WorldWideScience

Sample records for cyclic gmp-generating proteins

  1. Protein Misfolding Cyclic Amplification of Infectious Prions.

    Science.gov (United States)

    Moda, Fabio

    2017-01-01

    Transmissible spongiform encephalopathies, or prion diseases, are a group of incurable disorders caused by the accumulation of an abnormally folded prion protein (PrP(Sc)) in the brain. According to the "protein-only" hypothesis, PrP(Sc) is the infectious agent able to propagate the disease by acting as a template for the conversion of the correctly folded prion protein (PrP(C)) into the pathological isoform. Recently, the mechanism of PrP(C) conversion has been mimicked in vitro using an innovative technique named protein misfolding cyclic amplification (PMCA). This technology represents a great tool for studying diverse aspects of prion biology in the field of basic research and diagnosis. Moreover, PMCA can be expanded for the study of the misfolding process associated to other neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and frontotemporal lobar degeneration. © 2017 Elsevier Inc. All rights reserved.

  2. Protein misfolding cyclic amplification of infectious prions.

    Science.gov (United States)

    Morales, Rodrigo; Duran-Aniotz, Claudia; Diaz-Espinoza, Rodrigo; Camacho, Manuel V; Soto, Claudio

    2012-06-28

    Prions are proteinaceous infectious agents responsible for the transmission of prion diseases. The lack of a procedure for cultivating prions in the laboratory has been a major limitation to the study of the unorthodox nature of this infectious agent and the molecular mechanism by which the normal prion protein (PrP(C)) is converted into the abnormal isoform (PrP(Sc)). Protein misfolding cyclic amplification (PMCA), described in detail in this protocol, is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA involves incubating materials containing minute amounts of infectious prions with an excess of PrP(C) and boosting the conversion by cycles of sonication to fragment the converting units, thereby leading to accelerated prion replication. PMCA is able to detect the equivalent of a single molecule of infectious PrP(Sc) and propagate prions that maintain high infectivity, strain properties and species specificity. A single PMCA assay takes little more than 3 d to replicate a large amount of prions, which could take years in an in vivo situation. Since its invention 10 years ago, PMCA has helped to answer fundamental questions about this intriguing infectious agent and has been broadly applied in research areas that include the food industry, blood bank safety and human and veterinary disease diagnosis.

  3. ACTH, cyclic nucleotides, and brain protein phosphorylation in vitro

    NARCIS (Netherlands)

    Zwiers, H; Veldhuis, H D; Schotman, P; Gispen, W H

    1976-01-01

    Endogenous phosphorylation of proteins from rat brain synaptosomal plasma membranes was studied in vitro. Cyclic AMP (cAMP) markedly stimulated(32)P incorporation in three protein bands with molecular weights of 75,000, 57,000, and 54,000, respectively. The effect of the behaviorally active peptide

  4. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik;

    2014-01-01

    Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable...... protein-like structures in water. However, short peptides can be induced to fold into protein-like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine-tune three-dimensional structure. Such constrained cyclic...... peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...

  5. Identification of novel cyclic nucleotide binding proteins in Trypanosoma cruzi.

    Science.gov (United States)

    Jäger, Adriana V; De Gaudenzi, Javier G; Mild, Jesica G; Mc Cormack, Bárbara; Pantano, Sergio; Altschuler, Daniel L; Edreira, Martin M

    2014-12-01

    Cyclic AMP has been implicated as second messenger in a wide range of cellular processes. In the protozoan parasite Trypanosoma cruzi, cAMP is involved in the development of the parasite's life cycle. While cAMP effectors have been widely studied in other eukaryotic cells, little is known about cAMP's mechanism of action in T. cruzi. To date, only a cAMP-dependent protein kinase A (PKA) has been cloned and characterised in this parasite; however experimental evidence indicates the existence of cAMP-dependent, PKA-independent events. In order to identify new cAMP binding proteins as potential cAMP effectors, we carried out in silico studies using the predicted T. cruzi proteome. Using a combination of search methods 27 proteins with putative cNMP binding domains (CBDs) were identified. Phylogenetic analysis of the CBDs presented a homogeneous distribution, with sequences segregated into two main branches: one containing kinases-like proteins and the other gathering hypothetical proteins with different function or no other known. Comparative modelling of the strongest candidates provides support for the hypothesis that these proteins may give rise to structurally viable cyclic nucleotide binding domains. Pull-down and nucleotide displacement assays strongly suggest that TcCLB.508523.80 could bind cAMP and eventually be a new putative PKA-independent cAMP effector in T. cruzi.

  6. The critical roles of cyclic AMP/cyclic AMP-dependent protein kinase in platelet physiology

    Institute of Scientific and Technical Information of China (English)

    Rong YAN; Suping LI; Kesheng DAI

    2009-01-01

    Platelets are the primary players in both thrombosis and hemostasis.Cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are important signaling molecules in the regulation of platelet function,such as adhesion,aggregation,and secretion.Elevation of intracellular cAMP,which induces the activation of PKA,results in the inhibition of platelet function.Thus,tight control of the intracellular cAMP/PKA signaling pathway has great implications for platelet-dependent hemostasis and effective cardiovascular therapy.In this review,we summarize the PKA substrates and their contributions to platelet function,especially the advancing understanding of the cAMP/PKA-dependent signaling pathway in platelet physiology.In addition,we suggest the possibility that cAMP/PKA is involved in the platelet procoagulant process and receptor ectodomain shedding.

  7. Chemotaxis to cyclic AMP and folic acid is mediated by different G proteins in Dictyostelium discoideum

    NARCIS (Netherlands)

    Kesbeke, Fanja; Haastert, Peter J.M. van; Wit, René J.W. de; Snaar-Jagalska, B. Ewa

    1990-01-01

    Mutant Frigid A (fgdA) of Dictyostelium discoideum is defective in a functional Gα2 subunit of a G protein and is characterized by a complete blockade of the cyclic AMP-mediated sensory transduction steps, including cyclic AMP relay, chemotaxis and the cyclic GMP response. Folic acid-mediated transm

  8. Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms.

    Science.gov (United States)

    Chou, Shan-Ho; Galperin, Michael Y

    2016-01-01

    Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub)micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms.

  9. Cyclic coordinate descent: A robotics algorithm for protein loop closure.

    Science.gov (United States)

    Canutescu, Adrian A; Dunbrack, Roland L

    2003-05-01

    In protein structure prediction, it is often the case that a protein segment must be adjusted to connect two fixed segments. This occurs during loop structure prediction in homology modeling as well as in ab initio structure prediction. Several algorithms for this purpose are based on the inverse Jacobian of the distance constraints with respect to dihedral angle degrees of freedom. These algorithms are sometimes unstable and fail to converge. We present an algorithm developed originally for inverse kinematics applications in robotics. In robotics, an end effector in the form of a robot hand must reach for an object in space by altering adjustable joint angles and arm lengths. In loop prediction, dihedral angles must be adjusted to move the C-terminal residue of a segment to superimpose on a fixed anchor residue in the protein structure. The algorithm, referred to as cyclic coordinate descent or CCD, involves adjusting one dihedral angle at a time to minimize the sum of the squared distances between three backbone atoms of the moving C-terminal anchor and the corresponding atoms in the fixed C-terminal anchor. The result is an equation in one variable for the proposed change in each dihedral. The algorithm proceeds iteratively through all of the adjustable dihedral angles from the N-terminal to the C-terminal end of the loop. CCD is suitable as a component of loop prediction methods that generate large numbers of trial structures. It succeeds in closing loops in a large test set 99.79% of the time, and fails occasionally only for short, highly extended loops. It is very fast, closing loops of length 8 in 0.037 sec on average.

  10. EXPRESSED PROTEIN LIGATION. A NEW TOOL FOR THE BIOSYNTHESIS OF CYCLIC POLYPEPTIDES

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, R; Camarero, J A

    2004-11-11

    The present paper reviews the use of expressed protein ligation for the biosynthesis of backbone cyclic polypeptides. This general method allows the in vivo and in vitro biosynthesis of cyclic polypeptides using recombinant DNA expression techniques. Biosynthetic access to backbone cyclic peptides opens the possibility to generate cell-based combinatorial libraries that can be screened inside living cells for their ability to attenuate or inhibit cellular processes.

  11. Activation of the adenylyl cyclase/cyclic AMP/protein kinase A pathway in endothelial cells exposed to cyclic strain

    Science.gov (United States)

    Cohen, C. R.; Mills, I.; Du, W.; Kamal, K.; Sumpio, B. E.

    1997-01-01

    The aim of this study was to assess the involvement of the adenylyl cyclase/cyclic AMP/protein kinase A pathway (AC) in endothelial cells (EC) exposed to different levels of mechanical strain. Bovine aortic EC were seeded to confluence on flexible membrane-bottom wells. The membranes were deformed with either 150 mm Hg (average 10% strain) or 37.5 mm Hg (average 6% strain) vacuum at 60 cycles per minute (0.5 s strain; 0.5 s relaxation) for 0-60 min. The results demonstrate that at 10% average strain (but not 6% average strain) there was a 1.5- to 2.2-fold increase in AC, cAMP, and PKA activity by 15 min when compared to unstretched controls. Further studies revealed an increase in cAMP response element binding protein in EC subjected to the 10% average strain (but not 6% average strain). These data support the hypothesis that cyclic strain activates the AC/cAMP/PKA signal transduction pathway in EC which may occur by exceeding a strain threshold and suggest that cyclic strain may stimulate the expression of genes containing cAMP-responsive promoter elements.

  12. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

    Science.gov (United States)

    An, Shi-qi; Caly, Delphine L; McCarthy, Yvonne; Murdoch, Sarah L; Ward, Joseph; Febrer, Melanie; Dow, J Maxwell; Ryan, Robert P

    2014-10-01

    Bis-(3',5') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d)∼2 µM). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  13. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

    Directory of Open Access Journals (Sweden)

    Shi-qi An

    2014-10-01

    Full Text Available Bis-(3',5' cyclic di-guanylate (cyclic di-GMP is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc. This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d∼2 µM. Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  14. Detection of gamma-irradiation effect on DNA and protein using magnetic sensor and cyclic voltammetry.

    Science.gov (United States)

    Park, Duck-Gun; Song, Hoon; Kishore, M B; Vértesy, G; Lee, Duk-Hyun

    2013-11-01

    In this study, a magnetic sensor utilizing Planar Hall Resistance (PHR) and cyclic Voltammetry (CV) for detecting the radiation effect was fabricated. Specifically, we applied in parallel a PHR sensor and CV device to monitor the irradiation effect on DNA and protein respectively. Through parallel measurements, we demonstrated that the PHR sensor and CV are sensitive enough to measure irradiation effect. The PHR voltage decreased by magnetic nanobead labeled DNA was slightly recovered after gamma ray irradiation. The behavior of cdk inhibitor protein p21 having a sandwich structure of Au/protein G/Ab/Ag/Ab was checked by monitoring the cyclic Voltammetry signal in analyzing the gamma ray irradiation effect.

  15. Protein mimics by attachment of cyclic peptides to molecular scaffolds

    NARCIS (Netherlands)

    van de Langemheen, W.

    2014-01-01

    The interaction between proteins is important in all biological functions. In practically every cellular process protein complexes have been identified as essential components. Defects or disturbance in the regulation of protein-protein interactions are responsible for many diseases. Therefore, the

  16. Detection of cyclic di-AMP using a competitive ELISA with a unique pneumococcal cyclic di-AMP binding protein

    Science.gov (United States)

    Underwood, Adam J.; Zhang, Yang; Metzger, Dennis W.; Bai, Guangchun

    2014-01-01

    Cyclic di-AMP (c-di-AMP) is a signaling molecule that has been shown to play important roles in bacterial physiology and infections. Currently, c-di-AMP detection and quantification relies mostly on the use of high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS). In this study, a competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of c-di-AMP was developed, which utilizes a novel pneumococcal c-di-AMP binding protein (CabP) and a newly commercialized c-di-AMP derivative. With this new method, c-di-AMP concentrations in biological samples can be quickly and accurately quantified. Furthermore, this assay is much more efficient than current methods as it requires less overall cost and training while processing many samples at once. Therefore, this assay can be extensively used in research into c-di-AMP signaling. PMID:25239824

  17. cyclic monophosphate

    African Journals Online (AJOL)

    Administrator

    2006-10-02

    Oct 2, 2006 ... Second messengers are small transient molecules that transmit and/or modulate environmental or hormonal signals ... cyclases (pGCs), and soluble cytosolic guanylyl cyclases ... Figure 2. Model of cGMP generation and cGMP dependent cellular effects. ..... dynamics of colonic epithelial proliferation.

  18. Cyclic AMP-receptor proteins in heart muscle of rats flown on Cosmos 1887

    Science.gov (United States)

    Mednieks, Maija I.; Popova, Irina A.; Grindeland, Richard E.

    1991-01-01

    The cellular compartmentalization of the cyclic AMP-receptor proteins in heart ventricular tissue obtained from rats flown on the Cosmos 1887 is determined. Photoaffinity labeling of soluble and particular cell fractions with a (32P)-8-azido analog of cyclic AMP is followed by electrophoretic separation of the proteins and by autoradiographic identification of the labeled isoforms of cAPK R subunits. It is shown that RII in the particulate subcellular fraction was significantly decreased in heart cells from rats in the flight group when compared to controls. Protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins exhibited some variability in tissues of individual animals, but showed no changes that could be directly attributed to flight conditions. No significant change was apparent in the distribution of RI or RII cyclic AMP binding in the soluble fractions. It is inferred that the cardiac cell integrity or its protein content is not compromised under flight conditions.

  19. Cyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets.

    LENUS (Irish Health Repository)

    Gegenbauer, Kristina

    2013-11-01

    Regulator of G-protein signaling 18 (RGS18) is a GTPase-activating protein that turns off Gq signaling in platelets. RGS18 is regulated by binding to the adaptor protein 14-3-3 via phosphorylated serine residues S49 and S218 on RGS18. In this study we confirm that thrombin, thromboxane A2, or ADP stimulate the interaction of RGS18 and 14-3-3 by increasing the phosphorylation of S49. Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. To understand the effect of S216 phosphorylation we studied the phosphorylation kinetics of S49, S216, and S218 using Phos-tag gels and phosphorylation site-specific antibodies in transfected cells and in platelets. Cyclic nucleotide-induced detachment of 14-3-3 from RGS18 coincides initially with double phosphorylation of S216 and S218. This is followed by dephosphorylation of S49 and S218. Dephosphorylation of S49 and S218 might be mediated by protein phosphatase 1 (PP1) which is linked to RGS18 by the regulatory subunit PPP1R9B (spinophilin). We conclude that PKA and PKG induced S216 phosphorylation triggers the dephosphorylation of the 14-3-3 binding sites of RGS18 in platelets.

  20. Design of cyclic peptides that bind protein surfaces with antibody-like affinity.

    Science.gov (United States)

    Millward, Steven W; Fiacco, Stephen; Austin, Ryan J; Roberts, Richard W

    2007-09-21

    There is a pressing need for new molecular tools to target protein surfaces with high affinity and specificity. Here, we describe cyclic messenger RNA display with a trillion-member covalent peptide macrocycle library. Using this library, we have designed a number of high-affinity, redox-insensitive, cyclic peptides that target the signaling protein G alpha i1. In addition to cyclization, our library construction took advantage of an expanded genetic code, utilizing nonsense suppression to insert N-methylphenylalanine as a 21st amino acid. The designed macrocycles exhibit several intriguing features. First, the core motif seen in all of the selected variants is the same and shares an identical context with respect to the macrocyclic scaffold, consistent with the idea that selection simultaneously optimizes both the cyclization chemistry and the structural placement of the binding epitope. Second, detailed characterization of one molecule, cyclic G alpha i binding peptide (cycGiBP), demonstrates substantially enhanced proteolytic stability relative to that of the parent linear molecule. Third and perhaps most important, the cycGiBP peptide binds the target with very high affinity ( K i approximately 2.1 nM), similar to those of many of the best monoclonal antibodies and higher than that of the betagamma heterodimer, an endogenous G alpha i1 ligand. Overall the work provides a general route to design novel, low-molecular-weight, high-affinity ligands that target protein surfaces.

  1. Crystallization of a pentapeptide-repeat protein by reductive cyclic pentylation of free amines with glutaraldehyde

    Energy Technology Data Exchange (ETDEWEB)

    Vetting, Matthew W., E-mail: vetting@aecom.yu.edu; Hegde, Subray S.; Blanchard, John S. [Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

    2009-05-01

    A method to modify proteins with glutaraldehyde under reducing conditions is presented. Treatment with glutaraldehyde and dimethylaminoborane was found to result in cyclic pentylation of free amines and facilitated the structural determination of a protein previously recalcitrant to the formation of diffraction quality crystals. The pentapeptide-repeat protein EfsQnr from Enterococcus faecalis protects DNA gyrase from inhibition by fluoroquinolones. EfsQnr was cloned and purified to homogeneity, but failed to produce diffraction-quality crystals in initial crystallization screens. Treatment of EfsQnr with glutaraldehyde and the strong reducing agent borane–dimethylamine resulted in a derivatized protein which produced crystals that diffracted to 1.6 Å resolution; their structure was subsequently determined by single-wavelength anomalous dispersion. Analysis of the derivatized protein using Fourier transform ion cyclotron resonance mass spectrometry indicated a mass increase of 68 Da per free amino group. Electron-density maps about a limited number of structurally ordered lysines indicated that the modification was a cyclic pentylation of free amines, producing piperidine groups.

  2. Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

    Directory of Open Access Journals (Sweden)

    Hou Ssu-Yu

    2010-06-01

    Full Text Available Abstract Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors (statins have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin. Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2 formation, and phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP phosphorylation, and endothelial nitric oxide synthase (eNOS expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP-eNOS/NO-cyclic

  3. Moderate cyclic tensile strain alters the assembly of cartilage extracellular matrix proteins in vitro.

    Science.gov (United States)

    Bleuel, Judith; Zaucke, Frank; Brüggemann, Gert-Peter; Heilig, Juliane; Wolter, Marie-Louise; Hamann, Nina; Firner, Sara; Niehoff, Anja

    2015-06-01

    Mechanical loading influences the structural and mechanical properties of articular cartilage. The cartilage matrix protein collagen II essentially determines the tensile properties of the tissue and is adapted in response to loading. The collagen II network is stabilized by the collagen II-binding cartilage oligomeric matrix protein (COMP), collagen IX, and matrilin-3. However, the effect of mechanical loading on these extracellular matrix proteins is not yet understood. Therefore, the aim of this study was to investigate if and how chondrocytes assemble the extracellular matrix proteins collagen II, COMP, collagen IX, and matrilin-3 in response to mechanical loading. Primary murine chondrocytes were applied to cyclic tensile strain (6%, 0.5 Hz, 30 min per day at three consecutive days). The localization of collagen II, COMP, collagen IX, and matrilin-3 in loaded and unloaded cells was determined by immunofluorescence staining. The messenger ribo nucleic acid (mRNA) expression levels and synthesis of the proteins were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and western blots. Immunofluorescence staining demonstrated that the pattern of collagen II distribution was altered by loading. In loaded chondrocytes, collagen II containing fibrils appeared thicker and strongly co-stained for COMP and collagen IX, whereas the collagen network from unloaded cells was more diffuse and showed minor costaining. Further, the applied load led to a higher amount of COMP in the matrix, determined by western blot analysis. Our results show that moderate cyclic tensile strain altered the assembly of the extracellular collagen network. However, changes in protein amount were only observed for COMP, but not for collagen II, collagen IX, or matrilin-3. The data suggest that the adaptation to mechanical loading is not always the result of changes in RNA and/or protein expression but might also be the result of changes in matrix assembly and structure.

  4. A Novel Indirect Sequence Readout Component in the E. coli Cyclic AMP Receptor Protein Operator

    DEFF Research Database (Denmark)

    Lindemose, Søren; Nielsen, Peter Eigil; Valentin-Hansen, Poul

    2014-01-01

    binding sites in the E. coli genome, but the exact role of the N6 region in CRP interaction has not previously been systematic examined. Here we employ an in vitro selection system based on a randomized N6 spacer region to demonstrate that CRP binding to the lacP1 site may be enhanced up to 14-fold......The cyclic AMP receptor protein (CRP) from Escherichia coli has been extensively studied for several decades. In particular, a detailed characterization of CRP interaction with DNA has been obtained. The CRP dimer recognizes a consensus sequence AANTGTGANNNNNNTCACANTT through direct amino acid...

  5. Crystal structure of cyclic nucleotide-binding-like protein from Brucella abortus.

    Science.gov (United States)

    He, Zheng; Gao, Yuan; Dong, Jing; Ke, Yuehua; Li, Xuemei; Chen, Zeliang; Zhang, Xuejun C

    2015-12-25

    The cyclic nucleotide-binding (CNB)-like protein (CNB-L) from Brucella abortus shares sequence homology with CNB domain-containing proteins. We determined the crystal structure of CNB-L at 2.0 Å resolution in the absence of its C-terminal helix and nucleotide. The 3D structure of CNB-L is in a two-fold symmetric form. Each protomer shows high structure similarity to that of cGMP-binding domain-containing proteins, and likely mimics their nucleotide-free conformation. A key residue, Glu17, mediates the dimerization and prevents binding of cNMP to the canonical ligand-pocket. The structurally observed dimer of CNB-L is stable in solution, and thus is likely to be biologically relevant.

  6. Nuclear envelope proteins modulate proliferation of vascular smooth muscle cells during cyclic stretch application.

    Science.gov (United States)

    Qi, Ying-Xin; Yao, Qing-Ping; Huang, Kai; Shi, Qian; Zhang, Ping; Wang, Guo-Liang; Han, Yue; Bao, Han; Wang, Lu; Li, Hai-Peng; Shen, Bao-Rong; Wang, Yingxiao; Chien, Shu; Jiang, Zong-Lai

    2016-05-10

    Cyclic stretch is an important inducer of vascular smooth muscle cell (VSMC) proliferation, which is crucial in vascular remodeling during hypertension. However, the molecular mechanism remains unclear. We studied the effects of emerin and lamin A/C, two important nuclear envelope proteins, on VSMC proliferation in hypertension and the underlying mechano-mechanisms. In common carotid artery of hypertensive rats in vivo and in cultured cells subjected to high (15%) cyclic stretch in vitro, VSMC proliferation was increased significantly, and the expression of emerin and lamin A/C was repressed compared with normotensive or normal (5%) cyclic stretch controls. Using targeted siRNA to mimic the repressed expression of emerin or lamin A/C induced by 15% stretch, we found that VSMC proliferation was enhanced under static and 5%-stretch conditions. Overexpression of emerin or lamin A/C reversed VSMC proliferation induced by 15% stretch. Hence, emerin and lamin A/C play critical roles in suppressing VSMC hyperproliferation induced by hyperstretch. ChIP-on-chip and MOTIF analyses showed that the DNAs binding with emerin contain three transcription factor motifs: CCNGGA, CCMGCC, and ABTTCCG; DNAs binding with lamin A/C contain the motifs CVGGAA, GCCGCYGC, and DAAGAAA. Protein/DNA array proved that altered emerin or lamin A/C expression modulated the activation of various transcription factors. Furthermore, accelerating local expression of emerin or lamin A/C reversed cell proliferation in the carotid artery of hypertensive rats in vivo. Our findings establish the pathogenetic role of emerin and lamin A/C repression in stretch-induced VSMC proliferation and suggest mechanobiological mechanism underlying this process that involves the sequence-specific binding of emerin and lamin A/C to specific transcription factor motifs.

  7. Control of Vibrio fischeri lux gene transcription by a cyclic AMP receptor protein-luxR protein regulatory circuit.

    OpenAIRE

    1988-01-01

    Expression of the Vibrio fischeri luminescence genes (lux genes) requires two transcriptional activators: the V. fischeri luxR gene product with autoinducer and the cyclic AMP (cAMP) receptor protein (CRP) with cAMP. It has been established that autoinducer and the luxR gene product are required for transcriptional activation of the luxICDABE operon, which contains a gene required for autoinducer synthesis and genes required for light emission. However, the role of cAMP-CRP in the induction o...

  8. Purification and Characterization of Cyclic AMP-Binding Protein from Ganoderma lucidum

    Institute of Scientific and Technical Information of China (English)

    WANG Qi; KIM Jung-Sik; CHUNG Ki-Chul

    2004-01-01

    Cyclic AMP-binding protein was purified 30 fold from the mycelia of Ganoderma lucidum by the methods of ammonium sulfate precipitation, DEAE-cellulose, phospho-cellulose ion exchange chromatography and Sephacryl S-100 gel filtration. The molecular mass of the purified protein is 34.5 kDa and 17 kDa by Sephacryl S-100 gel filtration and SDS-ployacrylamide gel electrophoresis, respectively. From these results it is suggested that the protein has a homometric dimmer structure. The pI of the purified protein is pH 8. 2 by native isoelectric focusing gel. The half-life of the protein activity in 10% glycerol at 4 ℃ is 7 d in crude extract, but its half-life is only 3 d under purifying conditions. The optimal conditions of the protein activity are at 1 ℃ and pH 7. 5. Its activity is increased 6 times by 1 mmol/L Zn2+ and is slightly inhibited by cGMP,Cu2+ and Mn2+.

  9. Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein

    DEFF Research Database (Denmark)

    Zhang, Hang; Xiong, Xiao-feng; Boesgaard, Michael W

    2017-01-01

    Extracellular signals perceived by G protein-coupled receptors are transmitted via G proteins, and subsequent intracellular signaling cascades result in a plethora of physiological responses. The natural product cyclic depsipeptides YM-254890 and FR900359 are the only known compounds...

  10. The CytR repressor antagonizes cyclic AMP-cyclic AMP receptor protein activation of the deoCp2 promoter of Escherichia coli K-12

    DEFF Research Database (Denmark)

    Søgaard-Andersen, L; Martinussen, J; Møllegaard, N E

    1990-01-01

    We have investigated the regulation of the Escherichia coli deoCp2 promoter by the CytR repressor and the cyclic AMP (cAMP) receptor protein (CRP) complexed to cAMP. Promoter regions controlled by these two proteins characteristically contain tandem cAMP-CRP binding sites. Here we show that (i) C...... are required for efficient CytR repression of deoCp2. Models for the action of CytR are discussed in light of these findings.......We have investigated the regulation of the Escherichia coli deoCp2 promoter by the CytR repressor and the cyclic AMP (cAMP) receptor protein (CRP) complexed to cAMP. Promoter regions controlled by these two proteins characteristically contain tandem cAMP-CRP binding sites. Here we show that (i) Cyt......R selectively regulated cAMP-CRP-dependent initiations, although transcription started from the same site in deoCp2 in the absence or presence of cAMP-CRP; (ii) deletion of the uppermost cAMP-CRP target (CRP-2) resulted in loss of CytR regulation, but had only a minor effect on positive control by the c...

  11. Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclic amplification with beads (PMCAb.

    Directory of Open Access Journals (Sweden)

    Chad J Johnson

    Full Text Available Protein misfolding cyclic amplification (PMCA has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD agent without compromising the specificity of the assay (i.e., no false positive results. Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7 × 10(-13 dilution of 10% brain homogenate (1.3 fg of source brain. Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP1536(+/- mice allowed detection of CWD agent from the 10(-6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 10(5. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility.

  12. Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclical amplification with beads (PMCAb)

    Science.gov (United States)

    Johnson, Chad J.; Aiken, Judd M.; McKenzie, Debbie; Samuel, Michael D.; Pedersen, Joel A.

    2012-01-01

    Protein misfolding cyclic amplification (PMCA) has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb) has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD) agent without compromising the specificity of the assay (i.e., no false positive results). Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7×10−13 dilution of 10% brain homogenate (1.3 fg of source brain). Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP)1536+/−mice) allowed detection of CWD agent from the 10−6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 105. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility.

  13. Structure-Based Design and Synthesis of Potent Cyclic Peptides Inhibiting the YAP-TEAD Protein-Protein Interaction.

    Science.gov (United States)

    Zhang, Zhisen; Lin, Zhaohu; Zhou, Zheng; Shen, Hong C; Yan, S Frank; Mayweg, Alexander V; Xu, Zhiheng; Qin, Ning; Wong, Jason C; Zhang, Zhenshan; Rong, Yiping; Fry, David C; Hu, Taishan

    2014-09-11

    The YAP-TEAD protein-protein interaction (PPI) mediates the oncogenic function of YAP, and inhibitors of this PPI have potential usage in treatment of YAP-involved cancers. Here we report the design and synthesis of potent cyclic peptide inhibitors of the YAP-TEAD interaction. A truncation study of YAP interface 3 peptide identified YAP(84-100) as a weak peptide inhibitor (IC50 = 37 μM), and an alanine scan revealed a beneficial mutation, D94A. Subsequent replacement of a native cation-π interaction with an optimized disulfide bridge for conformational constraint and synergistic effect between macrocyclization and modification at positions 91 and 93 greatly boosted inhibitory activity. Peptide 17 was identified with an IC50 of 25 nM, and the binding affinity (K d = 15 nM) of this 17mer peptide to TEAD1 proved to be stronger than YAP(50-171) (K d = 40 nM).

  14. Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence- accelerated mouse

    Institute of Scientific and Technical Information of China (English)

    Zhanwei Zhang; Ting Zhang; Keli Dong

    2012-01-01

    At 8 weeks after intragastric administration of icariin to senescence-accelerated mice (P8 strain), Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increased. Immunohistochemical staining and western blot assay detected signifi-cantly increased levels of cyclic adenosine monophosphate response element binding protein. These results suggest that icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels and improves learning and memory functions in hippo-campus of the senescence-accelerated mouse.

  15. Cyclic AMP-dependent protein kinase phosphorylation facilitates GABA(B) receptor-effector coupling.

    Science.gov (United States)

    Couve, A; Thomas, P; Calver, A R; Hirst, W D; Pangalos, M N; Walsh, F S; Smart, T G; Moss, S J

    2002-05-01

    GABA (gamma-aminobutyric acid)(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). Basal phosphorylation of this residue is evident in rat brain membranes and in cultured neurons. Phosphorylation of Ser892 is modulated positively by pathways that elevate cAMP concentration, such as those involving forskolin and beta-adrenergic receptors. GABA(B) receptor agonists reduce receptor phosphorylation, which is consistent with PKA functioning in the control of GABA(B)-activated currents. Mechanistically, phosphorylation of Ser892 specifically enhances the membrane stability of GABA(B) receptors. We conclude that signaling pathways that activate PKA may have profound effects on GABA(B) receptor-mediated synaptic inhibition. These results also challenge the accepted view that phosphorylation is a universal negative modulator of G protein-coupled receptors.

  16. Detection of cyclic diguanylate G-octaplex assembly and interaction with proteins.

    Directory of Open Access Journals (Sweden)

    Ori J Lieberman

    Full Text Available Bacterial signaling networks control a wide variety of cellular processes including growth, metabolism, and pathogenesis. Bis-(3'-5'-cyclic dimeric guanosine monophosphate (cdiGMP is a secondary signaling nucleotide that controls cellulose synthesis, biofilm formation, motility and virulence in a wide range of gram-negative bacterial species. CdiGMP is a dynamic molecule that forms different tertiary structures in vitro, including a trans-monomer, cis-monomer, cis-dimer and G-octaplex (G8. Although the monomer and dimer have been shown to be physiologically relevant in modulating protein activity and transcription, the biological effects of the cdiGMP G8 has not yet been described. Here, we have developed a TLC-based assay to detect radiolabeled cdiGMP G8 formation. Utilizing the radiolabeled cdiGMP G8, we have also shown a novel inhibitory interaction between the cdiGMP G8 and HIV-1 reverse transcriptase and that the cdiGMP G8 does not interact with proteins from Pseudomonas aeruginosa known to bind monomeric and dimeric cdiGMP. These results suggest that the radiolabeled cdiGMP G8 can be used to measure interactions between the cdiGMP G8 and cellular proteins, providing an avenue through which the biological significance of this molecule could be investigated.

  17. Detection of cyclic diguanylate G-octaplex assembly and interaction with proteins.

    Science.gov (United States)

    Lieberman, Ori J; DeStefano, Jeffrey J; Lee, Vincent T

    2013-01-01

    Bacterial signaling networks control a wide variety of cellular processes including growth, metabolism, and pathogenesis. Bis-(3'-5')-cyclic dimeric guanosine monophosphate (cdiGMP) is a secondary signaling nucleotide that controls cellulose synthesis, biofilm formation, motility and virulence in a wide range of gram-negative bacterial species. CdiGMP is a dynamic molecule that forms different tertiary structures in vitro, including a trans-monomer, cis-monomer, cis-dimer and G-octaplex (G8). Although the monomer and dimer have been shown to be physiologically relevant in modulating protein activity and transcription, the biological effects of the cdiGMP G8 has not yet been described. Here, we have developed a TLC-based assay to detect radiolabeled cdiGMP G8 formation. Utilizing the radiolabeled cdiGMP G8, we have also shown a novel inhibitory interaction between the cdiGMP G8 and HIV-1 reverse transcriptase and that the cdiGMP G8 does not interact with proteins from Pseudomonas aeruginosa known to bind monomeric and dimeric cdiGMP. These results suggest that the radiolabeled cdiGMP G8 can be used to measure interactions between the cdiGMP G8 and cellular proteins, providing an avenue through which the biological significance of this molecule could be investigated.

  18. Using protein misfolding cyclic amplification generates a highly neurotoxic PrP dimer causing neurodegeneration.

    Science.gov (United States)

    Yang, XiuJin; Yang, LiFeng; Zhou, XiangMei; Khan, Sher Hayat; Wang, HuiNuan; Yin, XiaoMin; Yuan, Zhen; Song, ZhiQi; Wu, WenYu; Zhao, DeMing

    2013-11-01

    Under the "protein-only" hypothesis, prion-based diseases are proposed to result from an infectious agent that is an abnormal isoform of the prion protein in the scrapie form, PrP(Sc). However, since PrP(Sc) is highly insoluble and easily aggregates in vivo, this view appears to be overly simplistic, implying that the presence of PrP(Sc) may indirectly cause neurodegeneration through its intermediate soluble form. We generated a neurotoxic PrP dimer with partial pathogenic characteristics of PrP(Sc) by protein misfolding cyclic amplification in the presence of 1-palmitoyl-2-oleoylphosphatidylglycerol consisting of recombinant hamster PrP (23-231). After intracerebral injection of the PrP dimer, wild-type hamsters developed signs of neurodegeneration. Clinical symptoms, necropsy findings, and histopathological changes were very similar to those of transmissible spongiform encephalopathies. Additional investigation showed that the toxicity is primarily related to cellular apoptosis. All results suggested that we generated a new neurotoxic form of PrP, PrP dimer, which can cause neurodegeneration. Thus, our study introduces a useful model for investigating PrP-linked neurodegenerative mechanisms.

  19. Post-translational Analysis of Arabidopsis thaliana Proteins in Response to Cyclic Guanosine Monophosphate Treatment

    KAUST Repository

    Parrott, Brian

    2011-12-12

    The introduction of mass spectrometry techniques to the field of biology has made possible the exploration of the proteome as a whole system as opposed to prior techniques, such as anti-body based assays or yeast two-hybrid studies, which were strictly limited to the study of a few proteins at a time. This practice has allowed for a systems biology approach of exploring the proteome, with the possibility of viewing entire pathways over increments of time. In this study, the effect of treating Arabidopsis thaliana suspension culture cells with 3’,5’-cyclic guanosine monophosphate (cGMP), which is a native second messenger, was examined. Samples were collected at four time points and proteins were extracted and enriched for both oxidation and phosphorylation before analysis via mass spectrometry. Preliminary results suggest a tendency towards an increased number of phosphorylated proteins as a result of cGMP treatment. The data also showed a sharp increase in methionine oxidation in response to the treatment, occurring within the first ten minutes. This finding suggests that cGMP may utilize methionine oxidation as a mechanism of signal transduction. As such, this study corroborates a growing body of evidence supporting the inclusion of methionine oxidation in intracellular signaling pathways.

  20. The CytR repressor antagonizes cyclic AMP-cyclic AMP receptor protein activation of the deoCp2 promoter of Escherichia coli K-12

    DEFF Research Database (Denmark)

    Søgaard-Andersen, Lotte; Martinussen, J; Møllegaard, N E

    1990-01-01

    We have investigated the regulation of the Escherichia coli deoCp2 promoter by the CytR repressor and the cyclic AMP (cAMP) receptor protein (CRP) complexed to cAMP. Promoter regions controlled by these two proteins characteristically contain tandem cAMP-CRP binding sites. Here we show that (i) Cyt......R selectively regulated cAMP-CRP-dependent initiations, although transcription started from the same site in deoCp2 in the absence or presence of cAMP-CRP; (ii) deletion of the uppermost cAMP-CRP target (CRP-2) resulted in loss of CytR regulation, but had only a minor effect on positive control by the c...... are required for efficient CytR repression of deoCp2. Models for the action of CytR are discussed in light of these findings....

  1. Rgg protein structure-function and inhibition by cyclic peptide compounds.

    Science.gov (United States)

    Parashar, Vijay; Aggarwal, Chaitanya; Federle, Michael J; Neiditch, Matthew B

    2015-04-21

    Peptide pheromone cell-cell signaling (quorum sensing) regulates the expression of diverse developmental phenotypes (including virulence) in Firmicutes, which includes common human pathogens, e.g., Streptococcus pyogenes and Streptococcus pneumoniae. Cytoplasmic transcription factors known as "Rgg proteins" are peptide pheromone receptors ubiquitous in Firmicutes. Here we present X-ray crystal structures of a Streptococcus Rgg protein alone and in complex with a tight-binding signaling antagonist, the cyclic undecapeptide cyclosporin A. To our knowledge, these represent the first Rgg protein X-ray crystal structures. Based on the results of extensive structure-function analysis, we reveal the peptide pheromone-binding site and the mechanism by which cyclosporin A inhibits activation of the peptide pheromone receptor. Guided by the Rgg-cyclosporin A complex structure, we predicted that the nonimmunosuppressive cyclosporin A analog valspodar would inhibit Rgg activation. Indeed, we found that, like cyclosporin A, valspodar inhibits peptide pheromone activation of conserved Rgg proteins in medically relevant Streptococcus species. Finally, the crystal structures presented here revealed that the Rgg protein DNA-binding domains are covalently linked across their dimerization interface by a disulfide bond formed by a highly conserved cysteine. The DNA-binding domain dimerization interface observed in our structures is essentially identical to the interfaces previously described for other members of the XRE DNA-binding domain family, but the presence of an intermolecular disulfide bond buried in this interface appears to be unique. We hypothesize that this disulfide bond may, under the right conditions, affect Rgg monomer-dimer equilibrium, stabilize Rgg conformation, or serve as a redox-sensitive switch.

  2. The RGS protein Crg2 regulates pheromone and cyclic AMP signaling in Cryptococcus neoformans.

    Science.gov (United States)

    Shen, Gui; Wang, Yan-Li; Whittington, Amy; Li, Lie; Wang, Ping

    2008-09-01

    Crg1 and Crg2 are regulators of G-protein signaling homologs found in the human fungal pathogen Cryptococcus neoformans. Crg1 negatively regulates pheromone responses and mating through direct inhibition of Galpha subunits Gpa2 and Gpa3. It has also been proposed that Crg2 has a role in mating, as genetic crosses involving Deltacrg2 mutants resulted in formation of hyperfilaments. We found that mutation of Gpa2 and Gpa3 partially suppressed the hyperfilamentation, mutation of Gpa3 alleviated Deltacrg2-specfic cell swelling, and mutation of the mitogen-activated protein kinase Cpk1 blocked both processes. These findings indicate that Gpa2 and Gpa3 function downstream of Crg2 and that Gpa3 is also epistatic to Crg2 in a Cpk1-dependent morphogenesis process linked to mating. Significantly, we found that Deltacrg2 mutants formed enlarged capsules that mimic cells expressing a constitutively active GPA1(Q284L) allele and that the levels of intracellular cyclic AMP (cAMP) were also elevated, suggesting that Crg2 also negatively regulates the Gpa1-cAMP signaling pathway. We further showed that Crg2 interacted with Gpa3 and Gpa1, but not Gpa2, in a pulldown assay and that Crg2 maintained a higher in vitro GTPase-activating protein activity toward Gpa3 and Gpa1 than to Gpa2. Finally, we found that dysregulation of cAMP due to the Crg2 mutation attenuated virulence in a murine model of cryptococcosis. Taken together, our study reveals Crg2 as an RGS (regulator of G-protein signaling) protein of multiregulatory function, including one that controls mating distinctly from Crg1 and one that serves as a novel inhibitor of Gpa1-cAMP signaling.

  3. Pre-symptomatic detection of prions by cyclic amplification of protein misfolding.

    Science.gov (United States)

    Soto, Claudio; Anderes, Laurence; Suardi, Silvia; Cardone, Franco; Castilla, Joaquin; Frossard, Marie-Jose; Peano, Sergio; Saa, Paula; Limido, Lucia; Carbonatto, Michaela; Ironside, James; Torres, Juan-Maria; Pocchiari, Maurizio; Tagliavini, Fabrizio

    2005-01-31

    Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders affecting humans and animals. At present, it is not possible to recognize individuals incubating the disease before the clinical symptoms appear. We investigated the effectiveness of the "Protein Misfolding Cyclic Amplification" (PMCA) technology to detect the protease-resistance disease-associated prion protein (PrP(res)) in pre-symptomatic stages. PMCA allowed detection of PrP(res) in the brain of pre-symptomatic hamsters, enabling a clear identification of infected animals as early as two weeks after inoculation. Furthermore, PMCA was able to amplify minute quantities of PrP(res) from a variety of experimental and natural TSEs. Finally, PMCA allowed the demonstration of PrP(res) in an experimentally infected cow 32 month post-inoculation, that did not show clinical signs and was negative by standard Western blot analysis. Our findings indicate that PMCA may be useful for the development of an ultra-sensitive diagnostic test to minimize the risk of further propagation of TSEs.

  4. Hindbrain raphe stimulation boosts cyclic adenosine monophosphate and signaling proteins in the injured spinal cord.

    Science.gov (United States)

    Carballosa-Gonzalez, Melissa M; Vitores, Alberto; Hentall, Ian D

    2014-01-16

    Early recovery from incomplete spinal cord contusion is improved by prolonged stimulation of the hindbrain's serotonergic nucleus raphe magnus (NRM). Here we examine whether increases in cyclic adenosine monophosphate (cAMP), an intracellular signaling molecule with several known restorative actions on damaged neural tissue, could play a role. Subsequent changes in cAMP-dependent phosphorylation of protein kinase A (PKA) and PKA-dependent phosphorylation of the transcription factor "cAMP response element-binding protein" (CREB) are also analyzed. Rats with moderate weight-drop injury at segment T8 received 2h of NRM stimulation beginning three days after injury, followed immediately by separate extraction of cervical, thoracic and lumbar spinal cord for immunochemical assay. Controls lacked injury, stimulation or both. Injury reduced cAMP levels to under half of normal in all three spinal regions. NRM stimulation completely restored these levels, while producing no significant change in non-injured rats. Pretreatment with the 5-HT7 receptor antagonist pimozide (1 mg/kg, intraperitoneal) lowered cAMP in non-injured rats to injury amounts, which were unchanged by NRM stimulation. The phosphorylated fraction of PKA (pPKA) and CREB (pCREB) was reduced significantly in all three regions after SCI and restored by NRM stimulation, except for pCREB in lumbar segments. In conclusion, SCI produces spreading deficits in cAMP, pPKA and pCREB that are reversible by Gs protein-coupled 5-HT receptors responding to raphe-spinal activity, although these signaling molecules are not reactive to NRM stimulation in normal tissue. These findings can partly explain the benefits of NRM stimulation after SCI. © 2013 Published by Elsevier B.V.

  5. Cyclic AMP Receptor Protein Acts as a Transcription Regulator in Response to Stresses in Deinococcus radiodurans.

    Directory of Open Access Journals (Sweden)

    Su Yang

    Full Text Available The cyclic AMP receptor protein family of transcription factors regulates various metabolic pathways in bacteria, and also play roles in response to environmental changes. Here, we identify four homologs of the CRP family in Deinococcus radiodurans, one of which tolerates extremely high levels of oxidative stress and DNA-damaging reagents. Transcriptional levels of CRP were increased under hydrogen peroxide (H2O2 treatment during the stationary growth phase, indicating that CRPs function in response to oxidative stress. By constructing all CRP single knockout mutants, we found that the dr0997 mutant showed the lowest tolerance toward H2O2, ultraviolet radiation, ionizing radiation, and mitomycin C, while the phenotypes of the dr2362, dr0834, and dr1646 mutants showed slight or no significant differences from those of the wild-type strain. Taking advantage of the conservation of the CRP-binding site in many bacteria, we found that transcription of 18 genes, including genes encoding chromosome-partitioning protein (dr0998, Lon proteases (dr0349 and dr1974, NADH-quinone oxidoreductase (dr1506, thiosulfate sulfurtransferase (dr2531, the DNA repair protein UvsE (dr1819, PprA (dra0346, and RecN (dr1447, are directly regulated by DR0997. Quantitative real-time polymerase chain reaction (qRT-PCR analyses showed that certain genes involved in anti-oxidative responses, DNA repair, and various cellular pathways are transcriptionally attenuated in the dr0997 mutant. Interestingly, DR0997 also regulate the transcriptional levels of all CRP genes in this bacterium. These data suggest that DR0997 contributes to the extreme stress resistance of D. radiodurans via its regulatory role in multiple cellular pathways, such as anti-oxidation and DNA repair pathways.

