stand their harsh environment. The overexpression of several genes present in an exclusive genomic island strongly suggests the importance of the proteins coded in this DNA region in the high tolerance of A. ferrooxidans ATCC 53993 to metals. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of copper on the composition and diversity of microbial communities in laboratory-scale swine manure composting.

PubMed

Yin, Yanan; Gu, Jie; Wang, Xiaojuan; Tuo, Xiaxia; Zhang, Kaiyu; Zhang, Li; Guo, Aiyun; Zhang, Xin

2018-06-01

This study investigated the effects of adding copper at 3 treatment levels (0 (control: CK), 200 (low: L), and 2000 (high: H) mg·kg -1 treatments) on the bacterial communities during swine manure composting. The abundances of the bacteria were determined by quantitative PCR and their compositions were evaluated by high-throughput sequencing. The results showed that the abundance of bacteria was inhibited by the H treatment during days 7-35, and principal component analysis clearly separated the H treatment from the CK and L treatments. Actinobacteria, Firmicutes, and Proteobacteria were the dominant bacterial taxa, and a high copper concentration decreased the abundances of bacteria that degrade cellulose and lignin (e.g., class Bacilli and genus Truepera), especially in the mesophilic and thermophilic phases. Moreover, network analysis showed that copper might alter the co-occurrence patterns of bacterial communities by changing the properties of the networks and the keystone taxa, and increase the competition by increasing negative associations between bacteria during composting. Temperature, water-soluble carbohydrates, and copper significantly affected the variations in the bacterial community according to redundancy analysis. The copper content mainly contributed to the bacterial community in the thermophilic and cooling phases, where it had positive relationships with potentially pathogenic bacteria (e.g., Corynebacterium_1 and Acinetobacter).

Factors Affecting the Supply of Strategic Raw Materials with Particular Reference to the Aerospace Manufacturing Industry

DTIC Science & Technology

1984-04-01

element, recovered from the working of many porphyry copper deposits. As copper capacity i» now far beyond requirements, molybdenum should not be in...Source» Cobalt is mostly recovered aa a by-product of copper and nickel mining but world production is highly localised. Total annual production is...aluminium alloy containing lithium, copper and magnesium is under test. Por corrosion resistance there can be an Interchange with niobium. However

Water Quality Criteria for Copper Based on the BLM Approach in the Freshwater in China

PubMed Central

Zhang, Yahui; Zang, Wenchao; Qin, Lumei; Zheng, Lei; Cao, Ying; Yan, Zhenguang; Yi, Xianliang; Zeng, Honghu; Liu, Zhengtao

2017-01-01

The bioavailability and toxicity of metals to aquatic organisms are highly dependent on water quality parameters in freshwaters. The biotic ligand model (BLM) for copper is an approach to generate the water quality criteria (WQC) with water chemistry in the ambient environment. However, few studies were carried out on the WQCs for copper based on the BLM approach in China. In the present study, the toxicity for copper to native Chinese aquatic organisms was conducted and the published toxicity data with water quality parameters to Chinese aquatic species were collected to derive the WQCs for copper by the BLM approach. The BLM-based WQCs (the criterion maximum criteria (CMC) and the criterion continuous concentration (CCC)) for copper in the freshwater for the nation and in the Taihu Lake were obtained. The CMC and CCC values for copper in China were derived to be 1.391 μg/L and 0.495 μg/L, respectively, and the CMC and CCC in the Taihu Lake were 32.194 μg/L and 9.697 μg/L. The high concentration of dissolved organic carbon might be a main reason which resulted in the higher WQC values in the Taihu Lake. The WQC of copper in the freshwater would provide a scientific foundation for water quality standards and the environment risk assessment in China. PMID:28166229

Affinity Purification of Proteins in Tag-Free Form: Split Intein-Mediated Ultrarapid Purification (SIRP).

PubMed

Guan, Dongli; Chen, Zhilei

2017-01-01

Proteins purified using affinity-based chromatography often exploit a recombinant affinity tag. Existing methods for the removal of the extraneous tag, needed for many applications, suffer from poor efficiency and/or high cost. Here we describe a simple, efficient, and potentially low-cost approach-split intein-mediated ultrarapid purification (SIRP)-for both the purification of the desired tagged protein from Escherichia coli lysate and removal of the tag in less than 1 h. The N- and C-fragment of a self-cleaving variant of a naturally split DnaE intein from Nostoc punctiforme are genetically fused to the N-terminus of an affinity tag and a protein of interest (POI), respectively. The N-intein/affinity tag is used to functionalize an affinity resin. The high affinity between the N- and C-fragment of DnaE intein enables the POI to be purified from the lysate via affinity to the resin, and the intein-mediated C-terminal cleavage reaction causes tagless POI to be released into the flow-through. The intein cleavage reaction is strongly inhibited by divalent ions (e.g., Zn 2+ ) under non-reducing conditions and is significantly enhanced by reducing conditions. The POI is cleaved efficiently regardless of the identity of the N-terminal amino acid except in the cases of threonine and proline, and the N-intein-functionalized affinity resin can be regenerated for multiple cycles of use.