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Sample records for cysteine string protein

  1. Phosphomimetic mutation of cysteine string protein-α increases the rate of regulated exocytosis by modulating fusion pore dynamics in PC12 cells.

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    Ning Chiang

    Full Text Available BACKGROUND: Cysteine string protein-α (CSPα is a chaperone to ensure protein folding. Loss of CSPα function associates with many neurological diseases. However, its function in modulating regulated exocytosis remains elusive. Although cspα-knockouts exhibit impaired synaptic transmission, overexpression of CSPα in neuroendocrine cells inhibits secretion. These seemingly conflicting results lead to a hypothesis that CSPα may undergo a modification that switches its function in regulating neurotransmitter and hormone secretion. Previous studies implied that CSPα undergoes phosphorylation at Ser10 that may influence exocytosis by altering fusion pore dynamics. However, direct evidence is missing up to date. METHODOLOGY/PRINCIPAL FINDINGS: Using amperometry, we investigated how phosphorylation at Ser10 of CSPα (CSPα-Ser10 modulates regulated exocytosis and if this modulation involves regulating a specific kinetic step of fusion pore dynamics. The real-time exocytosis of single vesicles was detected in PC12 cells overexpressing control vector, wild-type CSPα (WT, the CSPα phosphodeficient mutant (S10A, or the CSPα phosphomimetic mutants (S10D and S10E. The shapes of amperometric signals were used to distinguish the full-fusion events (i.e., prespike feet followed by spikes and the kiss-and-run events (i.e., square-shaped flickers. We found that the secretion rate was significantly increased in cells overexpressing S10D or S10E compared to WT or S10A. Further analysis showed that overexpression of S10D or S10E prolonged fusion pore lifetime compared to WT or S10A. The fraction of kiss-and-run events was significantly lower but the frequency of full-fusion events was higher in cells overexpressing S10D or S10E compared to WT or S10A. Advanced kinetic analysis suggests that overexpression of S10D or S10E may stabilize open fusion pores mainly by inhibiting them from closing. CONCLUSIONS/SIGNIFICANCE: CSPα may modulate fusion pore dynamics

  2. Cysteine string protein promotes proteasomal degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) by increasing its interaction with the C terminus of Hsp70-interacting protein and promoting CFTR ubiquitylation.

    Science.gov (United States)

    Schmidt, Béla Z; Watts, Rebecca J; Aridor, Meir; Frizzell, Raymond A

    2009-02-13

    Cysteine string protein (Csp) is a J-domain-containing protein whose overexpression blocks the exit of cystic fibrosis transmembrane conductance regulator (CFTR) from the endoplasmic reticulum (ER). Another method of blocking ER exit, the overexpression of Sar1-GTP, however, yielded twice as much immature CFTR compared with Csp overexpression. This finding suggested that Csp not only inhibits CFTR ER exit but also facilitates the degradation of immature CFTR. This was confirmed by treatment with a proteasome inhibitor, which returned the level of immature CFTR to that found in cells expressing Sar1-GTP only. CspH43Q, which does not interact with Hsc70/Hsp70 efficiently, did not promote CFTR degradation, suggesting that the pro-degradative effect of Csp requires Hsc70/Hsp70 binding/activation. In agreement with this, Csp overexpression increased the amount of Hsc70/Hsp70 co-immunoprecipitated with CFTR, whereas overexpression of CspH43Q did not. The Hsc70/Hsp70 binding partner C terminus of Hsp70-interacting protein (CHIP) can target CFTR for proteasome-mediated degradation. Csp overexpression also increased the amount of CHIP co-immunoprecipitated with CFTR. In addition, CHIP interacted directly with Csp, which was confirmed by in vitro binding experiments. Csp overexpression also increased CFTR ubiquitylation and reduced the half-life of immature CFTR. These findings indicate that Csp not only regulates the exit of CFTR from the ER, but that this action is accompanied by Hsc70/Hsp70 and CHIP-mediated CFTR degradation.

  3. Cysteine-rich mini-proteins in human biology.

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    Lavergne, Vincent; Taft, Ryan J; Alewood, Paul F

    2012-01-01

    Understanding the relationship between structure and function underpins both biochemistry and chemical biology, and has enabled the discovery of numerous agricultural and therapeutic agents. Small cysteine-rich proteins, which form a unique set of protein frameworks and folds, are found in all living organisms and often play crucial roles as hormones, growth factors, ion channel modulators and enzyme inhibitors in various biological pathways. Here we review secreted human cysteine-rich mini-proteins, classify them into broad families and briefly describe their structure and function. To systematically investigate this protein sub-class we designed a step-wise high throughput algorithm that is able to isolate the mature and active forms of human secreted cysteine-rich proteins (up to 200 amino acids in length) and extract their cysteine scaffolds. We limited our search to frameworks that contain an even number of cysteine residues (5% cysteine residues led to the identification of 22 cysteine-rich frameworks representing 21 protein families. Analysis of their molecular targets showed that these mini-proteins are frequently ligands for G protein- and enzyme-coupled receptors, transporters, extracellular enzyme inhibitors, and antimicrobial peptides. It is clear that these human secreted mini-proteins possess a wide diversity of frameworks and folds, some of which are conserved across the phylogenetic spectrum. Further study of these proteins will undoubtedly lead to insights into unresolved questions of basic biology, and the development of system-specific human therapeutics.

  4. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins.

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    Chunxiang Yao

    Full Text Available Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2, react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat, an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.

  5. Carbon Nanotubes Facilitate Oxidation of Cysteine Residues of Proteins.

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    Hirano, Atsushi; Kameda, Tomoshi; Wada, Momoyo; Tanaka, Takeshi; Kataura, Hiromichi

    2017-10-19

    The adsorption of proteins onto nanoparticles such as carbon nanotubes (CNTs) governs the early stages of nanoparticle uptake into biological systems. Previous studies regarding these adsorption processes have primarily focused on the physical interactions between proteins and nanoparticles. In this study, using reduced lysozyme and intact human serum albumin in aqueous solutions, we demonstrated that CNTs interact chemically with proteins. The CNTs induce the oxidation of cysteine residues of the proteins, which is accounted for by charge transfer from the sulfhydryl groups of the cysteine residues to the CNTs. The redox reaction simultaneously suppresses the intermolecular association of proteins via disulfide bonds. These results suggest that CNTs can affect the folding and oxidation degree of proteins in biological systems such as blood and cytosol.

  6. STRING 8--a global view on proteins and their functional interactions in 630 organisms

    DEFF Research Database (Denmark)

    Jensen, Lars Juhl; Kuhn, Michael; Stark, Manuel

    2008-01-01

    Functional partnerships between proteins are at the core of complex cellular phenotypes, and the networks formed by interacting proteins provide researchers with crucial scaffolds for modeling, data reduction and annotation. STRING is a database and web resource dedicated to protein-protein inter....... Version 8.0 of STRING covers about 2.5 million proteins from 630 organisms, providing the most comprehensive view on protein-protein interactions currently available. STRING can be reached at http://string-db.org/....

  7. Soft Cysteine Signaling Network: The Functional Significance of Cysteine in Protein Function and the Soft Acids/Bases Thiol Chemistry That Facilitates Cysteine Modification.

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    Wible, Ryan S; Sutter, Thomas R

    2017-03-20

    The unique biophysical and electronic properties of cysteine make this molecule one of the most biologically critical amino acids in the proteome. The defining sulfur atom in cysteine is much larger than the oxygen and nitrogen atoms more commonly found in the other amino acids. As a result of its size, the valence electrons of sulfur are highly polarizable. Unique protein microenvironments favor the polarization of sulfur, thus increasing the overt reactivity of cysteine. Here, we provide a brief overview of the endogenous generation of reactive oxygen and electrophilic species and specific examples of enzymes and transcription factors in which the oxidation or covalent modification of cysteine in those proteins modulates their function. The perspective concludes with a discussion of cysteine chemistry and biophysics, the hard and soft acids and bases model, and the proposal of the Soft Cysteine Signaling Network: a hypothesis proposing the existence of a complex signaling network governed by layered chemical reactivity and cross-talk in which the chemical modification of reactive cysteine in biological networks triggers the reorganization of intracellular biochemistry to mitigate spikes in endogenous or exogenous oxidative or electrophilic stress.

  8. Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families

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    Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A.; Turjanski, Adrián G.

    2015-01-01

    Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function. PMID:25741692

  9. Using an alignment of fragment strings for comparing protein structures

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    Friedberg, Iddo; Harder, Tim; Kolodny, Rachel

    2007-01-01

    MOTIVATION: Most methods that are used to compare protein structures use three-dimensional (3D) structural information. At the same time, it has been shown that a 1D string representation of local protein structure retains a degree of structural information. This type of representation can be a p....... The results of this study have immediate applications towards fast structure recognition, and for fold prediction and classification.......MOTIVATION: Most methods that are used to compare protein structures use three-dimensional (3D) structural information. At the same time, it has been shown that a 1D string representation of local protein structure retains a degree of structural information. This type of representation can...... be a powerful tool for protein structure comparison and classification, given the arsenal of sequence comparison tools developed by computational biology. However, in order to do so, there is a need to first understand how much information is contained in various possible 1D representations of protein structure...

  10. Replication of murine coronavirus requires multiple cysteines in the endodomain of spike protein

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    Yang, Jinhua; Lv, Jun; Wang, Yuyan; Gao, Shuang; Yao, Qianqian; Qu, Di; Ye, Rong, E-mail: yerong24@fudan.edu.cn

    2012-06-05

    A conserved cysteine-rich motif located between the transmembrane domain and the endodomain is essential for membrane fusion and assembly of coronavirus spike (S) protein. Here, we proved that three cysteines within the motif, but not dependent on position, are minimally required for the survival of the recombinant mouse hepatitis virus. When the carboxy termini with these mutated motifs of S proteins were respectively introduced into a heterogeneous protein, both incorporation into lipid rafts and S-palmitoylation of these recombinant proteins showed a similar quantity requirement to cysteine residues. Meanwhile, the redistribution of these proteins on cellular surface indicated that the absence of the positively charged rather than cysteine residues in the motif might lead the dramatic reduction in syncytial formation of some mutants with the deleted motifs. These results suggest that multiple cysteine as well as charged residues concurrently improves the membrane-associated functions of S protein in viral replication and cytopathogenesis.

  11. Electrostatics of cysteine residues in proteins: parameterization and validation of a simple model.

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    Salsbury, Freddie R; Poole, Leslie B; Fetrow, Jacquelyn S

    2012-11-01

    One of the most popular and simple models for the calculation of pK(a) s from a protein structure is the semi-macroscopic electrostatic model MEAD. This model requires empirical parameters for each residue to calculate pK(a) s. Analysis of current, widely used empirical parameters for cysteine residues showed that they did not reproduce expected cysteine pK(a) s; thus, we set out to identify parameters consistent with the CHARMM27 force field that capture both the behavior of typical cysteines in proteins and the behavior of cysteines which have perturbed pK(a) s. The new parameters were validated in three ways: (1) calculation across a large set of typical cysteines in proteins (where the calculations are expected to reproduce expected ensemble behavior); (2) calculation across a set of perturbed cysteines in proteins (where the calculations are expected to reproduce the shifted ensemble behavior); and (3) comparison to experimentally determined pK(a) values (where the calculation should reproduce the pK(a) within experimental error). Both the general behavior of cysteines in proteins and the perturbed pK(a) in some proteins can be predicted reasonably well using the newly determined empirical parameters within the MEAD model for protein electrostatics. This study provides the first general analysis of the electrostatics of cysteines in proteins, with specific attention paid to capturing both the behavior of typical cysteines in a protein and the behavior of cysteines whose pK(a) should be shifted, and validation of force field parameters for cysteine residues. Copyright © 2012 Wiley Periodicals, Inc.

  12. On Ramachandran angles, closed strings and knots in protein structure

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    Chen, Si; Niemi, Antti J.

    2016-08-01

    The Ramachandran angles (φ,\\psi ) of a protein backbone form the vertices of a piecewise geodesic curve on the surface of a torus. When the ends of the curve are connected to each other similarly, by a geodesic, the result is a closed string that in general wraps around the torus a number of times both in the meridional and the longitudinal directions. The two wrapping numbers are global characteristics of the protein structure. A statistical analysis of the wrapping numbers in terms of crystallographic x-ray structures in the protein data bank (PDB) reveals that proteins have no net chirality in the ϕ direction but in the ψ direction, proteins prefer to display chirality. A comparison between the wrapping numbers and the concept of folding index discloses a non-linearity in their relationship. Thus these three integer valued invariants can be used in tandem, to scrutinize and classify the global loop structure of individual PDB proteins, in terms of the overall fold topology.

  13. STRING: known and predicted protein-protein associations, integrated and transferred across organisms.

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    von Mering, Christian; Jensen, Lars J; Snel, Berend; Hooper, Sean D; Krupp, Markus; Foglierini, Mathilde; Jouffre, Nelly; Huynen, Martijn A; Bork, Peer

    2005-01-01

    A full description of a protein's function requires knowledge of all partner proteins with which it specifically associates. From a functional perspective, 'association' can mean direct physical binding, but can also mean indirect interaction such as participation in the same metabolic pathway or cellular process. Currently, information about protein association is scattered over a wide variety of resources and model organisms. STRING aims to simplify access to this information by providing a comprehensive, yet quality-controlled collection of protein-protein associations for a large number of organisms. The associations are derived from high-throughput experimental data, from the mining of databases and literature, and from predictions based on genomic context analysis. STRING integrates and ranks these associations by benchmarking them against a common reference set, and presents evidence in a consistent and intuitive web interface. Importantly, the associations are extended beyond the organism in which they were originally described, by automatic transfer to orthologous protein pairs in other organisms, where applicable. STRING currently holds 730,000 proteins in 180 fully sequenced organisms, and is available at http://string.embl.de/.

  14. Desulfurization of Cysteine-Containing Peptides Resulting from Sample Preparation for Protein Characterization by MS

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    Wang, Zhouxi; Rejtar, Tomas; Zhou, Zhaohui Sunny; Karger, Barry L.

    2010-01-01

    In this paper, we have examined two cysteine modifications resulting from sample preparation for protein characterization by MS: (1) a previously observed conversion of cysteine to dehydroalanine, now found in the case of disulfide mapping and (2) a novel modification corresponding to conversion of cysteine to alanine. Using model peptides, the conversion of cysteine to dehydroalanine via β-elimination of a disulfide bond was seen to result from the conditions of typical tryptic digestion (37 °C, pH 7.0– 9.0) without disulfide reduction and alkylation.. Furthermore, the surprising conversion of cysteine to alanine was shown to occur by heating cysteine containing peptides in the presence of a phosphine (TCEP). The formation of alanine from cysteine, investigated by performing experiments in H2O or D2O, suggested a radical-based desulfurization mechanism unrelated to β-elimination. Importantly, an understanding of the mechanism and conditions favorable for cysteine desulfurization provides insight for the establishment of improved sample preparation procedures of protein analysis. PMID:20049891

  15. Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents

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    Bernardim, Barbara; Cal, Pedro M. S. D.; Matos, Maria J.; Oliveira, Bruno L.; Martínez-Sáez, Nuria; Albuquerque, Inês S.; Perkins, Elizabeth; Corzana, Francisco; Burtoloso, Antonio C. B.; Jiménez-Osés, Gonzalo; Bernardes, Gonçalo J. L.

    2016-10-01

    Maleimides remain the reagents of choice for the preparation of therapeutic and imaging protein conjugates despite the known instability of the resulting products that undergo thiol-exchange reactions in vivo. Here we present the rational design of carbonylacrylic reagents for chemoselective cysteine bioconjugation. These reagents undergo rapid thiol Michael-addition under biocompatible conditions in stoichiometric amounts. When using carbonylacrylic reagents equipped with PEG or fluorophore moieties, this method enables access to protein and antibody conjugates precisely modified at pre-determined sites. Importantly, the conjugates formed are resistant to degradation in plasma and are biologically functional, as demonstrated by the selective imaging and detection of apoptotic and HER2+ cells, respectively. The straightforward preparation, stoichiometric use and exquisite cysteine selectivity of the carbonylacrylic reagents combined with the stability of the products and the availability of biologically relevant cysteine-tagged proteins make this method suitable for the routine preparation of chemically defined conjugates for in vivo applications.

  16. Accurate disulfide-bonding network predictions improve ab initio structure prediction of cysteine-rich proteins.

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    Yang, Jing; He, Bao-Ji; Jang, Richard; Zhang, Yang; Shen, Hong-Bin

    2015-12-01

    Cysteine-rich proteins cover many important families in nature but there are currently no methods specifically designed for modeling the structure of these proteins. The accuracy of disulfide connectivity pattern prediction, particularly for the proteins of higher-order connections, e.g., >3 bonds, is too low to effectively assist structure assembly simulations. We propose a new hierarchical order reduction protocol called Cyscon for disulfide-bonding prediction. The most confident disulfide bonds are first identified and bonding prediction is then focused on the remaining cysteine residues based on SVR training. Compared with purely machine learning-based approaches, Cyscon improved the average accuracy of connectivity pattern prediction by 21.9%. For proteins with more than 5 disulfide bonds, Cyscon improved the accuracy by 585% on the benchmark set of PDBCYS. When applied to 158 non-redundant cysteine-rich proteins, Cyscon predictions helped increase (or decrease) the TM-score (or RMSD) of the ab initio QUARK modeling by 12.1% (or 14.4%). This result demonstrates a new avenue to improve the ab initio structure modeling for cysteine-rich proteins. http://www.csbio.sjtu.edu.cn/bioinf/Cyscon/ zhng@umich.edu or hbshen@sjtu.edu.cn. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Restoration of proper trafficking to the cell surface for membrane proteins harboring cysteine mutations.

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    Lopez-Rodriguez, Angelica; Holmgren, Miguel

    2012-01-01

    A common phenotype for many genetic diseases is that the cell is unable to deliver full-length membrane proteins to the cell surface. For some forms of autism, hereditary spherocytosis and color blindness, the culprits are single point mutations to cysteine. We have studied two inheritable cysteine mutants of cyclic nucleotide-gated channels that produce achromatopsia, a common form of severe color blindness. By taking advantage of the reactivity of cysteine's sulfhydryl group, we modified these mutants with chemical reagents that attach moieties with similar chemistries to the wild-type amino acids' side chains. We show that these modifications restored proper delivery to the cell membrane. Once there, the channels exhibited normal functional properties. This strategy might provide a unique opportunity to assess the chemical nature of membrane protein traffic problems.

  18. Restoration of proper trafficking to the cell surface for membrane proteins harboring cysteine mutations.

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    Angelica Lopez-Rodriguez

    Full Text Available A common phenotype for many genetic diseases is that the cell is unable to deliver full-length membrane proteins to the cell surface. For some forms of autism, hereditary spherocytosis and color blindness, the culprits are single point mutations to cysteine. We have studied two inheritable cysteine mutants of cyclic nucleotide-gated channels that produce achromatopsia, a common form of severe color blindness. By taking advantage of the reactivity of cysteine's sulfhydryl group, we modified these mutants with chemical reagents that attach moieties with similar chemistries to the wild-type amino acids' side chains. We show that these modifications restored proper delivery to the cell membrane. Once there, the channels exhibited normal functional properties. This strategy might provide a unique opportunity to assess the chemical nature of membrane protein traffic problems.

  19. A Critical Role for Cysteine 57 in the Biological Functions of Selenium Binding Protein-1

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    Qi Ying

    2015-11-01

    Full Text Available The concentration of selenium-binding protein1 (SBP1 is often lower in tumors than in the corresponding tissue and lower levels have been associated with poor clinical outcomes. SBP1 binds tightly selenium although what role selenium plays in its biological functions remains unknown. Previous studies indicated that cysteine 57 is the most likely candidate amino acid for selenium binding. In order to investigate the role of cysteine 57 in SBP1, this amino acid was altered to a glycine and the mutated protein was expressed in human cancer cells. The SBP1 half-life, as well as the cellular response to selenite cytotoxicity, was altered by this change. The ectopic expression of SBP1GLY also caused mitochondrial damage in HCT116 cells. Taken together, these results indicated that cysteine 57 is a critical determinant of SBP1 function and may play a significant role in mitochondrial function.

  20. A miniaturized technique for assessing protein thermodynamics and function using fast determination of quantitative cysteine reactivity.

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    Isom, Daniel G; Marguet, Philippe R; Oas, Terrence G; Hellinga, Homme W

    2011-04-01

    Protein thermodynamic stability is a fundamental physical characteristic that determines biological function. Furthermore, alteration of thermodynamic stability by macromolecular interactions or biochemical modifications is a powerful tool for assessing the relationship between protein structure, stability, and biological function. High-throughput approaches for quantifying protein stability are beginning to emerge that enable thermodynamic measurements on small amounts of material, in short periods of time, and using readily accessible instrumentation. Here we present such a method, fast quantitative cysteine reactivity, which exploits the linkage between protein stability, sidechain protection by protein structure, and structural dynamics to characterize the thermodynamic and kinetic properties of proteins. In this approach, the reaction of a protected cysteine and thiol-reactive fluorogenic indicator is monitored over a gradient of temperatures after a short incubation time. These labeling data can be used to determine the midpoint of thermal unfolding, measure the temperature dependence of protein stability, quantify ligand-binding affinity, and, under certain conditions, estimate folding rate constants. Here, we demonstrate the fQCR method by characterizing these thermodynamic and kinetic properties for variants of Staphylococcal nuclease and E. coli ribose-binding protein engineered to contain single, protected cysteines. These straightforward, information-rich experiments are likely to find applications in protein engineering and functional genomics. Copyright © 2010 Wiley-Liss, Inc.

  1. Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

    National Research Council Canada - National Science Library

    Mason, Alexander F; Thordarson, Pall

    2016-01-01

    The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs...

  2. Protein redox chemistry: post-translational cysteine modifications that regulate signal transduction and drug pharmacology

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    Revati eWani

    2014-10-01

    Full Text Available The perception of reactive oxygen species (ROS has evolved over the past decade from agents of cellular damage to secondary messengers which modify signaling proteins in physiology and the disease state (e.g. cancer. New protein targets of specific oxidation are rapidly being identified. One emerging class of redox modification occurs to the thiol side chain of cysteine residues which can produce multiple chemically-distinct alterations to the protein (e.g. sulfenic/sulfinic/sulfonic acid, disulfides. These post-translational modifications (PTM are shown to affect the protein structure and function. Because redox-sensitive proteins can traffic between subcellular compartments that have different redox environments, cysteine oxidation enables a spatio-temporal control to signaling. Understanding ramifications of these oxidative modifications to the functions of signaling proteins is crucial for understanding cellular regulation as well as for informed-drug discovery process. The effects of EGFR oxidation of Cys797 on inhibitor pharmacology are presented to illustrate the principle. Taken together, cysteine redox PTM can impact both cell biology and drug pharmacology.

  3. Protein Analysis Meets Visual Word Recognition: A Case for String Kernels in the Brain

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    Hannagan, Thomas; Grainger, Jonathan

    2012-01-01

    It has been recently argued that some machine learning techniques known as Kernel methods could be relevant for capturing cognitive and neural mechanisms (Jakel, Scholkopf, & Wichmann, 2009). We point out that "String kernels," initially designed for protein function prediction and spam detection, are virtually identical to one contending proposal…

  4. Modification of peptide and protein cysteine thiol groups by conjugation with a degradation product of ascorbate.

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    Kay, Phyla; Wagner, J Richard; Gagnon, Hugo; Day, Robert; Klarskov, Klaus

    2013-09-16

    Ascorbate is an important water-soluble antioxidant, which when oxidized by reactive oxygen species is converted into dehydroascorbate (DHA). If not rapidly reduced back to ascorbate, DHA decomposes to a reactive 5-carbon compound (DHA*, +130 Da) that can modify reduced cysteinyl residues in peptides and proteins in vitro. The formation of cysteine adducts by DHA* was characterized by mass spectrometry using reduced insulin B-chain, α-lactalbumin, and hemoglobin. Mass spectrometry of DHA* modified insulin B-chain revealed the presence of one and two DHA* adducts. Enzymatic cleavage and tandem mass spectrometry of modified peptides allowed unambiguous localization of DHA* to the two cysteine residues in positions 7 and 19 of the insulin B-chain. Incubations of DHA with α-lactalbumin revealed that approximately 25% of the protein population was in a reduced state and could be modified by DHA*. The adduct was assigned to the N-terminally located cysteinyl residue in position 6. Incubation of hemoglobin with DHA followed by pepsin digestion and electrospray ionization tandem mass spectrometry (ESI-MSMS) of the peptide mixture allowed for the identification of three modified peptides. Tandem mass spectrometry of the modified peptides, two from the hemoglobin A-chain with identical mass and one from the hemoglobin B-chain, gave a complete series of y-type fragment ions, which were assigned to the cysteine containing peptides (100)LLSHCL(105) (A-chain), (101)LSHCLL(106) (A-chain), and (111)VCVLAHHFGKE(121) (B-chain). Although the DHA* adduct was lost from the peptides derived from α-lactalbumin and hemoglobin before fragmentation of the peptide bond, carbamidomethylation of the proteins prior to incubation with DHA abolished the formation of DHA*-protein adducts and confirmed that the target was indeed the cysteine thiol group. Future studies are focused on the modification of proteins by DHA* in cells and in vivo.

  5. The role of the unusual threonine string in the conversion of prion protein.

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    Abskharon, Romany; Wang, Fei; Vander Stel, Kayla J; Sinniah, Kumar; Ma, Jiyan

    2016-12-16

    The conversion of normal prion protein (PrP) into pathogenic PrP conformers is central to prion disease, but the mechanism remains unclear. The α-helix 2 of PrP contains a string of four threonines, which is unusual due to the high propensity of threonine to form β-sheets. This structural feature was proposed as the basis for initiating PrP conversion, but experimental results have been conflicting. We studied the role of the threonine string on PrP conversion by analyzing mouse Prnp(a) and Prnp(b) polymorphism that contains a polymorphic residue at the beginning of the threonine string, and PrP mutants in which threonine 191 was replaced by valine, alanine, or proline. The PMCA (protein misfolding cyclic amplification) assay was able to recapitulate the in vivo transmission barrier between PrP(a) and PrP(b). Relative to PMCA, the amyloid fibril growth assay is less restrictive, but it did reflect certain properties of in vivo prion transmission. Our results suggest a plausible theory explaining the apparently contradictory results in the role of the threonine string in PrP conversion and provide novel insights into the complicated relationship among PrP stability, seeded conformational change, and prion structure, which is critical for understanding the molecular basis of prion infectivity.

  6. Mechanical strength of 17,134 model proteins and cysteine slipknots.

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    Mateusz Sikora

    2009-10-01

    Full Text Available A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17,134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cysteine slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.

  7. Lack of the Matricellular Protein SPARC (Secreted Protein, Acidic and Rich in Cysteine) Attenuates Liver Fibrogenesis in Mice

    OpenAIRE

    Catalina Atorrasagasti; Estanislao Peixoto; Jorge B Aquino; Néstor Kippes; Mariana Malvicini; Laura Alaniz; Mariana Garcia; Flavia Piccioni; Fiore, Esteban J.; Juan Bayo; Ramón Bataller; Elizabeth Guruceaga; Fernando Corrales; Osvaldo Podhajcer; Guillermo Mazzolini

    2013-01-01

    Introduction Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matricellular protein involved in many biological processes and found over-expressed in cirrhotic livers. By mean of a genetic approach we herein provide evidence from different in vivo liver disease models suggesting a profibrogenic role for SPARC. Methods Two in vivo models of liver fibrosis, based on TAA administration and bile duct ligation, were developed on SPARC wild-type (SPARC+/+) an...

  8. Do cysteine residues regulate transient receptor potential canonical type 6 (TRPC6) channel protein expression?

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Krueger, Katharina

    2012-01-01

    The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed that patie......The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed...... that patients with chronic renal failure had significantly elevated homocysteine levels and TRPC6 mRNA expression levels in monocytes compared to control subjects. We further observed that administration of homocysteine or acetylcysteine significantly increased TRPC6 channel protein expression compared...

  9. Molecular variability in the cysteine rich protein of potato virus M

    OpenAIRE

    Tabasinejad, Fatemeh; Jafarpour, Behrooz; Zakiaghl, Mohammad; Siampour, Majid; Rowhani, Hamid; Mehrvar, Mohsen

    2015-01-01

    The potato virus M (PVM), belonging to the genus Carlavirus, is a worldwide endemic pathogen in potato fields. p11 is an 11–16 kDa protein encoded by the last open reading frame of PVM which contains cysteine rich proteins (CRPs) motif. CRPs have been identified as suppressors of gene silencing. In this study the p11 gene from 28 PVM isolates, including 16 new isolates from Iran, were used to determine the global genetic structure of PVM populations. Pairwise nucleotide sequence identity scor...

  10. Merging in-silico and in vitro salivary protein complex partners using the STRING database: A tutorial.

    Science.gov (United States)

    Crosara, Karla Tonelli Bicalho; Moffa, Eduardo Buozi; Xiao, Yizhi; Siqueira, Walter Luiz

    2018-01-16

    Protein-protein interaction is a common physiological mechanism for protection and actions of proteins in an organism. The identification and characterization of protein-protein interactions in different organisms is necessary to better understand their physiology and to determine their efficacy. In a previous in vitro study using mass spectrometry, we identified 43 proteins that interact with histatin 1. Six previously documented interactors were confirmed and 37 novel partners were identified. In this tutorial, we aimed to demonstrate the usefulness of the STRING database for studying protein-protein interactions. We used an in-silico approach along with the STRING database (http://string-db.org/) and successfully performed a fast simulation of a novel constructed histatin 1 protein-protein network, including both the previously known and the predicted interactors, along with our newly identified interactors. Our study highlights the advantages and importance of applying bioinformatics tools to merge in-silico tactics with experimental in vitro findings for rapid advancement of our knowledge about protein-protein interactions. Our findings also indicate that bioinformatics tools such as the STRING protein network database can help predict potential interactions between proteins and thus serve as a guide for future steps in our exploration of the Human Interactome. Our study highlights the usefulness of the STRING protein database for studying protein-protein interactions. The STRING database can collect and integrate data about known and predicted protein-protein associations from many organisms, including both direct (physical) and indirect (functional) interactions, in an easy-to-use interface. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Improved detection specificity for plasma proteins by targeting cysteine-containing peptides with photo-SRM.

    Science.gov (United States)

    Enjalbert, Quentin; Girod, Marion; Simon, Romain; Jeudy, Jérémy; Chirot, Fabien; Salvador, Arnaud; Antoine, Rodolphe; Dugourd, Philippe; Lemoine, Jérôme

    2013-03-01

    Targeted mass spectrometry using selected reaction monitoring (SRM) has emerged as an alternative to immunoassays for protein quantification owing to faster development time and higher multiplexing capability. However, the SRM strategy is faced with the high complexity of peptide mixtures after trypsin digestion of whole plasma or the cellular proteome that most of the time causes contamination, irremediably, by interfering compounds in the transition channels monitored. This problem becomes increasingly acute when the targeted protein is present at a low concentration. In this work, the merit of laser-induced photo-dissociation in the visible region at 473 nm implemented in an hybrid quadrupole linear ion-trap mass spectrometer (photo-SRM) was evaluated for detection specificity of cysteine-containing peptides in a group of plasma proteins after tagging with a dabcyl chromophore. Compared with conventional SRM, photo-SRM chromatograms have improved detection specificity for most of peptides monitored. Comparison of the signals obtained for the best proteotypic peptides in SRM mode and those recorded by photo-SRM of cysteine-containing peptides for the same proteins reveals either increased (up to 10-fold) or similar signal to photo-SRM detection. Finally, photo-SRM has extended response linearity across a calibration plot obtained by diluting human plasma in rat plasma, down to the lowest concentrations. Hence, photo-SRM may advantageously complement conventional SRM in assay of proteins in complex biological matrices.

  12. Purification and cloning of cysteine-rich proteins from Trimeresurus jerdonii and Naja atra venoms.

    Science.gov (United States)

    Jin, Yang; Lu, Qiumin; Zhou, Xingding; Zhu, Shaowen; Li, Rui; Wang, Wanyu; Xiong, Yuliang

    2003-10-01

    Three 26 kDa proteins, named as TJ-CRVP, NA-CRVP1 and NA-CRVP2, were isolated from the venoms of Trimeresurus jerdonii and Naja atra, respectively. The N-terminal sequences of TJ-CRVP and NA-CRVPs were determined. These components were devoid of the enzymatic activities tested, such as phospholipase A(2), arginine esterase, proteolysis, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase. Furthermore, these three components did not have the following biological activities: coagulant and anticoagulant activities, lethal activity, myotoxicity, hemorrhagic activity, platelet aggregation and platelet aggregation-inhibiting activities. These proteins are named as cysteine-rich venom protein (CRVP) because their sequences showed high level of similarity with mammalian cysteine-rich secretory protein (CRISP) family. Recently, some CRISP-like proteins were also isolated from several different snake venoms, including Agkistrodon blomhoffi, Trimeresurus flavoviridis, Lanticauda semifascita and king cobra. We presumed that CRVP might be a common component in snake venoms. Of particular interest, phylogenetic analysis and sequence alignment showed that NA-CRVP1 and ophanin, both from elapid snakes, share higher similarity with CRVPs from Viperidae snakes.

  13. S-glutathionylation of cryptic cysteines enhances titin elasticity by blocking protein folding

    Science.gov (United States)

    Alegre-Cebollada, Jorge; Kosuri, Pallav; Giganti, David; Eckels, Edward; Rivas-Pardo, Jaime Andrés; Hamdani, Nazha; Warren, Chad M.; Solaro, R. John; Linke, Wolfgang A.; Fernández, Julio M.

    2014-01-01

    The giant elastic protein titin is a determinant factor in how much blood fills the left ventricle during diastole, and thus in the etiology of heart disease. Titin has been identified as a target of S-glutathionylation, an end product of the nitric oxide signaling cascade that increases cardiac muscle elasticity. However, it is unknown how S-glutathionylation may regulate the elasticity of titin and cardiac tissue. Here we show that mechanical unfolding of titin immunoglobulin (Ig) domains exposes buried cysteine residues, which then can be S-glutathionylated. S-glutathionylation of cryptic cysteines greatly decreases the mechanical stability of the parent Ig domain as well as its ability to fold. Both effects favor a more extensible state of titin. Furthermore we demonstrate that S-glutathionylation of cryptic cysteines in titin mediates mechano-chemical modulation of the elasticity of human cardiomyocytes. We propose that posttranslational modification of cryptic residues is a general mechanism to regulate tissue elasticity. PMID:24630725

  14. Characterization of a family of novel cysteine- serine-rich nuclear proteins (CSRNP.

    Directory of Open Access Journals (Sweden)

    Sébastien Gingras

    2007-08-01

    Full Text Available Gene array analysis has been widely used to identify genes induced during T cell activation. Our studies identified an immediate early gene that is strongly induced in response to IL-2 in mouse T cells which we named cysteine- serine-rich nuclear protein-1 (CSRNP-1. The human ortholog was previously identified as an AXIN1 induced gene (AXUD1. The protein does not contain sequence defined domains or motifs annotated in public databases, however the gene is a member of a family of three mammalian genes that share conserved regions, including cysteine- and serine-rich regions and a basic domain, they encode nuclear proteins, possess transcriptional activation domain and bind the sequence AGAGTG. Consequently we propose the nomenclature of CSRNP-1, -2 and -3 for the family. To elucidate the physiological functions of CSRNP-1, -2 and -3, we generated mice deficient for each of these genes by homologous recombination in embryonic stem cells. Although the CSRNP proteins have the hallmark of transcription factors and CSRNP-1 expression is highly induced by IL-2, deletion of the individual genes had no obvious consequences on normal mouse development, hematopoiesis or T cell functions. However, combined deficiencies cause partial neonatal lethality suggesting that the genes have redundant functions.

  15. Cobra venom contains a pool of cysteine-rich secretory proteins.

    Science.gov (United States)

    Osipov, Alexey V; Levashov, Mikhail Yu; Tsetlin, Victor I; Utkin, Yuri N

    2005-03-04

    A large family of cysteine-rich secretory proteins (CRISPs) includes proteins of different origin, the function of the majority of CRISPs being unknown. For CRISPs isolated from snake venom, two types of activities were found: two proteins blocked cyclic nucleotide-gated ion channels, several others blocked potassium-stimulated smooth muscle contraction. Thus, snake CRISPs represent potentially valuable tools for studies of ion channels, which makes promising a search for new CRISPs. Here we report on the isolation of several novel CRISPs from the venoms of Asian cobra Naja kaouthia and African cobra Naja haje using a combination of different types of liquid chromatography. Four CRISP variants were identified in N. kaouthia venom and three proteins, one of them acidic, were found in N. haje venom. Acidic CRISP was found in a reptilian venom for the first time. Our data suggest that each cobra venom contains a pool of different CRISPs.

  16. Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of Freshwater Planaria.

    Directory of Open Access Journals (Sweden)

    Louise S Goupil

    2016-08-01

    Full Text Available Proteases perform numerous vital functions in flatworms, many of which are likely to be conserved throughout the phylum Platyhelminthes. Within this phylum are several parasitic worms that are often poorly characterized due to their complex life-cycles and lack of responsiveness to genetic manipulation. The flatworm Schmidtea mediterranea, or planaria, is an ideal model organism to study the complex role of protein digestion due to its simple life cycle and amenability to techniques like RNA interference (RNAi. In this study, we were interested in deconvoluting the digestive protease system that exists in the planarian gut. To do this, we developed an alcohol-induced regurgitation technique to enrich for the gut enzymes in S. mediterranea. Using a panel of fluorescent substrates, we show that this treatment produces a sharp increase in proteolytic activity. These enzymes have broad yet diverse substrate specificity profiles. Proteomic analysis of the gut contents revealed the presence of cysteine and metallo-proteases. However, treatment with class-specific inhibitors showed that aspartyl and cysteine proteases are responsible for the majority of protein digestion. Specific RNAi knockdown of the cathepsin B-like cysteine protease (SmedCB reduced protein degradation in vivo. Immunohistochemistry and whole-mount in situ hybridization (WISH confirmed that the full-length and active forms of SmedCB are found in secretory cells surrounding the planaria intestinal lumen. Finally, we show that the knockdown of SmedCB reduces the speed of tissue regeneration. Defining the roles of proteases in planaria can provide insight to functions of conserved proteases in parasitic flatworms, potentially uncovering drug targets in parasites.

  17. Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of Freshwater Planaria

    Science.gov (United States)

    Goupil, Louise S.; Ivry, Sam L.; Hsieh, Ivy; Suzuki, Brian M.; Craik, Charles S.; O’Donoghue, Anthony J.; McKerrow, James H.

    2016-01-01

    Proteases perform numerous vital functions in flatworms, many of which are likely to be conserved throughout the phylum Platyhelminthes. Within this phylum are several parasitic worms that are often poorly characterized due to their complex life-cycles and lack of responsiveness to genetic manipulation. The flatworm Schmidtea mediterranea, or planaria, is an ideal model organism to study the complex role of protein digestion due to its simple life cycle and amenability to techniques like RNA interference (RNAi). In this study, we were interested in deconvoluting the digestive protease system that exists in the planarian gut. To do this, we developed an alcohol-induced regurgitation technique to enrich for the gut enzymes in S. mediterranea. Using a panel of fluorescent substrates, we show that this treatment produces a sharp increase in proteolytic activity. These enzymes have broad yet diverse substrate specificity profiles. Proteomic analysis of the gut contents revealed the presence of cysteine and metallo-proteases. However, treatment with class-specific inhibitors showed that aspartyl and cysteine proteases are responsible for the majority of protein digestion. Specific RNAi knockdown of the cathepsin B-like cysteine protease (SmedCB) reduced protein degradation in vivo. Immunohistochemistry and whole-mount in situ hybridization (WISH) confirmed that the full-length and active forms of SmedCB are found in secretory cells surrounding the planaria intestinal lumen. Finally, we show that the knockdown of SmedCB reduces the speed of tissue regeneration. Defining the roles of proteases in planaria can provide insight to functions of conserved proteases in parasitic flatworms, potentially uncovering drug targets in parasites. PMID:27501047

  18. Bacterial Cysteine-Inducible Cysteine Resistance Systems.

    Science.gov (United States)

    Takumi, Kazuhiro; Nonaka, Gen

    2016-05-01

    Cysteine donates sulfur to macromolecules and occurs naturally in many proteins. Because low concentrations of cysteine are cytotoxic, its intracellular concentration is stringently controlled. In bacteria, cysteine biosynthesis is regulated by feedback inhibition of the activities of serine acetyltransferase (SAT) and 3-phosphoglycerate dehydrogenase (3-PGDH) and is also regulated at the transcriptional level by inducing the cysteine regulon using the master regulator CysB. Here, we describe two novel cysteine-inducible systems that regulate the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for biotechnological, medical, and industrial purposes. One locus, designated ccdA(formerly PAJ_0331), encodes a novel cysteine-inducible cysteine desulfhydrase (CD) that degrades cysteine, and its expression is controlled by the transcriptional regulator encoded byccdR(formerly PAJ_0332 orybaO), located just upstream of ccdA The other locus, designated cefA (formerly PAJ_3026), encodes a novel cysteine-inducible cysteine efflux pump that is controlled by the transcriptional regulator cefR(formerly PAJ_3027), located just upstream of cefA To our knowledge, this is the first example where the expression of CD and an efflux pump is regulated in response to cysteine and is directly involved in imparting resistance to excess levels of cysteine. We propose that ccdA and cefA function as safety valves that maintain homeostasis when the intra- or extracellular cysteine concentration fluctuates. Our findings contribute important insights into optimizing the production of cysteine and related biomaterials by P. ananatis Because of its toxicity, the bacterial intracellular cysteine level is stringently regulated at biosynthesis. This work describes the identification and characterization of two novel cysteine-inducible systems that regulate, through degradation and efflux, the cysteine

  19. Iron-Binding Protein Degradation by Cysteine Proteases of Naegleria fowleri.

    Science.gov (United States)

    Martínez-Castillo, Moisés; Ramírez-Rico, Gerardo; Serrano-Luna, Jesús; Shibayama, Mineko

    2015-01-01

    Naegleria fowleri causes acute and fulminant primary amoebic meningoencephalitis. This microorganism invades its host by penetrating the olfactory mucosa and then traveling up the mesaxonal spaces and crossing the cribriform plate; finally, the trophozoites invade the olfactory bulbs. During its invasion, the protozoan obtains nutrients such as proteins, lipids, carbohydrates, and cationic ions (e.g., iron, calcium, and sodium) from the host. However, the mechanism by which these ions are obtained, particularly iron, is poorly understood. In the present study, we evaluated the ability of N. fowleri to degrade iron-binding proteins, including hololactoferrin, transferrin, ferritin, and hemoglobin. Zymography assays were performed for each substrate under physiological conditions (pH 7 at 37°C) employing conditioned medium (CM) and total crude extracts (TCEs) of N. fowleri. Different degradation patterns with CM were observed for hololactoferrin, transferrin, and hemoglobin; however, CM did not cause ferritin degradation. In contrast, the TCEs degraded only hololactoferrin and transferrin. Inhibition assays revealed that cysteine proteases were involved in this process. Based on these results, we suggest that CM and TCEs of N. fowleri degrade iron-binding proteins by employing cysteine proteases, which enables the parasite to obtain iron to survive while invading the central nervous system.

  20. Iron-Binding Protein Degradation by Cysteine Proteases of Naegleria fowleri

    Directory of Open Access Journals (Sweden)

    Moisés Martínez-Castillo

    2015-01-01

    Full Text Available Naegleria fowleri causes acute and fulminant primary amoebic meningoencephalitis. This microorganism invades its host by penetrating the olfactory mucosa and then traveling up the mesaxonal spaces and crossing the cribriform plate; finally, the trophozoites invade the olfactory bulbs. During its invasion, the protozoan obtains nutrients such as proteins, lipids, carbohydrates, and cationic ions (e.g., iron, calcium, and sodium from the host. However, the mechanism by which these ions are obtained, particularly iron, is poorly understood. In the present study, we evaluated the ability of N. fowleri to degrade iron-binding proteins, including hololactoferrin, transferrin, ferritin, and hemoglobin. Zymography assays were performed for each substrate under physiological conditions (pH 7 at 37°C employing conditioned medium (CM and total crude extracts (TCEs of N. fowleri. Different degradation patterns with CM were observed for hololactoferrin, transferrin, and hemoglobin; however, CM did not cause ferritin degradation. In contrast, the TCEs degraded only hololactoferrin and transferrin. Inhibition assays revealed that cysteine proteases were involved in this process. Based on these results, we suggest that CM and TCEs of N. fowleri degrade iron-binding proteins by employing cysteine proteases, which enables the parasite to obtain iron to survive while invading the central nervous system.

  1. Cysteine-rich venom proteins from the snakes of Viperinae subfamily - molecular cloning and phylogenetic relationship.

    Science.gov (United States)

    Ramazanova, Anna S; Starkov, Vladislav G; Osipov, Alexey V; Ziganshin, Rustam H; Filkin, Sergey Yu; Tsetlin, Victor I; Utkin, Yuri N

    2009-01-01

    Cysteine-rich proteins found in animal venoms (CRISP-Vs) are members of a large family of cysteine-rich secretory proteins (CRISPs). CRISP-Vs acting on different ion channels were found in venoms or mRNA (cDNA) encoding CRISP-Vs were cloned from snakes of three main families (Elapidae, Colubridae and Viperidae). About thirty snake CRISP-Vs were sequenced so far, however no complete sequence for CRISP-V from Viperinae subfamily was reported. We have cloned and sequenced for the first time cDNAs encoding CRISP-Vs from Vipera nikolskii and Vipera berus vipers (Viperinae). The deduced mature CRISP-V amino acid sequences consist of 220 amino acid residues. Phylogenetic analysis showed that viper proteins are closely related to those of Crotalinae snakes. The presence of CRISP-V in the V. berus venom was revealed using a combination of gel-filtration chromatography, electrophoresis and MALDI mass spectrometry. The finding of the putative channel blocker in viper venom may indicate its action on prey nervous system.

  2. Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

    2017-01-01

    Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein, we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.

  3. Site selective fragmentation of peptides and proteins at quinone modified cysteine residues investigated by ESI-MS

    Science.gov (United States)

    Diedrich, Jolene K.; Julian, Ryan R.

    2010-01-01

    Described herein are several unique analytical applications utilizing mass spectrometry and the selective modification of the free thiol form of cysteine in both peptides and proteins by various quinones. This simple modification can be used to quantify the number of free or disulfide bound cysteines in a protein. In addition, quinone modification can also be used to easily probe the solvent accessibility of cysteine residues, which provides information about protein structure or folding state. Furthermore, the chromophoric properties of the quinone moiety can be leveraged for site specific photodissociation of the backbone. The photodissociation reveals both the presence and location of modified cysteine residues. For example, cleavage of the protein backbone of alpha Hemoglobin is observed selectively at a single cysteine out of 140 residues in the whole protein. This selective backbone fragmentation is accompanied by a parent ion mass loss which is unique to the modifying quinone. When combined, this information can be used to determine both the presence and site of modification generated by naturally occurring molecules, such as dopamine, which can harness quinone chemistry to modify proteins. PMID:20405909

  4. The synthesis and protein resistance of amphiphilic PDMS-b-(PDMS-g-cysteine) copolymers

    Science.gov (United States)

    Lei, Yufeng; Lin, Yaling; Zhang, Anqiang

    2017-10-01

    Zwitterionic polymers have been used to cope with nonspecific protein adsorption and bio-fouling problems for a wide range of materials, including biomedical devices, marine coatings and membrane separation. However, direct surface modification with highly water-soluble zwitterionic polymers is rather difficult due to their poor attachment to hydrophobic solid surfaces. In this work, we utilize the hydrophobic interaction to anchor zwitterionic polysiloxanes grafted with cysteine onto surfaces by adding an hydrophobic block of polydimethylsiloxanes, referred as PDMS-b-(PDMS-g-Cys)s. The synthesis involves only three steps of reactions, and the structures of each product were characterized using GPC, FT-IR and 1H NMR. The adsorption and protein resistance of PDMS-b-(PDMS-g-Cys)s on a gold surface are investigated with QCM-D. The results show that the hydrophobic interaction moieties of the additional PDMS blocks help the hydrophilic cysteine-grafted blocks stably attach and then function on the sensor. These findings suggest that the addition of hydrophobic moieties provides an effective approach to construct anti-fouling interfaces with zwitterionic polymers in aqueous solution.

  5. A parasite cysteine protease is key to host protein degradation and iron acquisition.

    Science.gov (United States)

    O'Brien, Theresa C; Mackey, Zachary B; Fetter, Richard D; Choe, Youngchool; O'Donoghue, Anthony J; Zhou, Min; Craik, Charles S; Caffrey, Conor R; McKerrow, James H

    2008-10-24

    Cysteine proteases of the Clan CA (papain) family are the predominant protease group in primitive invertebrates. Cysteine protease inhibitors arrest infection by the protozoan parasite, Trypanosoma brucei. RNA interference studies implicated a cathepsin B-like protease, tbcatB, as a key inhibitor target. Utilizing parasites in which one of the two alleles of tbcatb has been deleted, the key role of this protease in degradation of endocytosed host proteins is delineated. TbcatB deficiency results in a decreased growth rate and dysmorphism of the flagellar pocket and the subjacent endocytic compartment. Western blot and microscopic analysis indicate that deficiency in tbcatB results in accumulation of both host and parasite proteins, including the lysosomal marker p67. A critical function for parasitism is the degradation of host transferrin, which is necessary for iron acquisition. Substrate specificity analysis of recombinant tbcatB revealed the optimal peptide cleavage sequences for the enzyme and these were confirmed experimentally using FRET-based substrates. Degradation of transferrin was validated by SDS-PAGE and the specific cleavage sites identified by N-terminal sequencing. Because even a modest deficiency in tbcatB is lethal for the parasite, tbcatB is a logical target for the development of new anti-trypanosomal chemotherapy.

  6. Molecular variability in the cysteine rich protein of potato virus M.

    Science.gov (United States)

    Tabasinejad, Fatemeh; Jafarpour, Behrooz; Zakiaghl, Mohammad; Siampour, Majid; Rowhani, Hamid; Mehrvar, Mohsen

    2015-09-01

    The potato virus M (PVM), belonging to the genus Carlavirus, is a worldwide endemic pathogen in potato fields. p11 is an 11-16 kDa protein encoded by the last open reading frame of PVM which contains cysteine rich proteins (CRPs) motif. CRPs have been identified as suppressors of gene silencing. In this study the p11 gene from 28 PVM isolates, including 16 new isolates from Iran, were used to determine the global genetic structure of PVM populations. Pairwise nucleotide sequence identity scores showed that global PVM CRP sequence similarity was between 69.3 and 100 %. This genetic diversity divided the 28 isolates into two main divergent phylogenetic clades. The rate of genetic diversity and non-synonymous to synonymous mutations (dN/dS) were significantly different between these two clades. Analysis showed that PVM CP is under significant negative selection pressure with the global ω value of 0.260.

  7. Cysteine-Rich Secretory Proteins (CRISP and their role in mammalian fertilization

    Directory of Open Access Journals (Sweden)

    Débora J Cohen

    2011-01-01

    Full Text Available Epididymal protein CRISPI is a member of the CRISP (Cysteine-RIch Secretory proteins family and is involved in sperm-egg fusion through its interaction with complementary sites on the egg surface. Results from our laboratory have shown that this binding ability resides in a 12-amino-acid region corresponding to a highly conserved motif of the CRISP family, named Signature 2 (S2. In addition to this, our results revealed that CRISP1 could also be involved in the previous step of sperm binding to the zona pellucida, identifying a novel role for this protein in fertilization. As another approach to elucidate the participation of CRISP1 in fertilization, a mouse line containing a targeted disruption of CRISP1 was generated. Although CRISP1-deficient mice exhibited normal fertility, CRISP1-defficient sperm presented a decreased level of protein tyrosine phosphorylation during capacitation, and an impaired ability to fertilize both zona-intact and zona-free eggs in vitro, confirming the proposed roles for the protein in fertilization. Evidence obtained in our laboratory indicated that testicular CRISP2 would also be involved in sperm-egg fusion. Competition assays between CRISP1 and CRISP2, as well as the comparison of their corresponding S2 regions, suggest that both proteins bind to common complementary sites in the egg. Together, these results suggest a functional cooperation between CRISP1 and CRISP2 to ensure the success of fertilization.

  8. Two Conserved Cysteine Residues Are Required for the Masculinizing Activity of the Silkworm Masc Protein*

    Science.gov (United States)

    Katsuma, Susumu; Sugano, Yudai; Kiuchi, Takashi; Shimada, Toru

    2015-01-01

    We have recently discovered that the Masculinizer (Masc) gene encodes a CCCH tandem zinc finger protein, which controls both masculinization and dosage compensation in the silkworm Bombyx mori. In this study, we attempted to identify functional regions or residues that are required for the masculinizing activity of the Masc protein. We constructed a series of plasmids that expressed the Masc derivatives and transfected them into a B. mori ovary-derived cell line, BmN-4. To assess the masculinizing activity of the Masc derivatives, we investigated the splicing patterns of B. mori doublesex (Bmdsx) and the expression levels of B. mori IGF-II mRNA-binding protein, a splicing regulator of Bmdsx, in Masc cDNA-transfected BmN-4 cells. We found that two zinc finger domains are not required for the masculinizing activity. We also identified that the C-terminal 288 amino acid residues are sufficient for the masculinizing activity of the Masc protein. Further detailed analyses revealed that two cysteine residues, Cys-301 and Cys-304, in the highly conserved region among lepidopteran Masc proteins are essential for the masculinizing activity in BmN-4 cells. Finally, we showed that Masc is a nuclear protein, but its nuclear localization is not tightly associated with the masculinizing activity. PMID:26342076

  9. Two Conserved Cysteine Residues Are Required for the Masculinizing Activity of the Silkworm Masc Protein.

    Science.gov (United States)

    Katsuma, Susumu; Sugano, Yudai; Kiuchi, Takashi; Shimada, Toru

    2015-10-23

    We have recently discovered that the Masculinizer (Masc) gene encodes a CCCH tandem zinc finger protein, which controls both masculinization and dosage compensation in the silkworm Bombyx mori. In this study, we attempted to identify functional regions or residues that are required for the masculinizing activity of the Masc protein. We constructed a series of plasmids that expressed the Masc derivatives and transfected them into a B. mori ovary-derived cell line, BmN-4. To assess the masculinizing activity of the Masc derivatives, we investigated the splicing patterns of B. mori doublesex (Bmdsx) and the expression levels of B. mori IGF-II mRNA-binding protein, a splicing regulator of Bmdsx, in Masc cDNA-transfected BmN-4 cells. We found that two zinc finger domains are not required for the masculinizing activity. We also identified that the C-terminal 288 amino acid residues are sufficient for the masculinizing activity of the Masc protein. Further detailed analyses revealed that two cysteine residues, Cys-301 and Cys-304, in the highly conserved region among lepidopteran Masc proteins are essential for the masculinizing activity in BmN-4 cells. Finally, we showed that Masc is a nuclear protein, but its nuclear localization is not tightly associated with the masculinizing activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. A new family of giardial cysteine-rich non-VSP protein genes and a novel cyst protein.

    Directory of Open Access Journals (Sweden)

    Barbara J Davids

    2006-12-01

    Full Text Available Since the Giardia lamblia cyst wall is necessary for survival in the environment and host infection, we tested the hypothesis that it contains proteins other than the three known cyst wall proteins. Serial analysis of gene expression during growth and encystation revealed a gene, "HCNCp" (High Cysteine Non-variant Cyst protein, that was upregulated late in encystation, and that resembled the classic Giardia variable surface proteins (VSPs that cover the trophozoite plasmalemma. HCNCp is 13.9% cysteine, with many "CxxC" tetrapeptide motifs and a transmembrane sequence near the C-terminus. However, HCNCp has multiple "CxC" motifs rarely found in VSPs, and does not localize to the trophozoite plasmalemma. Moreover, the HCNCp C-terminus differed from the canonical VSP signature. Full-length epitope-tagged HCNCp expressed under its own promoter was upregulated during encystation with highest expression in cysts, including 42 and 21 kDa C-terminal fragments. Tagged HCNCp targeted to the nuclear envelope in trophozoites, and co-localized with cyst proteins to encystation-specific secretory vesicles during encystation. HCNCp defined a novel trafficking pathway as it localized to the wall and body of cysts, while the cyst proteins were exclusively in the wall. Unlike VSPs, HCNCp is expressed in at least five giardial strains and four WB subclones expressing different VSPs. Bioinformatics identified 60 additional large high cysteine membrane proteins (HCMp containing > or = 20 CxxC/CxC's lacking the VSP-specific C-terminal CRGKA. HCMp were absent or rare in other model or parasite genomes, except for Tetrahymena thermophila with 30. MEME analysis classified the 61 gHCMp genes into nine groups with similar internal motifs. Our data suggest that HCNCp is a novel invariant cyst protein belonging to a new HCMp family that is abundant in the Giardia genome. HCNCp and the other HCMp provide a rich source for developing parasite-specific diagnostic reagents

  11. Cysteine-Rich Atrial Secretory Protein from the Snail Achatina achatina: Purification and Structural Characterization.

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    Sergey Shabelnikov

    Full Text Available Despite extensive studies of cardiac bioactive peptides and their functions in molluscs, soluble proteins expressed in the heart and secreted into the circulation have not yet been reported. In this study, we describe an 18.1-kDa, cysteine-rich atrial secretory protein (CRASP isolated from the terrestrial snail Achatina achatina that has no detectable sequence similarity to any known protein or nucleotide sequence. CRASP is an acidic, 158-residue, N-glycosylated protein composed of eight alpha-helical segments stabilized with five disulphide bonds. A combination of fold recognition algorithms and ab initio folding predicted that CRASP adopts an all-alpha, right-handed superhelical fold. CRASP is most strongly expressed in the atrium in secretory atrial granular cells, and substantial amounts of CRASP are released from the heart upon nerve stimulation. CRASP is detected in the haemolymph of intact animals at nanomolar concentrations. CRASP is the first secretory protein expressed in molluscan atrium to be reported. We propose that CRASP is an example of a taxonomically restricted gene that might be responsible for adaptations specific for terrestrial pulmonates.

  12. Direct determination of the redox status of cysteine residues in proteins in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Satoshi [Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503 (Japan); Tatenaka, Yuki; Ohuchi, Yuya [Dojindo Laboratories, 2025-5 Tabaru, Mashiki-machi, Kumamoto 861-2202 (Japan); Hisabori, Toru, E-mail: thisabor@res.titech.ac.jp [Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503 (Japan); Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075 (Japan)

    2015-01-02

    Highlights: • A new DNA-maleimide which is cleaved by UV irradiation, DNA-PCMal, was developed. • DNA-PCMal can be used like DNA-Mal to analyze the redox state of cysteine residues. • It is useful for detecting the thiol redox status of a protein in vivo by Western blotting method. • Thus, DNA-PCMal can be a powerful tool for redox proteomics analysis. - Abstract: The redox states of proteins in cells are key factors in many cellular processes. To determine the redox status of cysteinyl thiol groups in proteins in vivo, we developed a new maleimide reagent, a photocleavable maleimide-conjugated single stranded DNA (DNA-PCMal). The DNA moiety of DNA-PCMal is easily removed by UV-irradiation, allowing DNA-PCMal to be used in Western blotting applications. Thereby the state of thiol groups in intracellular proteins can be directly evaluated. This new maleimide compound can provide information concerning redox proteins in vivo, which is important for our understanding of redox networks in the cell.

  13. Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines*

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    Müller, Alexandra; Eller, Jakob; Albrecht, Frank; Prochnow, Pascal; Kuhlmann, Katja; Bandow, Julia Elisabeth; Slusarenko, Alan John

    2016-01-01

    Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic-resistant strains. However, the precise mode of action of allicin is unknown. Here, we show that growth inhibition of Escherichia coli during allicin exposure coincides with a depletion of the glutathione pool and S-allylmercapto modification of proteins, resulting in overall decreased total sulfhydryl levels. This is accompanied by the induction of the oxidative and heat stress response. We identified and quantified the allicin-induced modification S-allylmercaptocysteine for a set of cytoplasmic proteins by using a combination of label-free mass spectrometry and differential isotope-coded affinity tag labeling of reduced and oxidized thiol residues. Activity of isocitrate lyase AceA, an S-allylmercapto-modified candidate protein, is largely inhibited by allicin treatment in vivo. Allicin-induced protein modifications trigger protein aggregation, which largely stabilizes RpoH and thereby induces the heat stress response. At sublethal concentrations, the heat stress response is crucial to overcome allicin stress. Our results indicate that the mode of action of allicin is a combination of a decrease of glutathione levels, unfolding stress, and inactivation of crucial metabolic enzymes through S-allylmercapto modification of cysteines. PMID:27008862

  14. Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines.