  6. A novel indirect sequence readout component in the E. coli cyclic AMP receptor protein operator.

    Science.gov (United States)

    Lindemose, Søren; Nielsen, Peter Eigil; Valentin-Hansen, Poul; Møllegaard, Niels Erik

    2014-03-21

    The cyclic AMP receptor protein (CRP) from Escherichia coli has been extensively studied for several decades. In particular, a detailed characterization of CRP interaction with DNA has been obtained. The CRP dimer recognizes a consensus sequence AANTGTGANNNNNNTCACANTT through direct amino acid nucleobase interactions in the major groove of the two operator half-sites. Crystal structure analyses have revealed that the interaction results in two strong kinks at the TG/CA steps closest to the 6-base-pair spacer (N6). This spacer exhibits high sequence variability among the more than 100 natural binding sites in the E. coli genome, but the exact role of the N6 region in CRP interaction has not previously been systematic examined. Here we employ an in vitro selection system based on a randomized N6 spacer region to demonstrate that CRP binding to the lacP1 site may be enhanced up to 14-fold or abolished by varying the N6 spacer sequences. Furthermore, on the basis of sequence analysis and uranyl (UO2(2+)) probing data, we propose that the underlying mechanism relies on N6 deformability.

  7. Dynamic fluctuations provide the basis of a conformational switch mechanism in apo cyclic AMP receptor protein.

    Science.gov (United States)

    Aykaç Fas, Burcu; Tutar, Yusuf; Haliloğlu, Türkan

    2013-01-01

    Escherichia coli cyclic AMP Receptor Protein (CRP) undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD) simulations and Gaussian Network Model (GNM). The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra- and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.

  8. Application of protein misfolding cyclic amplification to detection of prions in anaerobic digestate.

    Science.gov (United States)

    Gilroyed, Brandon H; Braithwaite, Shannon L; Price, Luke M; Reuter, Tim; Czub, Stefanie; Graham, Catherine; Balachandran, Arumuga; McAllister, Tim A; Belosevic, Miodrag; Neumann, Norman F

    2015-11-01

    The exceptional physio-chemical resistance of prions to established decontamination procedures poses a challenge to assessing the suitability of applied inactivation methods. Prion detection is limited by the sensitivity level of Western blotting or by the cost and time factors of bioassays. In addition, prion detection assays can be limited by either the unique or complex nature of matrices associated with environmental samples. To investigate anaerobic digestion (AD) as a practical and economical approach for potential conversion of specified risk materials (SRM) into value added products (i.e., renewable energy), challenges associated with detection of prions in a complex matrix need to be overcome to determine potential inactivation. Protein misfolding cyclic amplification (PMCA) assay, with subsequent Western blot visualization, was used to detect prions within the AD matrix. Anaerobic digestate initially inhibited the PMCA reaction and/or Western blot detection. However, at concentrations of ≤1% of anaerobic digestate, 263K scrapie prions could be amplified and semi-quantitatively detected. Infectious 263K prions were also proven to be bioavailable in the presence of high concentrations of digestate (10-90%). Development of the PMCA application to digestate provides extremely valuable insight into the potential degradation and/or fate of prions in complex biological matrices without requiring expensive and time-consuming bioassays.

  9. Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine

    OpenAIRE

    Rita Ghosh; Gretchen E. Garcia; Katherine Crosby; Hiroyasu Inoue; Thompson, Ian M.; Troyer, Dean A.; Kumar, Addanki P.

    2007-01-01

    We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Our data also indicate that the antiproliferative effects of NexrutineR are mediated in part by Akt and Cyclic AMP response element binding protein (CREB). Cyclooxygenase (Cox-2), a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2) and suppresses a...

  10. De Novo Generation of a Unique Cervid Prion Strain Using Protein Misfolding Cyclic Amplification

    Science.gov (United States)

    Meyerett-Reid, Crystal; Wyckoff, A. Christy; Spraker, Terry; Pulford, Bruce; Bender, Heather

    2017-01-01

    ABSTRACT Substantial evidence supports the hypothesis that prions are misfolded, infectious, insoluble, and protease-resistant proteins (PrPRES) devoid of instructional nucleic acid that cause transmissible spongiform encephalopathies (TSEs). Protein misfolding cyclic amplification (PMCA) has provided additional evidence that PrPRes acts as a template that can convert the normal cellular prion protein (PrPC) present in uninfected normal brain homogenate (NBH) into the infectious misfolded PrPRES isoform. Human PrPC has been shown to spontaneously convert to a misfolded pathological state causing sporadic Creutzfeldt-Jakob disease (sCJD). Several investigators have reported spontaneous generation of prions by in vitro assays, including PMCA. Here we tested the rate of de novo generation of cervid prions in our laboratory using our standard PMCA protocol and NBH from transgenic mice expressing cervid PrPC (TgCerPrP mice). We generated de novo prions in rounds 4, 5, and 7 at low cumulative rates of 1.6, 5.0, and 6.7%, respectively. The prions caused infectious chronic wasting disease (CWD) upon inoculation into normal uninfected TgCerPrP mice and displayed unique biochemical characteristics compared to other cervid prion strains. We conclude that PMCA of cervid PrPC from normal brain homogenate spontaneously generated a new cervid prion strain. These data support the potential for cervids to develop sporadic CWD. IMPORTANCE CWD is the only known TSE that affects free-ranging wildlife, specifically cervids such as elk, deer, moose, caribou, and reindeer. CWD has become endemic in both free-ranging and captive herds in North America, South Korea, and, most recently, northern Europe. The prion research community continues to debate the origins of CWD. Original foci of CWD emergence in Colorado and Wyoming coincident with the sheep TSE scrapie suggest that scrapie prions may have adapted to cervids to cause CWD. However, emerging evidence supports the idea that cervid Pr

  11. Dynamic fluctuations provide the basis of a conformational switch mechanism in apo cyclic AMP receptor protein.

    Directory of Open Access Journals (Sweden)

    Burcu Aykaç Fas

    Full Text Available Escherichia coli cyclic AMP Receptor Protein (CRP undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD simulations and Gaussian Network Model (GNM. The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra- and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.

  12. Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates

    Science.gov (United States)

    Brem, Jürgen; Cain, Ricky; Cahill, Samuel; McDonough, Michael A.; Clifton, Ian J.; Jiménez-Castellanos, Juan-Carlos; Avison, Matthew B.; Spencer, James; Fishwick, Colin W. G.; Schofield, Christopher J.

    2016-08-01

    β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as `transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs.

  13. Inhibition of thyrotropin-stimulated DNA synthesis by microinjection of inhibitors of cellular Ras and cyclic AMP-dependent protein kinase.

    Science.gov (United States)

    Kupperman, E; Wen, W; Meinkoth, J L

    1993-08-01

    Microinjection of a dominant interfering mutant of Ras (N17 Ras) caused a significant reduction in thyrotropin (thyroid-stimulating hormone [TSH])-stimulated DNA synthesis in rat thyroid cells. A similar reduction was observed following injection of the heat-stable protein kinase inhibitor of the cyclic AMP-dependent protein kinase. Coinjection of both inhibitors almost completely abolished TSH-induced DNA synthesis. In contrast to TSH, overexpression of cellular Ras protein did not stimulate the expression of a cyclic AMP response element-regulated reporter gene. Similarly, injection of N17 Ras had no effect on TSH-stimulated reporter gene expression. Moreover, overexpression of cellular Ras protein stimulated similar levels of DNA synthesis in the presence or absence of the heat-stable protein kinase inhibitor. Together, these results suggest that in Wistar rat thyroid cells, a full mitogenic response to TSH requires both Ras and cyclic APK-dependent protein kinase.

  14. Reverse relationship between malignancy and cyclic AMP-dependent protein kinase activity in Yoshida rat ascites hepatomas.

    Science.gov (United States)

    Miyamoto, K; Nakamura, S; Nomura, M; Yamamoto, H; Sanae, F; Hidaka, H

    1993-08-31

    Rat ascites hepatoma (AH) cells (10(6) cells/head) inoculated intraperitoneally into rats had host-killing ability (malignancy) in the order AH66F > AH44 > AH13 > AH7974 > AH109A > AH66 > AH130. The life span of the rats after inoculation closely correlated with the activity of cyclic AMP-dependent protein kinase (protein kinase A) in the tumor cells but not the activity of Ca2+/phospholipid-dependent protein kinase (protein kinase C). N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinoline-sulfonamide (H-87), a potent, selective inhibitor of protein kinase A, inhibited in vitro growth of these hepatoma cells with a similar potency and, intraperitoneally injected, prolonged the lives of rats bearing less malignant AH66 cells (with high protein kinase A activity) but did not affect the life span of rats bearing highly malignant AH66F cells (with low protein kinase A activity). On the other hand N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), an inhibitor of protein kinase C, inhibited AH66F cells more than AH66 cells, but did not influence the life span of rats bearing either hepatoma. From these results it is deduced that protein kinase A may be important in the regulation of malignancy and in vivo proliferation of AH cells.

  15. Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING.

    Science.gov (United States)

    Shi, Heping; Wu, Jiaxi; Chen, Zhijian J; Chen, Chuo

    2015-07-21

    Cyclic GMP-AMP containing a unique combination of mixed phosphodiester linkages (2'3'-cGAMP) is an endogenous second messenger molecule that activates the type-I IFN pathway upon binding to the homodimer of the adaptor protein STING on the surface of endoplasmic reticulum membrane. However, the preferential binding of the asymmetric ligand 2'3'-cGAMP to the symmetric dimer of STING represents a physicochemical enigma. Here we show that 2'3'-cGAMP, but not its linkage isomers, adopts an organized free-ligand conformation that resembles the STING-bound conformation and pays low entropy and enthalpy costs in converting into the active conformation. Our results demonstrate that analyses of free-ligand conformations can be as important as analyses of protein conformations in understanding protein-ligand interactions.

  16. A cyclic-olefin-copolymer microfluidic immobilized-enzyme reactor for rapid digestion of proteins from dried blood spots.

    Science.gov (United States)

    Wouters, Bert; Dapic, Irena; Valkenburg, Thalassa S E; Wouters, Sam; Niezen, Leon; Eeltink, Sebastiaan; Corthals, Garry L; Schoenmakers, Peter J

    2017-03-31

    A critical step in the bottom-up characterization of proteomes is the conversion of proteins to peptides, by means of endoprotease digestion. Nowadays this method typically uses overnight digestion and as such represents a considerable bottleneck for high-throughput analysis. This report describes protein digestion using an immobilized-enzyme reactor (IMER), which enables accelerated digestion times that are completed within seconds to minutes. For rapid digestion to occur, a cyclic-olefin-copolymer microfluidic reactor was constructed containing trypsin immobilized on a polymer monolithic material through a 2-vinyl-4,4-dimethylazlactone linker. The IMER was applied for the rapid offline digestion of both singular protein standards and a complex protein mixture prior to liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) analysis. The effects of protein concentration and residence time in the IMER were assessed for protein standards of varying molecular weight between 11 and 240kDa. Compared to traditional in-solution digestion, IMER-facilitated protein digestion at room temperature for 5min yielded similar results in terms of sequence coverage and number of identified peptides. Good repeatability was demonstrated with a relative standard deviation of 6% for protein-sequence coverage. The potential of the IMER was also demonstrated for a complex protein mixture in the analysis of dried blood spots. Compared to a traditional workflow a similar number of proteins could be identified, while reducing the total analysis time from 22.5h to 4h and importantly omitting the sample-pre-treatment steps (denaturation, reduction, and alkylation). The identified proteins from two workflows showed similar distributions in terms of molecular weight and hydrophobic character.

  17. Exploration of cone cyclic nucleotide-gated channel-interacting proteins using affinity purification and mass spectrometry.

    Science.gov (United States)

    Ding, Xi-Qin; Matveev, Alexander; Singh, Anil; Komori, Naoka; Matsumoto, Hiroyuki

    2014-01-01

    Photopic (cone) vision essential for color sensation, central vision, and visual acuity is mediated by the activation of photoreceptor cyclic nucleotide-gated (CNG) channels. Naturally occurring mutations in the cone channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. This work investigated the functional modulation of cone CNG channel by exploring the channel-interacting proteins. Retinal protein extracts prepared from cone-dominant Nrl (- / -) mice were used in CNGA3 antibody affinity purification, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separation and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis. The peptide mass fingerprinting of the tryptic digests and database search identified a number of proteins including spectrin alpha-2, ATPase (Na(+)/K(+) transporting) alpha-3, alpha and beta subunits of ATP synthase (H(+) transporting, mitochondrial F1 complex), and alpha-2 subunit of the guanine nucleotide-binding protein. In addition, the affinity-binding assays demonstrated an interaction between cone CNG channel and calmodulin but not cone Na(+)/Ca(2+)-K(+) exchanger in the mouse retina. Results of this study provide insight into our understanding of cone CNG channel-interacting proteins and the functional modulations.

  18. Cyclic RGD peptide incorporation on phage major coat proteins for improved internalization by HeLa cells.

    Science.gov (United States)

    Choi, Dong Shin; Jin, Hyo-Eon; Yoo, So Young; Lee, Seung-Wuk

    2014-02-19

    Delivering therapeutic materials or imaging reagents into specific tumor tissues is critically important for development of novel cancer therapeutics and diagnostics. Genetically engineered phages possess promising structural features to develop cancer therapeutic materials. For cancer targeting purposes, we developed a novel engineered phage that expressed cyclic RGD (cRGD) peptides on the pVIII major coat protein using recombinant DNA technology. Using a type 88 phage engineering approach, which inserts a new gene to express additional major coat protein in the noncoding region of the phage genome, we incorporated an additional pVIII major coat protein with relatively bulky cRGD and assembled heterogeneous major coat proteins on the F88.4 phage surfaces. With IPTG control, we could tune different numbers of cRGD peptide displayed on the phage particles up to 140 copies. The resulting phage with cRGD on the recombinant pVIII protein exhibited enhanced internalization efficiency into HeLa cells in a ligand density and conformational structure dependent manner when comparing with the M13 phages modified with either linear RGD on pVIII or cRGD on pIII. Our cRGD peptide engineered phage could be useful for cancer therapy or diagnostic purposes after further modifying the phage with drug molecules or contrast reagents in the future.

  19. Conformational analysis of PKI(5-22)amide, the active inhibitory fragment of the inhibitor protein of the cyclic AMP-dependent protein kinase.

    Science.gov (United States)

    Reed, J; De Ropp, J S; Trewhella, J; Glass, D B; Liddle, W K; Bradbury, E M; Kinzel, V; Walsh, D A

    1989-12-01

    Fourier-transform i.r. spectroscopy, 1H-n.m.r. spectroscopy and X-ray scattering were used to study the conformation and shape of the peptide PKI(5-22)amide, which contains the active site of the inhibitor protein of the cyclic AMP-dependent protein kinase [Cheng, Van Pattern, Smith & Walsh (1985) Biochem. J. 231, 655-661]. The X-ray-scattering solution studies show that the peptide has a compact structure with Rg 0.9 nm (9.0 A) and a linear maximum dimension of 2.5 nm (25A). Compatible with this, Fourier-transform i.r. and n.m.r. determinations indicate that the peptide contains approx. 26% alpha-helix located in the N-terminal one-third of the molecule. This region contains the phenylalanine residue that is one essential recognition determinant for high-affinity binding to the protein kinase catalytic site.

  20. A Cyclic di-GMP-binding Adaptor Protein Interacts with Histidine Kinase to Regulate Two-component Signaling.

    Science.gov (United States)

    Xu, Linghui; Venkataramani, Prabhadevi; Ding, Yichen; Liu, Yang; Deng, Yinyue; Yong, Grace Lisi; Xin, Lingyi; Ye, Ruijuan; Zhang, Lianhui; Yang, Liang; Liang, Zhao-Xun

    2016-07-29

    The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. In accordance with the role of SagS as a motile-sessile switch and biofilm growth factor, we show that HapZ impacts surface attachment and biofilm formation most likely by regulating the expression of a large number of genes. The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein.

  1. Structure-Based Design and Synthesis of Potent Cyclic Peptides Inhibiting the YAP–TEAD Protein–Protein Interaction

    Science.gov (United States)

    2014-01-01

    The YAP–TEAD protein–protein interaction (PPI) mediates the oncogenic function of YAP, and inhibitors of this PPI have potential usage in treatment of YAP-involved cancers. Here we report the design and synthesis of potent cyclic peptide inhibitors of the YAP–TEAD interaction. A truncation study of YAP interface 3 peptide identified YAP84–100 as a weak peptide inhibitor (IC50 = 37 μM), and an alanine scan revealed a beneficial mutation, D94A. Subsequent replacement of a native cation−π interaction with an optimized disulfide bridge for conformational constraint and synergistic effect between macrocyclization and modification at positions 91 and 93 greatly boosted inhibitory activity. Peptide 17 was identified with an IC50 of 25 nM, and the binding affinity (Kd = 15 nM) of this 17mer peptide to TEAD1 proved to be stronger than YAP50–171 (Kd = 40 nM). PMID:25221655

  2. Cyclic di-GMP sensing via the innate immune signaling protein STING.

    Science.gov (United States)

    Yin, Qian; Tian, Yuan; Kabaleeswaran, Venkataraman; Jiang, Xiaomo; Tu, Daqi; Eck, Michael J; Chen, Zhijian J; Wu, Hao

    2012-06-29

    Detection of foreign materials is the first step of successful immune responses. Stimulator of interferon genes (STING) was shown to directly bind cyclic diguanylate monophosphate (c-di-GMP), a bacterial second messenger, and to elicit strong interferon responses. Here we elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP. The CBD exhibits an α + β fold and is a dimer in the crystal and in solution. Surprisingly, one c-di-GMP molecule binds to the central crevice of a STING dimer, using a series of stacking and hydrogen bonding interactions. We show that STING is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT. The structures provide a remarkable example of pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system.

  3. Systematic Nomenclature for GGDEF and EAL Domain-Containing Cyclic Di-GMP Turnover Proteins of Escherichia coli.

    Science.gov (United States)

    Hengge, Regine; Galperin, Michael Y; Ghigo, Jean-Marc; Gomelsky, Mark; Green, Jeffrey; Hughes, Kelly T; Jenal, Urs; Landini, Paolo

    2016-01-01

    In recent years, Escherichia coli has served as one of a few model bacterial species for studying cyclic di-GMP (c-di-GMP) signaling. The widely used E. coli K-12 laboratory strains possess 29 genes encoding proteins with GGDEF and/or EAL domains, which include 12 diguanylate cyclases (DGC), 13 c-di-GMP-specific phosphodiesterases (PDE), and 4 "degenerate" enzymatically inactive proteins. In addition, six new GGDEF and EAL (GGDEF/EAL) domain-encoding genes, which encode two DGCs and four PDEs, have recently been found in genomic analyses of commensal and pathogenic E. coli strains. As a group of researchers who have been studying the molecular mechanisms and the genomic basis of c-di-GMP signaling in E. coli, we now propose a general and systematic dgc and pde nomenclature for the enzymatically active GGDEF/EAL domain-encoding genes of this model species. This nomenclature is intuitive and easy to memorize, and it can also be applied to additional genes and proteins that might be discovered in various strains of E. coli in future studies.

  4. Highly sensitive detection of small ruminant bovine spongiform encephalopathy within transmissible spongiform encephalopathy mixes by serial protein misfolding cyclic amplification.

    Science.gov (United States)

    Gough, Kevin C; Bishop, Keith; Maddison, Ben C

    2014-11-01

    It is assumed that sheep and goats consumed the same bovine spongiform encephalopathy (BSE)-contaminated meat and bone meal that was fed to cattle and precipitated the BSE epidemic in the United Kingdom that peaked more than 20 years ago. Despite intensive surveillance for cases of BSE within the small ruminant populations of the United Kingdom and European Union, no instances of BSE have been detected in sheep, and in only two instances has BSE been discovered in goats. If BSE is present within the small ruminant populations, it may be at subclinical levels, may manifest as scrapie, or may be masked by coinfection with scrapie. To determine whether BSE is potentially circulating at low levels within the European small ruminant populations, highly sensitive assays that can specifically detect BSE, even within the presence of scrapie prion protein, are required. Here, we present a novel assay based on the specific amplification of BSE PrP(Sc) using the serial protein misfolding cyclic amplification assay (sPMCA), which specifically amplified small amounts of ovine and caprine BSE agent which had been mixed into a range of scrapie-positive brain homogenates. We detected the BSE prion protein within a large excess of classical, atypical, and CH1641 scrapie isolates. In a blind trial, this sPMCA-based assay specifically amplified BSE PrP(Sc) within brain mixes with 100% specificity and 97% sensitivity when BSE agent was diluted into scrapie-infected brain homogenates at 1% (vol/vol).

  5. Identification and function of exchange proteins activated directly by cyclic AMP (Epac in mammalian spermatozoa.

    Directory of Open Access Journals (Sweden)

    Alvaro Miro-Moran

    Full Text Available The role of cAMP in spermatic functions was classically thought to be mediated exclusively through the activation of Protein Kinase A (PKA. However, it has recently been shown that cAMP also exerts its effects through a PKA-independent pathway activating a family of proteins known as Epac proteins. Therefore, many of the spermatic functions thought to be regulated by cAMP through the activation of PKA are again under study. We aimed to identify and to investigate the role of Epac proteins in spermatozoa using a specific permeable analog (8-Br-2'-O-Me-cAMP. Also, we aimed to study its relationship with E-cadherin, an adhesion protein involved in fertility. Our results demonstrate the presence and sub-cellular distribution of Epac 1 and Epac 2 in mammalian spermatozoa. Capacitation and the acrosome reaction induced a change in the localization of Epac proteins in sperm. Moreover, incubation with 8-Br-2'-O-Me-cAMP prompted an increase in Rap1 activation, in the scrambling of plasma membrane phospholipids (necessary for the capacitation process, the acrosome reaction, motility, and calcium mobilization, when spermatozoa were incubated in acrosome reaction conditions. Finally, the activation of Epac proteins induced a change in the distribution of E-cadherin. Therefore, the increase in the acrosome reaction, together with the increase in calcium (which is known to be essential for fertilization and the Epac nteraction with E-cadherin, might indicate that Epac proteins have an important role in gamete recognition and fertilization.

  6. From bedside to bench--meeting report of the 7th International Conference on cGMP "cGMP: generators, effectors and therapeutic implications" in Trier, Germany, from June 19th to 21st 2015.

    Science.gov (United States)

    Friebe, Andreas; Sandner, Peter; Seifert, Roland

    2015-12-01

    During the past decade, our knowledge on the physiology, pathophysiology, basic pharmacology, and clinical pharmacology of the second messenger (cGMP) has increased tremendously. It is now well-established that cGMP, generated by soluble and particulate guanylate cyclases, is highly compartmentalized in cells and regulates numerous body functions. New cGMP-regulated physiological functions include meiosis and temperature perception. cGMP is involved in the genesis of numerous pathologies including cardiovascular, pulmonary, endocrine, metabolic, neuropsychiatric, eye, and tumor diseases. Several new clinical uses of stimulators and activators of soluble guanylate cyclase and of phosphodiesterase inhibitors such as heart failure, kidney failure, cognitive disorders, obesity bronchial asthma, and osteoporosis are emerging. The combination of neprilysin inhibitors-enhancing stimulation of the particulate guanylate cyclase pathway by preventing natriuretic peptide degradation-with angiotensin AT1 receptor antagonists constitutes a novel promising strategy for heart failure treatment. The role of oxidative stress in cGMP signaling, application of cGMP sensors, and gene therapy for degenerative eye diseases are emerging topics. It is anticipated that cGMP research will further prosper over the next years and reach out into more and more basic and clinical disciplines.

  7. The Catabolite Repressor Protein-Cyclic AMP Complex Regulates csgD and Biofilm Formation in Uropathogenic Escherichia coli.

    Science.gov (United States)

    Hufnagel, David A; Evans, Margery L; Greene, Sarah E; Pinkner, Jerome S; Hultgren, Scott J; Chapman, Matthew R

    2016-12-15

    The extracellular matrix protects Escherichia coli from immune cells, oxidative stress, predation, and other environmental stresses. Production of the E. coli extracellular matrix is regulated by transcription factors that are tuned to environmental conditions. The biofilm master regulator protein CsgD upregulates curli and cellulose, the two major polymers in the extracellular matrix of uropathogenic E. coli (UPEC) biofilms. We found that cyclic AMP (cAMP) regulates curli, cellulose, and UPEC biofilms through csgD The alarmone cAMP is produced by adenylate cyclase (CyaA), and deletion of cyaA resulted in reduced extracellular matrix production and biofilm formation. The catabolite repressor protein (CRP) positively regulated csgD transcription, leading to curli and cellulose production in the UPEC isolate, UTI89. Glucose, a known inhibitor of CyaA activity, blocked extracellular matrix formation when added to the growth medium. The mutant strains ΔcyaA and Δcrp did not produce rugose biofilms, pellicles, curli, cellulose, or CsgD. Three putative CRP binding sites were identified within the csgD-csgB intergenic region, and purified CRP could gel shift the csgD-csgB intergenic region. Additionally, we found that CRP binded upstream of kpsMT, which encodes machinery for K1 capsule production. Together our work shows that cAMP and CRP influence E. coli biofilms through transcriptional regulation of csgD IMPORTANCE The catabolite repressor protein (CRP)-cyclic AMP (cAMP) complex influences the transcription of ∼7% of genes on the Escherichia coli chromosome (D. Zheng, C. Constantinidou, J. L. Hobman, and S. D. Minchin, Nucleic Acids Res 32:5874-5893, 2004, https://dx.doi.org/10.1093/nar/gkh908). Glucose inhibits E. coli biofilm formation, and ΔcyaA and Δcrp mutants show impaired biofilm formation (D. W. Jackson, J.W. Simecka, and T. Romeo, J Bacteriol 184:3406-3410, 2002, https://dx.doi.org/10.1128/JB.184.12.3406-3410.2002). We determined that the c

  8. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

    DEFF Research Database (Denmark)

    Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller

    2008-01-01

    Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent ......Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for c......AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho...

  9. Phenotype, virulence and immunogenicity of Edwardsiella ictaluri cyclic adenosine 3',5'-monophosphate receptor protein (Crp) mutants in catfish host.

    Science.gov (United States)

    Santander, Javier; Mitra, Arindam; Curtiss, Roy

    2011-12-01

    Edwardsiella ictaluri is an Enterobacteriaceae that causes lethal enteric septicemia in catfish. Being a mucosal facultative intracellular pathogen, this bacterium is an excellent candidate to develop immersion-oral live attenuated vaccines for the catfish aquaculture industry. Deletion of the cyclic 3',5'-adenosine monophosphate (cAMP) receptor protein (crp) gene in several Enterobacteriaceae has been utilized in live attenuated vaccines for mammals and birds. Here we characterize the crp gene and report the effect of a crp deletion in E. ictaluri. The E. ictaluri crp gene and encoded protein are similar to other Enterobacteriaceae family members, complementing Salmonella enterica Δcrp mutants in a cAMP-dependent fashion. The E. ictaluri Δcrp-10 in-frame deletion mutant demonstrated growth defects, loss of maltose utilization, and lack of flagella synthesis. We found that the E. ictaluri Δcrp-10 mutant was attenuated, colonized lymphoid tissues, and conferred immune protection against E. ictaluri infection to zebrafish (Danio rerio) and catfish (Ictalurus punctatus). Evaluation of the IgM titers indicated that bath immunization with the E. ictaluri Δcrp-10 mutant triggered systemic and skin immune responses in catfish. We propose that deletion of the crp gene in E. ictaluri is an effective strategy to develop immersion live attenuated antibiotic-sensitive vaccines for the catfish aquaculture industry.

  10. [Phosphodiesterase 3 mediates cross-talk between the protein kinase- and cGMP- dependent pathways and cyclic AMP metabolism].

    Science.gov (United States)

    Makuch, Edyta; Matuszyk, Janusz

    2012-07-20

    PDE3 is a dual-substrate phosphodiesterase responsible for hydrolyzing both cAMP and cGMP whilst being simultaneously inhibited by cGMP. This feature is related to presence of the 44 amino acid insert in the catalytic domain, which determines the mechanism of introduction of the cyclic nucleotide into the catalytic pocket of the enzyme. Once bound in the catalytic site cGMP results in steric hindrance for cAMP to enter the site. The regulatory domain of PDE3 consists of two hydrophobic regions: NHR1 and NHR2. Their presence defines the enzyme's intracellular localization, thus determining its participation in particular signaling cascades. Due to the properties of PDE3 this enzyme has exceptional importance for the cross-talk between cAMP-dependent signaling and other cascades. There are two different mechanisms of action of PDE3 enzymes in cell signaling pathways. In many signaling cascades assembly of a signalosome is necessary for phosphorylation and activation of the PDE3 proteins. In response to certain hormones and growth factors, PDE3 merges the metabolism of cAMP with protein kinase-dependent signaling pathways. PDE3 also controls the level of cAMP with regard to the alternating concentration of cGMP. This effect occurs in signaling cascades activated by natriuretic peptide.

  11. Cyclic di-GMP contributes to adaption and virulence of Bacillus thuringiensis through a riboswitch-regulated collagen adhesion protein.

    Science.gov (United States)

    Tang, Qing; Yin, Kang; Qian, Hongliang; Zhao, Youwen; Wang, Wen; Chou, Shan-Ho; Fu, Yang; He, Jin

    2016-07-06

    Cyclic di-GMP is a ubiquitous second messenger that regulates diverse cellular processes in bacteria by binding to various protein or riboswitch effectors. In Bacillus thuringiensis BMB171, a c-di-GMP riboswitch termed Bc2 RNA resides in the 5'-untranslated region (5'-UTR) of an mRNA that encodes a collagen adhesion protein (Cap). The expression of cap was strongly repressed in parent strain BMB171 because of the presence of Bc2 RNA but was significantly promoted in the Bc2 RNA markerless deletion mutant. Bc2 RNA acts as a genetic "on" switch, which forms an anti-terminator structure to promote cap read-through transcription upon c-di-GMP binding. As a result, cap transcription was de-repressed under high c-di-GMP levels. Therefore, Bc2 RNA regulates cap expression using a repression/de-repression model. Bc2 RNA-regulated Cap was also found to be tightly associated with motility, aggregation, exopolysaccharide secretion, biofilm formation, and virulence of B. thuringiensis BMB171 against its host insect Helicoverpa armigera.

  12. PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis.

    Science.gov (United States)

    Muñoz-Valle, José Francisco; Padilla-Gutiérrez, Jorge Ramón; Hernández-Bello, Jorge; Ruiz-Noa, Yeniley; Valle, Yeminia; Palafox-Sánchez, Claudia Azucena; Parra-Rojas, Isela; Gutiérrez-Ureña, Sergio Ramón; Rangel-Villalobos, Hector

    2017-08-10

    The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  13. An EAL domain protein and cyclic AMP contribute to the interaction between the two quorum sensing systems in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Xianxuan Zhou; Xiaoming Meng; Baolin Sun

    2008-01-01

    Quorum sensing (QS) is a bacterial cell-cell communication process by which bacteria communicate using extracellular signals called autoinducers. Two QS systems have been identified in Escherichia coli K-12,including an intact QS system 2 that is stimulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and a partial QS system 1 that consists of SdiA (suppressor of cell division inhibitor) responding to signals generated by other microbialspecies. The relationship between QS system 1 and system 2 in E. coli,however,remains obscure. Here,we show that an EAL domain protein,encoded by ydiV,,and cAMP are involved in the interaction between the two QS systems in E.coli. Expression of sdiA and ydiV is inhibited by glucose. SdiA binds to the ydiV promoter region in a dose-dependent,hut nonspecific,manner; extracellular autoinducer 1 from other species stimulates ydiV expression in an sdiA-depen-dent manner. Furthermore,we discovered that the double sdiA-ydiV mutation,but not the single mutation,causes a 2-fold decrease in intracellular cAMP concentration that leads to the inhibition of QS system 2. These results indicate that signaling pathways that respond to important environmental cues,such as autoinducers and glucose,are linkedtogether for their control in E. coll.

  14. The arabidopsis cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara

    2016-05-11

    Background Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals. Methods An affinity purification technique was used to identify cyclic nucleotide binding proteins in Arabidopsis thaliana. The identified proteins were subjected to a computational analysis that included a sequence, transcriptional co-expression and functional annotation analysis in order to assess their potential role in plant cyclic nucleotide signaling. Results A total of twelve cyclic nucleotide binding proteins were identified experimentally including key enzymes in the Calvin cycle and photorespiration pathway. Importantly, eight of the twelve proteins were shown to contain putative cyclic nucleotide binding domains. Moreover, the identified proteins are post-translationally modified by nitric oxide, transcriptionally co-expressed and annotated to function in hydrogen peroxide signaling and the defence response. The activity of one of these proteins, GLYGOLATE OXIDASE 1, a photorespiratory enzyme that produces hydrogen peroxide in response to Pseudomonas, was shown to be repressed by a combination of cGMP and nitric oxide treatment. Conclusions We propose that the identified proteins function together as points of cross-talk between cyclic nucleotide, nitric oxide and reactive oxygen species signaling during the defence response.

  15. Twin-column CaptureSMB: a novel cyclic process for protein A affinity chromatography.

    Science.gov (United States)

    Angarita, Monica; Müller-Späth, Thomas; Baur, Daniel; Lievrouw, Roel; Lissens, Geert; Morbidelli, Massimo

    2015-04-10

    A twin-column counter-current chromatography processes, CaptureSMB, was used for the protein A affinity capture of a monoclonal antibody (mAb). By means of sequential loading, the process improves the utilization of the stationary phase by achieving loadings much closer to the static binding capacity of the resin in comparison to batch chromatography. Using a mAb capture case study with protein A affinity chromatography, the performance and product quality obtained from CaptureSMB and batch processes were compared. The effect of the flow rate, column length and titer concentration on the process performance and product quality were evaluated. CaptureSMB showed superior performance compared to batch chromatography with respect to productivity, capacity utilization, product concentration and buffer consumption. A simplified economic evaluation showed that CaptureSMB could decrease resin costs of 10-30% depending on the manufacturing scenario.

  16. Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection

    Directory of Open Access Journals (Sweden)

    Li Junfa

    2005-09-01

    Full Text Available Abstract Background Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP/extracellular signal-regulated kinase (ERK kinase (MEK 1/2, PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. Results We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. Conclusion These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.

  17. Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

    Energy Technology Data Exchange (ETDEWEB)

    Haigh, Cathryn L., E-mail: chaigh@unimelb.edu.au [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); Drew, Simon C., E-mail: sdrew@unimelb.edu.au [Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010 (Australia)

    2015-06-05

    The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation.

  18. Molecular bases of cyclic and specific disulfide interchange between human ERO1alpha protein and protein-disulfide isomerase (PDI).

    Science.gov (United States)

    Masui, Shoji; Vavassori, Stefano; Fagioli, Claudio; Sitia, Roberto; Inaba, Kenji

    2011-05-06

    In the endoplasmic reticulum (ER) of human cells, ERO1α and protein-disulfide isomerase (PDI) constitute one of the major electron flow pathways that catalyze oxidative folding of secretory proteins. Specific and limited PDI oxidation by ERO1α is essential to avoid ER hyperoxidation. To investigate how ERO1α oxidizes PDI selectively among more than 20 ER-resident PDI family member proteins, we performed docking simulations and systematic biochemical analyses. Our findings reveal that a protruding β-hairpin of ERO1α specifically interacts with the hydrophobic pocket present in the redox-inactive PDI b'-domain through the stacks between their aromatic residues, leading to preferred oxidation of the C-terminal PDI a'-domain. ERO1α associated preferentially with reduced PDI, explaining the stepwise disulfide shuttle mechanism, first from ERO1α to PDI and then from oxidized PDI to an unfolded polypeptide bound to its hydrophobic pocket. The interaction of ERO1α with ERp44, another PDI family member protein, was also analyzed. Notably, ERO1α-dependent PDI oxidation was inhibited by a hyperactive ERp44 mutant that lacks the C-terminal tail concealing the substrate-binding hydrophobic regions. The potential ability of ERp44 to inhibit ERO1α activity may suggest its physiological role in ER redox and protein homeostasis.

  19. Molecular Bases of Cyclic and Specific Disulfide Interchange between Human ERO1α Protein and Protein-disulfide Isomerase (PDI)*

    Science.gov (United States)

    Masui, Shoji; Vavassori, Stefano; Fagioli, Claudio; Sitia, Roberto; Inaba, Kenji

    2011-01-01

    In the endoplasmic reticulum (ER) of human cells, ERO1α and protein-disulfide isomerase (PDI) constitute one of the major electron flow pathways that catalyze oxidative folding of secretory proteins. Specific and limited PDI oxidation by ERO1α is essential to avoid ER hyperoxidation. To investigate how ERO1α oxidizes PDI selectively among more than 20 ER-resident PDI family member proteins, we performed docking simulations and systematic biochemical analyses. Our findings reveal that a protruding β-hairpin of ERO1α specifically interacts with the hydrophobic pocket present in the redox-inactive PDI b′-domain through the stacks between their aromatic residues, leading to preferred oxidation of the C-terminal PDI a′-domain. ERO1α associated preferentially with reduced PDI, explaining the stepwise disulfide shuttle mechanism, first from ERO1α to PDI and then from oxidized PDI to an unfolded polypeptide bound to its hydrophobic pocket. The interaction of ERO1α with ERp44, another PDI family member protein, was also analyzed. Notably, ERO1α-dependent PDI oxidation was inhibited by a hyperactive ERp44 mutant that lacks the C-terminal tail concealing the substrate-binding hydrophobic regions. The potential ability of ERp44 to inhibit ERO1α activity may suggest its physiological role in ER redox and protein homeostasis. PMID:21398518

  20. Cyclic AMP response element binding protein and brain-derived neurotrophic factor: Molecules that modulate our mood?

    Indian Academy of Sciences (India)

    A Nair; V A Vaidya

    2006-09-01

    Depression is the major psychiatric ailment of our times, afflicting ∼20% of the population. Despite its prevalence, the pathophysiology of this complex disorder is not well understood. In addition, although antidepressants have been in existence for the past several decades, the mechanisms that underlie their therapeutic effects remain elusive. Building evidence implicates a role for the plasticity of specific neuro-circuitry in both the pathophysiology and treatment of depression. Damage to limbic regions is thought to contribute to the etiology of depression and antidepressants have been reported to reverse such damage and promote adaptive plasticity. The molecular pathways that contribute to the damage associated with depression and antidepressant-mediated plasticity are a major focus of scientific enquiry. The transcription factor cyclic AMP response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) are targets of diverse classes of antidepressants and are known to be regulated in animal models and in patients suffering from depression. Given their role in neuronal plasticity, CREB and BDNF have emerged as molecules that may play an important role in modulating mood. The purpose of this review is to discuss the role of CREB and BDNF in depression and as targets/mediators of antidepressant action.

  1. The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Tuttle, Traci R; Mierzwa, Michelle L; Wells, Susanne I; Fox, Sejal R; Ben-Jonathan, Nira

    2016-01-28

    Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with high mortality. Treatments, which can result in significant morbidity, have not substantially changed in three decades. The second messenger cyclic GMP (cGMP), which targets protein kinase G (PKG), is generated by guanylate cyclases (GCs), and is rapidly hydrolyzed by phosphodiesterases (PDEs). Activation of the cGMP/PKG pathway is antineoplastic in several cancer types, but its impact on HNSCC has not been fully exploited. We found differential expression of critical components of this pathway in four HNSCC cell lines. Several activators of soluble GC (sGC), as well as inhibitors of PDE5, increased intracellular cGMP, reduced cell viability, and induced apoptosis in HNSCC cells. The apoptotic effects of the sGC activator BAY 41-2272 and the PDE5 inhibitor Tadalafil (Cialis) were mediated by PKG. Furthermore, Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer.

  2. Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine

    Directory of Open Access Journals (Sweden)

    Rita Ghosh

    2007-11-01

    Full Text Available We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP model. Our data also indicate that the antiproliferative effects of NexrutineR are mediated in part by Akt and Cyclic AMP response element binding protein (CREB. Cyclooxygenase (Cox-2, a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2 and suppresses apoptosis. Treatment of LNCaP cells with NexrutineR reduced tumor necrosis factor α-induced enzymatic as well as promoter activities of Cox-2. NexrutineR also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating NexrutineR response. Immunohistochemical analysis of human prostate tumors show increased expression of CREB and DNA binding activity in high-grade tumors (three-fold higher in human prostate tumors compared to normal prostate; P = .01. We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like NexrutineR, demonstrating a prospective for development of NexrutineR for prostate cancer management.

  3. Influence of heating and cyclic tension on the induction of heat shock proteins and bone-related proteins by MC3T3-E1 cells.

    Science.gov (United States)

    Chung, Eunna; Sampson, Alana Cherrell; Rylander, Marissa Nichole

    2014-01-01

    Stress conditioning (e.g., thermal, shear, and tensile stress) of bone cells has been shown to enhance healing. However, prior studies have not investigated whether combined stress could synergistically promote bone regeneration. This study explored the impact of combined thermal and tensile stress on the induction of heat shock proteins (HSPs) and bone-related proteins by a murine preosteoblast cell line (MC3T3-E1). Cells were exposed to thermal stress using a water bath (44°C for 4 or 8 minutes) with postheating incubation (37°C for 4 hours) followed by exposure to cyclic strain (equibiaxial 3%, 0.2 Hz, cycle of 10-second tensile stress followed by 10-second rest). Combined thermal stress and tensile stress induced mRNA expression of HSP27 (1.41 relative fold induction (RFI) compared to sham-treated control), HSP70 (5.55 RFI), and osteopontin (1.44 RFI) but suppressed matrix metalloproteinase-9 (0.6 RFI) compared to the control. Combined thermal and tensile stress increased vascular endothelial growth factor (VEGF) secretion into the culture supernatant (1.54-fold increase compared to the control). Therefore, combined thermal and mechanical stress preconditioning can enhance HSP induction and influence protein expression important for bone tissue healing.

  4. Strain typing of classical scrapie by transgenic mouse bioassay using protein misfolding cyclic amplification to replace primary passage.

    Directory of Open Access Journals (Sweden)

    Katy E Beck

    Full Text Available According to traditional murine bioassay methodology, prions must be serially passaged within a new host before a stable phenotype, and therefore a strain, can be assigned. Prions often transmit with difficulty from one species to another; a property termed the transmission barrier. Transgenic mouse lines that over express prion protein (PrP genes of different species can circumvent the transmission barrier but serial passages may still be required, particularly if unknown strains are encountered. Here we sought to investigate whether protein misfolding cyclic amplification (PMCA, an in-vitro method of PrP(Sc replication, could be used to replace serial passage of VRQ/VRQ classical scrapie isolates undergoing strain typing in ovine transgenic tg338 mice. Two classical scrapie field isolates that do not readily transmit to wild-type mice underwent bioassay in tg338 mice pre- and post- PMCA and the phenotype of disease in inoculated mice was compared. For one of the sources investigated, the PMCA product gave rise to the same disease phenotypes in tg338 mice as traditional bioassay, as indicated by lesion profile, IHC analysis and Western blot, whilst the second source produced phenotypic characteristics which were not identical with those that arose through traditional bioassay. These data show that differences in the efficiency of PMCA as a strain-typing tool may vary between ovine classical scrapie isolates and therefore suggest that the ability of PMCA to replace serial passage of classical scrapie in tg338 mice may depend on the strain present in the initial source.

  5. Performance and carbon turnover in fast- and slow-growing broilers submitted to cyclic heat stress and fed on high-protein diets.

    Science.gov (United States)

    Campos, D M B; Macari, M; Fernadez-Alarcon, M F; Nogueira, W C L; de Souza, F A; Hada, F H; Lunedo, R; Denadai, J C

    2016-01-01

    Two experiments were conducted to test the hypothesis that when using similar protein/amino acid diets and environment temperature conditions, the performance and carbon turnover in muscle and liver tissues, as measured by the incorporation of stable isotopes ((13)C/(12)C), must be different between fast-growing Cobb 500® and slow-growing Label Rouge broilers. For both experiments (Cobb and Label Rouge), 21-d-old birds were distributed in a completely randomised, 3 × 3 factorial design; three environmental temperatures (cyclic heat stress ad libitum, 22°C ad libitum, and 22°C restricted) and three crude protein concentrations (189.1, 210 and 220 g/kg CP) were used. The Cobb 500® had better performance with higher concentrations of crude protein. Cyclic heat stress (a temperature factor), negatively affected this genetic strain's performance. For the Label Rouge birds, the crude protein concentrations in the diet presented inconsistent results and cyclic heat stress did not affect the performance. The carbon turnover rate was affected in the Cobb 500® strain, with a high protein content reducing carbon turnover in the evaluated tissues (liver and muscles). Feed intake had a greater impact on carbon turnover rates than cyclic heat stress. The Label Rouge birds were not affected by the evaluated factors, suggesting that genetic improvement has a leading role on tissue carbon turnover. There is a genetic influence on carbon turnover in the liver and muscle tissues of broiler chickens. In addition, genetically fast-growing broilers are more susceptible to variations in diet composition and environmental temperature than less rapidly growing animals.

  6. Cyclic derangements

    CERN Document Server

    Assaf, Sami H

    2010-01-01

    A classic problem in enumerative combinatorics is to count the number of derangements, that is, permutations with no fixed point. Inspired by a recent generalization to facet derangements of the hypercube by Gordon and McMahon, we generalize this problem to enumerating derangements in the wreath product of any finite cyclic group with the symmetric group. We also give q- and (q, t)-analogs for cyclic derangements, generalizing results of Brenti and Gessel.

  7. Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade.

    Science.gov (United States)

    Bahn, Yong-Sun; Hicks, Julie K; Giles, Steven S; Cox, Gary M; Heitman, Joseph

    2004-12-01

    The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Galpha subunit Gpa1 to control the adenylyl cyclase (Cac1). Aca1 interacted with the C terminus of Cac1 in the yeast two-hybrid system. By molecular and genetic approaches, Aca1 was shown to play a critical role in mating by regulating cell fusion and filamentous growth in a cAMP-dependent manner. Aca1 also regulates melanin and capsule production via the Cac1-cAMP-protein kinase A pathway. Genetic epistasis studies support models in which Aca1 and Gpa1 are necessary and sufficient components that cooperate to activate adenylyl cyclase. Taken together, these studies further define the cAMP signaling cascade controlling virulence of this ubiquitous human fungal pathogen.

  8. L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Xiang-Zhu Xie

    2016-01-01

    Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

  9. Sevoflurane effects on cyclic adenosine monophosphate response element binding protein, phosphorylated cyclic adenosine monophosphate response element binding protein, and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat model

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Ling Dan; Xianlin Zhu

    2009-01-01

    BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia.OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA.METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours.MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze.RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P<0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P<0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham

  10. Biologically relevant conformational features of linear and cyclic proteolipid protein (PLP) peptide analogues obtained by high-resolution nuclear magnetic resonance and molecular dynamics

    Science.gov (United States)

    Kordopati, Golfo G.; Tzoupis, Haralambos; Troganis, Anastassios N.; Tsivgoulis, Gerasimos M.; Golic Grdadolnik, Simona; Simal, Carmen; Tselios, Theodore V.

    2017-07-01

    Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are destroyed during the progress of multiple sclerosis (MS). The immunodominant PLP139-151 epitope is known to induce experimental autoimmune encephalomyelitis (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell receptor (TCR) during the formation of trimolecular complex with peptide-antigen and major histocompability complex. The conformational behavior of linear and cyclic peptide analogues of PLP, namely PLP139-151 and cyclic (139-151) (L144, R147) PLP139-151, have been studied in solution by means of nuclear magnetic resonance (NMR) methods in combination with unrestrained molecular dynamics simulations. The results indicate that the side chains of mutated amino acids in the cyclic analogue have different spatial orientation compared with the corresponding side chains of the linear analogue, which can lead to reduced affinity to TCR. NMR experiments combined with theoretical calculations pave the way for the design and synthesis of potent restricted peptides of immunodominant PLP139-151 epitope as well as non peptide mimetics that rises as an ultimate goal.

  11. An antisense oligodeoxynucleotide that depletes RI alpha subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells.

    Science.gov (United States)

    Yokozaki, H; Budillon, A; Tortora, G; Meissner, S; Beaucage, S L; Miki, K; Cho-Chung, Y S

    1993-02-15

    Enhanced expression of the RI alpha subunit of cyclic AMP-dependent protein kinase type I has been correlated with cancer cell growth. We provide evidence that RI alpha is a growth-inducing protein that may be essential for neoplastic cell growth. Human colon, breast, and gastric carcinoma and neuroblastoma cell lines exposed to a 21-mer human RI alpha antisense phosphorothioate oligodeoxynucleotide (S-oligodeoxynucleotide) exhibited growth inhibition with no sign of cytotoxicity. Mismatched sequence (random) S-oligodeoxynucleotides of the same length exhibited no effect. The growth inhibitory effect of RI alpha antisense oligomer correlated with a decrease in the RI alpha mRNA and protein levels and with an increase in RII beta (the regulatory subunit of protein kinase type II) expression. The growth inhibition was abolished, however, when cells were exposed simultaneously to both RI alpha and RII beta antisense S-oligodeoxynucleotides. The RII beta antisense S-oligodeoxynucleotide alone, exhibiting suppression of RII beta along with enhancement of RI alpha expression, led to slight stimulation of cell growth. These results demonstrate that two isoforms of cyclic AMP receptor proteins, RI alpha and RII beta, are reciprocally related in the growth control of cancer cells and that the RI alpha antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RI alpha, is a powerful biological tool toward suppression of malignancy.

  12. Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies.

    Directory of Open Access Journals (Sweden)

    Maxime Belondrade

    Full Text Available The prevalence of variant Creutzfeldt-Jakob disease (vCJD in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA. This assay allowed the specific detection of minute quantities (10-8 brain dilution of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions.

  13. Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies.

    Science.gov (United States)

    Belondrade, Maxime; Nicot, Simon; Béringue, Vincent; Coste, Joliette; Lehmann, Sylvain; Bougard, Daisy

    2016-01-01

    The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10-8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions.

  14. Toxoplasma gondii Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development

    Directory of Open Access Journals (Sweden)

    Tatsuki Sugi

    2016-05-01

    Full Text Available Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects warm-blooded vertebrates, including humans. Asexual reproduction in T. gondii allows it to switch between the rapidly replicating tachyzoite and quiescent bradyzoite life cycle stages. A transient cyclic AMP (cAMP pulse promotes bradyzoite differentiation, whereas a prolonged elevation of cAMP inhibits this process. We investigated the mechanism(s by which differential modulation of cAMP exerts a bidirectional effect on parasite differentiation. There are three protein kinase A (PKA catalytic subunits (TgPKAc1 to -3 expressed in T. gondii. Unlike TgPKAc1 and TgPKAc2, which are conserved in the phylum Apicomplexa, TgPKAc3 appears evolutionarily divergent and specific to coccidian parasites. TgPKAc1 and TgPKAc2 are distributed in the cytomembranes, whereas TgPKAc3 resides in the cytosol. TgPKAc3 was genetically ablated in a type II cyst-forming strain of T. gondii (PruΔku80Δhxgprt and in a type I strain (RHΔku80Δhxgprt, which typically does not form cysts. The Δpkac3 mutant exhibited slower growth than the parental and complemented strains, which correlated with a higher basal rate of tachyzoite-to-bradyzoite differentiation. 3-Isobutyl-1-methylxanthine (IBMX treatment, which elevates cAMP levels, maintained wild-type parasites as tachyzoites under bradyzoite induction culture conditions (pH 8.2/low CO2, whereas the Δpkac3 mutant failed to respond to the treatment. This suggests that TgPKAc3 is the factor responsible for the cAMP-dependent tachyzoite maintenance. In addition, the Δpkac3 mutant had a defect in the production of brain cysts in vivo, suggesting that a substrate of TgPKAc3 is probably involved in the persistence of this parasite in the intermediate host animals.

  15. Cyclic Voltammetry.

    Science.gov (United States)

    Evans, Dennis H.; And Others

    1983-01-01

    Cyclic voltammetry is a simple experiment that has become popular in chemical research because it can provide useful information about redox reactions in a form which is easily obtained and interpreted. Discusses principles of the method and illustrates its use in the study of four electrode reactions. (Author/JN)

  16. Cyclic Voltammetry.

    Science.gov (United States)

    Evans, Dennis H.; And Others

    1983-01-01

    Cyclic voltammetry is a simple experiment that has become popular in chemical research because it can provide useful information about redox reactions in a form which is easily obtained and interpreted. Discusses principles of the method and illustrates its use in the study of four electrode reactions. (Author/JN)

  17. The progestin levonorgestrel induces endothelium-independent relaxation of rabbit jugular vein via inhibition of calcium entry and protein kinase C: role of cyclic AMP

    Science.gov (United States)

    Herkert, Olaf; Kuhl, Herbert; Busse, Rudi; Schini-Kerth, Valérie B

    2000-01-01

    The progestin and oestrogen component of oral contraceptives have been involved in the development of venous thromboembolic events in women. In the present study we determined the vasoactive effects of sex steroids used in oral contraceptives in isolated preconstricted rabbit jugular veins in the presence of diclofenac and examined the underlying mechanisms.The natural hormone progesterone, the synthetic progestins levonorgestrel, 3-keto-desogestrel, gestodene and chlormadinone acetate, and the synthetic estrogen 17 α-ethinyloestradiol induced concentration-dependent relaxations of endothelium-intact veins constricted with U46619. Levonorgestrel also inhibited constrictions evoked by either a high potassium (K+) solution or phorbol myristate acetate (PMA) in the absence and presence of extracellular calcium (Ca2+). In addition, levonorgestrel depressed contractions evoked by Ca2+ and reduced 45Ca2+ influx in depolarized veins.Relaxations to levonorgestrel in U46619-constricted veins were neither affected by the presence of the endothelium nor by the inhibitor of soluble guanylyl cyclase, NS2028, but were significantly improved either by the selective cyclic AMP phosphodiesterase inhibitor rolipram or in the absence of diclofenac, and decreased by the protein kinase A inhibitor, Rp-8-CPT-cAMPS. Rolipram also potentiated relaxations to levonorgestrel in PMA-constricted veins in the presence, but not in the absence of extracellular Ca2+. Levonorgestrel increased levels of cyclic AMP and inhibited PMA-induced activation of protein kinase C in veins.These findings indicate that levonorgestrel caused endothelium-independent relaxations of jugular veins via inhibition of Ca2+ entry and of protein kinase C activation. In addition, the cyclic AMP effector pathway contributes to the levonorgestrel-induced relaxation possibly by depressing Ca2+ entry. PMID:10952682

  18. Anti-carbamylated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients: lack of correlation with anti-cyclic citrullinated protein antibodies and rheumatoid factor.

    Science.gov (United States)

    Alessandri, C; Bartosiewicz, I; Pendolino, M; Mancini, R; Colasanti, T; Pecani, A; Morello, F; Mastrangelo, A; Sabatinelli, D; Riccieri, V; Di Franco, M; Ceccarelli, F; Perricone, C; Conti, F; Valesini, G

    2015-01-01

    To investigate the prevalence of anti-carbamylated protein antibodies (anti-CarP) in the healthy first-degree relatives (HFDRs) of patients with rheumatoid arthritis (RA). We enrolled 141 HFDRs of 63 patients with RA diagnosed accordingly to the 2010 ACR/EULAR criteria. Fifty-six normal healthy subjects (NHS), sex- and age-matched, served as controls. Anti-CarP IgG, anti-cyclic citrullinated peptide antibody (anti-CCP) IgG and rheumatoid factors (RF) isotypes (IgG, IgA, IgM) were assessed by solid-phase ELISA. Anti-CarP were detectable in 13 HFDRs (9.2%), anti-CCP in 9 (6.3%), IgG-RF in 10 (7%), IgA-RF in 17 (12%), and IgM-RF in 13 (9.2%) HFDRs. Twenty-nine (46%) RA patients were positive for anti-CarP, 31 (49.2%) for anti-CCP, and 34 (53.9%) for RF. One NHS (1.7%) resulted positive for anti-CarP, none for anti-CCP and RF. Anti-CarP showed significantly higher serum levels in RA and HFDRs than in NHS (pautoantibodies tested in the HFDRs. Anti-CarP can be found in the sera of HFDRs of RA patients and their prevalence is significantly higher than in NHS. No correlation of anti-CarP with anti-CCP and RF antibodies in RA HFDRs was found.

  19. Repression of protein kinase C and stimulation of cyclic AMP response elements by fumonisin, a fungal encoded toxin which is a carcinogen.

    Science.gov (United States)

    Huang, C; Dickman, M; Henderson, G; Jones, C

    1995-04-15

    Fusarium moniliforme (FM) is a major fungal pathogen of corn and is involved with stalk rot disease. FM is widely spread throughout the world, including the United States. Most strains of FM produce several mycotoxins, the most prominent of which is called fumonisin. Recent epidemiological studies indicated that ingestion of fumonisin correlates with a higher incidence of esophageal cancer in Southern and Northern Africa and China. Furthermore, fumonisin causes a neurodegenerative disease in horses, induces hepatic cancer in rats, and induces pulmonary edema in swine. Considering that high levels of fumonisin have been detected in healthy and diseased corn grown in the United States, fumonisin may pose a health threat to humans and livestock animals. Structurally, fumonisin resembles sphingolipids which are present in the membranes of animal and plant cells. At the present time, very little is known concerning the mechanism by which fumonisin elicits its carcinogenic effect. Our studies indicate that fumonisin represses expression of protein kinase C and AP-1-dependent transcription. In contrast, fumonisin stimulated a simple promoter containing a single cyclic AMP response element. Since fumonisin did not alter protein kinase A activity, it appears that cyclic AMP response element activation was independent of protein kinase A. It is hypothesized that the ability of fumonisin to alter signal transduction pathways plays a role in carcinogenesis.

  20. Cyclic AMP-dependent protein kinase (cAPK) regulatory subunits are packaged and secreted by many exocrine and endocrine cells

    Energy Technology Data Exchange (ETDEWEB)

    Mednieks, M.I.; Hand, A.R.

    1986-05-01

    Regulatory (R) subunits of cAPK were identified by us as components of rat and human saliva by photoaffinity labeling with (/sup 32/P)-8-azido cyclic AMP. Photoaffinity labeling of purified rat parotid granule contents and immunogold labeling of thin sections with monoclonal antibodies showed the presence of R subunits in granules. The authors now report that cAPK R subunits are present in secretory granules and are apparently secreted by many exocrine and endocrine cell types. Labeling of thin sections of rat tissues with antibody to R subunits and protein A-gold shows gold particles over secretory granules of endocrine cells of the pituitary, pancreas and intestine. Zymogen granules of exocrine pancreatic acinar cells, the dense cores of secretory granules of seminal vesicle epithelial cells and secretory product in the seminal vesicle lumina were prominently labeled with gold. Photoaffinity labeling shows that pancreatic secretions and seminal vesicle contents have cAPK components. Phosphorylative modification of cellular proteins by cAMP controls hormonally stimulated protein secretion by many cell types. Although no catalytic activity was detected, identification of R subunits in granules and as secretory products indicates that they may have multiple roles in cellular mechanisms of action of cyclic AMP-mediated events in secretory cells.

  1. Cyclic multiverses

    CERN Document Server

    Marosek, Konrad; Balcerzak, Adam

    2015-01-01

    Starting with the idea of regularization of singularities due to the variability of the fundamental constants in cosmology we first study the cyclic universe models. We find two models of oscillating mass density and pressure regularized by varying gravitational constant $G$. Then, we extend this idea onto the multiverse containing cyclic individual universes with either growing or decreasing entropy though leaving the net entropy constant. In order to get the key idea, we consider the doubleverse with the same geometrical evolution of the two "parallel" universes with their physical evolution (physical coupling constants $c(t)$ and $G(t)$) being different. An interesting point is that there is a possibility to exchange the universes at the point of maximum expansion -- the fact which was already noticed in quantum cosmology. Similar scenario is also possible within the framework of Brans-Dicke theory.

  2. Complex structure and biochemical characterization of the Staphylococcus aureus cyclic diadenylate monophosphate (c-di-AMP)-binding protein PstA, the founding member of a new signal transduction protein family.

    Science.gov (United States)

    Campeotto, Ivan; Zhang, Yong; Mladenov, Miroslav G; Freemont, Paul S; Gründling, Angelika

    2015-01-30

    Signaling nucleotides are integral parts of signal transduction systems allowing bacteria to cope with and rapidly respond to changes in the environment. The Staphylococcus aureus PII-like signal transduction protein PstA was recently identified as a cyclic diadenylate monophosphate (c-di-AMP)-binding protein. Here, we present the crystal structures of the apo- and c-di-AMP-bound PstA protein, which is trimeric in solution as well as in the crystals. The structures combined with detailed bioinformatics analysis revealed that the protein belongs to a new family of proteins with a similar core fold but with distinct features to classical PII proteins, which usually function in nitrogen metabolism pathways in bacteria. The complex structure revealed three identical c-di-AMP-binding sites per trimer with each binding site at a monomer-monomer interface. Although distinctly different from other cyclic-di-nucleotide-binding sites, as the half-binding sites are not symmetrical, the complex structure also highlighted common features for c-di-AMP-binding sites. A comparison between the apo and complex structures revealed a series of conformational changes that result in the ordering of two anti-parallel β-strands that protrude from each monomer and allowed us to propose a mechanism on how the PstA protein functions as a signaling transduction protein.

  3. Specificity of the Cyclic GMP-Binding Activity and of a Cyclic GMP-Dependent Cyclic GMP Phosphodiesterase in Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Walsum, Hans van; Meer, Rob C. van der; Bulgakov, Roman; Konijn, Theo M.

    1982-01-01

    The nucleotide specificity of the cyclic GMP-binding activity in a homogenate of Dictyostelium discoideum was determined by competition of cyclic GMP derivatives with [8-3H] cyclic GMP for the binding sites. The results indicate that cyclic GMP is bound to the binding proteins by hydrogen bonds at N

  4. Identification of phosphorylation sites for adenosine 3',5'-cyclic phosphate dependent protein kinase on the voltage-sensitive sodium channel from Electrophorus electricus.

    Science.gov (United States)

    Emerick, M C; Agnew, W S

    1989-10-17

    The voltage-sensitive sodium channel from the electroplax of Electrophorus electricus is selectively phosphorylated by the catalytic subunit of cyclic-AMP-dependent protein kinase (protein kinase A) but not by protein kinase C. Under identical limiting conditions, the protein was phosphorylated 20% as rapidly as the synthetic model substrate kemptamide. A maximum of 1.7 +/- 0.6 equiv of phosphate is incorporated per mole. Phosphoamino acid analysis revealed labeled phosphoserine and phosphothreonine at a constant ratio of 3.3:1. Seven distinct phosphopeptides were identified among tryptic fragments prepared from radiolabeled, affinity-purified protein and resolved by HPLC. The three most rapidly labeled fragments were further purified and sequenced. Four phosphorylated amino acids were identified deriving from three consensus phosphorylation sites. These were serine 6, serine 7, and threonine 17 from the amino terminus and a residue within 47 amino acids of the carboxyl terminus, apparently serine 1776. The alpha-subunits of brain sodium channels, like the electroplax protein, are readily phosphorylated by protein kinase A. However, these are also phosphorylated by protein kinase C and exhibit a markedly different pattern of incorporation. Each of three brain alpha-subunits displays an approximately 200 amino acid segment between homologous repeat domains I and II, which is missing from the electroplax and skeletal muscle proteins [Noda et al. (1986) Nature (London) 320, 188; Kayano et al. (1988) FEBS Lett. 228, 1878; Trimmer et al. (1989) Neuron 3, 33]. Most of the phosphorylation of the brain proteins occurs on a cluster of consensus phosphorylation sites located in this segment. This contrasts with the pattern of highly active sites on the amino and carboxyl termini of the electroplax protein. The detection of seven labeled tryptic phosphopeptides compared to the maximal labeling stoichiometry of approximately 2 suggests that many of the acceptor sites on the

  5. Cyclic Vitalism

    DEFF Research Database (Denmark)

    Halse, Sven

    2014-01-01

    an enthusiastic worshipping of life, one that holds youth, health, strength and beauty as its primary attributes, and which was prevalent in all aspects of cultural life around 1900. But even the post war founders of the Vitalist re-conceptualisation of this era, Wolfdietrich Rasch and Gunter Martens, warned...... that also encompasses notions of destruction, decay and death. “All life symbols in literature around 1900 are at the same time symbols of death”. (Rasch, W. 1967:24) Through the analyses of three poems, this article aims to show concrete examples of how cyclic Vitalist thinking is embedded in poetry...

  6. Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2015-12-01

    Full Text Available Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-α (mAKAPα is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPα early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPα in the adult increased RGC death after optic nerve crush. Importantly, mAKAPα was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP after injury. These results identify mAKAPα as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury.

  7. Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems.

    Science.gov (United States)

    Roelofs, Kevin G; Jones, Christopher J; Helman, Sarah R; Shang, Xiaoran; Orr, Mona W; Goodson, Jonathan R; Galperin, Michael Y; Yildiz, Fitnat H; Lee, Vincent T

    2015-10-01

    Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP.

  8. Cyclic nucleotide-dependent protein kinases and some major substrates in the rat cerebellum after neonatal X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Dolphin, A.C.; Detre, J.A.; Schlichter, D.J.; Nairn, A.C.; Yeh, H.H.; Woodward, D.J.; Greengard, P.

    1983-02-01

    The levels of cAMP-dependent protein kinase (type I), or cGMP-dependent protein kinase, or protein I, and of a 23,000 MW substrate for the cGMP-dependent protein kinase were measured in cerebella from normal rats and in the cerebella from rats in which a selective loss of interneurons in the cerebellar cortex had been produced by X-irradiation. A decrease was observed in the concentrations of cAMP-dependent protein kinase and of protein I, whereas an increase was observed in the concentrations of cGMP-dependent protein kinase and of the 23,000 MW substrate. The data, taken together with the results of other studies, support the interpretation that cAMP-dependent protein kinase and protein I are distributed throughout the cerebellum, but that cGMP-dependent protein kinase and the 23,000 MW substrate are highly concentrated in Purkinje cells.

  9. Cyclic multiverses

    Science.gov (United States)

    Marosek, Konrad; Dąbrowski, Mariusz P.; Balcerzak, Adam

    2016-09-01

    Using the idea of regularization of singularities due to the variability of the fundamental constants in cosmology we study the cyclic universe models. We find two models of oscillating and non-singular mass density and pressure (`non-singular' bounce) regularized by varying gravitational constant G despite the scale factor evolution is oscillating and having sharp turning points (`singular' bounce). Both violating (big-bang) and non-violating (phantom) null energy condition models appear. Then, we extend this idea on to the multiverse containing cyclic individual universes with either growing or decreasing entropy though leaving the net entropy constant. In order to get an insight into the key idea, we consider the doubleverse with the same geometrical evolution of the two `parallel' universes with their physical evolution [physical coupling constants c(t) and G(t)] being different. An interesting point is that there is a possibility to exchange the universes at the point of maximum expansion - the fact which was already noticed in quantum cosmology. Similar scenario is also possible within the framework of Brans-Dicke theory where varying G(t) is replaced by the dynamical Brans-Dicke field φ(t) though these theories are slightly different.

  10. Comprehensive overexpression analysis of cyclic-di-GMP signalling proteins in the phytopathogen Pectobacterium atrosepticum reveals diverse effects on motility and virulence phenotypes.

    Science.gov (United States)

    Tan, H; West, J A; Ramsay, J P; Monson, R E; Griffin, J L; Toth, I K; Salmond, G P C

    2014-07-01

    Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a ubiquitous bacterial signalling molecule produced by diguanylate cyclases of the GGDEF-domain family. Elevated c-di-GMP levels or increased GGDEF protein expression is frequently associated with the onset of sessility and biofilm formation in numerous bacterial species. Conversely, phosphodiesterase-dependent diminution of c-di-GMP levels by EAL- and HD-GYP-domain proteins is often accompanied by increased motility and virulence. In this study, we individually overexpressed 23 predicted GGDEF, EAL or HD-GYP-domain proteins encoded by the phytopathogen Pectobacterium atrosepticum strain SCRI1043. MS-based detection of c-di-GMP and 5'-phosphoguanylyl-(3'-5')-guanosine in these strains revealed that overexpression of most genes promoted modest 1-10-fold changes in cellular levels of c-di-GMP, with the exception of the GGDEF-domain proteins ECA0659 and ECA3374, which induced 1290- and 7660-fold increases, respectively. Overexpression of most EAL domain proteins increased motility, while overexpression of most GGDEF domain proteins reduced motility and increased poly-β-1,6-N-acetyl-glucosamine-dependent flocculation. In contrast to domain-based predictions, overexpression of the EAL protein ECA3549 or the HD-GYP protein ECA3548 increased c-di-GMP concentrations and reduced motility. Most overexpression constructs altered the levels of secreted cellulases, pectinases and proteases, confirming c-di-GMP regulation of virulence in Pe. atrosepticum. However, there was no apparent correlation between virulence-factor induction and the domain class expressed or cellular c-di-GMP levels, suggesting that regulation was in response to specific effectors within the network, rather than total c-di-GMP concentration. Finally, we demonstrated that the cellular localization patterns vary considerably for GGDEF/EAL/HD-GYP proteins, indicating it is a likely factor restricting specific interactions within the c

  11. Characterization of a DNA-damage-recognition protein from F9 teratocarcinoma cells, which is inducible by retinoic acid and cyclic AMP.

    Science.gov (United States)

    Chao, C C; Sun, N K; Lin-Chao, S

    1993-02-15

    A nuclear protein that recognizes u.v.-damaged DNA was detected in extracts from murine F9 embryonic stem cells using a DNA-binding assay. The nuclear-protein-binding activity was increased in cells after treatment with retinoic acid/dibutyryl cyclic AMP (dbcAMP), with optimum induction at 6 days. In vitro treatment of nuclear extracts with agents that affect protein conformation (such as urea, Nonidet P40 and Ca2+) slightly modulated the damage-recognition activity. Furthermore, treatment of nuclear extracts with phosphatase dramatically inhibited the binding activity. In addition, damaged-DNA recognition of the nuclear extracts was effectively inhibited by damaged double- and single-stranded DNA. The expression of the nuclear protein with similar characteristics was abundant in HeLa cells and was increased in drug- or u.v.-resistant cells. The findings suggest that the recognition of a u.v.-DNA adduct is modulated, at least in part, by an activity that is induced during retinoic acid/dbcAMP-induced differentiation. These results also imply that the identified damage-recognition protein may be important for the sensitivity or resistance of mammalian cells to DNA damage.

  12. Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.

    Science.gov (United States)

    Mehta, Suresh L; Mendelev, Natalia; Kumari, Santosh; Andy Li, P

    2013-03-01

    Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and

  13. 2-substituted derivatives of adenosine and inosine cyclic 3',5'-phosphate. Synthesis, enzymic activity, and analysis of the structural requirements of the binding locale of the 2-substituent on bovine brain protein kinase.

    Science.gov (United States)

    Meyer, R B; Uno, H; Robins, R K; Simon, L N; Miller, J P

    1975-07-29

    A number of 2-substituted cyclic nucleotide derivatives were synthesized and investigated as activators of cAMP-dependent protein kinase and as substrates for and inhibitors of cAMP phosphodiesterase. Ring closure of 5-amino-1-beta-D-ribofuranosylimidazol-4-carboxamide cyclic 3',5'-phosphate (1) with various aldehydes according to a new procedure (Meyer, R. B., Jr., Shuman, D.A., and Robins, R. K. (1974), J. Am. Chem. Soc. 96, 4962) gave new derivatives of adenosine cyclic 3',5'-phosphate with the following 2-substituents: n-propyl, n-hexl, n-octyl, n-decyl, styryl, o-methoxyphenyl, and 2-thienyl. Alkylation of 2-mercaptoadenosine cyclic 3',5'-phosphate (20, Meyer et al., 1974) gave new cAMP derivatives with the following 2-substituent: ethylthio, n-propylthio, isopropylthio, allylthio, n-decylthio, and benzylthio. Deamination of 2-methyl-,2-n-butyl-, and 2-ethylthioadenosine cyclic 3',5'-phosphate. Using multiple regression analysis, a striking relationship was found between the relative potency of the compounds as activators of bovine brain cAMP-dependent protein kinase and parameters describing the hydrophobic, steric, and electronic character of the substituents on these compounds. All compounds were substrates for a cyclic nucleotide phosphodiesterase preparation from rabbit kidney. Additionally, the compounds were as a group, good inhibitors of the hydrolysis of cAMP by phosphodiesterase preparations from rabbit lung, beef heart, and dog heart.

  14. Cyclic Vitalism

    DEFF Research Database (Denmark)

    Halse, Sven

    2014-01-01

    of taking such a unilateral view of what constituted a Vitalist concept of life. It could lead to a misunderstanding of Vitalist way of thinking, Rasch said, if the focus were only set upon the enthusiastic surplus, the worshipping of youth and health. To Vitalists, life is more than that. It is a totality...... that also encompasses notions of destruction, decay and death. “All life symbols in literature around 1900 are at the same time symbols of death”. (Rasch, W. 1967:24) Through the analyses of three poems, this article aims to show concrete examples of how cyclic Vitalist thinking is embedded in poetry...... of the era. The analyses include a further sub-categorisation to capture the different types of Life Force dealt with in the texts. By way of an introduction, Vitalism is discussed within the context of the scientific and social developments of the 19th Century....

  15. Comparison of phosphorylation of ribosomal proteins from HeLa and Krebs II ascites-tumour cells by cyclic AMP-dependent and cyclic GMP-dependent protein kinases

    DEFF Research Database (Denmark)

    Issinger, O G; Beier, H; Speichermann, N

    1980-01-01

    identified by two-dimensional gel electrophoresis. Almost identical results were obtained when ribosomal subunits from HeLa or ascites-tumour cells were used. About 50-60% of the total radioactive phosphate incorporated into small-subunit ribosomal proteins by either kinase was associated with protein S6...

  16. Effects of selective inhibition of protein kinase C, cyclic AMP-dependent protein kinase, and Ca(2+)-calmodulin-dependent protein kinase on neurite development in cultured rat hippocampal neurons.

    Science.gov (United States)

    Cabell, L; Audesirk, G

    1993-06-01

    A variety of experimental evidence suggests that calmodulin and protein kinases, especially protein kinase C, may participate in regulating neurite development in cultured neurons, particularly neurite initiation. However, the results are somewhat contradictory. Further, the roles of calmodulin and protein kinases on many aspects of neurite development, such as branching or elongation of axons vs dendrites, have not been extensively studied. Cultured embryonic rat hippocampal pyramidal neurons develop readily identifiable axons and dendrites. We used this culture system and the new generation of highly specific protein kinase inhibitors to investigate the roles of protein kinases and calmodulin in neurite development. Neurons were cultured for 2 days in the continuous presence of calphostin C (a specific inhibitor of protein kinase C), KT5720 (inhibitor of cyclic AMP-dependent protein kinase), KN62 (inhibitor of Ca(2+)-calmodulin-dependent protein kinase II), or calmidazolium (inhibitor of calmodulin), each at concentrations from approximately 1 to 10 times the concentration reported in the literature to inhibit each kinase by 50%. The effects of phorbol 12-myristate 13-acetate (an activator of protein kinase C) and 4 alpha-phorbol 12,13-didecanoate (an inactive phorbol ester) were also tested. At concentrations that had no effect on neuronal viability, calphostin C reduced neurite initiation and axon branching without significantly affecting the number of dendrites per neuron, dendrite branching, dendrite length, or axon length. Phorbol 12-myristate 13-acetate increased axon branching and the number of dendrites per cell, compared to the inactive 4 alpha-phorbol 12,13-didecanoate. KT5720 inhibited only axon branching. KN62 reduced axon length, the number of dendrites per neuron, and both axon and dendrite branching. At low concentrations, calmidazolium had no effect on any aspect of neurite development, but at high concentrations, calmidazolium inhibited every

  17. Protein Misfolding Cyclic Amplification and Its Application%蛋白质错误折叠循环扩增技术及其应用

    Institute of Scientific and Technical Information of China (English)

    周瑞敏; 田婵; 董小平

    2008-01-01

    可传播性海绵状脑病是一类由朊病毒侵袭中枢神经系统而引起的致死性神经退行性疾病.在朊病毒病的病理过程中,细胞正常朊蛋白PrPc(cellular PrP)转化为异常构象的PrPSc(scrapie PrP)是至关重要的.目前,PrPSc转化增殖及致病机理仍不清楚.蛋白质错误折叠循环扩增(protein misfolding cyclic amplification,PMCA)技术的出现和应用,为研究朊病毒病的发病机制和发展敏感性高、特异性强的检测方法提供了很好的技术平台.

  18. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I

    Energy Technology Data Exchange (ETDEWEB)

    Strand, Deserah D.; Livingston, Aaron K.; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M.; Fisher, Nicholas; Froehlich, John E.; Cruz, Jeffrey A.; Minhas, Deepika; Hixson, Kim K.; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M.

    2017-01-13

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (hcef2) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force (pmf), activation of the photoprotective qE response, and the accumulation of H2O2 . Surprisingly, hcef2 was mapped to a nonsense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash induced thylakoid electric field suggest that these defect lead to accumulation of H2O2 in hcef2, which we have previously shown leads to activation of NDHrelated CEF. We observed similar increases in CEF and H2O2 accumulation in other translation defective mutants, suggesting that loss of coordination in plastid protein levels lead to imbalances in the photosynthetic energy balance that leads to increased CEF. These results, together with a large body of previous observations, support a general model in which processes that imbalances in chloroplast energetics result in the production of H2O2 , which activates CEF, either as a redox signal or by inducing deficits in ATP levels.

  19. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I

    Science.gov (United States)

    Strand, Deserah D.; Livingston, Aaron K.; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M.; Fisher, Nicholas; Froehlich, John E.; Cruz, Jeffrey A.; Minhas, Deepika; Hixson, Kim K.; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M.

    2017-01-01

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (hcef2) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force (pmf), activation of the photoprotective qE response, and the accumulation of H2O2. Surprisingly, hcef2 was mapped to a non-sense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex, and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash-induced thylakoid electric field suggest that these defect lead to accumulation of H2O2 in hcef2, which we have previously shown leads to activation of NDH-related CEF. We observed similar increases in CEF, as well as increases in H2O2 accumulation, in other translation defective mutants. This suggests that loss of coordination in plastid protein levels lead to imbalances in photosynthetic energy balance that leads to an increase in CEF. These results taken together with a large body of previous observations, support a general model in which processes that lead to imbalances in chloroplast energetics result in the production of H2O2, which in turn activates CEF. This activation could be from either H2O2 acting as a redox signal, or by a secondary effect from H2O2 inducing a deficit in ATP. PMID:28133462

  20. Mucin-like glycoprotein secretion is mediated by cyclic-AMP and protein kinase C signal transduction pathways in rat corneal epithelium.

    Science.gov (United States)

    Nakamura, M; Endo, K; Nakata, K

    1998-05-01

    Ocular surface mucin is secreted from both goblet cells in the conjunctival epithelium and corneal epithelial cells. To clarify its mechanism of secretion in corneal epithelial cells, a rat cornea organ culture system was used to evaluate the second messenger roles of cyclic-AMP (cAMP), cyclic-GMP (cGMP) and protein kinase C (PKC) in modulating mucin-like glycoprotein secretion. Rat cornea sections (3 mm diameter) were cultured in TC-199 medium, and radiolabeled with sodium sulfate for 18 hr. After washing, the corneas were treated with various second messenger modulating agents for 30 min. The culture media were reacted with Dolichos biflorus (DBA)-lectin, and mucin-like glycoprotein was isolated. Then the radioactivity of DBA-binding mucin-like glycoprotein was isolated. Then the radioactivity of DBA-binding mucin-like glycoprotein was measured. There was a time-dependent increase in mucin-like glycoprotein was measured. There was a time-dependent increase in mucin-like glycoprotein secretion, whereas after corneal epithelial debridement the secretion was markedly inhibited by 81%. Mucin-like glycoprotein secretion was stimulated in a dose-dependent manner following elevation of cAMP levels by exposure to either forskolin, dibutyryl cAMP or 3-isobutyl-1-methylxanthine. Concomitant exposure to the cAMP dependent protein kinase inhibitor, KT5720 completely inhibited their stimulatory effects. Neither exposure to dibutyryl cGMP nor nitroprusside affected mucin-like glycoprotein secretion. Stimulation by PKC, phorbol 12, 13-dibutyrate (PDBu) also increased mucin-like glycoprotein secretion in a dose-dependent fashion. The PKC inhibitor, calphostin C completely inhibited the stimulation by PDBu of mucine-like glycoprotein secretion. These results demonstrate that corneal epithelial cells secrete mucin-like glycoprotein, which is mediated by cAMP and PKC signal transduction pathways.

  1. The amount of citrullinated proteins in synovial tissue is related to serum anti-cyclic citrullinated peptide (anti-CCP) antibody levels.

    Science.gov (United States)

    Olivares-Martínez, Elizabeth; Hernández-Ramírez, Diego F; Núñez-Álvarez, Carlos A; Cabral, Antonio R; Llorente, Luis

    2016-01-01

    The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes. Patients with high amount of citrullinated proteins in synovial tissue (3 out of 7) have high levels of anti-CCP in serum. However, in the remaining 4 patients, the amount of synovial citrullinated proteins was minimal and their sera showed low levels of anti-CCP antibodies. Furthermore, we observed an increase in PADI2 mRNA expression in RA synovial tissue compared with OA patients (p = 0.02). We detected PADI3 mRNA in the synovial tissue of RA patients, but not in the tissue of OA patients. Even though fibroblast-type synoviocytes in RA are not the main source of PADs in the synovial tissue, they express PADI2 mRNA moderately, PADI4 mRNA weakly, while there is no detectable expression of PADI3 mRNA. In conclusion, we found a variety of citrullinated proteins in the synovial tissue of RA patients and the amount of such proteins is related to serum concentration of anti-CCP antibodies. We identified the presence of PADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with RA.

  2. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding.

    Science.gov (United States)

    Ouyang, Songying; Song, Xianqiang; Wang, Yaya; Ru, Heng; Shaw, Neil; Jiang, Yan; Niu, Fengfeng; Zhu, Yanping; Qiu, Weicheng; Parvatiyar, Kislay; Li, Yang; Zhang, Rongguang; Cheng, Genhong; Liu, Zhi-Jie

    2012-06-29

    STING is an essential signaling molecule for DNA and cyclic di-GMP (c-di-GMP)-mediated type I interferon (IFN) production via TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway. It contains an N-terminal transmembrane region and a cytosolic C-terminal domain (CTD). Here, we describe crystal structures of STING CTD alone and complexed with c-di-GMP in a unique binding mode. The strictly conserved aa 153-173 region was shown to be cytosolic and participated in dimerization via hydrophobic interactions. The STING CTD functions as a dimer and the dimerization was independent of posttranslational modifications. Binding of c-di-GMP enhanced interaction of a shorter construct of STING CTD (residues 139-344) with TBK1. This suggests an extra TBK1 binding site, other than serine 358. This study provides a glimpse into the unique architecture of STING and sheds light on the mechanism of c-di-GMP-mediated TBK1 signaling.

  3. The Xanthomonas oryzae pv. oryzae PilZ Domain Proteins Function Differentially in Cyclic di-GMP Binding and Regulation of Virulence and Motility.

    Science.gov (United States)

    Yang, Fenghuan; Tian, Fang; Chen, Huamin; Hutchins, William; Yang, Ching-Hong; He, Chenyang

    2015-07-01

    The PilZ domain proteins have been demonstrated to be one of the major types of receptors mediating cyclic di-GMP (c-di-GMP) signaling pathways in several pathogenic bacteria. However, little is known about the function of PilZ domain proteins in c-di-GMP regulation of virulence in the bacterial blight pathogen of rice Xanthomonas oryzae pv. oryzae. Here, the roles of PilZ domain proteins PXO_00049 and PXO_02374 in c-di-GMP binding, regulation of virulence and motility, and subcellular localization were characterized in comparison with PXO_02715, identified previously as an interactor with the c-di-GMP receptor Filp to regulate virulence. The c-di-GMP binding motifs in the PilZ domains were conserved in PXO_00049 and PXO_02374 but were less well conserved in PXO_02715. PXO_00049 and PXO_02374 but not PXO_02715 proteins bound to c-di-GMP with high affinity in vitro, and the R(141) and R(10) residues in the PilZ domains of PXO_00049 and PXO_02374, respectively, were crucial for c-di-GMP binding. Gene deletion of PXO_00049 and PXO_02374 resulted in significant increases in virulence and hrp gene transcription, indicating their negative regulation of virulence via type III secretion system expression. All mutants showed significant changes in sliding motility but not exopolysaccharide production and biofilm formation. In trans expression of the full-length open reading frame (ORF) of each gene in the relevant mutants led to restoration of the phenotype to wild-type levels. Moreover, PXO_00049 and PXO_02374 displayed mainly multisite subcellular localizations, whereas PXO_02715 showed nonpolar distributions in the X. oryzae pv. oryzae cells. Therefore, this study demonstrated the different functions of the PilZ domain proteins in mediation of c-di-GMP regulation of virulence and motility in X. oryzae pv. oryzae.

  4. A cyclic and intermittent very low-protein diet can have beneficial effects against advanced diabetic nephropathy in Wistar fatty (fa/fa) rats, an animal model of type 2 diabetes and obesity.

    Science.gov (United States)

    Kitada, Munehiro; Ogura, Yoshio; Suzuki, Taeko; Monnno, Itaru; Kanasaki, Keizo; Watanabe, Ai; Koya, Daisuke

    2017-08-12

    A low-protein diet (LPD), particularly, very low-protein diet (VLPD) is expected for reno-protection in advanced chronic kidney disease, including diabetic nephropathy. We previously also demonstrated that a VLPD clearly improved advanced diabetic nephropathy in a type 2 diabetes and obesity rat. However, clinically, an everyday long-term VLPD contributes to poor adherence, which may be related to controvertial results of an LPD on the suppression for diabetic nephropathy, and has nutritional issues, such as sarcopenia or protein-energy wasting. The aim of this study is to elucidate the reno-protective effect of a cyclic and intermittent VLPD, not an everyday VLPD, against the advanced experimental diabetic nephropathy. Diabetic male Wistar fatty (fa/fa) rats (WFRs) were treated with a standard diet (STD; 23.84% protein) or a cyclic and intermittent VLPD (5.77% protein) consisting of an STD for 3 days and a VLPD for 4 days a week for 20 weeks beginning at 24 weeks of age. A cyclic and intermittent VLPD significantly improved renal hypertrophy, and significantly decreased urinary albumin and liver-type fatty acid binding protein (L-FABP) excretion without changes in body weight or exacerbation of HbA1c levels in diabetic rats. Additionally, diabetes-induced renal injuries including fibrosis, tubular cell damage and inflammation were significantly ameliorated by a cyclic and intermittent VLPD in diabetic rats. Thus, based on our experimental data, a cyclic and intermittent VLPD may be a dietary regimen that is easy to continue and has a less risk of malnutrition, compared to an everyday long-term VLPD, against advanced diabetic nephropathy. This article is protected by copyright. All rights reserved.

  5. The Diagnostic Utility of Anti-cyclic Citrullinated Peptide Antibodies, Matrix Metalloproteinase-3, Rheumatoid Factor, Erythrocyte Sedimentation Rate, and C-reactive Protein in Patients with Erosive and Non-erosive Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    O. Shovman

    2005-01-01

    Full Text Available Objective: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3, anti-cyclic citrullinated peptide (CCP antibodies, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP in patients with erosive and non-erosive rheumatoid arthritis (RA.

  6. Conservation of major surface protein 1 genes of Anaplasma marginale during cyclic transmission between ticks and cattle.

    Science.gov (United States)

    Bowie, Michael V; de la Fuente, Jose; Kocan, Katherine M; Blouin, Edmour F; Barbet, Anthony F

    2002-01-09

    Bovine anaplasmosis is a rickettsial disease of world-wide economic importance caused by Anaplasma marginale. Several major surface proteins with conserved gene sequences have been examined as potential candidates for vaccines and/or diagnostic assays. Major surface protein 1 (MSP1) is composed of polypeptides MSP1a and MSP1b. MSP1a is expressed from the single copy gene msp1 alpha and MSP1b is expressed by members of the msp1 beta multigene family. In order to determine if the msp1 genes are conserved, primers specific for msp1 alpha, msp1 beta(1), and msp1 beta(2) genes were synthesized and used to amplify msp1 sequences of A. marginale from tick cell cultures, from cattle during acute and chronic infections and from salivary glands of Dermacentor variabilis. Protein sequences of MSP1a, MSP1b(1) and MSP1b(2) were conserved during the life cycle of the parasite. No amino acid changes were observed in MSP1a. However, small variations were observed in the MSP1b(1) and MSP1b(2) protein sequences, which could be attributed to recombination, selection for sub-populations of A. marginale in the vertebrate host and/or PCR errors. Several isolate-specific sequences were also observed. Based on the information obtained in this study, the MSP1 protein appears to be fairly well conserved and a potential vaccine candidate.

  7. Assay of adenosine 3',5' cyclic monophosphate by stimulation of protein kinase: a method not involving radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Handa, A.K.; Bressan, R.A.

    1980-03-01

    In order to meet a need for a cAMP assay which is not subject to interference by compounds in plant extracts, and which is suitable for use on occasions separated by many /sup 32/P half-lives, an assay based on cAMP-dependent protein kinase has been developed which does not require the use of (..gamma..-/sup 32/P)ATP. Instead of measuring the cAMP-stimulated increase in the rate of transfer of (..gamma..-/sup 32/P) phosphate from (..gamma..-/sup 32/P)ATP to protein, the rate of loss of ATP from the reaction mixture is determined. The ATP remaining after the protein kinase reaction is assayed by ATP-dependent chemiluminescence of the firefly luciferin-luciferase system. Under conditions of the protein kinase reaction in which a readily measurable decrease in ATP concentration occurs, the logarithm of the concentration of ATP decreases in proportion to the cAMP concentration, i.e., the reaction can be described by the equation: (ATP) = (ATP)/sub 0/ e/sup -(cAMP)kt/. The assay based on this relationship can detect less than 1 pmol of cAMP. The levels of cAMP found with this assay after partial purification of the cAMP from rat tissue, algal cells, and the media in which the cells were grown agreed with measurements made by the cAMP binding-competition assay of Gilman, and the potein kinase stimulation assay based on transfer of (/sup 32/P) phosphate from (..gamma..-/sup 32/P)ATP to protein. All of the enzymes and chemicals required for the assay of cAMP by protein kinase catalyzed loss of ATP can be stored frozen for months, making the assay suitable for occasional use.

  8. Exchange Protein Activated by Cyclic AMP 2 (Epac2) Plays a Specific and Time-Limited Role in Memory Retrieval

    NARCIS (Netherlands)

    Ostroveanu, Anghelus; van der Zee, Eddy A.; Eisel, Ulrich L. M.; Schmidt, Martina; Nijholt, Ingrid M.

    2010-01-01

    Knowledge on the molecular mechanisms involved in memory retrieval is limited due to the lack of tools to study this stage of the memory process. Here we report that exchange proteins activated by cAMP (Epac) play a surprisingly specific role in memory retrieval. Intrahippocampal injection of the

  9.  Phosphodiesterase 3 mediates cross-talk between the protein kinase- and cGMP- dependent pathways and cyclic AMP metabolism

    Directory of Open Access Journals (Sweden)

    Edyta Makuch

    2012-07-01

    Full Text Available  PDE3 is a dual-substrate phosphodiesterase responsible for hydrolyzing both cAMP and cGMP whilst being simultaneously inhibited by cGMP. This feature is related to presence of the 44 amino acid insert in the catalytic domain, which determines the mechanism of introduction of the cyclic nucleotide into the catalytic pocket of the enzyme. Once bound in the catalytic site cGMP results in steric hindrance for cAMP to enter the site. The regulatory domain of PDE3 consists of two hydrophobic regions: NHR1 and NHR2. Their presence defines the enzyme’s intracellular localization, thus determining its participation in particular signaling cascades. Due to the properties of PDE3 this enzyme has exceptional importance for the cross-talk between cAMP-dependent signaling and other cascades. There are two different mechanisms of action of PDE3 enzymes in cell signaling pathways. In many signaling cascades assembly of a signalosome is necessary for phosphorylation and activation of the PDE3 proteins. In response to certain hormones and growth factors, PDE3 merges the metabolism of cAMP with protein kinase-dependent signaling pathways. PDE3 also controls the level of cAMP with regard to the alternating concentration of cGMP. This effect occurs in signaling cascades activated by natriuretic peptide.