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    Müller, Alexandra; Eller, Jakob; Albrecht, Frank; Prochnow, Pascal; Kuhlmann, Katja; Bandow, Julia Elisabeth; Slusarenko, Alan John; Leichert, Lars Ingo Ole

    2016-05-27

    Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic-resistant strains. However, the precise mode of action of allicin is unknown. Here, we show that growth inhibition of Escherichia coli during allicin exposure coincides with a depletion of the glutathione pool and S-allylmercapto modification of proteins, resulting in overall decreased total sulfhydryl levels. This is accompanied by the induction of the oxidative and heat stress response. We identified and quantified the allicin-induced modification S-allylmercaptocysteine for a set of cytoplasmic proteins by using a combination of label-free mass spectrometry and differential isotope-coded affinity tag labeling of reduced and oxidized thiol residues. Activity of isocitrate lyase AceA, an S-allylmercapto-modified candidate protein, is largely inhibited by allicin treatment in vivo Allicin-induced protein modifications trigger protein aggregation, which largely stabilizes RpoH and thereby induces the heat stress response. At sublethal concentrations, the heat stress response is crucial to overcome allicin stress. Our results indicate that the mode of action of allicin is a combination of a decrease of glutathione levels, unfolding stress, and inactivation of crucial metabolic enzymes through S-allylmercapto modification of cysteines. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Soilborne wheat mosaic virus (SBWMV 19K protein belongs to a class of cysteine rich proteins that suppress RNA silencing

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    Howard Amanda

    2005-03-01

    Full Text Available Abstract Amino acid sequence analyses indicate that the Soilborne wheat mosaic virus (SBWMV 19K protein is a cysteine-rich protein (CRP and shares sequence homology with CRPs derived from furo-, hordei-, peclu- and tobraviruses. Since the hordei- and pecluvirus CRPs were shown to be pathogenesis factors and/or suppressors of RNA silencing, experiments were conducted to determine if the SBWMV 19K CRP has similar activities. The SBWMV 19K CRP was introduced into the Potato virus X (PVX viral vector and inoculated to tobacco plants. The SBWMV 19K CRP aggravated PVX-induced symptoms and restored green fluorescent protein (GFP expression to GFP silenced tissues. These observations indicate that the SBWMV 19K CRP is a pathogenicity determinant and a suppressor of RNA silencing.

  16. Protein cysteine S-guanylation and electrophilic signal transduction by endogenous nitro-nucleotides.

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    Ahmed, Khandaker Ahtesham; Sawa, Tomohiro; Akaike, Takaaki

    2011-06-01

    Nitric oxide (NO), a gaseous free radical that is synthesized in organisms by nitric oxide synthases, participates in a critical fashion in the regulation of diverse physiological functions such as vascular and neuronal signal transduction, host defense, and cell death regulation. Two major pathways of NO signaling involve production of the second messenger guanosine 3',5'-cyclic monophosphate (cGMP) and posttranslational modification (PTM) of redox-sensitive cysteine thiols of proteins. We recently clarified the physiological formation of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) as the first demonstration, since the discovery of cGMP more than 40 years ago, of a new second messenger derived from cGMP in mammals. 8-Nitro-cGMP is electrophilic and reacts efficiently with sulfhydryls of proteins to produce a novel PTM via cGMP adduction, a process that we named protein S-guanylation. 8-Nitro-cGMP may regulate electrophilic signaling on the basis of its electrophilicity through induction of S-guanylation of redox sensor proteins. Examples include S-guanylation of the redox sensor protein Kelch-like ECH-associated protein 1 (Keap1), which leads to activation of NF-E2-related factor 2 (Nrf2)-dependent expression of antioxidant and cytoprotective genes. This S-guanylation-mediated activation of an antioxidant adaptive response may play an important role in cytoprotection during bacterial infections and oxidative stress. Identification of new redox-sensitive proteins as targets for S-guanylation may help development of novel therapeutics for oxidative stress- and inflammation-related disorders and vascular diseases as well as understanding of cellular protection against oxidative stress.

  17. Cysteine-rich protein 1 (CRP1 regulates actin filament bundling

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    Fraley Tamara S

    2005-12-01

    Full Text Available Abstract Background Cysteine-rich protein 1 (CRP1 is a LIM domain containing protein localized to the nucleus and the actin cytoskeleton. CRP1 has been demonstrated to bind the actin-bundling protein α-actinin and proposed to modulate the actin cytoskeleton; however, specific regulatory mechanisms have not been identified. Results CRP1 expression increased actin bundling in rat embryonic fibroblasts. Although CRP1 did not affect the bundling activity of α-actinin, CRP1 was found to stabilize the interaction of α-actinin with actin bundles and to directly bundle actin microfilaments. Using confocal and photobleaching fluorescence resonance energy transfer (FRET microscopy, we demonstrate that there are two populations of CRP1 localized along actin stress fibers, one associated through interaction with α-actinin and one that appears to bind the actin filaments directly. Consistent with a role in regulating actin filament cross-linking, CRP1 also localized to the membrane ruffles of spreading and PDGF treated fibroblasts. Conclusion CRP1 regulates actin filament bundling by directly cross-linking actin filaments and stabilizing the interaction of α-actinin with actin filament bundles.

  18. Covalent protein modification with ISG15 via a conserved cysteine in the hinge region.

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    Veronika N Bade

    Full Text Available The ubiquitin-like protein ISG15 (interferon-stimulated gene of 15 kDa is strongly induced by type I interferons and displays antiviral activity. As other ubiquitin-like proteins (Ubls, ISG15 is post-translationally conjugated to substrate proteins by an isopeptide bond between the C-terminal glycine of ISG15 and the side chains of lysine residues in the substrates (ISGylation. ISG15 consists of two ubiquitin-like domains that are separated by a hinge region. In many orthologs, this region contains a single highly reactive cysteine residue. Several hundred potential substrates for ISGylation have been identified but only a few of them have been rigorously verified. In order to investigate the modification of several ISG15 substrates, we have purified ISG15 conjugates from cell extracts by metal-chelate affinity purification and immunoprecipitations. We found that the levels of proteins modified by human ISG15 can be decreased by the addition of reducing agents. With the help of thiol blocking reagents, a mutational analysis and miRNA mediated knock-down of ISG15 expression, we revealed that this modification occurs in living cells via a disulphide bridge between the substrates and Cys78 in the hinge region of ISG15. While the ISG15 activating enzyme UBE1L is conjugated by ISG15 in the classical way, we show that the ubiquitin conjugating enzyme Ubc13 can either be classically conjugated by ISG15 or can form a disulphide bridge with ISG15 at the active site cysteine 87. The latter modification would interfere with its function as ubiquitin conjugating enzyme. However, we found no evidence for an ISG15 modification of the dynamin-like GTPases MxA and hGBP1. These findings indicate that the analysis of potential substrates for ISG15 conjugation must be performed with great care to distinguish between the two types of modification since many assays such as immunoprecipitation or metal-chelate affinity purification are performed with little or no

  19. Seed storage protein deficiency improves sulfur amino acid content in common bean (Phaseolus vulgaris L.): redirection of sulfur from gamma-glutamyl-S-methyl-cysteine.

    Science.gov (United States)

    Taylor, Meghan; Chapman, Ralph; Beyaert, Ronald; Hernández-Sebastià, Cinta; Marsolais, Frédéric

    2008-07-23

    The contents of sulfur amino acids in seeds of common bean ( Phaseolus vulgaris L.) are suboptimal for nutrition. They accumulate large amounts of a gamma-glutamyl dipeptide of S-methyl-cysteine, a nonprotein amino acid that cannot substitute for methionine or cysteine in the diet. Protein accumulation and amino acid composition were characterized in three genetically related lines integrating a progressive deficiency in major seed storage proteins, phaseolin, phytohemagglutinin, and arcelin. Nitrogen, carbon, and sulfur contents were comparable among the three lines. The contents of S-methyl-cysteine and gamma-glutamyl-S-methyl-cysteine were progressively reduced in the mutants. Sulfur was shifted predominantly to the protein cysteine pool, while total methionine was only slightly elevated. Methionine and cystine contents (mg per g protein) were increased by up to ca. 40%, to levels slightly above FAO guidelines on amino acid requirements for human nutrition. These findings may be useful to improve the nutritional quality of common bean.

  20. Characterization of methionine oxidation and methionine sulfoxide reduction using methionine-rich cysteine-free proteins

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    Liang Xinwen

    2012-10-01

    Full Text Available Abstract Background Methionine (Met residues in proteins can be readily oxidized by reactive oxygen species to Met sulfoxide (MetO. MetO is a promising physiological marker of oxidative stress and its inefficient repair by MetO reductases (Msrs has been linked to neurodegeneration and aging. Conventional methods of assaying MetO formation and reduction rely on chromatographic or mass spectrometry procedures, but the use of Met-rich proteins (MRPs may offer a more streamlined alternative. Results We carried out a computational search of completely sequenced genomes for MRPs deficient in cysteine (Cys residues and identified several proteins containing 20% or more Met residues. We used these MRPs to examine Met oxidation and MetO reduction by in-gel shift assays and immunoblot assays with antibodies generated against various oxidized MRPs. The oxidation of Cys-free MRPs by hydrogen peroxide could be conveniently monitored by SDS-PAGE and was specific for Met, as evidenced by quantitative reduction of these proteins with Msrs in DTT- and thioredoxin-dependent assays. We found that hypochlorite was especially efficient in oxidizing MRPs. Finally, we further developed a procedure wherein antibodies made against oxidized MRPs were isolated on affinity resins containing same or other oxidized or reduced MRPs. This procedure yielded reagents specific for MetO in these proteins, but proved to be ineffective in developing antibodies with broad MetO specificity. Conclusion Our data show that MRPs provide a convenient tool for characterization of Met oxidation, MetO reduction and Msr activities, and could be used for various aspects of redox biology involving reversible Met oxidation.

  1. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein.

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    Berlin Londono-Renteria

    2015-10-01

    Full Text Available Dengue virus (DENV is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were ≥5-fold differentially upregulated during flavivirus infection of the mosquito. Here, we examined the impact of silencing 100 of the most highly upregulated gene targets on DENV infection in its mosquito vector. We identified 20 genes that reduced DENV infection by at least 60% when silenced. We focused on one gene, a putative cysteine rich venom protein (SeqID AAEL000379; CRVP379, whose silencing significantly reduced DENV infection in Aedes aegypti cells. Here, we examine the requirement for CRVP379 during DENV infection of the mosquito and investigate the mechanisms surrounding this phenomenon. We also show that blocking CRVP379 protein with either RNAi or specific antisera inhibits DENV infection in Aedes aegypti. This work identifies a novel mosquito gene target for controlling DENV infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

  2. Formation of S-(carboxymethyl)-cysteine in rat liver mitochondrial proteins: effects of caloric and methionine restriction.

    Science.gov (United States)

    Naudí, Alba; Jové, Mariona; Cacabelos, Daniel; Ayala, Victoria; Cabre, Rosanna; Caro, Pilar; Gomez, José; Portero-Otín, Manuel; Barja, Gustavo; Pamplona, Reinald

    2013-02-01

    Maillard reaction contributes to the chemical modification and cross-linking of proteins. This process plays a significant role in the aging process and determination of animal longevity. Oxidative conditions promote the Maillard reaction. Mitochondria are the primary site of oxidants due to the reactive molecular species production. Mitochondrial proteome cysteine residues are targets of oxidative attack due to their specific chemistry and localization. Their chemical, non-enzymatic modification leads to dysfunctional proteins, which entail cellular senescence and organismal aging. Previous studies have consistently shown that caloric and methionine restrictions, nutritional interventions that increase longevity, decrease the rate of mitochondrial oxidant production and the physiological steady-state levels of markers of oxidative damage to macromolecules. In this scenario, we have detected S-(carboxymethyl)-cysteine (CMC) as a new irreversible chemical modification in mitochondrial proteins. CMC content in mitochondrial proteins significantly correlated with that of the lysine-derived analog N (ε)-(carboxymethyl)-lysine. The concentration of CMC is, however, one order of magnitude lower compared with CML likely due in part to the lower content of cysteine with respect to lysine of the mitochondrial proteome. CMC concentrations decreases in liver mitochondrial proteins of rats subjected to 8.5 and 25 % caloric restriction, as well as in 40 and 80 % methionine restriction. This is associated with a concomitant and significant increase in the protein content of sulfhydryl groups. Data presented here evidence that CMC, a marker of Cys-AGE formation, could be candidate as a biomarker of mitochondrial damage during aging.

  3. New Cysteine-Rich Ice-Binding Protein Secreted from Antarctic Microalga, Chloromonas sp.

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    Jung, Woongsic; Campbell, Robert L; Gwak, Yunho; Kim, Jong Im; Davies, Peter L; Jin, EonSeon

    2016-01-01

    Many microorganisms in Antarctica survive in the cold environment there by producing ice-binding proteins (IBPs) to control the growth of ice around them. An IBP from the Antarctic freshwater microalga, Chloromonas sp., was identified and characterized. The length of the Chloromonas sp. IBP (ChloroIBP) gene was 3.2 kb with 12 exons, and the molecular weight of the protein deduced from the ChloroIBP cDNA was 34.0 kDa. Expression of the ChloroIBP gene was up- and down-regulated by freezing and warming conditions, respectively. Western blot analysis revealed that native ChloroIBP was secreted into the culture medium. This protein has fifteen cysteines and is extensively disulfide bonded as shown by in-gel mobility shifts between oxidizing and reducing conditions. The open-reading frame of ChloroIBP was cloned and over-expressed in Escherichia coli to investigate the IBP's biochemical characteristics. Recombinant ChloroIBP produced as a fusion protein with thioredoxin was purified by affinity chromatography and formed single ice crystals of a dendritic shape with a thermal hysteresis activity of 0.4±0.02°C at a concentration of 5 mg/ml. In silico structural modeling indicated that the three-dimensional structure of ChloroIBP was that of a right-handed β-helix. Site-directed mutagenesis of ChloroIBP showed that a conserved region of six parallel T-X-T motifs on the β-2 face was the ice-binding region, as predicted from the model. In addition to disulfide bonding, hydrophobic interactions between inward-pointing residues on the β-1 and β-2 faces, in the region of ice-binding motifs, were crucial to maintaining the structural conformation of ice-binding site and the ice-binding activity of ChloroIBP.

  4. New Cysteine-Rich Ice-Binding Protein Secreted from Antarctic Microalga, Chloromonas sp.

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    Woongsic Jung

    Full Text Available Many microorganisms in Antarctica survive in the cold environment there by producing ice-binding proteins (IBPs to control the growth of ice around them. An IBP from the Antarctic freshwater microalga, Chloromonas sp., was identified and characterized. The length of the Chloromonas sp. IBP (ChloroIBP gene was 3.2 kb with 12 exons, and the molecular weight of the protein deduced from the ChloroIBP cDNA was 34.0 kDa. Expression of the ChloroIBP gene was up- and down-regulated by freezing and warming conditions, respectively. Western blot analysis revealed that native ChloroIBP was secreted into the culture medium. This protein has fifteen cysteines and is extensively disulfide bonded as shown by in-gel mobility shifts between oxidizing and reducing conditions. The open-reading frame of ChloroIBP was cloned and over-expressed in Escherichia coli to investigate the IBP's biochemical characteristics. Recombinant ChloroIBP produced as a fusion protein with thioredoxin was purified by affinity chromatography and formed single ice crystals of a dendritic shape with a thermal hysteresis activity of 0.4±0.02°C at a concentration of 5 mg/ml. In silico structural modeling indicated that the three-dimensional structure of ChloroIBP was that of a right-handed β-helix. Site-directed mutagenesis of ChloroIBP showed that a conserved region of six parallel T-X-T motifs on the β-2 face was the ice-binding region, as predicted from the model. In addition to disulfide bonding, hydrophobic interactions between inward-pointing residues on the β-1 and β-2 faces, in the region of ice-binding motifs, were crucial to maintaining the structural conformation of ice-binding site and the ice-binding activity of ChloroIBP.

  5. Secreted protein acidic and rich in cysteine is a matrix scavenger chaperone.

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    Alexandre Chlenski

    Full Text Available Secreted Protein Acidic and Rich in Cysteine (SPARC is one of the major non-structural proteins of the extracellular matrix (ECM in remodeling tissues. The functional significance of SPARC is emphasized by its origin in the first multicellular organisms and its high degree of evolutionary conservation. Although SPARC has been shown to act as a critical modulator of ECM remodeling with profound effects on tissue physiology and architecture, no plausible molecular mechanism of its action has been proposed. In the present study, we demonstrate that SPARC mediates the disassembly and degradation of ECM networks by functioning as a matricellular chaperone. While it has low affinity to its targets inside the cells where the Ca(2+ concentrations are low, high extracellular concentrations of Ca(2+ activate binding to multiple ECM proteins, including collagens. We demonstrated that in vitro, this leads to the inhibition of collagen I fibrillogenesis and disassembly of pre-formed collagen I fibrils by SPARC at high Ca(2+ concentrations. In cell culture, exogenous SPARC was internalized by the fibroblast cells in a time- and concentration-dependent manner. Pulse-chase assay further revealed that internalized SPARC is quickly released outside the cell, demonstrating that SPARC shuttles between the cell and ECM. Fluorescently labeled collagen I, fibronectin, vitronectin, and laminin were co-internalized with SPARC by fibroblasts, and semi-quantitative Western blot showed that SPARC mediates internalization of collagen I. Using a novel 3-dimensional model of fluorescent ECM networks pre-deposited by live fibroblasts, we demonstrated that degradation of ECM depends on the chaperone activity of SPARC. These results indicate that SPARC may represent a new class of scavenger chaperones, which mediate ECM degradation, remodeling and repair by disassembling ECM networks and shuttling ECM proteins into the cell. Further understanding of this mechanism may provide

  6. Topological Dissection of the Membrane Transport Protein Mhp1 Derived from Cysteine Accessibility and Mass Spectrometry.

    Science.gov (United States)

    Calabrese, Antonio N; Jackson, Scott M; Jones, Lynsey N; Beckstein, Oliver; Heinkel, Florian; Gsponer, Joerg; Sharples, David; Sans, Marta; Kokkinidou, Maria; Pearson, Arwen R; Radford, Sheena E; Ashcroft, Alison E; Henderson, Peter J F

    2017-09-05

    Cys accessibility and quantitative intact mass spectrometry (MS) analyses have been devised to study the topological transitions of Mhp1, the membrane protein for sodium-linked transport of hydantoins from Microbacterium liquefaciens. Mhp1 has been crystallized in three forms (outward-facing open, outward-facing occluded with substrate bound, and inward-facing open). We show that one natural cysteine residue, Cys327, out of three, has an enhanced solvent accessibility in the inward-facing (relative to the outward-facing) form. Reaction of the purified protein, in detergent, with the thiol-reactive N-ethylmalemide (NEM), results in modification of Cys327, suggesting that Mhp1 adopts predominantly inward-facing conformations. Addition of either sodium ions or the substrate 5-benzyl-l-hydantoin (L-BH) does not shift this conformational equilibrium, but systematic co-addition of the two results in an attenuation of labeling, indicating a shift toward outward-facing conformations that can be interpreted using conventional enzyme kinetic analyses. Such measurements can afford the Km for each ligand as well as the stoichiometry of ion-substrate-coupled conformational changes. Mutations that perturb the substrate binding site either result in the protein being unable to adopt outward-facing conformations or in a global destabilization of structure. The methodology combines covalent labeling, mass spectrometry, and kinetic analyses in a straightforward workflow applicable to a range of systems, enabling the interrogation of changes in a protein's conformation required for function at varied concentrations of substrates, and the consequences of mutations on these conformational transitions.

  7. Identification of endogenously S-nitrosylated proteins in Arabidopsis plantlets: effect of cold stress on cysteine nitrosylation level.

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    Puyaubert, Juliette; Fares, Abasse; Rézé, Nathalie; Peltier, Jean-Benoît; Baudouin, Emmanuel

    2014-02-01

    S-nitrosylation is a nitric oxide (NO)-based post-translational modification regulating protein function and signalling. We used a combination between the biotin switch method and labelling with isotope-coded affinity tag to identify endogenously S-nitrosylated peptides in Arabidopsis thaliana proteins extracted from plantlets. The relative level of S-nitrosylation in the identified peptides was compared between unstressed and cold-stress seedlings. We thereby detected 62 endogenously nitrosylated peptides out of which 20 are over-nitrosylated following cold exposure. Taken together these data provide a new repertoire of endogenously S-nitrosylated proteins in Arabidopsis with cysteine S-nitrosylation site. Furthermore they highlight the quantitative modification of the S-nitrosylation status of specific cysteine following cold stress. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. In vivo inhibition of cysteine proteases provides evidence for the involvement of 'senescence-associated vacuoles' in chloroplast protein degradation during dark-induced senescence of tobacco leaves.

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    Carrión, Cristian A; Costa, María Lorenza; Martínez, Dana E; Mohr, Christina; Humbeck, Klaus; Guiamet, Juan J

    2013-11-01

    Breakdown of leaf proteins, particularly chloroplast proteins, is a massive process in senescing leaves. In spite of its importance in internal N recycling, the mechanism(s) and the enzymes involved are largely unknown. Senescence-associated vacuoles (SAVs) are small, acidic vacuoles with high cysteine peptidase activity. Chloroplast-targeted proteins re-localize to SAVs during senescence, suggesting that SAVs might be involved in chloroplast protein degradation. SAVs were undetectable in mature, non-senescent tobacco leaves. Their abundance, visualized either with the acidotropic marker Lysotracker Red or by green fluorescent protein (GFP) fluorescence in a line expressing the senescence-associated cysteine protease SAG12 fused to GFP, increased during senescence induction in darkness, and peaked after 2-4 d, when chloroplast dismantling was most intense. Increased abundance of SAVs correlated with higher levels of SAG12 mRNA. Activity labelling with a biotinylated derivative of the cysteine protease inhibitor E-64 was used to detect active cysteine proteases. The two apparently most abundant cysteine proteases of senescing leaves, of 40kDa and 33kDa were detected in isolated SAVs. Rubisco degradation in isolated SAVs was completely blocked by E-64. Treatment of leaf disks with E-64 in vivo substantially reduced degradation of Rubisco and leaf proteins. Overall, these results indicate that SAVs contain most of the cysteine protease activity of senescing cells, and that SAV cysteine proteases are at least partly responsible for the degradation of stromal proteins of the chloroplast.

  9. Sulphoxythiocarbamates modify cysteine residues in HSP90 causing degradation of client proteins and inhibition of cancer cell proliferation.

    Science.gov (United States)

    Zhang, Y; Dayalan Naidu, S; Samarasinghe, K; Van Hecke, G C; Pheely, A; Boronina, T N; Cole, R N; Benjamin, I J; Cole, P A; Ahn, Y-H; Dinkova-Kostova, A T

    2014-01-07

    Heat shock protein 90 (HSP90) has a key role in the maintenance of the cellular proteostasis. However, HSP90 is also involved in stabilisation of oncogenic client proteins and facilitates oncogene addiction and cancer cell survival. The development of HSP90 inhibitors for cancer treatment is an area of growing interest as such agents can affect multiple pathways that are linked to all hallmarks of cancer. This study aimed to test the hypothesis that targeting cysteine residues of HSP90 will lead to degradation of client proteins and inhibition of cancer cell proliferation. Combining chemical synthesis, biological evaluation, and structure-activity relationship analysis, we identified a new class of HSP90 inhibitors. Click chemistry and protease-mass spectrometry established the sites of modification of the chaperone. The mildly electrophilic sulphoxythiocarbamate alkyne (STCA) selectively targets cysteine residues of HSP90, forming stable thiocarbamate adducts. Without interfering with the ATP-binding ability of the chaperone, STCA destabilises the client proteins RAF1, HER2, CDK1, CHK1, and mutant p53, and decreases proliferation of breast cancer cells. Addition of a phenyl or a tert-butyl group in tandem with the benzyl substituent at nitrogen increased the potency. A new compound, S-4, was identified as the most robust HSP90 inhibitor within a series of 19 derivatives. By virtue of their cysteine reactivity, sulphoxythiocarbamates target HSP90, causing destabilisation of its client oncoproteins and inhibiting cell proliferation.

  10. Recombinant Staphylococcal protein A with cysteine residue for preparation of affinity chromatography stationary phase and immunosensor applications

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    Gorbatiuk O. B.

    2015-04-01

    Full Text Available Aim. Engineering of recombinant Staphylococcal protein A with cysteine residue (SPA-Cys for preparation of affinity chromatography stationary phase and formation of bioselective element of immunosensor. Methods. DNA sequences encoding IgG-binding region of SPA, His-tag and cysteine were genetically fused and expressed in E. coli. SPA-Cys was immobilized on maleimide-functionalized silica beads for affinity chromatography stationary phase preparation and on a gold sensor surface as a bioselective element of immunosensor. Results. SPA-Cys was expressed at a high-level in a soluble form. The target protein was purified and showed a high IgG-binding activity. The capacity of the obtained SPA-Cys-based affinity chromatography stationary phase was 10–12 mg of IgG /ml. The purity of eluted IgG was more than 95 % in one-step purification procedure. The developed SPA-Cys-based bioselective element of immunosensor selectively interacted with human IgG and did not interact with the control proteins. Conclusions. The recombinant Staphylococcal protein A with cysteine residue was successfully used for the preparation of affinity chromatography stationary phase and formation of the bioselective element of immunosensor.

  11. Quantitation of Human Metallothionein Isoforms: A Family of Small, Highly Conserved, Cysteine-rich Proteins*

    Science.gov (United States)

    Mehus, Aaron A.; Muhonen, Wallace W.; Garrett, Scott H.; Somji, Seema; Sens, Donald A.; Shabb, John B.

    2014-01-01

    Human metallothioneins (MTs) are important regulators of metal homeostasis and protectors against oxidative damage. Their altered mRNA expression has been correlated with metal toxicity and a variety of cancers. Current immunodetection methods lack the specificity to distinguish all 12 human isoforms. Each, however, can be distinguished by the mass of its acetylated, cysteine-rich, hydrophilic N-terminal tryptic peptides. These properties were exploited to develop a bottom-up MALDI-TOF/TOF-MS-based method for their simultaneous quantitation. Key features included enrichment of N-terminal acetylated peptides by strong cation exchange chromatography, optimization of C18 reversed-phase chromatography, and control of methionine oxidation. Combinations of nine isoforms were identified in seven cell lines and two tissues. Relative quantitation was accomplished by comparing peak intensities of peptides generated from pooled cytosolic proteins alkylated with 14N- or 15N-iodoacetamide. Absolute quantitation was achieved using 15N-iodoacetamide-labeled synthetic peptides as internal standards. The method was applied to the cadmium induction of MTs in human kidney HK-2 epithelial cells expressing recombinant MT-3. Seven isoforms were detected with abundances spanning almost 2 orders of magnitude and inductions up to 12-fold. The protein-to-mRNA ratio for MT-1E was one-tenth that of other MTs, suggesting isoform-specific differences in protein expression efficiency. Differential expression of MT-1G1 and MT-1G2 suggested tissue- and cell-specific alternative splicing for the MT-1G isoform. Protein expression of MT isoforms was also evaluated in human breast epithelial cancer cell lines. Estrogen-receptor-positive cell lines expressed only MT-2 and MT-1X, whereas estrogen-receptor-negative cell lines additionally expressed MT-1E. The combined expression of MT isoforms was 38-fold greater in estrogen-receptor-negative cell lines than in estrogen-receptor-positive cells. These

  12. Quantitation of human metallothionein isoforms: a family of small, highly conserved, cysteine-rich proteins.

    Science.gov (United States)

    Mehus, Aaron A; Muhonen, Wallace W; Garrett, Scott H; Somji, Seema; Sens, Donald A; Shabb, John B

    2014-04-01

    Human metallothioneins (MTs) are important regulators of metal homeostasis and protectors against oxidative damage. Their altered mRNA expression has been correlated with metal toxicity and a variety of cancers. Current immunodetection methods lack the specificity to distinguish all 12 human isoforms. Each, however, can be distinguished by the mass of its acetylated, cysteine-rich, hydrophilic N-terminal tryptic peptides. These properties were exploited to develop a bottom-up MALDI-TOF/TOF-MS-based method for their simultaneous quantitation. Key features included enrichment of N-terminal acetylated peptides by strong cation exchange chromatography, optimization of C18 reversed-phase chromatography, and control of methionine oxidation. Combinations of nine isoforms were identified in seven cell lines and two tissues. Relative quantitation was accomplished by comparing peak intensities of peptides generated from pooled cytosolic proteins alkylated with ¹⁴N- or ¹⁵N-iodoacetamide. Absolute quantitation was achieved using ¹⁵N-iodoacetamide-labeled synthetic peptides as internal standards. The method was applied to the cadmium induction of MTs in human kidney HK-2 epithelial cells expressing recombinant MT-3. Seven isoforms were detected with abundances spanning almost 2 orders of magnitude and inductions up to 12-fold. The protein-to-mRNA ratio for MT-1E was one-tenth that of other MTs, suggesting isoform-specific differences in protein expression efficiency. Differential expression of MT-1G1 and MT-1G2 suggested tissue- and cell-specific alternative splicing for the MT-1G isoform. Protein expression of MT isoforms was also evaluated in human breast epithelial cancer cell lines. Estrogen-receptor-positive cell lines expressed only MT-2 and MT-1X, whereas estrogen-receptor-negative cell lines additionally expressed MT-1E. The combined expression of MT isoforms was 38-fold greater in estrogen-receptor-negative cell lines than in estrogen-receptor-positive cells

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

    DEFF Research Database (Denmark)

    Balogh, Ria K.; Gyurcsik, Béla; Hunyadi-Gulyás, Éva

    2016-01-01

    . 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...... 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....

  14. Click-PEGylation - A mobility shift approach to assess the redox state of cysteines in candidate proteins.

    Science.gov (United States)

    van Leeuwen, Lucie A G; Hinchy, Elizabeth C; Murphy, Michael P; Robb, Ellen L; Cochemé, Helena M

    2017-07-01

    The redox state of cysteine thiols is critical for protein function. Whereas cysteines play an important role in the maintenance of protein structure through the formation of internal disulfides, their nucleophilic thiol groups can become oxidatively modified in response to diverse redox challenges and thereby function in signalling and antioxidant defences. These oxidative modifications occur in response to a range of agents and stimuli, and can lead to the existence of multiple redox states for a given protein. To assess the role(s) of a protein in redox signalling and antioxidant defence, it is thus vital to be able to assess which of the multiple thiol redox states are present and to investigate how these alter under different conditions. While this can be done by a range of mass spectrometric-based methods, these are time-consuming, costly, and best suited to study abundant proteins or to perform an unbiased proteomic screen. One approach that can facilitate a targeted assessment of candidate proteins, as well as proteins that are low in abundance or proteomically challenging, is by electrophoretic mobility shift assays. Redox-modified cysteine residues are selectively tagged with a large group, such as a polyethylene glycol (PEG) polymer, and then the proteins are separated by electrophoresis followed by immunoblotting, which allows the inference of redox changes based on band shifts. However, the applicability of this method has been impaired by the difficulty of cleanly modifying protein thiols by large PEG reagents. To establish a more robust method for redox-selective PEGylation, we have utilised a Click chemistry approach, where free thiol groups are first labelled with a reagent modified to contain an alkyne moiety, which is subsequently Click-reacted with a PEG molecule containing a complementary azide function. This strategy can be adapted to study reversibly reduced or oxidised cysteines. Separation of the thiol labelling step from the PEG

  15. Cosmic strings

    Science.gov (United States)

    Vachaspati, Tanmay; Pogosian, Levon; Steer, Danièle A.

    2015-06-01

    "Strings" are solutions of certain field theories, whose energy is concentrated along an infinite line. Strings exist in many field theories motivated by particle physics, and this suggests that they may exist in the universe -- hence the name "cosmic strings". String solutions are also present in condensed matter systems where they are called "vortices". In cosmological applications, strings are generally curved, dynamical, and may form closed loops. The energy of a string remains concentrated along a time-dependent curve for a duration that is very long compared to the dynamical time of the string.

  16. Giardia duodenalis Surface Cysteine Proteases Induce Cleavage of the Intestinal Epithelial Cytoskeletal Protein Villin via Myosin Light Chain Kinase.

    Directory of Open Access Journals (Sweden)

    Amol Bhargava

    Full Text Available Giardia duodenalis infections are among the most common causes of waterborne diarrhoeal disease worldwide. At the height of infection, G. duodenalis trophozoites induce multiple pathophysiological processes within intestinal epithelial cells that contribute to the development of diarrhoeal disease. To date, our understanding of pathophysiological processes in giardiasis remains incompletely understood. The present study reveals a previously unappreciated role for G. duodenalis cathepsin cysteine proteases in intestinal epithelial pathophysiological processes that occur during giardiasis. Experiments first established that Giardia trophozoites indeed produce cathepsin B and L in strain-dependent fashion. Co-incubation of G. duodenalis with human enterocytes enhanced cathepsin production by Assemblage A (NF and S2 isolates trophozoites, but not when epithelial cells were exposed to Assemblage B (GSM isolate trophozoites. Direct contact between G. duodenalis parasites and human intestinal epithelial monolayers resulted in the degradation and redistribution of the intestinal epithelial cytoskeletal protein villin; these effects were abolished when parasite cathepsin cysteine proteases were inhibited. Interestingly, inhibition of parasite proteases did not prevent degradation of the intestinal tight junction-associated protein zonula occludens 1 (ZO-1, suggesting that G. duodenalis induces multiple pathophysiological processes within intestinal epithelial cells. Finally, this study demonstrates that G. duodenalis-mediated disruption of villin is, at least, in part dependent on activation of myosin light chain kinase (MLCK. Taken together, this study indicates a novel role for parasite cathepsin cysteine proteases in the pathophysiology of G. duodenalis infections.

  17. NFAP2, a novel cysteine-rich anti-yeast protein from Neosartorya fischeri NRRL 181: isolation and characterization

    OpenAIRE

    T?th, Lili?na; Kele, Zolt?n; Borics, Attila; Nagy, L?szl? G.; V?radi, Gy?rgyi; Vir?gh, M?t?; Tak?, Mikl?s; V?gv?lgyi, Csaba; Galg?czy, L?szl?

    2016-01-01

    The increasing incidence of fungal infections and damages due to drug-resistant fungi urges the development of new antifungal strategies. The cysteine-rich antifungal proteins from filamentous ascomycetes provide a feasible base for protection against molds due to their potent antifungal activity on them. In contrast to this, they show no or weak activity on yeasts, hence their applicability against this group of fungi is questionable. In the present study a 5.6?kDa anti-yeast protein (NFAP2)...

  18. Laser capture microdissection for protein and NanoString RNA analysis.

    Science.gov (United States)

    Golubeva, Yelena; Salcedo, Rosalba; Mueller, Claudius; Liotta, Lance A; Espina, Virginia

    2013-01-01

    Laser capture microdissection (LCM) allows the precise procurement of enriched cell populations from a heterogeneous tissue, or live cell culture, under direct microscopic visualization. Histologically enriched cell populations can be procured by harvesting cells of interest directly or isolating specific cells by ablating unwanted cells. The basic components of laser microdissection technology are (a) visualization of cells via light microscopy, (b) transfer of laser energy to a thermolabile polymer with either the formation of a polymer-cell composite (capture method) or transfer of laser energy via an ultraviolet laser to photovolatize a region of tissue (cutting method), and (c) removal of cells of interest from the heterogeneous tissue section. The capture and cutting methods (instruments) for laser microdissection differ in the manner by which cells of interest are removed from the heterogeneous sample. Laser energy in the capture method is infrared (810 nm), while in the cutting mode the laser is ultraviolet (355 nm). Infrared lasers melt a thermolabile polymer that adheres to the cells of interest, whereas ultraviolet lasers ablate cells for either removal of unwanted cells or excision of a defined area of cells. LCM technology is applicable to an array of applications including mass spectrometry, DNA genotyping and loss-of-heterozygosity analysis, RNA transcript profiling, cDNA library generation, proteomics discovery, and signal kinase pathway profiling. This chapter describes LCM using an Arcturus(XT) instrument for downstream protein sample analysis and using an mmi CellCut Plus® instrument for RNA analysis via NanoString technology.

  19. S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate.

    Science.gov (United States)

    Alderson, Nathan L; Wang, Yuping; Blatnik, Matthew; Frizzell, Norma; Walla, Michael D; Lyons, Timothy J; Alt, Nadja; Carson, James A; Nagai, Ryoji; Thorpe, Suzanne R; Baynes, John W

    2006-06-01

    S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

  20. Irreversible Cysteine-Selective Protein Labeling Employing Modular Electrophilic Tetrafluoroethylation Reagents

    Czech Academy of Sciences Publication Activity Database

    Václavík, Jiří; Zschoche, R.; Klimánková, Iveta; Matoušek, V.; Beier, Petr; Hilvert, D.; Togni, A.

    2017-01-01

    Roč. 23, č. 27 (2017), s. 6490-6494 ISSN 0947-6539 R&D Projects: GA ČR(CZ) GA17-00598S Institutional support: RVO:61388963 Keywords : bioconjugation * cysteine * enzymes * fluorine * fluoroalkylation * hypervalent iodine Subject RIV: CC - Organic Chemistry Impact factor: 5.317, year: 2016

  1. The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells.

    Science.gov (United States)

    Kumar, S Mathan; Haridoss, Madhumitha; Swaminathan, Kavitha; Gopal, Ramesh Kumar; Clemens, Dahn; Dey, Aparajita

    2017-02-01

    Alcohol-mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) plus 100 mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed. Pretreatment of 100 mM ethanol treated VL-17A cells with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) had opposite effects. Thus, altered GSH level through exogenous agents may either potentiate or ameliorate chronic alcohol-mediated protein adduct formation and change the cysteine level in chronic alcohol treated VL-17A cells. The gene expression of non-treated and ethanol-treated hepatocytes in 2 microarray datasets was also compared to locate differentially expressed genes involved in cysteine metabolism. The study demonstrates that increased protein adducts formation and changes in cysteine concentration occur under chronic alcohol condition in liver cells which may increase alcohol-mediated oxidative injury.

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

    DEFF Research Database (Denmark)

    Balogh, Ria K.; Gyurcsik, Béla; Hunyadi-Gulyás, Éva

    2016-01-01

    , 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......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...

  3. Role of cysteine-protease CGHC motifs of ER-60, a protein disulfide isomerase, in hepatic apolipoprotein B100 degradation.

    Science.gov (United States)

    Rutledge, Angela C; Qiu, Wei; Zhang, Rianna; Urade, Reiko; Adeli, Khosrow

    2013-09-01

    Apolipoprotein B100 (apoB), the structural component of very low density lipoproteins (VLDL), is susceptible to misfolding and subsequent degradation by several intracellular pathways. ER-60, which has been implicated in apoB degradation, is a protein disulfide isomerase (PDI) that forms or rearranges disulfide bonds in substrate proteins and also possesses cysteine protease activity. To determine which ER-60 function is important for apoB degradation, adenoviruses encoding wild-type human ER-60 or a mutant form of human ER-60 (C60A, C409A) that lacked cysteine protease activity were overexpressed in HepG2 cells. Overexpression of wild-type ER-60 in HepG2 cells promoted apoB degradation and impaired apoB secretion, but mutant ER-60 overexpression did not. In McArdle RH-7777 cells, VLDL secretion was markedly inhibited following overexpression of wild-type but not mutant ER-60, an effect that could be blocked by oleate treatment. Mutant ER-60 was not trapped on apoB as it was with the control substrate tapasin, suggesting that ER-60's role in apoB degradation is likely unrelated to its protein disulfide isomerase activity. Thus, ER-60 may participate in apoB degradation by acting as a cysteine protease. We postulate that apoB cleavage by ER-60 within the ER lumen could facilitate proteasomal degradation of the C-terminus of translocationally-arrested apoB. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Low-cysteine alpha-keratins and corneous beta-proteins are initially formed in the regenerating tail epidermis of lizard.

    Science.gov (United States)

    Alibardi, L; Michieli, F; Dalla Valle, L

    2017-01-01

    During tail regeneration in lizards, the stratified regenerating epidermis progressively gives rise to neogenic scales that form a new epidermal generation. Initially, a soft, un-scaled, pliable, and extensible epidermis is formed that is progressively replaced by a resistant but non-extensible scaled epidermis. This suggests that the initial corneous proteins are later replaced with harder corneous proteins. Using PCR and immunocytochemistry, the present study shows an upregulation in the synthesis of low-cysteine type I and II alpha-keratins and of corneous beta-proteins with a medium cysteine content and a low content in glycine (formerly termed beta-keratins) produced at the beginning of epidermal regeneration. Quantitative PCR indicates upregulation in the production of alpha-keratin mRNAs, particularly of type I, between normal and the thicker regenerating epidermis. PCR-data also indicate a higher upregulation for cysteine-rich corneous beta-proteins and a high but less intense upregulation of low glycine corneous protein mRNAs at the beginning of scale regeneration. Immunolabeling confirms the localization of these proteins, and in particular of beta-proteins with a medium content in cysteine initially formed in the wound epidermis and later in the differentiating corneous layers of regenerating scales. It is concluded that the wound epidermis initially contains alpha-keratins and corneous beta-proteins with a lower cysteine content than more specialized beta-proteins later formed in the mature scales. These initial corneous proteins are likely related to the pliability of the wound epidermis while more specialized alpha-keratins and beta-proteins richer in glycine and cysteine are synthesized later in the mature and inflexible scales. J. Morphol. 278:119-130, 2017. ©© 2016 Wiley Periodicals,Inc. © 2016 Wiley Periodicals, Inc.

  5. Mass spectrometry characterization of the thermal decomposition/digestion (TDD) at cysteine in peptides and proteins in the condensed phase.

    Science.gov (United States)

    Basile, Franco; Zhang, Shaofeng; Kandar, Sujit Kumar; Lu, Liang

    2011-11-01

    We report on the characterization by mass spectrometry (MS) of a rapid, reagentless and site-specific cleavage at the N-terminus of the amino acid cysteine (C) in peptides and proteins induced by the thermal decomposition at 220-250 °C for 10 s in solid samples. This thermally induced cleavage at C occurs under the same conditions and simultaneously to our previously reported thermally induced site-specific cleavage at the C-terminus of aspartic acid (D) (Zhang, S.; Basile, F. J. Proteome Res. 2007, 6, (5), 1700-1704). The C cleavage proceeds through cleavage of the nitrogen and α-carbon bond (N-terminus) of cysteine and produces modifications at the cleavage site with an amidation (-1 Da) of the N-terminal thermal decomposition product and a -32 Da mass change of the C-terminal thermal decomposition product, the latter yielding either an alanine or β-alanine residue at the N-terminus site. These modifications were confirmed by off-line thermal decomposition electrospray ionization (ESI)-MS, tandem MS (MS/MS) analyses and accurate mass measurements of standard peptides. Molecular oxygen was found to be required for the thermal decomposition and cleavage at C as it induced an initial cysteine thiol side chain oxidation to sulfinic acid. Similar to the thermally induced D cleavage, missed cleavages at C were also observed. The combined thermally induced digestion process at D and C, termed thermal decomposition/digestion (TDD), was observed on several model proteins tested under ambient conditions and the site-specificity of the method confirmed by MS/MS.

  6. Lack of the matricellular protein SPARC (secreted protein, acidic and rich in cysteine attenuates liver fibrogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Catalina Atorrasagasti

    Full Text Available INTRODUCTION: Secreted Protein, Acidic and Rich in Cysteine (SPARC is a matricellular protein involved in many biological processes and found over-expressed in cirrhotic livers. By mean of a genetic approach we herein provide evidence from different in vivo liver disease models suggesting a profibrogenic role for SPARC. METHODS: Two in vivo models of liver fibrosis, based on TAA administration and bile duct ligation, were developed on SPARC wild-type (SPARC(+/+ and knock-out (SPARC(-/- mice. Hepatic SPARC expression was analyzed by qPCR. Fibrosis was assessed by Sirius Red staining, and the maturation state of collagen fibers was analyzed using polarized light. Necroinflammatory activity was evaluated by applying the Knodell score and liver inflammatory infiltration was characterized by immunohistochemistry. Hepatic stellate cell activation was assessed by α-SMA immunohistochemistry. In addition, pro-fibrogenic genes and inflammatory cytokines were measured by qPCR and/or ELISA. Liver gene expression profile was analyzed in SPARC(-/- and SPARC(+/+ mice using Affymetrix Mouse Gene ST 1.0 array. RESULTS: SPARC expression was found induced in fibrotic livers of mouse and human. SPARC(-/- mice showed a reduction in the degree of inflammation, mainly CD4+ cells, and fibrosis. Consistently, collagen deposits and mRNA expression levels were decreased in SPARC(-/- mice when compared to SPARC(+/+ mice; in addition, MMP-2 expression was increased in SPARC(-/- mice. A reduction in the number of activated myofibroblasts was observed. Moreover, TGF-β1 expression levels were down-regulated in the liver as well as in the serum of TAA-treated knock-out animals. Ingenuity Pathway Analysis (IPA analysis suggested several gene networks which might involve protective mechanisms of SPARC deficiency against liver fibrogenesis and a better established machinery to repair DNA and detoxify from external chemical stimuli. CONCLUSIONS: Overall our data suggest that

  7. Cysteine specific targeting of the functionally distinct peroxiredoxin and glutaredoxin proteins by the investigational disulfide BNP7787.

    Science.gov (United States)

    Parker, Aulma R; Petluru, Pavankumar N; Nienaber, Vicki L; Badger, John; Leverett, Betsy D; Jair, Kamwing; Sridhar, Vandana; Logan, Cheyenne; Ayala, Philippe Y; Kochat, Harry; Hausheer, Frederick H

    2015-03-18

    Glutaredoxin (Grx), peroxiredoxin (Prx), and thioredoxin (Trx) are redoxin family proteins that catalyze different types of chemical reactions that impact cell growth and survival through functionally distinct intracellular pathways. Much research is focused on understanding the roles of these redoxin proteins in the development and/or progression of human diseases. Grx and Prx are overexpressed in human cancers, including human lung cancers. BNP7787 is a novel investigational agent that has been evaluated in previous clinical studies, including non-small cell lung cancer (NSCLC) studies. Herein, data from activity assays, mass spectrometry analyses, and X-ray crystallographic studies indicate that BNP7787 forms mixed disulfides with select cysteine residues on Grx and Prx and modulates their function. Studies of interactions between BNP7787 and Trx have been conducted and reported separately. Despite the fact that Trx, Grx, and Prx are functionally distinct proteins that impact oxidative stress, cell proliferation and disease processes through different intracellular pathways, BNP7787 can modify each protein and appears to modulate function through mechanisms that are unique to each target protein. Tumor cells are often genomically heterogeneous containing subpopulations of cancer cells that often express different tumor-promoting proteins or that have multiple dysregulated signaling pathways modulating cell proliferation and drug resistance. A multi-targeted agent that simultaneously modulates activity of proteins important in mediating cell proliferation by functionally distinct intracellular pathways could have many potentially useful therapeutic applications.

  8. Cysteine Specific Targeting of the Functionally Distinct Peroxiredoxin and Glutaredoxin Proteins by the Investigational Disulfide BNP7787

    Directory of Open Access Journals (Sweden)

    Aulma R. Parker

    2015-03-01

    Full Text Available Glutaredoxin (Grx, peroxiredoxin (Prx, and thioredoxin (Trx are redoxin family proteins that catalyze different types of chemical reactions that impact cell growth and survival through functionally distinct intracellular pathways. Much research is focused on understanding the roles of these redoxin proteins in the development and/or progression of human diseases. Grx and Prx are overexpressed in human cancers, including human lung cancers. BNP7787 is a novel investigational agent that has been evaluated in previous clinical studies, including non-small cell lung cancer (NSCLC studies. Herein, data from activity assays, mass spectrometry analyses, and X-ray crystallographic studies indicate that BNP7787 forms mixed disulfides with select cysteine residues on Grx and Prx and modulates their function. Studies of interactions between BNP7787 and Trx have been conducted and reported separately. Despite the fact that Trx, Grx, and Prx are functionally distinct proteins that impact oxidative stress, cell proliferation and disease processes through different intracellular pathways, BNP7787 can modify each protein and appears to modulate function through mechanisms that are unique to each target protein. Tumor cells are often genomically heterogeneous containing subpopulations of cancer cells that often express different tumor-promoting proteins or that have multiple dysregulated signaling pathways modulating cell proliferation and drug resistance. A multi-targeted agent that simultaneously modulates activity of proteins important in mediating cell proliferation by functionally distinct intracellular pathways could have many potentially useful therapeutic applications.

  9. Identification of thioredoxin h-reducible disulphides in proteornes by differential labelling of cysteines: Insight into recognition and regulation of proteins in barley seeds by thioredoxin h

    DEFF Research Database (Denmark)

    Maeda, Kenji; Finnie, Christine; Svensson, Birte

    2005-01-01

    , thioredoxin h-reducible disulphide bonds in individual target proteins are identified using a novel strategy based on differential alkylation of cysteine thiol groups by iodoacetamide and 4-vinylpyridine. This method enables the accessible cysteine side chains in the thiol form (carbamidomethylated...... alpha-amylase/subtilisin inhibitor (BASI) by barley thioredoxin h isoform 1 was analysed. Furthermore, the method was coupled with two-dimensional electrophoresis for convenient thioredoxin h-reducible disulphide identification in barley seed extracts without the need for protein purification...

  10. Identification and Gene Expression Analysis of a Taxonomically Restricted Cysteine-Rich Protein Family in Reef-Building Corals

    Science.gov (United States)

    Sunagawa, Shinichi; DeSalvo, Michael K.; Voolstra, Christian R.; Reyes-Bermudez, Alejandro; Medina, Mónica

    2009-01-01

    The amount of genomic sequence information continues to grow at an exponential rate, while the identification and characterization of genes without known homologs remains a major challenge. For non-model organisms with limited resources for manipulative studies, high-throughput transcriptomic data combined with bioinformatics methods provide a powerful approach to obtain initial insights into the function of unknown genes. In this study, we report the identification and characterization of a novel family of putatively secreted, small, cysteine-rich proteins herein named Small Cysteine-Rich Proteins (SCRiPs). Their discovery in expressed sequence tag (EST) libraries from the coral Montastraea faveolata required the performance of an iterative search strategy based on BLAST and Hidden-Markov-Model algorithms. While a discernible homolog could neither be identified in the genome of the sea anemone Nematostella vectensis, nor in a large EST dataset from the symbiotic sea anemone Aiptasia pallida, we identified SCRiP sequences in multiple scleractinian coral species. Therefore, we postulate that this gene family is an example of lineage-specific gene expansion in reef-building corals. Previously published gene expression microarray data suggest that a sub-group of SCRiPs is highly responsive to thermal stress. Furthermore, data from microarray experiments investigating developmental gene expression in the coral Acropora millepora suggest that different SCRiPs may play distinct roles in the development of corals. The function of these proteins remains to be elucidated, but our results from in silico, transcriptomic, and phylogenetic analyses provide initial insights into the evolution of SCRiPs, a novel, taxonomically restricted gene family that may be responsible for a lineage-specific trait in scleractinian corals. PMID:19283069

  11. Identification and gene expression analysis of a taxonomically restricted cysteine-rich protein family in reef-building corals.

    Directory of Open Access Journals (Sweden)

    Shinichi Sunagawa

    Full Text Available The amount of genomic sequence information continues to grow at an exponential rate, while the identification and characterization of genes without known homologs remains a major challenge. For non-model organisms with limited resources for manipulative studies, high-throughput transcriptomic data combined with bioinformatics methods provide a powerful approach to obtain initial insights into the function of unknown genes. In this study, we report the identification and characterization of a novel family of putatively secreted, small, cysteine-rich proteins herein named Small Cysteine-Rich Proteins (SCRiPs. Their discovery in expressed sequence tag (EST libraries from the coral Montastraea faveolata required the performance of an iterative search strategy based on BLAST and Hidden-Markov-Model algorithms. While a discernible homolog could neither be identified in the genome of the sea anemone Nematostella vectensis, nor in a large EST dataset from the symbiotic sea anemone Aiptasia pallida, we identified SCRiP sequences in multiple scleractinian coral species. Therefore, we postulate that this gene family is an example of lineage-specific gene expansion in reef-building corals. Previously published gene expression microarray data suggest that a sub-group of SCRiPs is highly responsive to thermal stress. Furthermore, data from microarray experiments investigating developmental gene expression in the coral Acropora millepora suggest that different SCRiPs may play distinct roles in the development of corals. The function of these proteins remains to be elucidated, but our results from in silico, transcriptomic, and phylogenetic analyses provide initial insights into the evolution of SCRiPs, a novel, taxonomically restricted gene family that may be responsible for a lineage-specific trait in scleractinian corals.

  12. Modulation of endogenous Cysteine Protease Inhibitor (ICP) 1 expression in Entamoeba histolytica affects amoebic adhesion to Extracellular Matrix proteins.

    Science.gov (United States)

    Lee, Young Ah; Saito-Nakano, Yumiko; Kim, Kyeong Ah; Min, Arim; Nozaki, Tomoyoshi; Shin, Myeong Heon

    2015-02-01

    Entamoeba histolytica is an enteric tissue-invading protozoan parasite that causes amoebic colitis and occasionally liver abscess in humans. During tissue invasion, amoebic adhesion to host components is an important event for host cell death leading to successful invasion and infection. Among amoebic virulence factors, Gal/GalNAc lectin is known to be major adhesion factor to host cells. In this study, we investigated the role of amoebic secreted CP (Cysteine Proteases) in amoebic adhesion to extracellular matrix (ECM) protein using CP inhibitor and E. histolytica strains in which the endogenous inhibitor of cysteine protease (ICP) 1 gene was overexpressed (ICP1(+)) or repressed by antisense small RNA-mediated gene silencing (ICP1(-)). We found that pretreatment of wild-type amoebae with CP inhibitor E64, or thiol-group modifiers such as diamide and N-Ethylmaleimide resulted in a significant decrease in adhesion to laminin and collagen ECM proteins. Furthermore, ICP1(+) strain, with a reduction of secreted CP activity, exhibited reduced ability by 40% to adhere to laminin. In contrast, ICP1(-) strain, with a 1.9-fold increase of secreted CP activity, showed a two-fold increase in amoebic adherence to laminin compared to the control strain. In addition, total amount of secreted CP5 was decreased in ICP1(+) amoeba. Conversely, total amount of secreted CP1 and mature-form CP5 were increased in ICP1(-) amoeba. We also found that ICP1 was secreted into extracellular milieu. These results suggest that secreted CP activity by E. histolytica may be an important factor affecting adhesion to host proteins, and regulation of CP secretion by ICP plays a major role in pathogenesis. This study provides insight into the CP-mediated tissue pathogenesis in amoeba-invaded lesions during human amoebiasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Bowed Strings

    Science.gov (United States)

    Rossing, Thomas D.; Hanson, Roger J.

    In the next eight chapters, we consider some aspects of the science of bowed string instruments, old and new. In this chapter, we present a brief discussion of bowed strings, a subject that will be developed much more thoroughly in Chap. 16. Chapters 13-15 discuss the violin, the cello, and the double bass. Chapter 17 discusses viols and other historic string instruments, and Chap. 18 discusses the Hutchins-Schelleng violin octet.

  14. Conserved extracellular cysteine residues and cytoplasmic loop-loop interplay are required for functionality of the heptahelical MLO protein.

    Science.gov (United States)

    Elliott, Candace; Müller, Judith; Miklis, Marco; Bhat, Riyaz A; Schulze-Lefert, Paul; Panstruga, Ralph

    2005-01-01

    We performed a structure-function analysis of the plasma membrane-localized plant-specific barley (Hordeum vulgare) MLO (powdery-mildew-resistance gene o) protein. Invariant cysteine and proline residues, located either in extracellular loops or transmembrane domains that have been conserved in MLO proteins for more than 400 million years, were found to be essential for MLO functionality and/or stability. Similarly to many metazoan G-protein-coupled receptors known to function as homo- and hetero-oligomers, FRET (fluorescence resonance energy transfer) analysis revealed evidence for in planta MLO dimerization/oligomerization. Domain-swap experiments with closely related wheat and rice as well as diverged Arabidopsis MLO isoforms demonstrated that the identity of the C-terminal cytoplasmic tail contributes to MLO activity. Likewise, analysis of a progressive deletion series revealed that integrity of the C-terminus determines both MLO accumulation and functionality. A series of domain swaps of cytoplasmic loops with the wheat (Triticum aestivum) orthologue, TaMLO-B1, provided strong evidence for co-operative loop-loop interplay either within the protein or between MLO molecules. Our data indicate extensive intramolecular co-evolution of cytoplasmic domains in the evolutionary history of the MLO protein family.

  15. Conserved extracellular cysteine residues and cytoplasmic loop–loop interplay are required for functionality of the heptahelical MLO protein

    Science.gov (United States)

    Elliott, Candace; Müller, Judith; Miklis, Marco; Bhat, Riyaz A.; Schulze-Lefert, Paul; Panstruga, Ralph

    2004-01-01

    We performed a structure–function analysis of the plasma membrane-localized plant-specific barley (Hordeum vulgare) MLO (powdery-mildew-resistance gene o) protein. Invariant cysteine and proline residues, located either in extracellular loops or transmembrane domains that have been conserved in MLO proteins for more than 400 million years, were found to be essential for MLO functionality and/or stability. Similarly to many metazoan G-protein-coupled receptors known to function as homo- and hetero-oligomers, FRET (fluorescence resonance energy transfer) analysis revealed evidence for in planta MLO dimerization/oligomerization. Domain-swap experiments with closely related wheat and rice as well as diverged Arabidopsis MLO isoforms demonstrated that the identity of the C-terminal cytoplasmic tail contributes to MLO activity. Likewise, analysis of a progressive deletion series revealed that integrity of the C-terminus determines both MLO accumulation and functionality. A series of domain swaps of cytoplasmic loops with the wheat (Triticum aestivum) orthologue, TaMLO-B1, provided strong evidence for co-operative loop–loop interplay either within the protein or between MLO molecules. Our data indicate extensive intramolecular co-evolution of cytoplasmic domains in the evolutionary history of the MLO protein family. PMID:15352871

  16. Identification, Characterization and Down-Regulation of Cysteine Protease Genes in Tobacco for Use in Recombinant Protein Production.

    Directory of Open Access Journals (Sweden)

    Kishor Duwadi

    Full Text Available Plants are an attractive host system for pharmaceutical protein production. Many therapeutic proteins have been produced and scaled up in plants at a low cost compared to the conventional microbial and animal-based systems. The main technical challenge during this process is to produce sufficient levels of recombinant proteins in plants. Low yield is generally caused by proteolytic degradation during expression and downstream processing of recombinant proteins. The yield of human therapeutic interleukin (IL-10 produced in transgenic tobacco leaves was found to be below the critical level, and may be due to degradation by tobacco proteases. Here, we identified a total of 60 putative cysteine protease genes (CysP in tobacco. Based on their predicted expression in leaf tissue, 10 candidate CysPs (CysP1-CysP10 were selected for further characterization. The effect of CysP gene silencing on IL-10 accumulation was examined in tobacco. It was found that the recombinant protein yield in tobacco could be increased by silencing CysP6. Transient expression of CysP6 silencing construct also showed an increase in IL-10 accumulation in comparison to the control. Moreover, CysP6 localizes to the endoplasmic reticulum (ER, suggesting that ER may be the site of IL-10 degradation. Overall results suggest that CysP6 is important in determining the yield of recombinant IL-10 in tobacco leaves.

  17. Oxidation of cysteine to cysteic acid in proteins by peroxyacids, as monitored by immobilized pH gradients.

    Science.gov (United States)

    Chiari, M; Ettori, C; Righetti, P G; Colonna, S; Gaggero, N; Negri, A

    1991-05-01

    It has often been debated whether the presence of persulfate in a polyacrylamide gel could lead to the oxidation of cysteine (Cys) in proteins to cysteic acid. In fact, direct incubation of bovine serum albumin (BSA) with peroxodisulfate and periodate barely alters the isoelectric point (pI) and does not produce any cysteic acid. In contrast, caroate (peroxomonosulfate) and perphthalate strongly lower the pI of BSA. In the former case it as demonstrated that 4-Cys (of a total of 35) were converted into cysteic acid. Perphthalate was found to be, by far, the strongest oxidant: 15 (of 35) Cys residues were oxidized to cysteic acid and all methionine groups were destroyed.

  18. String Theory

    OpenAIRE

    Marino Beiras, Marcos

    2011-01-01

    We give an overview of the relations between matrix models and string theory, focusing on topological string theory and the Dijkgraaf--Vafa correspondence. We discuss applications of this correspondence and its generalizations to supersymmetric gauge theory, enumerative geometry and mirror symmetry. We also present a brief overview of matrix quantum mechanical models in superstring theory.