  10. Crystal structure of cGMP-dependent protein kinase Iβ cyclic nucleotide-binding-B domain : Rp-cGMPS complex reveals an apo-like, inactive conformation.

    Science.gov (United States)

    Campbell, James C; VanSchouwen, Bryan; Lorenz, Robin; Sankaran, Banumathi; Herberg, Friedrich W; Melacini, Giuseppe; Kim, Choel

    2017-01-01

    The R-diastereomer of phosphorothioate analogs of cGMP, Rp-cGMPS, is one of few known inhibitors of cGMP-dependent protein kinase I (PKG I); however, its mechanism of inhibition is currently not fully understood. Here, we determined the crystal structure of the PKG Iβ cyclic nucleotide-binding domain (PKG Iβ CNB-B), considered a 'gatekeeper' for cGMP activation, bound to Rp-cGMPS at 1.3 Å. Our structural and NMR data show that PKG Iβ CNB-B bound to Rp-cGMPS displays an apo-like structure with its helical domain in an open conformation. Comparison with the cAMP-dependent protein kinase regulatory subunit (PKA RIα) showed that this conformation resembles the catalytic subunit-bound inhibited state of PKA RIα more closely than the apo or Rp-cAMPS-bound conformations. These results suggest that Rp-cGMPS inhibits PKG I by stabilizing the inactive conformation of CNB-B. © 2016 Federation of European Biochemical Societies.

  11. Sodium depletion enhances renal expression of (pro)renin receptor via cyclic GMP-protein kinase G signaling pathway.

    Science.gov (United States)

    Huang, Jiqian; Siragy, Helmy M

    2012-02-01

    (Pro)renin receptor (PRR) is expressed in renal vasculature, glomeruli, and tubules. The physiological regulation of this receptor is not well established. We hypothesized that sodium depletion increases PRR expression through cGMP- protein kinase G (PKG) signaling pathway. Renal PRR expressions were evaluated in Sprague-Dawley rats on normal sodium or low-sodium diet (LS) and in cultured rat proximal tubular cells and mouse renal inner medullary collecting duct cells exposed to LS concentration. LS augmented PRR expression in renal glomeruli, proximal tubules, distal tubules, and collecting ducts. LS also increased cGMP production and PKG activity. In cells exposed to normal sodium, cGMP analog increased PKG activity and upregulated PRR expression. In cells exposed to LS, blockade of guanylyl cyclase with 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one decreased PKG activity and downregulated PRR expression. PKG inhibition decreased phosphatase protein phosphatase 2A activity; suppressed LS-mediated phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, c-Jun, and nuclear factor-κB p65; and attenuated LS-mediated PRR upregulation. LS also enhanced DNA binding of cAMP response element binding protein 1 to cAMP response elements, nuclear factor-κB p65 to nuclear factor-κB elements, and c-Jun to activator protein 1 elements in PRR promoter in proximal tubular cells. We conclude that sodium depletion upregulates renal PRR expression via the cGMP-PKG signaling pathway by enhancing binding of cAMP response element binding protein 1, nuclear factor-κB p65, and c-Jun to PRR promotor.

  12. Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI.

    Science.gov (United States)

    Ichinohe, T; Takayama, H; Ezumi, Y; Yanagi, S; Yamamura, H; Okuma, M

    1995-11-24

    Platelet glycoprotein (GP) VI is a so-far uncharacterized 62-kDa membrane protein, whose deficiency results in selective impairment in collagen-induced platelet aggregation. Our group previously reported a human polyclonal antibody (anti-p62 IgG) that induces activation of normal, but not of GPVI-deficient, platelets in an Fc-independent manner. The F(ab')2 fragments of this antibody (F(ab')2-anti-p62) stimulated tyrosine phosphorylation of numerous proteins, which was not prevented even in the presence of cAMP-increasing agents such as prostacyclin. Pretreatment of platelets with the protein-tyrosine kinase (PTK) inhibitor tyrphostin A47 completely abolished F(ab')2-anti-p62-induced platelet aggregation in parallel with dose-dependent inhibition of protein-tyrosine phosphorylation, indicating an essential requirement of PTK activity for generating GPVI-mediated signaling. We found that two cytosolic PTKs, c-Src and Syk, became rapidly activated in response to F(ab')2-anti-p62 in a way insensitive to elevation of cAMP. In contrast, in the presence of prostacyclin, F(ab')2-anti-p62 did not stimulate tyrosine phosphorylation of the focal adhesion kinase. cAMP-insensitive activation of c-Src and Syk was also observed in collagen but not thrombin-stimulated platelets. Moreover, either F(ab')2-anti-p62 or collagen stimulated cAMP-insensitive tyrosine phosphorylation of phospholipase C-gamma 2. These results indicate that the receptor-mediated activation of several PTKs in platelets is regulated through a cAMP-sensitive or -insensitive mechanism depending on the nature of each stimulus, and also suggest that GPVI engagement is coupled to cAMP-insensitive activation of c-Src and Syk accompanied by tyrosine phosphorylation of numerous substrates including phospholipase C-gamma 2 in a manner similar to collagen stimulation.

  13. Growth hormone release from chicken anterior pituitary cells in primary culture: TRH and hpGRF synergy, protein synthesis, and cyclic adenosine 3'5'-monophosphate.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1989-01-01

    Our earlier work showed that the effects of thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) on growth hormone (GH) release are synergistic (greater than additive) in a primary culture of chicken adenohypophyseal cells. The purpose of the present studies was to investigate the possible participation of protein synthesis and cyclic adenosine 3'5'-monophosphate (cAMP) in GH release. Following culture (48 hr), cells were incubated for 2 hr with test agents. Cycloheximide (an inhibitor of protein synthesis) had no effect on basal (absence of test agent) GH release or hpGRF-induced GH release. However, cycloheximide abolished the synergy between TRH and hpGRF. Although neither TRH nor hpGRF alone stimulated GH production (intracellular GH plus GH release) during a 2-hr incubation period, in combination these secretagogues increased total GH. These findings suggest that GH release from the chicken somatotroph under conditions of TRH and hpGRF synergy requires protein synthesis. In other studies, cells were exposed to agents inducing the formation of cAMP and either TRH or hpGRF. 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX; 10(-3) M) alone stimulated GH release to values between 30 and 50% over the basal value. The combined effects of each of these agents and TRH on GH release were synergistic. Similarly, IBMX and hpGRF exerted synergistic effects on GH release. In contrast, no synergy was shown between hpGRF and either 8 Br-cAMP or forskolin; their combined actions were less than additive.

  14. Presenilins regulate neurotrypsin gene expression and neurotrypsin-dependent agrin cleavage via cyclic AMP response element-binding protein (CREB) modulation.

    Science.gov (United States)

    Almenar-Queralt, Angels; Kim, Sonia N; Benner, Christopher; Herrera, Cheryl M; Kang, David E; Garcia-Bassets, Ivan; Goldstein, Lawrence S B

    2013-12-06

    Presenilins, the catalytic components of the γ-secretase complex, are upstream regulators of multiple cellular pathways via regulation of gene transcription. However, the underlying mechanisms and the genes regulated by these pathways are poorly characterized. In this study, we identify Tequila and its mammalian ortholog Prss12 as genes negatively regulated by presenilins in Drosophila larval brains and mouse embryonic fibroblasts, respectively. Prss12 encodes the serine protease neurotrypsin, which cleaves the heparan sulfate proteoglycan agrin. Altered neurotrypsin activity causes serious synaptic and cognitive defects; despite this, the molecular processes regulating neurotrypsin expression and activity are poorly understood. Using γ-secretase drug inhibitors and presenilin mutants in mouse embryonic fibroblasts, we found that a mature γ-secretase complex was required to repress neurotrypsin expression and agrin cleavage. We also determined that PSEN1 endoproteolysis or processing of well known γ-secretase substrates was not essential for this process. At the transcriptional level, PSEN1/2 removal induced cyclic AMP response element-binding protein (CREB)/CREB-binding protein binding, accumulation of activating histone marks at the neurotrypsin promoter, and neurotrypsin transcriptional and functional up-regulation that was dependent on GSK3 activity. Upon PSEN1/2 reintroduction, this active epigenetic state was replaced by a methyl CpG-binding protein 2 (MeCP2)-containing repressive state and reduced neurotrypsin expression. Genome-wide analysis revealed hundreds of other mouse promoters in which CREB binding is similarly modulated by the presence/absence of presenilins. Our study thus identifies Tequila and neurotrypsin as new genes repressed by presenilins and reveals a novel mechanism used by presenilins to modulate CREB signaling based on controlling CREB recruitment.

  15. Effect of Increased Cyclic AMP Concentration on Muscle Protein Synthesis and Beta-Adrenergic Receptor Expression in Chicken Skeletal Muscle Cells in Culture

    Science.gov (United States)

    Young, R. B.; Vaughn, J. R.; Bridge, K. Y.; Smith, C. K.

    1998-01-01

    Analogies of epinephrine are known to cause hypertrophy of skeletal muscle when fed to animals. These compounds presumably exert their physiological action through interaction with the P-adrenergic receptor. Since the intracellular signal generated by the Beta-adrenergic receptor is cyclic AMP (cAMP), experiments were initiated in cell culture to determine if artificial elevation of cAMP by treatment with forskolin would alter muscle protein metabolism and P-adrenergic receptor expression. Chicken skeletal muscle cells after 7 days in culture were treated with 0.2-30 micrometers forskolin for a total of three days. At the end of the treatment period, both the concentration of cAMP and the quantity of myosin heavy chain (MHC) were measured. Concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. In contrast, the quantity of MHC was increased approximately 50% above control cells at 0.2 micrometers forskolin, but exhibited a gradual decline at higher levels of forskolin so that the quantity of MHC in cells treated with 30 micrometers forskolin was not significantly different from controls. Curiously, the intracellular concentration of cAMP which elicited the maximum increase in the quantity of MHC was only 40% higher than cAMP concentration in control cells.

  16. Macrophage inflammatory protein 1alpha inhibits postentry steps of human immunodeficiency virus type 1 infection via suppression of intracellular cyclic AMP.

    Science.gov (United States)

    Amella, Carol-Ann; Sherry, Barbara; Shepp, David H; Schmidtmayerova, Helena

    2005-05-01

    Primary isolates of human immunodeficiency virus type 1 (HIV-1) predominantly use chemokine receptor CCR5 to enter target cells. The natural ligands of CCR5, the beta-chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES, interfere with HIV-1 binding to CCR5 receptors and decrease the amount of virions entering cells. Although the inhibition of HIV-1 entry by beta-chemokines is well documented, their effects on postentry steps of the viral life cycle and on host cell components that control the outcome of infection after viral entry are not well defined. Here, we show that all three beta-chemokines, and MIP-1alpha in particular, inhibit postentry steps of the HIV-1 life cycle in primary lymphocytes, presumably via suppression of intracellular levels of cyclic AMP (cAMP). Productive HIV-1 infection of primary lymphocytes requires cellular activation. Cell activation increases intracellular cAMP, which is required for efficient synthesis of proviral DNA during early steps of viral infection. Binding of MIP-1alpha to cognate receptors decreases activation-induced intracellular cAMP levels through the activation of inhibitory G proteins. Furthermore, inhibition of one of the downstream targets of cAMP, cAMP-dependent PKA, significantly inhibits synthesis of HIV-1-specific DNA without affecting virus entry. These data reveal that beta-chemokine-mediated inhibition of virus replication in primary lymphocytes combines inhibitory effects at the entry and postentry levels and imply the involvement of beta-chemokine-induced signaling in postentry inhibition of HIV-1 infection.

  17. Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study.

    Science.gov (United States)

    Bøyesen, Pernille; Hoff, Mari; Odegård, Sigrid; Haugeberg, Glenn; Syversen, Silje W; Gaarder, Per I; Okkenhaug, Cecilie; Kvien, Tore K

    2009-01-01

    Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration. 163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up. During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively. Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.

  18. Evaluation of Anti-Cyclic Citrullinated Peptide Autoantibodies and C-Reactive Protein in Common Autoimmune Skin Diseases with and without Arthritis.

    Science.gov (United States)

    Kumari, Bandana; Kumar, Pawan; Chaudhary, Radha Krishna Prasad

    2017-07-01

    Anti-Cyclic Citrullinated Peptides (CCPs) are a well known diagnostic and prognostic noble marker for rheumatoid arthritis. C-Reactive Protein (CRP) is an acute phase protein whose level rises in response to inflammation. This study was undertaken to show the role of the two markers (anti-CCPs and CRP) in autoimmune skin disorder and their association with associated arthritis in these disorder. Serum anti-CCP antibodies and CRP was measured in 50 patients of autoimmune skin disease of which 28 were of psoriasis, 12 of Systemic Lupus Erythematosus (SLE) and 10 of Pemphigus Vulgaris (PV). These patients were categorised in two groups, with associated arthritis and without arthritis. The serum level of anti-CCP and CRP was correlated with the presence or absence of arthritis in these patients. Control group consists of 20 healthy subjects in which these two parameters were measured. Out of total of 50 patients, anti-CCP was raised in 36.37% of patients with associated arthritis and 12.82% of patients without arthritis whereas CRP was raised in 63.63% of patients with arthritis and 35.89% of patients without arthritis. Mean serum anti-CCP in patient with arthritis was 15.78±13.94 U/ml and without arthritis was 7.56±7.68 U/ml with p=0.01 which was statistically significant. Mean serum CRP in arthritis was 21.11±15.51 mg/l and CRP without arthritis was 13.14±12.27 mg/l with p=0.07 which was statistically not significant. Although both anti-CCP and CRP are valuable markers for autoimmune skin disorder, anti-CCP seems to show significant association with arthritis.

  19. CAP1, an adenylate cyclase-associated protein gene, regulates bud-hypha transitions, filamentous growth, and cyclic AMP levels and is required for virulence of Candida albicans.

    Science.gov (United States)

    Bahn, Y S; Sundstrom, P

    2001-05-01

    In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains with CAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in the cap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles of CAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficient cap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.

  20. Nitration of Tyrosine 247 Inhibits Protein Kinase G-1α Activity by Attenuating Cyclic Guanosine Monophosphate Binding*

    Science.gov (United States)

    Aggarwal, Saurabh; Gross, Christine M.; Rafikov, Ruslan; Kumar, Sanjiv; Fineman, Jeffrey R.; Ludewig, Britta; Jonigk, Danny; Black, Stephen M.

    2014-01-01

    The cGMP-dependent protein kinase G-1α (PKG-1α) is a downstream mediator of nitric oxide and natriuretic peptide signaling. Alterations in this pathway play a key role in the pathogenesis and progression of vascular diseases associated with increased vascular tone and thickness, such as pulmonary hypertension. Previous studies have shown that tyrosine nitration attenuates PKG-1α activity. However, little is known about the mechanisms involved in this event. Utilizing mass spectrometry, we found that PKG-1α is susceptible to nitration at tyrosine 247 and 425. Tyrosine to phenylalanine mutants, Y247F- and Y425F-PKG-1α, were both less susceptible to nitration than WT PKG-1α, but only Y247F-PKG-1α exhibited preserved activity, suggesting that the nitration of Tyr247 is critical in attenuating PKG-1α activity. The overexpression of WT- or Y247F-PKG-1α decreased the proliferation of pulmonary artery smooth muscle cells (SMC), increased the expression of SMC contractile markers, and decreased the expression of proliferative markers. Nitrosative stress induced a switch from a contractile to a synthetic phenotype in cells expressing WT- but not Y247F-PKG-1α. An antibody generated against 3-NT-Y247 identified increased levels of nitrated PKG-1α in humans with pulmonary hypertension. Finally, to gain a more mechanistic understanding of how nitration attenuates PKG activity, we developed a homology model of PKG-1α. This model predicted that the nitration of Tyr247 would decrease the affinity of PKG-1α for cGMP, which we confirmed using a [3H]cGMP binding assay. Our study shows that the nitration of Tyr247 and the attenuation of cGMP binding is an important mechanism regulating in PKG-1α activity and SMC proliferation/differentiation. PMID:24469460

  1. Nitration of tyrosine 247 inhibits protein kinase G-1α activity by attenuating cyclic guanosine monophosphate binding.

    Science.gov (United States)

    Aggarwal, Saurabh; Gross, Christine M; Rafikov, Ruslan; Kumar, Sanjiv; Fineman, Jeffrey R; Ludewig, Britta; Jonigk, Danny; Black, Stephen M

    2014-03-14

    The cGMP-dependent protein kinase G-1α (PKG-1α) is a downstream mediator of nitric oxide and natriuretic peptide signaling. Alterations in this pathway play a key role in the pathogenesis and progression of vascular diseases associated with increased vascular tone and thickness, such as pulmonary hypertension. Previous studies have shown that tyrosine nitration attenuates PKG-1α activity. However, little is known about the mechanisms involved in this event. Utilizing mass spectrometry, we found that PKG-1α is susceptible to nitration at tyrosine 247 and 425. Tyrosine to phenylalanine mutants, Y247F- and Y425F-PKG-1α, were both less susceptible to nitration than WT PKG-1α, but only Y247F-PKG-1α exhibited preserved activity, suggesting that the nitration of Tyr(247) is critical in attenuating PKG-1α activity. The overexpression of WT- or Y247F-PKG-1α decreased the proliferation of pulmonary artery smooth muscle cells (SMC), increased the expression of SMC contractile markers, and decreased the expression of proliferative markers. Nitrosative stress induced a switch from a contractile to a synthetic phenotype in cells expressing WT- but not Y247F-PKG-1α. An antibody generated against 3-NT-Y247 identified increased levels of nitrated PKG-1α in humans with pulmonary hypertension. Finally, to gain a more mechanistic understanding of how nitration attenuates PKG activity, we developed a homology model of PKG-1α. This model predicted that the nitration of Tyr(247) would decrease the affinity of PKG-1α for cGMP, which we confirmed using a [(3)H]cGMP binding assay. Our study shows that the nitration of Tyr(247) and the attenuation of cGMP binding is an important mechanism regulating in PKG-1α activity and SMC proliferation/differentiation.

  2. Cyclic Vomiting Syndrome

    Science.gov (United States)

    ... or the flu eating certain foods, such as chocolate or cheese, or additives such as caffeine, nitrites— ... people with cyclic vomiting syndrome. Eating, Diet, and Nutrition During the prodrome and vomiting phases of cyclic ...

  3. Superextensions of cyclic semigroups

    Directory of Open Access Journals (Sweden)

    V. M. Gavrylkiv

    2013-06-01

    Full Text Available Given a cyclic semigroup $S$ we study right and left zeros,singleton left ideals, the minimal ideal, left cancelable andright cancelable elements of superextensions $lambda(S$ andcharacterize cyclic semigroups whose superextensions arecommutative.

  4. Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal synaptic potentiation and pain hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Ceng Luo

    Full Text Available Synaptic long-term potentiation (LTP at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes. Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear. Here, we found that Protein Kinase G1 (PKG-I localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP. Using the Cre-lox P system, we generated nociceptor-specific knockout mice lacking PKG-I specifically in presynaptic terminals of nociceptors in the spinal cord, but not in post-synaptic neurons or elsewhere (SNS-PKG-I(-/- mice. Patch clamp recordings showed that activity-induced LTP at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG was completely abolished in SNS-PKG-I(-/- mice, although basal synaptic transmission was not affected. Analyses of synaptic failure rates and paired-pulse ratios indicated a role for presynaptic PKG-I in regulating the probability of neurotransmitter release. Inositol 1,4,5-triphosphate receptor 1 and myosin light chain kinase were recruited as key phosphorylation targets of presynaptic PKG-I in nociceptive neurons. Finally, behavioural analyses in vivo showed marked defects in SNS-PKG-I(-/- mice in several models of activity-induced nociceptive hypersensitivity, and pharmacological studies identified a clear contribution of PKG-I expressed in spinal terminals of nociceptors. Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are

  5. Cyclic Railway Timetable Optimization

    NARCIS (Netherlands)

    L.W.P. Peeters (Leon)

    2003-01-01

    textabstractCyclic Railway Timetable Optimization describes mathematical models and solution methods for constructing high quality cyclic railway timetables. In a cyclic timetable, a train for a certain destination leaves a certain station at the same time every cycle time, say every half an hour,

  6. Neonatal handling and the maternal odor preference in rat pups: involvement of monoamines and cyclic AMP response element-binding protein pathway in the olfactory bulb.

    Science.gov (United States)

    Raineki, C; De Souza, M A; Szawka, R E; Lutz, M L; De Vasconcellos, L F T; Sanvitto, G L; Izquierdo, I; Bevilaqua, L R; Cammarota, M; Lucion, A B

    2009-03-03

    Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age.

  7. Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects reveal the critical role of PKA's catalytic subunits in anxiety

    Science.gov (United States)

    Briassoulis, George; Keil, Margaret F.; Naved, Bilal; Liu, Sophie; Starost, Matthew F.; Nesterova, Maria; Gokarn, Nirmal; Batistatos, Anna; Wu, T. John; Stratakis, Constantine A.

    2016-01-01

    Cyclic adenosine mono-phosphate-dependent protein kinase (PKA) is critically involved in the regulation of behavioral responses. Previous studies showed that PKA's main regulatory subunit, R1α, is involved in anxiety-like behaviors. The purpose of this study was to determine how the catalytic subunit, Cα, might affect R1α's function and determine its effects on anxiety-related behaviors. The marble bury (MB) and elevated plus maze (EPM) tests were used to assess anxiety-like behavior and the hotplate test to assess nociception in wild type (WT) mouse, a Prkar1a heterozygote (Prkar1a+/-) mouse with haploinsufficiency for the regulatory subunit (R1α), a Prkaca heterozygote (Prkaca+/-) mouse with haploinsufficiency for the catalytic subunit (Cα), and a double heterozygote mouse (Prkar1a+/-/Prkaca+/-) with haploinsufficiency for both R1α and Cα. We then examined specific brain nuclei involved in anxiety. Results of MB test showed a genotype effect, with increased anxiety-like behavior in Prkar1a+/- and Prkar1a+/-/Prkaca+/- compared to WT mice. In the EPM, Prkar1a+/- spent significantly less time in the open arms, while Prkaca+/- and Prkar1a+/-/Prkaca+/- mice displayed less exploratory behavior compared to WT mice. The loss of one Prkar1a allele was associated with a significant increase in PKA activity in the basolateral (BLA) and central (CeA) amygdala and ventromedial hypothalamus (VMH) in both Prkar1a+/- and Prkar1a+/- /Prkaca+/- mice. Alterations of PKA activity induced by haploinsufficiency of its main regulatory or most important catalytic subunits result in anxiety-like behaviors. The BLA, CeA, and VMH are implicated in mediating these PKA effects in brain. PMID:26992826

  8. Suppression of Virulence of Toxigenic Vibrio cholerae by Anethole through the Cyclic AMP (cAMP)-cAMP Receptor Protein Signaling System.

    Science.gov (United States)

    Zahid, M Shamim Hasan; Awasthi, Sharda Prasad; Asakura, Masahiro; Chatterjee, Shruti; Hinenoya, Atsushi; Faruque, Shah M; Yamasaki, Shinji

    2015-01-01

    Use of natural compounds as antivirulence drugs could be an alternative therapeutic approach to modify the outcome of bacterial infections, particularly in view of growing resistance to available antimicrobials. Here, we show that sub-bactericidal concentration of anethole, a component of sweet fennel seed, could suppress virulence potential in O1 El Tor biotype strains of toxigenic Vibrio cholerae, the causative agent of the ongoing 7th cholera pandemic. The expression of cholera toxin (CT) and toxin coregulated pilus (TCP), the major virulence factors of V. cholerae, is controlled through a regulatory cascade involving activation of ToxT with synergistic coupling interaction of ToxR/ToxS with TcpP/TcpH. We present evidence that anethole inhibits in vitro expression of CT and TCP in a toxT-dependent but toxR/toxS-independent manner and through repression of tcpP/tcpH, by using bead-ELISA, western blotting and quantitative real-time RT-PCR assays. The cyclic AMP (cAMP)-cAMP receptor protein (CRP) is a well-studied global signaling system in bacterial pathogens, and this complex is known to suppress expression of tcpP/tcpH in V. cholerae. We find that anethole influences the virulence regulatory cascade by over-expressing cyaA and crp genes. Moreover, suppression of toxigenic V. cholerae-mediated fluid accumulation in ligated ileum of rabbit by anethole demonstrates its potentiality as an antivirulence drug candidate against the diseases caused by toxigenic V. cholerae. Taken altogether, these results revealing a mechanism of virulence inhibition in V. cholerae by the natural compound anethole, may have relevance in designing antivirulence compounds, particularly against multiple antibiotic resistant bacterial pathogens.

  9. The cyclic AMP receptor protein, CRP, is required for both virulence and expression of the minimal CRP regulon in Yersinia pestis biovar microtus.

    Science.gov (United States)

    Zhan, Lingjun; Han, Yanping; Yang, Lei; Geng, Jing; Li, Yingli; Gao, He; Guo, Zhaobiao; Fan, Wei; Li, Gang; Zhang, Lianfeng; Qin, Chuan; Zhou, Dongsheng; Yang, Ruifu

    2008-11-01

    The cyclic AMP receptor protein (CRP) is a bacterial regulator that controls more than 100 promoters, including those involved in catabolite repression. In the present study, a null deletion of the crp gene was constructed for Yersinia pestis bv. microtus strain 201. Microarray expression analysis disclosed that at least 6% of Y. pestis genes were affected by this mutation. Further reverse transcription-PCR and electrophoretic mobility shift assay analyses disclosed a set of 37 genes or putative operons to be the direct targets of CRP, and thus they constitute the minimal CRP regulon in Y. pestis. Subsequent primer extension and DNase I footprinting assays mapped transcriptional start sites, core promoter elements, and CRP binding sites within the DNA regions upstream of pla and pst, revealing positive and direct control of these two laterally acquired plasmid genes by CRP. The crp disruption affected both in vitro and in vivo growth of the mutant and led to a >15,000-fold loss of virulence after subcutaneous infection but a pestis and, particularly, is more important for infection by subcutaneous inoculation. It can further be concluded that the reduced in vivo growth phenotype of the crp mutant should contribute, at least partially, to its attenuation of virulence by both routes of infection. Consistent with a previous study of Y. pestis bv. medievalis, lacZ reporter fusion analysis indicated that the crp deletion resulted in the almost absolute loss of pla promoter activity. The plasminogen activator encoded by pla was previously shown to specifically promote Y. pestis dissemination from peripheral infection routes (subcutaneous infection [flea bite] or inhalation). The above evidence supports the notion that in addition to the reduced in vivo growth phenotype, the defect of pla expression in the crp mutant will greatly contribute to the huge loss of virulence of this mutant strain in subcutaneous infection.

  10. Functional Similarities between the Listeria monocytogenes Virulence Regulator PrfA and Cyclic AMP Receptor Protein: the PrfA* (Gly145Ser) Mutation Increases Binding Affinity for Target DNA

    OpenAIRE

    Vega, Yolanda; Dickneite, Carmen; Ripio, Maria Teresa; Böckmann, Regine; González Zörn, Bruno; Novella, Susanna; Dominguez-Bernal, Gustavo; Goebel, Werner; Vazquez-Boland, Jose A

    1998-01-01

    Most Listeria monocytogenes virulence genes are positively regulated by the PrfA protein, a transcription factor sharing sequence similarities with cyclic AMP (cAMP) receptor protein (CRP). Its coding gene, prfA, is regulated by PrfA itself via an autoregulatory loop mediated by the upstream PrfA-dependent plcA promoter. We have recently characterized prfA* mutants from L. monocytogenes which, as a result of a single amino acid substitution in PrfA, Gly145Ser, constitutively overexpress prfA ...

  11. Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-serine 239 phosphorylation.

    Science.gov (United States)

    Holt, Andrew W; Martin, Danielle N; Shaver, Patti R; Adderley, Shaquria P; Stone, Joshua D; Joshi, Chintamani N; Francisco, Jake T; Lust, Robert M; Weidner, Douglas A; Shewchuk, Brian M; Tulis, David A

    2016-09-01

    Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls

  12. Cyclic phosphonium ionic liquids

    Directory of Open Access Journals (Sweden)

    Sharon I. Lall-Ramnarine

    2014-01-01

    Full Text Available Ionic liquids (ILs incorporating cyclic phosphonium cations are a novel category of materials. We report here on the synthesis and characterization of four new cyclic phosphonium bis(trifluoromethylsulfonylamide ILs with aliphatic and aromatic pendant groups. In addition to the syntheses of these novel materials, we report on a comparison of their properties with their ammonium congeners. These exemplars are slightly less conductive and have slightly smaller self-diffusion coefficients than their cyclic ammonium congeners.

  13. Supplementary Material for: The arabidopsis cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara

    2016-01-01

    Abstract Background Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals. Methods An affinity purification technique was used to identify cyclic nucleotide binding proteins in Arabidopsis thaliana. The identified proteins were subjected to a computational analysis that included a sequence, transcriptional co-expression and functional annotation analysis in order to assess their potential role in plant cyclic nucleotide signaling. Results A total of twelve cyclic nucleotide binding proteins were identified experimentally including key enzymes in the Calvin cycle and photorespiration pathway. Importantly, eight of the twelve proteins were shown to contain putative cyclic nucleotide binding domains. Moreover, the identified proteins are post-translationally modified by nitric oxide, transcriptionally co-expressed and annotated to function in hydrogen peroxide signaling and the defence response. The activity of one of these proteins, GLYGOLATE OXIDASE 1, a photorespiratory enzyme that produces hydrogen peroxide in response to Pseudomonas, was shown to be repressed by a combination of cGMP and nitric oxide treatment. Conclusions We propose that the identified proteins function together as points of cross-talk between cyclic nucleotide, nitric oxide and reactive oxygen species signaling during the defence response.

  14. Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP–PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides

    Science.gov (United States)

    The cyclic AMP (cAMP)-PKA pathway is a central signaling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signaling in fungal biology has been well documented. Two key conserved components, adenylate cyclase (AC) and ca...

  15. Affordable Cyclic Voltammetry

    Science.gov (United States)

    Stewart, Greg; Kuntzleman, Thomas S.; Amend, John R.; Collins, Michael J.

    2009-01-01

    Cyclic voltammetry is an important component of the undergraduate chemical curriculum. Unfortunately, undergraduate students rarely have the opportunity to conduct experiments in cyclic voltammetry owing to the high cost of potentiostats, which are required to control these experiments. By using MicroLab data acquisition interfaces in conjunction…

  16. Affordable Cyclic Voltammetry

    Science.gov (United States)

    Stewart, Greg; Kuntzleman, Thomas S.; Amend, John R.; Collins, Michael J.

    2009-01-01

    Cyclic voltammetry is an important component of the undergraduate chemical curriculum. Unfortunately, undergraduate students rarely have the opportunity to conduct experiments in cyclic voltammetry owing to the high cost of potentiostats, which are required to control these experiments. By using MicroLab data acquisition interfaces in conjunction…

  17. Cyclic anamorphic cosmology

    CERN Document Server

    Ijjas, Anna

    2016-01-01

    Cyclic models of the universe have the advantage of avoiding initial conditions problems related to postulating any sort of beginning in time. To date, the only known viable examples of cyclic models have been ekpyrotic. In this paper, we show that the recently proposed anamorphic scenario can also be made cyclic. The key to the cyclic completion is a classically stable, non-singular bounce. Remarkably, even though the bounce construction was originally developed to connect a period of contraction with a period of expansion both described by Einstein gravity, we show here that it can naturally be modified to connect an ordinary contracting phase described by Einstein gravity with a phase of anamorphic smoothing. The paper will present the basic principles and steps in constructing cyclic anamorphic models.

  18. Mutations of PKA cyclic nucleotide-binding domains reveal novel aspects of cyclic nucleotide selectivity.

    Science.gov (United States)

    Lorenz, Robin; Moon, Eui-Whan; Kim, Jeong Joo; Schmidt, Sven H; Sankaran, Banumathi; Pavlidis, Ioannis V; Kim, Choel; Herberg, Friedrich W

    2017-07-06

    Cyclic AMP and cyclic GMP are ubiquitous second messengers that regulate the activity of effector proteins in all forms of life. The main effector proteins, the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and the 3',5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG), are preferentially activated by cAMP and cGMP, respectively. However, the molecular basis of this cyclic nucleotide selectivity is still not fully understood. Analysis of isolated cyclic nucleotide-binding (CNB) domains of PKA regulatory subunit type Iα (RIα) reveals that the C-terminal CNB-B has a higher cAMP affinity and selectivity than the N-terminal CNB-A. Here, we show that introducing cGMP-specific residues using site-directed mutagenesis reduces the selectivity of CNB-B, while the combination of two mutations (G316R/A336T) results in a cGMP-selective binding domain. Furthermore, introducing the corresponding mutations (T192R/A212T) into the PKA RIα CNB-A turns this domain into a highly cGMP-selective domain, underlining the importance of these contacts for achieving cGMP specificity. Binding data with the generic purine nucleotide 3',5'-cyclic inosine monophosphate (cIMP) reveal that introduced arginine residues interact with the position 6 oxygen of the nucleobase. Co-crystal structures of an isolated CNB-B G316R/A336T double mutant with either cAMP or cGMP reveal that the introduced threonine and arginine residues maintain their conserved contacts as seen in PKG I CNB-B. These results improve our understanding of cyclic nucleotide binding and the molecular basis of cyclic nucleotide specificity. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  19. Cyclic modular beta-sheets.

    Science.gov (United States)

    Woods, R Jeremy; Brower, Justin O; Castellanos, Elena; Hashemzadeh, Mehrnoosh; Khakshoor, Omid; Russu, Wade A; Nowick, James S

    2007-03-07

    The development of peptide beta-hairpins is problematic, because folding depends on the amino acid sequence and changes to the sequence can significantly decrease folding. Robust beta-hairpins that can tolerate such changes are attractive tools for studying interactions involving protein beta-sheets and developing inhibitors of these interactions. This paper introduces a new class of peptide models of protein beta-sheets that addresses the problem of separating folding from the sequence. These model beta-sheets are macrocyclic peptides that fold in water to present a pentapeptide beta-strand along one edge; the other edge contains the tripeptide beta-strand mimic Hao [JACS 2000, 122, 7654] and two additional amino acids. The pentapeptide and Hao-containing peptide strands are connected by two delta-linked ornithine (deltaOrn) turns [JACS 2003, 125, 876]. Each deltaOrn turn contains a free alpha-amino group that permits the linking of individual modules to form divalent beta-sheets. These "cyclic modular beta-sheets" are synthesized by standard solid-phase peptide synthesis of a linear precursor followed by solution-phase cyclization. Eight cyclic modular beta-sheets 1a-1h containing sequences based on beta-amyloid and macrophage inflammatory protein 2 were synthesized and characterized by 1H NMR. Linked cyclic modular beta-sheet 2, which contains two modules of 1b, was also synthesized and characterized. 1H NMR studies show downfield alpha-proton chemical shifts, deltaOrn delta-proton magnetic anisotropy, and NOE cross-peaks that establish all compounds but 1c and 1g to be moderately or well folded into a conformation that resembles a beta-sheet. Pulsed-field gradient NMR diffusion experiments show little or no self-association at low (

  20. Selective modulation of protein kinase isozymes by the site-selective analog 8-chloroadenosine 3',5'-cyclic monophosphate provides a biological means for control of human colon cancer cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Ally, S.; Tortora, G.; Clair, T.; Grieco, D.; Merlo, G.; Katsaros, D.; Ogreid, D.; Doeskeland, S.O.; Jahnsen, T.; Cho-Chung, Yoonsang

    1988-09-01

    Differential expression of type I and type II cAMP-dependent protein kinase isozymes has been linked to growth regulation and differentiation. The authors examined the expression of protein kinase isozymes in the LS 174T human colon cancer cell line during 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cAMP)-induced growth inhibition. Two species of R/sup II/ (the regulatory subunit of protein kinase type II) with apparent M/sub r/ 52,000 (R/sup II//sub 52/) and M/sub r/ 56,000 (R/sup II//sub 56/) and a single species of R/sup I/ (the regulatory subunit of protein kinase type I) with M/sub r/ 48,000 were identified in the cancer cells. R/sup I/ and both forms of R/sup II/ were covalently labeled with 8-azidoadenosine 3',5'-cyclic (/sup 32/P)monophosphate, and two anti-R/sup II/ antibodies that exclusively recognize either R/sup II//sub 52/ or R/sup II//sub 56/ resolved two forms of the R/sup II/ receptors. 8-Cl-cAMP caused transcriptional activation of the R/sup II//sub 52/ receptor gene and inactivation of the R/sup I/ receptor gene. Thus, differential regulation of various forms of cAMP receptor proteins is involved in 8-Cl-cAMP-induced regulation of cancer cell growth, and nuclear translocation of R/sup II//sub 52/ receptor protein appears to be an early event in such differential regulation.

  1. Supramolecular nesting of cyclic polymers.

    Science.gov (United States)

    Kondratuk, Dmitry V; Perdigão, Luís M A; Esmail, Ayad M S; O'Shea, James N; Beton, Peter H; Anderson, Harry L

    2015-04-01

    Advances in template-directed synthesis make it possible to create artificial molecules with protein-like dimensions, directly from simple components. These synthetic macromolecules have a proclivity for self-organization that is reminiscent of biopolymers. Here, we report the synthesis of monodisperse cyclic porphyrin polymers, with diameters of up to 21 nm (750 C–C bonds). The ratio of the intrinsic viscosities for cyclic and linear topologies is 0.72, indicating that these polymers behave as almost ideal flexible chains in solution. When deposited on gold surfaces, the cyclic polymers display a new mode of two-dimensional supramolecular organization, combining encapsulation and nesting; one nanoring adopts a near-circular conformation, thus allowing a second nanoring to be captured within its perimeter, in a tightly folded conformation. Scanning tunnelling microscopy reveals that nesting occurs in combination with stacking when nanorings are deposited under vacuum, whereas when they are deposited directly from solution under ambient conditions there is stacking or nesting, but not a combination of both.

  2. 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.

  3. Real Topological Cyclic Homology

    DEFF Research Database (Denmark)

    Høgenhaven, Amalie

    The main topics of this thesis are real topological Hochschild homology and real topological cyclic homology. If a ring or a ring spectrum is equipped with an anti-involution, then it induces additional structure on the topological Hochschild homology spectrum. The group O(2) acts on the spectrum......, where O(2) is the semi-direct product of T, the multiplicative group of complex number of modulus 1, by the group G=Gal(C/R). We refer to this O(2)-spectrum as the real topological Hochschild homology. This generalization leads to a G-equivariant version of topological cyclic homology, which we call...... real topological cyclic homology. The first part of the thesis computes the G-equivariant homotopy type of the real topological cyclic homology of spherical group rings at a prime p with anti-involution induced by taking inverses in the group. The second part of the thesis investigates the derived G...

  4. Crystallization and preliminary X-ray diffraction analyses of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Nobuhiro [Institute 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); Fujimoto, Zui [Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); Morita, Takashi [Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan); Mizuno, Hiroshi, E-mail: mizuno-hiroshi@aist.go.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); Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan)

    2005-08-01

    Crystals of pseudechetoxin and pseudecin, potent peptidic inhibitors of cyclic nucleotide-gated ion channels, have been prepared and X-ray diffraction data have been collected to 2.25 and 1.90 Å resolution, respectively. Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction of retinal and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins are structurally classified as cysteine-rich secretory proteins and exhibit structural features that are quite distinct from those of other known small peptidic channel blockers. This article describes the crystallization and preliminary X-ray diffraction analyses of these toxins. Crystals of PsTx belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 60.30, b = 61.59, c = 251.69 Å, and diffraction data were collected to 2.25 Å resolution. Crystals of Pdc also belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with similar unit-cell parameters a = 60.71, b = 61.67, c = 251.22 Å, and diffraction data were collected to 1.90 Å resolution.

  5. Cup products in Hopf cyclic cohomology via cyclic modules I

    CERN Document Server

    Rangipour, Bahram

    2007-01-01

    This is the first one in a series of two papers on the continuation of our study in cup products in Hopf cyclic cohomology. In this note we construct cyclic cocycles of algebras out of Hopf cyclic cocycles of algebras and coalgebras. In the next paper we consider producing Hopf cyclic cocycle from "equivariant" Hopf cyclic cocycles. Our approach in both situations is based on (co)cyclic modules and bi(co)cyclic modules together with Eilenberg-Zilber theorem which is different from the old definition of cup products defined via traces and cotraces on DG algebras and coalgebras.

  6. Cyclic polymers from alkynes

    Science.gov (United States)

    Roland, Christopher D.; Li, Hong; Abboud, Khalil A.; Wagener, Kenneth B.; Veige, Adam S.

    2016-08-01

    Cyclic polymers have dramatically different physical properties compared with those of their equivalent linear counterparts. However, the exploration of cyclic polymers is limited because of the inherent challenges associated with their synthesis. Conjugated linear polyacetylenes are important materials for electrical conductivity, paramagnetic susceptibility, optical nonlinearity, photoconductivity, gas permeability, liquid crystallinity and chain helicity. However, their cyclic analogues are unknown, and therefore the ability to examine how a cyclic topology influences their properties is currently not possible. We have solved this challenge and now report a tungsten catalyst supported by a tetraanionic pincer ligand that can rapidly polymerize alkynes to form conjugated macrocycles in high yield. The catalyst works by tethering the ends of the polymer to the metal centre to overcome the inherent entropic penalty of cyclization. Gel-permeation chromatography, dynamic and static light scattering, viscometry and chemical tests are all consistent with theoretical predictions and provide unambiguous confirmation of a cyclic topology. Access to a wide variety of new cyclic polymers is now possible by simply choosing the appropriate alkyne monomer.

  7.  Phosphodiesterase 3 mediates cross-talk between the protein kinase- and cGMP- dependent pathways and cyclic AMP metabolism

    OpenAIRE

    Edyta Makuch; Janusz Matuszyk

    2012-01-01

     PDE3 is a dual-substrate phosphodiesterase responsible for hydrolyzing both cAMP and cGMP whilst being simultaneously inhibited by cGMP. This feature is related to presence of the 44 amino acid insert in the catalytic domain, which determines the mechanism of introduction of the cyclic nucleotide into the catalytic pocket of the enzyme. Once bound in the catalytic site cGMP results in steric hindrance for cAMP to enter the site. The regulatory domain of PDE3 consists of two hydrophobic regio...

  8. The evolution of Momordica cyclic peptides.

    Science.gov (United States)

    Mahatmanto, Tunjung; Mylne, Joshua S; Poth, Aaron G; Swedberg, Joakim E; Kaas, Quentin; Schaefer, Hanno; Craik, David J

    2015-02-01

    Cyclic proteins have evolved for millions of years across all kingdoms of life to confer structural stability over their acyclic counterparts while maintaining intrinsic functional properties. Here, we show that cyclic miniproteins (or peptides) from Momordica (Cucurbitaceae) seeds evolved in species that diverged from an African ancestor around 19 Ma. The ability to achieve head-to-tail cyclization of Momordica cyclic peptides appears to have been acquired through a series of mutations in their acyclic precursor coding sequences following recent and independent gene expansion event(s). Evolutionary analysis of Momordica cyclic peptides reveals sites that are under selection, highlighting residues that are presumably constrained for maintaining their function as potent trypsin inhibitors. Molecular dynamics of Momordica cyclic peptides in complex with trypsin reveals site-specific residues involved in target binding. In a broader context, this study provides a basis for selecting Momordica species to further investigate the biosynthesis of the cyclic peptides and for constructing libraries that may be screened against evolutionarily related serine proteases implicated in human diseases. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Effect of dicer-like proteins2 and 4 and RNA-dependent RNA polymerase1 as RNA silencing components on cyclic mosaic symptom development in tobacco infected with the Cucumber mosaic virus

    Directory of Open Access Journals (Sweden)

    Anurag Sunpapao

    2013-12-01

    Full Text Available The Nicotiana tabacum genome contains four Dicer-like proteins (DCLs and six RNA-dependent RNA polymerase (RDR homologues involved in the RNA silencing mechanism employed against viral infection. DCL1 synthesizes 18-21 nt-long microRNA, whereas DCL2, DCL3 and DCL4 produce 22 nt, 24 nt and 21 nt-long siRNA, respectively, in the RNA silencing process. This study aimed to clarify which components among these are involved in changes in the amount of virus and the development of symptoms in Cucumber mosaic virus (CMV-infected tobacco. Infected transgenic tobacco lines with a single down-regulation of DCL2, DCL4, RDR1 or a double down-regulation of both DCL2 and 4 were analyzed. The amounts of viral RNA in young developing leaves in transgenic tobacco lines were examined by Northern blot analysis. Most transgenic plants inoculated with CMV Pepo, a virulent strain, exhibited cyclic mosaic symptoms. The amount of viral RNA in single down-regulated lines varied based on leaf position in a similar manner to that noted in non-transgenic tobacco, while that of the double down-regulated line did not. Furthermore, the expression of RNA-silencing-related genes during high and low CMV infection did not differ among the transgenic plants. These results suggested that (i changes in the amounts of the virus in the developing leaves of all the single down-regulated lines were associated with cyclic symptom expression in fully expanded leaves, and (ii the lower expression of DCL2, DCL4 and RDR1 may be sufficient to establish cyclic symptom development.