  19. Export of a Cysteine-Free Misfolded Secretory Protein from the Endoplasmic Reticulum for Degradation Requires Interaction with Protein Disulfide Isomerase

    Science.gov (United States)

    Gillece, Pauline; Luz, José Manuel; Lennarz, William J.; de la Cruz, Francisco Javier; Römisch, Karin

    1999-01-01

    Protein disulfide isomerase (PDI) interacts with secretory proteins, irrespective of their thiol content, late during translocation into the ER; thus, PDI may be part of the quality control machinery in the ER. We used yeast pdi1 mutants with deletions in the putative peptide binding region of the molecule to investigate its role in the recognition of misfolded secretory proteins in the ER and their export to the cytosol for degradation. Our pdi1 deletion mutants are deficient in the export of a misfolded cysteine-free secretory protein across the ER membrane to the cytosol for degradation, but ER-to-Golgi complex transport of properly folded secretory proteins is only marginally affected. We demonstrate by chemical cross-linking that PDI specifically interacts with the misfolded secretory protein and that mutant forms of PDI have a lower affinity for this protein. In the ER of the pdi1 mutants, a higher proportion of the misfolded secretory protein remains associated with BiP, and in export-deficient sec61 mutants, the misfolded secretory protein remain bounds to PDI. We conclude that the chaperone PDI is part of the quality control machinery in the ER that recognizes terminally misfolded secretory proteins and targets them to the export channel in the ER membrane. PMID:10613903

  20. Bosonic strings

    CERN Document Server

    Jost, Jürgen

    2007-01-01

    This book presents a mathematical treatment of Bosonic string theory from the point of view of global geometry. As motivation, Jost presents the theory of point particles and Feynman path integrals. He provides detailed background material, including the geometry of Teichmüller space, the conformal and complex geometry of Riemann surfaces, and the subtleties of boundary regularity questions. The high point is the description of the partition function for Bosonic strings as a finite-dimensional integral over a moduli space of Riemann surfaces. Jost concludes with some topics related to open and closed strings and D-branes. Bosonic Strings is suitable for graduate students and researchers interested in the mathematics underlying string theory.

  1. The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle.

    Science.gov (United States)

    Arredondo, Silvia A; Kappe, Stefan H I

    2017-06-01

    During their life cycle Plasmodium parasites rely upon an arsenal of proteins that establish key interactions with the host and vector, and between the parasite sexual stages, with the purpose of ensuring infection, reproduction and proliferation. Among these is a group of secreted or membrane-anchored proteins known as the six-cysteine (6-cys) family. This is a small but important family with only 14 members thus far identified, each stage-specifically expressed during the parasite life cycle. 6-cys proteins often localise at the parasite surface or interface with the host and vector, and are conserved in different Plasmodium species. The unifying feature of the family is the s48/45 domain, presumably involved in adhesion and structurally related to Ephrins, the ligands of Eph receptors. The most prominent s48/45 members are currently under functional investigation and are being pursued as vaccine candidates. In this review, we examine what is known about the 6-cys family, their structure and function, and discuss future research directions. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  2. Resonance Raman spectra of plastocyanin and pseudoazurin: evidence for conserved cysteine ligand conformations in cupredoxins (blue copper proteins).

    Science.gov (United States)

    Han, J; Adman, E T; Beppu, T; Codd, R; Freeman, H C; Huq, L L; Loehr, T M; Sanders-Loehr, J

    1991-11-12

    New resonance Raman (RR) spectra at 15 K are reported for poplar (Populus nigra) and oleander (Oleander nerium) plastocyanins and for Alcaligenes faecalis pseudoazurin. The spectra are compared with those of other blue copper proteins (cupredoxins). In all cases, nine or more vibrational modes between 330 and 460 cm-1 can be assigned to a coupling of the Cu-S(Cys) stretch with Cys ligand deformations. The fact that these vibrations occur at a relatively constant set of frequencies is testimony to the highly conserved ground-state structure of the Cu-Cys moiety. Shifts of the vibrational modes by 1-3 cm-1 upon deuterium exchange can be correlated with N-H...S hydrogen bonds from the protein backbone to the sulfur of the Cys ligand. There is marked variability in the intensities of these Cys-related vibrations, such that each class of cupredoxin has its own pattern of RR intensities. For example, plastocyanins from poplar, oleander, French bean, and spinach have their most intense feature at approximately 425 cm-1; azurins show greatest intensity at approximately 410 cm-1, stellacyanin and ascorbate oxidase at approximately 385 cm-1, and nitrite reductase at approximately 360 cm-1. These variable intensity patterns are related to differences in the electronic excited-state structures. We propose that they have a basis in the protein environment of the copper-cysteinate chromophore. A further insight into the vibrational spectra is provided by the structures of the six cupredoxins for which crystallographic refinements at high resolution are available (plastocyanins from P. nigra, O. nerium, and Enteromorpha prolifera, pseudoazurin from A. faecalis, azurin from Alcaligenes denitrificans, and cucumber basic blue protein). The average of the Cu-S(Cys) bond lengths is 2.12 +/- 0.05 A. Since the observed range of bond lengths falls within the precision of the determinations, this variation is considered insignificant. The Cys ligand dihedral angles are also highly

  3. β-Cyanoalanine Synthase Is a Mitochondrial Cysteine Synthase-Like Protein in Spinach and Arabidopsis1

    Science.gov (United States)

    Hatzfeld, Yves; Maruyama, Akiko; Schmidt, Ahlert; Noji, Masaaki; Ishizawa, Kimiharu; Saito, Kazuki

    2000-01-01

    β-Cyano-alanine synthase (CAS; EC 4.4.1.9) plays an important role in cyanide metabolism in plants. Although the enzymatic activity of β-cyano-Ala synthase has been detected in a variety of plants, no cDNA or gene has been identified so far. We hypothesized that the mitochondrial cysteine synthase (CS; EC 4.2.99.8) isoform, Bsas3, could actually be identical to CAS in spinach (Spinacia oleracea) and Arabidopsis. An Arabidopsis expressed sequence tag database was searched for putative Bsas3 homologs and four new CS-like isoforms, ARAth;Bsas1;1, ARAth;Bsas3;1, ARAth;Bsas4;1, and ARAth;Bsas4;2, were identified in the process. ARAth;Bsas3;1 protein was homologous to the mitochondrial SPIol;Bsas3;1 isoform from spinach, whereas ARAth;Bsas4;1 and ARAth;Bsas4;2 proteins defined a new class within the CS-like proteins family. In contrast to spinach SPIol;Bsas1;1 and SPIol;Bsas2;1 recombinant proteins, spinach SPIol;Bsas3;1 and Arabidopsis ARAth;Bsas3;1 recombinant proteins exhibited preferred substrate specificities for the CAS reaction rather than for the CS reaction, which identified these Bsas3 isoforms as CAS. Immunoblot studies supported this conclusion. This is the first report of the identification of CAS synthase-encoding cDNAs in a living organism. A new nomenclature for CS-like proteins in plants is also proposed. PMID:10889265

  4. NRF2 cysteine residues are critical for oxidant/electrophile-sensing, Kelch-like ECH-associated protein-1-dependent ubiquitination-proteasomal degradation, and transcription activation.

    Science.gov (United States)

    He, Xiaoqing; Ma, Qiang

    2009-12-01

    Cells respond to oxidants and electrophiles by activating receptor/transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) to coordinate the induction of cytoprotective genes critical for defense against oxidative and other stresses. Activation involves blocking the ubiquitination-proteasomal degradation of Nrf2. Modification of cysteine thiol groups by inducers in the linker region of Kelch-like ECH-associated protein-1 (Keap1), which congregates Nrf2 into the Keap1/Cul3 E3 complex for ubiquitination, is important but not sufficient for activation of Nrf2. Here we show that evolutionarily conserved cysteine residues of Nrf2 are critical for Nrf2 regulation. FlAsH (an arsenic-based fluorophore) and phenylarsine oxide (PAO) potently induce Nrf2 target genes and bind to Nrf2 in vitro and in vivo. Binding is inhibited by prototypical inducers arsenic and tert-butylhydroquinone. PAO affinity pull-down and mutation of individual cysteine to alanine reveal that Cys235, Cys311, Cys316, Cys414, and Cys506 are critical for binding, and binding is modulated by intramolecular interactions. To corroborate the functions of cysteine residues, Nrf2 wild-type or mutants are expressed in Nrf2 knockout cells to reconstitute Nrf2 regulation. Nrf2 mutants have reduced t(1/2) that inversely correlates with increased binding to Keap1 and polyubiquitination of mutant proteins. It is remarkable that the mutants fail to respond to arsenic for Nrf2 activation and gene induction. Furthermore, mutations at Cys119, Cys235, and Cys506 impede binding of Nrf2 to endogenous antioxidant response element and to coactivator cAMP response element-binding protein-binding protein/p300. The findings demonstrate that Nrf2 cysteine residues critically regulate oxidant/electrophile sensing, repress Keap1-dependent ubiquitination-proteasomal degradation, and promote recruitment of coactivators, such that chemical sensing, receptor activation, and transcription activation are integrated at the

  5. Impact of Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression on Prognosis After Surgical Resection for Biliary Carcinoma.

    Science.gov (United States)

    Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

    2017-06-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that influences chemotherapy effectiveness and prognosis. The aim of this study was to investigate whether SPARC expression correlates with the postoperative survival of patients treated with surgical resection for biliary carcinoma. SPARC expression in resected biliary carcinoma specimens was investigated immunohistochemically in 175 patients. The relationship between SPARC expression and prognosis after surgery was evaluated using univariate and multivariate analyses. High SPARC expression in peritumoral stroma was found in 61 (35%) patients. In all patients, stromal SPARC expression was significantly associated with overall survival (OS) (P = 0.006). Multivariate analysis revealed that high stromal SPARC expression was an independent risk factor for poor OS (HR 1.81, P = 0.006). Moreover, high stromal SPARC expression was independently associated with poor prognosis in a subset of 118 patients treated with gemcitabine-based adjuvant chemotherapy (HR 2.04, P = 0.010) but not in the 57 patients who did not receive adjuvant chemotherapy (P = 0.21). Stromal SPARC expression correlated with the prognosis of patients with resectable biliary carcinoma, and its significance was enhanced in patients treated with adjuvant gemcitabine-based chemotherapy.

  6. Folding machineries displayed on a cation-exchanger for the concerted refolding of cysteine- or proline-rich proteins

    Directory of Open Access Journals (Sweden)

    Lee Dae-Hee

    2009-03-01

    Full Text Available Abstract Background Escherichia coli has been most widely used for the production of valuable recombinant proteins. However, over-production of heterologous proteins in E. coli frequently leads to their misfolding and aggregation yielding inclusion bodies. Previous attempts to refold the inclusion bodies into bioactive forms usually result in poor recovery and account for the major cost in industrial production of desired proteins from recombinant E. coli. Here, we describe the successful use of the immobilized folding machineries for in vitro refolding with the examples of high yield refolding of a ribonuclease A (RNase A and cyclohexanone monooxygenase (CHMO. Results We have generated refolding-facilitating media immobilized with three folding machineries, mini-chaperone (a monomeric apical domain consisting of residues 191–345 of GroEL and two foldases (DsbA and human peptidyl-prolyl cis-trans isomerase by mimicking oxidative refolding chromatography. For efficient and simple purification and immobilization simultaneously, folding machineries were fused with the positively-charged consecutive 10-arginine tag at their C-terminal. The immobilized folding machineries were fully functional when assayed in a batch mode. When the refolding-facilitating matrices were applied to the refolding of denatured and reduced RNase A and CHMO, both of which contain many cysteine and proline residues, RNase A and CHMO were recovered in 73% and 53% yield of soluble protein with full enzyme activity, respectively. Conclusion The refolding-facilitating media presented here could be a cost-efficient platform and should be applicable to refold a wide range of E. coli inclusion bodies in high yield with biological function.

  7. Crovirin, a snake venom cysteine-rich secretory protein (CRISP with promising activity against Trypanosomes and Leishmania.

    Directory of Open Access Journals (Sweden)

    Camila M Adade

    2014-10-01

    Full Text Available The neglected human diseases caused by trypanosomatids are currently treated with toxic therapy with limited efficacy. In search for novel anti-trypanosomatid agents, we showed previously that the Crotalus viridis viridis (Cvv snake venom was active against infective forms of Trypanosoma cruzi. Here, we describe the purification of crovirin, a cysteine-rich secretory protein (CRISP from Cvv venom with promising activity against trypanosomes and Leishmania.Crude venom extract was loaded onto a reverse phase analytical (C8 column using a high performance liquid chromatographer. A linear gradient of water/acetonitrile with 0.1% trifluoroacetic acid was used. The peak containing the isolated protein (confirmed by SDS-PAGE and mass spectrometry was collected and its protein content was measured. T. cruzi trypomastigotes and amastigotes, L. amazonensis promastigotes and amastigotes and T. brucei rhodesiense procyclic and bloodstream trypomastigotes were challenged with crovirin, whose toxicity was tested against LLC-MK2 cells, peritoneal macrophages and isolated murine extensor digitorum longus muscle. We purified a single protein from Cvv venom corresponding, according to Nano-LC MS/MS sequencing, to a CRISP of 24,893.64 Da, henceforth referred to as crovirin. Human infective trypanosomatid forms, including intracellular amastigotes, were sensitive to crovirin, with low IC50 or LD50 values (1.10-2.38 µg/ml. A considerably higher concentration (20 µg/ml of crovirin was required to elicit only limited toxicity on mammalian cells.This is the first report of CRISP anti-protozoal activity, and suggests that other members of this family might have potential as drugs or drug leads for the development of novel agents against trypanosomatid-borne neglected diseases.

  8. Secreted protein acidic and rich in cysteine (SPARC is associated with nasopharyngeal carcinoma metastasis and poor prognosis

    Directory of Open Access Journals (Sweden)

    Wang Hai-Yun

    2012-02-01

    Full Text Available Abstract Background The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC in nasopharyngeal carcinoma (NPC specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC Methods NPC tissue microarrays (TMAs were constructed from Sun Yat-sen University Cancer Center (SYSUCC, another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs induced by Bmi-1 (NPEC2 Bmi-1. The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Results The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001. SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium. In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001 and WHO histological classification (P = 0.023. NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P P P Conclusions SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.

  9. Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against Trypanosomes and Leishmania.

    Science.gov (United States)

    Adade, Camila M; Carvalho, Ana Lúcia O; Tomaz, Marcelo A; Costa, Tatiana F R; Godinho, Joseane L; Melo, Paulo A; Lima, Ana Paula C A; Rodrigues, Juliany C F; Zingali, Russolina B; Souto-Padrón, Thaïs

    2014-10-01

    The neglected human diseases caused by trypanosomatids are currently treated with toxic therapy with limited efficacy. In search for novel anti-trypanosomatid agents, we showed previously that the Crotalus viridis viridis (Cvv) snake venom was active against infective forms of Trypanosoma cruzi. Here, we describe the purification of crovirin, a cysteine-rich secretory protein (CRISP) from Cvv venom with promising activity against trypanosomes and Leishmania. Crude venom extract was loaded onto a reverse phase analytical (C8) column using a high performance liquid chromatographer. A linear gradient of water/acetonitrile with 0.1% trifluoroacetic acid was used. The peak containing the isolated protein (confirmed by SDS-PAGE and mass spectrometry) was collected and its protein content was measured. T. cruzi trypomastigotes and amastigotes, L. amazonensis promastigotes and amastigotes and T. brucei rhodesiense procyclic and bloodstream trypomastigotes were challenged with crovirin, whose toxicity was tested against LLC-MK2 cells, peritoneal macrophages and isolated murine extensor digitorum longus muscle. We purified a single protein from Cvv venom corresponding, according to Nano-LC MS/MS sequencing, to a CRISP of 24,893.64 Da, henceforth referred to as crovirin. Human infective trypanosomatid forms, including intracellular amastigotes, were sensitive to crovirin, with low IC50 or LD50 values (1.10-2.38 µg/ml). A considerably higher concentration (20 µg/ml) of crovirin was required to elicit only limited toxicity on mammalian cells. This is the first report of CRISP anti-protozoal activity, and suggests that other members of this family might have potential as drugs or drug leads for the development of novel agents against trypanosomatid-borne neglected diseases.

  10. Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation

    Directory of Open Access Journals (Sweden)

    Ma Yuliang

    2011-05-01

    Full Text Available Abstract Background Accumulation of aberrant proteins to form Lewy bodies (LBs is a hallmark of Parkinson's disease (PD. Ubiquitination-mediated degradation of aberrant, misfolded proteins is critical for maintaining normal cell function. Emerging evidence suggests that oxidative/nitrosative stress compromises the precisely-regulated network of ubiquitination in PD, particularly affecting parkin E3 ligase activity, and contributes to the accumulation of toxic proteins and neuronal cell death. Results To gain insight into the mechanism whereby cell stress alters parkin-mediated ubiquitination and LB formation, we investigated the effect of oxidative stress. We found significant increases in oxidation (sulfonation and subsequent aggregation of parkin in SH-SY5Y cells exposed to the mitochondrial complex I inhibitor 1-methyl-4-phenlypyridinium (MPP+, representing an in vitro cell-based PD model. Exposure of these cells to direct oxidation via pathological doses of H2O2 induced a vicious cycle of increased followed by decreased parkin E3 ligase activity, similar to that previously reported following S-nitrosylation of parkin. Pre-incubation with catalase attenuated H2O2 accumulation, parkin sulfonation, and parkin aggregation. Mass spectrometry (MS analysis revealed that H2O2 reacted with specific cysteine residues of parkin, resulting in sulfination/sulfonation in regions of the protein similar to those affected by parkin mutations in hereditary forms of PD. Immunohistochemistry or gel electrophoresis revealed an increase in aggregated parkin in rats and primates exposed to mitochondrial complex I inhibitors, as well as in postmortem human brain from patients with PD with LBs. Conclusion These findings show that oxidative stress alters parkin E3 ligase activity, leading to dysfunction of the ubiquitin-proteasome system and potentially contributing to LB formation.

  11. Cysteine-containing peptide tag for site-specific conjugation of proteins

    Science.gov (United States)

    Backer, Marina V.; Backer, Joseph M.

    2008-04-08

    The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

  12. Differential labelling of cysteines for simultaneous identification of thioredoxin h-reducible disulphides in native protein extracts: insight into recognition and regulation of proteins in barley seeds by thioredoxin h

    DEFF Research Database (Denmark)

    Maeda, Kenji; Finnie, Christine; Svensson, Birte

    2005-01-01

    , thioredoxin h-reducible disulphide bonds in individual target proteins are identified using a novel strategy based on differential alkylation of cysteine thiol groups by iodoacetamide and 4-vinylpyridine. This method enables the accessible cysteine side chains in the thiol form (carbamidomethylated......-amylase/subtilisin inhibitor (BASI) by barley thioredoxin h isoform 1 was analysed. Furthermore, the method was coupled with twodimensional electrophoresis for convenient thioredoxin h-reducible disulphide identification in barley seed extracts without the need for protein purification or production of recombinant proteins...

  13. Structures of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels: implications for movement of the C-terminal cysteine-rich domain

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Nobuhiro [Department of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan); Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); Yamazaki, Yasuo [Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan); Brown, R. Lane [Neurological Science Institute, Oregon Health and Science University, Beaverton, Oregon 97006 (United States); Fujimoto, Zui [Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); Morita, Takashi, E-mail: tmorita@my-pharm.ac.jp [Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan); Mizuno, Hiroshi, E-mail: tmorita@my-pharm.ac.jp [Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); VALWAY Technology Center, NEC Soft Ltd, Koto-ku, Tokyo 136-8627 (Japan); Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, Tsukuba, Ibaraki 305-8566 (Japan); Department of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan)

    2008-10-01

    The structures of pseudechetoxin and pseudecin suggest that both proteins bind to cyclic nucleotide-gated ion channels in a manner in which the concave surface occludes the pore entrance. Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteine-rich secretory protein (CRISP) family containing an N-terminal pathogenesis-related proteins of group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinities on CNG channels are different: PsTx blocks both the olfactory and retinal channels with ∼15–30-fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn{sup 2+}-bound Pdc were determined. The structures revealed that most of the amino-acid-residue differences between PsTx and Pdc are located around the concave surface formed between the PR-1 domain and the CRD, suggesting that the concave surface is functionally important for CNG-channel binding and inhibition. A structural comparison in the presence and absence of Zn{sup 2+} ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn{sup 2+} binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.

  14. Substitution of a conserved cysteine-996 in a cysteine-rich motif of the laminin {alpha}2-chain in congenital muscular dystrophy with partial deficiency of the protein

    Energy Technology Data Exchange (ETDEWEB)

    Nissinen, M.; Xu Zhang; Tryggvason, K. [Univ. of Oulu (Finland)

    1996-06-01

    Congenital muscular dystrophies (CMDs) are autosomal recessive muscle disorders of early onset. Approximately half of CMD patients present laminin {alpha}2-chain (merosin) deficiency in muscle biopsies, and the disease locus has been mapped to the region of the LAMA2 gene (6q22-23) in several families. Recently, two nonsense mutations in the laminin {alpha}2-chain gene were identified in CMD patients exhibiting complete deficiency of the laminin {alpha}2-chain in muscle biopsies. However, a subset of CMD patients with linkage to LAMA2 show only partial absence of the laminin {alpha}2-chain around muscle fibers, by immunocytochemical analysis. In the present study we have identified a homozygous missense mutation in the {alpha}2-chain gene of a consanguineous Turkish family with partial laminin {alpha}2-chain deficiency. The T{r_arrow}C transition at position 3035 in the cDNA sequence results in a Cys996{r_arrow}Arg substitution. The mutation that affects one of the conserved cysteine-rich repeats in the short arm of the laminin {alpha}2-chain should result in normal synthesis of the chain and in formation and secretion of a heterotrimeric laminin molecule. Muscular dysfunction is possibly caused either by abnormal disulfide cross-links and folding of the laminin repeat, leading to the disturbance of an as yet unknown binding function of the laminin {alpha}2-chain and to shorter half-life of the muscle-specific laminin-2 and laminin-4 isoforms, or by increased proteolytic sensitivity, leading to truncation of the short arm. 42 refs., 7 figs.

  15. Cysteine Proteinase-1 and Cut Protein Isoform Control Dendritic Innervation of Two Distinct Sensory Fields by a Single Neuron

    Directory of Open Access Journals (Sweden)

    Gray R. Lyons

    2014-03-01

    Full Text Available Dendrites often exhibit structural changes in response to local inputs. Although mechanisms that pattern and maintain dendritic arbors are becoming clearer, processes regulating regrowth, during context-dependent plasticity or after injury, remain poorly understood. We found that a class of Drosophila sensory neurons, through complete pruning and regeneration, can elaborate two distinct dendritic trees, innervating independent sensory fields. An expression screen identified Cysteine proteinase-1 (Cp1 as a critical regulator of this process. Unlike known ecdysone effectors, Cp1-mutant ddaC neurons pruned larval dendrites normally but failed to regrow adult dendrites. Cp1 expression was upregulated/concentrated in the nucleus during metamorphosis, controlling production of a truncated Cut homeodomain transcription factor. This truncated Cut, but not the full-length protein, allowed Cp1-mutant ddaC neurons to regenerate higher-order adult dendrites. These results identify a molecular pathway needed for dendrite regrowth after pruning, which allows the same neuron to innervate distinct sensory fields.

  16. Residue Modification and Mass Spectrometry for the Investigation of Structural and Metalation Properties of Metallothionein and Cysteine-Rich Proteins

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    Gordon W. Irvine

    2017-04-01

    Full Text Available Structural information regarding metallothioneins (MTs has been hard to come by due to its highly dynamic nature in the absence of metal-thiolate cluster formation and crystallization difficulties. Thus, typical spectroscopic methods for structural determination are limited in their usefulness when applied to MTs. Mass spectrometric methods have revolutionized our understanding of protein dynamics, structure, and folding. Recently, advances have been made in residue modification mass spectrometry in order to probe the hard-to-characterize structure of apo- and partially metalated MTs. By using different cysteine specific alkylation reagents, time dependent electrospray ionization mass spectrometry (ESI-MS, and step-wise “snapshot” ESI-MS, we are beginning to understand the dynamics of the conformers of apo-MT and related species. In this review we highlight recent papers that use these and similar techniques for structure elucidation and attempt to explain in a concise manner the data interpretations of these complex methods. We expect increasing resolution in our picture of the structural conformations of metal-free MTs as these techniques are more widely adopted and combined with other promising tools for structural elucidation.

  17. Unfolding Thermodynamics of Cysteine-Rich Proteins and Molecular Thermal-Adaptation of Marine Ciliates

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    Giorgia Cazzolli

    2013-11-01

    Full Text Available Euplotes nobilii and Euplotes raikovi are phylogenetically closely allied species of marine ciliates, living in polar and temperate waters, respectively. Their evolutional relation and the sharply different temperatures of their natural environments make them ideal organisms to investigate thermal-adaptation. We perform a comparative study of the thermal unfolding of disulfide-rich protein pheromones produced by these ciliates. Recent circular dichroism (CD measurements have shown that the two psychrophilic (E. nobilii and mesophilic (E. raikovi protein families are characterized by very different melting temperatures, despite their close structural homology. The enhanced thermal stability of the E. raikovi pheromones is realized notwithstanding the fact that these proteins form, as a rule, a smaller number of disulfide bonds. We perform Monte Carlo (MC simulations in a structure-based coarse-grained (CG model to show that the higher stability of the E. raikovi pheromones is due to the lower locality of the disulfide bonds, which yields a lower entropy increase in the unfolding process. Our study suggests that the higher stability of the mesophilic E. raikovi phermones is not mainly due to the presence of a strongly hydrophobic core, as it was proposed in the literature. In addition, we argue that the molecular adaptation of these ciliates may have occurred from cold to warm, and not from warm to cold. To provide a testable prediction, we identify a point-mutation of an E. nobilii pheromone that should lead to an unfolding temperature typical of that of E. raikovi pheromones.

  18. iPreny-PseAAC: Identify C-terminal Cysteine Prenylation Sites in Proteins by Incorporating Two Tiers of Sequence Couplings into PseAAC.

    Science.gov (United States)

    Xu, Yan; Wang, Zu; Li, Chunhui; Chou, Kuo-Chen

    2017-01-01

    Occurring at the cysteine residue in the C-terminal of a protein, prenylation is a special kind of post-translational modification (PTM), which may play a key role for statin in altering immune function. Therefore, knowledge of the prenylation sites in proteins is important for drug development as well as for in-depth understanding the biological process concerned. Given a query protein whose C-terminal contains some cysteine residues, which one can be of prenylation or none of them can be prenylated? To address this problem, we have developed a new predictor, called "iPreny-PseAAC", by incorporating two tiers of sequence pair coupling effects into the general form of PseAAC (pseudo amino acid composition). It has been observed by four different cross-validation approaches that all the important indexes in reflecting its prediction quality are quite high and fully consistent to each other. It is anticipated that the iPreny-PseAAC predictor holds very high potential to become a useful high throughput tool in identifying protein C-terminal cysteine prenylation sites and the other relevant areas. To maximize the convenience for most experimental biologists, the webserver for the new predictor has been established at http://app.aporc.org/iPreny-PseAAC/, by which users can easily get their desired results without needing to go through the mathematical details involved in this paper. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Biochemical characterization of RAR1 cysteine- and histidine-rich domains (CHORDs): a novel class of zinc-dependent protein-protein interaction modules.

    Science.gov (United States)

    Heise, Charles T; Le Duff, Cécile S; Boter, Marta; Casais, Catarina; Airey, Joanne E; Leech, Andrew P; Amigues, Béatrice; Guerois, Raphaël; Moore, Geoffrey R; Shirasu, Ken; Kleanthous, Colin

    2007-02-13

    Disease resistance in plants requires the activation of defense signaling pathways to prevent the spread of infection. The protein Required for Mla12 Resistance (RAR1) is a component of such pathways, which contains cysteine- and histidine-rich domains (CHORDs) that bind zinc. CHORDs are 60 amino acid domains, usually arranged in tandem, found in almost all eukaryotes, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. In the case of RAR1, CHORD-I is known to interact with heat-shock protein 90 (HSP90) and CHORD-II is known to interact with the Suppressor of the G2 allele of Skp1 (SGT1). The focus of this work on RAR1 from barley and Arabidopsis was to address the paucity of biochemical information on RAR1 and its constituent CHORDs, particularly the role of the metal ion. Sedimentation experiments indicated RAR1 to be an extended monomer in solution with few intramolecular interactions. This was reinforced by denaturation experiments, where little difference between the stability of the individual domains and intact RAR1 could be detected by intrinsic tryptophan fluorescence. Electrospray ionization-mass spectrometry and atomic absorption showed that, contrary to previous reports, RAR1 binds five zinc ions; each CHORD binds two, and the plant-specific, 20 amino acid cysteine- and histidine-containing motif (CCCH motif) located between the two CHORDs binds the fifth. Fluorescence, ultraviolet circular dichroism (UV CD), and nuclear magnetic resonance (NMR) spectroscopy further demonstrated that zinc ions are essential for maintaining CHORD structure. Finally, we used isothermal titratrion colarimetry to show that zinc is essential for the specific binding interactions of CHORD-II with SGT1. Our study provides the first biochemical and biophysical data on the zinc metalloprotein RAR1, defines its metal stoichiometry and that of its

  20. The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, William J. [University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom); Public Health England, Porton Down, Salisbury SP4 0JG (United Kingdom); Kirby, Jonathan M. [Public Health England, Porton Down, Salisbury SP4 0JG (United Kingdom); Thiyagarajan, Nethaji [University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom); Chambers, Christopher J.; Davies, Abigail H. [University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom); Public Health England, Porton Down, Salisbury SP4 0JG (United Kingdom); Roberts, April K.; Shone, Clifford C. [Public Health England, Porton Down, Salisbury SP4 0JG (United Kingdom); Acharya, K. Ravi, E-mail: bsskra@bath.ac.uk [University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom)

    2014-07-01

    The crystal structure of Cwp84, an S-layer protein from Clostridium difficile is presented for the first time. The cathepsin L-like fold of cysteine protease domain, a newly observed ‘lectin-like’ domain and several other features are described. Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhoea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. The mechanism of C. difficile surface-layer (S-layer) biogenesis is also largely unknown but involves the post-translational cleavage of a single polypeptide (surface-layer protein A; SlpA) into low- and high-molecular-weight subunits by Cwp84, a surface-located cysteine protease. Here, the first crystal structure of the surface protein Cwp84 is described at 1.4 Å resolution and the key structural components are identified. The truncated Cwp84 active-site mutant (amino-acid residues 33–497; C116A) exhibits three regions: a cleavable propeptide and a cysteine protease domain which exhibits a cathepsin L-like fold followed by a newly identified putative carbohydrate-binding domain with a bound calcium ion, which is referred to here as a lectin-like domain. This study thus provides the first structural insights into Cwp84 and a strong base to elucidate its role in the C. difficile S-layer maturation mechanism.

  1. Oxidative stress in mammalian cells impinges on the cysteines redox state of human XRCC3 protein and on its cellular localization.

    Directory of Open Access Journals (Sweden)

    Pierre-Marie Girard

    Full Text Available In vertebrates, XRCC3 is one of the five Rad51 paralogs that plays a central role in homologous recombination (HR, a key pathway for maintaining genomic stability. While investigating the potential role of human XRCC3 (hXRCC3 in the inhibition of DNA replication induced by UVA radiation, we discovered that hXRCC3 cysteine residues are oxidized following photosensitization by UVA. Our in silico prediction of the hXRCC3 structure suggests that 6 out of 8 cysteines are potentially accessible to the solvent and therefore potentially exposed to ROS attack. By non-reducing SDS-PAGE we show that many different oxidants induce hXRCC3 oxidation that is monitored in Chinese hamster ovarian (CHO cells by increased electrophoretic mobility of the protein and in human cells by a slight decrease of its immunodetection. In both cell types, hXRCC3 oxidation was reversed in few minutes by cellular reducing systems. Depletion of intracellular glutathione prevents hXRCC3 oxidation only after UVA exposure though depending on the type of photosensitizer. In addition, we show that hXRCC3 expressed in CHO cells localizes both in the cytoplasm and in the nucleus. Mutating all hXRCC3 cysteines to serines (XR3/S protein does not affect the subcellular localization of the protein even after exposure to camptothecin (CPT, which typically induces DNA damages that require HR to be repaired. However, cells expressing mutated XR3/S protein are sensitive to CPT, thus highlighting a defect of the mutant protein in HR. In marked contrast to CPT treatment, oxidative stress induces relocalization at the chromatin fraction of both wild-type and mutated protein, even though survival is not affected. Collectively, our results demonstrate that the DNA repair protein hXRCC3 is a target of ROS induced by environmental factors and raise the possibility that the redox environment might participate in regulating the HR pathway.

  2. Plasmodium Cysteine Repeat Modular Proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host

    Directory of Open Access Journals (Sweden)

    Mota Maria M

    2011-03-01

    Full Text Available Abstract Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp3 and Δpcrmp4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp3 and Δpcrmp4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life

  3. Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in Clinical Isolates of Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Sanchita Das

    2015-08-01

    Full Text Available Resistance emergence against antileishmanial drugs, particularly Sodium Antimony Gluconate (SAG has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. Cysteine leucine rich protein (CLrP, was recognized as one of the overexpressed proteins in resistant isolates, as observed in differential proteomics between sensitive and resistant isolates of L. donovani. The present study deals with the characterization of CLrP and for its possible connection with SAG resistance.In pursuance of deciphering the role of CLrP in SAG resistance, gene was cloned, over-expressed in E. coli system and thereafter antibody was raised. The expression profile of CLrP and was found to be over-expressed in SAG resistant clinical isolates of L. donovani as compared to SAG sensitive ones when investigated by real-time PCR and western blotting. CLrP has been characterized through bioinformatics, immunoblotting and immunolocalization analysis, which reveals its post-translational modification along with its dual existence in the nucleus as well as in the membrane of the parasite. Further investigation using a ChIP assay confirmed its DNA binding potential. Over-expression of CLrP in sensitive isolate of L. donovani significantly decreased its responsiveness to SAG (SbV and SbIII and a shift towards the resistant mode was observed. Further, a significant increase in its infectivity in murine macrophages has been observed.The study reports the differential expression of CLrP in SAG sensitive and resistant isolates of L. donovani. Functional intricacy of CLrP increases with dual localization, glycosylation and DNA binding potential of the protein. Further over-expressing CLrP in sensitive isolate of L. donovani shows significantly decreased sensitivity towards SAG and increased infectivity as well, thus assisting the parasite in securing a safe niche. Results indicates the possible contribution of CLr

  4. Expression and localization of cysteine-rich secretory protein-3 (CRISP-3) in the prepubertal and postpubertal male horse.

    Science.gov (United States)

    Fedorka, C E; Scoggin, K E; Squires, E L; Ball, B A; Troedsson, M H T

    2017-01-01

    The seminal plasma protein, cysteine-rich secretory protein-3 (CRISP-3), has been correlated with increased fertility and first-cycle conception rates, and has been suggested to be involved in the modulation of polymorphonuclear neutrophil and phagocytosis of spermatozoa during the inflammatory response to breeding in the horse. Previous research demonstrated that equine CRISP-3 is located in both the ampulla of the vas deferens and the seminal vesicles. However, this was done with nonquantitative laboratory techniques. In humans and rodents, CRISP-3 has been described as an androgen-dependent protein, but the effect of androgens on the expression of CRISP-3 has not been investigated in the horse. The objectives of this study were to (a) confirm and quantify the expression of CRISP-3 in the male equine reproductive tract, (b) describe the localization of CRISP-3 within the specific tissues which express it, and (c) determine if expression of CRISP-3 increases after puberty. We hypothesized that expression of CRISP-3 would be expressed in both the ampulla of the vas deferens and the seminal vesicles, and expression would increase after puberty. Tissues were collected postmortem from three prepubertal colts (3 years). Tissue samples were collected from the ampulla of vas deferens, seminal vesicles, bulbourethral gland, prostate gland, testis, as well as the cauda, corpus, and caput aspects of the epididymis. Quantitative real-time polymerase chain reaction and immunohistochemistry (IHC) were performed using an equine-specific CRISP-3 designed primer and monocolonal antibody. A mixed linear additive model was used to compare mRNA expression between age groups, and significance was set to P CRISP-3 mRNA was found primarily in the ampulla of vas deferens with lesser expression in the seminal vesicles. Expression of CRISP-3 was higher in the postpubertal stallion when compared with the prepubertal colt for the ampulla (P CRISP-3 is primarily located in the glandular

  5. Teaching Strings.

    Science.gov (United States)

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    Intended primarily for use by instrumental music teachers who do not have a major concentration in strings, this guide provides pertinent basic resources, materials, teaching--learning expectation, and a general overall guide to achievement levels at various stages of development. Discussions are presented of Choosing the Proper Method Book,…

  6. String phenomenology

    CERN Document Server

    Ibáñez, Luis E

    2015-01-01

    This chapter reviews a number of topics in the field of string phenomenology, focusing on orientifold/F-theory models yielding semirealistic low-energy physics. The emphasis is on the extraction of the low-energy effective action and possible tests of specific models at the LHC.

  7. Design of novel synthetic MTS conjugates of bile acids for site-directed sulfhydryl labeling of cysteine residues in bile acid binding and transporting proteins.

    Science.gov (United States)

    Ray, Abhijit; Banerjee, Antara; Chang, Cheng; Khantwal, Chandra M; Swaan, Peter W

    2006-03-15

    The purpose of this study was to design bile acid-containing methanethiosulfonate (MTS) agents with appropriate physical attributes to effectively modify the cysteine residues present in the human apical sodium-dependent bile acid transporter. Four physical properties including surface area, molecular volume, ClogP, and dipole moment were calculated for each semiempirically optimized structure of MTS compounds. The specificity of the synthesized bile acid-MTS conjugate toward native cysteines and putative bile acid interacting domains of hASBT was supported by the effect of 1mM cholyl-MTS, cholylglycyl-MTS, and 3-amino-cholyl-MTS on uptake activity, that displayed a significant decrease in TCA affinity (K(T)=69.9+/-4.5, 69.01+/-6.2, and 63.24+/-0.26 microM and J(max)=35.8+/-0.3, 24.03+/-1.22, 46.49+/-5.01 pmol mg protein min(-1), respectively). These compounds prove to be effective tools in probing the structural and functional effects of cysteine residues in bile acid binding and transporting proteins.

  8. Influence of protein-micelle ratios and cysteine residues on the kinetic stability and unfolding rates of human mitochondrial VDAC-2.

    Directory of Open Access Journals (Sweden)

    Svetlana Rajkumar Maurya

    Full Text Available Delineating the kinetic and thermodynamic factors which contribute to the stability of transmembrane β-barrels is critical to gain an in-depth understanding of membrane protein behavior. Human mitochondrial voltage-dependent anion channel isoform 2 (hVDAC-2, one of the key anti-apoptotic eukaryotic β-barrel proteins, is of paramount importance, owing to its indispensable role in cell survival. We demonstrate here that the stability of hVDAC-2 bears a strong kinetic contribution that is dependent on the absolute micellar concentration used for barrel folding. The refolding efficiency and ensuing stability is sensitive to the lipid-to-protein (LPR ratio, and displays a non-linear relationship, with both low and high micellar amounts being detrimental to hVDAC-2 structure. Unfolding and aggregation process are sequential events and show strong temperature dependence. We demonstrate that an optimal lipid-to-protein ratio of 2600∶1 - 13,000∶1 offers the highest protection against thermal denaturation. Activation energies derived only for lower LPRs are ∼17 kcal mol(-1 for full-length hVDAC-2 and ∼23 kcal mol(-1 for the Cys-less mutant, suggesting that the nine cysteine residues of hVDAC-2 impart additional malleability to the barrel scaffold. Our studies reveal that cysteine residues play a key role in the kinetic stability of the protein, determine barrel rigidity and thereby give rise to strong micellar association of hVDAC-2. Non-linearity of the Arrhenius plot at high LPRs coupled with observation of protein aggregation upon thermal denaturation indicates that contributions from both kinetic and thermodynamic components stabilize the 19-stranded β-barrel. Lipid-protein interaction and the linked kinetic contribution to free energy of the folded protein are together expected to play a key role in hVDAC-2 recycling and the functional switch at the onset of apoptosis.

  9. The role of cysteine residues in redox regulation and protein stability of Arabidopsis thaliana starch synthase 1

    DEFF Research Database (Denmark)

    Skryhan, Katsiaryna; Cuesta-Seijo, Jose A.; Nielsen, Morten M

    2015-01-01

    Starch biosynthesis in Arabidopsis thaliana is strictly regulated. In leaf extracts, starch synthase 1 (AtSS1) responds to the redox potential within a physiologically relevant range. This study presents data testing two main hypotheses: 1) that specific thiol-disulfide exchange in AtSS1 influences...... its catalytic function 2) that each conserved Cys residue has an impact on AtSS1 catalysis. Recombinant AtSS1 versions carrying combinations of cysteine-to-serine substitutions were generated and characterized in vitro. The results demonstrate that AtSS1 is activated and deactivated...... is in the reduced and active form during the day with active photosynthesis. Cys164 and Cys545 were the key cysteine residues involved in regulatory disulfide formation upon oxidation. A C164S_C545S double mutant had considerably decreased redox sensitivity as compared to wild type AtSS1 (30% vs 77%). Michaelis...

  10. Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: Functional convergence of a common protein fold

    Energy Technology Data Exchange (ETDEWEB)

    Casados-Vázquez, Luz E.; Lara-González, Samuel; Brieb, Luis G. (LNGB-Mexico)

    2012-04-18

    Cysteine proteases (CP) are key pathogenesis and virulence determinants of protozoan parasites. Entamoeba histolytica contains at least 50 cysteine proteases; however, only three (EhCP1, EhCP2 and EhCP5) are responsible for approximately 90% of the cysteine protease activity in this parasite. CPs are expressed as inactive zymogens. Because the processed proteases are potentially cytotoxic, protozoan parasites have developed mechanisms to regulate their activity. Inhibitors of cysteine proteases (ICP) of the chagasin-like inhibitor family (MEROPS family I42) were recently identified in bacteria and protozoan parasites. E. histolytica contains two ICP-encoding genes of the chagasin-like inhibitor family. EhICP1 localizes to the cytosol, whereas EhICP2 is targeted to phagosomes. Herein, we report two crystal structures of EhICP2. The overall structure of EhICP2 consists of eight {beta}-strands and closely resembles the immunoglobulin fold. A comparison between the two crystal forms of EhICP2 indicates that the conserved BC, DE and FG loops form a flexible wedge that may block the active site of CPs. The positively charged surface of the wedge-forming loops in EhICP2 contrasts with the neutral surface of the wedge-forming loops in chagasin. We postulate that the flexibility and positive charge observed in the DE and FG loops of EhICP2 may be important to facilitate the initial binding of this inhibitor to the battery of CPs present in E. histolytica.

  11. Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel.

    Science.gov (United States)

    Wang, Jing; Shen, Bing; Guo, Min; Lou, Xiaohua; Duan, Yuanyuan; Cheng, Xin Ping; Teng, Maikun; Niu, Liwen; Liu, Qun; Huang, Qingqiu; Hao, Quan

    2005-08-02

    Cysteine-rich secretory proteins (CRISPs) are widespread in snake venoms. Some members of these CRISPs recently have been found to block L-type Ca(2+) channels or cyclic nucleotide-gated ion (CNG) channels. Here, natrin purified from Naja atra venom, a member of the CRISP family, can induce a further contractile response in the endothelium-denuded thoracic aorta of mouse which has been contracted by a high-K(+) solution. Further experiments show it can block the high-conductance calcium-activated potassium (BK(Ca)) channel in a concentration-dependent manner with an IC(50) of 34.4 nM and a Hill coefficient of 1.02, which suggests that only a single natrin molecule is required to bind an ion channel to block BK(Ca) current. The crystal structure of natrin displaying two domains in tandem shows its cysteine-rich domain (CRD) has relatively independent flexibility, especially for the C-terminal long loop (loop I) of CRD to participate in the interface of two domains. On the basis of previous studies of CNG channel and L-Ca(2+) channel blockers, and the sequence and structural comparison of natrin and stecrisp, the deviation of the vital loop I of CRD is suggested to contribute to different effects of some CRISPs in protein-protein interaction.

  12. Crystal Structure of a Hidden Protein, YcaC, a Putative Cysteine Hydrolase from Pseudomonas aeruginosa, with and without an Acrylamide Adduct

    Directory of Open Access Journals (Sweden)

    Morten K. Grøftehauge

    2015-07-01

    Full Text Available As part of the ongoing effort to functionally and structurally characterize virulence factors in the opportunistic pathogen Pseudomonas aeruginosa, we determined the crystal structure of YcaC co-purified with the target protein at resolutions of 2.34 and 2.56 Å without a priori knowledge of the protein identity or experimental phases. The three-dimensional structure of YcaC adopts a well-known cysteine hydrolase fold with the putative active site residues conserved. The active site cysteine is covalently bound to propionamide in one crystal form, whereas the second form contains an S-mercaptocysteine. The precise biological function of YcaC is unknown; however, related prokaryotic proteins have functions in antibacterial resistance, siderophore production and NADH biosynthesis. Here, we show that YcaC is exceptionally well conserved across both bacterial and fungal species despite being non-ubiquitous. This suggests that whilst YcaC may not be part of an integral pathway, the function could confer a significant evolutionary advantage to microbial life.

  13. String Gas Cosmology

    OpenAIRE

    Brandenberger, Robert H.

    2008-01-01

    String gas cosmology is a string theory-based approach to early universe cosmology which is based on making use of robust features of string theory such as the existence of new states and new symmetries. A first goal of string gas cosmology is to understand how string theory can effect the earliest moments of cosmology before the effective field theory approach which underlies standard and inflationary cosmology becomes valid. String gas cosmology may also provide an alternative to the curren...

  14. Is string theory a theory of strings?

    OpenAIRE

    Johnson, Clifford V.; Kaloper, Nemanja; Khuri, Ramzi R.; Myers, Robert C.

    1995-01-01

    Recently a great deal of evidence has been found indicating that type IIA string theory compactified on K3 is equivalent to heterotic string theory compactified on T^4. Under the transformation which relates the two theories, the roles of fundamental and solitonic string solutions are interchanged. In this letter we show that there exists a solitonic membrane solution of the heterotic string theory which becomes a singular solution of the type IIA theory, and should therefore be interpreted a...

  15. Regulation of cysteine dioxygenase degradation is mediated by intracellular cysteine levels and the ubiquitin–26 S proteasome system in the living rat

    OpenAIRE

    Dominy, John E.; Hirschberger, Lawrence L.; Coloso, Relicardo M.; Stipanuk, Martha H.

    2006-01-01

    Mammalian metabolism of ingested cysteine is conducted principally within the liver. The liver tightly regulates its intracellular cysteine pool to keep levels high enough to meet the many catabolic and anabolic pathways for which cysteine is needed, but low enough to prevent toxicity. One of the enzymes the liver uses to regulate cysteine levels is CDO (cysteine dioxygenase). Catalysing the irreversible oxidation of cysteine, CDO protein is up-regulated in the liver in response to the dietar...

  16. Evidence for string substructure

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, O.

    1996-06-01

    The author argues that the behavior of string theory at high temperature and high longitudinal boosts, combined with the emergence of p-branes as necessary ingredients in various string dualities, point to a possible reformulation of strings, as well as p-branes, as composites of bits. He reviews the string-bit models, and suggests generalizations to incorporate p-branes.

  17. STRING v9.1

    DEFF Research Database (Denmark)

    Franceschini, A.; Simonovic, M.; Roth, A.

    2013-01-01

    for certain model organisms and functional systems. Currently, protein interactions and associations are annotated at various levels of detail in online resources, ranging from raw data repositories to highly formalized pathway databases. For many applications, a global view of all the available interaction...... data is desirable, including lower-quality data and/or computational predictions. The STRING database (http://string-db.org/) aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated, resulting in comprehensive protein...

  18. Transport of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2)

    Science.gov (United States)

    Tsirulnikov, Kirill; Abuladze, Natalia; Koag, Myong-Chul; Newman, Debra; Scholz, Karoline; Bondar, Galyna; Zhu, Quansheng; Avliyakulov, Nuraly K.; Dekant, Wolfgang; Faull, Kym; Kurtz, Ira; Pushkin, Alexander

    2010-01-01

    N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (Ac-DCVC) and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) are the glutathione conjugation pathway metabolites of a common industrial contaminant and potent nephrotoxicant trichloroethylene (TCE). Ac-DCVC and DCVC are accumulated in the renal proximal tubule where they may be secreted into the urine by an unknown apical transporter(s). In this study we explored the hypothesis that the apical transport of Ac-DCVC and/or DCVC may be mediated by the multidrug resistance associated protein 2 (Mrp2, ABCC2), which is known to mediate proximal tubular apical ATP-dependent transport of glutathione and numerous xenobiotics and endogenous substances conjugated with glutathione. Transport experiments using membrane vesicles prepared from mouse proximal tubule derived cells expressing mouse Mrp2 utilizing ATPase assay and direct measurements of Ac-DCVC/DCVC using liquid chromatography/tandem mass-spectrometry (LC/MS/MS) demonstrated that mouse Mrp2 mediates ATP-dependent transport of Ac-DCVC. Expression of mouse Mrp2 antisense mRNA significantly inhibited the vectorial basolateral to apical transport of Ac-DCVC but not DCVC in mouse proximal tubule derived cells endogenously expressing mouse Mrp2. The results suggest that Mrp2 may be involved in the renal secretion of Ac-DCVC. PMID:20060011

  19. Identification and characterization of bacterial cysteine dioxygenases: a new route of cysteine degradation for eubacteria.

    Science.gov (United States)

    Dominy, John E; Simmons, Chad R; Karplus, P Andrew; Gehring, Amy M; Stipanuk, Martha H

    2006-08-01

    In metazoa and fungi, the catabolic dissimilation of cysteine begins with its sulfoxidation to cysteine sulfinic acid by the enzyme cysteine dioxygenase (CDO). In these organisms, CDO plays an important role in the homeostatic regulation of steady-state cysteine levels and provides important oxidized metabolites of cysteine such as sulfate and taurine. To date, there has been no experimental evidence for the presence of CDO in prokaryotes. Using PSI-BLAST searches and crystallographic information about the active-site geometry of mammalian CDOs, we identified a total of four proteins from Bacillus subtilis, Bacillus cereus, and Streptomyces coelicolor A3(2) that shared low overall identity to CDO (13 to 21%) but nevertheless conserved important active-site residues. These four proteins were heterologously expressed and purified to homogeneity by a single-step immobilized metal affinity chromatography procedure. The ability of these proteins to oxidize cysteine to cysteine sulfinic acid was then compared against recombinant rat CDO. The kinetic data strongly indicate that these proteins are indeed bona fide CDOs. Phylogenetic analyses of putative bacterial CDO homologs also indicate that CDO is distributed among species within the phyla of Actinobacteria, Firmicutes, and Proteobacteria. Collectively, these data suggest that a large subset of eubacteria is capable of cysteine sulfoxidation. Suggestions are made for how this novel pathway of cysteine metabolism may play a role in the life cycle of the eubacteria that have it.

  20. A protein extract and a cysteine protease inhibitor enriched fraction from Jatropha curcas seed cake have in vitro anti-Toxoplasma gondii activity.

    Science.gov (United States)

    Soares, A M S; Carvalho, L P; Melo, E J T; Costa, H P S; Vasconcelos, I M; Oliveira, J T A

    2015-06-01

    Toxoplasma gondii is a parasite of great medical and veterinary importance that has worldwide distribution and causes toxoplasmosis. There are few treatments available for toxoplasmosis and the search for plant extracts and compounds with anti-Toxoplasma activity is of utmost importance for the discovery of new active drugs. The objective of this study was to investigate the action of a protein extract and a protease inhibitor enriched fraction from J. curcas seed cake on developing tachyzoites of T. gondii-infected Vero cells. The protein extract (JcCE) was obtained after solubilization of the J. curcas seed cake with 100 mM sodium borate buffer, pH 10, centrifugation and dialysis of the resulting supernatant with the extracting buffer. JcCE was used for the in vitro assays of anti-Toxoplasma activity at 0.01, 0.1, 0.5, 1.5, 3.0 and 5.0 mg/ml concentration for 24 h. The results showed that JcCE reduced the percentage of infection and the number of intracellular parasites, but had no effect on the morphology of Vero cells up to 3.0 mg/mL. The cysteine protease inhibitor enriched fraction, which was obtained after chromatography of JcCE on Sephadex G-75 and presented a unique protein band following SDS-PAGE, reduced both the number of T. gondii infected cells and intracellular parasites. These results suggest that both JcCE and the cysteine protease inhibitor enriched fraction interfere with the intracellular growth of T. gondii. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Novel 1:1 labeling and purification process for C-terminal thioester and single cysteine recombinant proteins using generic peptidic toolbox reagents.

    Science.gov (United States)

    Portal, Christophe F; Seifert, Jan-Marcus; Buehler, Christof; Meisner-Kober, Nicole-Claudia; Auer, Manfred

    2014-07-16

    We developed a versatile set of chemical labeling reagents which allow dye ligation to the C-terminus of a protein or a single internal cysteine and target purification in a simple two-step process. This simple process results in a fully 1:1 labeled conjugate suitable for all quantitative fluorescence spectroscopy and imaging experiments. We refer to a "generic labeling toolbox" because of the flexibility to choose one of many available dyes, spacers of different lengths and compositions which increase the target solubility, a variety of affinity purification tags, and different cleavage chemistries to release the 1:1 labeled proteins. Studying protein function in vitro or in the context of live cells and organisms is of vital importance in biological research. Although label free detection technologies gain increasing interest in molecular recognition science, fluorescence spectroscopy is still the most often used detection technique for assays and screens both in academic as well as in industrial groups. For generations, fluorescence spectroscopists have labeled their proteins of interest with small fluorescent dyes by random chemical linking on the proteins' exposed lysines and cysteines. Chemical reactions with a certain excess of activated esters or maleimides of longer wavelength dyes hardly ever result in quantitative labeling of the target protein. Most of the time, more than one exposed amino acid side chain reacts. This results in a mixture of dye-protein complexes of different labeling stoichiometries and labeling sites. Only mass spectrometry allows resolving the precise chemical composition of the conjugates. In "classical" ensemble averaging fluorescent experiments, these labeled proteins are still useful, and quantification of, e.g., ligand binding experiments, is achieved via knowledge of the overall protein concentration and a fluorescent signal change which is proportional to the amount of complex formed. With the development of fluorescence

  2. Molecular mechanisms involved in gamete interaction: evidence for the participation of cysteine-rich secretory proteins (CRISP) in sperm-egg fusion.

    Science.gov (United States)

    Da Ros, V; Busso, D; Cohen, D J; Maldera, J; Goldweic, N; Cuasnicu, P S

    2007-01-01

    Epididymal protein DE and testicular protein Tpx-1 are two cysteine-rich secretory proteins also known as CRISP-1 and CRISP-2, respectively. DE/ CRISP-1 is localised on the equatorial segment of acrosome-reacted sperm and participates in rat gamete fusion through its binding to egg-complementary sites. Recent results using bacterially-expressed recombinant fragments of DE as well as synthetic peptides revealed that the ability of DE to bind to the egg surface and inhibit gamete fusion resides in a region of 12 amino acids corresponding to an evolutionary conserved motif of the CRISP family (Signature 2). Given the high degree of homology between DE/CRISP-1 and Tpx-1/CRISP-2, we also explored the potential participation of the testicular intra-acrosomal protein in gamete fusion. Results showing the ability of recombinant Tpx-1 to bind to the surface of rat eggs (evaluated by indirect immunofluorescence) and to significantly inhibit zona-free egg penetration, support the participation of this protein in gamete fusion through its interaction with egg-binding sites. Interestingly, rat Tpx-1 exhibits only two substitutions in Signature 2 when compared to this region in DE. Together, these results provide evidence for the involvement of both epididymal DE/CRISP-1 and testicular Tpx-1/CRISP-2 in gamete fusion suggesting the existence of a functional cooperation between homologue molecules as a mechanism to ensure the success of fertilisation.

  3. String solitons

    CERN Document Server

    Duff, M.J.; Lu, J.X.; Duff, M J; Khuri, Ramzi R; Lu, J X

    1995-01-01

    We review the status of solitons in superstring theory, with a view to understanding the strong coupling regime. These {\\it solitonic} solutions are non-singular field configurations which solve the empty-space low-energy field equations (generalized, whenever possible, to all orders in \\alpha'), carry a non-vanishing topological ``magnetic" charge and are stabilized by a topological conservation law. They are compared and contrasted with the {\\it elementary} solutions which are singular solutions of the field equations with a \\sigma-model source term and carry a non-vanishing Noether ``electric" charge. In both cases, the solutions of most interest are those which preserve half the spacetime supersymmetries and saturate a Bogomol'nyi bound. They typically arise as the extreme mass=charge limit of more general two-parameter solutions with event horizons. We also describe the theory {\\it dual} to the fundamental string for which the roles of elementary and soliton solutions are interchanged. In ten spacetime d...

  4. Novel cathepsin B and cathepsin B-like cysteine protease of Naegleria fowleri excretory-secretory proteins and their biochemical properties.

    Science.gov (United States)

    Lee, Jinyoung; Kim, Jong-Hyun; Sohn, Hae-Jin; Yang, Hee-Jong; Na, Byoung-Kuk; Chwae, Yong-Joon; Park, Sun; Kim, Kyongmin; Shin, Ho-Joon

    2014-08-01

    Naegleria fowleri causes a lethal primary amoebic meningoencephalitis (PAM) in humans and experimental animals, which leads to death within 7-14 days. Cysteine proteases of parasites play key roles in nutrient uptake, excystment/encystment, host tissue invasion, and immune evasion. In this study, we cloned N. fowleri cathepsin B (nfcpb) and cathepsin B-like (nfcpb-L) genes from our cDNA library of N. fowleri. The full-length sequences of genes were 1,038 and 939 bp (encoded 345 and 313 amino acids), and molecular weights were 38.4 and 34 kDa, respectively. Also, nfcpb and nfcpb-L showed a 56 and 46 % identity to Naegleria gruberi cathepsin B and cathepsin B-like enzyme, respectively. Recombinant NfCPB (rNfCPB) and NfCPB-L (rNfCPB-L) proteins were expressed by the pEX5-NT/TOPO vector that was transformed into Escherichia coli BL21, and they showed 38.4 and 34 kDa bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis using their respective antibodies. Proteolytic activity of refolded rNfCPB and rNfCPB-L was maximum at a pH of 4.5, and the most effective substrate was Z-LR-MCA. rNfCPB and rNfCPB-L showed proteolytic activity for several proteins such as IgA, IgG, IgM, collagen, fibronectin, hemoglobin, and albumin. These results suggested that NfCPB and NfCPB-L cysteine protease are important components of the N. fowleri ESP, and they may play important roles in host tissue invasion and immune evasion as pathogens that cause N. fowleri PAM.

  5. Hordeum vulgare cysteine protease heterologous expressed in yeast

    DEFF Research Database (Denmark)

    Rosenkilde, Anne Lind; Dionisio, Giuseppe; Holm, Preben Bach

    During germination of barley seeds, the mobilization of protein is essential and Cysteine Proteases accounts for more than 90 % of the total proteolytic activity in the degradation of barley seed storage proteins [1]. Cysteine proteases exist as pro-enzyme until activated through reduction...... of the active site cysteines and via removal of the pro-domain. The complement of cysteine proteases is comprehensive and for detailed studies of the individual components of this complement, a fast and efficient eukaryotic expression platform is highly desirable. One of the key cysteine proteases in Barley...

  6. Closed String Amplitudes from Gauge Fixed String Field Theory

    OpenAIRE

    Drukker, Nadav

    2002-01-01

    Closed string diagrams are derived from cubic open string field theory using a gauge fixed kinetic operator. The basic idea is to use a string propagator that does not generate a boundary to the world sheet. Using this propagator and the closed string vertex, the moduli space of closed string surfaces is covered, so closed string scattering amplitudes should be reproduced. This kinetic operator could be a gauge fixed form of the string field theory action around the closed string vacuum.

  7. Investigating possible biological targets of Bj-CRP, the first cysteine-rich secretory protein (CRISP) isolated from Bothrops jararaca snake venom.

    Science.gov (United States)

    Lodovicho, Marina E; Costa, Tássia R; Bernardes, Carolina P; Menaldo, Danilo L; Zoccal, Karina F; Carone, Sante E; Rosa, José C; Pucca, Manuela B; Cerni, Felipe A; Arantes, Eliane C; Tytgat, Jan; Faccioli, Lúcia H; Pereira-Crott, Luciana S; Sampaio, Suely V

    2017-01-04

    Cysteine-rich secretory proteins (CRISPs) are commonly described as part of the protein content of snake venoms, nevertheless, so far, little is known about their biological targets and functions. Our study describes the isolation and characterization of Bj-CRP, the first CRISP isolated from Bothrops jararaca snake venom, also aiming at the identification of possible targets for its actions. Bj-CRP was purified using three chromatographic steps (Sephacryl S-200, Source 15Q and C18) and showed to be an acidic protein of 24.6kDa with high sequence identity to other snake venom CRISPs. This CRISP was devoid of proteolytic, hemorrhagic or coagulant activities, and it did not affect the currents from 13 voltage-gated potassium channel isoforms. Conversely, Bj-CRP induced inflammatory responses characterized by increase of leukocytes, mainly neutrophils, after 1 and 4h of its injection in the peritoneal cavity of mice, also stimulating the production of IL-6. Bj-CRP also acted on the human complement system, modulating some of the activation pathways and acting directly on important components (C3 and C4), thus inducing the generation of anaphylatoxins (C3a, C4a and C5a). Therefore, our results for Bj-CRP open up prospects for better understanding this class of toxins and its biological actions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Changes in rubisco, cysteine-rich proteins and antioxidant system of spinach (Spinacia oleracea L.) due to sulphur deficiency, cadmium stress and their combination.