  10. Generalized Wideband Cyclic MUSIC

    Directory of Open Access Journals (Sweden)

    Zhang-Meng Liu

    2009-01-01

    Full Text Available The method of Spectral Correlation-Signal Subspace Fitting (SC-SSF fails to separate wideband cyclostationary signals with coherent second-order cyclic statistics (SOCS. Averaged Cyclic MUSIC (ACM method made up for the drawback to some degree via temporally averaging the cyclic cross-correlation of the array output. This paper interprets ACM from another perspective and proposes a new DOA estimation method by generalizing ACM for wideband cyclostationary signals. The proposed method successfully makes up for the aforementioned drawback of SC-SSF and obtains a more satisfying performance than ACM. It is also demonstrated that ACM is a simplified form of the proposed method when only a single spectral frequency is exploited, and the integration of the frequencies within the signal bandwidth helps the new method to outperform ACM.

  11. The cyclic reduction algorithm

    Science.gov (United States)

    Bini, Dario; Meini, Beatrice

    2009-05-01

    Cyclic reduction is an algorithm invented by G.H. Golub and R. W. Hockney in the mid 1960s for solving linear systems related to the finite differences discretization of the Poisson equation over a rectangle. Among the algorithms of Gene Golub, it is one of the most versatile and powerful ever created. Recently, it has been applied to solve different problems from different applicative areas. In this paper we survey the main features of cyclic reduction, relate it to properties of analytic functions, recall its extension to solving more general finite and infinite linear systems, and different kinds of nonlinear matrix equations, including algebraic Riccati equations, with applications to Markov chains, queueing models and transport theory. Some new results concerning the convergence properties of cyclic reduction and its applicability are proved under very weak assumptions. New formulae for overcoming breakdown are provided.

  12. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim

    2011-01-01

    -suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings......OBJECTIVE: Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte......-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. RESULTS: Median baseline COMP...

  13. Cyclic Vomiting Syndrome

    Science.gov (United States)

    ... digestive diseases specialist (gastroenterologist). If you or your child is in the middle of a severe vomiting episode, the doctor may ... system disorders There's no cure for cyclic vomiting syndrome, so treatment ... may be prescribed: Anti-nausea drugs Sedatives Medications ...

  14. Cyclic Voltammetry Experiment.

    Science.gov (United States)

    Van Benschoten, James J.; And Others

    1983-01-01

    Describes a three-part experiment designed to introduce cyclic voltammetry to graduate/undergraduate students. Part 1 demonstrates formal reduction potential, redox electron transfer, diffusion coefficient, and electrochemical reversibility. Part 2 investigates electrochemical behavior of acetaminophen. Part 3 examines such experimental variables…

  15. On Expanded Cyclic Codes

    CERN Document Server

    Wu, Yingquan

    2008-01-01

    The paper has a threefold purpose. The first purpose is to present an explicit description of expanded cyclic codes defined in $\\GF(q^m)$. The proposed explicit construction of expanded generator matrix and expanded parity check matrix maintains the symbol-wise algebraic structure and thus keeps many important original characteristics. The second purpose of this paper is to identify a class of constant-weight cyclic codes. Specifically, we show that a well-known class of $q$-ary BCH codes excluding the all-zero codeword are constant-weight cyclic codes. Moreover, we show this class of codes achieve the Plotkin bound. The last purpose of the paper is to characterize expanded cyclic codes utilizing the proposed expanded generator matrix and parity check matrix. We analyze the properties of component codewords of a codeword and particularly establish the precise conditions under which a codeword can be represented by a subbasis. With the new insights, we present an improved lower bound on the minimum distance of...

  16. Cyclic Voltammetry Experiment.

    Science.gov (United States)

    Van Benschoten, James J.; And Others

    1983-01-01

    Describes a three-part experiment designed to introduce cyclic voltammetry to graduate/undergraduate students. Part 1 demonstrates formal reduction potential, redox electron transfer, diffusion coefficient, and electrochemical reversibility. Part 2 investigates electrochemical behavior of acetaminophen. Part 3 examines such experimental variables…

  17. Effect of glucagon on cyclic AMP, albumin metabolism and incorporation of 14C-leucine into proteins in isolated parenchymal rat liver cells

    DEFF Research Database (Denmark)

    Dich, J; Gluud, C N

    1976-01-01

    wet wt. This is about the rate found in the perfused liver, Glucagon (10(-8-10(-6) M) inhibited albumin secretion and the incorporation of 14C-leucine into albumin, into total proteins in the medium and into total proteins in the cell suspension. The effect of glucagon on albumin secretion...

  18. Ga and Gß Proteins Regulate the Cyclic AMP Pathway That Is Required for Development and Pathogenicity of the Phytopathogen Mycosphaerella graminicola

    NARCIS (Netherlands)

    Mehrabi, A.; M'Barek, Ben S.; Lee, van der T.A.J.; Waalwijk, C.; Wit, de P.J.G.M.; Kema, G.H.J.

    2009-01-01

    We identified and functionally characterized genes encoding three G alpha proteins and one G beta protein in the dimorphic fungal wheat pathogen Mycosphaerella graminicola, which we designated MgGpa1, MgGpa2, MgGpa3, and MgGpb1, respectively. Sequence comparisons and phylogenetic analyses showed

  19. Mlc is a transcriptional activator with a key role in integrating cyclic AMP receptor protein and integration host factor regulation of leukotoxin RNA synthesis in Aggregatibacter actinomycetemcomitans

    Science.gov (United States)

    Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cAMP receptor protein (CRP) indirectly increases ltxA expression...

  20. Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2012-02-01

    Full Text Available Nitric oxide (NO is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP and the cGMP-dependent kinase (PKG are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ were used. We observed that long-term exposure to the NO donor (24 h, NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.

  1. Cyclic Voltammograms from First Principles

    DEFF Research Database (Denmark)

    Karlberg, Gustav; Jaramillo, Thomas; Skulason, Egill

    2007-01-01

    Cyclic voltammetry is a fundamental experimental tool for characterizing electrochemical surfaces. Whereas cyclic voltammetry is widely used within the field of electrochemistry, a way to quantitatively and directly relate the cyclic voltammogram to ab initio calculations has been lacking, even f...

  2. Dynamics of cyclic machines

    CERN Document Server

    Vulfson, Iosif

    2015-01-01

    This book focuses on modern methods of oscillation analysis in machines, including cyclic action mechanisms (linkages, cams, steppers, etc.). It presents schematization techniques and mathematical descriptions of oscillating systems, taking into account the variability of the parameters and nonlinearities, engineering evaluations of dynamic errors, and oscillation suppression methods. The majority of the book is devoted to the development of new methods of dynamic analysis and synthesis for cyclic machines that form regular oscillatory systems with multiple duplicate modules.  There are also sections examining aspects of general engineering interest (nonlinear dissipative forces, systems with non-stationary constraints, impacts and pseudo-impacts in clearances, etc.)  The examples in the book are based on the widely used results of theoretical and experimental studies as well as engineering calculations carried out in relation to machines used in the textile, light, polygraphic and other industries. Particu...

  3. The Cyclic Model Simplified

    CERN Document Server

    Steinhardt, P J; Steinhardt, Paul J.; Turok, Neil

    2004-01-01

    The Cyclic Model attempts to resolve the homogeneity, isotropy, and flatness problems and generate a nearly scale-invariant spectrum of fluctuations during a period of slow contraction that precedes a bounce to an expanding phase. Here we describe at a conceptual level the recent developments that have greatly simplified our understanding of the contraction phase and the Cyclic Model overall. The answers to many past questions and criticisms are now understood. In particular, we show that the contraction phase has equation of state w>1 and that contraction with w>1 has a surprisingly similar properties to inflation with w < -1/3. At one stroke, this shows how the model is different from inflation and why it may work just as well as inflation in resolving cosmological problems.

  4. Diagnosis of Cyclic Vomiting

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-12-01

    Full Text Available In a study at Children’s Hospital, Ann Arbor, MI, and Children’s Memorial Hospital, Chicago, designed primarily to compare cost-effectiveness of three methods of management of cyclic vomiting cases, one group of patients received an extensive diagnostic evaluation, a second was treated with empiric antimigraine drugs for 2 months, and a third an upper GI series with small-bowel follow-through (UGI-SBFT plus empiric therapy.

  5. Geometry of Cyclic Pursuit

    Science.gov (United States)

    2009-12-18

    analysis of the equilibria based on linearization of the shape dynamics. In [10], the authors extend their analysis to incorporate feedback control...differentiable curves in R2, deriving our dynamics from the natural Frenet frame equations (see, e.g., [5] for details). (A three- dimensional analysis of...cyclic pursuit formulated in terms of the natural Frenet frame equations is a topic of ongoing work.) As is depicted in figure 1, we let ri denote the

  6. Functional roles of arcA, etrA, cyclic AMP (cAMP)-cAMP receptor protein, and cya in the arsenate respiration pathway in Shewanella sp. strain ANA-3.

    Science.gov (United States)

    Murphy, Julie N; Durbin, K James; Saltikov, Chad W

    2009-02-01

    Microbial arsenate respiration can enhance arsenic release from arsenic-bearing minerals--a process that can cause arsenic contamination of water. In Shewanella sp. strain ANA-3, the arsenate respiration genes (arrAB) are induced under anaerobic conditions with arsenate and arsenite. Here we report how genes that encode anaerobic regulator (arcA and etrA [fnr homolog]) and carbon catabolite repression (crp and cya) proteins affect arsenate respiration in ANA-3. Transcription of arcA, etrA, and crp in ANA-3 was similar in cells grown on arsenate and cells grown under aerobic conditions. ANA-3 strains lacking arcA and etrA showed minor to moderate growth defects, respectively, with arsenate. However, crp was essential for growth on arsenate. In contrast to the wild-type strain, arrA was not induced in the crp mutant in cultures shifted from aerobic to anaerobic conditions containing arsenate. This indicated that cyclic AMP (cAMP)-cyclic AMP receptor (CRP) activates arr operon transcription. Computation analysis for genome-wide CRP binding motifs identified a putative binding motif within the arr promoter region. This was verified by electrophoretic mobility shift assays with cAMP-CRP and several DNA probes. Lastly, four putative adenylate cyclase (cya) genes were identified in the genome. One particular cya-like gene was differentially expressed under aerobic versus arsenate respiration conditions. Moreover, a double mutant lacking two of the cya-like genes could not grow with arsenate as a terminal electron acceptor; exogenous cAMP could complement growth of the double cya mutant. It is concluded that the components of the carbon catabolite repression system are essential to regulating arsenate respiratory reduction in Shewanella sp. strain ANA-3.

  7. CCAAT/enhancer-binding protein delta activates insulin-like growth factor-I gene transcription in osteoblasts. Identification of a novel cyclic AMP signaling pathway in bone

    Science.gov (United States)

    Umayahara, Y.; Ji, C.; Centrella, M.; Rotwein, P.; McCarthy, T. L.

    1997-01-01

    Insulin-like growth factor-I (IGF-I) plays a key role in skeletal growth by stimulating bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other cAMP-activating agents enhanced IGF-I gene transcription in cultured primary rat osteoblasts through promoter 1, the major IGF-I promoter, and identified a short segment of the promoter, termed HS3D, that was essential for hormonal regulation of IGF-I gene expression. We now demonstrate that CCAAT/enhancer-binding protein (C/EBP) delta is a major component of a PGE2-stimulated DNA-protein complex involving HS3D and find that C/EBPdelta transactivates IGF-I promoter 1 through this site. Competition gel shift studies first indicated that a core C/EBP half-site (GCAAT) was required for binding of a labeled HS3D oligomer to osteoblast nuclear proteins. Southwestern blotting and UV-cross-linking studies showed that the HS3D probe recognized a approximately 35-kDa nuclear protein, and antibody supershift assays indicated that C/EBPdelta comprised most of the PGE2-activated gel-shifted complex. C/EBPdelta was detected by Western immunoblotting in osteoblast nuclear extracts after treatment of cells with PGE2. An HS3D oligonucleotide competed effectively with a high affinity C/EBP site from the rat albumin gene for binding to osteoblast nuclear proteins. Co-transfection of osteoblast cell cultures with a C/EBPdelta expression plasmid enhanced basal and PGE2-activated IGF-I promoter 1-luciferase activity but did not stimulate a reporter gene lacking an HS3D site. By contrast, an expression plasmid for the related protein, C/EBPbeta, did not alter basal IGF-I gene activity but did increase the response to PGE2. In osteoblasts and in COS-7 cells, C/EBPdelta, but not C/EBPbeta, transactivated a reporter gene containing four tandem copies of HS3D fused to a minimal promoter; neither transcription factor stimulated a gene with four copies of an HS3D mutant that was unable to bind osteoblast

  8. CCAAT/enhancer-binding protein delta activates insulin-like growth factor-I gene transcription in osteoblasts. Identification of a novel cyclic AMP signaling pathway in bone

    Science.gov (United States)

    Umayahara, Y.; Ji, C.; Centrella, M.; Rotwein, P.; McCarthy, T. L.

    1997-01-01

    Insulin-like growth factor-I (IGF-I) plays a key role in skeletal growth by stimulating bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other cAMP-activating agents enhanced IGF-I gene transcription in cultured primary rat osteoblasts through promoter 1, the major IGF-I promoter, and identified a short segment of the promoter, termed HS3D, that was essential for hormonal regulation of IGF-I gene expression. We now demonstrate that CCAAT/enhancer-binding protein (C/EBP) delta is a major component of a PGE2-stimulated DNA-protein complex involving HS3D and find that C/EBPdelta transactivates IGF-I promoter 1 through this site. Competition gel shift studies first indicated that a core C/EBP half-site (GCAAT) was required for binding of a labeled HS3D oligomer to osteoblast nuclear proteins. Southwestern blotting and UV-cross-linking studies showed that the HS3D probe recognized a approximately 35-kDa nuclear protein, and antibody supershift assays indicated that C/EBPdelta comprised most of the PGE2-activated gel-shifted complex. C/EBPdelta was detected by Western immunoblotting in osteoblast nuclear extracts after treatment of cells with PGE2. An HS3D oligonucleotide competed effectively with a high affinity C/EBP site from the rat albumin gene for binding to osteoblast nuclear proteins. Co-transfection of osteoblast cell cultures with a C/EBPdelta expression plasmid enhanced basal and PGE2-activated IGF-I promoter 1-luciferase activity but did not stimulate a reporter gene lacking an HS3D site. By contrast, an expression plasmid for the related protein, C/EBPbeta, did not alter basal IGF-I gene activity but did increase the response to PGE2. In osteoblasts and in COS-7 cells, C/EBPdelta, but not C/EBPbeta, transactivated a reporter gene containing four tandem copies of HS3D fused to a minimal promoter; neither transcription factor stimulated a gene with four copies of an HS3D mutant that was unable to bind osteoblast

  9. Spatial Memory in the Morris Water Maze and Activation of Cyclic AMP Response Element-Binding (CREB) Protein within the Mouse Hippocampus

    Science.gov (United States)

    Porte, Yves; Buhot, Marie Christine; Mons, Nicole E.

    2008-01-01

    We investigated the spatio-temporal dynamics of learning-induced cAMP response element-binding protein activation/phosphorylation (pCREB) in mice trained in a spatial reference memory task in the water maze. Using immunohistochemistry, we examined pCREB immunoreactivity (pCREB-ir) in hippocampal CA1 and CA3 and related brain structures. During the…

  10. Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus.

    Science.gov (United States)

    Hattiangady, Bharathi; Rao, Muddanna S; Shetty, Geetha A; Shetty, Ashok K

    2005-10-01

    The hippocampus is very susceptible to aging. Severely diminished dentate neurogenesis at middle age is one of the most conspicuous early changes in the aging hippocampus, which is likely linked to an early decline in the concentration of neurotrophic factors and signaling proteins that influence neurogenesis. We analyzed three proteins that are well-known to promote dentate neurogenesis and learning and memory function in the dentate gyrus and the hippocampal CA1 and CA3 subfields of young, middle-aged and aged F344 rats. These include the brain-derived neurotrophic factor (BDNF), the transcription factor phosphorylated cyclic AMP response element binding protein (p-CREB) and the neuropeptide neuropeptide Y (NPY). The BDNF was analyzed via ELISA and BDNF immunohistochemistry, the p-CREB through densitometric analysis of p-CREB immunopositive cells, and the NPY via stereological counting of NPY-immunopositive interneurons. We provide new evidence that the BDNF concentration, the p-CREB immunoreactivity and the number of NPY immunopositive interneurons decline considerably by middle age in both dentate gyrus and CA1 and CA3 subfields of the hippocampus. However, both BDNF concentration and NPY immunopositive interneuron numbers exhibit no significant decrease between middle age and old age. In contrast, the p-CREB immunoreactivity diminishes further during this period, which is also associated with reduced BDNF immunoreaction within the soma of dentate granule cells and hippocampal pyramidal neurons. Collectively, these results suggest that severely dampened dentate neurogenesis observed at middle age is linked at least partially to reduced concentrations of BDNF, p-CREB and NPY, as each of these proteins is a positive regulator of dentate neurogenesis. Dramatically diminished CREB phosphorylation (and persistently reduced levels of BDNF and NPY) at old age may underlie the learning and memory impairments observed during senescence.

  11. Cyclic Nucleotide Signalling in Kidney Fibrosis

    Directory of Open Access Journals (Sweden)

    Elisabeth Schinner

    2015-01-01

    Full Text Available Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.

  12. Mechanisms of lung neutrophil activation after hemorrhage or endotoxemia: roles of reactive oxygen intermediates, NF-kappa B, and cyclic AMP response element binding protein.

    Science.gov (United States)

    Shenkar, R; Abraham, E

    1999-07-15

    Acute inflammatory lung injury occurs frequently in the setting of severe infection or blood loss. Accumulation of activated neutrophils in the lungs and increased pulmonary proinflammatory cytokine levels are major characteristics of acute lung injury. In the present experiments, we examined mechanisms leading to neutrophil accumulation and activation in the lungs after endotoxemia or hemorrhage. Levels of IL-1 beta, TNF-alpha, and macrophage inflammatory protein-2 mRNA were increased in lung neutrophils from endotoxemic or hemorrhaged mice compared with those present in lung neutrophils from control mice or in peripheral blood neutrophils from endotoxemic, hemorrhaged, or control mice. The transcriptional regulatory factors NF-kappa B and cAMP response element binding protein were activated in lung but not blood neutrophils after hemorrhage or endotoxemia. Xanthine oxidase inhibition, achieved by feeding allopurinol or tungsten-containing diets, did not affect neutrophil trafficking to the lungs after hemorrhage or endotoxemia. Xanthine oxidase inhibition did prevent hemorrhage- but not endotoxemia-induced increases in proinflammatory cytokine expression among lung neutrophils. Hemorrhage- or endotoxemia-associated activation of NF-kappa B in lung neutrophils was not affected by inhibition of xanthine oxidase. cAMP response element binding protein activation was increased after hemorrhage, but not endotoxemia, in mice fed xanthine oxidase-inhibiting diets. Our results indicate that xanthine oxidase modulates cAMP response element binding protein activation and proinflammatory cytokine expression in lung neutrophils after hemorrhage, but not endotoxemia. These findings suggest that the mechanisms leading to acute inflammatory lung injury after hemorrhage differ from those associated with endotoxemia.

  13. Intracellular Production of Cyclic Peptide Libraries with SICLOPPS.

    Science.gov (United States)

    Osher, Eliot L; Tavassoli, Ali

    2017-01-01

    Cyclic peptides are an important class of molecules that are increasingly viewed as an ideal scaffold for inhibition of protein-protein interactions (PPI). Here we detail an approach that enables the intracellular synthesis of cyclic peptide libraries of around 10(8) members. The method utilizes split intein mediated circular ligation of peptides and proteins (SICLOPPS), taking advantage of split intein splicing to cyclize a library of peptide sequences. SICLOPPS allows the ring size, set residues and number of random residues within a library to be predetermined by the user. SICLOPPS libraries have been combined with a variety of cell-based screens to identify cyclic peptide inhibitors of a variety of enzymes and protein-protein interactions.

  14. The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

    Directory of Open Access Journals (Sweden)

    Roberts-Thomson Sarah J

    2006-07-01

    Full Text Available Abstract Background The vanilloid receptor 1 (TRPV1 is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+ responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.

  15. Macrophage Inflammatory Protein 1α Inhibits Postentry Steps of Human Immunodeficiency Virus Type 1 Infection via Suppression of Intracellular Cyclic AMP

    OpenAIRE

    2005-01-01

    Primary isolates of human immunodeficiency virus type 1 (HIV-1) predominantly use chemokine receptor CCR5 to enter target cells. The natural ligands of CCR5, the β-chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES, interfere with HIV-1 binding to CCR5 receptors and decrease the amount of virions entering cells. Although the inhibition of HIV-1 entry by β-chemokines is well documented, their effects on postentry steps of the viral life cycle and on host cell components...

  16. Functional cyclic AMP response element in the breast cancer resistance protein (BCRP/ABCG2) promoter modulates epidermal growth factor receptor pathway- or androgen withdrawal-mediated BCRP/ABCG2 transcription in human cancer cells.

    Science.gov (United States)

    Xie, Yi; Nakanishi, Takeo; Natarajan, Karthika; Safren, Lowell; Hamburger, Anne W; Hussain, Arif; Ross, Douglas D

    2015-03-01

    Phosphorylated cyclic-AMP (cAMP) response element binding protein (p-CREB) is a downstream effector of a variety of important signaling pathways. We investigated whether the human BCRP promoter contains a functional cAMP response element (CRE). 8Br-cAMP, a cAMP analogue, increased the activity of a BCRP promoter reporter construct and BCRP mRNA in human carcinoma cells. Epidermal growth factor receptor (EGFR) pathway activation also led to an increase in p-CREB and in BCRP promoter reporter activity via two major downstream EGFR signaling pathways: the phosphotidylinositol-3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK) pathway. EGF treatment increased the phosphorylation of EGFR, AKT, ERK and CREB, while simultaneously enhancing BCRP mRNA and functional protein expression. EGF-stimulated CREB phosphorylation and BCRP induction were diminished by inhibition of EGFR, PI3K/AKT or RAS/MAPK signaling. CREB silencing using RNA interference reduced basal levels of BCRP mRNA and diminished the induction of BCRP by EGF. Chromatin immunoprecipitation assays confirmed that a putative CRE site on the BCRP promoter bound p-CREB by a point mutation of the CRE site abolished EGF-induced stimulation of BCRP promoter reporter activity. Furthermore, the CREB co-activator, cAMP-regulated transcriptional co-activator (CRTC2), is involved in CREB-mediated BCRP transcription: androgen depletion of LNCaP human prostate cancer cells increased both CREB phosphorylation and CRTC2 nuclear translocation, and enhanced BCRP expression. Silencing CREB or CRTC2 reduced basal BCRP expression and BCRP induction under androgen-depletion conditions. This novel CRE site plays a central role in mediating BCRP gene expression in several human cancer cell lines following activation of multiple cancer-relevant signaling pathways.

  17. Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP).

    Science.gov (United States)

    Kim, Henna; Youn, Suk-Jun; Kim, Seong Ok; Ko, Junsang; Lee, Jie-Oh; Choi, Byong-Seok

    2015-06-26

    Although it was only recently identified as a second messenger, c-di-AMP was found to have fundamental importance in numerous bacterial functions such as ion transport. The potassium transporter protein, KtrA, was identified as a c-di-AMP receptor. However, the co-crystallization of c-di-AMP with the protein has not been studied. Here, we determined the crystal structure of the KtrA RCK_C domain in complex with c-di-AMP. The c-di-AMP nucleotide, which adopts a U-shaped conformation, is bound at the dimer interface of RCK_C close to helices α3 and α4. c-di-AMP interacts with KtrA RCK_C mainly by forming hydrogen bonds and hydrophobic interactions. c-di-AMP binding induces the contraction of the dimer, bringing the two monomers of KtrA RCK_C into close proximity. The KtrA RCK_C was able to interact with only c-di-AMP, but not with c-di-GMP, 3',3-cGAMP, ATP, and ADP. The structure of the KtrA RCK_C domain and c-di-AMP complex would expand our understanding about the mechanism of inactivation in Ktr transporters governed by c-di-AMP.

  18. Ekpyrotic and Cyclic Cosmology

    CERN Document Server

    Lehners, Jean-Luc

    2008-01-01

    Ekpyrotic and cyclic cosmologies provide theories of the very early and of the very late universe. In these models, the big bang is described as a collision of branes - and thus the big bang is not the beginning of time. Before the big bang, there is an ekpyrotic phase with equation of state w=P/rho >> 1 (where P is the average pressure and rho the average energy density) during which the universe slowly contracts. This phase resolves the standard cosmological puzzles and generates a nearly scale-invariant spectrum of cosmological perturbations containing a significant non-gaussian component. At the same time it produces small-amplitude gravitational waves with a blue spectrum. The dark energy dominating the present-day cosmological evolution is reinterpreted as a small attractive force between our brane and a parallel one. This force eventually induces a new ekpyrotic phase and a new brane collision, leading to the idea of a cyclic universe. This review discusses the detailed properties of these models, thei...

  19. Ekpyrotic and cyclic cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Lehners, Jean-Luc [Princeton Center for Theoretical Science, Jadwin Hall, Princeton University, Princeton NJ 08544 (United States)], E-mail: jlehners@princeton.edu

    2008-09-15

    Ekpyrotic and cyclic cosmologies provide theories of the very early and of the very late universe. In these models, the big bang is described as a collision of branes - and thus the big bang is not the beginning of time. Before the big bang, there is an ekpyrotic phase with equation of state w=P/({rho}) >>1 (where P is the average pressure and {rho} the average energy density) during which the universe slowly contracts. This phase resolves the standard cosmological puzzles and generates a nearly scale-invariant spectrum of cosmological perturbations containing a significant non-Gaussian component. At the same time it produces small-amplitude gravitational waves with a blue spectrum. The dark energy dominating the present-day cosmological evolution is reinterpreted as a small attractive force between our brane and a parallel one. This force eventually induces a new ekpyrotic phase and a new brane collision, leading to the idea of a cyclic universe. This review discusses the detailed properties of these models, their embedding in M-theory and their viability, with an emphasis on open issues and observational signatures.

  20. [Asthma and cyclic neutropenia].

    Science.gov (United States)

    Salazar Cabrera, A N; Berrón Pérez, R; Ortega Martell, J A; Onuma Takane, E

    1996-01-01

    We report a male with history of recurrent infections (recurrent oral aphtous disease [ROAD], middle ear infections and pharyngo amigdalitis) every 3 weeks since he was 7 months old. At the age of 3 years cyclic neutropenia was diagnosed with cyclic fall in the total neutrophil count in blood smear every 21 days and prophylactic antimicrobial therapy was indicated. Episodic events every 3 weeks of acute asthma and allergic rhinitis were detected at the age of 6 years old and specific immunotherapy to Bermuda grass was given during 3 years with markedly improvement in his allergic condition but not in the ROAD. He came back until the age of 16 with episodic acute asthma and ROAD. The total neutrophil count failed to 0 every 21 days and surprisingly the total eosinophil count increased up to 2,000 at the same time, with elevation of serum IgE (412 Ul/mL). Specific immunotherapy to D.pt. and Aller.a. and therapy with timomodulin was indicated. After 3 months we observed clinical improvement in the asthmatic condition and the ROAD disappeared, but the total neutrophil count did not improve. We present this case as a rare association between 2 diseases with probably no etiological relationship but may be physiopatological that could help to understand more the pathogenesis of asthma.

  1. Dynamic Cyclic Thiodepsipeptide Libraries from Thiol-Thioester Exchange

    Science.gov (United States)

    2010-04-01

    the reaction dynamics are discussed. Cyclic peptides have been described as “privileged structures” for drug design because so many natural and...inhibitors, which hold promise for treatment of cancer.4 As drug scaffolds, cyclic peptides are advantageous because they mimic native protein structure...but instead an influence of chirality on the accessibility of the thioester or thiol. We also investigated the effect of positively charged amino

  2. Microgravity changes in heart structure and cyclic-AMP metabolism

    Science.gov (United States)

    Philpott, D. E.; Fine, A.; Kato, K.; Egnor, R.; Cheng, L.

    1985-01-01

    The effects of microgravity on cardiac ultrastructure and cyclic AMP metabolism in tissues of rats flown on Spacelab 3 are reported. Light and electron microscope studies of cell structure, measurements of low and high Km phosphodiesterase activity, cyclic AMP-dependent protein kinase activity, and regulatory subunit compartmentation show significant deviations in flight animals when compared to ground controls. The results indicate that some changes have occurred in cellular responses associated with catecholamine receptor interactions and intracellular signal processing.

  3. Fragmentations of protonated cyclic-glycylglycine and cyclic-alanylalanine

    NARCIS (Netherlands)

    Shek, P. Y. I.; Lau, J. K. C.; Zhao, J. F.; Grzetic, J.; Verkerk, U. H.; Oomens, J.; Hopkinson, A. C.; Siu, K. W. M.

    2012-01-01

    Collision-induced dissociation has been used to study the fragmentations of two protonated diketopiperazines, protonated cyclic-glycylglycine and cyclic-alanylalanine. Protonated cyclo-AA lost CO and (CO + NH3) at low collision energies, channels attributed to dissociation of the O-protonated

  4. Cows are not mice: the role of cyclic AMP, phosphodiesterases, and adenosine monophosphate-activated protein kinase in the maintenance of meiotic arrest in bovine oocytes.

    Science.gov (United States)

    Bilodeau-Goeseels, Sylvie

    2011-01-01

    Meiotic maturation in mammalian oocytes is initiated during fetal development, and is then arrested at the dictyate stage - possibly for several years. Oocyte meiosis resumes in preovulatory follicles in response to the lutenizing hormone (LH) surge or spontaneously when competent oocytes are removed from follicles and cultured. The mechanisms involved in meiotic arrest and resumption in bovine oocytes are not fully understood, and several studies point to important differences between oocytes from rodent and livestock species. This paper reviews earlier and contemporary studies on the effects of cAMP-elevating agents and phosphodiesterase (PDE) enzyme inhibitors on the maintenance of meiotic arrest in bovine oocytes in vitro. Contrary to results obtained with mouse oocytes, bovine oocyte meiosis is inhibited by activators of the energy sensor adenosine monophosphate-activated protein kinase (AMPK, mammalian gene PRKA), which is activated by AMP, the degradation product of cAMP. It is not clear whether or not the effects were due to AMPK activation, and they may depend on culture conditions. Evidence suggests that other signaling pathways (for example, the cGMP/nitric oxide pathway) are involved in bovine oocyte meiotic arrest, but further studies are needed to understand the interactions between the signaling pathways that lead to maturation promoting factor (MPF) being inactive or active. An improved understanding of the mechanisms involved in the control of bovine oocyte meiosis will facilitate better control of the process in vitro, resulting in increased developmental competence and increased efficiency of in vitro embryo production procedures.

  5. Effects of pyridoxine on a high-fat diet-induced reduction of cell proliferation and neuroblast differentiation depend on cyclic adenosine monophosphate response element binding protein in the mouse dentate gyrus.

    Science.gov (United States)

    Yoo, Dae Young; Kim, Woosuk; Yoo, Ki-Yeon; Nam, Sung Min; Chung, Jin Young; Yoon, Yeo Sung; Won, Moo-Ho; Hwang, In Koo

    2012-08-01

    In this study, we challenged pyridoxine to mice fed a high-fat diet (HFD) and investigated the effects of pyridoxine on HFD-induced phenotypes such as blood glucose, reduction of cell proliferation and neuroblast differentiation in the dentate gyrus using Ki67 and doublecortin (DCX), respectively. Mice were fed a commercially available low-fat diet (LFD) as control diet or HFD (60% fat) for 8 weeks. After 5 weeks of LFD or HFD treatment, 350 mg/kg pyridoxine was administered for 3 weeks. The administration of pyridoxine significantly decreased body weight in the HFD-treated group. In addition, there were no significant differences in hepatic histology and pancreatic insulin-immunoreactive (-ir) and glucagon-ir cells of the HFD-treated group after pyridoxine treatment. In the HFD-fed group, Ki67-positive nuclei and DCX-ir neuroblasts were significantly decreased in the dentate gyrus compared with those in the LFD-fed mice. However, the administration of pyridoxine significantly increased Ki67-positive nuclei and DCX-ir neuroblasts in the dentate gyrus in both LFD- and HFD-fed mice. In addition, the administration of pyridoxine significantly increased the protein levels of glutamic acid decarboxylase 67 (GAD67) and brain-derived neurotrophic factor (BDNF) and the immunoreactivity of phosphorylated cyclic AMP response element binding protein (pCREB) compared with the vehicle-treated LFD- and HFD-fed mice. In contrast, the administration of pyridoxine significantly decreased HFD-induced malondialdehyde (MDA) levels in the hippocampus. These results showed that pyridoxine supplement reduced the HFD-induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus via controlling the levels of GAD67, pCREB, BDNF, and MDA.

  6. Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma.

    Science.gov (United States)

    Zhang, Jun-qing; Yao, Qing-he; Kuang, Yong-qin; Ma, Yuan; Yang, Li-bin; Huang, Hai-dong; Cheng, Jing-ming; Yang, Tao; Liu, En-yu; Liang, Liang; Fan, Ke-xia; Zhao, Kai; Xia, Xun; Gu, Jian-wen

    2014-10-01

    Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain (P RNA expression was significantly elevated in the tumors (P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade (P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score (P = .03), and high CREB-1 expression correlated positively with mean tumor diameter (P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time. Copyright © 2014. Published by Elsevier Inc.

  7. Parathyroid hormone induces transcription of collagenase in rat osteoblastic cells by a mechanism using cyclic adenosine 3',5'-monophosphate and requiring protein synthesis

    Science.gov (United States)

    Scott, D. K.; Brakenhoff, K. D.; Clohisy, J. C.; Quinn, C. O.; Partridge, N. C.

    1992-01-01

    Collagenase is synthesized and secreted by rat osteoblastic cells in response to PTH. We have previously demonstrated that this effect involves a substantial increase in collagenase mRNA via transcription. Northern blots and nuclear run-on assays were performed to further investigate the induction of collagenase by PTH in the rat osteoblastic cell line UMR 106-01. Detectable amounts of collagenase mRNA were not apparent until 2 h of PTH treatment, showed the greatest abundance at 4 h, and declined to approximately 30% of maximum by 8 h. The changes in the rate of transcription of the collagenase gene in response to PTH paralleled and preceded the changes in the steady state mRNA levels. After an initial lag period of about 1 h, collagenase transcription rates increased from very low levels to a maximal response at 2 h, returning to about 50% of maximum by 10 h. The increased transcriptional rate of the collagenase gene was found to be dependent on the concentration of PTH, with a half-maximal response at approximately 7 x 10(-10) M rat PTH-(1-34) and a maximal effect with a dose of 10(-8) M. The PTH-mediated induction of collagenase transcriptional activity was completely abolished by cycloheximide, while transcription of the beta-actin gene was unaffected by the translation inhibitor. These data suggest that a protein factor(s) is required for PTH-mediated transcriptional induction of collagenase. Since PTH increases intracellular levels of several potential second messengers, agents that mimic these substances were employed to determine which signal transduction pathway is predominant in the PTH-mediated stimulation of collagenase transcription.(ABSTRACT TRUNCATED AT 250 WORDS).

  8. Cyclic cohomology of Hopf algebras

    NARCIS (Netherlands)

    Crainic, M.

    2001-01-01

    We give a construction of ConnesMoscovicis cyclic cohomology for any Hopf algebra equipped with a character Furthermore we introduce a noncommutative Weil complex which connects the work of Gelfand and Smirnov with cyclic cohomology We show how the Weil complex arises naturally when looking at Hopf

  9. Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of cerebral ischemia rats and improves behavioral deficits.

    Science.gov (United States)

    Zhao, Yu; Xiao, Ming; He, Wenbo; Cai, Zhiyou

    2015-01-01

    The cAMP response element binding protein (CREB) plays an important role in the mechanism of cognitive impairment and is also pivotal in the switch from short-term to long-term memory. Brain-derived neurotrophic factor (BDNF) seems a promising avenue in the treatment of cerebral ischemia injury since this neurotrophin could stimulate structural plasticity and repair cognitive impairment. Several findings have displayed that the dysregulation of the CREB-BDNF cascade has been involved in cognitive impairment. The aim of this study was to investigate the effect of cerebral ischemia on learning and memory as well as on the levels of CREB, phosphorylated CREB (pCREB), and BDNF, and to determine the effect of minocycline on CREB, pCREB, BDNF, and behavioral functional recovery after cerebral ischemia. The animal model was established by permanent bilateral occlusion of both common carotid arteries. Behavior was evaluated 5 days before decapitation with Morris water maze and open-field task. Four days after permanent bilateral occlusion of both common carotid arteries, minocycline was administered by douche via the stomach for 4 weeks. CREB and pCREB were examined by Western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry. BDNF was measured by immunohistochemistry and Western blotting. The model rats after minocycline treatment swam shorter distances than control rats before finding the platform (P=0.0007). The number of times the platform position was crossed for sham-operation rats was more than that of the model groups in the corresponding platform location (P=0.0021). The number of times the platform position was crossed for minocycline treatment animals was significantly increased compared to the model groups in the corresponding platform position (P=0.0016). CREB, pCREB, and BDNF were downregulated after permanent bilateral occlusion of both common carotid arteries in the model group. Minocycline increased the expression of CREB

  10. Adenosine 3':5'-cyclic monophosphate in higher plants: Isolation and characterization of adenosine 3':5'-cyclic monophosphate from Kalanchoe and Agave.

    Science.gov (United States)

    Ashton, A R; Polya, G M

    1977-07-01

    1.3':5'-Cyclic AMP was extensively purified from Kalanchoe daigremontiana and Agave americana by neutral alumina and anion- and cation-exchange column chromatography. Inclusion of 3':5'-cyclic [8-3H]AMP from the point of tissue extraction permitted calculation of yields. The purification procedure removed contaminating material that was shown to interfere with the 3':5'-cyclic AMP estimation and characterization procedures. 2. The partially purified 3':5'-cyclic AMP was quantified by means of a radiochemical saturation assay using an ox heart 3':5'-cyclic AMP-binding protein and by an assay involving activation of a mammalian protein kinase. 3. The plant 3':5'-cyclic AMP co-migrated with 3':5'-cyclic [8-3H]AMP on cellulose chromatography, poly(ethyleneimine)-cellulose chromatography and silica-gel t.l.c. developed with several solvent systems. 4. The plant 3':5'-cyclic AMP was degraded by ox heart 3':5'-cyclic nucleotide phosphodiesterase at the same rates as authentic 3':5'-cyclic AMP. 1-Methyl-3-isobutylxanthine (1 mM), a specific inhibitor of the 3':5'-cyclic nucleotide phosphodieterase, completely inhibited such degradation. 5. The concentrations of 3':5'-cyclic AMP satisfying the above criteria in Kalanchoe and Agave were 2-6 and 1 pmol/g fresh wt. respectively. Possible bacterial contribution to these analyses was estimated to be less than 0.002pmol/g fresh wt. Evidence for the occurrence of 3':5'-cyclic AMP in plants is discussed.

  11. Establishment of Protein Misfolding Cyclic Amplification for 22L PrPSc%22L毒株朊蛋白错误折叠循环扩增方法的建立

    Institute of Scientific and Technical Information of China (English)

    李建疆; 李泽鸿; 万家余; 高宏伟

    2010-01-01

    参考Saborio和Soto创建的名为蛋白质错误折叠循环扩增(protein misfolding cyclic amplification,PMCA)的方法建立一种22L毒株系朊蛋白错误折叠循环扩增方法,以便研究22L毒株系异常朊蛋白(scrapie PrP,PrPSc)的合成机制.在阴离子去污剂十二烷基硫酸钠(SDS)存在的条件下,这种方法可以通过超声降解从而重复扩增产物,并在仓鼠脑匀浆中快速有效的模仿体内朊病毒PrPSc的复制,因此可以在几个小时内高浓度扩增PrPSc.已有试验结果发现,PrPSc体外转化率在使用粗提的脑组织匀浆时比使用纯化重组PrP更高,这个发现暗示着高效率的PrPSc转化可能还需要探索其他未知的宿主因素.研究结果表明,建立的这种改良的PMCA技术可用于研究PrPSc合成的生物化学机制,以此来进行诊断与治疗方法的研究.

  12. Functional Characterization of Cyclic Adenosine Monphosphate (cAMP)Recptor Protein Gene (crp) from Erwinia amylovora%梨火疫菌(Erwinia amylovora)环腺苷酸受体蛋白基因(crp)的功能分析

    Institute of Scientific and Technical Information of China (English)

    刘倩倩; 于洋洋; 宋俊贤; 胡白石; 范加勤; 刘凤权

    2010-01-01

    梨火疫菌(Erwinia amylovora)可引起梨、苹果等蔷薇科(Rosaceae)植物的火疫病.在菊欧文氏菌(Erwinia chrysanthemi)中,由crp基因编码的环腺苷酸受体蛋白(cyclic adenosine monphosphate(cAMP)receptor protein,CRP)对果胶酶基因的表达调控和菌株致病性起着重要的作用.本研究首次鉴定并克隆出梨火疫菌中的crp同源基因,命名为Eacrp,并通过同源重组的方法,构建了梨火疫菌的crp基因突变体Ea△crp以及互补子,进行了致病性、过敏性反应、胞外多糖、鞭毛运动等一系列相关表型的鉴定.结果表明,crp基因影响着梨火疫菌的致病性、胞外多糖、游动性、生长情况等多种生物学特性,然而,Ea△crp仍能引起烟草过敏性反应,并且在过氧化氢敏感度以及沉降性、生物膜和AI-2信号分子的生成方面与野生型菌株相比差异明显.本研究结果说明,梨火疫菌crp基因对病菌的胞外多糖分泌、生长、游动性以及致病性方面具有关键作用.

  13. Cyclic $n$-gonal Surfaces

    CERN Document Server

    Broughton, S Allen

    2010-01-01

    A cyclic $n$-gonal surface is a compact Riemann surface $X$ of genus $g\\geq 2$ admitting a cyclic group of conformal automorphisms $C$ of order $n$ such that the quotient space $X/C$ has genus 0. In this paper, we provide an overview of ongoing research into automorphism groups of cyclic $n$-gonal surfaces. Much of the paper is expository or will appear in forthcoming papers, so proofs are usually omitted. Numerous explicit examples are presented illustrating the computational methods currently being used to study these surfaces.

  14. Cyclic Nucleotide-Dependent Protein Kinases, IV. Widespread Occurrence of Adenosine 3′,5′-monophosphate-dependent Protein Kinase in Various Tissues and Phyla of the Animal Kingdom

    National Research Council Canada - National Science Library

    J. F. Kuo; Paul Greengard

    1969-01-01

    Adenosine 3 ,5 -monophosphate-dependent protein kinase activity was found in about thirty sources including many mammalian tissues as well as species representative of eight different invertebrate phyla...

  15. Visualization of cyclic nucleotide dynamics in neurons

    Directory of Open Access Journals (Sweden)

    Kirill eGorshkov

    2014-12-01

    Full Text Available The second messengers cAMP and cGMP transduce many neuromodulatory signals from hormones and neurotransmitters into specific functional outputs. Their production, degradation and signaling are spatiotemporally regulated to achieve high specificity in signal transduction. The development of genetically encodable fluorescent biosensors has provided researchers with useful tools to study these versatile second messengers and their downstream effectors with unparalleled spatial and temporal resolution in cultured cells and living animals. In this review, we introduce the general design of these fluorescent biosensors and describe several of them in more detail. Then we discuss a few examples of using cyclic nucleotide fluorescent biosensors to study regulation of neuronal function and finish with a discussion of advances in the field. Although there has been significant progress made in understanding how the specific signaling of cyclic nucleotide second messengers is achieved, the mechanistic details in complex cell types like neurons are only just beginning to surface. Current and future fluorescent protein reporters will be essential to elucidate the role of cyclic nucleotide signaling dynamics in the functions of individual neurons and their networks.

  16. Identification of cholinergic and non-cholinergic neurons in the pons expressing phosphorylated cyclic adenosine monophosphate response element-binding protein as a function of rapid eye movement sleep.

    Science.gov (United States)

    Datta, S; Siwek, D F; Stack, E C

    2009-09-29

    Recent studies have shown that in the pedunculopontine tegmental nucleus (PPT), increased neuronal activity and kainate receptor-mediated activation of intracellular protein kinase A (PKA) are important physiological and molecular steps for the generation of rapid eye movement (REM) sleep. In the present study performed on rats, phosphorylated cyclic AMP response element-binding protein (pCREB) immunostaining was used as a marker for increased intracellular PKA activation and as a reflection of increased neuronal activity. To identify whether activated cells were either cholinergic or noncholinergic, the PPT and laterodorsal tegmental nucleus (LDT) cells were immunostained for choline acetyltransferase (ChAT) in combination with pCREB or c-Fos. The results demonstrated that during high rapid eye movement sleep (HR, approximately 27%), significantly higher numbers of cells expressed pCREB and c-Fos in the PPT, of which 95% of pCREB-expressing cells were ChAT-positive. With HR, the numbers of pCREB-positive cells were also significantly higher in the medial pontine reticular formation (mPRF), pontine reticular nucleus oral (PnO), and dorsal subcoeruleus nucleus (SubCD) but very few in the locus coeruleus (LC) and dorsal raphe nucleus (DRN). Conversely, with low rapid eye movement sleep (LR, approximately 2%), the numbers of pCREB expressing cells were very few in the PPT, mPRF, PnO, and SubCD but significantly higher in the LC and DRN. The results of regression analyses revealed significant positive relationships between the total percentages of REM sleep and numbers of ChAT+/pCREB+ (Rsqr=0.98) cells in the PPT and pCREB+ cells in the mPRF (Rsqr=0.88), PnO (Rsqr=0.87), and SubCD (Rsqr=0.84); whereas significantly negative relationships were associated with the pCREB+ cells in the LC (Rsqr=0.70) and DRN (Rsqr=0.60). These results provide evidence supporting the hypothesis that during REM sleep, the PPT cholinergic neurons are active, whereas the LC and DRN neurons are

  17. Prognosis of Cyclic Vomiting Syndrome

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2016-03-01

    Full Text Available Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH.

  18. Design of a cyclic multiverse

    National Research Council Canada - National Science Library

    Piao, Yun-Song

    2010-01-01

    Recently, it has been noticed that the amplification of the amplitude of curvature perturbation cycle by cycle can lead to a cyclic multiverse scenario, in which the number of universes increases cycle by cycle...

  19. Algebraic curves of maximal cyclicity

    Science.gov (United States)

    Caubergh, Magdalena; Dumortier, Freddy

    2006-01-01

    The paper deals with analytic families of planar vector fields, studying methods to detect the cyclicity of a non-isolated closed orbit, i.e. the maximum number of limit cycles that can locally bifurcate from it. It is known that this multi-parameter problem can be reduced to a single-parameter one, in the sense that there exist analytic curves in parameter space along which the maximal cyclicity can be attained. In that case one speaks about a maximal cyclicity curve (mcc) in case only the number is considered and of a maximal multiplicity curve (mmc) in case the multiplicity is also taken into account. In view of obtaining efficient algorithms for detecting the cyclicity, we investigate whether such mcc or mmc can be algebraic or even linear depending on certain general properties of the families or of their associated Bautin ideal. In any case by well chosen examples we show that prudence is appropriate.

  20. Cyclic Cushing's syndrome: an overview.

    Science.gov (United States)

    Albiger, Nora Maria Elvira; Scaroni, Carla M; Mantero, Franco

    2007-11-01

    Cyclic Cushing's syndrome (CS) is a disorder in which glucocorticoid levels are alternately normal and high, the latter occurring in episodes that can last from a few days to several months. It is more common in children than in adults. Cyclic CS may be either of the two different forms of CS (ACTH-dependent or -independent CS). Clinically, it may present with one or many symptoms, depending on the duration of disease activity and the timing of the fluctuations. A serotoninergic influence, cyclic changes in central dopaminergic tone, spontaneous episodic hemorrhage in the tumor, and the action of inflammatory cytokines with antitumor properties are some of the mechanisms suggested to explain the physiopathology of this phenomenon but the exact mechanism remains to be clarified. The cyclic pattern of hypercortisolism can delay the final diagnosis of CS and make it difficult to interpret the results of dynamic tests. Patients may have paradoxical responses to dexamethasone that can reflect increasing or decreasing levels of endogenous activity. Hormone assessments have to be repeated periodically when a diagnosis of CS is suspected. The cyclic pattern can also interfere with medical treatment because patients may show unexpected clinical and biochemical signs of hypocortisolism when cortisol secretion cyclically returns to normal, so an accurate follow-up is mandatory in these patients.

  1. Transitive oriented 3-Hypergraphs of cyclic orders

    OpenAIRE

    2012-01-01

    In this paper we introduce the definition of transitivity for oriented 3-hypergraphs in order to study partial and complete cyclic orders. This definition allow us to give sufficient conditions on a partial cyclic order to be totally extendable. Furthermore, we introduce the 3-hypergraph associated to a cyclic permutation and characterize it in terms of cyclic comparability 3-hypergraphs.

  2. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis.

    Science.gov (United States)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim; Hetland, Merete L; Ejbjerg, Bo; Stengaard-Pedersen, Kristian; Jacobsen, Søren; Lottenburger, Tine; Ellingsen, Torkell; Andersen, Lis S; Hansen, Ib; Skjødt, Henrik; Pedersen, Jens K; Lauridsen, Ulrik B; Svendsen, Anders; Tarp, Ulrik; Pødenphant, Jan; Østergaard, Mikkel; Junker, Peter

    2011-08-01

    Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings. A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals. Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by

  3. Fluorescence-Based Reporter for Gauging Cyclic Di-GMP Levels in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Rybtke, Morten T.; Borlee, Bradley R.; Murakami, Keiji

    2012-01-01

    The increased tolerance toward the host immune system and antibiotics displayed by biofilm-forming Pseudomonas aeruginosa and other bacteria in chronic infections such as cystic fibrosis bronchopneumonia is of major concern. Targeting of biofilm formation is believed to be a key aspect...... of antipathogenic compounds. Here we describe the development of fluorescent monitors that can gauge the cellular level of cyclic di-GMP in P. aeruginosa. We have created cyclic di-GMP level reporters by transcriptionally fusing the cyclic di-GMP-responsive cdrA promoter to genes encoding green fluorescent protein....... We show that the reporter constructs give a fluorescent readout of the intracellular level of cyclic di-GMP in P. aeruginosa strains with different levels of cyclic di-GMP. Furthermore, we show that the reporters are able to detect increased turnover of cyclic di-GMP mediated by treatment of P...

  4. Physiological Functions of Cyclic Electron Transport Around Photosystem I in Sustaining Photosynthesis and Plant Growth.

    Science.gov (United States)

    Yamori, Wataru; Shikanai, Toshiharu

    2016-04-29

    The light reactions in photosynthesis drive both linear and cyclic electron transport around photosystem I (PSI). Linear electron transport generates both ATP and NADPH, whereas PSI cyclic electron transport produces ATP without producing NADPH. PSI cyclic electron transport is thought to be essential for balancing the ATP/NADPH production ratio and for protecting both photosystems from damage caused by stromal overreduction. Two distinct pathways of cyclic electron transport have been proposed in angiosperms: a major pathway that depends on the PROTON GRADIENT REGULATION 5 (PGR5) and PGR5-LIKE PHOTOSYNTHETIC PHENOTYPE 1 (PGRL1) proteins, which are the target site of antimycin A, and a minor pathway mediated by the chloroplast NADH dehydrogenase-like (NDH) complex. Recently, the regulation of PSI cyclic electron transport has been recognized as essential for photosynthesis and plant growth. In this review, we summarize the possible functions and importance of the two pathways of PSI cyclic electron transport.

  5. Manual for Cyclic Triaxial Test

    DEFF Research Database (Denmark)

    Shajarati, Amir; Sørensen, Kris Wessel; Nielsen, Søren Kjær

    /dynamic triaxial cell is overall constructed in the same way as the static triaxial cell at Aalborg University, but with the ability to apply any kind of load sequence to the test sample. When conducting cyclic triaxial tests, it is recommended that the manual is followed very tediously since there are many steps...... and if they are done improperly or in the wrong order there is a risk of destroying the test sample or obtaining invalid results.......This manual describes the different steps that is included in the procedure for conducting a cyclic triaxial test at the geotechnical Laboratory at Aalborg University. Furthermore it contains a chapter concerning some of the background theory for the static triaxial tests. The cyclic...

  6. Hopf cyclic cohomology and transverse characteristic classes

    CERN Document Server

    Moscovici, Henri

    2010-01-01

    By refining the cyclic cohomological apparatus for computing the Hopf cyclic cohomology of the Hopf algebras associated to infinite primitive Cartan-Lie pseudogroup, we explicitly identify, as a Hopf cyclic complex, the image of the canonical homomorphism from the Gelfand-Fuks complex to the Bott complex for equivariant cohomology. Distinct from the original realization due to A. Connes and the first named author of the cyclic cohomology of such Hopf algebras as differentiable cyclic cohomology, this construction provides a convenient front-end model for their Hopf cyclic cohomology. Relying on it, we produce characteristic homomorphisms from newly developed models for Hopf cyclic characteristic classes to the cyclic cohomology of the convolution algebras of \\'etale holonomy groupoids, which in particular work in the relative case with no compactness restriction. As an illustration, we apply the latter feature to transfer the universal Hopf cyclic Chern classes found by us in a previous paper, and produce in ...

  7. Design of a cyclic multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Piao Yunsong, E-mail: yspiao@gucas.ac.c [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)

    2010-08-09

    Recently, it has been noticed that the amplification of the amplitude of curvature perturbation cycle by cycle can lead to a cyclic multiverse scenario, in which the number of universes increases cycle by cycle. However, this amplification will also inevitably induce either the ultimate end of corresponding cycle, or the resulting spectrum of perturbations inside corresponding universe is not scale invariant, which baffles the existence of observable universes. In this Letter, we propose a design of a cyclic multiverse, in which the observable universe can emerges naturally. The significance of a long period of dark energy before the turnaround of each cycle for this implementing is shown.

  8. Recursive processing of cyclic graphs.

    Science.gov (United States)

    Bianchini, Monica; Gori, Marco; Sarti, Lorenzo; Scarselli, Franco

    2006-01-01

    Recursive neural networks are a powerful tool for processing structured data. According to the recursive learning paradigm, the input information consists of directed positional acyclic graphs (DPAGs). In fact, recursive networks are fed following the partial order defined by the links of the graph. Unfortunately, the hypothesis of processing DPAGs is sometimes too restrictive, being the nature of some real-world problems intrinsically cyclic. In this paper, a methodology is proposed, which allows us to process any cyclic directed graph. Therefore, the computational power of recursive networks is definitely established, also clarifying the underlying limitations of the model.

  9. Cyclic adenosine 3'-5'-monophosphate (cAMP) exerts proliferative and anti-proliferative effects in pituitary cells of different types by activating both cAMP-dependent protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac).

    Science.gov (United States)

    Vitali, E; Peverelli, E; Giardino, E; Locatelli, M; Lasio, G B; Beck-Peccoz, P; Spada, A; Lania, A G; Mantovani, G

    2014-03-05

    In the pituitary the activation of cyclic adenosine 3'-5'-monophosphate (cAMP) dependent pathways generates proliferative signals in somatotrophs, whereas in pituitary cells of other lineages its effect remains uncertain. Moreover, the specific role of the two main cAMP effectors, protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac), has not been defined. Aim of this study was to investigate the effect of cAMP on pituitary adenomatous cells proliferation and to identify PKA and Epac differential involvement. We found that cAMP increased DNA synthesis and cyclin D1 expression in somatotropinomas, whereas it reduced both parameters in prolactinomas and nonfunctioning adenomas, these effects being replicated in corresponding cell lines. Moreover, the divergent cAMP effects were mimicked by Epac and PKA analogs, which activated Rap1 and CREB, respectively. In conclusion, we demonstrated that cAMP exerted opposite effects on different pituitary cell types proliferation, these effects being mediated by both Epac and PKA.

  10. TANGO-Inspired Design of Anti-Amyloid Cyclic Peptides.

    Science.gov (United States)

    Lu, Xiaomeng; Brickson, Claire R; Murphy, Regina M

    2016-09-21

    β-Amyloid peptide (Aβ) self-associates into oligomers and fibrils, in a process that is believed to directly lead to neuronal death in Alzheimer's disease. Compounds that bind to Aβ, and inhibit fibrillogenesis and neurotoxicity, are of interest as an anti-Alzheimer therapeutic strategy. Peptides are particularly attractive for this purpose, because they have advantages over small molecules in their ability to disrupt protein-protein interactions, yet they are amenable to tuning of their properties through chemical means, unlike antibodies. Self-complementation and peptide library screening are two strategies that have been employed in the search for peptides that bind to Aβ. We have taken a different approach, by designing Aβ-binding peptides using transthyretin (TTR) as a template. Previously, we demonstrated that a cyclic peptide, with sequence derived from the known Aβ-binding site on TTR, suppressed Aβ aggregation into fibrils and protected neurons against Aβ toxicity. Here, we searched for cyclic peptides with improved efficacy, by employing the algorithm TANGO, designed originally to identify amyloidogenic sequences in proteins. By using TANGO as a guide to predict the effect of sequence modifications on conformation and aggregation, we synthesized a significantly improved cyclic peptide. We demonstrate that the peptide, in binding to Aβ, redirects Aβ toward protease-sensitive, nonfibrillar aggregates. Cyclic peptides designed using this strategy have attractive solubility, specificity, and stability characteristics.

  11. Cyclic-di-GMP and cyclic-di-AMP activate the NLRP3 inflammasome.

    Science.gov (United States)

    Abdul-Sater, Ali A; Tattoli, Ivan; Jin, Lei; Grajkowski, Andrzej; Levi, Assaf; Koller, Beverly H; Allen, Irving C; Beaucage, Serge L; Fitzgerald, Katherine A; Ting, Jenny P-Y; Cambier, John C; Girardin, Stephen E; Schindler, Christian

    2013-10-01

    The cyclic dinucleotides 3'-5'diadenylate (c-diAMP) and 3'-5' diguanylate (c-diGMP) are important bacterial second messengers that have recently been shown to stimulate the secretion of type I Interferons (IFN-Is) through the c-diGMP-binding protein MPYS/STING. Here, we show that physiologically relevant levels of cyclic dinucleotides also stimulate a robust secretion of IL-1β through the NLRP3 inflammasome. Intriguingly, this response is independent of MPYS/STING. Consistent with most NLRP3 inflammasome activators, the response to c-diGMP is dependent on the mobilization of potassium and calcium ions. However, in contrast to other NLRP3 inflammasome activators, this response is not associated with significant changes in mitochondrial potential or the generation of mitochondrial reactive oxygen species. Thus, cyclic dinucleotides activate the NLRP3 inflammasome through a unique pathway that could have evolved to detect pervasive bacterial pathogen-associated molecular patterns associated with intracellular infections.

  12. Color visualization of cyclic magnitudes

    Science.gov (United States)

    Restrepo, Alfredo; Estupiñán, Viviana

    2014-02-01

    We exploit the perceptual, circular ordering of the hues in a technique for the visualization of cyclic variables. The hue is thus meaningfully used for the indication of variables such as the azimuth and the units of the measurement of time. The cyclic (or circular) variables may be both of the continuous type or the discrete type; among the first there is azimuth and among the last you find the musical notes and the days of the week. A correspondence between the values of a cyclic variable and the chromatic hues, where the natural circular ordering of the variable is respected, is called a color code for the variable. We base such a choice of hues on an assignment of of the unique hues red, yellow, green and blue, or one of the 8 even permutations of this ordered list, to 4 cardinal values of the cyclic variable, suitably ordered; color codes based on only 3 cardinal points are also possible. Color codes, being intuitive, are easy to remember. A possible low accuracy when reading instruments that use this technique is compensated by fast, ludic and intuitive readings; also, the use of a referential frame makes readings precise. An achromatic version of the technique, that can be used by dichromatic people, is proposed.

  13. Cyclic Codes of Length 2

    Indian Academy of Sciences (India)

    Manju Pruthi

    2001-11-01

    In this paper explicit expressions of + 1 idempotents in the ring $R = F_q[X]/\\langle X^{2^m}-1\\rangle$ are given. Cyclic codes of length 2 over the finite field , of odd characteristic, are defined in terms of their generator polynomials. The exact minimum distance and the dimension of the codes are obtained.

  14. Powers of Convex-Cyclic Operators

    Directory of Open Access Journals (Sweden)

    Fernando León-Saavedra

    2014-01-01

    Full Text Available A bounded operator T on a Banach space X is convex cyclic if there exists a vector x such that the convex hull generated by the orbit Tnxn≥0 is dense in X. In this note we study some questions concerned with convex-cyclic operators. We provide an example of a convex-cyclic operator T such that the power Tn fails to be convex cyclic. Using this result we solve three questions posed by Rezaei (2013.

  15. CYCLIC CODES OVER FORMAL POWER SERIES RINGS

    Institute of Scientific and Technical Information of China (English)

    Dougherty Steven T.; Liu Hongwei

    2011-01-01

    In this article, cyclic codes and negacyclic codes over formal power series rings are studied. The structure of cyclic codes over this class of rings is given, and the relationship between these codes and cyclic codes over finite chain rings is obtained. Using an isomorphism between cyclic and negacyclic codes over formal power series rings, the structure of negacyclic codes over the formal power series rings is obtained.

  16. 40 CFR 721.2120 - Cyclic amide.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Cyclic amide. 721.2120 Section 721... Cyclic amide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a cyclic amide (PMN P-92-131) is subject to reporting under this section for...

  17. The cyclic theory of Hopf algebroids

    NARCIS (Netherlands)

    Kowalzig, N.; Posthuma, H.

    2011-01-01

    We give a systematic description of the cyclic cohomology theory of Hopf alge\\-broids in terms of its associated category of modules. Then we introduce a dual cyclic homology theory by applying cyclic duality to the underlying cocyclic object. We derive general structure theorems for these theories

  18. The Cyclic Graph of a Finite Group

    Directory of Open Access Journals (Sweden)

    Xuan Long Ma

    2013-01-01

    and characterize certain finite groups whose cyclic graphs have some properties. Then, we present some properties of the cyclic graphs of the dihedral groups D2n and the generalized quaternion groups Q4n for some n. Finally, we present some parameters about the cyclic graphs of finite noncyclic groups of order up to 14.

  19. Cyclical Fluctuations in Workplace Accidents

    OpenAIRE

    Boone, J.; J. C. VAN OURS

    2002-01-01

    This Paper presents a theory and an empirical investigation on cyclical fluctuations in workplace accidents. The theory is based on the idea that reporting an accident dents the reputation of a worker and raises the probability that he is fired. Therefore a country with a high or an increasing unemployment rate has a low (reported) workplace accident rate. The empirical investigation concerns workplace accidents in OECD countries. The analysis confirms that workplace accident rates are invers...

  20. 丙泊酚对大鼠海马cAMP效应元件结合蛋白磷酸化和cAMP效应元件结合蛋白mRNA表达水平的影响%Effects of propofol on cyclic AMP response element binding protein phosphorylation and cyclic AMP response element binding protein mRNA expression in hippocampus of rats

    Institute of Scientific and Technical Information of China (English)

    张英; 吴新海; 郑利民

    2011-01-01

    Objective to investigate the effects of propofol on cyclic AMP response element binding protein (CREB) phosphorylation and CREB mRNA expression in hippocampus of rats. Methods Sixty -four male Sprague -Dawley (SD) rats weighting 250 g-280 g were randomly divided into 2 groups (n=32) with Randomization Adviser 1.0 software: normal saline treated (Group S) and propofol treated (Group P). Animals of both groups underwent a continuous multiple -trial inhibitory avoidance training. The times of trial needed for each animal to attain the learning criterion( 100 seconds) were recorded. Each animal was given intraperitoneal propofol 9 mg/kg or normal saline 2 ml/kg at 15 min before training. The memory retention was tested at 1, 3 and 24 h( n=8, at each time point) after the training session and the memory latency was recorded. Animals were sacrificed at 15 min after reagent administration (T0) and after the memory testing (T1~3). Hippocampus was obtained to determine the phosphorylation of CRKB (pCREB) and CREB mRNA expression. Results The times of trials required for the rats to learn the task in Group S and Group P is 1 (0.25) and 3 (1.25), respectively. Learning ability was significantly impaired in rats of Group P(P<0.01 ). Rats of Group S had a median retention latency more than 300 s at each memory testing. The median retention latency of rats in Group P at T1, T2and T3 was 319( 144) s, 131( 114) s and 56(30) s, respectively. Compared with group S, there was a decrease of CREB phosphorylation expression at T0-3 in Group P (P<0.01). The CREB mRNA expression in Group P was decreased at T3 (P<0.01). Conclusion Propofol can inhibit CREB phosphorylation, and downregulate CREB mRNA expression in hippocampus of rats.%目的 探讨丙泊酚对大鼠海马cAMP效应元件结合蛋白(cAMP response element binding protein,CREB)磷酸化和CREB mRNA表达水平的影响.方法 成年雄性SD大鼠64只,体重250 g~280 g,采用RandA1.0随机分组软件

  1. Protein

    Science.gov (United States)

    ... Food Service Resources Additional Resources About FAQ Contact Protein Protein is found throughout the body—in muscle, ... the heart and respiratory system, and death. All Protein Isn’t Alike Protein is built from building ...

  2. Sectoral Shifts and Cyclical Fluctuations Sectoral Shifts and Cyclical Fluctuations

    Directory of Open Access Journals (Sweden)

    Richard Rogerson

    1991-03-01

    Full Text Available Sectoral Shifts and Cyclical Fluctuations This paper studies a two sector real business cycle model in which the sectors experience different trend rates of growth and labor mobility is costly. Predictions are derived concerning the correlation between sectoral reallocation of workers and the cycle. This correlation may be positive or negative depending upon whether the growing sector displays larger or smaller fluctuations than the shrinking sector. The post- World War II period has witnessed two major patterns of sectoral change in industrialized countries: movement out of agriculture and movement out of the industrial sector. The model's basic prediction is shown to be consistent with the observed pattern of reallocation.

  3. The cyclical component factor model

    DEFF Research Database (Denmark)

    Dahl, Christian Møller; Hansen, Henrik; Smidt, John

    Forecasting using factor models based on large data sets have received ample attention due to the models' ability to increase forecast accuracy with respect to a range of key macroeconomic variables in the US and the UK. However, forecasts based on such factor models do not uniformly outperform...... the simple autoregressive model when using data from other countries. In this paper we propose to estimate the factors based on the pure cyclical components of the series entering the large data set. Monte Carlo evidence and an empirical illustration using Danish data shows that this procedure can indeed...

  4. Cyclic voltammetry of supported BLMs

    Science.gov (United States)

    Murgasova, Renata; Sabo, Jan; Ottova, Angelica L.; Tien, H. T.

    1996-06-01

    The transfer of an electron across a bilayer lipid membrane (BLM) is one of the BLMs most exciting processes. A number of well known electron mediators have been investigated using the method of cyclic voltammetry on a Teflon coated platinum wire, the tip of which has been modified by a self-assembled bilayer lipid membrane (s-BLM). The electrical capacitance of the s-BLM system was measured as a function of frequency. The results are discussed in terms of electron transfer and redox reactions.

  5. Analysis of substrate specificity and kinetics of cyclic nucleotide phosphodiesterases with N'-methylanthraniloyl-substituted purine and pyrimidine 3',5'-cyclic nucleotides by fluorescence spectrometry.

    Directory of Open Access Journals (Sweden)

    Daniel Reinecke

    Full Text Available As second messengers, the cyclic purine nucleotides adenosine 3',5'-cyclic monophosphate (cAMP and guanosine 3',5'-cyclic monophosphate (cGMP play an essential role in intracellular signaling. Recent data suggest that the cyclic pyrimidine nucleotides cytidine 3',5'-cyclic monophosphate (cCMP and uridine 3',5'-cyclic monophosphate (cUMP also act as second messengers. Hydrolysis by phosphodiesterases (PDEs is the most important degradation mechanism for cAMP and cGMP. Elimination of cUMP and cCMP is not completely understood, though. We have shown that human PDEs hydrolyze not only cAMP and cGMP but also cyclic pyrimidine nucleotides, indicating that these enzymes may be important for termination of cCMP- and cUMP effects as well. However, these findings were acquired using a rather expensive HPLC/mass spectrometry assay, the technical requirements of which are available only to few laboratories. N'-Methylanthraniloyl-(MANT-labeled nucleotides are endogenously fluorescent and suitable tools to study diverse protein/nucleotide interactions. In the present study, we report the synthesis of new MANT-substituted cyclic purine- and pyrimidine nucleotides that are appropriate to analyze substrate specificity and kinetics of PDEs with more moderate technical requirements. MANT-labeled nucleoside 3',5'-cyclic monophosphates (MANT-cNMPs are shown to be substrates of various human PDEs and to undergo a significant change in fluorescence upon cleavage, thus allowing direct, quantitative and continuous determination of hydrolysis via fluorescence detection. As substrates of several PDEs, MANT-cNMPs show similar kinetics to native nucleotides, with some exceptions. Finally, they are shown to be also appropriate tools for PDE inhibitor studies.

  6. The biosynthesis of cyclic carotenes.

    Science.gov (United States)

    Williams, R J; Britton, G; Goodwin, T W

    1967-10-01

    1. The incorporation of (3RS)-[2-(14)C,(4R)-4-(3)H(1)]mevalonic acid into various cyclic carotenes in the fruit of the tomato mutant delta has been studied. The results confirm our previous view that the alpha-ionone ring of alpha-carotene does not arise by isomerization of a beta-ionone residue, and show that the same is also true for the alpha-ionone ring of delta- and in-carotene and alpha-zeacarotene. 2. The incorporation of (3RS)-[2-(14)C,2-(3)H(2)]mevalonic acid into alpha- and beta-carotene in carrot roots has been studied. The results show that the beta-ionone ring of beta-carotene does not arise by isomerization of the alpha-ionone residue of alpha-carotene. 3. These experiments show that alpha- and beta-ionone rings in cyclic carotenes are formed independently, probably by elimination of different protons from the same carbonium ion intermediates.

  7. [Cyclic Cushing's Syndrome - rare or rarely recognized].

    Science.gov (United States)

    Kiałka, Marta; Doroszewska, Katarzyna; Mrozińska, Sandra; Milewicz, Tomasz; Stochmal, Ewa

    2015-01-01

    Cyclic Cushing's syndrome is a type of Cushing's disease which is characterized by alternating periods of increasing and decreasing levels of cortisol in the blood. The diagnostic criteria for cyclic Cushing's syndrome are at least three periods of hypercortisolism alternating with at least two episodes of normal levels of serum cortisol concentration. The epidemiology, signs, symptoms, pathogenesis and treatment of cyclic Cushing's syndrome have been discussed.

  8. Cyclic Cohomology of the Weyl Algebra

    CERN Document Server

    Willwacher, Thomas

    2008-01-01

    We give an explicit formula for symplectically basic representatives of the cyclic cohomology of the Weyl algebra. This paper can be seen as cyclic addendum to the paper by Feigin, Felder and Shoikhet, where the analogous Hochschild case was treated. As an application, we prove a generalization of a Theorem of Nest and Tsygan concerning the relation of the Todd class and the cyclic cohomology of the differential operators on a complex manifold.

  9. Cyclic and Inductive Calculi are equivalent

    CERN Document Server

    Voicu, Razvan

    2011-01-01

    Brotherston and Simpson [citation] have formalized and investigated cyclic reasoning, reaching the important conclusion that it is at least as powerful as inductive reasoning (specifically, they showed that each inductive proof can be translated into a cyclic proof). We add to their investigation by proving the converse of this result, namely that each inductive proof can be translated into an inductive one. This, in effect, establishes the equivalence between first order cyclic and inductive calculi.

  10. Cyclic and Inductive Calculi are equivalent

    OpenAIRE

    Razvan VOICU; Li, Mengran

    2011-01-01

    Brotherston and Simpson [citation] have formalized and investigated cyclic reasoning, reaching the important conclusion that it is at least as powerful as inductive reasoning (specifically, they showed that each inductive proof can be translated into a cyclic proof). We add to their investigation by proving the converse of this result, namely that each inductive proof can be translated into an inductive one. This, in effect, establishes the equivalence between first order cyclic and inductive...

  11. Cell reorientation under cyclic stretching

    CERN Document Server

    Livne, Ariel; Geiger, Benjamin

    2014-01-01

    Mechanical cues from the extracellular microenvironment play a central role in regulating the structure, function and fate of living cells. Nevertheless, the precise nature of the mechanisms and processes underlying this crucial cellular mechanosensitivity remains a fundamental open problem. Here we provide a novel framework for addressing cellular sensitivity and response to external forces by experimentally and theoretically studying one of its most striking manifestations -- cell reorientation to a uniform angle in response to cyclic stretching of the underlying substrate. We first show that existing approaches are incompatible with our extensive measurements of cell reorientation. We then propose a fundamentally new theory that shows that dissipative relaxation of the cell's passively-stored, two-dimensional, elastic energy to its minimum actively drives the reorientation process. Our theory is in excellent quantitative agreement with the complete temporal reorientation dynamics of individual cells, measu...

  12. Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Kjelstrup, Susanne; Hansen, Paula Melo Paulon; Thomsen, Line Elnif;

    2013-01-01

    Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides...

  13. Cyclic electrophoretic and chromatographic separation methods

    NARCIS (Netherlands)

    Eijkel, Jan C.T.; Berg, van den Albert; Manz, Andreas

    2004-01-01

    A review is given of the application of cyclic analytical methods in capillary electroseparation (CE) and liquid chromatography (LC) systems. Cyclic methods have been used since the early sixties in chromatographic systems to overcome pressure limitations to resolution. From the early nineties on th

  14. Cyclicality in Losses on Bank Loans

    NARCIS (Netherlands)

    B. Keijsers (Bart); B.F. Diris (Bart); H.J.W.G. Kole (Erik)

    2015-01-01

    markdownabstract__Abstract__ Cyclicality in the losses of bank loans is important for bank risk management. Because loans have a different risk profile than bonds, evidence of cyclicality in bond losses need not apply to loans. Based on unique data we show that the default rate and loss given defau

  15. Cyclic malyl anthocyanins in Dianthus caryophyllus.

    Science.gov (United States)

    Nakayama, M; Koshioka, M; Yoshida, H; Kan, Y; Fukui, Y; Koike, A; Yamaguchi, M

    2000-12-01

    3,5-Di-O-(beta-glucopyranosyl) pelargonidin 6''-O-4,6'''-O-1-cyclic malate and a previously reported cyanidin equivalent, 3,5-di-O-(beta-glucopyranosyl) cyanidin 6''-O-4,6'''-O-1-cyclic malate were identified from petals of deep pink and red-purple flower cultivars of Dianthus caryophyllus, respectively.

  16. Products in Hopf-Cyclic Cohomology

    CERN Document Server

    Kaygun, Atabey

    2007-01-01

    We construct several pairings in Hopf-cyclic cohomology of (co)module (co)algebras with arbitrary coefficients. The key ideas instrumental in constructing these pairings are the derived functor interpretation of Hopf-cyclic and equivariant cyclic (co)homology, and the Yoneda interpretation of Ext-groups. As a special case of one of these pairings, we recover the Connes-Moscovici characteristic map in Hopf-cyclic cohomology. We also prove that this particular pairing, along with few others, would stay the same if we replace the derived category of (co)cyclic modules with the homotopy category of (special) towers of $X$-complexes, or the derived category of mixed complexes.

  17. Brucella β 1,2 cyclic glucan is an activator of human and mouse dendritic cells.

    Directory of Open Access Journals (Sweden)

    Anna Martirosyan

    Full Text Available Bacterial cyclic glucans are glucose polymers that concentrate within the periplasm of alpha-proteobacteria. These molecules are necessary to maintain the homeostasis of the cell envelope by contributing to the osmolarity of Gram negative bacteria. Here, we demonstrate that Brucella β 1,2 cyclic glucans are potent activators of human and mouse dendritic cells. Dendritic cells activation by Brucella β 1,2 cyclic glucans requires TLR4, MyD88 and TRIF, but not CD14. The Brucella cyclic glucans showed neither toxicity nor immunogenicity compared to LPS and triggered antigen-specific CD8(+ T cell responses in vivo. These cyclic glucans also enhanced antigen-specific CD4(+ and CD8(+ T cell responses including cross-presentation by different human DC subsets. Brucella β 1,2 cyclic glucans increased the memory CD4(+ T cell responses of blood mononuclear cells exposed to recombinant fusion proteins composed of anti-CD40 antibody and antigens from both hepatitis C virus and Mycobacterium tuberculosis. Thus cyclic glucans represent a new class of adjuvants, which might contribute to the development of effective antimicrobial therapies.

  18. Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not?

    NARCIS (Netherlands)

    Nini, A. van; Cheung, K.; Fusconi, M.; Stammen-Vogelzangs, J.; Drenth, J.P.H.; Dall'aglio, A.C.; Bianchi, F.B.; Bakker-Jonges, L.E.; Venrooij, W.J.W. van; Pruijn, G.J.M.; Zendman, A.J.W.

    2007-01-01

    BACKGROUND: Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum

  19. Improvement on the competitive binding assay for the measurement of cyclic AMP by using ammonium sulphate precipitation.

    Science.gov (United States)

    Santa-Coloma, T A; Bley, M A; Charreau, E H

    1987-08-01

    The protein-binding assay developed by Brown, Albano, Ekins, Sgherzi & Tampion [(1971) Biochem. J. 121, 561-562] and Brown, Ekins & Albano [(1972) Adv. Cyclic Nucleotide Res. 2, 25-40] was modified by using precipitation with (NH4)2SO4 of the protein-cyclic AMP complex instead of adsorption of the free nucleotide on charcoal. The half-life of the protein-cyclic AMP complex obtained in the presence of charcoal was lower than that of the (NH4)2SO4-precipitated complex. In consequence, owing to the great stability of the precipitated protein-cyclic AMP complex, this method allows more accurate and reproducible determinations.

  20. Targeting cyclic di-GMP signalling: a strategy to control biofilm formation?

    Science.gov (United States)

    Caly, Delphine L; Bellini, Domenico; Walsh, Martin A; Dow, J Maxwell; Ryan, Robert P

    2015-01-01

    Cyclic di-GMP is a second messenger found in almost all eubacteria that acts to regulate a wide range of functions including developmental transitions, adhesion and biofilm formation. Cyclic di-GMP is synthesised from two GTP molecules by diguanylate cyclases that have a GGDEF domain and is degraded by phosphodiesterases with either an EAL or an HD-GYP domain. Proteins with these domains often contain additional signal input domains, suggesting that their enzymatic activity may be modulated as a response to different environmental or cellular cues. Cyclic di-GMP exerts a regulatory action through binding to diverse receptors that include a small protein domain called PilZ, enzymatically inactive GGDEF, EAL or HD-GYP domains, transcription factors and riboswitches. In many bacteria, high cellular levels of cyclic di-GMP are associated with a sessile, biofilm lifestyle, whereas low levels of the nucleotide promote motility and virulence factor synthesis in pathogens. Elucidation of the roles of cyclic di-GMP signalling in biofilm formation has suggested strategies whereby modulation of the levels of the nucleotide or interference with signalling pathways may lead to inhibition of biofilm formation or promotion of biofilm dispersal. In this review we consider these approaches for the control of biofilm formation, beginning with an overview of cyclic di-GMP signalling and the different ways that it can act in regulation of biofilm dynamics.

  1. Combinatorial Library Screening Coupled to Mass Spectrometry to Identify Valuable Cyclic Peptides.

    Science.gov (United States)

    Camperi, Silvia A; Giudicessi, Silvana L; Martínez-Ceron, María C; Gurevich-Messina, Juan M; Saavedra, Soledad L; Acosta, Gerardo; Cascone, Osvaldo; Erra-Balsells, Rosa; Albericio, Fernando

    2016-06-02

    Combinatorial library screening coupled to mass spectrometry (MS) analysis is a practical approach to identify useful peptides. Cyclic peptides can have high biological activity, selectivity, and affinity for target proteins, and high stability against proteolytic degradation. Here we describe two strategies to prepare combinatorial libraries suitable for MS analysis to accelerate the discovery of cyclic peptide structures. Both approaches use ChemMatrix resin and the linker 4-hydroxymethylbenzoic acid. One strategy involves the synthesis of a one-bead-two-peptides library in which each bead contains both the cyclic peptide and its linear counterpart to facilitate MS analysis. The other protocol is based on the synthesis of a cyclic depsipeptide library in which a glycolamidic ester group is incorporated by adding glycolic acid. After library screening, the ring is opened and the peptide is released simultaneously for subsequent MS analysis. © 2016 by John Wiley & Sons, Inc.

  2. Review cyclic peptides on a merry-go-round; towards drug design.

    Science.gov (United States)

    Tapeinou, Anthi; Matsoukas, Minos-Timotheos; Simal, Carmen; Tselios, Theodore

    2015-09-01

    Peptides and proteins are attractive initial leads for the rational design of bioactive molecules. Several natural cyclic peptides have recently emerged as templates for drug design due to their resistance to chemical or enzymatic hydrolysis and high selectivity to receptors. The development of practical protocols that mimic the power of nature's strategies remains paramount for the advancement of novel peptide-based drugs. The de novo design of peptide mimetics (nonpeptide molecules or cyclic peptides) for the synthesis of linear or cyclic peptides has enhanced the progress of therapeutics and diverse areas of science and technology. In the case of metabolically unstable peptide ligands, the rational design and synthesis of cyclic peptide analogues has turned into an alternative approach for improved biological activity.

  3. 环磷酸腺苷激活的交换蛋白介导的信号通路在视网膜中的作用%Exchange proteins activated directly by cyclic adenosinemonophosphate-mediated signal pathway and its role in the retina

    Institute of Scientific and Technical Information of China (English)

    胡单萍

    2015-01-01

    环磷酸腺苷激活的交换蛋白(Epac)是鸟嘌呤核苷酸交换蛋白因子,与环磷酸腺苷(cAMP)高亲和力地结合后能激活下游的多种信号分子,如Rap和Ras等,这些信号分子可参与多种细胞的生理和病理过程.Ras和Rap能靶向诱导光感受器的生长、分化及增生,Ras可通过酪氨酸蛋白激酶信号传递(Ras/Raf/MEK/ERK)参与年龄相关性黄斑变性(AMD)和增生性玻璃体视网膜病变(PVR)等疾病的发生.就近年来Epac的研究进展及其下游信号分子在视网膜内的功能进行综述.%Exchange proteins activated directly by cyclic adenosinemonophosphate (Epac) is one of cyclic adenosinemonophosphate (cAMP)-regulated guanine nucleotide exchange factors.When Epac closely binds with cAMP,it can activate many downstream signal molecules,such as Rap and Ras,etc.By activating several effectors,Epac regulates a multitude of important physiological and pathological processes.Ras and Rap play important effects on the differentiation and proliferation of photoreceptors.Ras may participate in the pathogenesis and development of age-related macular degeneration (AMD) and prolifereative vitreo-retinopathy (PVR) through Ras/Raf-1/MEK/ERK cascade.Therefore,further studies about the role of Epac and its downstream signals in the retina may provide numerous directions both in research and treatment of retinal diseases.The researching progress in Epac and the functions of the downstream signaling molecules of Epac in the retina were reviewed.

  4. Cyclic Shearing Deformation Behavior of Saturated Clays

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The apparatus for static and dynamic universal triaxial and torsional shear soil testing is employed to perform stress-controlled cyclic single-direction torsional shear tests and two-direction coupled shear tests under unconsolidated-undrained conditions. Through a series of tests on saturated clay, the effects of initial shear stress and stress reversal on the clay's strain-stress behavior are examined, and the behavior of pore water pressure is studied. The experimental results indicate that the patterns of stress-strain relations are distinctly influenced by the initial shear stress in the cyclic single-direction shear tests. When the initial shear stress is large and no stress reversal occurs, the predominant deformation behavior is characterized by an accumulative effect. When the initial shear stress is zero and symmetrical cyclic stress occurs, the predominant deformation behavior is characterized by a cyclic effect. The pore water pressure fluctuates around the confining pressure with the increase of cycle number. It seems that the fluctuating amplitude increases with the increase of the cyclic stress. But a buildup of pore water pressure does not occur. The deformations of clay samples under the complex initial and the cyclic coupled stress conditions include the normal deviatoric deformation and horizontal shear deformation, the average deformation and cyclic deformation. A general strain failure criterion taking into account these deformations is recommended and is proved more stable and suitable compared to the strain failure criteria currently used.

  5. Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available AIM: Human periodontal ligament (PDL cells incur changes in morphology and express proteins in response to cyclic strain. However, it is not clear whether cyclic strain, especially excessive cyclic strain, induces PDL cell apoptosis and if so, what mechanism(s are responsible. The aim of the present study was to elucidate the molecular mechanisms by which pathological levels of cyclic strain induce human PDL cell apoptosis. MATERIALS AND METHODS: Human PDL cells were obtained from healthy premolar tissue. After three to five passages in culture, the cells were subjected to 20% cyclic strain at a frequency of 0.1 Hz for 6 or 24 h using an FX-5000T system. Morphological changes of the cells were assessed by inverted phase-contrast microscopy, and apoptosis was detected by fluorescein isothiocyanate (FITC-conjugated annexin V and propidium iodide staining followed by flow cytometry. Protein expression was evaluated by Western blot analysis. RESULTS: The number of apoptotic human PDL cells increased in a time-dependent manner in response to pathological cyclic strain. The stretched cells were oriented parallel to each another with their long axes perpendicular to the strain force vector. Cleaved caspase-3 and poly-ADP-ribose polymerase (PARP protein levels increased in response to pathological cyclic strain over time, while Rho GDP dissociation inhibitor alpha (RhoGDIα decreased. Furthermore, knock-down of RhoGDIα by targeted siRNA transfection increased stretch-induced apoptosis and upregulated cleaved caspase-3 and PARP protein levels. Inhibition of caspase-3 prevented stretch-induced apoptosis, but did not change RhoGDIα protein levels. CONCLUSION: The overall results suggest that pathological-level cyclic strain not only influenced morphology but also induced apoptosis in human PDL cells through the RhoGDIα/caspase-3/PARP pathway. Our findings provide novel insight into the mechanism of apoptosis induced by pathological cyclic strain in

  6. Discrete cyclic porphyrin arrays as artificial light-harvesting antenna.

    Science.gov (United States)

    Aratani, Naoki; Kim, Dongho; Osuka, Atsuhiro

    2009-12-21

    The importance of photosynthesis has driven researchers to seek ways to mimic its fundamental features in simplified systems. The absorption of a photon by light-harvesting (antenna) complexes made up of a large number of protein-embedded pigments initiates photosynthesis. Subsequently the many pigments within the antenna system shuttle that photon via an efficient excitation energy transfer (EET) until it encounters a reaction center. Since the 1995 discovery of the circularly arranged chromophoric assemblies in the crystal structure of light-harvesting antenna complex LH2 of purple bacteria Rps. Acidophila, many designs of light-harvesting antenna systems have focused on cyclic porphyrin wheels that allow for efficient EET. In this Account, we review recent research in our laboratories in the synthesis of covalently and noncovalently linked discrete cyclic porphyrin arrays as models of the photosynthetic light-harvesting antenna complexes. On the basis of the silver(I)-promoted oxidative coupling strategy, we have prepared a series of extremely long yet discrete meso-meso-linked porphyrin arrays and covalently linked large porphyrin rings. We examined the photophysical properties of these molecules using steady-state absorption, fluorescence, fluorescence lifetime, fluorescence anisotropy decay, and transient absorption measurements. Both the pump-power dependence on the femtosecond transient absorption and the transient absorption anisotropy decay profiles are directly related to the EET processes within the porphyrin rings. Within these structures, the exciton-exciton annihilation time and the polarization anisotropy rise time are well-described in terms of the Forster-type incoherent energy hopping model. In noncoordinating solvents such as CHCl(3), meso-pyridine-appended zinc(II) porphyrins and their meso-meso-linked dimers spontaneously assemble to form tetrameric porphyrin squares and porphyrin boxes, respectively. In the latter case, we have demonstrated

  7. General solution of cyclic Leibniz rule

    CERN Document Server

    Kadoh, Daisuke

    2015-01-01

    We study the general solution of the cyclic Leibniz rule (CLR) which was recently proposed as a new approach to the lattice supersymmetry. Introducing some mathematical preliminaries associated with the cyclic symmetry, we find the general solution of the 2-body CLR for the naive symmetric difference operator. The main theorems of this paper state that the general solution can be uniquely expressed as (A) a linear combination of the two fundamental solutions with cyclic invariant coefficients, and (B) a linear combination of the minimal solutions with complex coefficients. Moreover, an extension to the general difference operators is also discussed.

  8. Monopod bucket foundations under cyclic lateral loading

    OpenAIRE

    Foglia, Aligi; Ibsen, Lars Bo

    2014-01-01

    The monopod bucket foundation can be a cost-reducing sub-structure for offshore wind turbines. To avoid problems during the turbine operation, the long-term effect of cyclic loading must be considered in the design of the foundation. In this paper a 1g testing rig is adopted to extend the knowledge on bucket foundations under lateral cyclic loading. The test setup is described in detail and a comprehensive experimental campaign is presented. The foundation is subjected to cyclic overturning m...

  9. Cyclic Control Optimization for a Smart Rotor

    DEFF Research Database (Denmark)

    Bergami, Leonardo; Henriksen, Lars Christian

    2012-01-01

    The paper presents a method to determine cyclic control trajectories for a smart rotor undergoing periodic-deterministic load variations. The control trajectories result from a constrained optimization problem, where the cost function to minimize is given by the variation of the blade root flapwise...... bending moment within a rotor revolution. The method is applied to a rotor equipped with trailing edge flaps, and capable of individual blade pitching. Results show that the optimized cyclic control significantly alleviates the load variations from periodic disturbances; the combination of both cyclic...

  10. Development of novel cyclic peptides as pro-apoptotic agents.

    Science.gov (United States)

    Brindisi, Margherita; Maramai, Samuele; Brogi, Simone; Fanigliulo, Emanuela; Butini, Stefania; Guarino, Egeria; Casagni, Alice; Lamponi, Stefania; Bonechi, Claudia; Nathwani, Seema M; Finetti, Federica; Ragonese, Francesco; Arcidiacono, Paola; Campiglia, Pietro; Valenti, Salvatore; Novellino, Ettore; Spaccapelo, Roberta; Morbidelli, Lucia; Zisterer, Daniela M; Williams, Clive D; Donati, Alessandro; Baldari, Cosima; Campiani, Giuseppe; Ulivieri, Cristina; Gemma, Sandra

    2016-07-19

    Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel. Starting from these peptide-hits, we herein describe the synthesis and the biological investigation of linear and cyclic peptides structurally related to PEP2. While linear peptides (2a,b, 3a,b, 4, 6a-f) were found inactive in cell-based assays, biological analysis revealed a pro-apoptotic effect for most of the cyclic peptides (5a-g). Cellular permeability of 5a (and also of 2a,b) on HL60 cells was assessed through confocal microscopy analysis. Further cellular studies on a panel of leukemic cell lines (HL60, Jurkat, MEC, EBVB) and solid tumor cell lines (breast cancer MCF-7 cells, human melanoma A375 and 501Mel cells, and murine melanoma B16F1 cells) confirmed the pro-apoptotic effect of the cyclic peptides. Cell cycle analysis revealed that treatment with 5a, 5c, 5d or 5f resulted in an increase in the number of cells in the sub-G0/G1 peak. Direct interaction with tubulin (turbidimetric assay) and with microtubules (immunostaining experiments) was assessed in vitro for the most promising compounds.

  11. Mortar constituent of concrete under cyclic compression

    Science.gov (United States)

    Maher, A.; Darwin, D.