    Science.gov (United States)

    Bagheri, Rita; Ahmad, Javed; Bashir, Humayra; Iqbal, Muhammad; Qureshi, M Irfan

    2017-03-01

    Sulphur (S) deficiency, cadmium (Cd) toxicity and their combinations are of wide occurrence throughout agricultural lands. We assessed the impact of short-term (2 days) and long-term (4 days) applications of cadmium (40 μg/g soil) on spinach plants grown on sulphur-sufficient (300 μM SO42-) and sulphur-deficient (30 μM SO42-) soils. Compared with the control (+S and -Cd), oxidative stress was increased by S deficiency (-S and -Cd), cadmium (+S and +Cd) and their combination stress (-S and +Cd) in the order of (S deficiency) leaf proteins showed a high vulnerability of rubisco large subunit (RbcL) to S deficiency. Rubisco small subunit (RbcS) was particularly sensitive to Cd as well as dual stress (+Cd and -S) but increased with Cd in the presence of S. Cysteine content in low molecular weight proteins/peptide was also affected, showing a significant increase under cadmium treatment. Components of ascorbate-glutathione antioxidant system altered their levels, showing the maximum decline in ascorbate (ASA), dehydroascorbate (DHA), total ascorbate (ASA + DHA, hereafter TA), glutathione (GSH) and total glutathione (GSH + GSSG, hereafter TG) under S deficiency. However, total ascorbate and total glutathione increased, besides a marginal increase in their reduced and oxidized forms, when Cd was applied in the presence of sufficient S. Sulphur supply also helped in increasing the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR) and catalase (CAT) under Cd stress. However, their activity suffered by S deficiency and by Cd stress during S deficiency. Each stress declined the contents of soluble protein and photosynthetic pigments; the highest decline in contents of protein and pigments occurred under S deficiency and dual stress respectively. The fresh and dry weights, although affected adversely by every stress, declined most under dual stress. It may be concluded that an optimal level of S is required during Cd stress

  9. Association of the cysteine-rich secretory protein-3 (CRISP-3) and some of its polymorphisms with the quality of cryopreserved stallion semen.

    Science.gov (United States)

    Usuga, Alexandra; Rojano, Benjamín A; Restrepo, Giovanni

    2017-08-31

    Contribution of seminal plasma proteins to semen freezability has been reported in several species, suggesting these proteins as genetic markers. The aim of this study was to evaluate the relationship between cysteine-rich secretory protein-3 (CRISP-3) and some of its single-nucleotide polymorphisms (SNPs) with post-thawing semen quality in stallions. DNA was obtained from 100 stallions, regions of interest were amplified by polymerase chain reaction and sequenced. Evaluated SNPs within the equine CRISP-3 gene were CRISP3c.+199A>G (SNP1), CRISP3c.+566C>A (SNP2), CRISP3c.+622G>A (SNP3) and CRISP3c.+716A>G (SNP4). CRISP-3 protein content in seminal plasma was determined by enzyme-linked immunosorbent assay. Semen from 30 stallions was cryopreserved and post-thaw motility, kinetics, abnormal morphology (AM), sperm vitality (SV) and membrane integrity (MI) were evaluated. Generalized linear models were fitted and means were compared using Tukey's test. Correlation and regression analyses were performed. For SNP1 and SNP3, the AA genotype had the highest results for motility and MI; for SNP2, the best results for motility and AM were obtained with the CC genotype. For SNP4, the GG genotype had the lowest results, except for MI. A high level of CRISP-3 protein in seminal plasma had the best results for motility, kinetics, SV and AM. In conclusion, there was a relationship between CRISP-3 genotype and seminal plasma protein and post-thawing semen quality in stallions.

  10. A single cysteine post-translational oxidation suffices to compromise globular proteins kinetic stability and promote amyloid formation

    Directory of Open Access Journals (Sweden)

    Patrizia Marinelli

    2018-04-01

    Full Text Available Oxidatively modified forms of proteins accumulate during aging. Oxidized protein conformers might act as intermediates in the formation of amyloids in age-related disorders. However, it is not known whether this amyloidogenic conversion requires an extensive protein oxidative damage or it can be promoted just by a discrete, localized post-translational modification of certain residues. Here, we demonstrate that the irreversible oxidation of a single free Cys suffices to severely perturb the folding energy landscape of a stable globular protein, compromise its kinetic stability, and lead to the formation of amyloids under physiological conditions. Experiments and simulations converge to indicate that this specific oxidation-promoted protein aggregation requires only local unfolding. Indeed, a large scale analysis indicates that many cellular proteins are at risk of undergoing this kind of deleterious transition; explaining how oxidative stress can impact cell proteostasis and subsequently lead to the onset of pathological states. Keywords: Protein oxidation, Protein misfolding, Protein aggregation, Oxidative stress, Post-translational modification

  11. The mycotoxin patulin induces intra- and intermolecular protein crosslinks in vitro involving cysteine, lysine, and histidine side chains, and alpha-amino groups.

    Science.gov (United States)

    Fliege, R; Metzler, M

    1999-11-30

    As previous studies have indicated a multiple electrophilic reactivity of patulin (PAT) towards simple thiol nucleophiles, we have methodically investigated the ability of PAT to covalently crosslink proteins in vitro. By means of sodium dodecylsulphate polyacrylamide gel electrophoresis, the formation of PAT-induced intermolecular protein-protein crosslinks was clearly demonstrated for bovine serum albumin containing one thiol group per molecule, but also for the thiol-free hen egg lysozyme. Characterization of the crosslink sites was carried out by (1) modulation of the thiol groups with N-ethylimaleimide and 2-iminothiolane; (2) comparison with various known crosslinking agents, i.e. phenylenedimaleimide, glutardialdehyde, and dimethylsuberimidate, and (3) fluorescence incorporation studies using dansyl-labeled amino acids and a fluorescent glutathione derivative. The thiol group of cysteine was preferred for PAT-mediated crosslink reactions, but the side chains of lysine and histidine, and alpha-amino groups also exhibited reactivity. PAT can act both as a homobifunctional as well as a heterobifunctional crosslinking agent. The initial formation of a monoadduct with a thiol group appears to activate PAT for the subsequent reaction with an amino group, but also leads to rapid loss of further electrophilic properties when no second nucleophile for crosslink completion is available. Studies using microtubule proteins as a protein with experimentally controllable quarternary structure and a proposed cellular target for PAT toxicity emphasized the influence of specific sterical conditions on crosslink formation at low protein concentrations. Non-polymerized microtubule proteins, i.e. tubulin alpha,beta-dimers, formed a defined product with PAT consisting of an intramolecularly crosslinked beta-tubulin, whereas guanosine triphosphate- or paclitaxel-induced polymerization to microtubule-like quarternary structures prior to treatment with PAT gave rise to

  12. Dynamics of Carroll strings

    Energy Technology Data Exchange (ETDEWEB)

    Cardona, Biel [Departament d’Estructura i Constituents de la Matèriaand Institut de Ciències del Cosmos (ICCUB) Facultat de Física, Universitat de Barcelona,Diagonal 647, E-08028 Barcelona, Catalonia (Spain); Gomis, Joaquim [Departament d’Estructura i Constituents de la Matèriaand Institut de Ciències del Cosmos (ICCUB) Facultat de Física, Universitat de Barcelona,Diagonal 647, E-08028 Barcelona, Catalonia (Spain); Department of Physics, Faculty of Science, Chulalongkorn University,Bangkok 10330 (Thailand); Pons, Josep M. [Departament d’Estructura i Constituents de la Matèriaand Institut de Ciències del Cosmos (ICCUB) Facultat de Física, Universitat de Barcelona,Diagonal 647, E-08028 Barcelona, Catalonia (Spain)

    2016-07-11

    We construct the canonical action of a Carroll string doing the Carroll limit of a canonical relativistic string. We also study the Killing symmetries of the Carroll string, which close under an infinite dimensional algebra. The tensionless limit and the Carroll p-brane action are also discussed.

  13. String Math 2017

    CERN Document Server

    The series of String-Math conferences has developed into a central event on the interface between mathematics and physics related to string theory, quantum field theory and neighboring subjects. The conference will take place from July 24-28 in the main building of Hamburg university. The String-Math conference is organised by the University of Hamburg jointly with DESY Hamburg.

  14. Fingerprints in Compressed Strings

    DEFF Research Database (Denmark)

    Bille, Philip; Cording, Patrick Hagge; Gørtz, Inge Li

    2013-01-01

    The Karp-Rabin fingerprint of a string is a type of hash value that due to its strong properties has been used in many string algorithms. In this paper we show how to construct a data structure for a string S of size N compressed by a context-free grammar of size n that answers fingerprint queries...

  15. D19S Mutation of the Cationic, Cysteine-Rich Protein PAF: Novel Insights into Its Structural Dynamics, Thermal Unfolding and Antifungal Function.

    Directory of Open Access Journals (Sweden)

    Christoph Sonderegger

    Full Text Available The cysteine-rich, cationic, antifungal protein PAF is abundantly secreted into the culture supernatant of the filamentous Ascomycete Penicillium chrysogenum. The five β-strands of PAF form a compact β-barrel that is stabilized by three disulphide bonds. The folding of PAF allows the formation of four surface-exposed loops and distinct charged motifs on the protein surface that might regulate the interaction of PAF with the sensitive target fungus. The growth inhibitory activity of this highly stable protein against opportunistic fungal pathogens provides great potential in antifungal drug research. To understand its mode of action, we started to investigate the surface-exposed loops of PAF and replaced one aspartic acid at position 19 in loop 2 that is potentially involved in PAF active or binding site, with a serine (Asp19 to Ser19. We analysed the overall effects, such as unfolding, electrostatic changes, sporadic conformers and antifungal activity when substituting this specific amino acid to the fairly indifferent amino acid serine. Structural analyses revealed that the overall 3D solution structure is virtually identical with that of PAF. However, PAFD19S showed slightly increased dynamics and significant differences in the surface charge distribution. Thermal unfolding identified PAFD19S to be rather a two-state folder in contrast to the three-state folder PAF. Functional comparison of PAFD19S and PAF revealed that the exchange at residue 19 caused a dramatic loss of antifungal activity: the binding and internalization of PAFD19S by target cells was reduced and the protein failed to trigger an intracellular Ca2+ response, all of which are closely linked to the antifungal toxicity of PAF. We conclude that the negatively charged residue Asp19 in loop 2 is essential for full function of the cationic protein PAF.

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

    Directory of Open Access Journals (Sweden)

    Tatjana P Kristensen

    2014-03-01

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

  17. Protein flexibility and cysteine reactivity: influence of mobility on the H-bond network and effects on pKa prediction.

    Science.gov (United States)

    Marino, Stefano M

    2014-08-01

    Thanks to its chemical plasticity, cysteine (Cys) is a very versatile player in proteins. A major determinant of Cys reactivity is pKa: the ability to predict it is deemed critical in redox bioinformatics. I considered different computational methods for pKa predictions and ultimately applied one (propka, ppka1) to various datasets; for all residues I assessed the effect of (1) hydrogen bonding, electrostatics and solvation on predictions and (2) protein mobility on pKa variability. Particularly for Cys, exposure and H-bond contributions heavily dictated propka predictions. The prominence of H-bond contributions was previously reported: this may explain the effectiveness of ppka1 (with Cys, tested in a benchmark). However ppka1 was also very sensitive to protein mobility; I assessed the effects of mobility on particularly large (compared to previous studies) datasets of structural ensembles; I found that exposed Cys presented the highest pKa variability, ascribable to correspondingly high H-bond fluctuations associated with protein flexibility. The benefit of including protein dynamics in pKa predictions was previously proposed, but empirical methods were never tested in this sense; instead, giving their outstanding speed, they could lend particularly well to this purpose. I devised a strategy combining short range molecular dynamics with ppka1; the protocol aimed to mitigate high ppka1 variability by including a "statistical view" of fast conformational changes. Tested in a benchmark, the strategy lead to improved performances. These results provide new insights on Cys bioinformatics (pKa prediction protocols) and Cys biology (effect of mobility on exposed Cys properties).

  18. D19S Mutation of the Cationic, Cysteine-Rich Protein PAF: Novel Insights into Its Structural Dynamics, Thermal Unfolding and Antifungal Function.

    Science.gov (United States)

    Sonderegger, Christoph; Fizil, Ádám; Burtscher, Laura; Hajdu, Dorottya; Muñoz, Alberto; Gáspári, Zoltán; Read, Nick D; Batta, Gyula; Marx, Florentine

    2017-01-01

    The cysteine-rich, cationic, antifungal protein PAF is abundantly secreted into the culture supernatant of the filamentous Ascomycete Penicillium chrysogenum. The five β-strands of PAF form a compact β-barrel that is stabilized by three disulphide bonds. The folding of PAF allows the formation of four surface-exposed loops and distinct charged motifs on the protein surface that might regulate the interaction of PAF with the sensitive target fungus. The growth inhibitory activity of this highly stable protein against opportunistic fungal pathogens provides great potential in antifungal drug research. To understand its mode of action, we started to investigate the surface-exposed loops of PAF and replaced one aspartic acid at position 19 in loop 2 that is potentially involved in PAF active or binding site, with a serine (Asp19 to Ser19). We analysed the overall effects, such as unfolding, electrostatic changes, sporadic conformers and antifungal activity when substituting this specific amino acid to the fairly indifferent amino acid serine. Structural analyses revealed that the overall 3D solution structure is virtually identical with that of PAF. However, PAFD19S showed slightly increased dynamics and significant differences in the surface charge distribution. Thermal unfolding identified PAFD19S to be rather a two-state folder in contrast to the three-state folder PAF. Functional comparison of PAFD19S and PAF revealed that the exchange at residue 19 caused a dramatic loss of antifungal activity: the binding and internalization of PAFD19S by target cells was reduced and the protein failed to trigger an intracellular Ca2+ response, all of which are closely linked to the antifungal toxicity of PAF. We conclude that the negatively charged residue Asp19 in loop 2 is essential for full function of the cationic protein PAF.

  19. String Mining in Bioinformatics

    Science.gov (United States)

    Abouelhoda, Mohamed; Ghanem, Moustafa

    Sequence analysis is a major area in bioinformatics encompassing the methods and techniques for studying the biological sequences, DNA, RNA, and proteins, on the linear structure level. The focus of this area is generally on the identification of intra- and inter-molecular similarities. Identifying intra-molecular similarities boils down to detecting repeated segments within a given sequence, while identifying inter-molecular similarities amounts to spotting common segments among two or multiple sequences. From a data mining point of view, sequence analysis is nothing but string- or pattern mining specific to biological strings. For a long time, this point of view, however, has not been explicitly embraced neither in the data mining nor in the sequence analysis text books, which may be attributed to the co-evolution of the two apparently independent fields. In other words, although the word "data-mining" is almost missing in the sequence analysis literature, its basic concepts have been implicitly applied. Interestingly, recent research in biological sequence analysis introduced efficient solutions to many problems in data mining, such as querying and analyzing time series [49,53], extracting information from web pages [20], fighting spam mails [50], detecting plagiarism [22], and spotting duplications in software systems [14].

  20. Cysteine proteinases and cystatins

    Directory of Open Access Journals (Sweden)

    Adeliana S. Oliveira

    2003-01-01

    Full Text Available This review describeds the definition, localization, functions and examples of cysteine proteinases and their protein inhibitors in vertebrate, non-vertebrate animals and plants. These inhibitors are related with defense mechanisms of plant against pests. It also describes the factors involved in the specific cysteine proteinase-cystatin interaction and high degree of affinity and large specificity in this interaction which are not only represented by the compatibility between amino acid residues of the active site involved in catalysis, but also of all amino acid residues that participante in the enzyme-inhibitor interaction.Nesta revisão foram descritas definições, localizações, funções e exemplos de proteinases cisteínicas e suas proteinas inibidoras em animais vertebrados e invertebrados e plantas. Tratamos principalmente com aqueles inibidores que são relatados com o mecanismo de defesa da planta contra pestes. Em adição, comentamos sobre recentes trabalhos que contribuíram para uma melhor compreenção dos fatores envolvidos na interação específica proteinase cisteínica-cistatina. Por outro lado, chamamos atenção para o alto grau de afinidade e grande especificidade na interação que não são apenas representadas pela compatibilidade entre os residuos de aminoácidos do sítio ativo envolvidos na catalise, mas também de todos os resíduos de aminoácidos que participam da interação enzima-inibidor.

  1. Closed Strings From Nothing

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, Albion

    2001-07-25

    We study the physics of open strings in bosonic and type II string theories in the presence of unstable D-branes. When the potential energy of the open string tachyon is at its minimum, Sen has argued that only closed strings remain in the perturbative spectrum. We explore the scenario of Yi and of Bergman, Hori and Yi, who argue that the open string degrees of freedom are strongly coupled and disappear through confinement. We discuss arguments using open string field theory and worldsheet boundary RG flows, which seem to indicate otherwise. We then describe a solitonic excitation of the open string tachyon and gauge field with the charge and tension of a fundamental closed string. This requires a double scaling limit where the tachyon is taken to its minimal value and the electric field is taken to its maximum value. The resulting flux tube has an unconstrained spatial profile; and for large fundamental string charge, it appears to have light, weakly coupled open strings living in the core. We argue that the flux tube acquires a size or order {alpha}' through sigma model and string coupling effects; and we argue that confinement effects make the light degrees of freedom heavy and strongly interacting.

  2. Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma

    DEFF Research Database (Denmark)

    Udby, Lene; Sørensen, Ole E; Pass, Jesper

    2004-01-01

    (28 kDa), we hypothesized that CRISP-3 in plasma was bound to another component. This was supported by size-exclusion chromatography and immunoprecipitation of plasma proteins. The binding partner was identified by mass spectrometry as alpha(1)B-glycoprotein (A1BG), which is a known plasma protein...... and is held together by strong electrostatic forces. Similar complexes have been described between toxins from snake venom and A1BG-like plasma proteins from opossum species. In these cases, complex formation inhibits the toxic effect of snake venom metalloproteinases or myotoxins and protects the animal from...... of unknown function and a member of the immunoglobulin superfamily. We demonstrate that CRISP-3 is a specific and high-affinity ligand of A1BG with a dissociation constant in the nanomolar range as evidenced by surface plasmon resonance. The A1BG-CRISP-3 complex is noncovalent with a 1:1 stoichiometry...

  3. Harvey murine sarcoma virus p21 ras protein: biological and biochemical significance of the cysteine nearest the carboxy terminus

    DEFF Research Database (Denmark)

    Willumsen, B M; Norris, K; Papageorge, A G

    1984-01-01

    Previous studies of premature chain termination mutants and in frame deletion mutants of the p21 ras transforming protein encoded by the transforming gene of Harvey murine sarcoma virus (Ha-MuSV) have suggested that the C terminus is required for cellular transformation, lipid binding, and membrane...

  4. Combined treatment with troglitazone and lovastatin inhibited epidermal growth factor-induced migration through the downregulation of cysteine-rich protein 61 in human anaplastic thyroid cancer cells.

    Directory of Open Access Journals (Sweden)

    Li-Han Chin

    Full Text Available Our previous studies have demonstrated that epidermal growth factor (EGF can induce cell migration through the induction of cysteine-rich protein 61 (Cyr61 in human anaplastic thyroid cancer (ATC cells. The aim of the present study was to determine the inhibitory effects of combined treatment with the peroxisome proliferator-activated receptor-γ (PPARγ ligand troglitazone and the cholesterol-lowering drug lovastatin at clinically achievable concentrations on ATC cell migration. Combined treatment with 5 μM troglitazone and 1 μM lovastatin exhibited no cytotoxicity but significantly inhibited EGF-induced migration, as determined using wound healing and Boyden chamber assays. Cotreatment with troglitazone and lovastatin altered the epithelial-to-mesenchymal-transition (EMT -related marker gene expression of the cells; specifically, E-cadherin expression increased and vimentin expression decreased. In addition, cotreatment reduced the number of filopodia, which are believed to be involved in migration, and significantly inhibited EGF-induced Cyr61 mRNA and protein expression as well as Cyr61 secretion. Moreover, the phosphorylation levels of 2 crucial signal molecules for EGF-induced Cyr61 expression, the cAMP response element-binding protein (CREB and extracellular signal-regulated kinase (ERK, were decreased in cells cotreated with troglitazone and lovastatin. Performing a transient transfection assay revealed that the combined treatment significantly suppressed Cyr61 promoter activity. These results suggest that combined treatment with low doses of troglitazone and lovastatin effectively inhibits ATC cell migration and may serve as a novel therapeutic strategy for metastatic ATC.

  5. DMSA-Coated Iron Oxide Nanoparticles Greatly Affect the Expression of Genes Coding Cysteine-Rich Proteins by Their DMSA Coating.

    Science.gov (United States)

    Zhang, Ling; Wang, Xin; Zou, Jinglu; Liu, Yingxun; Wang, Jinke

    2015-10-19

    The dimercaptosuccinic acid (DMSA) was widely used to coat iron oxide nanoparticles (FeNPs); however, its intracellular cytotoxicity remains to be adequately elucidated. This study analyzed the differentially expressed genes (DEGs) in four mammalian cells treated by a DMSA-coated magnetite FeNP at various doses at different times. The results revealed that about one-fourth of DEGs coded cysteine-rich proteins (CRPs) in all cells under each treatment, indicating that the nanoparticles greatly affected the expressions of CRP-coding genes. Additionally, about 26% of CRP-coding DEGs were enzyme genes in all cells, indicating that the nanoparticles greatly affected the expression of enzyme genes. Further experiments with the nanoparticles and a polyethylenimine (PEI)-coated magnetite FeNP revealed that the effect mainly resulted from DMSA carried into cells by the nanoparticles. This study thus first reported the cytotoxicity of DMSA at the gene transcription level as coating molecules of FeNPs. This study provides new insight into the molecular mechanism by which the DMSA-coated nanoparticles resulted in the transcriptional changes of many CRP-coding genes in cells. This study draws attention toward the intracellular cytotoxicity of DMSA as a coating molecule of nanoparticles, which has very low toxicity as an orally administered antidote due to its extracellular distribution.

  6. Doubled strings, negative strings and null waves

    Energy Technology Data Exchange (ETDEWEB)

    Blair, Chris D.A. [Theoretische Natuurkunde, Vrije Universiteit Brussel, and the International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium)

    2016-11-08

    We revisit the fundamental string (F1) solution in the doubled formalism. We show that the wave-like solution of double field theory (DFT) corresponding to the F1/pp-wave duality pair is more properly a solution of the DFT action coupled to a doubled sigma model action. The doubled string configuration which sources the pp-wave can be thought of as static gauge with the string oriented in a dual direction. We also discuss the DFT solution corresponding to a vibrating string, carrying both winding and momentum. We further show that the solution dual to the F1 in both time and space can be viewed as a “negative string” solution. Negative branes are closely connected to certain exotic string theories which involve unusual signatures for both spacetime and brane worldvolumes. In order to better understand this from the doubled point of view, we construct a variant of DFT suitable for describing theories in which the fundamental string has a Euclidean worldsheet, for which T-dualities appear to change the spacetime signature.

  7. Solution structure of the tandem acyl carrier protein domains from a polyunsaturated fatty acid synthase reveals beads-on-a-string configuration.

    Directory of Open Access Journals (Sweden)

    Uldaeliz Trujillo

    Full Text Available The polyunsaturated fatty acid (PUFA synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP domains in tandem. This conserved tandem arrangement has been implicated in both amplification of fatty acid production (additive effect and in structural stabilization of the multidomain protein (synergistic effect. While the more accepted model is one in which domains act independently, recent reports suggest that ACP domains may form higher oligomers. Elucidating the three-dimensional structure of tandem arrangements may therefore give important insights into the functional relevance of these structures, and hence guide bioengineering strategies. In an effort to elucidate the three-dimensional structure of tandem repeats from deep-sea anaerobic bacteria, we have expressed and purified a fragment consisting of five tandem ACP domains from the PUFA synthase from Photobacterium profundum. Analysis of the tandem ACP fragment by analytical gel filtration chromatography showed a retention time suggestive of a multimeric protein. However, small angle X-ray scattering (SAXS revealed that the multi-ACP fragment is an elongated monomer which does not form a globular unit. Stokes radii calculated from atomic monomeric SAXS models were comparable to those measured by analytical gel filtration chromatography, showing that in the gel filtration experiment, the molecular weight was overestimated due to the elongated protein shape. Thermal denaturation monitored by circular dichroism showed that unfolding of the tandem construct was not cooperative, and that the tandem arrangement did not stabilize the protein. Taken together, these data are consistent with an elongated beads-on-a-string arrangement of the tandem ACP domains in PUFA synthases, and speak against synergistic biocatalytic effects promoted by quaternary structuring. Thus, it is possible to envision bioengineering strategies which simply involve the artificial linking of

  8. Solution Structure of the Tandem Acyl Carrier Protein Domains from a Polyunsaturated Fatty Acid Synthase Reveals Beads-on-a-String Configuration

    KAUST Repository

    Trujillo, Uldaeliz

    2013-02-28

    The polyunsaturated fatty acid (PUFA) synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP) domains in tandem. This conserved tandem arrangement has been implicated in both amplification of fatty acid production (additive effect) and in structural stabilization of the multidomain protein (synergistic effect). While the more accepted model is one in which domains act independently, recent reports suggest that ACP domains may form higher oligomers. Elucidating the three-dimensional structure of tandem arrangements may therefore give important insights into the functional relevance of these structures, and hence guide bioengineering strategies. In an effort to elucidate the three-dimensional structure of tandem repeats from deep-sea anaerobic bacteria, we have expressed and purified a fragment consisting of five tandem ACP domains from the PUFA synthase from Photobacterium profundum. Analysis of the tandem ACP fragment by analytical gel filtration chromatography showed a retention time suggestive of a multimeric protein. However, small angle X-ray scattering (SAXS) revealed that the multi-ACP fragment is an elongated monomer which does not form a globular unit. Stokes radii calculated from atomic monomeric SAXS models were comparable to those measured by analytical gel filtration chromatography, showing that in the gel filtration experiment, the molecular weight was overestimated due to the elongated protein shape. Thermal denaturation monitored by circular dichroism showed that unfolding of the tandem construct was not cooperative, and that the tandem arrangement did not stabilize the protein. Taken together, these data are consistent with an elongated beads-on-a-string arrangement of the tandem ACP domains in PUFA synthases, and speak against synergistic biocatalytic effects promoted by quaternary structuring. Thus, it is possible to envision bioengineering strategies which simply involve the artificial linking of multiple ACP

  9. The Cysteine Protease–Cysteine Protease Inhibitor System Explored in Soybean Nodule Development

    Directory of Open Access Journals (Sweden)

    Marian Dorcas Quain

    2013-08-01

    Full Text Available Almost all protease families have been associated with plant development, particularly senescence, which is the final developmental stage of every organ before cell death. Proteolysis remobilizes and recycles nitrogen from senescent organs that is required, for example, seed development. Senescence-associated expression of proteases has recently been characterized using large-scale gene expression analysis seeking to identify and characterize senescence-related genes. Increasing activities of proteolytic enzymes, particularly cysteine proteases, are observed during the senescence of legume nodules, in which a symbiotic relationship between the host plant and bacteria (Rhizobia facilitate the fixation of atmospheric nitrogen. It is generally considered that cysteine proteases are compartmentalized to prevent uncontrolled proteolysis in nitrogen-fixing nodules. In addition, the activities of cysteine proteases are regulated by endogenous cysteine protease inhibitors called cystatins. These small proteins form reversible complexes with cysteine proteases, leading to inactivation. However, very little is currently known about how the cysteine protease-cysteine protease inhibitor (cystatin system is regulated during nodule development. Moreover, our current understanding of the expression and functions of proteases and protease inhibitors in nodules is fragmented. To address this issue, we have summarized the current knowledge and techniques used for studying proteases and their inhibitors including the application of “omics” tools, with a particular focus on changes in the cysteine protease-cystatin system during nodule development.

  10. Crystal Structure of Mammalian Cysteine dioxygenase: A Novel Mononuclear Iron Center for Cysteine Thiol Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons,C.; Liu, Q.; Huang, Q.; Hao, Q.; Begley, T.; Karplus, P.; Stipanuk, M.

    2006-01-01

    Cysteine dioxygenase is a mononuclear iron-dependent enzyme responsible for the oxidation of cysteine with molecular oxygen to form cysteinesulfinate. This reaction commits cysteine to either catabolism to sulfate and pyruvate or to the taurine biosynthetic pathway. Cysteine dioxygenase is a member of the cupin superfamily of proteins. The crystal structure of recombinant rat cysteine dioxygenase has been determined to 1.5 Angstroms resolution, and these results confirm the canonical cupin {beta}-sandwich fold and the rare cysteinyl-tyrosine intramolecular crosslink (between Cys93 and Tyr157) seen in the recently reported murine cysteine dioxygenase structure. In contrast to the catalytically inactive mononuclear Ni(II) metallocenter present in the murine structure, crystallization of a catalytically competent preparation of rat cysteine dioxygenase revealed a novel tetrahedrally coordinated mononuclear iron center involving three histidines (His86, His88, and His140) and a water molecule. Attempts to acquire a structure with bound ligand using either co-crystallization or soaks with cysteine revealed the formation of a mixed disulfide involving Cys164 near the active site, which may explain previously observed substrate inhibition. This work provides a framework for understanding the molecular mechanisms involved in thiol dioxygenation and sets the stage for exploring the chemistry of both the novel mononuclear iron center and the catalytic role of the cysteinyl-tyrosine linkage.

  11. Reconstruction of Cysteine Biosynthesis Using Engineered Cysteine-Free and Methionine-Free Enzymes

    Science.gov (United States)

    Wang, Kendrick; Fujishima, Kosuke; Abe, Nozomi; Nakahigashi, Kenji; Endy, Drew; Rothschild, Lynn J.

    2016-01-01

    Ten of the proteinogenic amino acids can be generated abiotically while the remaining thirteen require biology for their synthesis. Paradoxically, the biosynthesis pathways observed in nature require enzymes that are made with the amino acids they produce. For example, Escherichia coli produces cysteine from serine via two enzymes that contain cysteine. Here, we substituted alternate amino acids for cysteine and also methionine, which is biosynthesized from cysteine, in serine acetyl transferase (CysE) and O-acetylserine sulfhydrylase (CysM). CysE function was rescued by cysteine-and-methionine-free enzymes and CysM function was rescued by cysteine-free enzymes. Structural modeling suggests that methionine stabilizes CysM and is present in the active site of CysM. Cysteine is not conserved among CysE and CysM protein orthologs, suggesting that cysteine is not functionally important for its own synthesis. Engineering biosynthetic enzymes that lack the amino acids being synthesized provides insights into the evolution of amino acid biosynthesis and pathways for bioengineering.

  12. Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β3-adrenoceptor stimulation.

    Science.gov (United States)

    Yoshioka, Yasuhiro; Kadoi, Hisatsugu; Yamamuro, Akiko; Ishimaru, Yuki; Maeda, Sadaaki

    2016-02-05

    Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. Since neurons rely on the supply of GSH from astrocytes to maintain optimal intracellular GSH concentrations, the GSH concentration of astrocytes is important for the survival of neighboring neurons against oxidative stress. The neurotransmitter noradrenaline is known to modulate the functions of astrocytes and has been suggested to have neuroprotective properties in neurodegenerative diseases. To elucidate the mechanisms underlying the neuroprotective properties of noradrenaline, in this study, we investigated the effect of noradrenaline on the concentrations of intracellular GSH in human U-251 malignant glioma (MG; astrocytoma) cells. Treatment of the cells with noradrenaline for 24h concentration-dependently increased their intracellular GSH concentration. This increase was inhibited by a non-selective β-adrenoceptor antagonist propranolol and by a selective β3-adrenoceptor antagonist SR59230A, but not by a non-selective α-adrenoceptor antagonist phenoxybenzamine, or by a selective β1-adrenoceptor antagonist atenolol or by a selective β2-adrenoceptor antagonist butoxamine. In addition, the selective β3-adrenoceptor agonist CL316243 increased the intracellular GSH in U-251 MG cells. Treatment of the cells with noradrenaline (10μM) for 24h increased the protein level of the catalytic subunit of glutamate-cysteine ligase (GCLc), the rate-limiting enzyme of GSH synthesis; and this increase was inhibited by SR59230A. These results thus suggest that noradrenaline increased the GSH concentration in astrocytes by inducing GCLc protein in them via β3-adrenoceptor stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. BPS Alice strings

    Science.gov (United States)

    Chatterjee, Chandrasekhar; Nitta, Muneto

    2017-09-01

    When a charged particle encircles around an Alice string, it changes the sign of the electric charge. In this paper we find a BPS-saturated Alice string in U(1)×SO(3) gauge theory with charged complex scalar fields belonging to the vector representation. After performing BPS completion we solve the BPS equations numerically. We further embed the Alice string into an N = 1 supersymmetric gauge theory to show that it is half BPS.

  14. Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation

    DEFF Research Database (Denmark)

    Eriksson, Christer; Frängsmyr, Lars; Danielsson Niemi, Liza

    2007-01-01

    glycoforms I and II/III correlate with Se(-) and Se(+) phenotypes, respectively (p Streptococcus suis) or sialic acid- (Streptococcus mutans) binding bacteria......Glycoprotein gp-340 aggregates bacteria in saliva as part of innate defence at mucosal surfaces. We have detected size- and glycoforms of gp-340 between human saliva samples (n = 7) and lung gp-340 from a proteinosis patient using antibodies and lectins in Western blots and ELISA measurements...... bands. Purified I to IV proteins all revealed a N-terminal sequence TGGWIP upon Edman degradation. Moreover, purified gp-340 from the seven donors and lung gp-340 shared N-glycans, sialylated Galbeta1-3GalNAc and (poly)lactosamine structures. However, the larger size gp-340 grouping II/III (n = 4...

  15. L-Cysteine Metabolism and Fermentation in Microorganisms.

    Science.gov (United States)

    Takagi, Hiroshi; Ohtsu, Iwao

    L-Cysteine is an important amino acid both biologically and commercially. Although most amino acids are industrially produced by microbial fermentation, L-cysteine has been mainly produced by protein hydrolysis. Due to environmental and safety problems, synthetic or biotechnological products have been preferred in the market. Here, we reviewed L-cysteine metabolism, including biosynthesis, degradation, and transport, and biotechnological production (including both enzymatic and fermentation processes) of L-cysteine. The metabolic regulation of L-cysteine including novel sulfur metabolic pathways found in microorganisms is also discussed. Recent advancement in biochemical studies, genome sequencing, structural biology, and metabolome analysis has enabled us to use various approaches to achieve direct fermentation of L-cysteine from glucose. For example, worldwide companies began to supply L-cysteine and its derivatives produced by bacterial fermentation. These companies successfully optimized the original metabolism of their private strains. Basically, a combination of three factors should be required for improving L-cysteine fermentation: that is, (1) enhancing biosynthesis: overexpression of the altered cysE gene encoding feedback inhibition-insensitive L-serine O-acetyltransferase (SAT), (2) weakening degradation: knockout of the genes encoding L-cysteine desulfhydrases, and (3) exploiting export system: overexpression of the gene involved in L-cysteine transport. Moreover, we found that "thiosulfate" is much more effective sulfur source than commonly used "sulfate" for L-cysteine production in Escherichia coli, because thiosulfate is advantageous for saving consumption of NADPH and relating energy molecules.

  16. String theory for dummies

    CERN Document Server

    Zimmerman Jones, Andrew

    2010-01-01

    Making Everything Easier!. String Theory for Dummies. Learn:. The basic concepts of this controversial theory;. How string theory builds on physics concepts;. The different viewpoints in the field;. String theory's physical implications. Andrew Zimmerman Jones. Physics Guide, About.com. with Daniel Robbins, PhD in Physics. Your plain-English guide to this complex scientific theory. String theory is one of the most complicated sciences being explored today. Not to worry though! This informative guide clearly explains the basics of this hot topic, discusses the theory's hypotheses and prediction

  17. Cysteines as Redox Molecular Switches and Targets of Disease

    Directory of Open Access Journals (Sweden)

    Annamaria Fra

    2017-06-01

    Full Text Available Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated with many hereditary and acquired diseases. Mutations in the primary protein sequence (gain or loss of a cysteine are most frequent in membrane and secretory proteins, correlating with the key roles of disulfide bonds. On the contrary, in the cytosol and nucleus, aberrant post-translational oxidative modifications of thiol groups, reflecting redox changes in the surrounding environment, are a more frequent cause of dysregulation of protein function. This essay highlights the regulatory functions performed by protein cysteine residues and provides a framework for understanding how mutation and/or (inactivation of this key amino acid can cause disease.

  18. S-nitrosylation of TRIM72 at cysteine 144 is critical for protection against oxidation-induced protein degradation and cell death.

    Science.gov (United States)

    Kohr, Mark J; Evangelista, Alicia M; Ferlito, Marcella; Steenbergen, Charles; Murphy, Elizabeth

    2014-04-01

    Oxidative stress and membrane damage following myocardial ischemia/reperfusion injury are important contributors to cardiomyocyte death and the loss of myocardial function. Our previous study identified cysteine 144 (C144) of tripartite motif-containing protein 72 (TRIM72) as a potential site for S-nitrosylation (SNO). TRIM72 is a cardioprotective membrane repair protein that can be both activated and targeted for degradation by different oxidative modifications. Consistent with the potential regulation of TRIM72 by various oxidative modifications, we found that SNO levels increased at C144 of TRIM72 with ischemic preconditioning. Therefore, to investigate the role of C144 in the regulation of TRIM72 function, we mutated C144 of TRIM72 to a serine residue (TRIM72(C144S)), and expressed either TRIM72(WT) or TRIM72(C144S) in HEK-293 cells, which lack endogenous TRIM72, in order to examine the effect of this mutation on the functional stability of TRIM72 and on cell survival. We hypothesized that SNO of TRIM72 stabilizes the protein, thus allowing for membrane repair and enhanced cell survival. Upon treatment with hydrogen peroxide (H2O2), we found that TRIM72(WT) levels were decreased, but not TRIM72(C144S) and this correlated with increased H2O2-induced cell death in TRIM72(WT) cells. Additionally, we found that treatment with the cardioprotective S-nitrosylating agent S-nitrosoglutathione (GSNO), was able to preserve TRIM72(WT) protein levels and enhance TRIM72(WT)-mediated cell survival, but had no effect on TRIM72(C144S) levels. Consistent with our hypothesis, GSNO was also found to increase SNO levels and inhibit H2O2-induced irreversible oxidation for TRIM72(WT) without affecting TRIM72(C144S). In further support of our hypothesis, GSNO blocked the ischemia/reperfusion-induced decrease in TRIM72 levels and reduced infarct size in a Langendorff-perfused heart model. The results of these studies have important implications for cardioprotection and suggest that

  19. Optimal Packed String Matching

    DEFF Research Database (Denmark)

    Ben-Kiki, Oren; Bille, Philip; Breslauer, Dany

    2011-01-01

    instructions. The main string-matching instruction is available in commodity processors (i.e., Intel’s SSE4.2 and AVX Advanced String Operations); the other maximal-suffix instruction is only required during pattern preprocessing. In the absence of these two specialized instructions, we propose theoretically...

  20. StringForce

    DEFF Research Database (Denmark)

    Barendregt, Wolmet; Börjesson, Peter; Eriksson, Eva

    2017-01-01

    In this paper, we present the forced collaborative interaction game StringForce. StringForce is developed for a special education context to support training of collaboration skills, using readily available technologies and avoiding the creation of a "mobile bubble". In order to play String......Force two or four physically collocated tablets are required. These tablets are connected to form one large shared game area. The game can only be played by collaborating. StringForce extends previous work, both technologically and regarding social-emotional training. We believe String......Force to be an interesting demo for the IDC community, as it intertwines several relevant research fields, such as mobile interaction and collaborative gaming in the special education context....

  1. String-Math 2015

    CERN Document Server

    2015-01-01

    Welcome to String-Math 2015 at Sanya. The conference will be opened in December 31, 2015- January 4, 2016. String theory plays a central role in theoretical physics as a candidate for the quantum theory unifying gravity with other interactions. It has profound connections with broad branches of modern mathematics ever since the birth. In the last decades, the prosperous interaction, built upon the joint efforts from both mathematicians and physicists, has given rise to marvelous deep results in supersymmetric gauge theory, topological string, M-theory and duality on the physics side as well as in algebraic geometry, differential geometry, algebraic topology, representation theory and number theory on the mathematics side. The interplay is two-fold. The mathematics has provided powerful tools to fulfill the physical interconnection of ideas and clarify physical structures to understand the nature of string theory. On the other hand, ideas from string theory and quantum field theory have been a source of sign...

  2. Midgut cysteine protease-inhibiting activity in Trichoplusia ni protects the peritrophic membrane from degradation by plant cysteine proteases.

    Science.gov (United States)

    Li, Changyou; Song, Xiaozhao; Li, Guoxun; Wang, Ping

    2009-10-01

    The action of plant cysteine proteases on the midgut peritrophic membrane (PM) of a polyphagous herbivorous lepidopteran, Trichoplusia ni, was studied. Proteins in PMs isolated from T. ni larvae were confirmed to be highly resistant to the serine proteinases trypsin and chymotrypsin, but were susceptible to degradation by plant cysteine proteases, which is consistent with the known molecular and biochemical characteristics of the T. ni PM proteins. However, the PM proteins were not degraded by plant cysteine proteases in larvae or in the presence of larval midgut fluid in vitro. With further biochemical analysis, cysteine protease-inhibiting activity was identified in the midgut fluid of T. ni larvae. The cysteine protease-inhibiting activity was heat resistant and active in the tested pH range from 6.0 to 10.0, but could be suppressed by thiol reducing reagents or reduced by treatment with catalase. In addition to T. ni, cysteine protease-inhibiting activity was also identified from two other polyphagous Lepidoptera species, Helicoverpa zea and Heliothis virescens. In conclusion, results from this study uncovered that herbivorous insects may counteract the attack of plant cysteine proteases on the PM by inhibiting the potentially insecticidal cysteine proteases from plants in the digestive tract. However, the biochemical identity of the cysteine protease-inhibiting activity in midgut fluid has yet to be identified.

  3. The expression analysis of cysteine proteinase-like protein in wild-type and nm2 mutant silkworm (Lepidoptera: Bombyx mori).

    Science.gov (United States)

    Wu, Fan; Kang, Lequn; Wang, Pingyang; Zhao, Qiaoling

    2016-07-15

    The mutant of non-molting in the 2nd instar (nm2) is a recently discovered mutant of Bombyx mori. The mutant cannot molt and exuviate and died successively in premolting of 2nd instar. In this study, two dimensional gel electrophoresis (2-DE) was performed to screen the differential expression of epidermis proteins in pre-molting larvae of 2nd instar between the wild-type and nm2 mutant. Interestingly, a cysteine proteinase-like (BmCP-like) protein in nm2 was significantly higher than that of the wild-type. The transcription profiles of BmCP-like gene were investigated by quantitative real-time PCR (qRT-PCR), and the result revealed that BmCP-like mRNA was remarkably higher in nm2 than that of the wild-type. The transcription level of BmCP-like was high in the epidermis while low in the midgut and hemocytes, and fluctuate with development, while the highest in the newly molted larvae of 3rd and lowest in the pre-molting of the 1st and 2nd instar. The body of injected BmCP-like RNAi of 2nd larvae formed a dark spots around the injection place. These results suggested the BmCP-like gene play a key role in the degradation of the cuticle and epidermis layer during molting of 1st and 2nd instar silkworm. Furthermore, the ORF of BmCP-like gene in nm2 was the same to the wild-type. These studies give us a hint that BmCP-like gene maybe not the major gene responsible for nm2, but BmCP-like gene might participate in the immune systems of silkworm, and the upregulation of BmCP-like transcription in the nm2 mutant might be induced by the disadvantages that limit the growth and development of silkworm in order to survive. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. In-silico prediction and modeling of the Entamoeba histolytica proteins: Serine-rich Entamoeba histolytica protein and 29 kDa Cysteine-rich protease.

    Science.gov (United States)

    Manochitra, Kumar; Parija, Subhash Chandra

    2017-01-01

    Amoebiasis is the third most common parasitic cause of morbidity and mortality, particularly in countries with poor hygienic settings. There exists an ambiguity in the diagnosis of amoebiasis, and hence there arises a necessity for a better diagnostic approach. Serine-rich Entamoeba histolyticaprotein (SREHP), peroxiredoxin and Gal/GalNAc lectin are pivotal in E. histolyticavirulence and are extensively studied as diagnostic and vaccine targets. For elucidating the cellular function of these proteins, details regarding their respective quaternary structures are essential. However, studies in this aspect are scant. Hence, this study was carried out to predict the structure of these target proteins and characterize them structurally as well as functionally using appropriate in-silicomethods. The amino acid sequences of the proteins were retrieved from National Centre for Biotechnology Information database and aligned using ClustalW. Bioinformatic tools were employed in the secondary structure and tertiary structure prediction. The predicted structure was validated, and final refinement was carried out. The protein structures predicted by i-TASSER were found to be more accurate than Phyre2 based on the validation using SAVES server. The prediction suggests SREHP to be an extracellular protein, peroxiredoxin a peripheral membrane protein while Gal/GalNAc lectin was found to be a cell-wall protein. Signal peptides were found in the amino-acid sequences of SREHP and Gal/GalNAc lectin, whereas they were not present in the peroxiredoxin sequence. Gal/GalNAc lectin showed better antigenicity than the other two proteins studied. All the three proteins exhibited similarity in their structures and were mostly composed of loops. The structures of SREHP and peroxiredoxin were predicted successfully, while the structure of Gal/GalNAc lectin could not be predicted as it was a complex protein composed of sub-units. Also, this protein showed less similarity with the available

  5. Evolution Of Cosmic Strings

    CERN Document Server

    Vanchurin, V

    2005-01-01

    We investigate the evolution of finite loops and infinite strings as a part of a complete cosmic string network. We give dynamical arguments showing that the structures on infinite strings should obey a scaling law. We perform a simulation of the network which uses functional forms for the string position and thus is exact to the limits of computer arithmetic. The effective box size of our simulation is at least two orders of magnitude larger than what was previously reached. Our results confirm that the wiggles on the strings obey a scaling law described by universal power spectrum. The average distance between long strings also scales accurately with the time. Production functions of string loops do not show scaling. With low intercommutation probability p the true scaling régime is not reached until very late cosmic times, which makes it difficult to simulate such evolutions. Via the expansion of the box technique, we were able to reach scaling with a wide range of p. The physical correlation ...

  6. Heterologous expression of Hordeum vulgare cysteine protease in yeast

    DEFF Research Database (Denmark)

    Rosenkilde, Anne Lind; Dionisio, Giuseppe; Holm, Preben B

    Cysteine Proteases accounts for more than 90 % of the total proteolytic activity in the degradation of barley seed storage proteins during germination. Several Cysteine proteases have been identified in barley. One of the key enzymes, Hordeum vulgare endoprotease B2 (HvEPB2) was cloned...

  7. The STRING database in 2011

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Franceschini, Andrea; Kuhn, Michael

    2011-01-01

    An essential prerequisite for any systems-level understanding of cellular functions is to correctly uncover and annotate all functional interactions among proteins in the cell. Toward this goal, remarkable progress has been made in recent years, both in terms of experimental measurements...... and computational prediction techniques. However, public efforts to collect and present protein interaction information have struggled to keep up with the pace of interaction discovery, partly because protein-protein interaction information can be error-prone and require considerable effort to annotate. Here, we......, and accessory information such as protein domains and 3D structures is made available, all within a stable and consistent identifier space. New features in STRING include an interactive network viewer that can cluster networks on demand, updated on-screen previews of structural information including homology...

  8. String theory for pedestrians

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    In this 3-lecture series I will discuss the basics of string theory, some physical applications, and the outlook for the future. I will begin with the main concepts of the classical theory and the application to the study of cosmic superstrings. Then I will turn to the quantum theory and discuss applications to the investigation of hadronic spectra and the recently discovered quark-gluon plasma. I will conclude with a sketch of string models of particle physics and showing some avenues that may lead to a complete formulation of string theory.

  9. Final Report: "Strings 2014"

    Energy Technology Data Exchange (ETDEWEB)

    Witten, Edward

    2015-10-21

    The Strings 2014 meeting was held at Princeton University June 23-27, 2014, co-sponsored by Princeton University and the Institute for Advanced Study. The goal of the meeting was to provide a stimulating and up-to-date overview of research in string theory and its relations to other areas of physics and mathematics, ranging from geometry to quantum field theory, condensed matter physics, and more. This brief report lists committee members and speakers but contains no scientific information. Note that the talks at Strings 2014 were videotaped and are available on the conference website: http://physics.princeton.edustrings2014/Talk_titles.shtml.

  10. Identification and Functional Analysis of Escherichia coli Cysteine Desulfhydrases

    OpenAIRE

    Awano, Naoki; WADA, Masaru; Mori, Hirotada; Nakamori, Shigeru; Takagi, Hiroshi

    2005-01-01

    In Escherichia coli, three additional proteins having l-cysteine desulfhydrase activity were identified as O-acetylserine sulfhydrylase-A, O-acetylserine sulfhydrylase-B, and MalY protein, in addition to tryptophanase and cystathionine β-lyase, which have been reported previously. The gene disruption for each protein was significantly effective for overproduction of l-cysteine and l-cystine. Growth phenotype and transcriptional analyses suggest that tryptophanase contributes primarily to l-cy...

  11. String Phenomenology at the LHC

    CERN Document Server

    Anchordoqui, Luis A; Lüst, Dieter; Stieberger, Stephan; Taylor, Tomasz R

    2009-01-01

    We consider extensions of the standard model based on open strings ending on D-branes, with gauge bosons due to strings attached to stacks of D-branes and chiral matter due to strings stretching between intersecting D-branes. Assuming that the fundamental string mass scale is in the TeV range and the theory is weakly coupled, we review possible signals of string physics at the Large Hadron Collider.

  12. International conference on string theory

    CERN Document Server

    2017-01-01

    The Strings 2017 conference is part of the "Strings" series of annual conferences, that bring the entire string theory community together. It will include reviews of major developments in the field, and specialized talks on specific topics. There will also be several public lectures given by conference participants, a pre-Strings school at the Technion, and a post-Strings workshop at the Weizmann Institute.

  13. International conference on string theory

    CERN Document Server

    2016-01-01

    The Strings conference is an annual event that brings the entire string theory community together. Since the 1980s, it has grown to be the largest and most important conference in the field. The aim is to review recent developments in string theory and to stimulate scientific exchanges among the participants. This is the second Strings conference organised in Beijing, after Strings 2006. Following the tradition, besides scientific talks, the conference will also include some public lectures open to a general audience.

  14. String Theory Rocks!

    CERN Multimedia

    2008-01-01

    String Theory supporters argue that the universe we live in has eleven dimensions, out of which three spacial dimensions and a temporal one, which define the void and the space-time environment we experience daily.

  15. String theory compactifications

    CERN Document Server

    Graña, Mariana

    2017-01-01

    The lectures in this book provide graduate students and non-specialist researchers with a concise introduction to the concepts and formalism required to reduce the ten-dimensional string theories to the observable four-dimensional space-time - a procedure called string compactification. The text starts with a very brief introduction to string theory, first working out its massless spectrum and showing how the condition on the number of dimensions arises. It then dwells on the different possible internal manifolds, from the simplest to the most relevant phenomenologically, thereby showing that the most elegant description is through an extension of ordinary Riemannian geometry termed generalized geometry, which was first introduced by Hitchin. Last but not least, the authors review open problems in string phenomenology, such as the embedding of the Standard Model and obtaining de Sitter solutions.

  16. String-math 2012

    CERN Document Server

    Katz, Sheldon; Klemm, Albrecht; Morrison, David R

    2015-01-01

    This volume contains the proceedings of the conference String-Math 2012, which was held July 16-21, 2012, at the Hausdorff Center for Mathematics, Universitat Bonn. This was the second in a series of annual large meetings devoted to the interface of mathematics and string theory. These meetings have rapidly become the flagship conferences in the field. Topics include super Riemann surfaces and their super moduli, generalized moonshine and K3 surfaces, the latest developments in supersymmetric and topological field theory, localization techniques, applications to knot theory, and many more. The contributors include many leaders in the field, such as Sergio Cecotti, Matthias Gaberdiel, Rahul Pandharipande, Albert Schwarz, Anne Taormina, Johannes Walcher, Katrin Wendland, and Edward Witten. This book will be essential reading for researchers and students in this area and for all mathematicians and string theorists who want to update themselves on developments in the math-string interface.

  17. Manipulating Strings in Python

    Directory of Open Access Journals (Sweden)

    William J. Turkel

    2012-07-01

    Full Text Available This lesson is a brief introduction to string manipulation techniques in Python. Knowing how to manipulate strings plays a crucial role in most text processing tasks. If you’d like to experiment with the following lessons, you can write and execute short programs as we’ve been doing, or you can open up a Python shell / Terminal to try them out on the command line.

  18. Cysteine Biosynthesis Controls Serratia marcescens Phospholipase Activity.

    Science.gov (United States)

    Anderson, Mark T; Mitchell, Lindsay A; Mobley, Harry L T

    2017-08-15

    Serratia marcescens causes health care-associated opportunistic infections that can be difficult to treat due to a high incidence of antibiotic resistance. One of the many secreted proteins of S. marcescens is the PhlA phospholipase enzyme. Genes involved in the production and secretion of PhlA were identified by screening a transposon insertion library for phospholipase-deficient mutants on phosphatidylcholine-containing medium. Mutations were identified in four genes (cyaA, crp, fliJ, and fliP) that are involved in the flagellum-dependent PhlA secretion pathway. An additional phospholipase-deficient isolate harbored a transposon insertion in the cysE gene encoding a predicted serine O-acetyltransferase required for cysteine biosynthesis. The cysE requirement for extracellular phospholipase activity was confirmed using a fluorogenic phospholipase substrate. Phospholipase activity was restored to the cysE mutant by the addition of exogenous l-cysteine or O-acetylserine to the culture medium and by genetic complementation. Additionally, phlA transcript levels were decreased 6-fold in bacteria lacking cysE and were restored with added cysteine, indicating a role for cysteine-dependent transcriptional regulation of S. marcescens phospholipase activity. S. marcescenscysE mutants also exhibited a defect in swarming motility that was correlated with reduced levels of flhD and fliA flagellar regulator gene transcription. Together, these findings suggest a model in which cysteine is required for the regulation of both extracellular phospholipase activity and surface motility in S. marcescensIMPORTANCESerratia marcescens is known to secrete multiple extracellular enzymes, but PhlA is unusual in that this protein is thought to be exported by the flagellar transport apparatus. In this study, we demonstrate that both extracellular phospholipase activity and flagellar function are dependent on the cysteine biosynthesis pathway. Furthermore, a disruption of cysteine biosynthesis

  19. String scattering amplitudes and deformed cubic string field theory

    Science.gov (United States)

    Lai, Sheng-Hong; Lee, Jen-Chi; Lee, Taejin; Yang, Yi

    2018-01-01

    We study string scattering amplitudes by using the deformed cubic string field theory which is equivalent to the string field theory in the proper-time gauge. The four-string scattering amplitudes with three tachyons and an arbitrary string state are calculated. The string field theory yields the string scattering amplitudes evaluated on the world sheet of string scattering whereas the conventional method, based on the first quantized theory brings us the string scattering amplitudes defined on the upper half plane. For the highest spin states, generated by the primary operators, both calculations are in perfect agreement. In this case, the string scattering amplitudes are invariant under the conformal transformation, which maps the string world sheet onto the upper half plane. If the external string states are general massive states, generated by non-primary field operators, we need to take into account carefully the conformal transformation between the world sheet and the upper half plane. We show by an explicit calculation that the string scattering amplitudes calculated by using the deformed cubic string field theory transform into those of the first quantized theory on the upper half plane by the conformal transformation, generated by the Schwarz-Christoffel mapping.

  20. Efficient Disk-Based Techniques for Manipulating Very Large String Databases

    KAUST Repository

    Allam, Amin

    2017-05-18

    Indexing and processing strings are very important topics in database management. Strings can be database records, DNA sequences, protein sequences, or plain text. Various string operations are required for several application categories, such as bioinformatics and entity resolution. When the string count or sizes become very large, several state-of-the-art techniques for indexing and processing such strings may fail or behave very inefficiently. Modifying an existing technique to overcome these issues is not usually straightforward or even possible. A category of string operations can be facilitated by the suffix tree data structure, which basically indexes a long string to enable efficient finding of any substring of the indexed string, and can be used in other operations as well, such as approximate string matching. In this document, we introduce a novel efficient method to construct the suffix tree index for very long strings using parallel architectures, which is a major challenge in this category. Another category of string operations require clustering similar strings in order to perform application-specific processing on the resulting possibly-overlapping clusters. In this document, based on clustering similar strings, we introduce a novel efficient technique for record linkage and entity resolution, and a novel method for correcting errors in a large number of small strings (read sequences) generated by the DNA sequencing machines.

  1. Determining cysteine oxidation status using differential alkylation

    Science.gov (United States)

    Schilling, Birgit; Yoo, Chris B.; Collins, Christopher J.; Gibson, Bradford W.

    2004-08-01

    Oxidative damage to proteins plays a major role in aging and in the pathology of many degenerative diseases. Under conditions of oxidative stress, reactive oxygen and nitrogen species can modify key redox sensitive amino acid side chains leading to altered biological activities or structures of the targeted proteins. This in turn can affect signaling or regulatory control pathways as well as protein turnover and degradation efficiency in the proteasome. Cysteine residues are particularly susceptible to oxidation, primarily through reversible modifications (e.g., thiolation and nitrosylation), although irreversible oxidation can lead to products that cannot be repaired in vivo such as sulfonic acid. This report describes a strategy to determine the overall level of reversible cysteine oxidation using a stable isotope differential alkylation approach in combination with mass spectrometric analysis. This method employs 13C-labeled alkylating reagents, such as N-ethyl-[1,4-13C2]-maleimide, bromo-[1,2-13C2]-acetic acid and their non-labeled counterparts to quantitatively assess the level of cysteine oxidation at specific sites in oxidized proteins. The differential alkylation protocol was evaluated using standard peptides and proteins, and then applied to monitor and determine the level of oxidative damage induced by diamide, a mild oxidant. The formation and mass spectrometric analysis of irreversible cysteine acid modification will also be discussed as several such modifications have been identified in subunits of the mitochondrial electron transport chain complexes. This strategy will hopefully contribute to our understanding of the role that cysteine oxidation plays in such chronic diseases such as Parkinson's disease, where studies in animal and cell models have shown oxidative damage to mitochondrial Complex I to be a specific and early target.

  2. The Protein Interaction of RNA Helicase B (RhlB) and Polynucleotide Phosphorylase (PNPase) Contributes to the Homeostatic Control of Cysteine in Escherichia coli*

    Science.gov (United States)

    Tseng, Yi-Ting; Chiou, Ni-Ting; Gogiraju, Rajinikanth; Lin-Chao, Sue

    2015-01-01

    PNPase, one of the major enzymes with 3′ to 5′ single-stranded RNA degradation and processing activities, can interact with the RNA helicase RhlB independently of RNA degradosome formation in Escherichia coli. Here, we report that loss of interaction between RhlB and PNPase impacts cysteine homeostasis in E. coli. By random mutagenesis, we identified a mutant RhlBP238L that loses 75% of its ability to interact with PNPase but retains normal interaction with RNase E and RNA, in addition to exhibiting normal helicase activity. Applying microarray analyses to an E. coli strain with impaired RNA degradosome formation, we investigated the biological consequences of a weakened interaction between RhlB and PNPase. We found significant increases in 11 of 14 genes involved in cysteine biosynthesis. Subsequent Northern blot analyses showed that the up-regulated transcripts were the result of stabilization of the cysB transcript encoding a transcriptional activator for the cys operons. Furthermore, Northern blots of PNPase or RhlB mutants showed that RhlB-PNPase plays both a catalytic and structural role in regulating cysB degradation. Cells expressing the RhlBP238L mutant exhibited an increase in intracellular cysteine and an enhanced anti-oxidative response. Collectively, this study suggests a mechanism by which bacteria use the PNPase-RhlB exosome-like complex to combat oxidative stress by modulating cysB mRNA degradation. PMID:26494621

  3. Exceptional groups from open strings

    OpenAIRE

    Gaberdiel, Matthias R.; Zwiebach, Barton

    1997-01-01

    We consider type IIB theory compactified on a two-sphere in the presence of mutually nonlocal 7-branes. The BPS states associated with the gauge vectors of exceptional groups are seen to arise from open strings connecting the 7-branes, and multi-pronged open strings capable of ending on more than two 7-branes. These multi-pronged strings are built from open string junctions that arise naturally when strings cross 7-branes. The different string configurations can be multiplied as traditional o...