    1980-10-01

    The behavior of the mortar constituent of concrete under cyclic compression was studied and a simple analytic model was developed to represent its cyclic behavior. Experimental work consisted of monotonic and cyclic compressive loading of mortar. Two mixes were used, with proportions corresponding to concretes having water cement ratios of 0.5 and 0.6. Forty-four groups of specimens were tested at ages ranging from 5 to 70 days. complete monotonic and cyclic stress strain envelopes were obtained. A number of loading regimes were investigated, including cycles to a constant maximum strain. Major emphasis was placed on tests using relatively high stress cycles. Degradation was shown to be a continuous process and a function of both total strain and load history. No stability or fatigue limit was apparent.

  12. Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway

    OpenAIRE

    Shufen Angeline Ong; Jen Jen Tan; Wai Loon Tew; Ken-Shiung Chen

    2011-01-01

    All living organisms exhibit autonomous daily physiological and behavioural rhythms to help them synchronize with the environment. Entrainment of circadian rhythm is achieved via activation of cyclic AMP (cAMP) and mitogen-activated protein kinase signaling pathways. NonO (p54nrb) is a multifunctional protein involved in transcriptional activation of the cAMP pathway and is involved in circadian rhythm control. Rasd1 is a monomeric G protein implicated to play a pivotal role in potentiating b...

  13. The Permutation Groups and the Equivalence of Cyclic and Quasi-Cyclic Codes

    CERN Document Server

    Guenda, Kenza

    2010-01-01

    We give the class of finite groups which arise as the permutation groups of cyclic codes over finite fields. Furthermore, we extend the results of Brand and Huffman et al. and we find the properties of the set of permutations by which two cyclic codes of length p^r can be equivalent. We also find the set of permutations by which two quasi-cyclic codes can be equivalent.

  14. Cyclic Voltammetry And Linear Sweep Voltammetry Study Of Cyclic Tertiary Amines

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ping; TIAN JinPing; YIN YingWu

    2001-01-01

    @@ Cyclic six membered a-aminonitrile have proved to be very versatile synthetic intermediates and have been widely used in the construction of a large number of indole alkaloids. In order to obtain some information about the mechanisn of electrochemical synthesis of aaminonitrile. Electrochemistry behaviors that include cyclic voltammetry and linear sweep voltammetry of cyclic tertiary amines which including N-benzylpiperidine (NBP), 1-(l-Methoxycarbonyl ethyl) piperidine (MCEP), N-methylcarbonylppiperidine (NMCP), Nethylpiperidine(NEP) was studied.

  15. Cyclic Voltammetry And Linear Sweep Voltammetry Study Of Cyclic Tertiary Amines

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Ping

    2001-01-01

    Cyclic six membered a-aminonitrile have proved to be very versatile synthetic intermediates and have been widely used in the construction of a large number of indole alkaloids. In order to obtain some information about the mechanisn of electrochemical synthesis of aaminonitrile. Electrochemistry behaviors that include cyclic voltammetry and linear sweep voltammetry of cyclic tertiary amines which including N-benzylpiperidine (NBP), 1-(l-Methoxycarbonyl ethyl) piperidine (MCEP), N-methylcarbonylppiperidine (NMCP), Nethylpiperidine(NEP) was studied.……

  16. Cyclic Oxonitriles: Stereodivergent Grignard Addition-Alkylations

    OpenAIRE

    Fleming, Fraser F.; Wei, Guoqing; Zhang, Zhiyu; Steward, Omar W.

    2007-01-01

    Sequential carbonyl addition-conjugate addition of Grignard reagents to cyclic 5–7–membered oxoalkenenitriles efficiently generates cyclic magnesiated nitriles. Alkylations of these magnesiated nitriles exhibit diastereoselectivities that depend intimately on the size of the carbocyclic ring: 5-membered oxonitriles generate magnesiated nitriles whose alkylations are controlled by steric constraints whereas 6- and 7-membered oxonitriles generate internally coordinated, C-magnesiated nitriles w...

  17. Total synthesis of cyclic heptapeptide euryjanicin B

    Institute of Scientific and Technical Information of China (English)

    Chun Mei Zhang; Jun Xiang Guo; Liang Wang; Xiao Yun Chai; Hong Gang Hu; Qiu Ye Wu

    2011-01-01

    The first synthesis of the naturally occurring cyclic peptide euryjanicin B has been achieved. A general method was described to synthesize the cyclic peptide by a two-step solid-phase/solution synthesis strategy. All the amino acids in this study are L-configuration, The linear heptapeptide was assembled by standard Fmoc chemistry on solid-phase and subsequently cyclization was carried out by solution method.

  18. Cyclic Period in the CBE Model

    CERN Document Server

    Frampton, Paul H

    2016-01-01

    In a cyclic entropy model in which the extroverse is jettisoned at turnaround with a Come Back Empty (CBE) assumption, we address matching of the contaction scale factor $\\hat{a}(t)=f(t_T){a}(t)$ to the expansion scale factor $a(t)$, where $f(t_T)$ is the ratio at turnaround of the introverse to extroverse radii. Such matching is necessary for infinite cyclicity and fixes the CBE period at $\\sim 2.6Ty$.

  19. Synthesis of Chiral Amino Cyclic Phosphoric Acids

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Chirai amino cyclic phosphoric acids, 5-amino-2-hydroxy-4- (4-nitrophenyl)-l, 3,2-dioxaphospho- rinane 2-oxide and 2-hydroxy-4- (4-methylsulfonylphenyl)-5-phthalimido-1,3,2-dioxaphos phorinane 2-oxide are synthesized in good over yields (64. 2% and 72. 8% respectively) from 2-amino-l-aryl-l,3-propanediols. The different reaction conditions are necessary in hydrolysis reactions of amino cyclic phosphonyl chlorides.

  20. Antimicrobial cyclic peptides for plant disease control.

    Science.gov (United States)

    Lee, Dong Wan; Kim, Beom Seok

    2015-03-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  1. Antimicrobial Cyclic Peptides for Plant Disease Control

    Directory of Open Access Journals (Sweden)

    Dong Wan Lee

    2015-03-01

    Full Text Available Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  2. Cyclic behaviors of amorphous shape memory polymers.

    Science.gov (United States)

    Yu, Kai; Li, Hao; McClung, Amber J W; Tandon, Gyaneshwar P; Baur, Jeffery W; Qi, H Jerry

    2016-04-01

    Cyclic loading conditions are commonly encountered in the applications of shape memory polymers (SMPs), where the cyclic characteristics of the materials determine their performance during the service life, such as deformation resistance, shape recovery speed and shape recovery ratio. Recent studies indicate that in addition to the physical damage or some other irreversible softening effects, the viscoelastic nature could also be another possible reason for the degraded cyclic behavior of SMPs. In this paper, we explore in detail the influence of the viscoelastic properties on the cyclic tension and shape memory (SM) behavior of an epoxy based amorphous thermosetting polymer. Cyclic experiments were conducted first, which show that although the epoxy material does not have any visible damage or irreversible softening effect during deformation, it still exhibits obvious degradation in the cyclic tension and SM behaviors. A linear multi-branched model is utilized to assist in the prediction and understanding of the mechanical responses of amorphous SMPs. Parametric studies based on the applied model suggest that the shape memory performance can be improved by adjusting programming and recovery conditions, such as lowering the loading rate, increasing the programming temperature, and reducing the holding time.

  3. Some Structure Properties of the Cyclic Fuzzy Group Family

    Institute of Scientific and Technical Information of China (English)

    Hacl Akta(s); Naim (C)a(g)man

    2005-01-01

    In crisp environment, the notion of cyclic group on a set is well known. We study an extension of this classical notion to the fuzzy sets to define the concept of cyclic fuzzy subgroups. By using these cyclic fuzzy subgroups, we then define a cyclic fuzzy group family and investigate its structure properties.

  4. Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells.

    Science.gov (United States)

    Zhang, Bingyu; Luo, Qing; Chen, Zhe; Sun, Jinghui; Xu, Baiyao; Ju, Yang; Song, Guanbin

    2015-03-01

    Bone marrow stromal cells (BMSCs, also broadly known as bone marrow-derived mesenchymal stem cells) are multipotent stem cells that have a self-renewal capacity and multilineage differentiation potential. Mechanical stretching plays a vital role in regulating the proliferation and differentiation of BMSCs. However, little is known about the effects of cyclic stretching on BMSC migration and invasion. In this study, using a custom-made cell-stretching device, we studied the effects of cyclic mechanical stretching on rat BMSC migration and invasion using a Transwell Boyden Chamber. The protein secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was detected by gelatin zymography, and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) was measured by western blot. We found that cyclic mechanical stretching with 10% amplitude at 1Hz frequency for 8h promotes BMSC migration, but reduces BMSC invasion. FAK and ERK1/2 signals were activated in BMSCs after exposure to cyclic stretching. In the presence of the FAK phosphorylation blocker PF573228 or the ERK1/2 phosphorylation blocker PD98059, the cyclic-stretch-promoted migration of BMSCs was completely suppressed. On the other hand, cyclic mechanical stretching reduced the secretion of MMP-2 and MMP-9 in BMSCs, and PF573228 suppressed the cyclic-stretch-reduced secretion of MMP-2 and MMP-9. The decrease of BMSC invasion induced by mechanical stretching is partially restored by PF573228 but remained unaffected by PD98059. Taken together, these data show that cyclic mechanical stretching promotes BMSC migration via the FAK-ERK1/2 signalling pathway, but reduces BMSC invasion by decreasing secretion of MMP-2 and MMP-9 via FAK, independent of the ERK1/2 signal.

  5. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia.

    Science.gov (United States)

    Abraham, E; Arcaroli, J; Shenkar, R

    2001-01-01

    Acute lung injury is frequently associated with sepsis or blood loss and is characterized by a proinflammatory response and infiltration of activated neutrophils into the lungs. Hemorrhage or endotoxemia result in activation of cAMP response element-binding protein (CREB) and NF-kappa B in lung neutrophils as well as increased expression of proinflammatory cytokines, such as TNF-alpha and macrophage-inflammatory peptide-2, by these cells. Activation of the extracellular regulated kinase (ERK) pathway occurs in stress responses and is involved in CREB activation. In the present experiments, hemorrhage or endotoxemia produced increased activation of mitogen-activated protein kinase kinase (MEK)1/2 and ERK2 (p42), but not of ERK1 (p44), in lung neutrophils. ERK1, ERK2, and MEK1/2 were not activated in peripheral blood neutrophils after hemorrhage or endotoxemia. Inhibition of xanthine oxidase led to further increase in the activation of MEK1/2 and ERK2 in lung neutrophils after hemorrhage, but not after endotoxemia. Alpha-adrenergic blockade before hemorrhage resulted in increased activation in lung neutrophils of MEK1/2, ERK1, ERK2, and CREB, but decreased activation of NF-kappa B. In contrast, alpha-adrenergic blockade before endotoxemia was associated with decreased activation of MEK1/2, ERK2, and CREB, but increased activation of NF-kappa B. Beta-adrenergic blockade before hemorrhage did not alter MEK1/2 or ERK1 activation in lung neutrophils, but decreased activation of ERK2 and CREB, while increasing activation of NF-kappa B. Beta-adrenergic inhibition before endotoxemia did not affect activation of MEK1/2, ERK1, ERK2, CREB, or NF-kappa B. These data indicate that the pathways leading to lung neutrophil activation after hemorrhage are different from those induced by endotoxemia.

  6. Separation of effects of adenosine on energy metabolism from those on cyclic AMP in rat thymic lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nordeen, S.K.; Young, D.A.

    1977-08-10

    In rat thymic lymphocytes incubated for 2 h without exogenous energy-providing substrate, adenosine may be substituted for glucose as a means of maximally restoring energy metabolism and those cellular functions whose rates are sensitive to small changes in the energy balance, such as protein synthesis and uridine utilization for RNA synthesis. Since effects of adenosine in thymocytes and other cells have frequently been attributed to changes in cyclic AMP, this report investigates its possible involvement in these glucose-like restorative actions of adenosine. Although the same range of doses of adenosine effective at raising cyclic AMP also elicit roughly parallel stimulations of protein synthesis and uridine utilization, further results dissociate the restorative actions from those on cyclic AMP. (a) Other purine nucleosides mimic the glucose-like actions of adenosine without increasing cyclic AMP; (b) conversely, prostaglandin E/sub 1/ mimics the cyclic AMP response without restoring energy metabolism or energy-dependent functions; and (c) potentiation of the cyclic AMP response, either by inhibiting phosphodiesterase or adenosine deaminase, does not enhance the restorative response to a range of doses of adenosine. Finally, cyclic AMP-mediated glycogenolysis cannot account for the glucose-like effects since addition of adenosine increases, not decreases, levels of glycogen.

  7. Solid-state NMR [13C,15N] resonance assignments of the nucleotide-Binding Domain of a bacterial Cyclic Nucleotide-Gated Channel

    NARCIS (Netherlands)

    Cukkemane, A.A.; Nand, D.; Gradmann, S.H.E.; Weingarth, M.H.; Kaupp, U.B.; Baldus, M.

    2012-01-01

    Channels regulated by cyclic nucleotides are key signalling proteins in several biological pathways. The regulatory aspect is conferred by a C-terminal cyclic nucleotide-binding domain (CNBD). We report resonance assignments of the CNBD of a bacterial mlCNG channel obtained using 2D and 3D solid-sta

  8. Open reading frame ssr2016 is required for antimycin A-sensitive photosystem I-driven cyclic electron flow in the cyanobacterium Synechocystis sp. PCC 6803

    NARCIS (Netherlands)

    Yeremenko, N.; Jeanjean, R.; Prommeenate, P.; Krasikov, V.; Nixon, P.J.; Vermaas, W.F.J.; Havaux, M.; Matthijs, H.C.P.

    2005-01-01

    Open reading frame ssr2016 encodes a protein with substantial sequence similarities to PGR5 identified as a component of the antimycin A-sensitive ferredoxin:plastoquinone reductase (FQR) in PSI cyclic photophosphorylation in Arabidopsis thaliana. We studied cyclic electron flow in Synechocystis sp.

  9. Regulation of cyclic GMP, cyclic amp and lactate dehydrogenase by putative neutrotransmitters in the C6 rat glioma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Bottenstein, J.E.; de Vellis, J.

    1977-01-01

    In C6 cells norepinephrine and dopamine caused transient increases in cyclic GMP and cyclic AMP, as well as an induction of lactate dehydrogenase. All of these responses were blocked by 1-propranolol, suggesting mediation by a ..beta..-receptor. Phentolamine potentiated the NE-increased cAMP levels by 5-fold when NE was used at suboptimal doses, suggesting the presence of ..cap alpha..-adrenergic receptors in C6 cells. Carbamylcholine decreased the levels of both cyclic nucleotides, with hexamethonium partially reversing the effect on cyclic GMP. Dibutyryl-cyclic GMP or carbamylcholine reduced catecholamine-induced cyclic AMP levels. Serotonin increased cyclic GMP levels 60% and decreased cyclic AMP levels 36%. Calcium- and magnesium-free media inhibited the norepinephrine-induced levels of cyclic GMP and cyclic AMP respectively.

  10. Regulation of cyclic GMP, cyclic AMP and lactate dehydrogenase by putative neurotransmitters in the C6 rat glioma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Bottenstein, J.E.; de Vellis, J.

    1978-01-01

    In C6 cells norepinephrine and dopamine caused transient increases in cyclic GMP and cyclic AMP, as well as an induction of lactate dehydrogenase. All of these responses were blocked by l-propranolol, suggesting mediation by a ..beta..-receptor. Phentolamine potentiated the NE-increased cAMP levels by 5-fold when NE was used at suboptimal doses, suggesting the presence of ..cap alpha..-adrenergic receptors in C6 cells. Carbamylcholine decreased the levels of both cyclic nucleotides, with hexamethonium partially reversing the effect on cyclic GMP. Dibutyryl-cyclic GMP or carbamylcholine reduced catecholamine-induced cyclic AMP levels. Serotonin increased cyclic GMP levels 60% and decreased cyclic AMP levels 36%. Calcium- and magnesium-free media inhibited the norepinephrine-induced levels of cyclic GMP and cyclic AMP respectively.

  11. Role of calcium signaling in down-regulation of aggrecan induced by cyclic tensile strain in annulus fibrosus cells

    Institute of Scientific and Technical Information of China (English)

    GUO Zhi-liang; ZHOU Yue; LI Hua-zhuang; CAO Guo-yong; TENG Hai-jun

    2006-01-01

    Objective:To study the role of intracellular calcium signal pathway in the down-regulation of aggrecan induced by cyclic tensile strain in the annulus fibrosus cells. Methods :The expression of aggrecan mRNA and core protein were respectively detected with RT-PCR and western blot after the channels transmitting calcium ions were blocked with EGTA, gadolinium and verapamil. Results:EGTA, gadolinium and verapamil partially prevented the effects of cyclic tensile strain on the expression of aggrecan in annulus fibrosus cells. Conclusion:The calcium signaling is involved in the down-regulation of proteoglycan resulting from cyclic tensile strain in the annulus fibrosus cells.

  12. The overlapping host responses to bacterial cyclic dinucleotides.

    Science.gov (United States)

    Abdul-Sater, Ali A; Grajkowski, Andrzej; Erdjument-Bromage, Hediye; Plumlee, Courtney; Levi, Assaf; Schreiber, Michael T; Lee, Carolyn; Shuman, Howard; Beaucage, Serge L; Schindler, Christian

    2012-02-01

    Macrophages respond to infection with Legionella pneumophila by the induction of inflammatory mediators, including type I Interferons (IFN-Is). To explore whether the bacterial second messenger cyclic 3'-5' diguanylate (c-diGMP) activates some of these mediators, macrophages were infected with L. pneumophila strains in which the levels of bacterial c-diGMP had been altered. Intriguingly, there was a positive correlation between c-diGMP levels and IFN-I expression. Subsequent studies with synthetic derivatives of c-diGMP, and newly described cyclic 3'-5' diadenylate (c-diAMP), determined that these molecules activate overlapping inflammatory responses in human and murine macrophages. Moreover, UV crosslinking studies determined that both dinucleotides physically associate with a shared set of host proteins. Fractionation of macrophage extracts on a biotin-c-diGMP affinity matrix led to the identification of a set of candidate host binding proteins. These studies suggest that mammalian macrophages can sense and mount a specific inflammatory response to bacterial dinucleotides.

  13. Cyclic Strain Enhances Cellular Uptake of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Jia Hu

    2015-01-01

    Full Text Available Nanoparticles (NPs have gained increasing interest in recent years due to their potential use as drug carrier, imaging, and diagnostic agents in pharmaceutical and biomedical applications. While many cells in vivo experience mechanical forces, little is known about the correlation of the mechanical stimulation and the internalization of NPs into cells. This paper investigates the effects of applied cyclic strain on NP uptake by cells. Bovine aortic endothelial cells (BAECs were cultured on collagen-coated culture plates and placed under cyclic equal-axial strains. NPs of sizes ranging from 50 to 200 nm were loaded at a concentration of 0.02 mg/mL and cyclic strains from 5 to 15% were applied to the cells for one hour. The cyclic strain results in a significant enhancement in NP uptake, which increases almost linearly with strain level. The enhanced uptake also depends on size of the NPs with the highest uptake observed on 100 nm NP. The effect of enhanced NP uptake lasts around 13 hours after cyclic stretch. Such in vitro cell stretch systems mimic physiological conditions of the endothelial cells in vivo and could potentially serve as a biomimetic platform for drug therapeutic evaluation.

  14. Cyclic transformation of orbital angular momentum modes

    CERN Document Server

    Schlederer, Florian; Fickler, Robert; Malik, Mehul; Zeilinger, Anton

    2015-01-01

    The spatial modes of photons are one realization of a QuDit, a quantum system that is described in a D-dimensional Hilbert space. In order to perform quantum information tasks with QuDits, a general class of D-dimensional unitary transformations is needed. Among these, cyclic transformations are an important special case required in many high-dimensional quantum communication protocols. In this paper, we experimentally demonstrate a cyclic transformation in the high-dimensional space of photonic orbital angular momentum (OAM). Using simple linear optical components, we show a successful four-fold cyclic transformation of OAM modes. Interestingly, our experimental setup was found by a computer algorithm. In addition to the four-cyclic transformation, the algorithm also found extensions to higher-dimensional cycles in a hybrid space of OAM and polarization. Besides being useful for quantum cryptography with QuDits, cyclic transformations are key for the experimental production of high-dimensional maximally enta...

  15. Cyclic transformation of orbital angular momentum modes

    Science.gov (United States)

    Schlederer, Florian; Krenn, Mario; Fickler, Robert; Malik, Mehul; Zeilinger, Anton

    2016-04-01

    The spatial modes of photons are one realization of a QuDit, a quantum system that is described in a D-dimensional Hilbert space. In order to perform quantum information tasks with QuDits, a general class of D-dimensional unitary transformations is needed. Among these, cyclic transformations are an important special case required in many high-dimensional quantum communication protocols. In this paper, we experimentally demonstrate a cyclic transformation in the high-dimensional space of photonic orbital angular momentum (OAM). Using simple linear optical components, we show a successful four-fold cyclic transformation of OAM modes. Interestingly, our experimental setup was found by a computer algorithm. In addition to the four-cyclic transformation, the algorithm also found extensions to higher-dimensional cycles in a hybrid space of OAM and polarization. Besides being useful for quantum cryptography with QuDits, cyclic transformations are key for the experimental production of high-dimensional maximally entangled Bell-states.

  16. Identification of a cyclic-di-GMP-modulating response regulator that impacts biofilm formation in a model sulfate reducing bacterium

    Directory of Open Access Journals (Sweden)

    Lara eRajeev

    2014-07-01

    Full Text Available We surveyed the eight putative cyclic-di-GMP-modulating response regulators (RRs in Desulfovibrio vulgaris Hildenborough that are predicted to function via two-component signaling. Using purified proteins, we examined cyclic-di-GMP production or turnover in vitro of all eight proteins. The two RRs containing only GGDEF domains (DVU2067, DVU0636 demonstrated cyclic-di-GMP production activity in vitro. Of the remaining proteins, three RRs with HD-GYP domains (DVU0722, DVUA0086 and DVU2933 were confirmed to be Mn2+ dependent phosphodiesterases in vitro and converted cyclic-di-GMP to its linear form, pGpG. DVU0408, containing both cyclic-di-GMP production (GGDEF and degradation domains (EAL, showed cyclic-di-GMP turnover activity in vitro also with production of pGpG. No cyclic-di-GMP related activity could be assigned to the RR DVU0330, containing a metal-dependent phosphohydrolase HD-OD domain, or to the HD-GYP domain RR, DVU1181. Studies included examining the impact of overexpressed cyclic-di-GMP-modulating RRs in the heterologous host E. coli and led to the identification of one RR, DVU0636, with increased cellulose production. Evaluation of a transposon mutant in DVU0636 indicated that the strain was impaired in biofilm formation and demonstrated an altered carbohydrate:protein ratio relative to the D. vulgaris wild type biofilms. However, grown in liquid lactate/sulfate medium, the DVU0636 transposon mutant showed no growth impairment relative to the wild-type strain. Among the eight candidates, only the transposon disruption mutant in the DVU2067 RR presented a growth defect in liquid culture. Our results indicate that, of the two diguanylate cyclases that function as part of two-component signaling, DVU0636 plays an important role in biofilm formation while the function of DVU2067 has pertinence in planktonic growth.

  17. Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of cerebral ischemia rats and improves behavioral deficits

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-02-01

    Full Text Available Yu Zhao,1 Ming Xiao,2 Wenbo He,3 Zhiyou Cai3 1Department of Neurology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People’s Republic of China Background and purpose: The cAMP response element binding protein (CREB plays an important role in the mechanism of cognitive impairment and is also pivotal in the switch from short-term to long-term memory. Brain-derived neurotrophic factor (BDNF seems a promising avenue in the treatment of cerebral ischemia injury since this neurotrophin could stimulate structural plasticity and repair cognitive impairment. Several findings have displayed that the dysregulation of the CREB–BDNF cascade has been involved in cognitive impairment. The aim of this study was to investigate the effect of cerebral ischemia on learning and memory as well as on the levels of CREB, phosphorylated CREB (pCREB, and BDNF, and to determine the effect of minocycline on CREB, pCREB, BDNF, and behavioral functional recovery after cerebral ischemia. Methods: The animal model was established by permanent bilateral occlusion of both common carotid arteries. Behavior was evaluated 5 days before decapitation with Morris water maze and open-field task. Four days after permanent bilateral occlusion of both common carotid arteries, minocycline was administered by douche via the stomach for 4 weeks. CREB and pCREB were examined by Western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry. BDNF was measured by immunohistochemistry and Western blotting. Results: The model rats after minocycline treatment swam shorter distances than control rats before finding the platform (P=0.0007. The number of times the

  18. The diagnostic utility of anti-cyclic citrullinated peptide antibodies, matrix metalloproteinase-3, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein in patients with erosive and non-erosive rheumatoid arthritis.

    Science.gov (United States)

    Shovman, O; Gilburd, B; Zandman-Goddard, G; Sherer, Y; Orbach, H; Gerli, R; Shoenfeld, Y

    2005-09-01

    To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.

  19. Evaluation of homogeneous electrocatalysts by cyclic voltammetry.

    Science.gov (United States)

    Rountree, Eric S; McCarthy, Brian D; Eisenhart, Thomas T; Dempsey, Jillian L

    2014-10-06

    The pursuit of solar fuels has motivated extensive research on molecular electrocatalysts capable of evolving hydrogen from protic solutions, reducing CO2, and oxidizing water. Determining accurate figures of merit for these catalysts requires the careful and appropriate application of electroanalytical techniques. This Viewpoint first briefly presents the fundamentals of cyclic voltammetry and highlights practical experimental considerations before focusing on the application of cyclic voltammetry for the characterization of electrocatalysts. Key metrics for comparing catalysts, including the overpotential (η), potential for catalysis (E(cat)), observed rate constant (k(obs)), and potential-dependent turnover frequency, are discussed. The cyclic voltammetric responses for a general electrocatalytic one-electron reduction of a substrate are presented along with methods to extract figures of merit from these data. The extension of this analysis to more complex electrocatalytic schemes, such as those responsible for H2 evolution and CO2 reduction, is then discussed.

  20. Cyclic distillation technology - A mini-review

    DEFF Research Database (Denmark)

    Bîldea, Costin Sorin; Pătruţ, Cătălin; Jørgensen, Sten Bay;

    2016-01-01

    Process intensification in distillation systems has received much attention during the past decades, with the aim of increasing both energy and separation efficiency. Various techniques, such as internal heat-integrated distillation, membrane distillation, rotating packed bed, dividing-wall columns...... and reactive distillation were studied and reported in literature. All these techniques employ the conventional continuous counter-current contact of vapor and liquid phases. Cyclic distillation technology is based on an alternative operating mode using separate phase movement which leads to key practical...... advantages in both chemical and biochemical processes. This article provides a mini-review of cyclic distillation technology. The topics covered include the working principle, design and control methods, main benefits and limitations as well as current industrial applications. Cyclic distillation can...

  1. Cyclic Polymer with Alternating Monomer Sequence.

    Science.gov (United States)

    Zhu, Wen; Li, Zi; Zhao, Youliang; Zhang, Ke

    2015-11-01

    Cyclic polymers with alternating monomer sequence are synthesized for the first time based on the ring-closure strategy. Well-defined telechelic alternating polymers are synthesized by reversible addition-fragmentation chain transfer polymerization by copolymerizing the electron acceptor monomer of N-benzylmaleimide and donor monomer of styrene with a feed ratio of 1 between them. The corresponding cyclic alternating polymers are then produced by the UV-induced Diels-Alder click reaction to ring-close the linear alternating polymer precursors under highly diluted reaction solution.

  2. On cyclic associative Abel-Grassman groupoids

    OpenAIRE

    Iqbal, Muhammad; Ahmad, Imtiaz; Shah, Muhammad; Ali, Muhammad Irfan

    2015-01-01

    A new subclass of AG-groupoids, so called, cyclic associative Abel-Grassman groupoids or CA-AG-groupoid is studied. These have been enumerated up to order $6$. A test for the verification of cyclic associativity for an arbitrary AG-groupoid has been introduced. Various properties of CA-AG-groupoids have been studied. Relationship among CA-AG-groupoids and other subclasses of AG-groupoids is investigated. It is shown that the subclass of CA-AG-groupoid is different from that of the AG{*}-group...

  3. Undrained Cyclic Behaviour of Dense Frederikshavn Sand

    DEFF Research Database (Denmark)

    Nielsen, Søren Kjær; Ibsen, Lars Bo; Sørensen, Kris Wessel

    2013-01-01

    A modified contour diagram is created for the Frederikshavn Sand in the undrained case for a relative density of ID = 80 %. It can be used to estimate the number of cycles to failure for a given combination of pore pressure, average and cyclic load ratio. The diagram is based on a series of undra......A modified contour diagram is created for the Frederikshavn Sand in the undrained case for a relative density of ID = 80 %. It can be used to estimate the number of cycles to failure for a given combination of pore pressure, average and cyclic load ratio. The diagram is based on a series...

  4. Cyclic Entropy: An Alternative to Inflationary Cosmology

    CERN Document Server

    Frampton, Paul Howard

    2015-01-01

    We address how to construct an infinitely cyclic universe model. A major consideration is to make the entropy cyclic which requires the entropy to be reset to zero in each cycle expansion to turnaround, to contraction, to bounce, etc. Here we reset entropy at the turnaround by selecting the visible universe from the multiverse which is generated by the accelerated expansion. In the model, the observed homogeneity is explained by the low entropy at the bounce, The observed flatness arises from the contraction together with the reduction in size between the expanding and contracting universe. The present flatness is predicted to be very precise.

  5. Ultrafast cyclic voltammetry with asymmetrical potential scan

    Institute of Scientific and Technical Information of China (English)

    Zhi Yong Guo; Xiang Qin Lin

    2008-01-01

    Based on the perfect ohmic drop compensation by online electronic positive feedback, ultrafast cyclic voltammetry withasymmetrical potential scan is achieved for the first time, with the reduction of anthracene acting as the test system. Compared withthe traditional cyclic voltammetry utilizing symmetrical triangular waveform as the excitation one, the new method allows a simplerapproach to mechanistic analysis of ultrafast chemical reactions coupled with a charge transfer. And perhaps more important, it alsoprovides a way to eliminate the interference of the adsorbed product in dynamic monitoring.

  6. Severe congenital cyclic neutropenia: A case report

    Science.gov (United States)

    Patil, Vidyavathi H; Hugar, Shivayogi M; Balikai, Girish; Patil, Sudha

    2016-01-01

    Congenital cyclic neutropenia syndrome is a constitutional genetic disorder which is characterized by very low number of neutrophils (neutropenia). Patients suffering from this disorder clinically present with neutropenia at early age, history of recurrent fever, ulcerations in the oral cavity, gingivitis, and other recurrent infections. This paper describes a case report of a child with recurrent mouth ulcers, fever, and later diagnosed with severe congenital cyclic neutropenia. This also emphasizes the importance of identification of rare causes of immunosuppressive conditions in children presenting with recurrent oral ulcers and poor dental hygiene, to prevent long-term complications of oral cavity and also morbidity and mortality secondary to neutropenic sepsis. PMID:27857902

  7. Regenerated Spider Silk Possess Mechanical Properties of Super- and Cyclic Contraction in Response to Environmental Humidity

    Science.gov (United States)

    Lu, Shan; Swaminathan, Ganesh; Evans, Samuel; Blackledge, Todd

    2013-06-01

    Major Ampullate (MA) spider silk is among the most impressive biomaterials due to its unparalleled mechanical properties, such as super-contraction and cyclic response to changes in humidity. Electro-spinning enables the generation of engineered silk fibers with controlled parameters and dimentions for various medical and commercial applications. However, their applications hinge on the ability to reproduce the mechanical properties such as a precise expansion-contraction response existed in natural silk fibers. Here, we successfully reproduced MA spider-silk fibers from solutions of natural MA silk proteins via electrospinning, which exhibit the super-contraction and cyclic response to humidity change in a manner mirroring the natural fibers.

  8. Development of a design methodology for high temperature cyclic applications of materials which experience cyclic softening

    Energy Technology Data Exchange (ETDEWEB)

    Marriott, D.L.; Stubbins, J.F. (Illinois Univ., Urbana, IL (USA). Dept. of Mechanical and Industrial Engineering)

    1988-12-01

    The project has as its original focus the high temperature behavior of 2.25 Cr-1 Mo steel, heat treated to produce a predominantly bainitic microstructure and the load carrying response of components made of this material. Experiments were carried out on uniform and notched specimens under both steady and cyclic loading using specially acquired electromechanical test machines. It emerged that a very important feature of mechanical behavior under the conditions of interest was the strong tendency of this material to cyclically soften, particularly at high temperature in the creep range, giving the illusion of a severe creep-fatigue interaction under certain conditions. This finding led to a significant component of the project being devoted to investigation of the effects of local, as opposed to generalized, cyclic softening, and the implications this phenomenon might have on the setting of allowable design stress limits. The format of this report is as follows: The second chapter is a review of the work carried out in approximately chronological order under the headings of work was carried out under the following: (1) 2.25 Cr 1 Mo Steel -- Elevated Temperature Fatigue and Environmental Effects; (2) Preliminary Studies of Advanced Austenitics; (3) A Uniaxial Constitutive Model for Cyclic Softening; (4) The Iso-Cyclic Stress-Strain Approach to Evaluation of Components in Cyclic Softening Materials; (5) Testing of High Temperature Austenitic Alloys; and (6) Design Methodology for Aging Materials -- Application to Cyclic Softening. 65 refs., 39 figs., 7 tabs.

  9. The coefficient of cyclic variation: a novel statistic to measure the magnitude of cyclic variation.

    Science.gov (United States)

    Fulford, Anthony Jc

    2014-01-01

    PERIODIC OR CYCLIC DATA OF KNOWN PERIODICITY ARE FREQUENTLY ENCOUNTERED IN EPIDEMIOLOGICAL AND BIOMEDICAL RESEARCH: for instance, seasonality provides a useful experiment of nature while diurnal rhythms play an important role in endocrine secretion. There is, however, little consensus on how to analysis these data and less still on how to measure association or effect size for the often complex patterns seen. A simple statistic, readily derived from Fourier regression models, provides a readily-understood measure cyclic variation in a wide variety of situations. The coefficient of cyclic variation or similar statistics derived from the variance of a Fourier series could provide a universal means of summarising the magnitude of periodic variation.

  10. Cloning and first functional characterization of a plant cyclic nucleotide-gated cation channel

    Energy Technology Data Exchange (ETDEWEB)

    Leng, Q.; Mercier, R.W.; Yao, W.; Berkowitz, G.A.

    1999-11-01

    Cyclic nucleotide-gated (cng) non-selective cation channels have been cloned from a number of animal systems. These channels are characterized by direct gating upon cAMO or cGMO binding to the intracellular portion of the channel protein, which leads to an increase in channel conductance. Animal cng channels are involved in signal transduction systems; they translate stimulus-induced changes in cytosolic cyclic nucleotide into altered cell membrane potential and/or cation flux as part of a signal cascade pathway. Putative plant homologs of animal cng channels have been identified. However, functional characterization (i.e., demonstration of cyclic-nucleotide-dependent ion currents) of a plant cng channel has not yet been accomplished. The authors report the cloning and first functional characterization of a plant member of this family of ion channels. The Arabidopsis cDNA AtCNGC2 encodes a polypeptide with deduced homology to the {alpha}-subunit of animal channels, and facilitates cyclic nucleotide-dependent cation currents upon expression in a number of heterologous systems. AtCNGC2 expression in a yeast mutant lacking a low-affinity K{sup +} uptake system complements growth inhibition only when lipophilic nucleotides are present in the culture medium. Voltage clamp analysis indicates that Xenopus lawvis oocytes injected with AtCNGC2 cRNA demonstrate cyclic-nucleotide-dependent, inward-rectifying K{sup +} currents. Human embryonic kidney cells (HEK293) transfected with AtCNGC2 cDNA demonstrate increased permeability to Ca{sup 2+} only in the presence of lipophilic cyclic nucleotides. The evidence presented here supports the functional classification of AtCNGC2 as a cyclic-nucleotide-gated cation channel, and presents the first direct evidence identifying a plant member of this ion channel family.

  11. The Structural Basis for the Sensing and Binding of Cyclic di-GMP by STING

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Under a research project funded by NSFC, Prof. Su Xiaodong and his team of the National Laboratory of Protein Engineering and Plant Genetic Engineering, BIOPIC, the School of Life Sciences of Peking Uni- versity, obtained remarkable achievement and published recently a paper entitled "The Structural Basis for the Sensing and Binding of Cyclic di-GMP by STING" on online Natural Structural and Molecular Biolo- gY. STING (stimulator of interferon genes) is an essential signaling adaptor that mediates cytokine pro- duction in response to microbial invasion by directly sensing bacterial secondary messengers such as the cy- clic dinucleotide bis-(3'-5')-cyclic dimeric GMP (e-di-GMP). STING's structure and its binding mecha- nism to cyclic dinucleotides were unknown. We report here the crystal structures of the STING cytoplas- mic domain and its complex with c-di-GMP, thus providing the structural basis for understanding STING function.

  12. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs.

    Science.gov (United States)

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-12-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH).

  13. Magnesium sulphate increases lymphocyte adenosine 3':5'-cyclic monophosphate in humans.

    Science.gov (United States)

    Von Mandach, U; Bürgi, M; Huch, R; Huch, A

    1993-01-01

    We determined the effect of i.v. magnesium sulphate, which is often combined with beta 2-adrenoceptor agonists for tocolytic therapy, on lymphocyte cyclic AMP production, extracellular magnesium and blood calcium concentrations. Sixteen healthy volunteers received i.v. magnesium sulphate 1 g h-1 over 8 h; seven volunteers also had infusion of NaCl 18 mg h-1 as control. Venous blood was taken pre- and post-infusion to determine basal lymphocyte cyclic AMP and the increase evoked by 0.1 mM isoprenaline, as well as serum and plasma concentrations of total and non-protein-bound magnesium and calcium. Following magnesium sulphate there was a significant rise in the isoprenaline-evoked increase in cyclic AMP (P < 0.05) and in the magnesium concentrations (P < 0.01) and a decrease in the free calcium concentration (P < 0.01). PMID:8385975

  14. Magnesium sulphate increases lymphocyte adenosine 3':5'-cyclic monophosphate in humans.

    Science.gov (United States)

    Von Mandach, U; Bürgi, M; Huch, R; Huch, A

    1993-03-01

    We determined the effect of i.v. magnesium sulphate, which is often combined with beta 2-adrenoceptor agonists for tocolytic therapy, on lymphocyte cyclic AMP production, extracellular magnesium and blood calcium concentrations. Sixteen healthy volunteers received i.v. magnesium sulphate 1 g h-1 over 8 h; seven volunteers also had infusion of NaCl 18 mg h-1 as control. Venous blood was taken pre- and post-infusion to determine basal lymphocyte cyclic AMP and the increase evoked by 0.1 mM isoprenaline, as well as serum and plasma concentrations of total and non-protein-bound magnesium and calcium. Following magnesium sulphate there was a significant rise in the isoprenaline-evoked increase in cyclic AMP (P < 0.05) and in the magnesium concentrations (P < 0.01) and a decrease in the free calcium concentration (P < 0.01).

  15. Cyclic Plastic Deformation and Welding Simulation

    NARCIS (Netherlands)

    Ten Horn, C.H.L.J.

    2003-01-01

    One of the concerns of a fitness for purpose analysis is the quantification of the relevant material properties. It is known from experiments that the mechanical properties of a material can change due to a monotonic plastic deformation or a cyclic plastic deformation. For a fitness for purpose anal

  16. Cyclic viscoelastoplasticity of polypropylene/nanoclay composites

    DEFF Research Database (Denmark)

    Drozdov, A.; Christiansen, Jesper de Claville

    2012-01-01

    Observations are reported on isotactic polypropylene/organically modified nanoclay hybrids with concentrations of filler ranging from 0 to 5 wt.% in cyclic tensile tests with a stress–controlled program (oscillations between various maximum stresses and the zero minimum stress). A pronounced effect...

  17. Strongly Cyclic and Strongly Irreducible Decomposition

    Institute of Scientific and Technical Information of China (English)

    纪友清; 韩黎明

    2001-01-01

    Let W be an injective unilateral weighted shift, and let W(n) be the orthogonal direct sum of n copies of W. In this paper, we prove that, if the commutant of W is strictly cyclic, then W(n) has a unique (SI) decomposition with respect to similarity for every natural number n.

  18. Cyclic Triaxial Loading of Cohesionless Silty Sand

    DEFF Research Database (Denmark)

    Sabaliauskas, Tomas; Ibsen, Lars Bo

    2015-01-01

    To engineer efficient structures offshore, we need to extend our knowledge of soil response. Cyclic loading and high water pressure encountered offshore greatly influence cohesionless soil performance. Silty sand from Frederikshavn wind turbine farm was tested using single diameter height samples...

  19. Cyclic electron flow: facts and hypotheses.

    Science.gov (United States)

    Finazzi, Giovanni; Johnson, Giles N

    2016-09-01

    Over the last 15 years, research into the process of cyclic electron flow in photosynthesis has seen a huge resurgence. Having been considered by some in the early 1990s as a physiologically unimportant artefact, it is now recognised as essential to normal plant growth. Here, we provide an overview of the major developments covered in this special issue of photosynthesis research.

  20. Monopod bucket foundations under cyclic lateral loading

    DEFF Research Database (Denmark)

    Foglia, Aligi; Ibsen, Lars Bo

    The monopod bucket foundation can be a cost-reducing sub-structure for offshore wind turbines. To avoid problems during the turbine operation, the long-term effect of cyclic loading must be considered in the design of the foundation. In this paper a 1g testing rig is adopted to extend the knowled...

  1. Monopod Bucket Foundations Under Cyclic Lateral Loading

    DEFF Research Database (Denmark)

    Foglia, Aligi; Ibsen, Lars Bo

    2016-01-01

    The monopod bucket foundation has the potential to become a cost-reducing substructure for offshore wind turbines. To avoid problems during the energy converter operation, the long-term effect of cyclic loading must be considered in the design of the foundation. In this paper, a 1-g testing rig i...

  2. A New Cyclic Peptide from Schnabelia tetradonta

    Institute of Scientific and Technical Information of China (English)

    Hui DOU; Yan ZHOU; Shu lin PENG; Li Sheng DING

    2003-01-01

    A new cyclic octapeptide (schnabepeptide B) was isolated from the aerial part ofSchnabelia tetradonta (Sun) C. Y. Wu et C. Chen (Lamiaceae). Its structure was elucidated ascyclo-(NH-Trp-Gly1-Leu1-Gly2-Pro1-Pro2-Leu2-Pro3-CO) on the basis of extensive 2D NMR andMS spectra.

  3. Steady state oxygen reduction and cyclic voltammetry

    DEFF Research Database (Denmark)

    Rossmeisl, Jan; Karlberg, Gustav; Jaramillo, Thomas;

    2008-01-01

    The catalytic activity of Pt and Pt3Ni for the oxygen reduction reaction is investigated by applying a Sabatier model based on density functional calculations. We investigate the role of adsorbed OH on the activity, by comparing cyclic voltammetry obtained from theory with previously published...

  4. Hopf Algebroids and Their Cyclic Theory

    NARCIS (Netherlands)

    Kowalzig, N.

    2009-01-01

    The main objective of this thesis is to clarify concepts of generalised symmetries in noncommutative geometry (i.e., the noncommutative analogue of groupoids and Lie algebroids) and their associated (co)homologies. These ideas are incorporated by the notion of Hopf algebroids and Hopf-cyclic (co)hom

  5. Cyclic Cratonic Carbonates and Phanerozoic Calcite Seas.

    Science.gov (United States)

    Wilkinson, Bruce H.

    1982-01-01

    Discusses causes of cyclicity in cratonic carbonate sequences and evidence for and potential significance of postulated primary calcite sediment components in past Paleozoic seas, outlining problems, focusing on models explaining existing data, and identifying background. Future sedimentary geologists will need to address these and related areas…

  6. STUDY OF CYCLIC AMP IN HUMAN SEMEN

    Institute of Scientific and Technical Information of China (English)

    JIANGNing

    1989-01-01

    It had been observed that there was a close relationship between cyclic AMP and the motility, energy metabolism, capaeitation and acrosome reaction of spermatozoa. In this study a radio-immunoassay procedure for measuring cAMP concentration in sperm and

  7. Scale invariant density perturbations from cyclic cosmology

    Science.gov (United States)

    Frampton, Paul Howard

    2016-04-01

    It is shown how quantum fluctuations of the radiation during the contraction era of a comes back empty (CBE) cyclic cosmology can provide density fluctuations which re-enter the horizon during the subsequent expansion era and at lowest order are scale invariant, in a Harrison-Zel’dovich-Peebles sense. It is necessary to be consistent with observations of large scale structure.

  8. Hopf Algebroids and Their Cyclic Theory

    NARCIS (Netherlands)

    Kowalzig, N.|info:eu-repo/dai/nl/304349755

    2009-01-01

    The main objective of this thesis is to clarify concepts of generalised symmetries in noncommutative geometry (i.e., the noncommutative analogue of groupoids and Lie algebroids) and their associated (co)homologies. These ideas are incorporated by the notion of Hopf algebroids and Hopf-cyclic

  9. The effect of p38MAPK on cyclic stretch in human facial hypertrophic scar fibroblast differentiation.

    Directory of Open Access Journals (Sweden)

    Qi-cui Du

    Full Text Available Hypertrophic scars (HTS, the excessive deposition of scar tissue by fibroblasts, is one of the most common skin disorders. Fibroblasts derived from surgical scar tissue produce high levels of α-smooth muscle actin (α-SMA and transforming growth factor-β1 (TGF-β1. However, the molecular mechanisms for this phenomenon is poorly understood. Thus, the purpose of this study was to evaluate the molecular mechanisms of HTS and their potential therapeutic implications. Fibroblasts derived from skin HTS were cultured and characterized in vitro. The fibroblasts were synchronized and randomly assigned to two groups: cyclic stretch and cyclic stretch pre-treated with SB203580 (a p38MAPK inhibitor. Cyclic stretch at 10% strain was applied at a loading frequency of 10 cycles per minute (i.e. 5 seconds of tension and 5 seconds of relaxation for 0 h, 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the expression of α-SMA and TGF-β1 mRNA and protein and the phosphorylation of p38MAPK. SB203580 reversed these effects and caused a decrease in matrix contraction. Furthermore, HTS fibroblast growth was partially blocked by p38MAPK inhibition. Therefore, the mechanism of cyclic stretch involves p38 MAPK, and its inhibition is suggested as a novel therapeutic strategy for HTS.