  4. PT-symmetric strings

    Energy Technology Data Exchange (ETDEWEB)

    Amore, Paolo, E-mail: paolo.amore@gmail.com [Facultad de Ciencias, CUICBAS, Universidad de Colima, Bernal Díaz del Castillo 340, Colima, Colima (Mexico); Fernández, Francisco M., E-mail: fernande@quimica.unlp.edu.ar [INIFTA (UNLP, CCT La Plata-CONICET), División Química Teórica, Diag. 113 y 64 (S/N), Sucursal 4, Casilla de Correo 16, 1900 La Plata (Argentina); Garcia, Javier [INIFTA (UNLP, CCT La Plata-CONICET), División Química Teórica, Diag. 113 y 64 (S/N), Sucursal 4, Casilla de Correo 16, 1900 La Plata (Argentina); Gutierrez, German [Facultad de Ciencias, CUICBAS, Universidad de Colima, Bernal Díaz del Castillo 340, Colima, Colima (Mexico)

    2014-04-15

    We study both analytically and numerically the spectrum of inhomogeneous strings with PT-symmetric density. We discuss an exactly solvable model of PT-symmetric string which is isospectral to the uniform string; for more general strings, we calculate exactly the sum rules Z(p)≡∑{sub n=1}{sup ∞}1/E{sub n}{sup p}, with p=1,2,… and find explicit expressions which can be used to obtain bounds on the lowest eigenvalue. A detailed numerical calculation is carried out for two non-solvable models depending on a parameter, obtaining precise estimates of the critical values where pair of real eigenvalues become complex. -- Highlights: •PT-symmetric Hamiltonians exhibit real eigenvalues when PT symmetry is unbroken. •We study PT-symmetric strings with complex density. •They exhibit regions of unbroken PT symmetry. •We calculate the critical parameters at the boundaries of those regions. •There are exact real sum rules for some particular complex densities.

  5. Cysteine degradation gene yhaM, encoding cysteine desulfidase, serves as a genetic engineering target to improve cysteine production in Escherichia coli

    National Research Council Canada - National Science Library

    Gen Nonaka; Kazuhiro Takumi

    2017-01-01

    .... Owing to its cytotoxicity, bacterial intracellular levels of cysteine are stringently controlled via several modes of regulation, including cysteine degradation by cysteine desulfhydrases and cysteine desulfidases...

  6. The Protein Interaction of RNA Helicase B (RhlB) and Polynucleotide Phosphorylase (PNPase) Contributes to the Homeostatic Control of Cysteine in Escherichia coli.

    Science.gov (United States)

    Tseng, Yi-Ting; Chiou, Ni-Ting; Gogiraju, Rajinikanth; Lin-Chao, Sue

    2015-12-11

    PNPase, one of the major enzymes with 3' to 5' single-stranded RNA degradation and processing activities, can interact with the RNA helicase RhlB independently of RNA degradosome formation in Escherichia coli. Here, we report that loss of interaction between RhlB and PNPase impacts cysteine homeostasis in E. coli. By random mutagenesis, we identified a mutant RhlB(P238L) that loses 75% of its ability to interact with PNPase but retains normal interaction with RNase E and RNA, in addition to exhibiting normal helicase activity. Applying microarray analyses to an E. coli strain with impaired RNA degradosome formation, we investigated the biological consequences of a weakened interaction between RhlB and PNPase. We found significant increases in 11 of 14 genes involved in cysteine biosynthesis. Subsequent Northern blot analyses showed that the up-regulated transcripts were the result of stabilization of the cysB transcript encoding a transcriptional activator for the cys operons. Furthermore, Northern blots of PNPase or RhlB mutants showed that RhlB-PNPase plays both a catalytic and structural role in regulating cysB degradation. Cells expressing the RhlB(P238L) mutant exhibited an increase in intracellular cysteine and an enhanced anti-oxidative response. Collectively, this study suggests a mechanism by which bacteria use the PNPase-RhlB exosome-like complex to combat oxidative stress by modulating cysB mRNA degradation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Introduction to strings and branes

    CERN Document Server

    West, Peter

    2012-01-01

    Supersymmetry, strings and branes are believed to be the essential ingredients in a single unified consistent theory of physics. This book gives a detailed, step-by-step introduction to the theoretical foundations required for research in strings and branes. After a study of the different formulations of the bosonic and supersymmetric point particles, the classical and quantum bosonic and supersymmetric string theories are presented. This book includes accounts of brane dynamics and D-branes and the T, S and U duality symmetries of string theory. The historical derivation of string theory is given as well as the sum over the world-sheet approach to the interacting string. More advanced topics include string field theory and Kac–Moody symmetries. The book contains pedagogical accounts of conformal quantum field theory, supergravity theories, Clifford algebras and spinors, and Lie algebras. It is essential reading for graduate students and researchers wanting to learn strings and branes.

  8. Tensionless strings from worldsheet symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Bagchi, Arjun [Center for Theoretical Physics, Massachusetts Institute of Technology,77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Chakrabortty, Shankhadeep; Parekh, Pulastya [Indian Institute of Science Education and Research,Dr Homi Bhabha Road, Pashan, Pune 411008, INDIA (India); Van Swinderen Institute for Particle Physics and Gravity, University of Groningen, Nijenborgh 4, 9747 AG Groningen (Netherlands)

    2016-01-27

    We revisit the construction of the tensionless limit of closed bosonic string theory in the covariant formulation in the light of Galilean conformal symmetry that rises as the residual gauge symmetry on the tensionless worldsheet. We relate the analysis of the fundamentally tensionless theory to the tensionless limit that is viewed as a contraction of worldsheet coordinates. Analysis of the quantum regime uncovers interesting physics. The degrees of freedom that appear in the tensionless string are fundamentally different from the usual string states. Through a Bogoliubov transformation on the worldsheet, we link the tensionless vacuum to the usual tensile vacuum. As an application, we show that our analysis can be used to understand physics of strings at very high temperatures and propose that these new degrees of freedom are naturally connected with the long-string picture of the Hagedorn phase of free string theory. We also show that tensionless closed strings behave like open strings.

  9. Matrix string partition function

    CERN Document Server

    Kostov, Ivan K; Kostov, Ivan K.; Vanhove, Pierre

    1998-01-01

    We evaluate quasiclassically the Ramond partition function of Euclidean D=10 U(N) super Yang-Mills theory reduced to a two-dimensional torus. The result can be interpreted in terms of free strings wrapping the space-time torus, as expected from the point of view of Matrix string theory. We demonstrate that, when extrapolated to the ultraviolet limit (small area of the torus), the quasiclassical expressions reproduce exactly the recently obtained expression for the partition of the completely reduced SYM theory, including the overall numerical factor. This is an evidence that our quasiclassical calculation might be exact.

  10. Instability of colliding metastable strings

    Energy Technology Data Exchange (ETDEWEB)

    Hiramatsu, Takashi [Kyoto Univ. (Japan). Yukawa Inst. for Theoretical Physics; Eto, Minoru [Yamagata Univ. (Japan). Dept. of Physics; Kamada, Kohei [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kobayashi, Tatsuo [Kyoto Univ. (Japan). Dept. of Physics; Ookouchi, Yutaka [Kyoto Univ. (Japan). Dept. of Physics; Kyoto Univ. (Japan). The Hakubi Center for Advanced Research

    2013-04-15

    We investigate the collision dynamics of two metastable strings which can be viewed as tube-like domain walls with winding numbers interpolating a false vacuum and a true vacuum. We find that depending on the relative angle and speed of two strings, instability of strings increases and the false vacuum is filled out by rapid expansion of the strings or of a remnant of the collision.

  11. Electrons initiate efficient formation of hydroperoxides from cysteine.

    Science.gov (United States)

    Gebicki, Janusz M

    2016-09-01

    Amino acid and protein hydroperoxides can constitute a significant hazard if formed in vivo. It has been suggested that cysteine can form hydroperoxides after intramolecular hydrogen transfer to the commonly produced cysteine sulfur-centered radical. The resultant cysteine-derived carbon-centered radicals can react with oxygen at almost diffusion-controlled rate, forming peroxyl radicals which can oxidize other molecules and be reduced to hydroperoxides in the process. No cysteine hydroperoxides have been found so far. In this study, dilute air-saturated cysteine solutions were exposed to radicals generated by ionizing radiation and the hydroperoxides measured by an iodide assay. Of the three primary radicals present, the hydroxyl, hydrogen atoms and hydrated electrons, the first two were ineffective. However, electrons did initiate the generation of hydroperoxides by removing the -SH group and forming cysteine-derived carbon radicals. Under optimal conditions, 100% of the electrons reacting with cysteine produced the hydroperoxides with a 1:1 stoichiometry. Maximum hydroperoxide yields were at pH 5.5, with fairly rapid decline under more acid or alkaline conditions. The hydroperoxides were stable between pH 3 and 7.5, and decomposed in alkaline solutions. The results suggest that formation of cysteine hydroperoxides initiated by electrons is an unlikely event under physiological conditions.

  12. Cache-oblivious String Dictionaries

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf

    2006-01-01

    We present static cache-oblivious dictionary structures for strings which provide analogues of tries and suffix trees in the cache-oblivious model. Our construction takes as input either a set of strings to store, a single string for which all suffixes are to be stored, a trie, a compressed trie...

  13. Novel aggregate formation of a frame-shift mutant protein of tissue-nonspecific alkaline phosphatase is ascribed to three cysteine residues in the C-terminal extension. Retarded secretion and proteasomal degradation.

    Science.gov (United States)

    Komaru, Keiichi; Ishida, Yoko; Amaya, Yoshihiro; Goseki-Sone, Masae; Orimo, Hideo; Oda, Kimimitsu

    2005-04-01

    In the majority of hypophosphatasia patients, reductions in the serum levels of alkaline phosphatase activity are caused by various missense mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. A unique frame-shift mutation due to a deletion of T at cDNA number 1559 [TNSALP (1559delT)] has been reported only in Japanese patients with high allele frequency. In this study, we examined the molecular phenotype of TNSALP (1559delT) using in vitro translation/translocation system and COS-1 cells transiently expressing this mutant protein. We showed that the mutant protein not only has a larger molecular size than the wild type enzyme by approximately 12 kDa, reflecting an 80 amino acid-long extension at its C-terminus, but that it also lacks a glycosylphosphatidylinositol anchor. In support of this, alkaline phosphatase activity of the cells expressing TNSALP (1559delT) was localized at the juxtanucleus position, but not on the cell surface. However, only a limited amount of the newly synthesized protein was released into the medium and the rest was polyubiquitinated, followed by degradation in the proteasome. SDS/PAGE and analysis by sucrose-density-gradient analysis indicated that TNSALP (1559delT) forms a disulfide-bonded high-molecular-mass aggregate. Interestingly, the aggregate form of TNSALP (1559delT) exhibited a significant enzyme activity. When all three cysteines at positions of 506, 521 and 577 of TNSALP (1559delT) were replaced with serines, the aggregation disappeared and instead this modified mutant protein formed a noncovalently associated dimer, strongly indicating that these cysteine residues in the C-terminal region are solely responsible for aggregate formation by cross-linking the catalytically active dimers. Thus, complete absence of TNSALP on cell surfaces provides a plausible explanation for a severe lethal phenotype of a homozygote hypophosphatasia patient carrying TNSALP (1559delT).

  14. Cysteine cathepsins and extracellular matrix degradation.

    Science.gov (United States)

    Fonović, Marko; Turk, Boris

    2014-08-01

    Cysteine cathepsins are normally found in the lysosomes where they are involved in intracellular protein turnover. Their ability to degrade the components of the extracellular matrix in vitro was first reported more than 25years ago. However, cathepsins were for a long time not considered to be among the major players in ECM degradation in vivo. During the last decade it has, however, become evident that abundant secretion of cysteine cathepsins into extracellular milieu is accompanying numerous physiological and disease conditions, enabling the cathepsins to degrade extracellular proteins. In this review we will focus on cysteine cathepsins and their extracellular functions linked with ECM degradation, including regulation of their activity, which is often enhanced by acidification of the extracellular microenvironment, such as found in the bone resorption lacunae or tumor microenvironment. We will further discuss the ECM substrates of cathepsins with a focus on collagen and elastin, including the importance of that for pathologies. Finally, we will overview the current status of cathepsin inhibitors in clinical development for treatment of ECM-linked diseases, in particular osteoporosis. Cysteine cathepsins are among the major proteases involved in ECM remodeling, and their role is not limited to degradation only. Deregulation of their activity is linked with numerous ECM-linked diseases and they are now validated targets in a number of them. Cathepsins S and K are the most attractive targets, especially cathepsin K as a major therapeutic target for osteoporosis with drugs targeting it in advanced clinical trials. Due to their major role in ECM remodeling cysteine cathepsins have emerged as an important group of therapeutic targets for a number of ECM-related diseases, including, osteoporosis, cancer and cardiovascular diseases. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All

  15. Inflationary string theory?

    Indian Academy of Sciences (India)

    microwave background. Furthermore, the success of this description indicates that inflation is likely to be associated with physics at energies considerably higher than the weak scale, for which string theory is arguably our most promising candidate. These observations strongly motivate a detailed search for inflation within ...

  16. On exceptional instanton strings

    Science.gov (United States)

    Del Zotto, Michele; Lockhart, Guglielmo

    2017-09-01

    According to a recent classification of 6d (1 , 0) theories within F-theory there are only six "pure" 6d gauge theories which have a UV superconformal fixed point. The corresponding gauge groups are SU(3) , SO(8) , F 4 , E 6 , E 7, and E 8. These exceptional models have BPS strings which are also instantons for the corresponding gauge groups. For G simply-laced, we determine the 2d N=(0,4) worldsheet theories of such BPS instanton strings by a simple geometric engineering argument. These are given by a twisted S 2 compactification of the 4d N=2 theories of type H 2 , D 4 , E 6 , E 7 and E 8 (and their higher rank generalizations), where the 6d instanton number is mapped to the rank of the corresponding 4d SCFT. This determines their anomaly polynomials and, via topological strings, establishes an interesting relation among the corresponding T 2 × S 2 partition functions and the Hilbert series for moduli spaces of G instantons. Such relations allow to bootstrap the corresponding elliptic genera by modularity. As an example of such procedure, the elliptic genera for a single instanton string are determined. The same method also fixes the elliptic genus for case of one F 4 instanton. These results unveil a rather surprising relation with the Schur index of the corresponding 4d N=2 models.

  17. String Theory and Quintessence

    OpenAIRE

    Hellerman, Simeon; Kaloper, Nemanja; Susskind, Leonard

    2001-01-01

    We discuss the obstacles for defining a set of observable quantities analogous to an S-matrix which are needed to formulate string theory in an accelerating universe. We show that the quintessence models with the equations of state $-1 < w

  18. New Z3 strings

    Directory of Open Access Journals (Sweden)

    Marco A.C. Kneipp

    2016-12-01

    Full Text Available We consider a Yang–Mills–Higgs theory with the gauge group SU(3 broken to its center Z3 by two scalar fields in the adjoint representation and obtain new Z3 strings asymptotic configurations with the gauge field and magnetic field in the direction of the step operators.

  19. On exceptional instanton strings

    NARCIS (Netherlands)

    Del Zotto, M.; Lockhart, G.

    According to a recent classification of 6d (1, 0) theories within F-theory there are only six “pure” 6d gauge theories which have a UV superconformal fixed point. The corresponding gauge groups are SU(3), SO(8), F4, E6, E7, and E8. These exceptional models have BPS strings which are also instantons

  20. Fingerprints in compressed strings

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Cording, Patrick Hagge

    2017-01-01

    In this paper we show how to construct a data structure for a string S of size N compressed into a context-free grammar of size n that supports efficient Karp–Rabin fingerprint queries to any substring of S. That is, given indices i and j, the answer to a query is the fingerprint of the substring S...

  1. Help from the strings

    CERN Multimedia

    2007-01-01

    "How can the nature of basic particles be defined beyond the mechanisms presiding over their creation? Besides the standard model of particle physics - resulting from the postulations of quantum mechanics - contemporary science has pinned its hopes on the totally new unifying notion provided by the highly mathematical string theory."(2 pages)

  2. String Cosmology: A Review

    Energy Technology Data Exchange (ETDEWEB)

    McAllister, Liam P.; Silverstein, Eva

    2007-10-22

    We give an overview of the status of string cosmology. We explain the motivation for the subject, outline the main problems, and assess some of the proposed solutions. Our focus is on those aspects of cosmology that benefit from the structure of an ultraviolet-complete theory.

  3. Cosmic string loop microlensing

    Science.gov (United States)

    Bloomfield, Jolyon K.; Chernoff, David F.

    2014-06-01

    Cosmic superstring loops within the galaxy microlens background point sources lying close to the observer-string line of sight. For suitable alignments, multiple paths coexist and the (achromatic) flux enhancement is a factor of two. We explore this unique type of lensing by numerically solving for geodesics that extend from source to observer as they pass near an oscillating string. We characterize the duration of the flux doubling and the scale of the image splitting. We probe and confirm the existence of a variety of fundamental effects predicted from previous analyses of the static infinite straight string: the deficit angle, the Kaiser-Stebbins effect, and the scale of the impact parameter required to produce microlensing. Our quantitative results for dynamical loops vary by O(1) factors with respect to estimates based on infinite straight strings for a given impact parameter. A number of new features are identified in the computed microlensing solutions. Our results suggest that optical microlensing can offer a new and potentially powerful methodology for searches for superstring loop relics of the inflationary era.

  4. The loop gravity string

    CERN Document Server

    Freidel, Laurent; Pranzetti, Daniele

    2016-01-01

    In this work we study canonical gravity in finite regions for which we introduce a generalisation of the Gibbons-Hawking boundary term including the Immirzi parameter. We study the canonical formulation on a spacelike hypersuface with a boundary sphere and show how the presence of this term leads to an unprecedented type of degrees of freedom coming from the restoration of the gauge and diffeomorphism symmetry at the boundary. In the presence of a loop quantum gravity state, these boundary degrees of freedom localize along a set of punctures on the boundary sphere. We demonstrate that these degrees of freedom are effectively described by auxiliary strings with a 3-dimensional internal target space attached to each puncture. We show that the string currents represent the local frame field, that the string angular momenta represent the area flux and that the string stress tensor represents the two dimensional metric on the boundary of the region of interest. Finally, we show that the commutators of these broken...

  5. Regulation of cysteine dioxygenase degradation is mediated by intracellular cysteine levels and the ubiquitin-26 S proteasome system in the living rat.

    Science.gov (United States)

    Dominy, John E; Hirschberger, Lawrence L; Coloso, Relicardo M; Stipanuk, Martha H

    2006-02-15

    Mammalian metabolism of ingested cysteine is conducted principally within the liver. The liver tightly regulates its intracellular cysteine pool to keep levels high enough to meet the many catabolic and anabolic pathways for which cysteine is needed, but low enough to prevent toxicity. One of the enzymes the liver uses to regulate cysteine levels is CDO (cysteine dioxygenase). Catalysing the irreversible oxidation of cysteine, CDO protein is up-regulated in the liver in response to the dietary intake of cysteine. In the present study, we have evaluated the contribution of the ubiquitin-26 S proteasome pathway to the diet-induced changes in CDO half-life. In the living rat, inhibition of the proteasome with PS1 (proteasome inhibitor 1) dramatically stabilized CDO in the liver under dietary conditions that normally favour its degradation. Ubiquitinated CDO intermediates were also seen to accumulate in the liver. Metabolic analyses showed that PS1 had a significant effect on sulphoxidation flux secondary to the stabilization of CDO but no significant effect on the intracellular cysteine pool. Finally, by a combination of in vitro hepatocyte culture and in vivo whole animal studies, we were able to attribute the changes in CDO stability specifically to cysteine rather than the metabolite 2-mercaptoethylamine (cysteamine). The present study represents the first demonstration of regulated ubiquitination and degradation of a protein in a living mammal, inhibition of which had dramatic effects on cysteine catabolism.

  6. Regulation of cysteine dioxygenase degradation is mediated by intracellular cysteine levels and the ubiquitin–26 S proteasome system in the living rat

    Science.gov (United States)

    Dominy, John E.; Hirschberger, Lawrence L.; Coloso, Relicardo M.; Stipanuk, Martha H.

    2005-01-01

    Mammalian metabolism of ingested cysteine is conducted principally within the liver. The liver tightly regulates its intracellular cysteine pool to keep levels high enough to meet the many catabolic and anabolic pathways for which cysteine is needed, but low enough to prevent toxicity. One of the enzymes the liver uses to regulate cysteine levels is CDO (cysteine dioxygenase). Catalysing the irreversible oxidation of cysteine, CDO protein is up-regulated in the liver in response to the dietary intake of cysteine. In the present study, we have evaluated the contribution of the ubiquitin–26 S proteasome pathway to the diet-induced changes in CDO half-life. In the living rat, inhibition of the proteasome with PS1 (proteasome inhibitor 1) dramatically stabilized CDO in the liver under dietary conditions that normally favour its degradation. Ubiquitinated CDO intermediates were also seen to accumulate in the liver. Metabolic analyses showed that PS1 had a significant effect on sulphoxidation flux secondary to the stabilization of CDO but no significant effect on the intracellular cysteine pool. Finally, by a combination of in vitro hepatocyte culture and in vivo whole animal studies, we were able to attribute the changes in CDO stability specifically to cysteine rather than the metabolite 2-mercaptoethylamine (cysteamine). The present study represents the first demonstration of regulated ubiquitination and degradation of a protein in a living mammal, inhibition of which had dramatic effects on cysteine catabolism. PMID:16262602

  7. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur.

    Science.gov (United States)

    Stipanuk, Martha H; Ueki, Iori

    2011-02-01

    Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H₂S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions.

  8. Specifications for Managed Strings, Second Edition

    Science.gov (United States)

    2010-05-01

    errno_t sprintf_m(string_mx *buf, const string_mx * fmt , int *count, ...); Runtime-Constraints buf and fmt shall reference valid managed...strings. The managed string fmt shall be a valid format compatible with the arguments after fmt . Description The sprintf_m function formats its...parameters after the third parameter into a string accord- ing to the format contained in the managed string fmt and stores the result in the managed string

  9. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.

    2006-01-01

    has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition......We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung...... and salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in alpha(2,3) linkage. A greater density of alpha(2,3)-linked sialic acids was present on the salivary gp-340...

  10. Real topological string amplitudes

    Energy Technology Data Exchange (ETDEWEB)

    Narain, K.S. [The Abdus Salam International Centre for Theoretical Physics (ICTP),Strada Costiera 11, Trieste, 34151 (Italy); Piazzalunga, N. [Simons Center for Geometry and Physics, State University of New York,Stony Brook, NY, 11794-3636 (United States); International School for Advanced Studies (SISSA) and INFN, Sez. di Trieste,via Bonomea 265, Trieste, 34136 (Italy); Tanzini, A. [International School for Advanced Studies (SISSA) and INFN, Sez. di Trieste,via Bonomea 265, Trieste, 34136 (Italy)

    2017-03-15

    We discuss the physical superstring correlation functions in type I theory (or equivalently type II with orientifold) that compute real topological string amplitudes. We consider the correlator corresponding to holomorphic derivative of the real topological amplitude G{sub χ}, at fixed worldsheet Euler characteristic χ. This corresponds in the low-energy effective action to N=2 Weyl multiplet, appropriately reduced to the orientifold invariant part, and raised to the power g{sup ′}=−χ+1. We show that the physical string correlator gives precisely the holomorphic derivative of topological amplitude. Finally, we apply this method to the standard closed oriented case as well, and prove a similar statement for the topological amplitude F{sub g}.

  11. Exploring String Theory Backgrounds

    CERN Document Server

    Williams, B P

    2004-01-01

    This thesis examines phenomenological and theoretical questions by exploring string theoretic backgrounds. Part I focuses on cosmology. First we propose that the induced metric along a brane moving through a curved bulk may be interpreted as the cosmology of the brane universe, providing a resolution to the apparent cosmological singularity on the brane. We then look at various decay channels of the certain meta-stable de Sitter vacua and show that there exist NS5-brane meditated decays which are much faster than decays to decompactification. Part II discusses a new class of nongeometric vacua in string theory. These backgrounds may be described locally as T2 fibrations. By enlarging the monodromy group of the fiber to include perturbative stringy duality symmetries we are able to explicitly construct nongeometric backgrounds.

  12. Confinement, monopoles and strings

    Energy Technology Data Exchange (ETDEWEB)

    Bochicchio, M. (Theoretical Physics Div., CERN, Geneva (Switzerland))

    1992-06-04

    I compute the ratio between the square root of the string tension for SU(2) and the renormalization group invariant scale as a function of the percolation temperature of a gas of magnetic monopoles. The key point in the computation is the derivation of an exact equivalence between the SU(N) lattice partition function in the gauge F{sub 01}{sup ch}=0 and a lattice gas of interacting charges and monopoles. The number and types of monopoles for SU(N) and more generally of magnetic defects for a gauge group G turn out to be determined by the root structure of the corresponding Lie algebra. At the same time the aforementioned equivalence determines precisely the string theory which effectively describes the fluctuations of large Wilson loops. (orig.).

  13. Axions in String Theory

    Energy Technology Data Exchange (ETDEWEB)

    Svrcek, Peter; /Stanford U., Phys. Dept. /SLAC; Witten, Edward; /Princeton, Inst. Advanced Study

    2006-06-09

    In the context of string theory, axions appear to provide the most plausible solution of the strong CP problem. However, as has been known for a long time, in many string-based models, the axion coupling parameter Fa is several orders of magnitude higher than the standard cosmological bounds. We re-examine this problem in a variety of models, showing that Fa is close to the GUT scale or above in many models that have GUT-like phenomenology, as well as some that do not. On the other hand, in some models with Standard Model gauge fields supported on vanishing cycles, it is possible for Fa to be well below the GUT scale.

  14. New Supersymmetric String Compactifications

    Energy Technology Data Exchange (ETDEWEB)

    Kachru, Shamit

    2002-11-25

    We describe a new class of supersymmetric string compactifications to 4d Minkowski space. These solutions involve type II strings propagating on (orientifolds of) non Calabi-Yau spaces in the presence of background NS and RR fluxes. The simplest examples have descriptions as cosets, generalizing the three-dimensional nilmanifold. They can also be thought of as twisted tori. We derive a formula for the (super)potential governing the light fields, which is generated by the fluxes and certain ''twists'' in the geometry. Detailed consideration of an example also gives strong evidence that in some cases, these exotic geometries are related by smooth transitions to standard Calabi-Yau or G2 compactifications of M-theory.

  15. Inactivation of glyceraldehyde-3-phosphate dehydrogenase by fumarate in diabetes: formation of S-(2-succinyl)cysteine, a novel chemical modification of protein and possible biomarker of mitochondrial stress.

    Science.gov (United States)

    Blatnik, Matthew; Frizzell, Norma; Thorpe, Suzanne R; Baynes, John W

    2008-01-01

    (2-succinyl)cysteine (2SC) is formed by a Michael addition reaction of the Krebs cycle intermediate, fumarate, with cysteine residues in protein. We investigated the role of fumarate in chemical modification and inhibition of the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in vitro and in tissues of diabetic rats. GAPDH was incubated with fumarate in PBS to assess effects of fumarate on enzyme activity in vitro. Sites of 2SC formation were determined by analysis of tryptic peptides by high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. 2SC and fumarate in gastrocnemius muscle of control and streptozotocin-induced diabetic rats were measured by liquid chromatography/tandem mass spectrometry and by gas chromatography/mass spectrometry, respectively. GAPDH was isolated from muscle by immunoprecipitation, and sites of modification of GAPDH were determined by mass spectrometry analysis. 2SC was found, both in vitro and in vivo, about equally at active-site Cys-149 and nucleophilic Cys-244. Inactivation of GAPDH by fumarate in vitro correlated with formation of 2SC. In diabetic compared with control rats, fumarate and 2SC concentration increased approximately fivefold, accompanied by an approximately 25% decrease in GAPDH specific activity. The fractional modification of GAPDH by 2SC was significantly increased in diabetic versus control animals, consistent with the decreased specific activity of GAPDH in muscle of diabetic animals. Fumarate contributes to inactivation of GAPDH in diabetes. 2SC may be a useful biomarker of mitochondrial stress in diabetes. Modification of GAPDH and other enzymes and proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications.

  16. Dual string apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Ageshin, M.S.; Bol' shakov, V.V.; Grishchenko, S.I.; Litvin, N.A.; Sorokin, V.I.

    1980-03-30

    The designers propose a string apparatus consisting of a reducer, an external tube, a rock-fracturing instrument, and a mechanism for leading the internal tubes. This mechanism consists of a shaft-mounted reducer which interacts with the outside tube by a spiral spring. Operational reliability and core retrieval are enhanced by reducing rotational vibration in the outside tube, and by permitting shifting in the reducer and movable shaft through the work of the spiral spring.

  17. Quantized string models

    Energy Technology Data Exchange (ETDEWEB)

    Fradkin, E.S.; Tseytlin, A.A.

    1982-10-15

    We discuss and compare the Lorentz covariant path integral quantization of the three bose string models, namely, the Nambu, Eguchi and Brink-Di Vecchai-Howe-Polyakov (BDHP) ones. Along with a critical review of the subject with some uncertainties and ambiguities clearly stated, various new results are presented. We work out the form of the BDHP string ansatz for the Wilson average and prove a formal inequivalence of the exact Nambu and BDHP models for any space-time dimension d. The above three models known to be equivalent on the classical level, are shown to be equivalent in a semiclassical approximation near a minimal surface and also in the leading 1/d-approximation for the static q-barq-potential. We analyze scattering amplitudes predicted by the BDHP string and find that when exactly calculated for d<26 they are different from the old dual ones, and possess a non-linear spectrum which may be considered as free from tachyons in the ground state.

  18. Thermodynamical string fragmentation

    Science.gov (United States)

    Fischer, Nadine; Sjöstrand, Torbjörn

    2017-01-01

    The observation of heavy-ion-like behaviour in pp collisions at the LHC suggests that more physics mechanisms are at play than traditionally assumed. The introduction e.g. of quark-gluon plasma or colour rope formation can describe several of the observations, but as of yet there is no established paradigm. In this article we study a few possible modifications to the Pythia event generator, which describes a wealth of data but fails for a number of recent observations. Firstly, we present a new model for generating the transverse momentum of hadrons during the string fragmentation process, inspired by thermodynamics, where heavier hadrons naturally are suppressed in rate but obtain a higher average transverse momentum. Secondly, close-packing of strings is taken into account by making the temperature or string tension environment-dependent. Thirdly, a simple model for hadron rescattering is added. The effect of these modifications is studied, individually and taken together, and compared with data mainly from the LHC. While some improvements can be noted, it turns out to be nontrivial to obtain effects as big as required, and further work is called for.

  19. Identification of a novel small cysteine-rich protein in the fraction from the biocontrol Fusarium oxysporum strain CS-20 that mitigates Fusarium wilt symptoms and triggers defense responses in tomato

    Directory of Open Access Journals (Sweden)

    Larisa A. Shcherbakova

    2016-01-01

    Full Text Available The biocontrol effect of the nonpathogenic F. oxysporum strain CS-20 against the tomato wilt pathogen F. oxysporum f. sp. lycopersici (FOL has been previously reported to be primarily plant-mediated. This study shows that CS-20 produces proteins, which elicit defense responses in tomato plants. Three protein-containing fractions were isolated from CS-20 biomass using size exclusion chromatography. Exposure of seedling roots to one of these fractions prior to inoculation with pathogenic FOL strains significantly reduced wilt severity. This fraction initiated an ion exchange response in cultured tomato cells resulting in a reversible alteration of extracellular pH; increased tomato chitinase activity, and induced systemic resistance by enhancing PR-1 expression in tomato leaves. Two other protein fractions were inactive in seedling protection. The main polypeptide (designated CS20EP, which was specifically present in the defense-inducing fraction and was not detected in inactive protein fractions, was identified. The nucleotide sequence encoding this protein was determined, and its complete amino acid sequence was deduced from direct Edman degradation (25 N-terminal amino acid residues and DNA sequencing. The CS20EP was found to be a small basic cysteine-rich protein with a pI of 9.87 and 23.43% of hydrophobic amino acid residues. BLAST search in the NCBI database showed that the protein is new; however, it displays 48% sequence similarity with a hypothetical protein FGSG_10784 from F. graminearum strain PH-1. The contribution of CS20EP to elicitation of tomato defense responses resulting in wilt mitigating is discussed.

  20. Modification of Keap1 Cysteine Residues by Sulforaphane

    Science.gov (United States)

    Hu, Chenqi; Eggler, Aimee L.; Mesecar, Andrew D.; van Breemen, Richard B.

    2011-01-01

    Activation of the transcription factor NF-E2-related factor-2 (Nrf2) through modification of Kelch-like ECH-associated protein 1 (Keap1) cysteines, leading to up-regulation of the antioxidant response element (ARE), is an important mechanism of cellular defense against reactive oxygen species and xenobiotic electrophiles. Sulforaphane, occurring in cruciferous vegetables such as broccoli, is a potent natural ARE activator that functions by modifying Keap1 cysteine residues, but there are conflicting in vitro and in vivo data regarding which of these cysteine residues react. Although most biological data indicate that modification of C151 is essential for sulforaphane action, some recent studies using mass spectrometry have failed to identify C151 as a site of Keap1 sulforaphane reaction. We have reconciled these conflicting data using mass spectrometry with a revised sample preparation protocol and confirmed that C151 is indeed among the most readily modified cysteines of Keap1 by sulforaphane. Previous mass spectrometry-based studies used iodoacetamide during sample preparation to derivatize free cysteine sulfhydryl groups causing loss of sulforaphane from highly reactive and reversible cysteine residues on Keap1 including C151. By omitting iodoacetamide from the protocol and reducing sample preparation time, our mass spectrometry-based studies now confirm previous cell-based studies which showed that sulforaphane reacts with at least four cysteine residues of Keap1 including C151. PMID:21391649

  1. Comparative assessment of a DNA and protein Leishmania donovani gamma glutamyl cysteine synthetase vaccine to cross-protect against murine cutaneous leishmaniasis caused by L. major or L. mexicana infection.

    Science.gov (United States)

    Campbell, S A; Alawa, J; Doro, B; Henriquez, F L; Roberts, C W; Nok, A; Alawa, C B I; Alsaadi, M; Mullen, A B; Carter, K C

    2012-02-08

    Leishmaniasis is a major health problem and it is estimated that 12 million people are currently infected. A vaccine which could cross-protect people against different Leishmania spp. would facilitate control of this disease as more than one species of Leishmania may be present. In this study the ability of a DNA vaccine, using the full gene sequence for L. donovani gamma glutamyl cysteine synthetase (γGCS) incorporated in the pVAX vector (pVAXγGCS), and a protein vaccine, using the corresponding recombinant L. donovani γGCS protein (LdγGCS), to protect against L. major or L. mexicana infection was evaluated. DNA vaccination gave transient protection against L. major and no protection against L. mexicana despite significantly enhancing specific antibody titres in vaccinated infected mice compared to infected controls. Vaccination with the LdγGCS protected against both species but only if the protein was incorporated into non-ionic surfactant vesicles for L. mexicana. The results of this study indicate that a L. donovani γGCS vaccine could be used to vaccinate against more than one Leishmania species but only if the recombinant protein is used. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Application of iTRAQ Reagents to Relatively Quantify the Reversible Redox State of Cysteine Residues

    Directory of Open Access Journals (Sweden)

    Brian McDonagh

    2012-01-01

    Full Text Available Cysteines are one of the most rarely used amino acids, but when conserved in proteins they often play critical roles in structure, function, or regulation. Reversible cysteine modifications allow for potential redox regulation of proteins. Traditional measurement of the relative absolute quantity of a protein between two samples is not always necessarily proportional to the activity of the protein. We propose application of iTRAQ reagents in combination with a previous thiol selection method to relatively quantify the redox state of cysteines both within and between samples in a single analysis. Our method allows for the identification of the proteins, identification of redox-sensitive cysteines within proteins, and quantification of the redox status of individual cysteine-containing peptides. As a proof of principle, we applied this technique to yeast alcohol dehydrogenase-1 exposed in vitro to H2O2 and also in vivo to the complex proteome of the Gram-negative bacterium Bacillus subtilis.

  3. Comparing double string theory actions

    Energy Technology Data Exchange (ETDEWEB)

    De Angelis, L. [Dipartimento di Fisica, Università degli Studi “Federico II” di Napoli,Complesso Universitario Monte S. Angelo ed. 6, via Cintia, 80126 Napoli (Italy); Gionti, S.J.G. [Specola Vaticana, Vatican City, V-00120, Vatican City State and Vatican Observatory Research Group, Steward Observatory, The University Of Arizona, 933 North Cherry Avenue, Tucson, Arizona 85721 (United States); Marotta, R.; Pezzella, F. [Istituto Nazionale di Fisica Nucleare, Sezione di Napoli,Complesso Universitario di Monte S. Angelo ed. 6, via Cintia, 80126 Napoli (Italy)

    2014-04-28

    Aimed to a deeper comprehension of a manifestly T-dual invariant formulation of string theory, in this paper a detailed comparison between the non-covariant action proposed by Tseytlin and the covariant one proposed by Hull is done. These are obtained by making both the string coordinates and their duals explicitly appear, on the same footing, in the world-sheet action, so “doubling” the string coordinates along the compact dimensions. After a discussion on the nature of the constraints in both the models and the relative quantization, it results that the string coordinates and their duals behave like “non-commuting” phase space coordinates but their expressions in terms of Fourier modes generate the oscillator algebra of the standard bosonic string. A proof of the equivalence of the two formulations is given. Furthermore, open-string solutions are also discussed.

  4. Cathepsin D inactivates cysteine proteinase inhibitors, cystatins.

    Science.gov (United States)

    Lenarcic, B; Kos, J; Dolenc, I; Lucovnik, P; Krizaj, I; Turk, V

    1988-07-29

    The formation of inactive complexes in excess molar amounts of human cathepsins H and L with their protein inhibitors human stefin A, human stefin B and chicken cystatin at pH 5.6 has been shown by measurement of enzyme activity coupled with reverse-phase HPLC not to involve covalent cleavage of the inhibitors. Inhibition must be the direct result of binding. On the contrary the interaction of cystatins with aspartic proteinase cathepsin D at pH 3.5 for 60 min followed by HPLC resulted in their inactivation accompanied by peptide bond cleavage at several sites, preferentially those involving hydrophobic amino acid residues. The released peptides do not inhibit papain and cathepsin L. These results explain reported elevated levels of cysteine proteinases and lead to the proposal that cathepsin D exerts an important function, through inactivation of cystatins, in the increased activities of cysteine proteinases in human diseases including muscular distrophy.

  5. Transcriptome Analysis Revealed Highly Expressed Genes Encoding Secondary Metabolite Pathways and Small Cysteine-Rich Proteins in the Sclerotium of Lignosus rhinocerotis.

    Directory of Open Access Journals (Sweden)

    Hui-Yeng Y Yap

    Full Text Available Lignosus rhinocerotis (Cooke Ryvarden (tiger milk mushroom has long been known for its nutritional and medicinal benefits among the local communities in Southeast Asia. However, the molecular and genetic basis of its medicinal and nutraceutical properties at transcriptional level have not been investigated. In this study, the transcriptome of L. rhinocerotis sclerotium, the part with medicinal value, was analyzed using high-throughput Illumina HiSeqTM platform with good sequencing quality and alignment results. A total of 3,673, 117, and 59,649 events of alternative splicing, novel transcripts, and SNP variation were found to enrich its current genome database. A large number of transcripts were expressed and involved in the processing of gene information and carbohydrate metabolism. A few highly expressed genes encoding the cysteine-rich cerato-platanin, hydrophobins, and sugar-binding lectins were identified and their possible roles in L. rhinocerotis were discussed. Genes encoding enzymes involved in the biosynthesis of glucans, six gene clusters encoding four terpene synthases and one each of non-ribosomal peptide synthetase and polyketide synthase, and 109 transcribed cytochrome P450 sequences were also identified in the transcriptome. The data from this study forms a valuable foundation for future research in the exploitation of this mushroom in pharmacological and industrial applications.

  6. Classical theory of radiating strings

    Science.gov (United States)

    Copeland, Edmund J.; Haws, D.; Hindmarsh, M.

    1990-01-01

    The divergent part of the self force of a radiating string coupled to gravity, an antisymmetric tensor and a dilaton in four dimensions are calculated to first order in classical perturbation theory. While this divergence can be absorbed into a renormalization of the string tension, demanding that both it and the divergence in the energy momentum tensor vanish forces the string to have the couplings of compactified N = 1 D = 10 supergravity. In effect, supersymmetry cures the classical infinities.

  7. A primer on string theory

    CERN Document Server

    Schomerus, Volker

    2017-01-01

    Since its conception in the 1960s, string theory has been hailed as one of the most promising routes we have to unify quantum mechanics and general relativity. This book provides a concise introduction to string theory explaining central concepts, mathematical tools and covering recent developments in physics including compactifications and gauge/string dualities. With string theory being a multidisciplinary field interfacing with high energy physics, mathematics and quantum field theory, this book is ideal for both students with no previous knowledge of the field and scholars from other disciplines who are looking for an introduction to basic concepts.

  8. Crystallization and preliminary X-ray analysis of ginkbilobin-2 from Ginkgo biloba seeds: a novel antifungal protein with homology to the extracellular domain of plant cysteine-rich receptor-like kinases

    Energy Technology Data Exchange (ETDEWEB)

    Miyakawa, Takuya; Sawano, Yoriko; Miyazono, Ken-ichi [Department of Applied Biochemical Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657 (Japan); Hatano, Ken-ichi [Department of Chemistry and Chemical Biology, Faculty of Engineering, Gunma University, Kiryu, Gunma 376-8515 (Japan); Tanokura, Masaru, E-mail: amtanok@mail.ecc.u-tokyo.ac.jp [Department of Applied Biochemical Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657 (Japan)

    2007-09-01

    Purification and crystallization of ginkbilobin-2 and its selenomethionine derivative allowed the collection of complete data to 2.38 Å resolution and multiwavelength anomalous diffraction data sets, respectively. The antifungal protein ginkbilobin-2 (Gnk2) from Ginkgo biloba seeds does not show homology to other pathogenesis-related proteins, but does show homology to the extracellular domain of plant cysteine-rich receptor-like kinases. Native Gnk2 purified from ginkgo nuts and the selenomethionine derivative of recombinant Gnk2 (SeMet-rGnk2) were crystallized by the sitting-drop vapour-diffusion method using different precipitants. X-ray diffraction data were collected from Gnk2 at 2.38 Å resolution and from SeMet-rGnk2 at 2.79 Å resolution using a synchrotron-radiation source. The crystals of both proteins belonged to the primitive cubic space group P2{sub 1}3, with unit-cell parameters a = b = c = 143.2 Å.

  9. Multi-environment QTL studies suggest a role for cysteine-rich protein kinase genes in quantitative resistance to blackleg disease in Brassica napus.

    Science.gov (United States)

    Larkan, Nicholas J; Raman, Harsh; Lydiate, Derek J; Robinson, Stephen J; Yu, Fengqun; Barbulescu, Denise M; Raman, Rosy; Luckett, David J; Burton, Wayne; Wratten, Neil; Salisbury, Philip A; Rimmer, S Roger; Borhan, M Hossein

    2016-08-24

    Resistance to the blackleg disease of Brassica napus (canola/oilseed rape), caused by the hemibiotrophic fungal pathogen Leptosphaeria maculans, is determined by both race-specific resistance (R) genes and quantitative resistance loci (QTL), or adult-plant resistance (APR). While the introgression of R genes into breeding material is relatively simple, QTL are often detected sporadically, making them harder to capture in breeding programs. For the effective deployment of APR in crop varieties, resistance QTL need to have a reliable influence on phenotype in multiple environments and be well defined genetically to enable marker-assisted selection (MAS). Doubled-haploid populations produced from the susceptible B. napus variety Topas and APR varieties AG-Castle and AV-Sapphire were analysed for resistance to blackleg in two locations over 3 and 4 years, respectively. Three stable QTL were detected in each population, with two loci appearing to be common to both APR varieties. Physical delineation of three QTL regions was sufficient to identify candidate defense-related genes, including a cluster of cysteine-rich receptor-like kinases contained within a 49 gene QTL interval on chromosome A01. Individual L. maculans isolates were used to define the physical intervals for the race-specific R genes Rlm3 and Rlm4 and to identify QTL common to both field studies and the cotyledon resistance response. Through multi-environment QTL analysis we have identified and delineated four significant and stable QTL suitable for MAS of quantitative blackleg resistance in B. napus, and identified candidate genes which potentially play a role in quantitative defense responses to L. maculans.

  10. Evolution of cysteine patterns in the large extracellular loop of tetraspanins from animals, fungi, plants and single-celled eukaryotes.

    Science.gov (United States)

    DeSalle, Rob; Mares, Roso; Garcia-España, Antonio

    2010-07-01

    By analyzing the evolution of cysteine patterns in the large extracellular loop (LEL) of tetraspanins across all eukaryotes, we report the following: (1) the origin of the cysteine-cysteine-glycine (CCG) motif in the common ancestor of unikonts (Animalia, fungi and amoebozoa); (2) tracing cysteine motifs on an eukaryotic phylogeny which includes protists, animals and plants match organismal evolution; (3) using this evolutionary approach we have determined some of the cysteines in these proteins that are involved in specific bonds in the LEL. Our study provides a framework to better understand tetraspanin formation, diversification and the evolutionary history of these important proteins. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Characterization and sequence analysis of cysteine and glycine-rich ...

    African Journals Online (AJOL)

    Cysteine and glycine rich protein, CSRP3 also referred to as the muscle LIM protein (MLP), has been investigated in native Egyptian cattle and buffalo (river buffalo). RNA extraction and cDNA synthesis were conducted from different tissue samples. Primers specific for CSRP3 were designed using known cDNA sequences ...

  12. Characterization and sequence analysis of cysteine and glycine-rich ...

    African Journals Online (AJOL)

    Tarek

    2011-04-18

    Apr 18, 2011 ... Cysteine and glycine rich protein, CSRP3 also referred to as the muscle LIM protein (MLP), has been investigated in native Egyptian cattle and buffalo (river buffalo). RNA extraction and cDNA synthesis were conducted from different tissue samples. Primers specific for CSRP3 were designed using known.

  13. Differential expression of cysteine desulfurases in soybean

    Directory of Open Access Journals (Sweden)

    Heis Marta D

    2011-11-01

    Full Text Available Abstract Background Iron-sulfur [Fe-S] clusters are prosthetic groups required to sustain fundamental life processes including electron transfer, metabolic reactions, sensing, signaling, gene regulation and stabilization of protein structures. In plants, the biogenesis of Fe-S protein is compartmentalized and adapted to specific needs of the cell. Many environmental factors affect plant development and limit productivity and geographical distribution. The impact of these limiting factors is particularly relevant for major crops, such as soybean, which has worldwide economic importance. Results Here we analyze the transcriptional profile of the soybean cysteine desulfurases NFS1, NFS2 and ISD11 genes, involved in the biogenesis of [Fe-S] clusters, by quantitative RT-PCR. NFS1, ISD11 and NFS2 encoding two mitochondrial and one plastid located proteins, respectively, are duplicated and showed distinct transcript levels considering tissue and stress response. NFS1 and ISD11 are highly expressed in roots, whereas NFS2 showed no differential expression in tissues. Cold-treated plants showed a decrease in NFS2 and ISD11 transcript levels in roots, and an increased expression of NFS1 and ISD11 genes in leaves. Plants treated with salicylic acid exhibited increased NFS1 transcript levels in roots but lower levels in leaves. In silico analysis of promoter regions indicated the presence of different cis-elements in cysteine desulfurase genes, in good agreement with differential expression of each locus. Our data also showed that increasing of transcript levels of mitochondrial genes, NFS1/ISD11, are associated with higher activities of aldehyde oxidase and xanthine dehydrogenase, two cytosolic Fe-S proteins. Conclusions Our results suggest a relationship between gene expression pattern, biochemical effects, and transcription factor binding sites in promoter regions of cysteine desulfurase genes. Moreover, data show proportionality between NFS1 and ISD11

  14. Towards optimal packed string matching

    DEFF Research Database (Denmark)

    Ben-Kiki, Oren; Bille, Philip; Breslauer, Dany

    2014-01-01

    -size string-matching instruction wssm is available in contemporary commodity processors. The other word-size maximum-suffix instruction wslm is only required during the pattern pre-processing. Benchmarks show that our solution can be efficiently implemented, unlike some prior theoretical packed string...

  15. String theory : physics or metaphysics?

    CERN Document Server

    Veneziano, Gabriele

    2010-01-01

    I will give arguments for why the enormous progress made during the last century on understanding elementary particles and their fundamental interactions suggests strings as the truly elementary constituents of Nature. I will then address the issue of whether the string paradigm can in principle be falsified or whether it should be considered as mere metaphysics.

  16. Cool Runnings For String 2

    CERN Multimedia

    2001-01-01

    String 2 is a series of superconducting magnets that are prototypes of those which will be installed in the LHC. It was cooled down to 1.9 Kelvin on September 14th. On Thursday last week, the dipoles of String 2 were successfully taken to nominal current, 11850 A.

  17. Deformations of topological open strings

    NARCIS (Netherlands)

    Hofman, C.; Ma, Whee Ky

    Deformations of topological open string theories are described, with an emphasis on their algebraic structure. They are encoded in the mixed bulk-boundary correlators. They constitute the Hochschild complex of the open string algebra - the complex of multilinear maps on the boundary Hilbert space.

  18. Solar-Cell String Conveyor

    Science.gov (United States)

    Frasch, W.; Ciavola, S.

    1982-01-01

    String-conveyor portion of solar-array assembly line holds silicon solar cells while assembled into strings and tested. Cells are transported collector-side-down, while uniform cell spacing and registration are maintained. Microprocessor on machine controls indexing of cells.

  19. Progress in string theory research

    CERN Document Server

    2016-01-01

    At the first look, the String Theory seems just an interesting and non-trivial application of the quantum mechanics and the special relativity to vibrating strings. By itself, the quantization of relativistic strings does not call the attention of the particle physicist as a significant paradigm shift. However, when the string quantization is performed by applying the standard rules of the perturbative Quantum Field Theory, one discovers that the strings in certain states have the same physical properties as the gravity in the flat space-time. Chapter one of this book reviews the construction of the thermal bosonic string and D-brane in the framework of the Thermo Field Dynamics (TFD). It briefly recalls the wellknown light-cone quantization of the bosonic string in the conformal gauge in flat space-time, and gives a bird’s eye view of the fundamental concepts of the TFD. Chapter two examines a visual model inspired by string theory, on the system of interacting anyons. Chapter three investigate the late-ti...

  20. String dualities and superpotential

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Tae-Won

    2010-09-15

    The main objective of this thesis is the computation of the superpotential induced by D5- branes in the type IIB string theory and by five-branes in the heterotic string theory. Both superpotentials have the same functional form which is the chain integral of the holomorphic three-form. Using relative (co)homology we can unify the flux and brane superpotential. The chain integral can be seen as an example of the Abel-Jacobi map. We discuss many structures such as mixed Hodge structure which allows for the computation of Picard-Fuchs differential equations crucial for explicit computations. We blow up the Calabi-Yau threefold along the submanifold wrapped by the brane to obtain geometrically more appropriate configuration. The resulting geometry is non-Calabi-Yau and we have a canonically given divisor. This blown-up geometry makes it possible to restrict our attention to complex structure deformations. However, the direct computation is yet very difficult, thus the main tool for computation will be the lift of the brane configuration to a F-theory compactification. In F-theory, since complex structure, brane and, if present, bundlemoduli are all contained in the complex structure moduli space of the elliptic Calabi-Yau fourfold, the computation can be dramatically simplified. The heterotic/F-theory duality is extended to include the blow-up geometry and thereby used to give the blow-up geometry amore physical meaning. (orig.)

  1. Poisson hierarchy of discrete strings

    Energy Technology Data Exchange (ETDEWEB)

    Ioannidou, Theodora, E-mail: ti3@auth.gr [Faculty of Civil Engineering, School of Engineering, Aristotle University of Thessaloniki, 54249, Thessaloniki (Greece); Niemi, Antti J., E-mail: Antti.Niemi@physics.uu.se [Department of Physics and Astronomy, Uppsala University, P.O. Box 803, S-75108, Uppsala (Sweden); Laboratoire de Mathematiques et Physique Theorique CNRS UMR 6083, Fédération Denis Poisson, Université de Tours, Parc de Grandmont, F37200, Tours (France); Department of Physics, Beijing Institute of Technology, Haidian District, Beijing 100081 (China)

    2016-01-28

    The Poisson geometry of a discrete string in three dimensional Euclidean space is investigated. For this the Frenet frames are converted into a spinorial representation, the discrete spinor Frenet equation is interpreted in terms of a transfer matrix formalism, and Poisson brackets are introduced in terms of the spinor components. The construction is then generalised, in a self-similar manner, into an infinite hierarchy of Poisson algebras. As an example, the classical Virasoro (Witt) algebra that determines reparametrisation diffeomorphism along a continuous string, is identified as a particular sub-algebra, in the hierarchy of the discrete string Poisson algebra. - Highlights: • Witt (classical Virasoro) algebra is derived in the case of discrete string. • Infinite dimensional hierarchy of Poisson bracket algebras is constructed for discrete strings. • Spinor representation of discrete Frenet equations is developed.

  2. Testing string theory at LHC?

    CERN Multimedia

    CERN. Geneva

    2002-01-01

    A theory with such mathematical beauty cannot be wrong: this is one of the main arguments in favour of string theory, which unifies all known physical theories of fundamental interactions in a single coherent description of the universe. But no one has ever observed strings, not even indirectly, nor the space of extra dimensions where they live. However there are good reasons to believe that the 'hidden' dimensions of string theory may be much larger than what we thought in the past and that they may be within experimental reach in the near future - together with the strings themselves. In my talk, I will give an elementary introduction of string theory and describe the main experimental predictions.Organiser(s): Jasper Kirkby / EP DivisionNote: Tea & coffee will be served at 16.00 hrs.

  3. Modification of Cysteine 179 of IκBα Kinase by Nimbolide Leads to Down-regulation of NF-κB-regulated Cell Survival and Proliferative Proteins and Sensitization of Tumor Cells to Chemotherapeutic Agents*

    Science.gov (United States)

    Gupta, Subash C.; Prasad, Sahdeo; Reuter, Simone; Kannappan, Ramaswamy; Yadav, Vivek R.; Ravindran, Jayaraj; Hema, Padmanabhan S.; Chaturvedi, Madan M.; Nair, Mangalam; Aggarwal, Bharat B.

    2010-01-01

    Reverse pharmacology, also called the “bedside to bench” approach, that deals with new uses for a well known molecular entity has been used extensively in cancer drug development to identify novel compounds and delineate their mechanisms of action. Here, we show that nimbolide, a triterpenoid isolated from Azadirachta indica, enhanced the apoptosis induced by inflammatory cytokines and chemotherapeutic agents in tumor cells. This limonoid abrogated the expression of proteins associated with cell survival (Bcl-2, Bcl-xL, IAP-1, and IAP-2), proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF), all regulated by nuclear factor (NF)-κB. Nimbolide inhibited the activation of NF-κB induced by carcinogens and inflammatory stimuli. Constitutively active NF-κB found in most tumor cells was also inhibited. We found that suppression of NF-κB activation by nimbolide was caused by inhibition of IκB kinase (IKK), which led to suppression of IκBα phosphorylation and degradation, nuclear translocation, DNA binding, and gene transcription. Reducing agent reversed the action of the limonoid, suggesting the involvement of a cysteine residue. Replacement of Cys179 of IKK-β with alanine abolished the effect of nimbolide, suggesting that Cys179 plays a critical role in inhibiting the NF-κB activation. Overall, our results indicate that nimbolide can sensitize tumor cells to chemotherapeutic agents through interaction with IKK, leading to inhibition of NF-κB-regulated proteins. PMID:20829362

  4. Modulation of Escherichia coli serine acetyltransferase catalytic activity in the cysteine synthase complex

    Czech Academy of Sciences Publication Activity Database

    Benoni, Roberto; De Bei, O.; Paredi, G.; Hayes, C. S.; Franko, N.; Mozzarelli, A.; Bettati, S.; Campanini, B.

    2017-01-01

    Roč. 591, č. 9 (2017), s. 1212-1224 ISSN 0014-5793 Institutional support: RVO:61388963 Keywords : cysteine synthase * protein-protein interaction * serine acetyltransferase Subject RIV: CE - Biochemistry Impact factor: 3.623, year: 2016

  5. iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins

    Directory of Open Access Journals (Sweden)

    Yan Xu

    2013-10-01

    Full Text Available As one of the most important and universal posttranslational modifications (PTMs of proteins, S-nitrosylation (SNO plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.

  6. Twist Field as Three String Interaction Vertex in Light Cone String Field Theory

    OpenAIRE

    Kishimoto, Isao; Moriyama, Sanefumi; Teraguchi, Shunsuke

    2006-01-01

    It has been suggested that matrix string theory and light-cone string field theory are closely related. In this paper, we investigate the relation between the twist field, which represents string interactions in matrix string theory, and the three-string interaction vertex in light-cone string field theory carefully. We find that the three-string interaction vertex can reproduce some of the most important OPEs satisfied by the twist field.

  7. A string theory which isn't about strings

    Science.gov (United States)

    Lee, Kanghoon; Rey, Soo-Jong; Rosabal, J. A.

    2017-11-01

    Quantization of closed string proceeds with a suitable choice of worldsheet vacuum. A priori, the vacuum may be chosen independently for left-moving and right-moving sectors. We construct ab initio quantized bosonic string theory with left-right asymmetric worldsheet vacuum and explore its consequences and implications. We critically examine the validity of new vacuum and carry out first-quantization using standard operator formalism. Remarkably, the string spectrum consists only of a finite number of degrees of freedom: string gravity (massless spin-two, Kalb-Ramond and dilaton fields) and two massive spin-two Fierz-Pauli fields. The massive spin-two fields have negative norm, opposite mass-squared, and provides a Lee-Wick type extension of string gravity. We compute two physical observables: tree-level scattering amplitudes and one-loop cosmological constant. Scattering amplitude of four dilatons is shown to be a rational function of kinematic invariants, and in D = 26 factorizes into contributions of massless spin-two and a pair of massive spin-two fields. The string one loop partition function is shown to perfectly agree with one loop Feynman diagram of string gravity and two massive spin-two fields. In particular, it does not exhibit modular invariance. We critically compare our construction with recent studies and contrast differences.

  8. Endosomal H2O2 production leads to localized cysteine sulfenic acid formation on proteins during lysophosphatidic acid-mediated cell signaling.

    Science.gov (United States)

    Klomsiri, Chananat; Rogers, LeAnn C; Soito, Laura; McCauley, Anita K; King, S Bruce; Nelson, Kimberly J; Poole, Leslie B; Daniel, Larry W

    2014-06-01

    Lysophosphatidic acid (LPA) is a growth factor for many cells including prostate and ovarian cancer-derived cell lines. LPA stimulates H2O2 production which is required for growth. However, there are significant gaps in our understanding of the spatial and temporal regulation of H2O2-dependent signaling and the way in which signals are transmitted following receptor activation. Herein, we describe the use of two reagents, DCP-Bio1 and DCP-Rho1, to evaluate the localization of active protein oxidation after LPA stimulation by detection of nascent protein sulfenic acids. We found that LPA stimulation causes internalization of LPA receptors into early endosomes that contain NADPH oxidase components and are sites of H2O2 generation. DCP-Rho1 allowed visualization of sulfenic acid formation, indicative of active protein oxidation, which was stimulated by LPA and decreased by an LPA receptor antagonist. Protein oxidation sites colocalized with LPAR1 and the endosomal marker EEA1. Concurrent with the generation of these redox signaling-active endosomes (redoxosomes) is the H2O2- and NADPH oxidase-dependent oxidation of Akt2 and PTP1B detected using DCP-Bio1. These new approaches therefore enable detection of active, H2O2-dependent protein oxidation linked to cell signaling processes. DCP-Rho1 may be a particularly useful protein oxidation imaging agent enabling spatial resolution due to the transient nature of the sulfenic acid intermediate it detects. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Cysteine-containing peptides having antioxidant properties

    Science.gov (United States)

    Bielicki, John K [Castro Valley, CA

    2008-10-21

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  10. Gravity and strings

    CERN Document Server

    Ortín, Tomás

    2015-01-01

    Self-contained and comprehensive, this definitive new edition of Gravity and Strings is a unique resource for graduate students and researchers in theoretical physics. From basic differential geometry through to the construction and study of black-hole and black-brane solutions in quantum gravity - via all the intermediate stages - this book provides a complete overview of the intersection of gravity, supergravity, and superstrings. Now fully revised, this second edition covers an extensive array of topics, including new material on non-linear electric-magnetic duality, the electric-tensor formalism, matter-coupled supergravity, supersymmetric solutions, the geometries of scalar manifolds appearing in 4- and 5-dimensional supergravities, and much more. Covering reviews of important solutions and numerous solution-generating techniques, and accompanied by an exhaustive index and bibliography, this is an exceptional reference work.

  11. Academic Training: String Theory

    CERN Multimedia

    Françoise Benz

    2005-01-01

    2004-2005 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 6, 7, 8, 9 and 10 June from 11.00 to 12.00 hrs - Auditorium, bldg. 500 on 6, 7, 8 & 10 June, TH Auditorium, bldg. 4, 3rd floor on 9 June String Theory by C. Johnson / Univ. of Southern California, USA ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt.

  12. Fermions on the electroweak string

    CERN Document Server

    Moreno, J M; Quirós, Mariano; Moreno, J M; Oaknin, D H; Quiros, M

    1995-01-01

    We construct a simple class of exact solutions of the electroweak theory including the naked Z--string and fermion fields. It consists in the Z--string configuration (\\phi,Z_\\theta), the {\\it time} and z components of the neutral gauge bosons (Z_{0,3},A_{0,3}) and a fermion condensate (lepton or quark) zero mode. The Z--string is not altered (no feed back from the rest of fields on the Z--string) while fermion condensates are zero modes of the Dirac equation in the presence of the Z--string background (no feed back from the {\\it time} and z components of the neutral gauge bosons on the fermion fields). For the case of the n--vortex Z--string the number of zero modes found for charged leptons and quarks is (according to previous results by Jackiw and Rossi) equal to |n|, while for (massless) neutrinos is |n|-1. The presence of fermion fields in its core make the obtained configuration a superconducting string, but their presence (as well as that of Z_{0,3},A_{0,3}) does not enhance the stability of the Z--stri...

  13. Deterministic indexing for packed strings

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Skjoldjensen, Frederik Rye

    2017-01-01

    Given a string S of length n, the classic string indexing problem is to preprocess S into a compact data structure that supports efficient subsequent pattern queries. In the deterministic variant the goal is to solve the string indexing problem without any randomization (at preprocessing time...... or query time). In the packed variant the strings are stored with several character in a single word, giving us the opportunity to read multiple characters simultaneously. Our main result is a new string index in the deterministic and packed setting. Given a packed string S of length n over an alphabet σ......, we show how to preprocess S in O(n) (deterministic) time and space O(n) such that given a packed pattern string of length m we can support queries in (deterministic) time O (m/α + log m + log log σ), where α = w/log σ is the number of characters packed in a word of size w = θ(log n). Our query time...

  14. String bit models for superstring

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, O.; Thorn, C.B.

    1995-12-31

    The authors extend the model of string as a polymer of string bits to the case of superstring. They mainly concentrate on type II-B superstring, with some discussion of the obstacles presented by not II-B superstring, together with possible strategies for surmounting them. As with previous work on bosonic string work within the light-cone gauge. The bit model possesses a good deal less symmetry than the continuous string theory. For one thing, the bit model is formulated as a Galilei invariant theory in (D {minus} 2) + 1 dimensional space-time. This means that Poincare invariance is reduced to the Galilei subgroup in D {minus} 2 space dimensions. Naturally the supersymmetry present in the bit model is likewise dramatically reduced. Continuous string can arise in the bit models with the formation of infinitely long polymers of string bits. Under the right circumstances (at the critical dimension) these polymers can behave as string moving in D dimensional space-time enjoying the full N = 2 Poincare supersymmetric dynamics of type II-B superstring.

  15. Plucked Strings and the Harpsichord

    Science.gov (United States)

    GIORDANO, N.; WINANS, J. P.

    1999-07-01

    The excitation of a harpsichord string when it is set into motion, i.e., plucked, by a plectrum is studied. We find that the amplitude of the resulting string vibration is approximately independent of the velocity with which the key is depressed. This result is in accord with conventional wisdom, but at odds with a recent theoretical model. A more realistic theoretical treatment of the plucking process is then described, and shown to be consistent with our measurements. The experiments reveal several other interesting aspects of the plectrum-string interaction.

  16. Geometry, topology, and string theory

    Energy Technology Data Exchange (ETDEWEB)

    Varadarajan, Uday [Univ. of California, Berkeley, CA (United States)

    2003-01-01

    A variety of scenarios are considered which shed light upon the uses and limitations of classical geometric and topological notions in string theory. The primary focus is on situations in which D-brane or string probes of a given classical space-time see the geometry quite differently than one might naively expect. In particular, situations in which extra dimensions, non-commutative geometries as well as other non-local structures emerge are explored in detail. Further, a preliminary exploration of such issues in Lorentzian space-times with non-trivial causal structures within string theory is initiated.

  17. Test particle trajectories near cosmic strings

    Indian Academy of Sciences (India)

    We present a detailed analysis of the motion of test particle in the gravitational field of cosmic strings in different situations using the Hamilton–Jacobi (H–J) formalism. We have discussed the trajectories near static cosmic string, cosmic string in Brans–Dicke theory and cosmic string in dilaton gravity.

  18. Emergence String and Mass Formulas of Hadrons

    CERN Document Server

    Chang, Yi-Fang

    2011-01-01

    Assume that hadrons are formed from the emergence string. Usual string should possess two moving states: oscillation and rotation, so we propose corresponding potential and the equation of the emergence string, whose energy spectrum is namely the GMO mass formula and its modified accurate mass formula. These are some relations between the string and observable experimental data.

  19. String matching with variable length gaps

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Vildhøj, Hjalte Wedel

    2012-01-01

    We consider string matching with variable length gaps. Given a string T and a pattern P consisting of strings separated by variable length gaps (arbitrary strings of length in a specified range), the problem is to find all ending positions of substrings in T that match P. This problem is a basic...

  20. String Formatting Considered Harmful for Novice Programmers

    Science.gov (United States)

    Hughes, Michael C.; Jadud, Matthew C.; Rodrigo, Ma. Mercedes T.

    2010-01-01

    In Java, "System.out.printf" and "String.format" consume a specialised kind of string commonly known as a format string. In our study of first-year students at the Ateneo de Manila University, we discovered that format strings present a substantial challenge for novice programmers. Focusing on their first laboratory we found…

  1. On the Classical String Solutions and String/Field Theory Duality

    OpenAIRE

    Aleksandrova, D.; Bozhilov, P.

    2003-01-01

    We classify almost all classical string configurations, considered in the framework of the semi-classical limit of the string/gauge theory duality. Then, we describe a procedure for obtaining the conserved quantities and the exact classical string solutions in general string theory backgrounds, when the string embedding coordinates depend non-linearly on the worldsheet time parameter.

  2. Barley (Hordeum vulgare L.) cysteine proteases: heterologous expression, purification and characterization

    DEFF Research Database (Denmark)

    Rosenkilde, Anne Lind; Dionisio, Giuseppe; Holm, Preben Bach

    2011-01-01

    During germination of barley seeds, mobilization of protein is essential and cysteine proteases accounts for more than 90 % of the total proteolytic activity in the degradation of barley seed storage proteins. Cysteine proteases exist as pro-enzyme and is activated through reduction of the active...... site cysteines and by removal of the pro-domain. The complement of cysteine proteases is comprehensive and for detailed studies of the individual components of this complement, a fast and efficient eukaryotic expression platform is highly desirable. A cDNA clone of the barley key cysteine endoprotease...... B2 (HvEPB2) was ligated into the Pichia pastoris expression vector pPICZ Aα and electrotransformed into Pichia pastoris strain KM71H. Heterologous protein production was induced with 2% MeOH and maximum yield were obtained after 4 days where the supernatant was harvested. Purification of HvEPB2 from...

  3. Can l-Cysteine and Vitamin D Rescue Vitamin D and Vitamin D Binding Protein Levels in Blood Plasma of African American Type 2 Diabetic Patients?

    OpenAIRE

    Jain, Sushil K.; Kahlon, Gunjan; Bass, Pat; Levine, Steven N.; Warden, Cassandra

    2015-01-01

    Abstract Aims: Vitamin D (VD) deficiency has become a worldwide epidemic, particularly affecting African Americans (AA). VD deficiency has been implicated in the excessive rate of complications associated with diabetes in AA. Blood levels of VD binding protein (VDBP) and glutathione (GSH) are lower in AA compared with those in Caucasians. This study tested the hypothesis that lower GSH levels are linked to VDBP and VD deficiency in AA-type 2 diabetic (AA-T2D) patients. Blood was analyzed from...

  4. Fermentative Production of Cysteine by Pantoea ananatis.

    Science.gov (United States)

    Takumi, Kazuhiro; Ziyatdinov, Mikhail Kharisovich; Samsonov, Viktor; Nonaka, Gen

    2017-03-01

    Cysteine is a commercially important amino acid; however, it lacks an efficient fermentative production method. Due to its cytotoxicity, intracellular cysteine levels are stringently controlled via several regulatory modes. Managing its toxic effects as well as understanding and deregulating the complexities of regulation are crucial for establishing the fermentative production of cysteine. The regulatory modes include feedback inhibition of key metabolic enzymes, degradation, efflux pumps, and the transcriptional regulation of biosynthetic genes by a master cysteine regulator, CysB. These processes have been extensively studied using Escherichia coli for overproducing cysteine by fermentation. In this study, we genetically engineered Pantoea ananatis, an emerging host for the fermentative production of bio-based materials, to identify key factors required for cysteine production. According to this and our previous studies, we identified a major cysteine desulfhydrase gene, ccdA (formerly PAJ_0331), involved in cysteine degradation, and the cysteine efflux pump genes cefA and cefB (formerly PAJ_3026 and PAJ_p0018, respectively), which may be responsible for downregulating the intracellular cysteine level. Our findings revealed that ccdA deletion and cefA and cefB overexpression are crucial factors for establishing fermentative cysteine production in P. ananatis and for obtaining a higher cysteine yield when combined with genes in the cysteine biosynthetic pathway. To our knowledge, this is the first demonstration of cysteine production in P. ananatis, which has fundamental implications for establishing overproduction in this microbe.IMPORTANCE The efficient production of cysteine is a major challenge in the amino acid fermentation industry. In this study, we identified cysteine efflux pumps and degradation pathways as essential elements and genetically engineered Pantoea ananatis, an emerging host for the fermentative production of bio-based materials, to establish

  5. Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles

    DEFF Research Database (Denmark)

    Serafimova, Iana M; Pufall, Miles A; Krishnan, Shyam

    2012-01-01

    of these electrophiles into a noncovalent kinase-recognition scaffold produced slowly dissociating, covalent inhibitors of the p90 ribosomal protein S6 kinase RSK2. A cocrystal structure revealed specific noncovalent interactions that stabilize the complex by positioning the electrophilic carbon near the targeted...... cysteine. Disruption of these interactions by protein unfolding or proteolysis promoted instantaneous cleavage of the covalent bond. Our results establish a chemistry-based framework for engineering sustained covalent inhibition without accumulating permanently modified proteins and peptides....

  6. M-theory and N=2 Strings

    OpenAIRE

    Martinec, Emil

    1997-01-01

    N=2 heterotic strings may provide a window into the physics of M-theory radically different than that found via the other supersymmetric string theories. In addition to their supersymmetric structure, these strings carry a four-dimensional self-dual structure, and appear to be completely integrable systems with a stringy density of states. These lectures give an overview of N=2 heterotic strings, as well as a brief discussion of possible applications of both ordinary and heterotic N=2 strings...

  7. Charting the landscape of supercritical string theory.

    Science.gov (United States)

    Hellerman, Simeon; Swanson, Ian

    2007-10-26

    Special solutions of string theory in supercritical dimensions can interpolate in time between theories with different numbers of spacetime dimensions and different amounts of world sheet supersymmetry. These solutions connect supercritical string theories to the more familiar string duality web in ten dimensions and provide a precise link between supersymmetric and purely bosonic string theories. Dimension quenching and c duality appear to be natural concepts in string theory, giving rise to large networks of interconnected theories.

  8. Cosmic string catalysis of skyrmion decay

    Science.gov (United States)

    Gregory, Ruth; Davis, Anne-Christine; Brandenberger, Robert

    1988-01-01

    The Callan-Witten picture is developed for monopole catalyzed skyrmion decay in order to analyze the corresponding cosmic string scenario. It is discovered that cosmic strings (both ordinary and superconducting) can catalyze proton decay, but that this catalysis only occurs on the scale of the core of the string. In order to do this we have to develop a vortex model for the superconducting string. An argument is also given for the difference in the enhancement factors for monopoles and strings.

  9. Hotspots of age-related protein degradation: the importance of neighboring residues for the formation of non-disulfide crosslinks derived from cysteine.

    Science.gov (United States)

    Friedrich, Michael G; Wang, Zhen; Oakley, Aaron J; Schey, Kevin L; Truscott, Roger J W

    2017-07-11

    Over time, the long-lived proteins that are present throughout the human body deteriorate. Typically, they become racemized, truncated, and covalently cross-linked. One reaction responsible for age-related protein cross-linking in the lens was elucidated recently and shown to involve spontaneous formation of dehydroalanine (DHA) intermediates from phosphoserine. Cys residues are another potential source of DHA, and evidence for this was found in many lens crystallins. In the human lens, some sites were more prone to forming non-disulfide covalent cross-links than others. Foremost among them was Cys5 in βA4 crystallin. The reason for this enhanced reactivity was investigated using peptides. Oxidation of Cys to cystine was a prerequisite for DHA formation, and DHA production was accelerated markedly by the presence of a Lys, one residue separated from Cys5. Modeling and direct investigation of the N-terminal sequence of βA4 crystallin, as well as a variety of homologous peptides, showed that the epsilon amino group of Lys can promote DHA production by nucleophilic attack on the alpha proton of cystine. Once a DHA residue was generated, it could form intermolecular cross-links with Lys and Cys. In the lens, the most abundant cross-link involved Cys5 of βA4 crystallin attached via a thioether bond to glutathione. These findings illustrate the potential of Cys and disulfide bonds to act as precursors for irreversible covalent cross-links and the role of nearby amino acids in creating 'hotpsots' for the spontaneous processes responsible for protein degradation in aged tissues. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  10. String and Sticky Tape Experiments.

    Science.gov (United States)

    Edge, R. D., Ed.

    1979-01-01

    Explains how to demonstrate the fundamentals of one dimensional kinematics such as Newton's third law of motion, and collision between bodies, using simple materials of marbles, strings, sticky tape, drinking straws, and rubber bands. (GA)

  11. Strings 2017 Amplitudes Review Talk

    OpenAIRE

    Carrasco, John Joseph

    2017-01-01

    Amplitudes review talk I gave at Strings 2017 in Tel Aviv. Broad audience, introducing color-kinematics/double copy, geometric picture, playful constructions (Z-theory), and applications to classical gravity solutions.2 files. PDF and Apple Keynote source.

  12. String theory and cosmological singularities

    Indian Academy of Sciences (India)

    time' can have a beginning or end. Well-known examples are singularities inside black holes and initial or final singularities in expanding or contracting universes. In recent times, string theory is providing new perspectives of such singularities ...

  13. String no-scale supergravity

    CERN Document Server

    López, J L

    1996-01-01

    We explore the postulates of string no-scale supergravity in the context of free-fermionic string models. The requirements of vanishing vacuum energy, flat directions of the scalar potential, and stable no-scale mechanism impose strong restrictions on possible string no-scale models, which must possess only two or three moduli, and a constrained massless spectrum. All soft-supersymmetry-breaking parameters involving untwisted fields are given explicitly and those involving twisted fields are conjectured. This class of models contain no free parameters, \\ie, in principle all supersymmetric particle masses and interactions are completely determined. A computerized search for free-fermionic models with the desired properties yields a candidate SU(5)\\times U(1) model, and evidence that all such models contain extra (\\r{10},\\rb{10}) matter representations that allow gauge coupling unification at the string scale. Our candidate model possesses a novel assignment of supersymmetry breaking scalar masses which gives v...

  14. Confining Strings with Topological Term

    CERN Document Server

    Diamantini, M Cristina; Trugenberger, Carlo Andrea

    1997-01-01

    We consider several aspects of `confining strings', recently proposed to describe the confining phase of gauge field theories. We perform the exact duality transformation that leads to the confining string action and show that it reduces to the Polyakov action in the semiclassical approximation. In 4D we introduce a `$\\theta$-term' and compute the low-energy effective action for the confining string in a derivative expansion. We find that the coefficient of the extrinsic curvature (stiffness) is negative, confirming previous proposals. In the absence of a $\\theta$-term, the effective string action is only a cut-off theory for finite values of the coupling e, whereas for generic values of $\\theta$, the action can be renormalized and to leading order we obtain the Nambu-Goto action plus a topological `spin' term that could stabilize the system.

  15. Spin chains and string theory.

    Science.gov (United States)

    Kruczenski, Martin

    2004-10-15

    Recently, an important test of the anti de Sitter/conformal field theory correspondence has been done using rotating strings with two angular momenta. We show that such a test can be described more generally as the agreement between two actions: one a low energy description of a spin chain appearing in the field theory side, and the other a limit of the string action in AdS5xS5. This gives a map between the mean value of the spin in the boundary theory and the position of the string in the bulk, and shows how a string action can emerge from a gauge theory in the large-N limit.

  16. String moduli inflation. An overview

    Energy Technology Data Exchange (ETDEWEB)

    Cicoli, Michele [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Quevedo, Fernando [Cambridge Univ. (United Kingdom). DAMTP/CMS; Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)

    2011-06-15

    We present an overview of inflationary models derived from string theory focusing mostly on closed string moduli as inflatons. After a detailed discussion of the {eta}-problem and different approaches to address it, we describe possible ways to obtain a de Sitter vacuum with all closed string moduli stabilised. We then look for inflationary directions and present some of the most promising scenarios where the inflatons are either the real or the imaginary part of Kaehler moduli. We pay particular attention on extracting potential observable implications, showing how most of the scenarios predict negligible gravitational waves and could therefore be ruled out by the Planck satellite. We conclude by briefly mentioning some open challenges in string cosmology beyond deriving just inflation. (orig.)

  17. Pattern recognition and string matching

    CERN Document Server

    Cheng, Xiuzhen

    2002-01-01

    The research and development of pattern recognition have proven to be of importance in science, technology, and human activity. Many useful concepts and tools from different disciplines have been employed in pattern recognition. Among them is string matching, which receives much theoretical and practical attention. String matching is also an important topic in combinatorial optimization. This book is devoted to recent advances in pattern recognition and string matching. It consists of twenty eight chapters written by different authors, addressing a broad range of topics such as those from classifica­ tion, matching, mining, feature selection, and applications. Each chapter is self-contained, and presents either novel methodological approaches or applications of existing theories and techniques. The aim, intent, and motivation for publishing this book is to pro­ vide a reference tool for the increasing number of readers who depend upon pattern recognition or string matching in some way. This includes student...

  18. String resonances at hadron colliders

    Science.gov (United States)

    Anchordoqui, Luis A.; Antoniadis, Ignatios; Dai, De-Chang; Feng, Wan-Zhe; Goldberg, Haim; Huang, Xing; Lüst, Dieter; Stojkovic, Dejan; Taylor, Tomasz R.

    2014-09-01

    We consider extensions of the standard model based on open strings ending on D-branes, with gauge bosons due to strings attached to stacks of D-branes and chiral matter due to strings stretching between intersecting D-branes. Assuming that the fundamental string mass scale Ms is in the TeV range and that the theory is weakly coupled, we discuss possible signals of string physics at the upcoming HL-LHC run (integrated luminosity =3000 fb-1) with a center-of-mass energy of √s =14 TeV and at potential future pp colliders, HE-LHC and VLHC, operating at √s =33 and 100 TeV, respectively (with the same integrated luminosity). In such D-brane constructions, the dominant contributions to full-fledged string amplitudes for all the common QCD parton subprocesses leading to dijets and γ +jet are completely independent of the details of compactification and can be evaluated in a parameter-free manner. We make use of these amplitudes evaluated near the first (n=1) and second (n=2) resonant poles to determine the discovery potential for Regge excitations of the quark, the gluon, and the color singlet living on the QCD stack. We show that for string scales as large as 7.1 TeV (6.1 TeV) lowest massive Regge excitations are open to discovery at the ≥5σ in dijet (γ +jet) HL-LHC data. We also show that for n=1 the dijet discovery potential at HE-LHC and VLHC exceedingly improves: up to 15 TeV and 41 TeV, respectively. To compute the signal-to-noise ratio for n=2 resonances, we first carry out a complete calculation of all relevant decay widths of the second massive level string states (including decays into massless particles and a massive n=1 and a massless particle), where we rely on factorization and conformal field theory techniques. Helicity wave functions of arbitrary higher spin massive bosons are also constructed. We demonstrate that for string scales Ms≲10.5 TeV (Ms≲28 TeV) detection of n =2 Regge recurrences at HE-LHC (VLHC) would become the smoking gun for D

  19. Supersymmetry and dual string solitons

    CERN Document Server

    Duff, Michael J; Khuri, R R; Rahmfeld, J; Ferrara, Sergio; Khuri, Ramzi R; Rahmfeld, Joachim

    1995-01-01

    We present new classes of string-like soliton solutions in (N=1; D=10) (N=2; D=6) and (N=4; D=4) heterotic string theory. Connections are made between the solution-generating subgroup of the T-duality group of the compactification and the number of spacetime supersymmetries broken. Analogous solutions are also noted in (N=1,2; D=4) compactifications, where a different form of supersymmetry breaking arises.

  20. Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

    Directory of Open Access Journals (Sweden)

    You Mie Lee

    Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

  1. Toward A Nonperturbative Topological String

    CERN Document Server

    Neitzke, A

    2005-01-01

    We discuss three examples of nonperturbative phenomena in the topological string. First, we consider the computation of amplitudes in N = 4 super Yang-Mills theory using the B model topological string as proposed by Witten. We give an argument suggesting that the computations using connected or disconnected D-instantons of the B model are in fact equivalent. Second, we formulate a conjecture that the squared modulus of the open topological string partition function can be defined nonperturbatively as the partition function of a mixed ensemble of BPS states in d = 4. This conjecture is an extension of a recent proposal for the closed topological string. In a particular example involving a non-compact Calabi- Yau threefold, we show that the conjecture passes some basic checks, and that the square of the open topological string amplitude has a natural interpretation in terms of 2-dimensional Yang-Mills theory, again generalizing known results for the closed string case. Third, we discuss an action for an abel...

  2. Virginia Tech String Project reaches out to elementary students with affordable string instruction

    OpenAIRE

    Virginia Tech News

    2007-01-01

    The Department of Music at Virginia Tech announces Virginia Tech String Project--a initiative to provide affordable quality string instruction to public and private school students while training future string music educators.

  3. In string theory, the fundamental string has a typical length scale.

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. In string theory, the fundamental string has a typical length scale. A string vibrating in its ground state appears to a low-energy observer like a point particle. Notes:

  4. On Field Theory of Open Strings, Tachyon Condensation and Closed Strings

    OpenAIRE

    Shatashvili, Samson L.

    2001-01-01

    I review the physical properties of different vacua in the background independent open string field theory. Talk presented at Strings 2001, Mumbai, India, http://theory.theory.tifr.res.in/strings/Proceedings/#sha-s.

  5. Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy

    DEFF Research Database (Denmark)

    Horne, A W; Duncan, W C; King, A E

    2009-01-01

    gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human...... chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P ... to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression...

  6. Cysteine-rich secretory protein-3 (CRISP3 is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene.

    Directory of Open Access Journals (Sweden)

    Franclim R Ribeiro

    Full Text Available A large percentage of prostate cancers harbor TMPRSS2-ERG gene fusions, leading to aberrant overexpression of the transcription factor ERG. The target genes deregulated by this rearrangement, however, remain mostly unknown. To address this subject we performed genome-wide mRNA expression analysis on 6 non-malignant prostate samples and 24 prostate carcinomas with (n = 16 and without (n = 8 TMPRSS2-ERG fusion as determined by FISH. The top-most differentially expressed genes and their associations with ERG over-expression were technically validated by quantitative real-time PCR and biologically validated in an independent series of 200 prostate carcinomas. Several genes encoding metabolic enzymes or extracellular/transmembrane proteins involved in cell adhesion, matrix remodeling and signal transduction pathways were found to be co-expressed with ERG. Within those significantly over-expressed in fusion-positive carcinomas, CRISP3 showed more than a 50-fold increase when compared to fusion-negative carcinomas, whose expression levels were in turn similar to that of non-malignant samples. In the independent validation series, ERG and CRISP3 mRNA levels were strongly correlated (r(s = 0.65, p<0.001 and both were associated with pT3 disease staging. Furthermore, immunohistochemistry results showed CRISP3 protein overexpression in 63% of the carcinomas and chromatin immunoprecipitation with an anti-ERG antibody showed that CRISP3 is a direct target of the transcription factor ERG. We conclude that ERG rearrangement is associated with significant expression alterations in genes involved in critical cellular pathways that define a subset of locally advanced PCa. In particular, we show that CRISP3 is a direct target of ERG that is strongly overexpressed in PCa with the TMPRSS2-ERG fusion gene.

  7. A selective Chemosensor for Cysteine

    Indian Academy of Sciences (India)

    of important cellular functions including detoxification and metabolism.1 Variation in the physiological level of thiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) is linked to a number of diseases associated with leucocyteloss, psoriasis, liver damage, slow growth, hair depigmentation, edema, lethargy, ...

  8. Secreted protein acidic and rich in cysteine (SPARC) induces lipotoxicity in neuroblastoma by regulating transport of albumin complexed with fatty acids.

    Science.gov (United States)

    Chlenski, Alexandre; Dobratic, Marija; Salwen, Helen R; Applebaum, Mark; Guerrero, Lisa J; Miller, Ryan; DeWane, Gillian; Solomaha, Elena; Marks, Jeremy D; Cohn, Susan L

    2016-11-22

    SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation. Based on the described chaperone function of SPARC, we hypothesized that SPARC binds albumin complexed with fatty acids and transports them to tumors. We show that SPARC binds albumin with Kd=18.9±2.3 uM, and enhances endothelial cell internalization and transendothelial transport of albumin in vitro. We also demonstrate that lipids induce toxicity in neuroblastoma cells and show that lipotoxicity is increased when cells are cultured in hypoxic conditions. Studies investigating the therapeutic potential of SPARC are warranted.

  9. Biotin Switch Assays for Quantitation of Reversible Cysteine Oxidation.

    Science.gov (United States)

    Li, R; Kast, J

    2017-01-01

    Thiol groups in protein cysteine residues can be subjected to different oxidative modifications by reactive oxygen/nitrogen species. Reversible cysteine oxidation, including S-nitrosylation, S-sulfenylation, S-glutathionylation, and disulfide formation, modulate multiple biological functions, such as enzyme catalysis, antioxidant, and other signaling pathways. However, the biological relevance of reversible cysteine oxidation is typically underestimated, in part due to the low abundance and high reactivity of some of these modifications, and the lack of methods to enrich and quantify them. To facilitate future research efforts, this chapter describes detailed procedures to target the different modifications using mass spectrometry-based biotin switch assays. By switching the modification of interest to a biotin moiety, these assays leverage the high affinity between biotin and avidin to enrich the modification. The use of stable isotope labeling and a range of selective reducing agents facilitate the quantitation of individual as well as total reversible cysteine oxidation. The biotin switch assay has been widely applied to the quantitative analysis of S-nitrosylation in different disease models and is now also emerging as a valuable research tool for other oxidative cysteine modifications, highlighting its relevance as a versatile, robust strategy for carrying out in-depth studies in redox proteomics. © 2017 Elsevier Inc. All rights reserved.

  10. Diversity, abundance and characterization of ruminal cysteine phytases suggest their important role in phytate degradation.

    Science.gov (United States)

    Huang, Huoqing; Zhang, Rui; Fu, Dawei; Luo, Jianjie; Li, Zhongyuan; Luo, Huiying; Shi, Pengjun; Yang, Peilong; Diao, Qiyu; Yao, Bin

    2011-03-01

    A novel class of cysteine phytase showing ability to degrade phytate has recently been isolated from rumen bacteria. To expand our knowledge of this enzyme class, a total of 101 distinct cysteine phytase gene fragments were identified from the ruminal genomic DNA of Bore goats and Holstein cows, and most of them shared low identities (cysteine phytase genes of goat rumens were cloned and their protein products were characterized. Four findings were revealed based on our results. (i) Compared with soil and water environment, where β-propeller phytase is the most important phytate-degrading enzyme, cysteine phytase is the major phytate-degrading enzyme in the anaerobic ruminal environment. (ii) Cysteine phytase fragments in the rumen contents of goat and cow have the same diversity profile, although most of the sequences and their abundance differ in the two species. (iii) Each species has their respective high-abundance genes, which may play major roles for phytate degradation. (iv) Compared with previously reported cysteine phytases that have pH optimum at 4.5, the pH optima of the two most abundant secreted goat cysteine phytases are 6.5 and 6.0, which are within the pH range found in the rumens. This study provides valuable information about the diversity, abundance and enzymatic properties of the ruminal cysteine phytases and emphasizes the important role(s) of these cysteine phytases probably in the terrestrial cycle of phosphorus. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  11. String Theory for Pedestrians (3/3)

    CERN Multimedia

    CERN. Geneva

    2009-01-01

    This is a non-technical rapid course on string theory. Lecture 1 is an introduction to the basics of the subject: classical and quantum strings, D(irichlet) branes and string-string dualities. In lecture 2 I will discuss string unification of the fundamental forces, covering both its successes and failures. Finally in lecture 3 I will review string models of black hole microstates, the holographic gauge/gravity duality and, if time permits, potential applications to the physics of the strong interactions.

  12. String Theory for Pedestrians (2/3)

    CERN Multimedia

    CERN. Geneva

    2009-01-01

    This is a non-technical rapid course on string theory. Lecture 1 is an introduction to the basics of the subject: classical and quantum strings, D(irichlet) branes and string-string dualities. In lecture 2 I will discuss string unification of the fundamental forces, covering both its successes and failures. Finally in lecture 3 I will review string models of black hole microstates, the holographic gauge/gravity duality and, if time permits, potential applications to the physics of the strong interactions.

  13. String Theory for Pedestrians (1/3)

    CERN Multimedia

    CERN. Geneva

    2009-01-01

    This is a non-technical rapid course on string theory. Lecture 1 is an introduction to the basics of the subject: classical and quantum strings, D(irichlet) branes and string-string dualities. In lecture 2 I will discuss string unification of the fundamental forces, covering both its successes and failures. Finally in lecture 3 I will review string models of black hole microstates, the holographic gauge/gravity duality and, if time permits, potential applications to the physics of the strong interactions.

  14. Ultrasensitive electrochemical immunosensing of tumor suppressor protein p53 in unprocessed human plasma and cell lysates using a novel nanocomposite based on poly-cysteine/graphene quantum dots/gold nanoparticle.

    Science.gov (United States)

    Hasanzadeh, Mohammad; Baghban, Hossein Navay; Shadjou, Nasrin; Mokhtarzadeh, Ahad

    2018-02-01

    An ultrasensitive electrochemical immunosensor for quantitation of tumor suppressor protein p53 based on ternary signal amplification strategy was fabricated. In this work, p53-antibody was immobilized onto a green and biocompatible nanocomposite containing poly l-cysteine (P-Cys) as conductive matrix and graphene quantum dots (GQDs)/gold nanoparticles (GNPs) as dual amplification elements. Therefore, a novel multilayer film based on P-Cys, GQDs, and GNPs was exploited to develop a highly sensitive immunosensor for detection of p53. Fully electrochemical methodology was used to prepare a new transducer on a gold surface which provided a high surface area to immobilize a high amount of the anti-p53. Under optimized condition the calibration curve for p53 concentration was linear up to 0.000197-0.016 pM (by SWV technique) and 0.195-50 pM (by DPV technique) with lower limit of quantification of 0.065 fM. Also, linear range and lower limit of quantification of p53 in unprocessed human plasma were 0.000592-1.296 pM and 0.065 fM, respectively. The method was applied to the assay of p53 in human plasma sample and normal and malignant cell line lysates such as normal cell Line from mouse C3H (L929), colon cancer cell-HCT, prostate cancer cell line PC-3, and human breast adenocarcinoma cell line-MCF7. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Cosmoparticle Physics and String Theory

    Science.gov (United States)

    Sjörs, Stefan

    This thesis deals with phenomenological and theoretical aspects of cosmoparticle physics and string theory. There are many open questions in these topics. In connection with cosmology we would like to understand the detailed properties of dark matter, dark energy, generation of primordial perturbations, etc., and in connection with particle physics we would like to understand the detailed properties of models that stabilize the electroweak scale, for instance supersymmetry. At the same time, we also need to understand these issues in a coherent theoretical framework. Such a framework is offered by string theory. In this thesis, I analyze the interplay between Higgs and dark matter physics in an effective field theory extension of the minimally supersymmetric standard model. I study a theory of modified gravity, where the graviton has acquired a mass, and show the explicit implementation of the Vainshtein mechanism, which allows one to put severe constraints on the graviton mass. I address the question of Planck scale corrections to inflation in string theory, and show how such corrections can be tamed. I study perturbations of warped throat regions of IIB string theory compactifications and classify allowed boundary conditions. Using this analysis, I determine the potential felt by an anti-D3-brane in such compactifications, using the explicit harmonic data on the conifold. I also address questions of perturbative quantum corrections in string theory and calculate one-loop corrections to the moduli space metric of Calabi-Yau orientifolds.

  16. String Resonances at Hadron Colliders

    CERN Document Server

    Anchordoqui, Luis A; Dai, De-Chang; Feng, Wan-Zhe; Goldberg, Haim; Huang, Xing; Lust, Dieter; Stojkovic, Dejan; Taylor, Tomasz R

    2014-01-01

    [Abridged] We consider extensions of the standard model based on open strings ending on D-branes. Assuming that the fundamental string mass scale M_s is in the TeV range and that the theory is weakly coupled, we discuss possible signals of string physics at the upcoming HL-LHC run (3000 fb^{-1}) with \\sqrt{s} = 14 TeV, and at potential future pp colliders, HE-LHC and VLHC, operating at \\sqrt{s} = 33 and 100 TeV, respectively. In such D-brane constructions, the dominant contributions to full-fledged string amplitudes for all the common QCD parton subprocesses leading to dijets and \\gamma + jet are completely independent of the details of compactification, and can be evaluated in a parameter-free manner. We make use of these amplitudes evaluated near the first (n=1) and second (n=2) resonant poles to determine the discovery potential for Regge excitations of the quark, the gluon, and the color singlet living on the QCD stack. We show that for string scales as large as 7.1 TeV (6.1 TeV), lowest massive Regge exc...

  17. STRING v10

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Franceschini, Andrea; Wyder, Stefan

    2015-01-01

    into families at various levels of phylogenetic resolution. Further improvements in version 10.0 include a completely redesigned prediction pipeline for inferring protein-protein associations from co-expression data, an API interface for the R computing environment and improved statistical analysis...

  18. Towards Inflation in String Theory

    Energy Technology Data Exchange (ETDEWEB)

    Kachru, Shamit

    2003-08-25

    We investigate the embedding of brane inflation into stable compactifications of string theory. At first sight a warped compactification geometry seems to produce a naturally flat inflation potential, evading one well-known difficulty of brane-antibrane scenarios. Careful consideration of the closed string moduli reveals a further obstacle: superpotential stabilization of the compactification volume typically modifies the inflation potential and renders it too steep for inflation. We discuss the non-generic conditions under which this problem does not arise. We conclude that brane inflation models can only work if restrictive assumptions about the method of volume stabilization, the warping of the internal space, and the source of inflationary energy are satisfied. We argue that this may not be a real problem, given the large range of available fluxes and background geometries in string theory.

  19. Precise Analysis of String Expressions

    DEFF Research Database (Denmark)

    Christensen, Aske Simon; Møller, Anders; Schwartzbach, Michael Ignatieff

    2003-01-01

    We perform static analysis of Java programs to answer a simple question: which values may occur as results of string expressions? The answers are summarized for each expression by a regular language that is guaranteed to contain all possible values. We present several applications of this analysis......, including statically checking the syntax of dynamically generated expressions, such as SQL queries. Our analysis constructs flow graphs from class files and generates a context-free grammar with a nonterminal for each string expression. The language of this grammar is then widened into a regular language...... through a variant of an algorithm previously used for speech recognition. The collection of resulting regular languages is compactly represented as a special kind of multi-level automaton from which individual answers may be extracted. If a program error is detected, examples of invalid strings...

  20. Multiloop string vertices from the path integral

    Energy Technology Data Exchange (ETDEWEB)

    Bochicchio, M.; Lerda, A.

    1989-02-02

    We derive the multiloop vertices for the bosonic string using path integral methods and establish a precise equivalence between the functional approach to string perturbation theory and the operator formalism on Riemann surfaces recently developed by various authors.

  1. Physical effects of massless cosmic strings

    Science.gov (United States)

    Fursaev, D. V.

    2017-11-01

    We study massless cosmic strings, which are one-dimensional objects moving with the speed of light. Perturbations of velocities of test bodies and anisotropy of the cosmic microwave background generated by massless cosmic strings are analyzed. These phenomena are analogous to the string wake effect and the Kaiser-Stebbins effect for standard (massive) cosmic strings. There are two regimes depending on the energy E of a massless string per unit length. At low energies, E G /c4≪1 , massless and massive strings act similarly. At high energies, E G /c4˜1 , massless string effects are quite different. Our work provides a method to describe different physical phenomena on spacetimes of massless strings which take into account the presence of a parabolic holonomy.

  2. Bianchi-type string cosmology

    CERN Document Server

    Batakis, N A

    1995-01-01

    Bianchi-type string cosmology involves generalizations of the FRW backgrounds with three transitive spacelike Killing symmetries, but without any a priori assumption of isotropy in the 3D sections of homogeneity. With emphasis on those cases with diagonal metrics and vanishing cosmological constant which which have not been previously examined in the literature, the present findings allow an overview and the classification of all Bianchi-type backgrounds. These string solutions (at least to lowest order in alpha prime) offer prototypes for the study of spatial anisotropy and its impact on the dynamics of the early universe.

  3. Cosmic string in gravity's rainbow

    Science.gov (United States)

    Momeni, Davood; Upadhyay, Sudhaker; Myrzakulov, Yerlan; Myrzakulov, Ratbay

    2017-09-01

    In this paper, we study the various cylindrical solutions (cosmic strings) in gravity's rainbow scenario. In particular, we calculate the gravitational field equations corresponding to energy-dependent background. Further, we discuss the possible Kasner, quasi-Kasner and non-Kasner exact solutions of the field equations. In this framework, we find that quasi-Kasner solutions cannot be realized in gravity's rainbow. Assuming only time-dependent metric functions, we also analyse the time-dependent vacuum cosmic strings in gravity's rainbow, which are completely different than the other GR solutions.

  4. Strings, paths, and standard tableaux

    CERN Document Server

    Dasmahapatra, S

    1996-01-01

    For the vacuum sectors of regime-III ABF models, we observe that two sets of combinatorial objects: the strings which parametrize the row-to-row transfer matrix eigenvectors, and the paths which parametrize the corner transfer matrix eigenvectors, can both be expressed in terms of the same set of standard tableaux. Furthermore, the momenta of the strings, the energies of the paths, and the charges of the tableaux are such that there is a weight-preserving bijection between the two sets of eigenvectors, wherein the tableaux play an interpolating role. This bijection is so natural, that we conjecture that it exists in general.

  5. The mechanism of cysteine detection in biological media by means of vanadium oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bezerra, A. G. [Universidade Tecnologica Federal do Parana, Departamento Academico de Fisica (Brazil); Barison, A. [Universidade Federal do Parana, Departamento de Quimica (Brazil); Oliveira, V. S. [Universidade Federal do Parana, Departamento de Fisica (Brazil); Foti, L.; Krieger, M. A. [Fundacao Oswaldo Cruz, Instituto de Biologia Molecular do Parana (Brazil); Dhalia, R.; Viana, I. F. T. [Fundacao Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhaes (Brazil); Schreiner, W. H., E-mail: wido@fisica.ufpr.br [Universidade Federal do Parana, Departamento de Fisica (Brazil)

    2012-09-15

    We report on the interaction of vanadate nanoparticles, produced using the laser ablation in liquids synthesis, with cysteine in biological molecules. Cysteine is a very important amino acid present in most proteins, but also because cysteine and the tripeptide glutathione are the main antioxidant molecules in our body system. Detailed UV-Vis absorption spectra and dynamic light scattering measurements were done to investigate the detection of cysteine in large biological molecules. The intervalence band of the optical absorption spectra shows capability for quantitative cysteine sensing in the {mu}M range in biological macromolecules. Tests included cytoplasmic repetitive antigen and flagellar repetitive antigen proteins of the Trypanosoma cruzi protozoa, as well as the capsid p24 proteins from Human Immunodeficiency Virus type 1 and type 2. Detailed NMR measurements for hydrogen, carbon, and vanadium nuclei show that cysteine in contact with the vanadate looses hydrogen of the sulphydryl side chain, while the vanadate is reduced. The subsequent detachment of two deprotonated molecules to form cystine and the slow return to the vanadate complete the oxidation-reduction cycle. Therefore, the vanadate acts as a charge exchanging catalyst on cysteine to form cystine. The NMR results also indicate that the nanoparticles are not formed by the common orthorhombic V{sub 2}O{sub 5} form.

  6. Understanding fields using strings: A review

    Indian Academy of Sciences (India)

    In addition to being a prime candidate for a fundamental unified theory of all interactions in nature, string theory provides a natural setting to understand gauge field theories. This is linked to the concept of '-branes': extended, solitonic excitations of string theory which can be studied using techniques of string theory and ...

  7. String loop divergences and effective lagrangians

    Science.gov (United States)

    Fischler, Willy; Klebanov, Igor; Susskind, Leonard

    1988-08-01

    We isolate logarithmic divergences from bosonic string amplitudes on a disc. These divergences are compared with ``tadpole'' divergences in the effective field theory, with a covariant cosmological term implied by the counting of string coupling constants. We find an inconsistency between the two. This might be a problem in eliminating divergences from the bosonic string. Work supported by NSF PHY 812280.

  8. Two-component Duality and Strings

    OpenAIRE

    Freund, Peter G. O.

    2007-01-01

    A phenomenologically successful two-component hadronic duality picture led to Veneziano's amplitude, the fundamental first step to string theory. This picture is briefly recalled and its two components are identified as the open strings (mesons and baryons) and closed strings (Pomeron).

  9. Symmetries and Interactions in Matrix String Theory

    NARCIS (Netherlands)

    Hacquebord, F.H.

    1999-01-01

    This PhD-thesis reviews matrix string theory and recent developments therein. The emphasis is put on symmetries, interactions and scattering processes in the matrix model. We start with an introduction to matrix string theory and a review of the orbifold model that flows out of matrix string theory

  10. String loop corrected hypermultiplet moduli spaces

    NARCIS (Netherlands)

    Robles-Llana, D.; Saueressig, Frank; Vandoren, S.

    2006-01-01

    Using constraints from supersymmetry and string perturbation theory, we determine the string loop corrections to the hypermultiplet moduli space of type II strings compactified on a generic Calabi-Yau threefold. The corresponding quaternion-Kähler manifolds are completely encoded in terms of a

  11. Are Stopped Strings Preferred in Sad Music?

    Directory of Open Access Journals (Sweden)

    David Huron

    2017-01-01

    Full Text Available String instruments may be played either with open strings (where the string vibrates between the bridge and a hard wooden nut or with stopped strings (where the string vibrates between the bridge and a performer's finger pressed against the fingerboard. Compared with open strings, stopped strings permit the use of vibrato and exhibit a darker timbre. Inspired by research on the timbre of sad speech, we test whether there is a tendency to use stopped strings in nominally sad music. Specifically, we compare the proportion of potentially open-to-stopped strings in a sample of slow, minor-mode movements with matched major-mode movements. By way of illustration, a preliminary analysis of Samuel Barber's famous Adagio from his Opus 11 string quartet shows that the selected key (B-flat minor provides the optimum key for minimizing open string tones. However, examination of a broader controlled sample of quartet movements by Haydn, Mozart and Beethoven failed to exhibit the conjectured relationship. Instead, major-mode movements were found to avoid possible open strings more than slow minor-mode movements.

  12. Some properties of Cosmic String Junctions

    Science.gov (United States)

    Karouby, Johanna

    2011-07-01

    Cosmic strings are linear concentrations of energy of macroscopic size. Since cosmic superstrings can form junctions, observing them would give some support to string theory. In the following, we study the lensing cosmic string junctions create, the shift in photons' wavelength passing through (leading to the Kaiser-Stebbins effect), and the gravitational radiation they emit.

  13. Introduction to the theory of strings

    Energy Technology Data Exchange (ETDEWEB)

    Peskin, M.E.

    1985-10-01

    These lectures present, from an introductory perspective, some basic aspects of the quantum theory of strings. They treat (1) the kinematics, spectrum, and scattering amplitude of the bosonic string, (2) the spectrum and supersymmetry of Green-Schwarz superstring, and (3) the identification of the underlying gauge invariances of the string theory. 43 refs.

  14. String theory in the bathtub

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    The presence of the surrounding medium makes their dynamics dramatically different from those of ordinary string-like objects propagating in empty space, leading to quite peculiar phenomena, observed in experiments and simulations. I will argue that the effective theory provides an optimal theoretical framework to understand such phenomena, and to make precise quantitative predictions about them.

  15. The Science of String Instruments

    CERN Document Server

    Rossing, Thomas D

    2010-01-01

    Many performing musicians, as well as instrument builders, are coming to realize the importance of understanding the science of musical instruments. This book explains how string instruments produce sound. It presents basic ideas in simple language, and it also translates some more sophisticated ideas in non-technical language. It should be of interest to performers, researchers, and instrument makers alike.

  16. String physics and black holes

    Energy Technology Data Exchange (ETDEWEB)

    Susskind, L. [Stanford Univ., CA (United States). Dept. of Physics; Uglum, J. [Stanford Univ., CA (United States). Dept. of Physics

    1996-02-01

    In these lectures we review the quantum physics of large Schwarzschild black holes. Hawking`s information paradox, the theory of the stretched horizon and the principle of black hole complementarity are covered. We then discuss how the ideas of black hole complementarity may be realized in string theory. Finally, arguments are given that the world may be a hologram. (orig.).

  17. Exotic Non-relativistic String

    CERN Document Server

    Casalbuoni, Roberto; Longhi, Giorgio

    2007-01-01

    We construct a classical non-relativistic string model in 3+1 dimensions. The model contains a spurion tensor field that is responsible for the non-commutative structure of the model. Under double dimensional reduction the model reduces to the exotic non-relativistic particle in 2+1 dimensions.

  18. Creative Activities for String Students.

    Science.gov (United States)

    Stabley, Nola Campbell

    2001-01-01

    Discusses how to teach improvisation, creativity, and movement to beginning music classroom students. Includes background information on teaching each concept and lesson plans to be used with beginning string students. Provides rhythm patterns, exercises, and an assignment used in the lessons. (CMK)

  19. Bianchi type I string cosmologies

    Indian Academy of Sciences (India)

    if a proper initial condition, viz., inflation is imposed on the very early universe. Various types of inflationary cosmologies are being considered and the string cosmology is one. It is generally believed that the very early universe underwent phase transitions, which gave rise to topologically stable structures; of particular ...

  20. Monads, strings, and M theory

    NARCIS (Netherlands)

    Hofman, C.; Park, J.-S.

    1997-01-01

    The recent developmen ts in string theory suggest that the space-time coordinates should be generalized to non-comm uting matrices. P ostulating this suggestion as the fun- damen tal geometrical principle, w e form ulate a candidate for covariant second quantized RNS superstrings as a topological

  1. String theory and cosmological singularities

    Indian Academy of Sciences (India)

    Abstract. In general relativity space-like or null singularities are common: they imply that 'time' can have a beginning or end. Well-known examples are singularities inside black holes and initial or final singularities in expanding or contracting universes. In recent times, string theory is providing new perspectives of such ...

  2. Localized gravity in string theory.

    Science.gov (United States)

    Karch, A; Randall, L

    2001-08-06

    We propose a string realization of the AdS4 brane in AdS5 that is known to localize gravity. Our theory is M D5 branes in the near horizon geometry of N D3 branes, where M and N are appropriately tuned.

  3. Defect branes as Alice strings

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Takashi [Theoretical Biology Laboratory, RIKEN,Wako 351-0198 (Japan); Sakatani, Yuho [Department of Physics and Astronomy,Seoul National University, Seoul 151-747 (Korea, Republic of)

    2015-03-25

    There exist various defect-brane backgrounds in supergravity theories which arise as the low energy limit of string theories. These backgrounds typically have non-trivial monodromies, and if we move a charged probe around the center of a defect, its charge will be changed by the action of the monodromy. During the process, the charge conservation law seems to be violated. In this paper, to resolve this puzzle, we examine a dynamics of the charge changing process and show that the missing charge of the probe is transferred to the background. We then explicitly construct the resultant background after the charge transfer process by utilizing dualities. This background has the same monodromy as the original defect brane, but has an additional charge which does not have any localized source. In the literature, such a charge without localized source is known to appear in the presence of Alice strings. We argue that defect branes can in fact be regarded as a realization of Alice strings in string theory and examine the charge transfer process from that perspective.

  4. Topological strings and quantum curves

    NARCIS (Netherlands)

    Hollands, L.

    2009-01-01

    This thesis presents several new insights on the interface between mathematics and theoretical physics, with a central role for Riemann surfaces. First of all, the duality between Vafa-Witten theory and WZW models is embedded in string theory. Secondly, this model is generalized to a web of

  5. Topological Strings and Integrable Hierarchies

    CERN Document Server

    Aganagic, M; Klemm, A D; Marino, M; Vafa, C; Aganagic, Mina; Dijkgraaf, Robbert; Klemm, Albrecht; Marino, Marcos; Vafa, Cumrun

    2006-01-01

    We consider the topological B-model on local Calabi-Yau geometries. We show how one can solve for the amplitudes by using W-algebra symmetries which encodes the symmetries of holomorphic diffeomorphisms of the Calabi-Yau. In the highly effective fermionic/brane formulation this leads to a free fermion description of the amplitudes. Furthermore we argue that topological strings on Calabi-Yau geometries provide a unifying picture connecting non-critical (super)strings, integrable hierarchies, and various matrix models. In particular we show how the ordinary matrix model, the double scaling limit of matrix models, and Kontsevich-like matrix model are all related and arise from studying branes in specific local Calabi-Yau three-folds. We also show how A-model topological string on P^1 and local toric threefolds (and in particular the topological vertex) can be realized and solved as B-model topological string amplitudes on a Calabi-Yau manifold.

  6. New Approaches to String Instruction.

    Science.gov (United States)

    Teaching Music, 1994

    1994-01-01

    Maintains that use of the Suzuki, Orff, and Dalcroze methods have assisted string teachers in helping music students achieve mastery from the beginning of instruction. Describes how these methods are used by five music teachers. Includes addresses of organizations that provide information about these music teaching methods. CFR)

  7. Enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from S-sulfocysteine increases L-cysteine production in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Nakatani Takeshi

    2012-05-01

    Full Text Available Abstract Background Escherichia coli has two L-cysteine biosynthetic pathways; one is synthesized from O-acetyl L-serine (OAS and sulfate by L-cysteine synthase (CysK, and another is produced via S-sulfocysteine (SSC from OAS and thiosulfate by SSC synthase (CysM. SSC is converted into L-cysteine and sulfite by an uncharacterized reaction. As thioredoxins (Trx1 and Trx2 and glutaredoxins (Grx1, Grx2, Grx3, Grx4, and NrdH are known as reductases of peptidyl disulfides, overexpression of such reductases might be a good way for improving L-cysteine production to accelerate the reduction of SSC in E. coli. Results Because the redox enzymes can reduce the disulfide that forms on proteins, we first tested whether these enzymes catalyze the reduction of SSC to L-cysteine. All His-tagged recombinant enzymes, except for Grx4, efficiently convert SSC into L-cysteine in vitro. Overexpression of Grx1 and NrdH enhanced a 15-40% increase in the E. coliL-cysteine production. On the other hand, disruption of the cysM gene cancelled the effect caused by the overexpression of Grx1 and NrdH, suggesting that its improvement was due to the efficient reduction of SSC under the fermentative conditions. Moreover, L-cysteine production in knockout mutants of the sulfite reductase genes (ΔcysI and ΔcysJ and the L-cysteine synthase gene (ΔcysK each decreased to about 50% of that in the wild-type strain. Interestingly, there was no significant difference in L-cysteine production between wild-type strain and gene deletion mutant of the upstream pathway of sulfite (ΔcysC or ΔcysH. These results indicate that sulfite generated from the SSC reduction is available as the sulfur source to produce additional L-cysteine molecule. It was finally found that in the E. coliL-cysteine producer that co-overexpress glutaredoxin (NrdH, sulfite reductase (CysI, and L-cysteine synthase (CysK, there was the highest amount of L-cysteine produced per cell. Conclusions In this work, we

  8. Maximal unbordered factors of random strings

    DEFF Research Database (Denmark)

    Cording, Patrick Hagge; Knudsen, Mathias Bæk Tejs

    2016-01-01

    A border of a string is a non-empty prefix of the string that is also a suffix of the string, and a string is unbordered if it has no border. Loptev, Kucherov, and Starikovskaya [CPM 2015] conjectured the following: If we pick a string of length n from a fixed alphabet uniformly at random......, then the expected length of the maximal unbordered factor is n − O(1). We prove that this conjecture is true by proving that the expected value is in fact n − Θ(σ−1), where σ is the size of the alphabet. We discuss some of the consequences of this theorem....

  9. Introduction to the relativistic string theory

    CERN Document Server

    Barbashov, B M

    1990-01-01

    This book presents a systematic and detailed account of the classical and quantum theory of the relativistic string and some of its modifications. Main attention is paid to the first-quantized string theory with possible applications to the string models of hadrons as well as to the superstring approach to unifications of all the fundamental interactions in the elementary particle physics and to the "cosmic" strings. Some new aspects are provided such as the consideration of the string in an external electromagnetic field and in the space-time of constant curvature (the de Sitter universe), th

  10. Growth and characterization of string ribbon

    Energy Technology Data Exchange (ETDEWEB)

    Hanoka, J.I. [Evergreen Solar, Inc., Waltham, MA (United States); Behnin, B.; Michel, J. [Massachusetts Inst. of Technology, Cambridge, MA (United States); Symko, M.; Sopori, B.L. [National Renewable Energy Lab., Golden, CO (United States)

    1995-08-01

    Evergreen Solar, a new photovoltaics company, makes solar cells and modules based on String Ribbon. String Ribbon is a silicon sheet growth method wherein two high temperature strings are pulled through a shallow melt of silicon and a crystalline silicon sheet then grows between the two strings. The strings serve to stabilize the edges of the growing silicon sheet. The growth process is primarily meniscus controlled and, compared to other silicon ribbon growth methods such as d-web and EFG, relatively insensitive to temperature fluctuations as great as {+-}10{degrees}C. Growth speed is about 2 cm/minute.

  11. Micro string resonators as temperature sensors

    DEFF Research Database (Denmark)

    Larsen, T.; Schmid, S.; Boisen, A.

    2013-01-01

    The resonance frequency of strings is highly sensitive to temperature. In this work we have investigated the applicability of micro string resonators as temperature sensors. The resonance frequency of strings is a function of the tensile stress which is coupled to temperature by the thermal...... to the low thermal mass of the strings. A temperature resolution of 2.5×10-4 °C has been achieved with silicon nitride strings. The theoretical limit for the temperature resolution of 8×10-8 °C has not been reached yet and requires further improvement of the sensor....

  12. Cysteine degradation gene yhaM, encoding cysteine desulfidase, serves as a genetic engineering target to improve cysteine production in Escherichia coli

    OpenAIRE

    Nonaka, Gen; Takumi, Kazuhiro

    2017-01-01

    Cysteine is an important amino acid for various industries; however, there is no efficient microbial fermentation-based production method available. Owing to its cytotoxicity, bacterial intracellular levels of cysteine are stringently controlled via several modes of regulation, including cysteine degradation by cysteine desulfhydrases and cysteine desulfidases. In Escherichia coli, several metabolic enzymes are known to exhibit cysteine degradative activities, however, their specificity and p...

  13. Hollow micro string based calorimeter device

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to a micron-scale calorimeter and a calorimetry method utilizing the micron-scale calorimeter. In accordance with the invention, there is provided a micron-scale calorimeter comprising a micro-channel string, being restrained at at least two longitudinally distanced...... positions so as to form a free released double clamped string in-between said two longitudinally distanced positions said micro-channel string comprising a microfluidic channel having a closed cross section and extending in the longitudinal direction of the hollow string, acoustical means adapted...... to oscillate the string at different frequencies by emitting sound waves towards the string, optical means adapted to detect oscillating frequencies of the string, and controlling means controlling the strength and frequency of the sound wave emitted by the acoustical means and receiving a signal from...

  14. Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.

    Science.gov (United States)

    Pakavathkumar, Prateep; Sharma, Gyanesh; Kaushal, Vikas; Foveau, Bénédicte; LeBlanc, Andrea C

    2015-09-24

    Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via the oxidation of their active site cysteine. Methylene blue, and derivatives, azure A and azure B competitively inhibited recombinant Caspase-6 (Casp6), and inhibited Casp6 activity in transfected human colon carcinoma cells and in serum-deprived primary human neuron cultures. Methylene blue also inhibited recombinant Casp1 and Casp3. Furthermore, methylene blue inhibited Casp3 activity in an acute mouse model of liver toxicity. Mass spectrometry confirmed methylene blue and azure B oxidation of the catalytic Cys163 cysteine of Casp6. Together, these results show a novel inhibitory mechanism of caspases via sulfenation of the active site cysteine. These results indicate that methylene blue or its derivatives could (1) have an additional effect against Alzheimer Disease by inhibiting brain caspase activity, (2) be used as a drug to prevent caspase activation in other conditions, and (3) predispose chronically treated individuals to cancer via the inhibition of caspases.

  15. Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains

    DEFF Research Database (Denmark)

    Bikker, Floris J; Ligtenberg, Antoon J M; End, Caroline

    2004-01-01

    The scavenger receptor cysteine-rich (SRCR) proteins form an archaic group of metazoan proteins characterized by the presence of SRCR domains. These proteins are classified in group A and B based on the number of conserved cysteine residues in their SRCR domains, i.e. six for group A and eight fo...

  16. Fermentative Production of Cysteine by Pantoea ananatis

    OpenAIRE

    Takumi, Kazuhiro; Ziyatdinov, Mikhail Kharisovich; Samsonov, Viktor; Nonaka, Gen

    2017-01-01

    Cysteine is a commercially important amino acid; however, it lacks an efficient fermentative production method. Due to its cytotoxicity, intracellular cysteine levels are stringently controlled via several regulatory modes. Managing its toxic effects as well as understanding and deregulating the complexities of regulation are crucial for establishing the fermentative production of cysteine. The regulatory modes include feedback inhibition of key metabolic enzymes, degradation, efflux pumps, a...

  17. Cathepsin B-like cysteine proteases confer intestinal cysteine protease activity in Haemonchus contortus.

    Science.gov (United States)

    Shompole, S; Jasmer, D P

    2001-01-26

    Cathepsin B-like cysteine protease genes (cbls) constitute large multigene families in parasitic and nonparasitic nematodes. Although expressed in the intestine of some nematodes, the biological and biochemical functions of the CBL proteins remain unresolved. Di- and tetra-oligopeptides were used as fluorogenic substrates and irreversible/competitive inhibitors to establish CBL functions in the intestine of the parasitic nematode Haemonchus contortus. Cysteine protease activity was detected against diverse substrates including the cathepsin B/L substrate FR, the caspase 1 substrate YVAD, the cathepsin B substrate RR, but not the CED-3 (caspase 3) substrate DEVD. The pH at which maximum activity was detected varied according to substrate and ranged from pH 5.0 to 7.0. Individual CBLs were affinity isolated using FA and YVAD substrates. pH influenced CBL affinity isolation in a substrate-specific manner that paralleled pH effects on individual substrates. N-terminal sequencing identified two isolated CBLs as H. contortus GCP-7 (33 kDa) and AC-4 (37 kDa). N termini of each began at a position consistent with proregion cleavage and protease activation. Isolation of the GCP-7 band by each peptide was preferentially inhibited when competed with a diazomethane-conjugated inhibitor, Z-FA-CHN(2), demonstrating one functional difference among CBLs and among inhibitors. Substrate-based histological analysis placed CBLs on the intestinal microvilli. Data indicate that CBLs are responsible for cysteine protease activity described from H. contortus intestine. Results also support a role of CBLs in nutrient digestion.

  18. NCBI nr-aa BLAST: CBRC-DSIM-02-0039 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DSIM-02-0039 ref|NP_001083797.1| cysteine-string protein [Xenopus laevis] sp|O...42196|CSP_XENLA Cysteine string protein (CSP) (Xcsp) gb|AAB69692.1| cysteine-string protein [Xenopus laevis] NP_001083797.1 0.046 46% ...

  19. Ballonet String Model of Molecules

    Directory of Open Access Journals (Sweden)

    Gavril NIAC

    2008-06-01

    Full Text Available Strings of ballonets, modelling rows of orbitals, are assembled to molecule models by crossing them properly. The ballonets at the ends of the strings of 2, 3, 4 or 5 spheres represent bonding orbitals of hydrogen with other elements like C, N or O (the proton being inside the sphere, as well as nonbonding orbitals. The ballonets between them are modelling bonding orbitals among elements other than hydrogen - except the double bond in diborane, the atomic cores laying at the junction of two or more spheres.Advantages of elastic sphere models range from self-adjusting bond angles to resistance when closing cycles like cyclopropane or modeling double bonds.Examples comprise alkanes, including platonic hydrocarbons, ethene, acetylene, and some inorganic molecules.

  20. Electric drill-string telemetry

    CERN Document Server

    Carcione, J M

    2003-01-01

    We design a numerical algorithm for simulation of low-frequency electric-signal transmission through a drill string. This is represented by a transmission line with varying geometrical and electromagnetic properties versus depth, depending on the characteristics of the drill-string/formation system. These properties are implicitly modeled by the series impedance and the shunt admittance of the transmission line. The differential equations are parabolic, since at low frequencies the wave field is diffusive. We use an explicit scheme for the solution of parabolic problems, based on a Chebyshev expansion of the evolution operator and the Fourier pseudospectral method to compute the spatial derivatives. The results are verified by comparison to analytical solutions obtained for the initial-value problem with a voltage source.

  1. Dilaton production in string cosmology

    CERN Document Server

    Gasperini, M

    1994-01-01

    We consider the coupled evolution of density, (scalar) metric and dilaton perturbations in the transition from a "stringy" phase of growing curvature and gravitational coupling to the standard radiation-dominated cosmology. We show that dilaton production, with a spectrum tilted towards large frequencies, emerges as a general property of this scenario. We discuss the frame-independence of the dilaton spectrum and of the inflationary properties of the metric background by using, as model of source, a pressureless gas of weakly interacting strings, which is shown to provide an approximate but consistent solution to the full system of background equations and string equations of motion. We combine various cosmological bounds on a growing dilaton spectrum with the bound on the dilaton mass obtained from tests of the equivalence principle, and we find allowed windows compatible with a universe presently dominated by a relic background of dilatonic dark matter.

  2. Introduction to bosonic string theory

    Energy Technology Data Exchange (ETDEWEB)

    Nunez, Carmen [Instituto de Astronomia y Fisica del Espacio, Buenos Aires (Argentina)], e-mail: carmen@iafe.uba.ar

    2009-07-01

    This is an introductory set of five lectures on bosonic string theory. The first one deals with the classical theory of bosonic strings. The second and third lectures cover quantization. Three basic quantization methods are sketched: the old covariant formalism, the light-cone gauge quantization, where the spectrum is derived and the Polyakov path integral formalism and in particular the partition function at one loop. Finally, the last lecture covers interactions, low energy effective action, the general idea of compactification and in particular toroidal compactification. The notes are based on books by Green, Schwarz and Witten, Polchinski, Lust and Theissen and Kaku and review papers by D'Hocker and Phong and O. Alvarez. (author)

  3. Wrapping rules (in) string theory

    Science.gov (United States)

    Bergshoeff, Eric A.; Riccioni, Fabio

    2018-01-01

    In this paper we show that the number of all 1/2-BPS branes in string theory compactified on a torus can be derived by universal wrapping rules whose formulation we present. These rules even apply to branes in less than ten dimensions whose ten-dimensional origin is an exotic brane. In that case the wrapping rules contain an additional combinatorial factor that is related to the highest dimension in which the ten-dimensional exotic brane, after compactification, can be realized as a standard brane. We show that the wrapping rules also apply to cases with less supersymmetry. As a specific example, we discuss the compactification of IIA/IIB string theory on ( T 4/ ℤ 2) × T n .

  4. A Closed String Tachyon Vacuum ?

    OpenAIRE

    Yang, Haitang; Zwiebach, Barton

    2005-01-01

    In bosonic closed string field theory the "tachyon potential" is a potential for the tachyon, the dilaton, and an infinite set of massive fields. Earlier computations of the potential did not include the dilaton and the critical point formed by the quadratic and cubic interactions was destroyed by the quartic tachyon term. We include the dilaton contributions to the potential and find that a critical point survives and appears to become more shallow. We are led to consider the existence of a ...

  5. Cosmological Consequences of String Axions

    Energy Technology Data Exchange (ETDEWEB)

    Kain, Ben

    2005-12-15

    Axion fluctuations generated during inflation lead to isocurvature and non-Gaussian temperature fluctuations in the cosmic microwave background radiation. Following a previous analysis for the model independent string axion we consider the consequences of a measurement of these fluctuations for two additional string axions. We do so independent of any cosmological assumptions except for the axions being massless during inflation. The first axion has been shown to solve the strong CP problem for most compactifications of the heterotic string while the second axion, which does not solve the strong CP problem, obeys a mass formula which is independent of the axion scale. We find that if gravitational waves interpreted as arising from inflation are observed by the PLANCK polarimetry experiment with a Hubble constant during inflation of H{sub inf} {approx}> 10{sup 13} GeV the existence of the first axion is ruled out and the second axion cannot obey the scale independent mass formula. In an appendix we quantitatively justify the often held assumption that temperature corrections to the zero temperature QCD axion mass may be ignored for temperatures T {approx}< {Lambda}{sub QCD}.

  6. IgG antibodies to endothelial protein C receptor-binding Cysteine-rich interdomain region domains of Plasmodium falciparum erythrocyte membrane protein 1 are acquired early in life in individuals exposed to malaria

    DEFF Research Database (Denmark)

    Turner, Louise; Lavstsen, Thomas; Mmbando, Bruno P

    2015-01-01

    Severe malaria syndromes are precipitated by Plasmodium falciparum parasites binding to endothelial receptors on the vascular lining. This binding is mediated by members of the highly variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. We have previously identified a subset of Pf...

  7. On the null origin of the ambitwistor string

    Energy Technology Data Exchange (ETDEWEB)

    Casali, Eduardo [Mathematical Institute, University of Oxford,Woodstock Road, Oxford, OX2 6GG (United Kingdom); Tourkine, Piotr [Department of Applied Mathematics and Theoretical Physics,Wilberforce Road, Cambridge, CB3 0WA (United Kingdom)

    2016-11-07

    In this paper we present the null string origin of the ambitwistor string. Classically, the null string is the tensionless limit of string theory, and so too is the ambitwistor string. Both have as constraint algebra the Galilean Conformal Algebra in two dimensions. But something interesting happens in the quantum theory since there is an ambiguity in quantizing the null string. We show that, given a particular choice of quantization scheme and a particular gauge, the null string coincides with the ambitwistor string both classically and quantum mechanically. We also show that the same holds for the spinning versions of the null string and ambitwistor string. With these results we clarify the relationship between the ambitwistor string, the null string, the usual string and the Hohm-Siegel-Zwiebach theory.

  8. On a possible connection of non-critical strings to certain aspects of quantum brain function

    CERN Document Server

    Mavromatos, Nikolaos E

    1997-01-01

    We review certain aspects of brain function which could be associated with non-critical (Liouville) string theory. In particular we simulate the physics of brain microtubules (MT) by using a (completely integrable) non-critical string, we discuss the collapse of the wave function as a result of quantum gravity effects due to abrupt conformational changes of the MT protein dimers, and we propose a new mechanism for memory coding.

  9. Cysteine sensing by plasmons of silver nanocubes

    Energy Technology Data Exchange (ETDEWEB)

    Elfassy, Eitan, E-mail: eitan.elfassi@gmail.com; Mastai, Yitzhak, E-mail: Yitzhak.Mastai@biu.ac.il; Salomon, Adi, E-mail: adi.salomon@biu.ac.il

    2016-09-15

    Noble metal nanoparticles are considered to be valuable nanostructures in the field of sensors due to their spectral response sensitivity to small changes in the surrounding refractive index which enables them to detect a small amount of molecules. In this research, we use silver nanocubes of about 50 nm length to detect low concentrations of cysteine, a semi-essential amino acid. Following cysteine adsorption onto the nanocubes, a redshift in the plasmonic modes was observed, enabling the detection of cysteine down to 10 µM and high sensitivity of about 125 nm/RIU (refractive index units). Furthermore, we found that multilayer adsorption of cysteine leads to the stabilization of the silver nanocubes. The cysteine growth onto the nanocubes was also characterized by high-resolution transmission electron microscopy (HR-TEM). - Highlights: • Silver nanocubes (50 nm length) are used to detect low concentrations of cysteine. • A redshift in the plasmonic modes was observed following cysteine adsorption onto the nanocubes. • The cysteine growth onto the nanocubes is also characterized by TEM.

  10. Keratin degradation by dermatophytes relies on cysteine dioxygenase and a sulfite efflux pump.

    Science.gov (United States)

    Grumbt, Maria; Monod, Michel; Yamada, Tsuyoshi; Hertweck, Christian; Kunert, Jiri; Staib, Peter

    2013-06-01

    Millions of people suffer from superficial infections caused by dermatophytes. Intriguingly, these filamentous fungi exclusively infect keratin-rich host structures such as hair, nails, and skin. Keratin is a hard, compact protein, and its utilization by dermatophytes for growth has long been discussed as a major virulence attribute. Here, we provide strong support for the hypothesis that keratin degradation is facilitated by the secretion of the reducing agent sulfite, which can cleave keratin-stabilizing cystine bonds. We discovered that sulfite is produced by dermatophytes from environmental cysteine, which at elevated concentrations is toxic for microbes and humans. We found that sulfite formation from cysteine relies on the key enzyme cysteine dioxygenase Cdo1. Sulfite secretion is supported by the sulfite efflux pump Ssu1. Targeted mutagenesis proved that dermatophyte mutants in either Cdo1 or Ssu1 were highly growth-sensitive to cysteine, and mutants in Ssu1 were specifically sensitive to sulfite. Most notably, dermatophyte mutants in Cdo1 and Ssu1 were specifically growth-defective on hair and nails. As keratin is rich in cysteine, our identified mechanism of cysteine conversion and sulfite efflux supports both cysteine and sulfite tolerance per se and progression of keratin degradation. These in vitro findings have implications for dermatophyte infection pathogenesis.

  11. Disrupted Hydrogen-Bond Network and Impaired ATPase Activity in an Hsc70 Cysteine Mutant.

    Science.gov (United States)

    O'Donnell, John P; Marsh, Heather M; Sondermann, Holger; Sevier, Carolyn S

    2018-02-20

    The ATPase domain of members of the 70 kDa heat shock protein (Hsp70) family shows a high degree of sequence, structural, and functional homology across species. A broadly conserved residue within the Hsp70 ATPase domain that captured our attention is an unpaired cysteine, positioned proximal to the site of nucleotide binding. Prior studies of several Hsp70 family members show this cysteine is not required for Hsp70 ATPase activity, yet select amino acid replacements of the cysteine can dramatically alter ATP hydrolysis. Moreover, post-translational modification of the cysteine has been reported to limit ATP hydrolysis for several Hsp70s. To better understand the underlying mechanism for how perturbation of this noncatalytic residue modulates Hsp70 function, we determined the structure for a cysteine-to-tryptophan mutation in the constitutively expressed, mammalian Hsp70 family member Hsc70. Our work reveals that the steric hindrance produced by a cysteine-to-tryptophan mutation disrupts the hydrogen-bond network within the active site, resulting in a loss of proper catalytic magnesium coordination. We propose that a similarly altered active site is likely observed upon post-translational oxidation. We speculate that the subtle changes we detect in the hydrogen-bonding network may relate to the previously reported observation that cysteine oxidation can influence Hsp70 interdomain communication.

  12. Large-spin expansions of GKP strings

    Science.gov (United States)

    Floratos, Emmanuel; Georgiou, George; Linardopoulos, Georgios

    2014-03-01

    We demonstrate that the large-spin expansion of the energy of Gubser-Klebanov-Polyakov (GKP) strings that rotate in ℝ × S2 and AdS3 can be expressed in terms of Lambert's W-function. We compute the leading, subleading and next-to-subleading series of exponential corrections to the infinite-volume dispersion relation of GKP strings that rotate in ℝ × S2. These strings are dual to the long = 4 SYM operators +… and provide their scaling dimensions at strong coupling. We also show that the strings obey a short-long (strings) duality. For the folded GKP strings that spin inside AdS3 and are dual to twist-2 operators, we confirm the known formulas for the leading and next-to-leading coefficients of their anomalous dimensions and derive the corresponding expressions for the next-to-next-to-leading coefficients.

  13. D-branes from Liouville strings

    CERN Document Server

    Ellis, Jonathan Richard; Nanopoulos, Dimitri V

    1997-01-01

    We develop quantization aspects of our Liouville approach to non-critical strings, proposing a path-integral formulation of a second quantization of string theory, that incorporates naturally the couplings of string sources to background fields. Such couplings are characteristic of macroscopic string solutions and/or D-brane theories. Resummation over world-sheet genera in the presence of stringy (\\sigma-model) soliton backgrounds, and recoil effects associated with logarithmic operators on the world sheet, play a crucial r\\^ole in inducing such sources as well-defined renormalization-group counterterms. Using our Liouville renormalization group approach, we derive the appropriate second-order equation of motion for the D brane. We discuss within this approach the appearance of open strings, whose ends carry non-trivial Chan-Paton-like quantum numbers related to the W_\\infty charges of two-dimensional string black holes.

  14. Cysteine degradation gene yhaM, encoding cysteine desulfidase, serves as a genetic engineering target to improve cysteine production in Escherichia coli.

    Science.gov (United States)

    Nonaka, Gen; Takumi, Kazuhiro

    2017-12-01

    Cysteine is an important amino acid for various industries; however, there is no efficient microbial fermentation-based production method available. Owing to its cytotoxicity, bacterial intracellular levels of cysteine are stringently controlled via several modes of regulation, including cysteine degradation by cysteine desulfhydrases and cysteine desulfidases. In Escherichia coli, several metabolic enzymes are known to exhibit cysteine degradative activities, however, their specificity and physiological significance for cysteine detoxification via degradation are unclear. Relaxing the strict regulation of cysteine is crucial for its overproduction; therefore, identifying and modulating the major degradative activity could facilitate the genetic engineering of a cysteine-producing strain. In the present study, we used genetic screening to identify genes that confer cysteine resistance in E. coli and we identified yhaM, which encodes cysteine desulfidase and decomposes cysteine into hydrogen sulfide, pyruvate, and ammonium. Phenotypic characterization of a yhaM mutant via growth under toxic concentrations of cysteine followed by transcriptional analysis of its response to cysteine showed that yhaM is cysteine-inducible, and its physiological role is associated with resisting the deleterious effects of cysteine in E. coli. In addition, we confirmed the effects of this gene on the fermentative production of cysteine using E. coli-based cysteine-producing strains. We propose that yhaM encodes the major cysteine-degrading enzyme and it has the most significant role in cysteine detoxification among the numerous enzymes reported in E. coli, thereby providing a core target for genetic engineering to improve cysteine production in this bacterium.

  15. Quantum fluctuations of the superconducting cosmic string

    Science.gov (United States)

    Zhang, Shoucheng

    1987-01-01

    Quantum fluctuations of the proposed superconducting string with Bose charge carriers are studied in terms of the vortices on the string world sheet. In the thermodynamical limit, it is found that they appear in the form of free vortices rather than as bound pairs. This fluctuation mode violates the topological conservation law on which superconductivity is based. However, this limit may not be reached. The critical size of the superconducting string is estimated as a function of the coupling constants involved.

  16. Quantum corrections to the string Bethe ansatz

    CERN Document Server

    Hernández, R; Hernandez, Rafael; Lopez, Esperanza

    2006-01-01

    One-loop corrections to the energy of semiclassical rotating strings contain both analytic and non-analytic terms in the 't Hooft coupling. Analytic contributions agree with the prediction from the string Bethe ansatz based on the classical S-matrix, but in order to include non-analytic contributions quantum corrections are required. We find a general expression for the first quantum correction to the string Bethe ansatz.

  17. Parameterized String Matching Algorithms with Application to ...

    African Journals Online (AJOL)

    In the parameterized string matching problem, a given pattern P is said to match with a sub-string t of the text T, if there exist a bijection from the symbols of P to the symbols of t. Salmela and Tarhio solve the parameterized string matching problem in sub-linear time by applying the concept of q-gram in the Horspool algorithm ...

  18. p-adic string theories provide lattice Discretization to the ordinary string worldsheet.

    Science.gov (United States)

    Ghoshal, Debashis

    2006-10-13

    A class of models called p-adic strings is useful in understanding the tachyonic instability of string theory. These are found to be empirically related to the ordinary strings in the p-->1 limit. We propose that these models provide discretization for the string worldsheet and argue that the limit is naturally thought of as a continuum limit in the sense of the renormalization group.

  19. Brane World Models Need Low String Scale

    CERN Document Server

    Antoniadis, Ignatios; Calmet, Xavier

    2011-01-01

    Models with large extra dimensions offer the possibility of the Planck scale being of order the electroweak scale, thus alleviating the gauge hierarchy problem. We show that these models suffer from a breakdown of unitarity at around three quarters of the low effective Planck scale. An obvious candidate to fix the unitarity problem is string theory. We therefore argue that it is necessary for the string scale to appear below the effective Planck scale and that the first signature of such models would be string resonances. We further translate experimental bounds on the string scale into bounds on the effective Planck scale.

  20. The transverse structure of the QCD string

    CERN Document Server

    Meyer, Harvey B

    2010-01-01

    The characterization of the transverse structure of the QCD string is discussed. We formulate a conjecture as to how the stress-energy tensor of the underlying gauge theory couples to the string degrees of freedom. A consequence of the conjecture is that the energy density and the longitudinal-stress operators measure the distribution of the transverse position of the string, to leading order in the string fluctuations, whereas the transverse-stress operator does not. We interpret recent numerical measurements of the transverse size of the confining string and show that the difference of the energy and longitudinal-stress operators is the appropriate probe to use when comparing with the next-to-leading order string prediction. Secondly we derive the constraints imposed by open-closed string duality on the transverse structure of the string. We show that a total of three independent `gravitational' form factors characterize the transverse profile of the closed string, and obtain the interpretation of recent ef...

  1. Effects of randomized supplementation of methionine or alanine on cysteine and glutathione production during the early phase of treatment of children with edematous malnutrition

    Science.gov (United States)

    We have shown that a low glutathione concentration and synthesis rate in erythrocytes are associated with a shortage of protein-derived cysteine in children with edematous severe acute malnutrition (SAM). We tested the hypothesis that methionine supplementation may increase protein-derived cysteine ...

  2. Mass spectrometric analysis of L-cysteine metabolism: physiological role and fate of L-cysteine in the enteric protozoan parasite Entamoeba histolytica.

    Science.gov (United States)

    Jeelani, Ghulam; Sato, Dan; Soga, Tomoyoshi; Watanabe, Haruo; Nozaki, Tomoyoshi

    2014-11-04

    L-cysteine is essential for virtually all living organisms, from bacteria to higher eukaryotes. Besides having a role in the synthesis of virtually all proteins and of taurine, cysteamine, glutathione, and other redox-regulating proteins, L-cysteine has important functions under anaerobic/microaerophilic conditions. In anaerobic or microaerophilic protozoan parasites, such as Entamoeba histolytica, L-cysteine has been implicated in growth, attachment, survival, and protection from oxidative stress. However, a specific role of this amino acid or related metabolic intermediates is not well understood. In this study, using stable-isotope-labeled L-cysteine and capillary electrophoresis-time of flight mass spectrometry, we investigated the metabolism of L-cysteine in E. histolytica. [U-(13)C3, (15)N]L-cysteine was rapidly metabolized into three unknown metabolites, besides L-cystine and L-alanine. These metabolites were identified as thiazolidine-4-carboxylic acid (T4C), 2-methyl thiazolidine-4-carboxylic acid (MT4C), and 2-ethyl-thiazolidine-4-carboxylic acid (ET4C), the condensation products of L-cysteine with aldehydes. We demonstrated that these 2-(R)-thiazolidine-4-carboxylic acids serve for storage of L-cysteine. Liberation of L-cysteine occurred when T4C was incubated with amebic lysates, suggesting enzymatic degradation of these L-cysteine derivatives. Furthermore, T4C and MT4C significantly enhanced trophozoite growth and reduced intracellular reactive oxygen species (ROS) levels when it was added to cultures, suggesting that 2-(R)-thiazolidine-4-carboxylic acids are involved in the defense against oxidative stress. Amebiasis is a human parasitic disease caused by the protozoan parasite Entamoeba histolytica. In this parasite, L-cysteine is the principal low-molecular-weight thiol and is assumed to play a significant role in supplying the amino acid during trophozoite invasion, particularly when the parasites move from the anaerobic intestinal lumen to highly

  3. The Cysteine S-Alkylation Reaction as a Synthetic Method to Covalently Modify Peptide Sequences.

    Science.gov (United States)

    Calce, Enrica; De Luca, Stefania

    2017-01-05

    Synthetic methodologies to chemically modify peptide molecules have long been investigated for their impact in the field of chemical biology. They allow the introduction of biochemical probes useful for studying protein functions, for manipulating peptides with therapeutic potential, and for structure-activity relationship investigations. The commonly used approach was the derivatization of an amino acid side chain. In this regard, the cysteine, for its unique reactivity, has been widely employed as the substrate for such modifications. Herein, we report on methodologies developed to modify the cysteine thiol group through the S-alkylation reaction. Some procedures perform the alkylation of cysteine derivatives, in order to prepare building blocks to be used during the peptide synthesis, whilst some others selectively modify peptide sequences containing a cysteine residue with a free thiol group, both in solution and in the solid phase. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Recent Developments in D=2 String Field Theory

    OpenAIRE

    Kaku, Michio

    1994-01-01

    In this review article, we review the recent developments in constructing string field theories that have been proposed, all of which correctly reproduce the correlation functions of two-dimensional string theory. These include: (a) free fermion field theory (b) collective string field theory (c) temporal gauge string field theory (d) non-polynomial string field theory. We analyze discrete states, the $w(\\infty)$ symmetry, and correlation functions in terms of these different string field the...

  5. Functional analysis of C1 family cysteine peptidases in the larval gut of Tenebrio molitor and Tribolium castaneum

    Science.gov (United States)

    We studied protein digestion the tenebrionids Tenebrio molitor and Tribolium castaneum, pests of stored grains and grain products, to identify potential targets for biopesticide development. Tenebrionid larvae have highly compartmentalized guts, with primarily cysteine peptidases in the acidic anter...

  6. Organometallic palladium reagents for cysteine bioconjugation

    Science.gov (United States)

    Vinogradova, Ekaterina V.; Zhang, Chi; Spokoyny, Alexander M.; Pentelute, Bradley L.; Buchwald, Stephen L.

    2015-10-01

    Reactions based on transition metals have found wide use in organic synthesis, in particular for the functionalization of small molecules. However, there are very few reports of using transition-metal-based reactions to modify complex biomolecules, which is due to the need for stringent reaction conditions (for example, aqueous media, low temperature and mild pH) and the existence of multiple reactive functional groups found in biomolecules. Here we report that palladium(II) complexes can be used for efficient and highly selective cysteine conjugation (bioconjugation) reactions that are rapid and robust under a range of bio-compatible reaction conditions. The straightforward synthesis of the palladium reagents from diverse and easily accessible aryl halide and trifluoromethanesulfonate precursors makes the method highly practical, providing access to a large structural space for protein modification. The resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody-drug conjugates. These palladium complexes show potential as benchtop reagents for diverse bioconjugation applications.

  7. A Note on Tensionless Strings in M-Theory

    OpenAIRE

    Davis, K.

    1996-01-01

    In this article we examine the appearance of tensionless strings in M-Theory. We subsequently interpret these tensionless strings in a String Theory context. In particular, we examine tensionless strings appearing in M-Theory on $S^{1}$, M-Theory on $S^{1} / {\\bf Z}_{2}$, and M-Theory on $T^{2}$; we then interpret the appearance of such strings in a String Theory context. Then we reverse this process and examine the appearance of some tensionless strings in String Theory. Subsequently we inte...

  8. Cysteine proteases: Modes of activation and future prospects as pharmacological targets

    Directory of Open Access Journals (Sweden)

    Sonia eVerma

    2016-04-01

    Full Text Available Proteolytic enzymes are crucial for a variety of biological processes in organisms ranging from lower (virus, bacteria and parasite to the higher organisms (mammals. Proteases cleave proteins into smaller fragments by catalyzing peptide bonds hydrolysis. Proteases are classified according to their catalytic site, and distributed into four major classes: cysteine proteases, serine proteases, aspartic proteases and metallo-proteases. This review will cover only cysteine proteases, papain family enzymes which are involved in multiple functions such as extracellular matrix turnover, antigen presentation, processing events, digestion, immune invasion, hemoglobin hydrolysis, parasite invasion, parasite egress and processing surface proteins. Therefore, they are promising drug targets for various diseases. For preventing unwanted digestion, cysteine proteases are synthesized as zymogens, and contain a pro-domain (regulatory and a mature domain (catalytic. The prodomain acts as an endogenous inhibitor of the mature enzyme. For activation of the mature enzyme, removal of the prodomain is necessary and achieved by different modes. The pro-mature domain interaction can be categorized as protein-protein interactions (PPIs and may be targeted in a range of diseases. Cysteine protease inhibitors are available that can block the active site but no such inhibitor available yet that can be targeted to block the pro-mature domain interactions and prevent it activation. This review specifically highlights the modes of activation (processing of papain family enzymes, which involve auto-activation, trans-activation and also clarifies the future aspects of targeting PPIs to prevent the activation of cysteine proteases.

  9. Cosmic R-string in thermal history

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Kohei [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kobayashi, Tatsuo [Kyoto Univ. (Japan). Dept. of Physics; Ohashi, Keisuke [Osaka City Univ. (Japan). Dept. of Mathematics and Physics; Ookouchi, Yutaka [Kyoto Univ. (Japan). Dept. of Physics; Kyoto Univ. (Japan). The Hakubi Center for Advanced Research

    2013-03-15

    We study stabilization of an unstable cosmic string associated with spontaneously broken U(1){sub R} symmetry, which otherwise causes a dangerous roll-over process. We demonstrate that in a gauge mediation model, messengers can receive enough corrections from the thermal plasma of the supersymmetric standard model particles to stabilize the unstable modes of the string.

  10. 5D Black Holes and Matrix Strings

    OpenAIRE

    Dijkgraaf, R; Verlinde, E.; Verlinde, H.

    1997-01-01

    We derive the world-volume theory, the (non)-extremal entropy and background geometry of black holes and black strings constructed out of the NS IIA fivebrane within the framework of matrix theory. The CFT description of strings propagating in the black hole geometry arises as an effective field theory.

  11. Recent Progress in String Inflationary Cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Rey, Soo-Jong

    2003-05-23

    Super-inflation driven by dilaton/moduli kinetic energy is naturally realized in compactified string theory. Discussed are selected topics of recent development in string inflationary cosmology: kinematics of super-inflation, graceful exit triggered by quantum back reaction, and classical and quantum power spectra of density and metric perturbations.

  12. String 2, test facility for the LHC

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    String 2 is the long chain seen to the right, representing one complete cell of bending dipoles, focusing quadrupoles and corrector magnets. On 17 June 2002 the test string reached the nominal running current of 11 860 A and magnetic field of 8.335 T for the LHC.

  13. String Theory: Big Problem for Small Size

    Science.gov (United States)

    Sahoo, S.

    2009-01-01

    String theory is the most promising candidate theory for a unified description of all the fundamental forces that exist in nature. It provides a mathematical framework that combines quantum theory with Einstein's general theory of relativity. The typical size of a string is of the order of 10[superscript -33] cm, called the Planck length. But due…

  14. Ultrasensitive string-based temperature sensors

    DEFF Research Database (Denmark)

    Larsen, Tom; Schmid, Silvan; Gronberg, L.

    2011-01-01

    Resonant strings are a promising concept for ultra sensitive temperature detection. We present an analytical model for the sensitivity with which we optimize the temperature response of resonant strings by varying geometry and material. The temperature sensitivity of silicon nitride and aluminum ...

  15. Plucked String on a Shoestring Budget

    Science.gov (United States)

    Gluck, Paul

    2009-01-01

    The physics of the plucked string has been treated in many articles and books. For our 12th-grade high school physics laboratory, we have built a cheap, simple sonometer apparatus for each pair of students on which they may investigate some interesting phenomena that arise when a string is plucked. Among these are the generation of harmonics…

  16. QCD string model for hybrid adiabatic potentials

    OpenAIRE

    Kalashnikova, Yu. S.; Kuzmenko, D. S.

    2001-01-01

    Hybrid adiabatic potentials are considered in the framework of the QCD string model. The einbein field formalism is applied to obtain the large-distance behaviour of adiabatic potentials. The calculated excitation curves are shown to be the result of interplay between potential-type longitudinal and string-type transverse vibrations. The results are compared with recent lattice data.

  17. An overview of progress in string theory

    Indian Academy of Sciences (India)

    2015-11-27

    Nov 27, 2015 ... There has been many interesting developments in string theory in last couple of years. The purpose of this article is to present a brief account of the progress made in string theory. The two invited talks by S R Das and S Mukhi in this volume contain more detailed accounts of our understanding of black hole ...

  18. A Computer String-Grammar of English.

    Science.gov (United States)

    Sager, Naomi

    This volume is the fourth in a series of detailed reports on a working computer program for the syntactic analysis of English sentences into their component strings. The report (1) records the considerations involved in various decisions among alternative grammatical formulations and presents the word-subclasses, the linguistic strings, etc., for…

  19. Querying and Mining Strings Made Easy

    KAUST Repository

    Sahli, Majed

    2017-10-13

    With the advent of large string datasets in several scientific and business applications, there is a growing need to perform ad-hoc analysis on strings. Currently, strings are stored, managed, and queried using procedural codes. This limits users to certain operations supported by existing procedural applications and requires manual query planning with limited tuning opportunities. This paper presents StarQL, a generic and declarative query language for strings. StarQL is based on a native string data model that allows StarQL to support a large variety of string operations and provide semantic-based query optimization. String analytic queries are too intricate to be solved on one machine. Therefore, we propose a scalable and efficient data structure that allows StarQL implementations to handle large sets of strings and utilize large computing infrastructures. Our evaluation shows that StarQL is able to express workloads of application-specific tools, such as BLAST and KAT in bioinformatics, and to mine Wikipedia text for interesting patterns using declarative queries. Furthermore, the StarQL query optimizer shows an order of magnitude reduction in query execution time.

  20. String Rearrangement Metrics: A Survey

    Science.gov (United States)

    Amir, Amihood; Levy, Avivit

    A basic assumption in traditional pattern matching is that the order of the elements in the given input strings is correct, while the description of the content, i.e. the description of the elements, may be erroneous. Motivated by questions that arise in Text Editing, Computational Biology, Bit Torrent and Video on Demand, and Computer Architecture, a new pattern matching paradigm was recently proposed by [2]. In this model, the pattern content remains intact, but the relative positions may change. Several papers followed the initial definition of the new paradigm. Each paper revealed new aspects in the world of string rearrangement metrics. This new unified view has already proven itself by enabling the solution of an open problem of the mathematician Cayley from 1849. It also gave better insight to problems that were already studied in different and limited situations, such as the behavior of different cost functions, and enabled deriving results for cost functions that were not yet sufficiently analyzed by previous research. At this stage, a general understanding of this new model is beginning to coalesce. The aim of this survey is to present an overview of this recent new direction of research, the problems, the methodologies, and the state-of-the-art.

  1. Little strings on D n orbifolds

    Science.gov (United States)

    Kim, Joonho; Lee, Kimyeong

    2017-10-01

    We explore two classes of 6d N=(1,0) little string theories obtained from type IIA/IIB NS5-branes probing D n singularities. Their tensor branches are described by effective gauge theories whose instanton solitons are macroscopic little strings. We specifically study two families of 2d N=(0,4) gauge theories which describe at low energy the worldsheet dynamics of the type IIA/IIB little strings. These gauge theories are useful to calculate the supersymmetric partition functions of the little string theories on R 4 × T 2. We establish the T-duality of the little string theories by utilizing their BPS spectra as a probe.

  2. Primordial anisotropies from cosmic strings during inflation

    Science.gov (United States)

    Jazayeri, Sadra; Sadr, Alireza Vafaei; Firouzjahi, Hassan

    2017-07-01

    In this work, we study the imprint of an individual primordial cosmic string within a Hubble patch on the inflationary power spectrum. A straight cosmic string induces two distinct contributions to the curvature perturbations power spectrum. The first type of correction respects the translation invariance while violating isotropy. This generates quadrupolar statistical anisotropy in cosmic microwave background maps, which is constrained by the Planck data. The second contribution breaks both homogeneity and isotropy, generating a dipolar power asymmetry in the variance of temperature fluctuations with its amplitude falling on small scales. We show that the strongest constraint on the tension of primordial cosmic strings is obtained from the quadrupolar anisotropy and argue that the mass scale of the underlying theory responsible for the formation of the string cannot be much higher than the grand unified theory scale. The predictions for the diagonal and off-diagonal components of the cosmic microwave background angular power spectrum induced by the string are presented.

  3. Applications Of Nonclassical Geometry To String Theory

    CERN Document Server

    Zunger, Y

    2003-01-01

    String theory is built on a foundation of geometry. This thesis examines several applications of geometry beyond the classical Riemannian geometry of curved surfaces. The first part considers the use of extended spaces with internal dimensions to each point (“twistors”) to probe systems with a great deal of symmetry but complicated dynamics. These systems are of critical interest in understanding holographic phenomena in string theory and the origins of entropy. We develop a twistor formulation of coset spaces and use this to write simplified actions for particles and strings on anti-de Sitter space, which are easier to quantize than the ordinary (highly nonlinear) actions. In the second part, we consider two aspects of noncommutative geometry, a generalization of ordinary geometry where points are “fuzzed out” and functions of space become noncommuting operators. We first examine strings with one endpoint on a D-brane in a background magnetic field. (Strings with both ...

  4. Strings, conformal fields and topology. An introduction

    Energy Technology Data Exchange (ETDEWEB)

    Kaku, Michio (City Coll., New York (USA). Dept. of Physics)

    1991-01-01

    String Theory has advanced at an astonishing pace in the last few years, and this book aims to acquaint the reader with the most active topics of research in the field. Building on the foundations laid in his Introduction to Superstrings, Professor Kaku discusses such topics as the classification of conformal string theories, knot theory, the Yang-Baxter relation, quantum groups, the non-polynominal closed string field theory, matrix models, and topological field theory. Several chapters review the fundamentals of string theory, making the presentation of the material self-contained while keeping overlap with the earlier book to a minimum. The book conveys the vitality of current research in string theory and places readers at its forefront. (orig.) With 40 figs. in 50 parts.

  5. Knotlike cosmic strings in the early universe

    Science.gov (United States)

    Duan, Yi-shi; Liu, Xin

    2004-02-01

    In this paper, the knotlike cosmic strings in the Riemann-Cartan space-time of the early universe are discussed. It has been revealed that the cosmic strings can just originate from the zero points of the complex scalar quintessence field. In these strings we mainly study the knotlike configurations. Based on the integral of Chern-Simons 3-form a topological invariant for knotlike cosmic strings is constructed, and it is shown that this invariant is just the total sum of all the self-linking and linking numbers of the knots family. Furthermore, it is also pointed out that this invariant is preserved in the branch processes during the evolution of cosmic strings.

  6. String theory of the Regge intercept.

    Science.gov (United States)

    Hellerman, S; Swanson, I

    2015-03-20

    Using the Polchinski-Strominger effective string theory in the covariant gauge, we compute the mass of a rotating string in D dimensions with large angular momenta J, in one or two planes, in fixed ratio, up to and including first subleading order in the large J expansion. This constitutes a first-principles calculation of the value for the order-J(0) contribution to the mass squared of a meson on the leading Regge trajectory in planar QCD with bosonic quarks. For open strings with Neumann boundary conditions, and for closed strings in D≥5, the order-J(0) term in the mass squared is exactly calculated by the semiclassical approximation. This term in the expansion is universal and independent of the details of the theory, assuming only D-dimensional Poincaré invariance and the absence of other infinite-range excitations on the string world volume, beyond the Nambu-Goldstone bosons.

  7. Plucked String on a Shoestring Budget

    Science.gov (United States)

    Gluck, Paul

    2009-01-01

    The physics of the plucked string has been treated in many articles and books.1-4 For our 12th-grade high school physics laboratory, we have built a cheap, simple sonometer apparatus for each pair of students on which they may investigate some interesting phenomena that arise when a string is plucked. Among these are the generation of harmonics (overtones) and the way their number depends on the length of a string and on where one plucks, the relation between the frequencies of the fundamental and those of the harmonics, and the way these are affected by changes in the length and the tension in the string. Such an experiment will help students appreciate the working of stringed musical instruments and, in particular, the contribution of overtones to the richness of sound produced.

  8. CMB temperature trispectrum of cosmic strings

    Science.gov (United States)

    Hindmarsh, Mark; Ringeval, Christophe; Suyama, Teruaki

    2010-03-01

    We provide an analytical expression for the trispectrum of the cosmic microwave background (CMB) temperature anisotropies induced by cosmic strings. Our result is derived for the small angular scales under the assumption that the temperature anisotropy is induced by the Gott-Kaiser-Stebbins effect. The trispectrum is predicted to decay with a noninteger power-law exponent ℓ-ρ with 6<ρ<7, depending on the string microstructure, and thus on the string model. For Nambu-Goto strings, this exponent is related to the string mean square velocity and the loop distribution function. We then explore two classes of wave number configuration in Fourier space, the kite and trapezium quadrilaterals. The trispectrum can be of any sign and appears to be strongly enhanced for all squeezed quadrilaterals.

  9. Identification, classification and expression pattern analysis of sugarcane cysteine proteinases

    Directory of Open Access Journals (Sweden)

    Gustavo Coelho Correa

    2001-12-01

    Full Text Available Cysteine proteases are peptidyl hydrolyses dependent on a cysteine residue at the active center. The physical and chemical properties of cysteine proteases have been extensively characterized, but their precise biological functions have not yet been completely understood, although it is known that they are involved in a number of events such as protein turnover, cancer, germination, programmed cell death and senescence. Protein sequences from different cysteine proteinases, classified as members of the E.C.3.4.22 sub-sub-class, were used to perform a T-BLAST-n search on the Brazilian Sugarcane Expressed Sequence Tags project (SUCEST data bank. Sequence homology was found with 76 cluster sequences that corresponded to possible cysteine proteinases. The alignments of these SUCEST clusters with the sequence of cysteine proteinases of known origins provided important information about the classification and possible function of these sugarcane enzymes. Inferences about the expression pattern of each gene were made by direct correlation with the SUCEST cDNA libraries from which each cluster was derived. Since no previous reports of sugarcane cysteine proteinases genes exists, this study represents a first step in the study of new biochemical, physiological and biotechnological aspects of sugarcane cysteine proteases.Proteinases cisteínicas são peptidil-hidrolases dependentes de um resíduo de cisteína em seu sítio ativo. As propriedades físico-químicas destas proteinases têm sido amplamente caracterizadas, entretanto suas funções biológicas ainda não foram completamente elucidadas. Elas estão envolvidas em um grande número de eventos, tais como: processamento e degradação protéica, câncer, germinação, morte celular programada e processos de senescência. Diferentes proteinases cisteínicas, classificadas pelo Comitê de Nomenclatura da União Internacional de Bioquímica e Biologia Molecular (IUBMB como pertencentes à sub

  10. Cysteine oxidative posttranslational modifications: emerging regulation in the cardiovascular system.

    Science.gov (United States)

    Chung, Heaseung S; Wang, Sheng-Bing; Venkatraman, Vidya; Murray, Christopher I; Van Eyk, Jennifer E

    2013-01-18

    In the cardiovascular system, changes in oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the posttranslational modification of proteins at critical cysteine thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. Although the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understand how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various cysteine oxidative posttranslational modifications and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other posttranslational modifications' signaling pathways though cross-talk. Finally, we review the increasing number of tools being developed to identify and quantify the various cysteine oxidative posttranslational modifications and how this will advance our understanding of redox-regulation.

  11. The cysteine proteinases of the pineapple plant.

    OpenAIRE

    Rowan, A D; Buttle, D J; Barrett, A J

    1990-01-01

    The pineapple plant (Ananas comosus) was shown to contain at least four distinct cysteine proteinases, which were purified by a procedure involving active-site-directed affinity chromatography. The major proteinase present in extracts of plant stem was stem bromelain, whilst fruit bromelain was the major proteinase in the fruit. Two additional cysteine proteinases were detected only in the stem: these were ananain and a previously undescribed enzyme that we have called comosain. Stem bromelai...

  12. Cysteine Network (CYSTEINET) Dysregulation in Parkinson's Disease: Role of N-acetylcysteine.

    Science.gov (United States)

    Martínez-Banaclocha, Marcos

    2016-01-01

    Reactive species have been regarded as by-products of cellular metabolism, which cause oxidative damage contributing to aging and neurodegenerative diseases. However, accumulated evidence support the notion that reactive species mediate intracellular and extracellular signals that regulate physiological functions including posttranslational protein modifications. Cysteine thiol groups of proteins are particularly susceptible to oxidative modifications by oxygen, nitrogen and sulfur species generating different products with critical roles in the cellular redox homeostasis. At physiological conditions, reactive species can function not only as intracellular second messengers with regulatory roles in many cellular metabolic processes but also as part of an ancestral biochemical network that controls cellular survival, regeneration, and death. To propose a biochemical network, called cellular cysteine network (CYSTEINET), which can be dysregulated in Parkinson's disease. Due to the fact that there are many cysteine-bearing proteins and cysteine-dependent enzymes susceptible to oxidative modifications, it is proposed that oxidative-changed proteins at cysteine residues may be critical for Parkinson's disease development. In the present review, I advance the concept that "cysteinet" is impaired in Parkinson's disease resulting in a functional and structural dysregulation of the matrix of interconnected cysteine-bearing proteins, which in conjunction with reactive species and glutathione regulate the cellular bioenergetic metabolism, the redox homeostasis, and the cellular survival. This network may represent an ancestral down-top system composed of a complex matrix of proteins with very different cellular functions, but bearing the same regulatory thiol radical. Finally, the possible role of N-acetylcysteine and derivatives to regulate "cysteinet" and slow down Parkinson's disease development and progression is discussed.

  13. Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica

    Directory of Open Access Journals (Sweden)

    Jeelani Ghulam

    2011-05-01

    Full Text Available Abstract Background Entamoeba histolytica, an enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. E. histolytica completely lacks glutathione metabolism but possesses L-cysteine as the principle low molecular weight thiol. L-Cysteine is essential for the structure, stability, and various protein functions, including catalysis, electron transfer, redox regulation, nitrogen fixation, and sensing for regulatory processes. Recently, we demonstrated that in E. histolytica, L-cysteine regulates various metabolic pathways including energy, amino acid, and phospholipid metabolism. Results In this study, employing custom-made Affymetrix microarrays, we performed time course (3, 6, 12, 24, and 48 h gene expression analysis upon L-cysteine deprivation. We identified that out of 9,327 genes represented on the array, 290 genes encoding proteins with functions in metabolism, signalling, DNA/RNA regulation, electron transport, stress response, membrane transport, vesicular trafficking/secretion, and cytoskeleton were differentially expressed (≥3 fold at one or more time points upon L-cysteine deprivation. Approximately 60% of these modulated genes encoded proteins of no known function and annotated as hypothetical proteins. We also attempted further functional analysis of some of the most highly modulated genes by L-cysteine depletion. Conclusions To our surprise, L-cysteine depletion caused only limited changes in the expression of genes involved in sulfur-containing amino acid metabolism and oxidative stress defense. In contrast, we observed significant changes in the expression of several genes encoding iron sulfur flavoproteins, a major facilitator super-family transporter, regulator of nonsense transcripts, NADPH-dependent oxido-reductase, short chain dehydrogenase, acetyltransferases, and various other genes involved in diverse cellular functions. This study represents the first

  14. Metabolism of captopril-L-cysteine, a captopril metabolite, in rats and dogs.

    Science.gov (United States)

    Kripalani, K J; Dean, A V; Migdalof, B H

    1983-12-01

    The metabolism of [14C]captopril-L-cysteine was studied in spontaneously hypertensive rats and pure-bred beagles after a single i.v. dose (4 mg/kg). During the first 24 h, concn. of total radioactivity in blood were similar in both species. Captopril was found in small amounts in the blood of both species. In rats, captopril, bound covalently but reversibly to plasma proteins (CP-PR), was the major component in blood (70%), whereas captopril-L-cysteine was a minor component (23%) of the total radioactivity. In dog blood, CP-PR constituted a smaller fraction (45%) of the total radioactivity than in the rat and captopril-L-cysteine was the major component (53%). In 72 h, 89-91% of the dose was excreted in the urine of rats and dogs. Captopril-L-cysteine accounted for 7% (rat) and 68% (dog) of the radioactivity in urine; captopril accounted for 75% (rat) and 7% (dog). Other metabolites were present in the urine of both species. The greater net conversion of captopril-L-cysteine to CP-PR and to captopril in rats helps explain why captopril-L-cysteine is excreted in urine as a major metabolite of captopril in dogs but only a minor one in rats.

  15. Coffee cysteine proteinases and related inhibitors with high expression during grain maturation and germination

    Directory of Open Access Journals (Sweden)

    Lepelley Maud

    2012-03-01

    Full Text Available Abstract Background Cysteine proteinases perform multiple functions in seeds, including participation in remodelling polypeptides and recycling amino acids during maturation and germination. Currently, few details exist concerning these genes and proteins in coffee. Furthermore, there is limited information on the cysteine proteinase inhibitors which influence the activities of these proteinases. Results Two cysteine proteinase (CP and four cysteine proteinase inhibitor (CPI gene sequences have been identified in coffee with significant expression during the maturation and germination of coffee grain. Detailed expression analysis of the cysteine proteinase genes CcCP1 and CcCP4 in Robusta using quantitative RT-PCR showed that these transcripts accumulate primarily during grain maturation and germination/post germination. The corresponding proteins were expressed in E. coli and purified, but only one, CcCP4, which has a KDDL/KDEL C-terminal sequence, was found to be active after a short acid treatment. QRT-PCR expression analysis of the four cysteine proteinase inhibitor genes in Robusta showed that CcCPI-1 is primarily expressed in developing and germinating grain and CcCPI-4 is very highly expressed during the late post germination period, as well as in mature, but not immature leaves. Transcripts corresponding to CcCPI-2 and CcCPI-3 were detected in most tissues examined at relatively similar, but generally low levels. Conclusions Several cysteine proteinase and cysteine proteinase inhibitor genes with strong, relatively specific expression during coffee grain maturation and germination are presented. The temporal expression of the CcCP1 gene suggests it is involved in modifying proteins during late grain maturation and germination. The expression pattern of CcCP4, and its close identity with KDEL containing CP proteins, implies this proteinase may play a role in protein and/or cell remodelling during late grain germination, and that it is

  16. Coffee cysteine proteinases and related inhibitors with high expression during grain maturation and germination.

    Science.gov (United States)

    Lepelley, Maud; Amor, Mohamed Ben; Martineau, Nelly; Cheminade, Gerald; Caillet, Victoria; McCarthy, James

    2012-03-01

    Cysteine proteinases perform multiple functions in seeds, including participation in remodelling polypeptides and recycling amino acids during maturation and germination. Currently, few details exist concerning these genes and proteins in coffee. Furthermore, there is limited information on the cysteine proteinase inhibitors which influence the activities of these proteinases. Two cysteine proteinase (CP) and four cysteine proteinase inhibitor (CPI) gene sequences have been identified in coffee with significant expression during the maturation and germination of coffee grain. Detailed expression analysis of the cysteine proteinase genes CcCP1 and CcCP4 in Robusta using quantitative RT-PCR showed that these transcripts accumulate primarily during grain maturation and germination/post germination. The corresponding proteins were expressed in E. coli and purified, but only one, CcCP4, which has a KDDL/KDEL C-terminal sequence, was found to be active after a short acid treatment. QRT-PCR expression analysis of the four cysteine proteinase inhibitor genes in Robusta showed that CcCPI-1 is primarily expressed in developing and germinating grain and CcCPI-4 is very highly expressed during the late post germination period, as well as in mature, but not immature leaves. Transcripts corresponding to CcCPI-2 and CcCPI-3 were detected in most tissues examined at relatively similar, but generally low levels. Several cysteine proteinase and cysteine proteinase inhibitor genes with strong, relatively specific expression during coffee grain maturation and germination are presented. The temporal expression of the CcCP1 gene suggests it is involved in modifying proteins during late grain maturation and germination. The expression pattern of CcCP4, and its close identity with KDEL containing CP proteins, implies this proteinase may play a role in protein and/or cell remodelling during late grain germination, and that it is likely to play a strong role in the programmed cell death

  17. Role of cysteine amino acid residues on the RNA binding activity of human thymidylate synthase

    OpenAIRE

    Lin, Xiukun; Liu, Jun; Maley, Frank; Chu, Edward

    2003-01-01

    The role of cysteine sulfhydryl residues on the RNA binding activity of human thymidylate synthase (TS) was investigated by mutating each cysteine residue on human TS to a corresponding alanine residue. Enzymatic activities of TS:C43A and TS:C210A mutant proteins were nearly identical to wild-type TS, while TS:C180A and TS:C199A mutants expressed >80% of wild-type enzyme activity. In contrast, TS:C195A was completely inactive. Mutant proteins, TS:C195A, TS:C199A and TS:C210A, retained RNA bin...

  18. The birth of string theory

    CERN Document Server

    Castellani, Elena; Colomo, Filippo; Di Vecchia, Paolo

    2012-01-01

    String theory is currently the best candidate for a unified theory of all forces and all forms of matter in nature. As such, it has become a focal point for physical and philosophical discussions. This unique book explores the history of the theory's early stages of development, as told by its main protagonists. The book journeys from the first version of the theory (the so-called dual resonance model) in the late sixties, as an attempt to describe the physics of strong interactions outside the framework of quantum field theory, to its reinterpretation around the mid-seventies as a quantum theory of gravity unified with the other forces, and its successive developments up to the superstring revolution in 1984. Providing important background information to current debates on the theory, this book is essential reading for students and researchers in physics, as well as historians and philosophers of science.

  19. Graviton spectra in string cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Galluccio, Massimo [Osservatorio Astronomico di Roma (Roma-IT); Litterio, Marco [Istituto Astronomico dell' Universita (Roma-IT); Occhionero, Franco [Osservatorio Astronomico di Roma (Roma-IT)

    1996-08-01

    We propose to uncover the signature of a stringy era in the primordial Universe by searching for a prominent peak in the relic graviton spectrum. This feature, which in our specific model terminates an ω³ increase and initiates an ω⁻⁷ decrease, is induced during the so far overlooked bounce of the scale factor between the collapsing deflationary era (or pre-Big Bang) and the expanding inflationary era (or post-Big Bang). We evaluate both analytically and numerically the frequency and the intensity of the peak and we show that they may likely fall in the realm of the new generation of interferometric detectors. The existence of a peak is at variance with ordinarily monotonic (either increasing or decreasing) graviton spectra of canonical cosmologies; its detection would therefore offer strong support to string cosmology.

  20. String-Corrected Black Holes

    Energy Technology Data Exchange (ETDEWEB)

    Hubeny, V.

    2005-01-12

    We investigate the geometry of four dimensional black hole solutions in the presence of stringy higher curvature corrections to the low energy effective action. For certain supersymmetric two charge black holes these corrections drastically alter the causal structure of the solution, converting seemingly pathological null singularities into timelike singularities hidden behind a finite area horizon. We establish, analytically and numerically, that the string-corrected two-charge black hole metric has the same Penrose diagram as the extremal four-charge black hole. The higher derivative terms lead to another dramatic effect--the gravitational force exerted by a black hole on an inertial observer is no longer purely attractive. The magnitude of this effect is related to the size of the compactification manifold.

  1. String Phenomenology: Past, Present and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Alon E. Faraggi

    2014-04-01

    Full Text Available The observation of a scalar resonance at the Large Hadron Collider (LHC, compatible with perturbative electroweak symmetry breaking, reinforces the Standard Model (SM parameterisation of all subatomic data. The logarithmic evolution of the SM gauge and matter parameters suggests that this parameterisation remains viable up to the Planck scale, where gravitational effects are of comparable strength. String theory provides a perturbatively consistent scheme to explore how the parameters of the Standard Model may be determined from a theory of quantum gravity. The free fermionic heterotic string models provide concrete examples of exact string solutions that reproduce the spectrum of the Minimal Supersymmetric Standard Model. Contemporary studies entail the development of methods to classify large classes of models. This led to the discovery of exophobic heterotic-string vacua and the observation of spinor-vector duality, which provides an insight to the global structure of the space of (2,0 heterotic-string vacua. Future directions entail the study of the role of the massive string states in these models and their incorporation in cosmological scenarios. A complementary direction is the formulation of quantum gravity from the principle of manifest phase space duality and the equivalence postulate of quantum mechanics, which suggest that space is compact. The compactness of space, which implies intrinsic regularisation, may be tightly related to the intrinsic finite length scale, implied by string phenomenology.

  2. Wave diffraction by a cosmic string

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Núñez, Isabel [Departament de Física Quàntica i Astrofísica, Facultat de Física, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona (Spain); Institut de Ciències del Cosmos (ICCUB), Facultat de Física, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona (Spain); Bulashenko, Oleg, E-mail: oleg.bulashenko@ub.edu [Departament de Física Quàntica i Astrofísica, Facultat de Física, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona (Spain)

    2016-08-26

    We show that if a cosmic string exists, it may be identified through characteristic diffraction pattern in the energy spectrum of the observed signal. In particular, if the string is on the line of sight, the wave field is shown to fit the Cornu spiral. We suggest a simple procedure, based on Keller's geometrical theory of diffraction, which allows to explain wave effects in conical spacetime of a cosmic string in terms of interference of four characteristic rays. Our results are supposed to be valid for scalar massless waves, including gravitational waves, electromagnetic waves, or even sound in case of condensed matter systems with analogous topological defects. - Highlights: • Gravitational waves could help us to reveal cosmic strings – topological defects of early Universe. • Wave diffraction in conical spacetime of a cosmic string is solved analytically. • The Cornu spiral is shown to appear when the string is on the line of sight. • For a string located within our galaxy, the highest amplification would occur at a frequency range of LIGO detector.

  3. Towards a kinetic theory of strings

    Science.gov (United States)

    Vanchurin, Vitaly

    2011-05-01

    We study the dynamics of strings by means of a distribution function f(A,B,x,t), defined on a 9+1D phase space, where A and B are the correlation vectors of right- and left-moving waves. We derive a transport equation (analogous to a Boltzmann transport equation for particles) that governs the evolution of long strings with Nambu-Goto dynamics, as well as reconnections taken into account. We also derive a system of coupled transport equations (analogous to a Bogoliubov-Born-Green-Kirkwood-Yvon hierarchy for particles) which can simultaneously describe long strings f˜(A,B,x,t) as well as simple loops f∘(A,B,x,t) made out of four correlation vectors. The formalism can be used to study nonlinear dynamics of fundamental strings, D-brane strings, or field theory strings. For example, the complicated semiscaling behavior of cosmic strings translates into a simple solution of the transport system at small energy densities.

  4. Highly excited strings I: Generating function

    Directory of Open Access Journals (Sweden)

    Dimitri P. Skliros

    2017-03-01

    Full Text Available This is the first of a series of detailed papers on string amplitudes with highly excited strings (HES. In the present paper we construct a generating function for string amplitudes with generic HES vertex operators using a fixed-loop momentum formalism. We generalise the proof of the chiral splitting theorem of D'Hoker and Phong to string amplitudes with arbitrary HES vertex operators (with generic KK and winding charges, polarisation tensors and oscillators in general toroidal compactifications E=RD−1,1×TDcr−D (with generic constant Kähler and complex structure target space moduli, background Kaluza–Klein (KK gauge fields and torsion. We adopt a novel approach that does not rely on a “reverse engineering” method to make explicit the loop momenta, thus avoiding a certain ambiguity pointed out in a recent paper by Sen, while also keeping the genus of the worldsheet generic. This approach will also be useful in discussions of quantum gravity and in particular in relation to black holes in string theory, non-locality and breakdown of local effective field theory, as well as in discussions of cosmic superstrings and their phenomenological relevance. We also discuss the manifestation of wave/particle (or rather wave/string duality in string theory.

  5. Reheating for closed string inflation

    Energy Technology Data Exchange (ETDEWEB)

    Cicoli, Michele [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Mazumdar, Anupam [Lancaster Univ. (United Kingdom). Physics Dept.; Copenhagen Univ. (Denmark). Niels Bohr Institute

    2010-05-15

    We point out some of the outstanding challenges for embedding inflationary cosmology within string theory studying the process of reheating for models where the inflaton is a closed string mode parameterising the size of an internal cycle of the compactification manifold. A realistic model of inflation must explain the tiny perturbations in the cosmic microwave background radiation and also how to excite the ordinary matter degrees of freedom after inflation, required for the success of Big Bang Nucleosynthesis. We study these issues focusing on two promising inflationary models embedded in LARGE volume type IIB flux compactifications. We show that phenomenological requirements and consistency of the effective field theory treatment imply the presence at low energies of a hidden sector together with a visible sector, where the Minimal Supersymmetric Standard Model fields are residing. A detailed calculation of the inflaton coupling to the fields of the hidden sector, visible sector, and moduli sector, reveals that the inflaton fails to excite primarily the visible sector fields, instead hidden sector fields are excited copiously after the end of inflation. This sets severe constraints on hidden sector model building where the most promising scenario emerges as a pure N=1 SYM theory, forbidding the kinematical decay of the inflaton to the hidden sector. In this case it is possible to reheat the Universe with the visible degrees of freedom even though in some cases we discover a new tension between TeV scale SUSY and reheating on top of the well-known tension between TeV scale SUSY and inflation. (orig.)

  6. The Structure of Cosmic String Wakes

    OpenAIRE

    Sornborger, A.; Brandenberger, R.; Fryxell, B.; Olson, K.

    1996-01-01

    The clustering of baryons and cold dark matter induced by a single moving string is analyzed numerically making use of a new three-dimensional Eulerian cosmological hydro code$^{1)}$ which is based on the PPM method to track the baryons and the PIC method to evolve the dark matter particles. A long straight string moving with a speed comparable to $c$ induces a planar overdensity (a``wake"). Since the initial perturbation is a velocity kick towards the plane behind the string and there is no ...

  7. A hybrid metaheuristic for closest string problem.

    Science.gov (United States)

    Mousavi, Sayyed Rasoul

    2011-01-01

    The Closest String Problem (CSP) is an optimisation problem, which is to obtain a string with the minimum distance from a number of given strings. In this paper, a new metaheuristic algorithm is investigated for the problem, whose main feature is relatively high speed in obtaining good solutions, which is essential when the input size is large. The proposed algorithm is compared with four recent algorithms suggested for the problem, outperforming them in more than 98% of the cases. It is also remarkably faster than all of them, running within 1 s in most of the experimental cases.

  8. String Balls at the LHC and Beyond

    CERN Document Server

    Dimopoulos, Savas K; Dimopoulos, Savas; Emparan, Roberto

    2002-01-01

    In string theory, black holes have a minimum mass below which they transition into highly excited long and jagged strings --- ``string balls''. These are the stringy progenitors of black holes; because they are lighter, in theories of TeV-gravity, they may be more accessible to the LHC or the VLHC. They share some of the characteristics of black holes, such as large production cross sections. Furthermore, they evaporate thermally at the Hagedorn temperature and give rise to high-multiplicity events containing hard primary photons and charged leptons, which have negligible standard-model background.

  9. Systems and methods for photovoltaic string protection

    Science.gov (United States)

    Krein, Philip T.; Kim, Katherine A.; Pilawa-Podgurski, Robert C. N.

    2017-10-25

    A system and method includes a circuit for protecting a photovoltaic string. A bypass switch connects in parallel to the photovoltaic string and a hot spot protection switch connects in series with the photovoltaic string. A first control signal controls opening and closing of the bypass switch and a second control signal controls opening and closing of the hot spot protection switch. Upon detection of a hot spot condition the first control signal closes the bypass switch and after the bypass switch is closed the second control signal opens the hot spot protection switch.

  10. The String and the Cosmic Bounce

    Directory of Open Access Journals (Sweden)

    Bozza V.

    2014-04-01

    Full Text Available String theory introduces a new fundamental scale (the string length that is expected to regularize the singularities of classical general relativity. In a cosmological context, the Big Bang is no longer regarded as the beginning of time, but just a transition between a Pre-Big Bang collapse phase and the current expansion. We will review old and recent attempts to build consistent bouncing cosmologies inspired to string theories, discussing their solved and unsolved problems, focussing on the observables that may distinguish them from standard inflationary scenarios.

  11. String Theory, Cosmology And Brany Geometry

    CERN Document Server

    Pokotilov, A

    2005-01-01

    Motivated by cosmological applications in this thesis we describe several string theory based models of the early Universe. The major property of these models is that they lead to inflationary-like expansion for early times. The interaction properties of fundamental strings, leading to the velocity dependent potentials are used to describe this accelerating expansion rate. Other types of extended objects such as fivebranes dual to fundamental strings are shown to lead to the similar cosmological implications. Our findings are consistent with recent astronomical observations of an accelerated expansion of the Universe and predict an asymptotically constant late time expansion rate.

  12. Tachyon Condensation and Spectrum of Strings on D-branes

    OpenAIRE

    Suyama, Takao

    2001-01-01

    We investigate spectrum of open strings on D-branes after tachyon condensation in bosonic string theory. We calculate 1-loop partition function of the string and show that its limiting forms coincide with partition functions of open strings with different boundary conditions.

  13. Exploring the mechanism of inhibition of human telomerase by cysteine-reactive compounds.

    Science.gov (United States)

    Kellermann, Guillaume; Dingli, Florent; Masson, Vanessa; Dauzonne, Daniel; Ségal-Bendirdjian, Evelyne; Teulade-Fichou, Marie-Paule; Loew, Damarys; Bombard, Sophie

    2017-03-01

    Telomerase is an almost universal cancer target that consists minimally of a core protein human telomerase reverse transcriptase (hTERT) and a RNA component human telomerase RNA (hTR). Some inhibitors of this enzyme are thought to function by the covalent binding to one or several cysteine residues; however, this inhibition mechanism has never been investigated because of the difficulty in producing telomerase. In this study, we use a recent method to produce recombinant hTERT to analyze the effect of cysteine-reactive inhibitors on telomerase. Using mass spectrometry and mutagenesis analysis, we identify several targeted residues in separated domains of the hTERT protein and show that cysteine-reactive reagents abolish the interaction with the CR4/5 region of hTR. © 2017 Federation of European Biochemical Societies.

  14. Strings and their compactification from the particle viewpoint

    Energy Technology Data Exchange (ETDEWEB)

    Slansky, R.

    1986-01-01

    A series of four lectures is given which deals with the particle formulation of string theory. An introductory lecture is given on where the idea of strings comes from and what strings are. An introduction is given to simple Lie algebras and their representations. Compactified strings and the heterotic theories are discussed, showing how infinite-dimensional Kac-Moody affine algebras can be spectrum generating algebras in (open) string theories. The spectrum of excited states of the heterotic string is examined, and comments are made on representations of affine algebras. Some aspects are shown of the algebraic structure of compactified closed bosonic strings. (LEW)

  15. Observation of Motion of Bowed Strings and Resonant Strings in Violin Performances

    Science.gov (United States)

    Matsutani, Akihiro

    2013-10-01

    The motion of a bowed string and a resonant string of a violin were simultaneously observed for the first time. The results of the direct observation of string motion in double stops and harmonics are also presented. The importance of the resonance was experimentally demonstrated from these observations. It is suggested that players should take account of the resonance and ideal Helmholtz motion in violin performances.

  16. Hagedorn Behavior of Little String Theories from string corrections to NS5-branes

    DEFF Research Database (Denmark)

    Harmark, Troels; Obers, N. A.

    2000-01-01

    We examine the Hagedorn behavior of little string theory using its conjectured duality with near-horizon NS5-branes. In particular, by studying the string-corrected NS5-brane supergravity solution, it is shown that tree-level corrections to the temperature vanish, while the leading one-loop string...... correction generates the correct temperature dependence of the entropy near the Hagedorn temperature. Finally, the Hagedorn behavior of ODp-brane theories, which are deformed versions of little string theory, is considered via their supergravity duals....

  17. Excited cosmic strings with superconducting currents

    Science.gov (United States)

    Hartmann, Betti; Michel, Florent; Peter, Patrick

    2017-12-01

    We present a detailed analysis of excited cosmic string solutions that possess superconducting currents. These currents can be excited inside the string core, and—if the condensate is large enough—can lead to the excitations of the Higgs field. Next to the case with global unbroken symmetry, we discuss also the effects of the gauging of this symmetry and show that excited condensates persist when coupled to an electromagnetic field. The space-time of such strings is also constructed by solving the Einstein equations numerically and we show how the local scalar curvature is modified by the excitation. We consider the relevance of our results on the cosmic string network evolution as well as observations of primordial gravitational waves and cosmic rays.

  18. Introduction to string and superstring theory II

    Energy Technology Data Exchange (ETDEWEB)

    Peskin, M.E.

    1987-03-01

    Conformal field theory is reviewed, then conformal invariance is used to rederive the basic results on the embedding dimensionality for bosonic and fermionic strings. The spectrum of the bosonic and the computation of scattering amplitudes are discussed. The formalism used is extended to clarify the origin of Yang-Mills gauge invariance in the open bosonic string theory. The question of the general-coordinate gauge invariance of string theory is addressed, presenting two disparate viewpoints on this question. A brief introduction is then given of the reduction from the idealized string theory in 10 extended dimensions to more realistic solutions in which all but 4 of these dimensions are compactified. The state of knowledge about the space-time supersymmetry of the superstring from the covariant viewpoint is outlined. An approach for identifying possible 6-dimensional spaces which might represent the form of the compact dimensions is discussed, and the orbifold scheme of compactification is presented. 77 refs., 18 figs. (LEW)

  19. The LHC test string first operational experience

    CERN Document Server

    Bézaguet, Alain-Arthur; Casas-Cubillos, J; Coull, L; Cruikshank, P; Dahlerup-Petersen, K; Faugeras, Paul E; Flemsæter, B; Guinaudeau, H; Hagedorn, Dietrich; Hilbert, B; Krainz, G; Kos, N; Lavielle, D; Lebrun, P; Leo, G; Mathewson, A G; Missiaen, D; Momal, F; Parma, Vittorio; Quesnel, Jean Pierre; Richter, D; Riddone, G; Rijllart, A; Rodríguez-Mateos, F; Rohmig, P; Saban, R I; Schmidt, R; Serio, L; Skiadelli, M; Suraci, A; Tavian, L; Walckiers, L; Wallén, E; Van Weelderen, R; Williams, L; McInturff, A

    1996-01-01

    CERN operates the first version of the LHC Test String which consists of one quadrupole and three 10-m twin aperture dipole magnets. An experimental programme aiming at the validation of the LHC systems started in February 1995. During this programme the string has been powered 100 times 35 of which at 12.4 kA or above. The experiments have yielded a number of results some of which, like quench recovery for cryogenics, have modified the design of subsystems of LHC. Others, like controlled helium leaks in the cold bore and quench propagation bewteen magnets, have given a better understanding on the evolution of the phenomena inside a string of superconducting magnets cooled at superfluid helium temperatures. Following the experimental programme, the string will be powered up and powered down in one hour cycles as a fatigue test of the structure thus simulating 20 years of operation of LHC.

  20. Towards a theory of the QCD string

    Energy Technology Data Exchange (ETDEWEB)

    Dubovsky, Sergei [Center for Cosmology and Particle Physics, Department of Physics, New York University,4 Washington place, New York, NY 10003 (United States); Gorbenko, Victor [Stanford Institute for Theoretical Physics, Department of Physics, Stanford University,382 Via Pueblo, Stanford, CA 94305 (United States)

    2016-02-03

    We construct a new model of four-dimensional relativistic strings with integrable dynamics on the worldsheet. In addition to translational modes this model contains a single massless pseudoscalar worldsheet field — the worldsheet axion. The axion couples to a topological density which counts the self-intersection number of a string. The corresponding coupling is fixed by integrability to Q=√((7/(16π)))≈0.37. We argue that this model is a member of a larger family of relativistic non-critical integrable string models. This family includes and extends conventional non-critical strings described by the linear dilaton CFT. Intriguingly, recent lattice data in SU(3) and SU(5) gluodynamics reveals the presence of a massive pseudoscalar axion on the worldsheet of confining flux tubes. The value of the corresponding coupling, as determined from the lattice data, is equal to Q{sub L}≈0.38±0.04.

  1. ABCD of Beta Ensembles and Topological Strings

    CERN Document Server

    Krefl, Daniel

    2012-01-01

    We study beta-ensembles with Bn, Cn, and Dn eigenvalue measure and their relation with refined topological strings. Our results generalize the familiar connections between local topological strings and matrix models leading to An measure, and illustrate that all those classical eigenvalue ensembles, and their topological string counterparts, are related one to another via various deformations and specializations, quantum shifts and discrete quotients. We review the solution of the Gaussian models via Macdonald identities, and interpret them as conifold theories. The interpolation between the various models is plainly apparent in this case. For general polynomial potential, we calculate the partition function in the multi-cut phase in a perturbative fashion, beyond tree-level in the large-N limit. The relation to refined topological string orientifolds on the corresponding local geometry is discussed along the way.

  2. Towards a theory of the QCD string

    Science.gov (United States)

    Dubovsky, Sergei; Gorbenko, Victor

    2016-02-01

    We construct a new model of four-dimensional relativistic strings with integrable dynamics on the worldsheet. In addition to translational modes this model contains a single massless pseudoscalar worldsheet field — the worldsheet axion. The axion couples to a topological density which counts the self-intersection number of a string. The corresponding coupling is fixed by integrability to Q=√{7/16π }≈ 0.37 . We argue that this model is a member of a larger family of relativistic non-critical integrable string models. This family includes and extends conventional non-critical strings described by the linear dilaton CFT. Intriguingly, recent lattice data in SU(3) and SU(5) gluodynamics reveals the presence of a massive pseudoscalar axion on the worldsheet of confining flux tubes. The value of the corresponding coupling, as determined from the lattice data, is equal to Q L ≈ 0 .38 ± 0 .04.

  3. Academic Training: String Theory for Pedestrians

    CERN Multimedia

    2007-01-01

    2006-2007 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 29, 30, 31 January 2007, from 11:00 to 12:00 Main Auditorium, bldg. 500 on 29 and 30 January, TH Auditorium, Bldg 4, 3-006, on 31 January String Theory for Pedestrians B. ZWIEBACH, MIT, Cambridge, USA In this 3-lecture series I will discuss the basics of string theory, some physical applications, and the outlook for the future. I will begin with the main concepts of the classical theory and the application to the study of cosmic superstrings. Then I will turn to the quantum theory and discuss applications to the investigation of hadronic spectra and the recently discovered quark-gluon plasma. I will conclude with a sketch of string models of particle physics and showing some avenues that may lead to a complete formulation of string theory.

  4. The approximability of the String Barcoding problem

    Directory of Open Access Journals (Sweden)

    Rizzi Romeo

    2006-08-01

    Full Text Available Abstract The String Barcoding (SBC problem, introduced by Rash and Gusfield (RECOMB, 2002, consists in finding a minimum set of substrings that can be used to distinguish between all members of a set of given strings. In a computational biology context, the given strings represent a set of known viruses, while the substrings can be used as probes for an hybridization experiment via microarray. Eventually, one aims at the classification of new strings (unknown viruses through the result of the hybridization experiment. In this paper we show that SBC is as hard to approximate as Set Cover. Furthermore, we show that the constrained version of SBC (with probes of bounded length is also hard to approximate. These negative results are tight.

  5. Testing string dynamics in lepton nucleus reactions

    Energy Technology Data Exchange (ETDEWEB)

    Gyulassy, M.; Pluemer, M.

    1989-10-01

    The sensitivity of nuclear attenuation of 10-100 GeV lepton nucleus ({ell}A) reactions to space-time aspects of hadronization is investigated within the context of the Lund string model. We consider two mechanisms for attenuation in a nucleus: final state cascading and string flip excitations. Implications for the evolution of the energy density in nuclear collisions are discussed. 16 refs., 10 figs.

  6. Electron string phenomenon: physics and use

    Science.gov (United States)

    Donets, Evgeny D.

    2004-01-01

    Electron string phenomenon arises as a result of phase transition of a state of multiply reflected electron beam to this new discovered state of one component electron plasma and can be easily observed in the reflex mode of EBIS operation. The transition goes via a strong instability, which causes considerable electron energy spread, which in its turn suppresses the instability. Electron string state is a stationary state of hot pure electron plasma, which is heated by injected electron beam and cooled because of electron loses. Electron string is quiet in broad regions of experimental parameters, so that it is used for confinement and ionization of positive ions by electron impact to highly charge states similar to electron beams in EBIS. Application of electron strings instead of electron beams for ion production allows to save about 99% of electric power of electron beam and simultaneously to improve reliability of an ion source considerably. The JINR EBIS `Krion-2' in the string mode of operation is used for production of N7+, Ar16+ and Fe24+ ion beams and their acceleration to relativistic energies on the facility of the JINR super conducting one turn injection synchrotron `Nuklotron'. The tubular electron string possibly can exist and it is under study now theoretically and experiments are prepared now. Estimations show that a Tubular Electron String Ion Source (TESIS) could have up to three orders of magnitude higher ion output then a Linear one (LESIS). In frames of nuclear astrophysics electron strings can be used for research of fusion nuclear reactions at low energies in conditions when both beam and target nuclei do not carry orbital electrons. The project NARITA — Nuclear Astrophysics Researches in an Ion Trap Apparatus is proposed. Polarization effects also can be studied.

  7. The Anthropic Landscape of String Theory

    OpenAIRE

    Susskind, Leonard

    2003-01-01

    In this lecture I make some educated guesses, about the landscape of string theory vacua. Based on the recent work of a number of authors, it seems plausible that the lanscape is unimaginably large and diverse. Whether we like it or not, this is the kind of behavior that gives credence to the Anthropic Principle. I discuss the theoretical and conceptual issues that arise in developing a cosmology based on the diversity of environments implicit in string theory.

  8. String field theory in the Siegel gauge

    Energy Technology Data Exchange (ETDEWEB)

    Bochicchio, M.

    1987-04-16

    We specialize the gauge-fixing procedure for the Witten action of the open bosonic string, given in a preceding paper, choosing the Siegel gauge. We find that the BRST-invariant gauge-fixed action is the gauge invariant one with ghost number unrestricted plus a gauge-fixing term. The BRST invariance of the measure in the functional integral is briefly discussed. As a technical tool the Hodge dual of a string functional is defined.

  9. The illusive sound of a Bundengan string

    Science.gov (United States)

    Parikesit, Gea O. F.; Kusumaningtyas, Indraswari

    2017-09-01

    The acoustics of a vibrating string is frequently used as a simple example of how physics can be applied in the field of art. In this paper we describe a simple experiment and analysis using a clipped string. This experiment can generate scientific curiosity among students because the sound generated by the string seem surprising to our senses. The first surprise comes from the gong-like sounds produced by the string, which we usually associate with metallic instruments rather than string instruments. The second surprise comes from the fact that when we shift the clip we perceive an increase of pitch, even though the measured value of the frequency with the maximum amplitude is actually decreased. We use high-speed video recording as well as audio spectral analysis to elucidate the physics behind these two surprises. A set of student activities is prepared to help them follow up their curiosity. Students can make their own clipped string, which is found in Indonesia in an instrument called Bundengan, by setting up their own prepared piano as invented by John Cage.

  10. String percolation threshold for elliptically bounded systems

    Science.gov (United States)

    Ramírez, J. E.; Fernández Téllez, A.; Bautista, I.

    2017-12-01

    It has been shown that a hot and dense deconfined nuclear matter state produced in ultra-relativistic heavy-ion collisions, can be quantitatively described by the String Percolation phenomenological model. The model address the phase transition in terms of the two-dimensional continuum percolation theory over strings, which are schematic representations of the fundamental interactions among the partons of the colliding nuclei in the initial state. In this work, we present an extension of the critical string density results including the eccentricity dependence on the initial state geometry focus on small string number with different density profile, small deviations from the different profile densities are found. The percolation threshold shows consistency with the thermodynamic limit for the uniform density profile with a large number of strings in the case of circular boundary system. A significant dependence on the eccentricity for a small number of strings compared to high occupancy systems is exhibited, the implications may become relevant in hadron-hadron or hadron-nucleus collision systems.

  11. String pair production in non homogeneous backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Bolognesi, S. [Department of Physics “E. Fermi” University of Pisa, and INFN - Sezione di Pisa,Largo Pontecorvo, 3, Ed. C, 56127 Pisa (Italy); Rabinovici, E. [Racah Institute of Physics, The Hebrew University of Jerusalem,91904 Jerusalem (Israel); Tallarita, G. [Departamento de Ciencias, Facultad de Artes Liberales,Universidad Adolfo Ibáñez, Santiago 7941169 (Chile)

    2016-04-28

    We consider string pair production in non homogeneous electric backgrounds. We study several particular configurations which can be addressed with the Euclidean world-sheet instanton technique, the analogue of the world-line instanton for particles. In the first case the string is suspended between two D-branes in flat space-time, in the second case the string lives in AdS and terminates on one D-brane (this realizes the holographic Schwinger effect). In some regions of parameter space the result is well approximated by the known analytical formulas, either the particle pair production in non-homogeneous background or the string pair production in homogeneous background. In other cases we see effects which are intrinsically stringy and related to the non-homogeneity of the background. The pair production is enhanced already for particles in time dependent electric field backgrounds. The string nature enhances this even further. For spacial varying electrical background fields the string pair production is less suppressed than the rate of particle pair production. We discuss in some detail how the critical field is affected by the non-homogeneity, for both time and space dependent electric field backgrouds. We also comment on what could be an interesting new prediction for the small field limit. The third case we consider is pair production in holographic confining backgrounds with homogeneous and non-homogeneous fields.

  12. Mechanical Properties of Nylon Harp Strings

    Directory of Open Access Journals (Sweden)

    Nicolas Lynch-Aird

    2017-05-01

    Full Text Available Monofilament nylon strings with a range of diameters, commercially marketed as harp strings, have been tested to establish their long-term mechanical properties. Once a string had settled into a desired stress state, the Young’s modulus was measured by a variety of methods that probe different time-scales. The modulus was found to be a strong function of testing frequency and also a strong function of stress. Strings were also subjected to cyclical variations of temperature, allowing various thermal properties to be measured: the coefficient of linear thermal expansion and the thermal sensitivities of tuning, Young’s modulus and density. The results revealed that the particular strings tested are divided into two groups with very different properties: stress-strain behaviour differing by a factor of two and some parametric sensitivities even having the opposite sign. Within each group, correlation studies allowed simple functional fits to be found to the key properties, which have the potential to be used in automated tuning systems for harp strings.

  13. Fast algorithms for approximate circular string matching.

    Science.gov (United States)

    Barton, Carl; Iliopoulos, Costas S; Pissis, Solon P

    2014-03-22

    Circular string matching is a problem which naturally arises in many biological contexts. It consists in finding all occurrences of the rotations of a pattern of length m in a text of length n. There exist optimal average-case algorithms for exact circular string matching. Approximate circular string matching is a rather undeveloped area. In this article, we present a suboptimal average-case algorithm for exact circular string matching requiring time O(n). Based on our solution for the exact case, we present two fast average-case algorithms for approximate circular string matching with k-mismatches, under the Hamming distance model, requiring time O(n) for moderate values of k, that is k=O(m/logm). We show how the same results can be easily obtained under the edit distance model. The presented algorithms are also implemented as library functions. Experimental results demonstrate that the functions provided in this library accelerate the computations by more than three orders of magnitude compared to a naïve approach. We present two fast average-case algorithms for approximate circular string matching with k-mismatches; and show that they also perform very well in practice. The importance of our contribution is underlined by the fact that the provided functions may be seamlessly integrated into any biological pipeline. The source code of the library is freely available at http://www.inf.kcl.ac.uk/research/projects/asmf/.

  14. Goedel universe from string theory

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shou-Long; Wei, Hao [Beijing Institute of Technology, School of Physics, Beijing (China); Feng, Xing-Hui; Lue, H. [Beijing Normal University, Department of Physics, Center for Advanced Quantum Studies, Beijing (China)

    2017-05-15

    The Goedel universe is a direct product of a line and a three-dimensional spacetime we call G{sub α}. In this paper, we show that the Goedel metrics can arise as exact solutions in Einstein-Maxwell-Axion, Einstein-Proca-Axion, or Freedman-Schwarz gauged supergravity theories. The last option allows us to embed the Goedel universe in string theory. The ten-dimensional spacetime is a direct product of a line and the nine-dimensional one of an S{sup 3} x S{sup 3} bundle over G{sub α}, and it can be interpreted as some decoupling limit of the rotating D1/D5/D5 intersection. For some appropriate parameter choice, the nine-dimensional metric becomes an AdS{sub 3} x S{sup 3} bundle over squashed 3-sphere. We also study the properties of the Goedel black holes that are constructed from the double Wick rotations of the Goedel metrics. (orig.)

  15. Antibody mapping and tissue localization of globular and cysteine-rich regions of perlecan domain III

    DEFF Research Database (Denmark)

    Couchman, J R; Ljubimov, A V; Sthanam, M

    1995-01-01

    Perlecan is the best-characterized basement membrane heparan sulfate proteoglycan. It has a large (approximately 400 KD) core protein consisting of five distinct domains. Domain III, a centrally located domain, contains three globular domains separated by cysteine-rich epidermal growth factor (EG...

  16. Improved stability of halohydrin dehalogenase from Agrobacterium radiobacter AD1 by replacement of cysteine residues

    NARCIS (Netherlands)

    Tang, Lixia; van Hylckama Vlieg, Johan E.T.; Lutje Spelberg, Jeffrey H.; Fraaije, Marco W.; Janssen, DB

    2002-01-01

    Halohydrin dehalogenase from Agrobacterium radiobacter AD1 is a homo-tetrameric protein containing three cysteines per 28 kDa subunit. Under oxidizing conditions the enzyme was found to be susceptible to inactivation which could be prevented by the addition of beta-mercaptoethanol or glycerol. Gel

  17. A Bayesian framework for cosmic string searches in CMB maps

    Science.gov (United States)

    Ciuca, Razvan; Hernández, Oscar F.

    2017-08-01

    There exists various proposals to detect cosmic strings from Cosmic Microwave Background (CMB) or 21 cm temperature maps. Current proposals do not aim to find the location of strings on sky maps, all of these approaches can be thought of as a statistic on a sky map. We propose a Bayesian interpretation of cosmic string detection and within that framework, we derive a connection between estimates of cosmic string locations and cosmic string tension Gμ. We use this Bayesian framework to develop a machine learning framework for detecting strings from sky maps and outline how to implement this framework with neural networks. The neural network we trained was able to detect and locate cosmic strings on noiseless CMB temperature map down to a string tension of Gμ=5 ×10-9 and when analyzing a CMB temperature map that does not contain strings, the neural network gives a 0.95 probability that Gμ<=2.3×10-9.

  18. CMB temperature bispectrum induced by cosmic strings

    Science.gov (United States)

    Hindmarsh, Mark; Ringeval, Christophe; Suyama, Teruaki

    2009-10-01

    The cosmic microwave background (CMB) bispectrum of the temperature anisotropies induced by a network of cosmic strings is derived for small angular scales, under the assumption that the principal cause of temperature fluctuations is the Gott-Kaiser-Stebbins effect. We provide analytical expressions for all isosceles triangle configurations in Fourier space. Their overall amplitude is amplified as the inverse cube of the angle and diverges for flat triangles. The isosceles configurations generically lead to a negative bispectrum with a power-law decay ℓ-6 for large multipole ℓ. However, collapsed triangles are found to be associated with a positive bispectrum whereas the squeezed triangles still exhibit negative values. We then compare our analytical estimates to a direct computation of the bispectrum from a set of 300 statistically independent temperature maps obtained from Nambu-Goto cosmic string simulations in a Friedmann-Lemaître-Robertson-Walker universe. We find good agreement for the overall amplitude, the power-law behavior, and the angle dependency of the various triangle configurations. At ℓ˜500 the cosmic string Gott-Kaiser-Stebbins effect contributes approximately the same equilateral CMB bispectrum amplitude as an inflationary model with |fNLloc|≃103, if the strings contribute about 10% of the temperature power spectrum at ℓ=10. Current bounds on fNL are not derived using cosmic string bispectrum templates, and so our fNL estimate cannot be used to derive bounds on strings. However it does suggest that string bispectrum templates should be included in the search of CMB non-Gaussianities.

  19. Vitamin B12 Inhibits Tau Fibrillization via Binding to Cysteine Residues of Tau.

    Science.gov (United States)

    Rafiee, Saharnaz; Asadollahi, Kazem; Riazi, Gholamhossein; Ahmadian, Shahin; Saboury, Ali Akbar

    2017-12-20

    Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregation including the regulation of cellular kinases and phosphatases activity and direct binding to tau protein. Vitamin B12 is one of the tau polymerization inhibitors, and its deficiency is linked to inactivation of protein phosphatase 2A and subsequently hyperphosphorylation and aggregation of tau protein. Regarding the structure and function of vitamin B12 and tau protein, we assumed that vitamin B12 is also able to directly bind to tau protein. Hence, we investigated the interaction of vitamin B12 with tau protein in vitro using fluorometry and circular dichrosim. Interaction studies was followed by investigation into the effect of vitamin B12 on tau aggregation using ThT fluorescence, circular dichroism, transmission electron microscopy, and SDS-PAGE. The results indicated that vitamin B12 interacts with tau protein and prevents fibrillization of tau protein. Blocking the cysteine residues of tau confirmed the cysteine-mediated binding of vitamin B12 to tau and showed that binding to cysteine is essential for inhibitory effect of vitamin B12 on tau aggregation. SDS-PAGE analysis indicated that vitamin B12 inhibits tau aggregation and that tau oligomers formed in the presence of vitamin B12 are mostly SDS-soluble. We propose that direct binding of vitamin B12 is another mechanism underlying the inhibitory role of vitamin B12 on tau aggregation and neurodegeneration.

  20. The influence of string length and repetition on chunking of digit strings.

    Science.gov (United States)

    Fendrich, David W; Arengo, Raina

    2004-08-01

    This study examined the effects of string length and repetitions on number processing with a data entry task. Participants read and entered strings of between three and eight digits and then typed them on the keypad of a computer. Chunking effects were found for all string lengths, with chunk sizes of as small as two digits. Chunk boundary placement varied depending on the length of a digit string, and chunking was avoided at positions between digit repetitions, even when those positions were otherwise common chunk boundaries. Digit repetitions significantly reduced the study time required to process a string prior to its entry. These results are interpreted as showing that flexible chunking strategies and the presence of repetitions are used to facilitate number processing.

  1. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt

    2011-01-01

    En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner.......En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner....

  2. 21 CFR 582.5271 - Cysteine.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cysteine. 582.5271 Section 582.5271 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

  3. (DHA) and L-cysteine supplementation

    African Journals Online (AJOL)

    ACER

    2012-02-21

    Feb 21, 2012 ... The aim of the present study was to investigate the effect of docosahexaenoic acid and L-cysteine supplementation on qualities of cryopreserved boar semen. A total of 30 ejaculates from 10 Yorkshire boars were included in the study. The semen was cryopreserved in lactose egg yolk base extender.

  4. Cysteine protease involving in autophagosomal degradation of mitochondria during encystation of Acanthamoeba.

    Science.gov (United States)

    Moon, Eun-Kyung; Hong, Yeonchul; Chung, Dong-Il; Kong, Hyun-Hee

    2012-10-01

    Using the microarray to identify encystation mediating factors, significantly higher expression of a cysteine protease gene was observed in cysts, compared with trophozoites. Results of real-time PCR analysis also showed a magnificent increase of cysteine protease levels during encystation of Acanthamoeba. We named the gene cyst specific cysteine protease (cscp) of Acanthamoeba. The purified recombinant protein of CSCP showed activities of papain and cathepsin B against the substrates. During encystation, EGFP fused CSCP showed colocalization with LysoTracker, an autophagosome marker, in transiently transfected amoeba. Amoeba transfected with siRNA against cscp was unable to form mature cysts. Undigested mitochondria in vacuole like structures were observed in cscp siRNA treated cells by transmission electron microscopy. These results provide evidence of the important role of CSCP in autophagosomal degradation of cell constituents, particularly mitochondria, during encystation of Acanthamoeba. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures.

    Science.gov (United States)

    Bostan, Hamed; Salim, Naomie; Hussein, Zeti Azura; Klappa, Peter; Shamsir, Mohd Shahir

    2012-01-01

    Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD) is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.

  6. CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures

    Directory of Open Access Journals (Sweden)

    Hamed Bostan

    2012-01-01

    Full Text Available Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.

  7. Electronic structures of the L-cysteine film on dental alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, K., E-mail: e7141@cc.saga-u.ac.jp [Synchrotron Light Application Center, Saga University, Saga 840-8502 (Japan); Tsujibayashi, T. [Department of Physics, Osaka Dental University, Osaka 573-1121 (Japan); Takahashi, K.; Azuma, J. [Synchrotron Light Application Center, Saga University, Saga 840-8502 (Japan); Kakimoto, K. [Department of Geriatric Dentistry, Osaka Dental University, Osaka 573-1121 (Japan); Kamada, M. [Synchrotron Light Application Center, Saga University, Saga 840-8502 (Japan)

    2011-04-15

    Research highlights: {yields} The electronic structures of dental alloys and L-cysteine film were studied by PES. {yields} The density of states in the dental alloy originates from Au and Cu as constituents. {yields} The Cu-3d states contribute dominantly to the occupied states near the Fermi level. {yields} The electronic structure of L-cysteine thin film is different from the thick film. {yields} The bonding between Cu-3d and S-3sp states are formed at the interface. - Abstract: Metal-organic interfaces have been attracting continuous attention in many fields including basic biosciences. The surface of dental alloys could be one of such interfaces since they are used in a circumstance full of organic compounds such as proteins and bacteria. In this work, electronic structures of Au-dominant dental alloys, which have Ag and Cu besides Au, and those of L-cysteine on the dental alloys have been studied by photoelectron spectroscopy with synchrotron radiation. It was found that the density of states in the dental alloy originate from gold and copper as constituents, and the Cu-3d states contribute dominantly to the occupied states near the Fermi level. It was also found that the electronic structure of the L-cysteine thin film on the dental alloy is different from that of the L-cysteine thick film. The result indicates the formation of the orbital bonding between Cu-3d and S-3sp states in the thin film on the dental alloy.

  8. T-Duality Group for Open String Theory

    OpenAIRE

    Kajiura, Hiroshige

    2001-01-01

    We study T-duality for open strings on tori $\\T^d$. The general boundary conditions for the open strings are constructed, and it is shown that T-duality group, which preserves the mass spectrum of closed strings, preserves also the mass spectrum of the open strings. The open strings are transformed to those with different boundary conditions by T-duality. We also discuss the T-duality for D-brane mass spectrum, and show that the D-branes and the open strings with both ends on them are transfo...

  9. Hypoallergenic Variant of the Major Egg White Allergen Gal d 1 Produced by Disruption of Cysteine Bridges.

    Science.gov (United States)

    Dhanapala, Pathum; Withanage-Dona, Dulashi; Tang, Mimi L K; Doran, Tim; Suphioglu, Cenk

    2017-02-21

    Gal d 1 (ovomucoid) is the dominant allergen in the chicken egg white. Hypoallergenic variants of this allergen can be used in immunotherapy as an egg allergy treatment approach. We hypothesised that disruption of two of the nine cysteine-cysteine bridges by site-directed mutagenesis will allow the production of a hypoallergenic variant of the protein; Methods: Two cysteine residues at C192 and C210 in domain III of the protein were mutated to alanine using site-directed mutagenesis, to disrupt two separate cysteine-cysteine bridges. The mutated and non-mutated proteins were expressed in Escherichia coli (E. coli) by induction with isopropyl β-d-1-thiogalactopyranoside (IPTG). The expressed proteins were analysed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting to confirm expression. Immunoglobulin E (IgE) reactivity of the two proteins was analysed, by immunoblotting, against a pool of egg-allergic patients' sera. A pool of non-allergic patients' sera was also used in a separate blot as a negative control; Results: Mutant Gal d 1 showed diminished IgE reactivity in the immunoblot by showing lighter bands when compared to the non-mutated version, although there was more of the mutant protein immobilised on the membrane when compared to the wild-type protein. The non-allergic negative control showed no bands, indicating an absence of non-specific binding of secondary antibody to the proteins; Conclusion: Disruption of two cysteine bridges in domain III of Gal d 1 reduces IgE reactivity. Following downstream laboratory and clinical testing, this mutant protein can be used in immunotherapy to induce tolerance to Gal d 1 and in egg allergy diagnosis.

  10. Hypoallergenic Variant of the Major Egg White Allergen Gal d 1 Produced by Disruption of Cysteine Bridges

    Directory of Open Access Journals (Sweden)

    Pathum Dhanapala

    2017-02-01

    Full Text Available Background: Gal d 1 (ovomucoid is the dominant allergen in the chicken egg white. Hypoallergenic variants of this allergen can be used in immunotherapy as an egg allergy treatment approach. We hypothesised that disruption of two of the nine cysteine-cysteine bridges by site-directed mutagenesis will allow the production of a hypoallergenic variant of the protein; Methods: Two cysteine residues at C192 and C210 in domain III of the protein were mutated to alanine using site-directed mutagenesis, to disrupt two separate cysteine-cysteine bridges. The mutated and non-mutated proteins were expressed in Escherichia coli (E. coli by induction with isopropyl β-d-1-thiogalactopyranoside (IPTG. The expressed proteins were analysed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE and immunoblotting to confirm expression. Immunoglobulin E (IgE reactivity of the two proteins was analysed, by immunoblotting, against a pool of egg-allergic patients’ sera. A pool of non-allergic patients’ sera was also used in a separate blot as a negative control; Results: Mutant Gal d 1 showed diminished IgE reactivity in the immunoblot by showing lighter bands when compared to the non-mutated version, although there was more of the mutant protein immobilised on the membrane when compared to the wild-type protein. The non-allergic negative control showed no bands, indicating an absence of non-specific binding of secondary antibody to the proteins; Conclusion: Disruption of two cysteine bridges in domain III of Gal d 1 reduces IgE reactivity. Following downstream laboratory and clinical testing, this mutant protein can be used in immunotherapy to induce tolerance to Gal d 1 and in egg allergy diagnosis.

  11. BOOK REVIEW: String Theory in a Nutshell

    Science.gov (United States)

    Skenderis, Kostas

    2007-11-01

    The book 'String Theory in a Nutshell' by Elias Kiritsis provides a comprehensive introduction to modern string theory. String theory is the leading candidate for a theory that successfully unifies all fundamental forces of nature, including gravity. The subject has been continuously developing since the early 1970s, with classic textbooks on the subject being those of Green, Schwarz and Witten (1987) and Polchinski (1998). Since the latter was published there have been substantial developments, in particular in understanding black holes and gravity/gauge theory dualities. A textbook treatment of this important material is clearly needed, both by students and researchers in string theory and by mathematicians and physicists working in related fields. This book has a good selection of material, starting from basics and moving into classic and modern topics. In particular, Kiritsis' presentation of the basic material is complementary to that of the earlier textbooks and he includes a number of topics which are not easily found or covered adequately elsewhere, for example, loop corrections to string effective couplings. Overall the book nicely covers the major advances of the last ten years, including (non-perturbative) string dualities, black hole physics, AdS/CFT and matrix models. It provides a concise but fairly complete introduction to these subjects which can be used both by students and by researchers. Moreover the emphasis is on results that are reasonably established, as is appropriate for a textbook; concise summaries are given for subjects which are still in flux, with references to relevant reviews and papers. A positive feature of the book is that the bibliography sections at the end of each chapter provide a comprehensive guide to the literature. The bibliographies point to reviews and pedagogical papers on subjects covered in this book as well as those that were omitted. It is rare for a textbook to contain such a self-contained and detailed guide to

  12. A Serendipitous Formation of a Cysteine-bridged Disaccharide ...

    African Journals Online (AJOL)

    N-acetyl-L-cysteine bearing free carboxylic acid and sulfhydryl groups was glycosylated with 1,2,3,4,6-Penta-O-acetyl-β- D-glucopyranoside in the presence of SnCl4 as a promoter to give the S-glycosylated cysteine in 64%yield. However, when excess donor was used, a previously unreported cysteine-bridged ...

  13. Septicemia caused by cysteine-dependent Escherichia coli.

    OpenAIRE

    Yuen, K Y; Seto, W H; Tsui, K H; Hui, W T

    1990-01-01

    A case of septicemia and urinary tract infection caused by cysteine-dependent Escherichia coli in a 70-year-old woman with bilateral staghorn calculi is described. This is the second report of a cysteine-dependent E. coli bacteremia. The bacterium was falsely susceptible to ampicillin and co-trimoxazole when tested on a medium without cysteine supplement.

  14. Nonassociativity, Malcev algebras and string theory

    Energy Technology Data Exchange (ETDEWEB)

    Guenaydin, M. [Institute for Gravitation and the Cosmos and Physics Department, Penn State University, University Park, PA (United States); Minic, D. [Department of Physics, Virginia Tech, Blacksburg, VA (United States)

    2013-10-15

    Nonassociative structures have appeared in the study of D-branes in curved backgrounds. In recent work, string theory backgrounds involving three-form fluxes, where such structures show up, have been studied in more detail. We point out that under certain assumptions these nonassociative structures coincide with nonassociative Malcev algebras which had appeared in the quantum mechanics of systems with non-vanishing three-cocycles, such as a point particle moving in the field of a magnetic charge. We generalize the corresponding Malcev algebras to include electric as well as magnetic charges. These structures find their classical counterpart in the theory of Poisson-Malcev algebras and their generalizations. We also study their connection to Stueckelberg's generalized Poisson brackets that do not obey the Jacobi identity and point out that nonassociative string theory with a fundamental length corresponds to a realization of his goal to find a non-linear extension of quantum mechanics with a fundamental length. Similar nonassociative structures are also known to appear in the cubic formulation of closed string field theory in terms of open string fields, leading us to conjecture a natural string-field theoretic generalization of the AdS/CFT-like (holographic) duality. (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  15. Comments On String Propagation Near Defects

    CERN Document Server

    Sahakyan, D

    2004-01-01

    This thesis investigates various aspects of string propagation near defects. In particular we study the effective theory describing NS5 branes in certain decoupling limit gs → 0, which is called Little String Theory (LST). The LST has a holographical description in terms of closed strings propagating in the near horizon geometry of NS5 branes. Using this description, we show that the high energy thermodynamics of LST is unstable; we exhibit a mode localized near the horizon of the black hole, which has mass that vanishes at high energy. We argue that the high temperature phase of the theory involves the condensation of this mode. Another aspect of the LST, which is addressed in the thesis, is the topological version of this theory. We argue that the topological LST is described in terms of N = 2 string in the background of NS5 branes. We show that this topological string can be used to efficiently compute the half-BPS F 4 terms in the low-energy effective action of the LST. Using the strong-weak c...

  16. Plant cysteine oxidases control the oxygen-dependent branch of the N-end-rule pathway.

    Science.gov (United States)

    Weits, Daan A; Giuntoli, Beatrice; Kosmacz, Monika; Parlanti, Sandro; Hubberten, Hans-Michael; Riegler, Heike; Hoefgen, Rainer; Perata, Pierdomenico; van Dongen, Joost T; Licausi, Francesco

    2014-03-06

    In plant and animal cells, amino-terminal cysteine oxidation controls selective proteolysis via an oxygen-dependent branch of the N-end rule pathway. It remains unknown how the N-terminal cysteine is specifically oxidized. Here we identify plant cysteine oxidase (PCO) enzymes that oxidize the penultimate cysteine of ERF-VII transcription factors by using oxygen as a co-substrate, thereby controlling the lifetime of these proteins. Consequently, ERF-VII proteins are stabilized under hypoxia and activate the molecular response to low oxygen while the expression of anaerobic genes is repressed in air. Members of the PCO family are themselves targets of ERF-VII transcription factors, generating a feedback loop that adapts the stress response according to the extent of the hypoxic condition. Our results reveal that PCOs act as sensor proteins for oxygen in plants and provide an example of how proactive regulation of the N-end rule pathway balances stress response to optimal growth and development in plants.

  17. Identification of a Novel Small Cysteine-Rich Protein in the Fraction from the Biocontrol Fusarium oxysporum Strain CS-20 that Mitigates Fusarium Wilt Symptoms and Triggers Defense Responses in Tomato

    OpenAIRE

    Shcherbakova, Larisa A.; Tatyana Igorevna Odintsova; Stakheev, Alexander A.; Fravel, Deborah R.; Sergey K. Zavriev

    2016-01-01

    The biocontrol effect of the non-pathogenic Fusarium oxysporum strain CS-20 against the tomato wilt pathogen F. oxysporum f. sp. lycopersici (FOL) has been previously reported to be primarily plant-mediated. This study shows that CS-20 produces proteins, which elicit defense responses in tomato plants. Three protein-containing fractions were isolated from CS-20 biomass using size exclusion chromatography. Exposure of seedling roots to one of these fractions prior to inoculation with pathogeni...

  18. Cysteine-based redox regulation and signalling in plants

    Directory of Open Access Journals (Sweden)

    Jérémy eCouturier

    2013-04-01

    Full Text Available Living organisms are subjected to oxidative stress conditions which are characterized by the production of reactive oxygen (ROS, nitrogen (RNS and sulfur (RSS species. In plants as in other organisms, many of these compounds have a dual function as they damage different types of macromolecules but they also likely fulfil an important role as secondary messengers. Owing to the reactivity of their thiol groups, some protein cysteine residues are particularly prone to oxidation by these molecules. In the past years, besides their recognized catalytic and regulatory functions, the modification of cysteine thiol group was increasingly viewed as either protective or redox signalling mechanisms. The most physiologically relevant reversible redox post-translational modifications (PTMs are disulfide bonds, sulfenic acids, S-glutathionylated adducts, S-nitrosothiols and to a lesser extent S-sulfenylamides, thiosulfinates and S-persulfides. These redox PTMs are mostly controlled by two oxidoreductase families, thioredoxins and glutaredoxins. This review focuses on recent advances highlighting the variety and physiological roles of these PTMs and the proteomic strategies used for their detection.

  19. Framework for the string theory landscape

    Science.gov (United States)

    Freivogel, B.; Susskind, L.

    2004-12-01

    It seems likely that string theory has a landscape of vacua that includes very many metastable de Sitter spaces. However, as emphasized by Banks, Dine, and Gorbatov, no current framework exists for examining these metastable vacua in string theory. In this paper we attempt to correct this situation by introducing an eternally inflating background in which the entire collection of accelerating cosmologies is present as intermediate states. The background is a classical solution which consists of a bubble of zero cosmological constant inside de Sitter space, separated by a domain wall. At early and late times the flat space region becomes infinitely big, so an S-matrix can be defined. Quantum mechanically, the system can tunnel to an intermediate state which is pure de Sitter space. We present evidence that a string theory S-matrix makes sense in this background, and that it contains metastable de Sitter space as an intermediate state.

  20. Little string origin of surface defects

    Science.gov (United States)

    Haouzi, Nathan; Schmid, Christian

    2017-05-01

    We derive a large class of codimension-two defects of 4d \\mathcal{N}=4 Super Yang-Mills (SYM) theory from the (2, 0) little string. The origin of the little string is type IIB theory compactified on an ADE singularity. The defects are D-branes wrapping the 2-cycles of the singularity. We use this construction to make contact with the description of SYM defects due to Gukov and Witten [1]. Furthermore, we provide a geometric perspective on the nilpotent orbit classification of codimension-two defects, and the connection to ADE-type Toda CFT. The only data needed to specify the defects is a set of weights of the algebra obeying certain constraints, which we give explicitly. We highlight the differences between the defect classification in the little string theory and its (2 , 0) CFT limit.

  1. Does string theory lead to extended inflation?

    Science.gov (United States)

    Campbell, Bruce A.; Linde, Andrei; Olive, Keith A.

    1991-05-01

    We consider the relationship between string theory and currently proposed models of extended inflation. In doing so, we discuss the conformal actions in string theory and in Jordan-Brans-Dicke gravity. We show explicitly the equivalence of pictures in which either gauge or gravitational couplings are changing with time. We demonstrate that the existence of the dilation in string theory does not naturally lead to extended inflation as currently discussed. We also discuss the resolution of the graceful exit problem of old inflation in Einstein gravity using either power-law inflation, or exponential inflation with a changing bubble formation rate. On leave of absence from School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455, USA.

  2. Noncommutativity of closed string zero modes

    Science.gov (United States)

    Freidel, Laurent; Leigh, Robert G.; Minic, Djordje

    2017-09-01

    We explore several consequences of the recently discovered intrinsic noncommutativity of the zero-mode sector of closed string theory. In particular, we illuminate the relation between T-duality and this intrinsic noncommutativity and also note that there is a simple closed string product, equivalent to the splitting-joining interaction of the pants diagram, that respects this noncommutativity and is covariant with respect to T-duality. We emphasize the central role played by the symplectic form ω on the space of zero modes. Furthermore, we begin an exploration of new noncommutative string backgrounds. In particular, we show that a constant nongeometric background field leads to a noncommutative space-time. We also comment on the nonassociativity that consequently arises in the presence of nontrivial flux. In this formulation, the H flux as well as the "nongeometric"Q , R , and F fluxes are simply the various components of the flux of an almost symplectic form.

  3. Hadronic density of states from string theory.

    Science.gov (United States)

    Pando Zayas, Leopoldo A; Vaman, Diana

    2003-09-12

    We present an exact calculation of the finite temperature partition function for the hadronic states corresponding to a Penrose-Güven limit of the Maldacena-Nùñez embedding of the N=1 super Yang-Mills (SYM) into string theory. It is established that the theory exhibits a Hagedorn density of states. We propose a semiclassical string approximation to the finite temperature partition function for confining gauge theories admitting a supergravity dual, by performing an expansion around classical solutions characterized by temporal windings. This semiclassical approximation reveals a hadronic energy density of states of a Hagedorn type, with the coefficient determined by the gauge theory string tension as expected for confining theories. We argue that our proposal captures primarily information about states of pure N=1 SYM theory, given that this semiclassical approximation does not entail a projection onto states of large U(1) charge.

  4. Tensor modes on the string theory landscape

    Energy Technology Data Exchange (ETDEWEB)

    Westphal, Alexander

    2012-06-15

    We attempt an estimate for the distribution of the tensor mode fraction r over the landscape of vacua in string theory. The dynamics of eternal inflation and quantum tunneling lead to a kind of democracy on the landscape, providing no bias towards large-field or small-field inflation regardless of the class of measure. The tensor mode fraction then follows the number frequency distributions of inflationary mechanisms of string theory over the landscape. We show that an estimate of the relative number frequencies for small-field vs large-field inflation, while unattainable on the whole landscape, may be within reach as a regional answer for warped Calabi-Yau flux compactifications of type IIB string theory.

  5. String lessons for higher-spin interactions

    Energy Technology Data Exchange (ETDEWEB)

    Sagnotti, A., E-mail: sagnotti@sns.i [Scuola Normale Superiore and INFN, Piazza dei Cavalieri, 7, I-56126 Pisa (Italy); Taronna, M., E-mail: m.taronna@sns.i [Scuola Normale Superiore and INFN, Piazza dei Cavalieri, 7, I-56126 Pisa (Italy)

    2011-01-21

    String Theory includes a plethora of higher-spin excitations, which clearly lie behind its most spectacular properties, but whose detailed behavior is largely unknown. Conversely, string interactions contain much useful information on higher-spin couplings, which can be very valuable in current attempts to characterize their systematics. We present a simplified form for the three-point (and four-point) amplitudes of the symmetric tensors belonging to the first Regge trajectory of the open bosonic string and relate them to local couplings and currents. These include the cases first discussed, from a field theory perspective, by Berends, Burgers and van Dam, and generalize their results in a suggestive fashion along lines recently explored by Boulanger, Metsaev and others. We also comment on the recovery of gauge symmetry in the low-tension limit, on the current-exchange amplitudes that can be built from these couplings and on the extension to mixed-symmetry states.

  6. String Lessons for Higher-Spin Interactions

    CERN Document Server

    Sagnotti, A

    2011-01-01

    String Theory includes a plethora of higher--spin excitations, which clearly lie behind its most spectacular properties, but whose detailed behavior is largely unknown. Conversely, string interactions contain much useful information on higher--spin couplings, which can be very valuable in current attempts to characterize their systematics. We present a simplified form for the three--point (and four--point) amplitudes of the symmetric tensors belonging to the first Regge trajectory of the open bosonic string and relate them to local couplings and currents. These include the cases first discussed, from a field theory perspective, by Berends, Burgers and van Dam, and generalize their results in a suggestive fashion along lines recently explored by Boulanger, Metsaev and others. We also comment on the recovery of gauge symmetry in the low--tension limit, on the current--exchange amplitudes that can be built from these couplings and on the extension to mixed--symmetry states.

  7. String theory and the scientific method

    CERN Document Server

    Dawid, Richard

    2013-01-01

    String theory has played a highly influential role in theoretical physics for nearly three decades and has substantially altered our view of the elementary building principles of the Universe. However, the theory remains empirically unconfirmed, and is expected to remain so for the foreseeable future. So why do string theorists have such a strong belief in their theory? This book explores this question, offering a novel insight into the nature of theory assessment itself. Dawid approaches the topic from a unique position, having extensive experience in both philosophy and high-energy physics. He argues that string theory is just the most conspicuous example of a number of theories in high-energy physics where non-empirical theory assessment has an important part to play. Aimed at physicists and philosophers of science, the book does not use mathematical formalism and explains most technical terms.

  8. Circular strings, wormholes, and minimum size

    Energy Technology Data Exchange (ETDEWEB)

    Garay, L.J.; Gonzalez-Diaz, P.F.; Mena Marugan, G.A.; Raya, J.M. [Centro de Fisica Miguel A. Catalan, Instituto de Matematicas y Fisica Fundamental, CSIC Serrano 121, 28006 Madrid (Spain)

    1997-06-01

    The quantization of circular strings in an anti{endash}de Sitter background spacetime is performed, obtaining a discrete spectrum for the string mass. A comparison with a four-dimensional homogeneous and isotropic spacetime coupled to a conformal scalar field shows that the string radius and the scale factor have the same classical solutions and that the quantum theories of these two models are formally equivalent. However, the physically relevant observables of these two systems have different spectra, although they are related to each other by a specific one-to-one transformation. We finally obtain a discrete spectrum for the spacetime size of both systems, which presents a nonvanishing lower bound. {copyright} {ital 1997} {ital The American Physical Society}

  9. Kahler stabilized, modular invariant heterotic string models

    Energy Technology Data Exchange (ETDEWEB)

    Gaillard, Mary K.; Gaillard, Mary K.; Nelson, Brent D.

    2007-03-19

    We review the theory and phenomenology of effective supergravity theories based on orbifold compactifications of the weakly-coupled heterotic string. In particular, we consider theories in which the four-dimensional theory displays target space modular invariance and where the dilatonic mode undergoes Kahler stabilization. A self-contained exposition of effective Lagrangian approaches to gaugino condensation and heterotic string theory is presented, leading to the development of the models of Binétruy, Gaillard and Wu. Various aspects of the phenomenology of this class of models are considered. These include issues of supersymmetry breaking and superpartner spectra, the role of anomalous U(1) factors, issues of flavor and R-parity conservation, collider signatures, axion physics, and early universe cosmology. For the vast majority of phenomenological considerations the theories reviewed here compare quite favorably to other string-derived models in the literature. Theoretical objections to the framework and directions for further research are identified and discussed.

  10. Directional drilling of a drill string

    Energy Technology Data Exchange (ETDEWEB)

    Forrest, J.; Catherall, R.; Stewar, W.M.; Pounds, R.J.

    1990-02-13

    A method is provide for controlling the direction of a drill bit at the downhole end of a drill string drilling from a surface. Two steerable stabilisers are provide at the downhole end of the drill string at locations spaced apart in the drilling direction. The orientation of the stabilisers is adjusted to create reactive forces from the bore hole to deflect the course of the bit in a desired direction. The stabilisers are suitably arranged eccentrically and circumferentially offset by 180 degrees {-+} 60 degree. In normal drilling, the drill string is rotated such that the stabilisers engage the bore hole to support a downhole motor against tilting. When off course drilling is sensed, the stabilisers are rotated to a position and stopped from rotation such that drilling forces generate reaction forces to cause a desired change of direction.

  11. Towards a Theory of the QCD String

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    I will review recent progress in understanding the dynamics of confining strings in non-supersymmetric gluodynamics in 3 and 4 space time dimensions. I will argue that the present lattice data allows to formulate a non-trivial straw man Ansatz for the worldsheet theory of long confining strings. According to this Ansatz, pure gluodynamics in 3D is described by a non-critical bosonic string theory without any extra local worldsheet degrees of freedom. I argue that the Ansatz allows to fix quantum numbers of (almost) all glueball states. I confront the resulting predictions with the properties of approximately 39 lightest glueball states observed on a lattice and find a good agreement.

  12. String theory--the physics of string-bending and other electric guitar techniques.

    Science.gov (United States)

    Grimes, David Robert

    2014-01-01

    Electric guitar playing is ubiquitous in practically all modern music genres. In the hands of an experienced player, electric guitars can sound as expressive and distinct as a human voice. Unlike other more quantised instruments where pitch is a discrete function, guitarists can incorporate micro-tonality and, as a result, vibrato and sting-bending are idiosyncratic hallmarks of a player. Similarly, a wide variety of techniques unique to the electric guitar have emerged. While the mechano-acoustics of stringed instruments and vibrating strings are well studied, there has been comparatively little work dedicated to the underlying physics of unique electric guitar techniques and strings, nor the mechanical factors influencing vibrato, string-bending, fretting force and whammy-bar dynamics. In this work, models for these processes are derived and the implications for guitar and string design discussed. The string-bending model is experimentally validated using a variety of strings and vibrato dynamics are simulated. The implications of these findings on the configuration and design of guitars is also discussed.

  13. String theory--the physics of string-bending and other electric guitar techniques.

    Directory of Open Access Journals (Sweden)

    David Robert Grimes

    Full Text Available Electric guitar playing is ubiquitous in practically all modern music genres. In the hands of an experienced player, electric guitars can sound as expressive and distinct as a human voice. Unlike other more quantised instruments where pitch is a discrete function, guitarists can incorporate micro-tonality and, as a result, vibrato and sting-bending are idiosyncratic hallmarks of a player. Similarly, a wide variety of techniques unique to the electric guitar have emerged. While the mechano-acoustics of stringed instruments and vibrating strings are well studied, there has been comparatively little work dedicated to the underlying physics of unique electric guitar techniques and strings, nor the mechanical factors influencing vibrato, string-bending, fretting force and whammy-bar dynamics. In this work, models for these processes are derived and the implications for guitar and string design discussed. The string-bending model is experimentally validated using a variety of strings and vibrato dynamics are simulated. The implications of these findings on the configuration and design of guitars is also discussed.

  14. String Theory - The Physics of String-Bending and Other Electric Guitar Techniques

    Science.gov (United States)

    Grimes, David Robert

    2014-01-01

    Electric guitar playing is ubiquitous in practically all modern music genres. In the hands of an experienced player, electric guitars can sound as expressive and distinct as a human voice. Unlike other more quantised instruments where pitch is a discrete function, guitarists can incorporate micro-tonality and, as a result, vibrato and sting-bending are idiosyncratic hallmarks of a player. Similarly, a wide variety of techniques unique to the electric guitar have emerged. While the mechano-acoustics of stringed instruments and vibrating strings are well studied, there has been comparatively little work dedicated to the underlying physics of unique electric guitar techniques and strings, nor the mechanical factors influencing vibrato, string-bending, fretting force and whammy-bar dynamics. In this work, models for these processes are derived and the implications for guitar and string design discussed. The string-bending model is experimentally validated using a variety of strings and vibrato dynamics are simulated. The implications of these findings on the configuration and design of guitars is also discussed. PMID:25054880

  15. Solution oxygen-17 NMR application for observing a peroxidized cysteine residue in oxidized human SOD1

    Science.gov (United States)

    Fujiwara, Noriko; Yoshihara, Daisaku; Sakiyama, Haruhiko; Eguchi, Hironobu; Suzuki, Keiichiro

    2016-12-01

    NMR active nuclei, 1H, 13C and 15N, are usually used for determination of protein structure. However, solution 17O-NMR application to proteins is extremely limited although oxygen is an essential element in biomolecules. Proteins are oxidized through cysteine residues by two types of oxidation. One is reversible oxidation such as disulphide bonding (Cys-S-S-Cys) and the other is irreversible oxidation to cysteine sulfinic acid (Cys-SO 2H) and cysteine sulfonic acid (Cys-SO 3H). Copper,Zinc-superoxide dismutase (SOD1) is a key enzyme in the protection of cells from the superoxide anion radical. The SH group at Cys 111 residue in human SOD1 is selectively oxidized to -SO 2H and -SO 3H with atmospheric oxygen, and this oxidized human SOD1 is also suggested to play an important role in the pathophysiology of various neurodegenerative diseases, probably mainly via protein aggregation. Therefore, information on the structural and the dynamics of the oxidized cysteine residue would be crucial for the understanding of protein aggregation mechanism. Although the -SO 3H group on proteins cannot be directly detected by conventional NMR techniques, we successfully performed the site-specific 17O-labeling of Cys 111 in SOD1 using ^{17}it {O}2 gas and the 17O-NMR analysis for the first time. We observed clear 17O signal derived from a protein molecule and show that 17O-NMR is a sensitive probe for studying the structure and dynamics of the 17O-labeled protein molecule. This novel and unique strategy can have great impact on many research fields in biology and chemistry.

  16. Chronometric Invariance and String Theory

    Science.gov (United States)

    Pollock, M. D.

    The Einstein-Hilbert Lagrangian R is expressed in terms of the chronometrically invariant quantities introduced by Zel'manov for an arbitrary four-dimensional metric gij. The chronometrically invariant three-space is the physical space γαβ = -gαβ+e2ϕ γαγβ, where e2ϕ = g00 and γα = g0α/g00, and whose determinant is h. The momentum canonically conjugate to γαβ is π α β =-√ {h}(Kα β -γ α β K), where Kα β =½ ∂ tγ α β and ∂t≡e-ϕ∂0 is the chronometrically invariant derivative with respect to time. The Wheeler-DeWitt equation for the wave function Ψ is derived. For a stationary space-time, such as the Kerr metric, παβ vanishes, implying that there is then no dynamics. The most symmetric, chronometrically-invariant space, obtained after setting ϕ = γα = 0, is Rα β =-λ (t)δ α β , where δαβ is constant and has curvature k. From the Friedmann and Raychaudhuri equations, we find that λ is constant only if k=1 and the source is a perfect fluid of energy-density ρ and pressure p=(γ-1)ρ, with adiabatic index γ=2/3, which is the value for a random ensemble of strings, thus yielding a three-dimensional de Sitter space embedded in four-dimensional space-time. Furthermore, Ψ is only invariant under the time-reversal operator {T} if γ=2/(2n-1), where n is a positive integer, the first two values n=1,2 defining the high-temperature and low-temperature limits ρ T±2, respectively, of the heterotic superstring theory, which are thus dual to one another in the sense T↔1/2π2α‧T.

  17. Gravitational Scattering Amplitudes and Closed String Field Theory in the Proper-Time Gauge

    OpenAIRE

    Lee, Taejin

    2017-01-01

    We construct a covariant closed string field theory by extending recent works on the covariant open string field theory in the proper-time gauge. Rewriting the string scattering amplitudes generated by the closed string field theory in terms of the Polyakov string path integrals, we identify the Fock space representations of the closed string vertices. We show that the Fock space representations of the closed string field theory may be completely factorized into those of the open string field...

  18. Entanglement branes in a two-dimensional string theory

    Science.gov (United States)

    Donnelly, William; Wong, Gabriel

    2017-09-01

    What is the meaning of entanglement in a theory of extended objects such as strings? To address this question we consider the spatial entanglement between two intervals in the Gross-Taylor model, the string theory dual to two-dimensional Yang-Mills theory at large N . The string diagrams that contribute to the entanglement entropy describe open strings with endpoints anchored to the entangling surface, as first argued by Susskind. We develop a canonical theory of these open strings, and describe how closed strings are divided into open strings at the level of the Hilbert space. We derive the modular Hamiltonian for the Hartle-Hawking state and show that the corresponding reduced density matrix describes a thermal ensemble of open strings ending on an object at the entangling surface that we call an entanglement brane, or E-brane.

  19. Deformation of the cubic open string field theory

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Taejin, E-mail: taejin@kangwon.ac.kr

    2017-05-10

    We study a consistent deformation of the cubic open bosonic string theory in such a way that the non-planar world sheet diagrams of the perturbative string theory are mapped onto their equivalent planar diagrams of the light-cone string field theory with some length parameters fixed. An explicit evaluation of the cubic string vertex in the zero-slope limit yields the correct relationship between the string coupling constant and the Yang–Mills coupling constant. The deformed cubic open string field theory is shown to produce the non-Abelian Yang–Mills action in the zero-slope limit if it is defined on multiple D-branes. Applying the consistent deformation systematically to multi-string world sheet diagrams, we may be able to calculate scattering amplitudes with an arbitrary number of external open strings.

  20. Deformation of the cubic open string field theory

    Directory of Open Access Journals (Sweden)

    Taejin Lee

    2017-05-01

    Full Text Available We study a consistent deformation of the cubic open bosonic string theory in such a way that the non-planar world sheet diagrams of the perturbative string theory are mapped onto their equivalent planar diagrams of the light-cone string field theory with some length parameters fixed. An explicit evaluation of the cubic string vertex in the zero-slope limit yields the correct relationship between the string coupling constant and the Yang–Mills coupling constant. The deformed cubic open string field theory is shown to produce the non-Abelian Yang–Mills action in the zero-slope limit if it is defined on multiple D-branes. Applying the consistent deformation systematically to multi-string world sheet diagrams, we may be able to calculate scattering amplitudes with an arbitrary number of external open strings.