  10. The effect of p38MAPK on cyclic stretch in human facial hypertrophic scar fibroblast differentiation.

    Science.gov (United States)

    Du, Qi-cui; Zhang, Dai-zun; Chen, Xiu-juan; Lan-Sun, Gui; Wu, Min; Xiao, Wen-lin

    2013-01-01

    Hypertrophic scars (HTS), the excessive deposition of scar tissue by fibroblasts, is one of the most common skin disorders. Fibroblasts derived from surgical scar tissue produce high levels of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1). However, the molecular mechanisms for this phenomenon is poorly understood. Thus, the purpose of this study was to evaluate the molecular mechanisms of HTS and their potential therapeutic implications. Fibroblasts derived from skin HTS were cultured and characterized in vitro. The fibroblasts were synchronized and randomly assigned to two groups: cyclic stretch and cyclic stretch pre-treated with SB203580 (a p38MAPK inhibitor). Cyclic stretch at 10% strain was applied at a loading frequency of 10 cycles per minute (i.e. 5 seconds of tension and 5 seconds of relaxation) for 0 h, 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the expression of α-SMA and TGF-β1 mRNA and protein and the phosphorylation of p38MAPK. SB203580 reversed these effects and caused a decrease in matrix contraction. Furthermore, HTS fibroblast growth was partially blocked by p38MAPK inhibition. Therefore, the mechanism of cyclic stretch involves p38 MAPK, and its inhibition is suggested as a novel therapeutic strategy for HTS.

  11. Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop

    Directory of Open Access Journals (Sweden)

    Gregory Upert

    2012-01-01

    Full Text Available Human immunodeficiency virus-1 (HIV-1 replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR, to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP cation-based vectors that efficiently deliver nucleotide analogs (PNAs into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins.

  12. Cyclic-di-GMP and cyclic-di-AMP activate the NLRP3 inflammasome

    OpenAIRE

    Abdul-Sater, Ali A.; Tattoli, Ivan; Jin, Lei; Grajkowski, Andrzej; Levi, Assaf; Koller, Beverly H.; Irving C Allen; Beaucage, Serge L.; Fitzgerald, Katherine A.; Ting, Jenny P.-Y.; Cambier, John C.; Stephen E Girardin; Schindler, Christian

    2013-01-01

    Cyclic dinucleotides have been recently shown to induce type I interferon secretion. This study shows they also activate the NLRP3 inflammasome to stimulate robust IL-1b secretion through a novel pathway that does not generate mitochondrial ROS.

  13. Cyclic stretching of soft substrates induces spreading and growth

    Science.gov (United States)

    Cui, Yidan; Hameed, Feroz M.; Yang, Bo; Lee, Kyunghee; Pan, Catherine Qiurong; Park, Sungsu; Sheetz, Michael

    2015-01-01

    In the body, soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity. To determine whether transient forces can substitute for a rigid matrix, we stretched soft pillar arrays. Surprisingly, 1–5% cyclic stretching over a frequency range of 0.01–10 Hz caused spreading and stress fibre formation (optimum 0.1 Hz) that persisted after 4 h of stretching. Similarly, stretching increased cell growth rates on soft pillars comparative to rigid substrates. Of possible factors linked to fibroblast growth, MRTF-A (myocardin-related transcription factor-A) moved to the nucleus in 2 h of cyclic stretching and reversed on cessation; but YAP (Yes-associated protein) moved much later. Knockdown of either MRTF-A or YAP blocked stretch-dependent growth. Thus, we suggest that the repeated pulling from a soft matrix can substitute for a stiff matrix in stimulating spreading, stress fibre formation and growth. PMID:25704457

  14. Dietary Habits of Young Athletes Going in for Cyclic Sports

    Directory of Open Access Journals (Sweden)

    S. G. Makarova

    2015-01-01

    Full Text Available In modern sports, outlining an adequate diet is one of the key issues in training young athletes. The following literature review presents new approaches to nutrition of young athletes going in for cyclic sports. These sports take a lot of energy, entail great strain and significant intensity of training. Correspondingly, the ratio of nutrients in athletes training for endurance tends to shift toward carbohydrates, the amount of which in the body should cover the increased need for workload as may be defined by the training process and the amount of workload. High-fat diets have proved irrelevant in terms of providing energy function; therefore, this nutritive approach was dismissed, since an athlete should have an about 25% share of fats of his/her menu’s total caloric value. According to modern standards, the amount of proteins in athletes’ menu should not exceed 1.2–1.6g per 1kg of body weight. To avoid the risk of dehydration and physical weakness, cyclic athletes should take sport drinks (in small portions prior to and following a training session (competition. They contain carbohydrates and electrolytes and therefore are more preferable than pure water. 

  15. Molecular Mechanisms of Gonadotropin-Releasing Hormone Signaling: Integrating Cyclic Nucleotides into the Network

    Directory of Open Access Journals (Sweden)

    Craig Alexander McArdle

    2013-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is the primary regulator of mammalian reproductive function in both males and females. It acts via G-protein coupled receptors on gonadotropes to stimulate synthesis and secretion of the gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These receptors couple primarily via G-proteins of the Gq/11 family, driving activation of phospholipase C and mediating GnRH effects on gonadotropin synthesis and secretion. There is also good evidence that GnRH causes activation of other heterotrimeric G-proteins (Gs and Gi with consequent effects on cyclic AMP production, as well as for effects on the soluble and particulate guanylyl cyclases that generate cGMP. Here we provide an overview of these pathways. We emphasise mechanisms underpinning pulsatile hormone signaling and the possible interplay of GnRH and autocrine or paracrine regulatory mechanisms in control of cyclic nucleotide signaling.

  16. SCATTERING BY CYCLIC POLYMERS AND COPOLYMERS AT LARGE SCATTERING VECTORS

    NARCIS (Netherlands)

    KOSMAS, M; BENOIT, H; HADZIIOANNOU, G

    1994-01-01

    General formulae allowing the evaluation of the form factors of cyclic block copolymers are established and graphs for cyclic copolymers of the form (A-B)(N) are shown. When N is large, the linear and the cyclic copolymer have the same behaviour. It is possible to extend at large angle an analytical

  17. Cyclic cocycles on deformation quantizations and higher index theorems

    NARCIS (Netherlands)

    Pflaum, M.J.; Posthuma, H.; Tang, X.

    2010-01-01

    We construct a nontrivial cyclic cocycle on the Weyl algebra of a symplectic vector space. Using this cyclic cocycle we construct an explicit, local, quasi-isomorphism from the complex of differential forms on a symplectic manifold to the complex of cyclic cochains of any formal deformation quantiza

  18. SCATTERING BY CYCLIC POLYMERS AND COPOLYMERS AT LARGE SCATTERING VECTORS

    NARCIS (Netherlands)

    KOSMAS, M; BENOIT, H; HADZIIOANNOU, G

    1994-01-01

    General formulae allowing the evaluation of the form factors of cyclic block copolymers are established and graphs for cyclic copolymers of the form (A-B)(N) are shown. When N is large, the linear and the cyclic copolymer have the same behaviour. It is possible to extend at large angle an analytical

  19. Transient Spectroscopic Properties of [60]Fullerene-Containing Cyclic Sulphoxide

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The properties of the triplet excited state of [60]fullerene-containing cyclic sulphoxide have been investigated by time-resolved absorption spectroscopy. Transient absorption bands of [60]fullerene-containing cyclic sulphoxide showed two decay-components, which were attributed to triplet excited states of different spin multiplicity. The properties of photoexcited states of [60]fullerene-containing cyclic sulphoxide are also reported.

  20. Cyclic cocycles on deformation quantizations and higher index theorems

    NARCIS (Netherlands)

    Pflaum, M.J.; Posthuma, H.; Tang, X.

    2010-01-01

    We construct a nontrivial cyclic cocycle on the Weyl algebra of a symplectic vector space. Using this cyclic cocycle we construct an explicit, local, quasi-isomorphism from the complex of differential forms on a symplectic manifold to the complex of cyclic cochains of any formal deformation

  1. Cyclic strain alters the expression and release of angiogenic factors by human tendon cells.

    Science.gov (United States)

    Mousavizadeh, Rouhollah; Khosravi, Shahram; Behzad, Hayedeh; McCormack, Robert G; Duronio, Vincent; Scott, Alex

    2014-01-01

    Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

  2. Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3', 3'-cGAMP).

    Science.gov (United States)

    Hallberg, Zachary F; Wang, Xin C; Wright, Todd A; Nan, Beiyan; Ad, Omer; Yeo, Jongchan; Hammond, Ming C

    2016-02-16

    Over 30 years ago, GGDEF domain-containing enzymes were shown to be diguanylate cyclases that produce cyclic di-GMP (cdiG), a second messenger that modulates the key bacterial lifestyle transition from a motile to sessile biofilm-forming state. Since then, the ubiquity of genes encoding GGDEF proteins in bacterial genomes has established the dominance of cdiG signaling in bacteria. However, the observation that proteobacteria encode a large number of GGDEF proteins, nearing 1% of coding sequences in some cases, raises the question of why bacteria need so many GGDEF enzymes. In this study, we reveal that a subfamily of GGDEF enzymes synthesizes the asymmetric signaling molecule cyclic AMP-GMP (cAG or 3', 3'-cGAMP). This discovery is unexpected because GGDEF enzymes function as symmetric homodimers, with each monomer binding to one substrate NTP. Detailed analysis of the enzyme from Geobacter sulfurreducens showed it is a dinucleotide cyclase capable of switching the major cyclic dinucleotide (CDN) produced based on ATP-to-GTP ratios. We then establish through bioinformatics and activity assays that hybrid CDN-producing and promiscuous substrate-binding (Hypr) GGDEF enzymes are found in other deltaproteobacteria. Finally, we validated the predictive power of our analysis by showing that cAG is present in surface-grown Myxococcus xanthus. This study reveals that GGDEF enzymes make alternative cyclic dinucleotides to cdiG and expands the role of this widely distributed enzyme family to include regulation of cAG signaling.

  3. A family of small cyclic amphipathic peptides (SCAmpPs) genes in citrus.

    Science.gov (United States)

    Belknap, William R; McCue, Kent F; Harden, Leslie A; Vensel, William H; Bausher, Michael G; Stover, Ed

    2015-04-16

    Citrus represents a crop of global importance both in economic impact and significance to nutrition. Citrus production worldwide is threatened by the disease Huanglongbing (HLB), caused by the phloem-limited pathogen Candidatus Liberibacter spp.. As a source of stable HLB-resistance has yet to be identified, there is considerable interest in characterization of novel disease-associated citrus genes. A gene family of Small Cyclic Amphipathic Peptides (SCAmpPs) in citrus is described. The citrus genomes contain 100-150 SCAmpPs genes, approximately 50 of which are represented in the citrus EST database. These genes encode small ~50 residue precursor proteins that are post-translationally processed, releasing 5-10 residue cyclic peptides. The structures of the SCAmpPs genes are highly conserved, with the small coding domains interrupted by a single intron and relatively extended untranslated regions. Some family members are very highly transcribed in specific citrus tissues, as determined by representation in tissue-specific cDNA libraries. Comparison of the ESTs of related SCAmpPs revealed an unexpected evolutionary profile, consistent with targeted mutagenesis of the predicted cyclic peptide domain. The SCAmpPs genes are displayed in clusters on the citrus chromosomes, with apparent association with receptor leucine-rich repeat protein arrays. This study focused on three SCAmpPs family members with high constitutive expression in citrus phloem. Unexpectedly high sequence conservation was observed in the promoter region of two phloem-expressed SCAmpPs that encode very distinct predicted cyclic products. The processed cyclic product of one of these phloem SCAmpPs was characterized by LC-MS-MS analysis of phloem tissue, revealing properties consistent with a K(+) ionophore. The SCAmpPs amino acid composition, protein structure, expression patterns, evolutionary profile and chromosomal distribution are consistent with designation as ribosomally synthesized defense

  4. Helical Two-Revolutional Cyclical Surface

    Directory of Open Access Journals (Sweden)

    Tatiana Olejníková

    2009-12-01

    Full Text Available Paper presents a family of helical two-revolutional cyclical surfaces, which arecreated by movement of the circle alongside the helical cycloidal curve, where circle islocated in the curve normal plane and its centre is on this curve. Helical cycloidal curvecan be created by simultaneous revolution of a point about two different axes 3o, 2o and byscrewing about axis 1o in the space. Form of the helical cycloidal curve and also of thehelical two-revolutional cyclical surface is dependent on the relative position of the threeaxes of revolutions, on multiples of angular velocities and orientations of separaterevolutions. Analytic representation, classification of surfaces and some of their geometricproperties are derived.

  5. The Hall Algebra of Cyclic Serial Algebra

    Institute of Scientific and Technical Information of China (English)

    郭晋云

    1994-01-01

    In this paper, orders <1 and <2 on ((Z)+)nm are introduced and also regarded as orders on the isomorphism classes of finite modules of finite .cyclic algebra R with n simple modules and all the indecomposable projective modules have length m through a one-to-one correspondence between ((Z)+)nm and the isomorphism classes of finite R modules. Using this we prove that the Hall algebra of a cyclic serial algebra is identified with its Loewy subalgebra, and its rational extension has a basis of BPW type, and is a (((Z)+)nm, <2) filtered ring with the associated graded ring as an iterated skew polynomial ring. These results are also generalized to the Hall algebra of a tube over a finite field.

  6. Bouncing and cyclic string gas cosmologies

    CERN Document Server

    Greene, Brian; Marnerides, Stefanos

    2008-01-01

    We show that, in the presence of a string gas, simple higher-derivative modifications to the effective action for gravity can lead to bouncing and cyclic cosmological models. The modifications bound the expansion rate and avoid singularities at finite times. In these models the scale factors can have long loitering phases that solve the horizon problem. Adding a potential for the dilaton gives a simple realization of the pre-big bang scenario. Entropy production in the cyclic phase drives an eventual transition to a radiation-dominated universe. As a test of the Brandenberger-Vafa scenario, we comment on the probability of decompactifying three spatial dimensions in this class of models.

  7. Cosmic Perturbations Through the Cyclic Ages

    CERN Document Server

    Erickson, J K; Steinhardt, P J; Turok, N G; Erickson, Joel K.; Gratton, Steven; Steinhardt, Paul J.; Turok, Neil

    2006-01-01

    We analyze the evolution of cosmological perturbations in the cyclic model, paying particular attention to their behavior and interplay over multiple cycles. Our key results are: (1) galaxies and large scale structure present in one cycle are generated by the quantum fluctuations in the preceding cycle without interference from perturbations or structure generated in earlier cycles and without interfering with structure generated in later cycles; (2) the ekpyrotic phase, an epoch of gentle contraction with equation of state $w\\gg 1$ preceding the hot big bang, makes the universe homogeneous, isotropic and flat within any given observer's horizon; and, (3) although the universe is uniform within each observer's horizon, the global structure of the cyclic universe is more complex, owing to the effects of superhorizon length perturbations, and cannot be described in a uniform Friedmann-Robertson-Walker picture. In particular, we show that the ekpyrotic phase is so effective in smoothing, flattening and isotropiz...

  8. Universal Cyclic Topology in Polymer Networks.

    Science.gov (United States)

    Wang, Rui; Alexander-Katz, Alfredo; Johnson, Jeremiah A; Olsen, Bradley D

    2016-05-01

    Polymer networks invariably possess topological defects: loops of different orders which have profound effects on network properties. Here, we demonstrate that all cyclic topologies are a universal function of a single dimensionless parameter characterizing the conditions for network formation. The theory is in excellent agreement with both experimental measurements of hydrogel loop fractions and Monte Carlo simulations without any fitting parameters. We demonstrate the superposition of the dilution effect and chain-length effect on loop formation. The one-to-one correspondence between the network topology and primary loop fraction demonstrates that the entire network topology is characterized by measurement of just primary loops, a single chain topological feature. Different cyclic defects cannot vary independently, in contrast to the intuition that the densities of all topological species are freely adjustable. Quantifying these defects facilitates studying the correlations between the topology and properties of polymer networks, providing a key step in overcoming an outstanding challenge in polymer physics.

  9. Detecting highly cyclic structure with complex eigenpairs

    CERN Document Server

    Klymko, Christine

    2016-01-01

    Many large, real-world complex networks have rich community structure that a network scientist seeks to understand. These communities may overlap or have intricate internal structure. Extracting communities with particular topological structure, even when they overlap with other communities, is a powerful capability that would provide novel avenues of focusing in on structure of interest. In this work we consider extracting highly-cyclic regions of directed graphs (digraphs). We demonstrate that embeddings derived from complex-valued eigenvectors associated with stochastic propagator eigenvalues near roots of unity are well-suited for this purpose. We prove several fundamental theoretic results demonstrating the connection between these eigenpairs and the presence of highly-cyclic structure and we demonstrate the use of these vectors on a few real-world examples.

  10. Generalized Toeplitz operators and cyclic vectors

    CERN Document Server

    Gassier, G; Zerouali, E H

    2003-01-01

    We give in this paper some asymptotic Von Neumann inequalities for power bounded operators in the class C subrho intersection C sub 1. and some spacial von Neumann inequalities associated with non zero elements of the point spectrum, when it is non void, of generalized Toeplitz operators. Introducing perturbed kernel, we consider classes C sub R which extend the classical classes C subrho. We give results about absolute continuity with respect to the Haar measure for operators in class C sub R intersection C sub 1. This allows us to give new results on cyclic vectors for such operators and provides invariant subspaces for their powers. Relationships between cyclic vectors for T and T* involving generalized Toeplitz operators are given and the commutativity of left brace T right brace', the commutant of T is discussed.

  11. Cyclic sieving, promotion, and representation theory

    CERN Document Server

    Rhoades, Brendon

    2010-01-01

    We prove a collection of conjectures of D. White \\cite{WComm}, as well as some related conjectures of Abuzzahab-Korson-Li-Meyer \\cite{AKLM} and of Reiner and White \\cite{ReinerComm}, \\cite{WComm}, regarding the cyclic sieving phenomenon of Reiner, Stanton, and White \\cite{RSWCSP} as it applies to jeu-de-taquin promotion on rectangular tableaux. To do this, we use Kazhdan-Lusztig theory and a characterization of the dual canonical basis of $\\mathbb{C}[x_{11}, ..., x_{nn}]$ due to Skandera \\cite{SkanNNDCB}. Afterwards, we extend our results to analyzing the fixed points of a dihedral action on rectangular tableaux generated by promotion and evacuation, suggesting a possible sieving phenomenon for dihedral groups. Finally, we give applications of this theory to cyclic sieving phenomena involving reduced words for the long elements of hyperoctohedral groups and noncrossing partitions.

  12. Cyclic and Quasi-Cyclic LDPC Codes on Row and Column Constrained Parity-Check Matrices and Their Trapping Sets

    CERN Document Server

    Huang, Qin; Lin, Shu; Abdel-Ghaffar, Khaled

    2010-01-01

    This paper is concerned with construction and structural analysis of both cyclic and quasi-cyclic codes, particularly LDPC codes. It consists of three parts. The first part shows that a cyclic code given by a parity-check matrix in circulant form can be decomposed into descendant cyclic and quasi-cyclic codes of various lengths and rates. Some fundamental structural properties of these descendant codes are developed, including the characterizations of the roots of the generator polynomial of a cyclic descendant code. The second part of the paper shows that cyclic and quasi-cyclic descendant LDPC codes can be derived from cyclic finite geometry LDPC codes using the results developed in first part of the paper. This enlarges the repertoire of cyclic LDPC codes. The third part of the paper analyzes the trapping sets of regular LDPC codes whose parity-check matrices satisfy a certain constraint on their rows and columns. Several classes of finite geometry and finite field cyclic and quasi-cyclic LDPC codes with l...

  13. Past Eras In Cyclic Cosmological Models

    CERN Document Server

    Frampton, Paul H

    2009-01-01

    In infinitely cyclic cosmology past eras are discussed using set theory and transfinite numbers. One consistent scenario, already in the literature, is where there is always a countably infinite number, $\\aleph_0$, of universes and no big bang. I describe here an alternative where the present number of universes is $\\aleph_0$ and in the infinite past there was only a finite number of universes. In this alternative model it is also possible that there was no big bang.

  14. Cyclical Variability of Prominences, CMEs and Flares

    Indian Academy of Sciences (India)

    J. L. Ballester

    2000-09-01

    Solar flares, prominences and CMEs are well known manifestations of solar activity. For many years, qualitative studies were made about the cyclical behaviour of such phenomena. Nowadays, more quantitative studies have been undertaken with the aim to understand the solar cycle dependence of such phenomena as well as peculiar behaviour, such as asymmetries and periodicities, occurring within the solar cycle. Here, we plan to review the more recent research concerning all these topics.

  15. Transversality for Cyclic Negative Feedback Systems

    OpenAIRE

    2014-01-01

    Transversality of stable and unstable manifolds of hyperbolic periodic trajectories is proved for monotone cyclic systems with negative feedback. Such systems in general are not in the category of monotone dynamical systems in the sense of Hirsch. Our main tool utilized in the proofs is the so-called cone of high rank. We further show that stable and unstable manifolds between a hyperbolic equilibrium and a hyperbolic periodic trajectory, or between two hyperbolic equilibria with different di...

  16. Breaking antidunes: Cyclic behavior due to hysteresis

    DEFF Research Database (Denmark)

    Deigaard, Rolf

    2006-01-01

    The cyclic behavior of breaking antidunes (growth, breaking of surface wave, obliteration) is investigated by use of a numerical model. The model includes the transition between supercritical and transcritical flow. As the antidune grows the flow becomes transcritical and a hydraulic jump is form...... upstream of the antidune crest. The relation between growth of the antidune and supercritical flow and between decay and transcritical flow is shown, and the significance of hysteresis in the flow conditions is investigated....

  17. Cyclic Strain Enhances Cellular Uptake of Nanoparticles

    OpenAIRE

    Jia Hu; Yaling Liu

    2015-01-01

    Nanoparticles (NPs) have gained increasing interest in recent years due to their potential use as drug carrier, imaging, and diagnostic agents in pharmaceutical and biomedical applications. While many cells in vivo experience mechanical forces, little is known about the correlation of the mechanical stimulation and the internalization of NPs into cells. This paper investigates the effects of applied cyclic strain on NP uptake by cells. Bovine aortic endothelial cells (BAECs) were cultured on ...

  18. Simple Current Actions of Cyclic Groups

    OpenAIRE

    Varga, Tamas

    2004-01-01

    Permutation actions of simple currents on the primaries of a Rational Conformal Field Theory are considered in the framework of admissible weighted permutation actions. The solution of admissibility conditions is presented for cyclic quadratic groups: an irreducible WPA corresponds to each subgroup of the quadratic group. As a consequence, the primaries of a RCFT with an order n integral or half-integral spin simple current may be arranged into multiplets of length k^2 (where k is a divisor o...

  19. Synthesis of a Cyclic Analogue of Galardin

    Institute of Scientific and Technical Information of China (English)

    马大为; 吴问根; 钱静; 郎深慧; 叶其壮

    2001-01-01

    A cyclic analogue 4 of galardin,a known MMP inhibitor,is designed to improve its selectivity.The synthesis of 4starts from dimethyl(S)-malate using diaselective alkylation and subsequent cyclization and amide formation as key steps.The compound 4 showed MMP inhibitory activity on all MMPs tested with IC50 ranging from 20.1 μM to 104 μM.

  20. General solution of the cyclic Leibniz rule

    Science.gov (United States)

    Kadoh, Daisuke; Ukita, Naoya

    2015-10-01

    We study the cyclic Leibniz rule (CLR) which was recently proposed as a new approach to the realization of supersymmetric quantum mechanics on the lattice. The CLR has an infinite number of solutions that give the different definitions of the lattice supersymmetric quantum mechanics. We show the general form of the solution for the naive symmetric difference operator and reveal the differences between the lattice models.

  1. Cyclic dominance in evolutionary games: A review

    CERN Document Server

    Szolnoki, Attila; Jiang, Luo-Luo; Szczesny, Bartosz; Rucklidge, Alastair M; Perc, Matjaz

    2014-01-01

    Rock is wrapped by paper, paper is cut by scissors, and scissors are crushed by rock. This simple game is popular among children and adults to decide on trivial disputes that have no obvious winner, but cyclic dominance is also at the heart of predator-prey interactions, the mating strategy of side-blotched lizards, the overgrowth of marine sessile organisms, and the competition in microbial populations. Cyclical interactions also emerge spontaneously in evolutionary games entailing volunteering, reward, punishment, and in fact are common when the competing strategies are three or more regardless of the particularities of the game. Here we review recent advances on the rock-paper-scissors and related evolutionary games, focusing in particular on pattern formation, the impact of mobility, and the spontaneous emergence of cyclic dominance. We also review mean-field and zero-dimensional rock-paper-scissors models and the application of the complex Ginzburg-Landau equation, and we highlight the importance and use...

  2. Scale Factor Duality for Conformal Cyclic Cosmologies

    CERN Document Server

    dS, U Camara; Sotkov, G M

    2016-01-01

    The scale factor duality is a symmetry of dilaton gravity which is known to lead to pre-big-bang cosmologies. A conformal time version of the scale factor duality (SFD) was recently implemented as a UV/IR symmetry between decelerated and accelerated phases of the post-big-bang evolution within Einstein gravity coupled to a scalar field. The problem investigated in the present paper concerns the employment of the conformal time SFD methods to the construction of pre-big-bang and cyclic extensions of these models. We demonstrate that each big-bang model gives rise to two qualitatively different pre-big-bang evolutions: a contraction/expansion SFD model and Penrose's Conformal Cyclic Cosmology (CCC). A few examples of SFD symmetric cyclic universes involving certain gauged K\\"ahler sigma models minimally coupled to Einstein gravity are studied. We also describe the specific SFD features of the thermodynamics and the conditions for validity of the generalized second law in the case of Gauss-Bonnet (GB) extension ...

  3. Scale factor duality for conformal cyclic cosmologies

    Science.gov (United States)

    Camara da Silva, U.; Alves Lima, A. L.; Sotkov, G. M.

    2016-11-01

    The scale factor duality is a symmetry of dilaton gravity which is known to lead to pre-big-bang cosmologies. A conformal time version of the scale factor duality (SFD) was recently implemented as a UV/IR symmetry between decelerated and accelerated phases of the post-big-bang evolution within Einstein gravity coupled to a scalar field. The problem investigated in the present paper concerns the employment of the conformal time SFD methods to the construction of pre-big-bang and cyclic extensions of these models. We demonstrate that each big-bang model gives rise to two qualitatively different pre-big-bang evolutions: a contraction/expansion SFD model and Penrose's Conformal Cyclic Cosmology (CCC). A few examples of SFD symmetric cyclic universes involving certain gauged Kähler sigma models minimally coupled to Einstein gravity are studied. We also describe the specific SFD features of the thermodynamics and the conditions for validity of the generalized second law in the case of Gauss-Bonnet (GB) extension of these selected CCC models.

  4. Cyclical period changes in Z Chamaeleontis

    CERN Document Server

    Baptista, R; Oliveira, E; Vrielmann, S; Woudt, P A; Catalan, M S

    2002-01-01

    We report the identification of cyclical changes in the orbital period of the eclipsing dwarf nova Z Cha. We used times of mid-eclipse collected from the literature and our new eclipse timings to construct an observed-minus-calculated diagram covering 30 years of observations (1972-2002). The data present cyclical variations that can be fitted by a linear plus sinusoidal function with period 28+/-2 yr and amplitude 1.0+/-0.2 minute. The statistical significance of this period by an F-test is larger than 99.9%. The derived fractional period change, Delta P/P= 4.4 x 10^{-7}, is comparable to that of other short-period cataclysmic variables (CVs), but is one order of magnitude smaller than those of the long-period CVs. Separate fits to the first and second half of the data lead to ephemerides with quite different cycle periods and amplitudes, indicating that the variation is not sinusoidal or, most probably, is not strictly periodic. The observed cyclical period change is possibly caused by a solar-type magnetic...

  5. Cosmology and Cosmogony in a Cyclic Universe

    Indian Academy of Sciences (India)

    Jayant V. Narlikar; Geoffrey Burbidge; R. G. Vishwakarma

    2007-06-01

    In this paper we discuss the properties of the quasi-steady state cosmological model (QSSC) developed in 1993 in its role as a cyclic model of the universe driven by a negative energy scalar field. We discuss the origin of such a scalar field in the primary creation process first described by F. Hoyle & J. V. Narlikar forty years ago. It is shown that the creation processes which take place in the nuclei of galaxies are closely linked to the high energy and explosive phenomena, which are commonly observed in galaxies at all redshifts. The cyclic nature of the universe provides a natural link between the places of origin of the microwave background radiation (arising in hydrogen burning in stars), and the origin of the lightest nuclei (H, D, He3 and He4). It also allows us to relate the large scale cyclic properties of the universe to events taking place in the nuclei of galaxies. Observational evidence shows that ejection of matter and energy from these centers in the form of compact objects, gas and relativistic particles is responsible for the population of quasi-stellar objects (QSOs) and gamma-ray burst sources in the universe. In the later parts of the paper we briefly discuss the major unsolved problems of this integrated cosmological and cosmogonical scheme – the understanding of the origin of the intrinsic redshifts, and the periodicities in the redshift distribution of the QSOs.

  6. Scale factor duality for conformal cyclic cosmologies

    Energy Technology Data Exchange (ETDEWEB)

    Silva, University Camara da; Lima, A.L. Alves; Sotkov, G.M. [Departamento de Física - CCE,Universidade Federal de Espirito Santo, 29075-900, Vitoria ES (Brazil)

    2016-11-16

    The scale factor duality is a symmetry of dilaton gravity which is known to lead to pre-big-bang cosmologies. A conformal time version of the scale factor duality (SFD) was recently implemented as a UV/IR symmetry between decelerated and accelerated phases of the post-big-bang evolution within Einstein gravity coupled to a scalar field. The problem investigated in the present paper concerns the employment of the conformal time SFD methods to the construction of pre-big-bang and cyclic extensions of these models. We demonstrate that each big-bang model gives rise to two qualitatively different pre-big-bang evolutions: a contraction/expansion SFD model and Penrose’s Conformal Cyclic Cosmology (CCC). A few examples of SFD symmetric cyclic universes involving certain gauged Kähler sigma models minimally coupled to Einstein gravity are studied. We also describe the specific SFD features of the thermodynamics and the conditions for validity of the generalized second law in the case of Gauss-Bonnet (GB) extension of these selected CCC models.

  7. Fractional Fourier domain analysis of cyclic multirate signal processing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The cyclic filter banks, which are used widely in the image subband coding, refer to signal processing on the finite field. This study investigates the fractional Fourier domain (FRFD) analysis of cyclic multirate systems based on the fractional circular convolution and chirp period. The proposed theorems include the fractional Fourier domain analysis of cyclic decimation and cyclic interpolation, the noble identities of cyclic decimation and cyclic interpolation in the FRFD, the polyphase represen-tation of cyclic signal in the FRFD, and the perfect reconstruction condition for the cyclic filter banks in the FRFD. Furthermore, this paper proposes the design methods for perfect reconstruction cyclic filter bank and cyclic filter bank with chirp modulation in the FRFD. The proposed theorems extend the multirate signal processing in the FRFD, which also advance the applications of the theorems of filter bank in the FRFD on the finite signal field, such as digital image processing. At last, the proposed design methods for the cyclic filter banks in the FRFD are validated by simulations.

  8. Multiaxial elastoplastic cyclic loading of austenitic 316L steel

    Directory of Open Access Journals (Sweden)

    V. Mazánová

    2017-04-01

    Full Text Available Cyclic stress-strain response and fatigue damage character has been investigated in austenitic stainless steel 316L. Hollow cylindrical specimens have been cyclically deformed in combined tension-compression and torsion under constant strain rate condition and different constant strain and shear strain amplitudes. In-phase and 90° out-of-phase cyclic straining was applied and the stress response has been monitored. Cyclic hardening/softening curves were assessed in both channels. Cyclic softening followed for higher strain amplitudes by long-term cyclic hardening was observed. Cyclic stress-strain curves were determined. Study of the surface damage in fractured specimens revealed the types and directions of principal cracks and the sources of fatigue crack initiation in slip bands.

  9. Local serotonin mediates cyclic strain-induced phenotype transformation, matrix degradation, and glycosaminoglycan synthesis in cultured sheep mitral valves.

    Science.gov (United States)

    Lacerda, Carla M R; Kisiday, John; Johnson, Brennan; Orton, E Christopher

    2012-05-15

    This study addressed the following questions: 1) Does cyclic tensile strain induce protein expression patterns consistent with myxomatous degeneration in mitral valves? 2) Does cyclic strain induce local serotonin synthesis in mitral valves? 3) Are cyclic strain-induced myxomatous protein expression patterns in mitral valves dependent on local serotonin? Cultured sheep mitral valve leaflets were subjected to 0, 10, 20, and 30% cyclic strain for 24 and 72 h. Protein levels of activated myofibroblast phenotype markers, α-smooth muscle actin (α-SMA) and nonmuscle embryonic myosin (SMemb); matrix catabolic enzymes, matrix metalloprotease (MMP) 1 and 13, and cathepsin K; and sulfated glycosaminoglycan (GAG) content in mitral valves increased with increased cyclic strain. Serotonin was present in the serum-free media of cultured mitral valves and concentrations increased with cyclic strain. Expression of the serotonin synthetic enzyme tryptophan hydroxylase 1 (TPH1) increased in strained mitral valves. Pharmacologic inhibition of the serotonin 2B/2C receptor or TPH1 diminished expression of phenotype markers (α-SMA and SMemb) and matrix catabolic enzyme (MMP1, MMP13, and cathepsin K) expression in 10- and 30%-strained mitral valves. These results provide first evidence that mitral valves synthesize serotonin locally. The results further demonstrate that tensile loading modulates local serotonin synthesis, expression of effector proteins associated with mitral valve degeneration, and GAG synthesis. Inhibition of serotonin diminishes strain-mediated protein expression patterns. These findings implicate serotonin and tensile loading in mitral degeneration, functionally link the pathogeneses of serotoninergic (carcinoid, drug-induced) and degenerative mitral valve disease, and have therapeutic implications.

  10. Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Kjelstrup, Susanne; Hansen, Paula Melo Paulon; Thomsen, Line Elnif;

    2013-01-01

    Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides......, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered...

  11. Phosphodiesterase 4 and compartmentalization of cyclic AMP signaling

    Institute of Scientific and Technical Information of China (English)

    WANG ZhengChao; SHI FangXiong

    2007-01-01

    Cyclic AMP (cAMP), as a second messenger, plays a critical role in cellular signaling transduction. However, it is not clear how this apparently identical cAMP signal induces divergent physiological responses. The potential explanation that cAMP signaling is compartmentalized was proposed by Buxton and Brunton twenty years ago. Compartmentalization of cAMP signaling allows spatially distinct pools of protein kinase A (PKA) to be differently activated. Research on cAMP signaling has regained impetus in many fields of life sciences due to the progress in understanding cAMP signaling complexity and functional diversity. The cAMP/PKA signaling compartments are maintained by A-kinase anchoring proteins (AKAPs) which bind PKA and other signaling proteins, and by PDEs which hydrolyse cAMP and thus terminate PKA activity. PDE4 enzymes belong to PDE superfamily and stand at a crossroad that allows them to integrate various signaling pathways with that of cAMP in spatially distinct compartments. In the current review, the nomenclature, taxonomy and gene expression of PDE4, and the system and region of its effect are described. In addition, the idiographic molecules, mechanisms, and regulation models of PDE4 are summarized. Furthermore, the important roles PDE4 plays in the maturation of rat granulosa cells and cAMP signaling compartmentalization are discussed.

  12. Efficient Synthesis of Cyclic Block Copolymers by Rotaxane Protocol by Linear/Cyclic Topology Transformation.

    Science.gov (United States)

    Valentina, Stephanie; Ogawa, Takahiro; Nakazono, Kazuko; Aoki, Daisuke; Takata, Toshikazu

    2016-06-20

    High-yielding synthesis of cyclic block copolymer (CBC) using the rotaxane protocol by linear-cyclic polymer topology transformation was first demonstrated. Initial complexation of OH-terminated sec-ammonium salt and a crown ether was followed by the successive living ring-opening polymerizations of two lactones to a linear block copolymer having a rotaxane structure by the final capping of the propagation end. CBC was obtained in a high yield by an exploitation of the mechanical linkage through the translational movement of the rotaxane component to transform polymer structure from linear to cyclic. Furthermore, the change of the polymer topology was translated into a macroscopic change in crystallinity of the block copolymer.

  13. Statistical damage constitutive model for rocks subjected to cyclic stress and cyclic temperature

    Science.gov (United States)

    Zhou, Shu-Wei; Xia, Cai-Chu; Zhao, Hai-Bin; Mei, Song-Hua; Zhou, Yu

    2017-08-01

    A constitutive model of rocks subjected to cyclic stress-temperature was proposed. Based on statistical damage theory, the damage constitutive model with Weibull distribution was extended. Influence of model parameters on the stress-strain curve for rock reloading after stress-temperature cycling was then discussed. The proposed model was initially validated by rock tests for cyclic stress-temperature and only cyclic stress. Finally, the total damage evolution induced by stress-temperature cycling and reloading after cycling was explored and discussed. The proposed constitutive model is reasonable and applicable, describing well the stress-strain relationship during stress-temperature cycles and providing a good fit to the test results. Elastic modulus in the reference state and the damage induced by cycling affect the shape of reloading stress-strain curve. Total damage induced by cycling and reloading after cycling exhibits three stages: initial slow increase, mid-term accelerated increase, and final slow increase.

  14. Cyclic AMP and cyclic GMP levels in glandular stomach of restrained rats.

    Science.gov (United States)

    Zarrindast, M R; Sharghi, G; Gerayesh-Nejad, S; Djahanguiri, B

    1977-10-01

    Cyclic AMP and cyclic GMP were measured in glandular stomach of rats subjected to saline administration, cold (4 degrees C), restraint and restraint+cold after 15, 30, 60, 90 and 120 minutes. All animals subjected to restraint+cold had gastric ulceration after 2 hours. A significant but transient decrease in cAMP was observed 15 minutes after restraint+cold. A marked, sustained and significant decrease of cGMP was observed in the same group of animals. It is concluded that it seems unlikely to be a correlation between cAMP and cGMP changes of the stomach and the restraint-induced gastric ulceration.

  15. Isolation of a Cyclic (Alkyl(aminogermylene

    Directory of Open Access Journals (Sweden)

    Liliang Wang

    2016-07-01

    Full Text Available A 1,4-addition of a dichlorogermylene dioxane complex with α,β-unsaturated imine 1 gave a dichlorogermane derivative 2 bearing a GeC3N five-membered ring skeleton. By reducing 2 with KC8, cyclic (alkyl(aminogermylene 3 was synthesized and fully characterized. Germylene 3 readily reacted with TEMPO, N2O and S8, producing the 1:2 adduct 4, the oxo-bridged dimer 5 and the sulfido-bridged dimer 6, respectively.

  16. Periodic cyclic homology of affine Hecke algebras

    CERN Document Server

    Solleveld, Maarten

    2009-01-01

    This is the author's PhD-thesis, which was written in 2006. The version posted here is identical to the printed one. Instead of an abstract, the short list of contents: Preface 5 1 Introduction 9 2 K-theory and cyclic type homology theories 13 3 Affine Hecke algebras 61 4 Reductive p-adic groups 103 5 Parameter deformations in affine Hecke algebras 129 6 Examples and calculations 169 A Crossed products 223 Bibliography 227 Index 237 Samenvatting 245 Curriculum vitae 253

  17. Cyclic groups and quantum logic gates

    Science.gov (United States)

    Pourkia, Arash; Batle, J.; Raymond Ooi, C. H.

    2016-10-01

    We present a formula for an infinite number of universal quantum logic gates, which are 4 by 4 unitary solutions to the Yang-Baxter (Y-B) equation. We obtain this family from a certain representation of the cyclic group of order n. We then show that this discrete family, parametrized by integers n, is in fact, a small sub-class of a larger continuous family, parametrized by real numbers θ, of universal quantum gates. We discuss the corresponding Yang-Baxterization and related symmetries in the concomitant Hamiltonian.

  18. Simple Current Actions of Cyclic Groups

    CERN Document Server

    Varga, T

    2004-01-01

    Permutation actions of simple currents on the primaries of a Rational Conformal Field Theory are considered in the framework of admissible weighted permutation actions. The solution of admissibility conditions is presented for cyclic quadratic groups: an irreducible WPA corresponds to each subgroup of the quadratic group. As a consequence, the primaries of a RCFT with an order n integral or half-integral spin simple current may be arranged into multiplets of length k^2 (where k is a divisor of n) or 3k^2 if the spin of the simple current is half-integral and k is odd.

  19. A cyclic universe approach to fine tuning

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, Stephon, E-mail: stephon.alexander@dartmouth.edu [Department of Physics and Astronomy, Dartmouth College, Hanover, NH 03755 (United States); Department of Physics, Brown University, Providence, RI 02906 (United States); Cormack, Sam, E-mail: samuel.c.cormack.gr@dartmouth.edu [Department of Physics and Astronomy, Dartmouth College, Hanover, NH 03755 (United States); Gleiser, Marcelo, E-mail: marcelo.gleiser@dartmouth.edu [Department of Physics and Astronomy, Dartmouth College, Hanover, NH 03755 (United States)

    2016-06-10

    We present a closed bouncing universe model where the value of coupling constants is set by the dynamics of a ghost-like dilatonic scalar field. We show that adding a periodic potential for the scalar field leads to a cyclic Friedmann universe where the values of the couplings vary randomly from one cycle to the next. While the shuffling of values for the couplings happens during the bounce, within each cycle their time-dependence remains safely within present observational bounds for physically-motivated values of the model parameters. Our model presents an alternative to solutions of the fine tuning problem based on string landscape scenarios.

  20. Expression of matrix metalloproteinases and ovarian morphological changes in androgenized cyclic female guinea pigs.

    Science.gov (United States)

    Li, Jun-rong; Shen, Ting; Wang, Yan-li; Wei, Quan-wei; Shi, Fang-xiong

    2016-02-01

    This study was conducted to investigate expression of matrix metalloproteinases (MMPs) and ovarian morphological changes in androgenized cyclic female guinea pigs. Adult cyclic female guinea pigs were injected daily for 28 days with medium doses of testosterone propionate (TP; 1 mg/100g), high doses of TP (2 mg/100g), or saline (control). Serum concentrations of testosterone, estradiol (E2), and progesterone (P4) were measured. Histologic sections of ovaries were stained with hematoxylin-eosin and by immunohistochemistry. Expressions of steroidogenic acute regulatory protein, proliferating cell nuclear antigen, and MMP-2 and MMP-9 in the ovary were characterized by immunohistochemistry. After 28 days of TP injection, serum testosterone concentrations were increased dose-dependently. An appropriate dosage of TP could induce permanent anovulation in guinea pigs, making them a potential model for human polycystic ovary syndrome. MMP-2 and MMP-9 are jointly involved in the growth and atresia of ovarian follicles in cyclic guinea pigs. Increased numbers of atretic antral follicles in the ovary might be associated with the observed high expression of MMP-2 in androgenized cyclic guinea pigs.

  1. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity

    Science.gov (United States)

    Osbourne, Devon O; Soo, Valerie WC; Konieczny, Igor; Wood, Thomas K

    2014-01-01

    Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease. PMID:24874800

  2. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity.

    Science.gov (United States)

    Osbourne, Devon O; Soo, Valerie W C; Konieczny, Igor; Wood, Thomas K

    2014-01-01

    Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease.

  3. The Arabidopsis thaliana Cyclic-Nucleotide-Dependent Response – a Quantitative Proteomic and Phosphoproteomic Analysis

    KAUST Repository

    Alqurashi, May M.

    2013-11-01

    Protein phosphorylation governs many regulatory pathways and an increasing number of kinases, proteins that transfer phosphate groups, are in turn activated by cyclic nucleotides. One of the cyclic nucleotides, cyclic adenosine monophosphate (cAMP), has been shown to be a second messenger in abiotic and biotic stress responses. However, little is known about the precise role of cAMP in plants and in the down-stream activation of kinases, and hence cAMP-dependent phosphorylation. To increase our understanding of the role of cAMP, proteomic and phosphoproteomic profiles of Arabidopsis thaliana suspension culture cells were analyzed before and after treatment of cells with two different concentrations of 8-Bromo-cAMP (1 µM and 100 nM) and over a time-course of one hour. A comparative quantitative analysis was undertaken using two- dimensional gel electrophoresis and the Delta 2D software (DECODON) followed by protein spot identification by tandem mass spectrometry combined with Mascot and Scaffold. Differentially expressed proteins and regulated phosphoproteins were categorized according to their biological function using bioinformatics tools. The results revealed that the treatment with 1 µM and 100 nM 8-Bromo-cAMP was sufficient to induce specific concentration- and time-dependent changes at the proteome and phosphoproteome levels. In particular, different phosphorylation patterns were observed overtime preferentially affecting proteins in a number of functional categories, notably phosphatases, proteins that remove phosphate groups. This suggests that cAMP both transiently activates and deactivates proteins through specific phosphorylation events and provides new insight into biological mechanisms and functions at the systems level.

  4. The cyclic cystine ladder of theta-defensins as a stable, bifunctional scaffold: A proof-of-concept study using the integrin-binding RGD motif.

    Science.gov (United States)

    Conibear, Anne C; Bochen, Alexander; Rosengren, K Johan; Stupar, Petar; Wang, Conan; Kessler, Horst; Craik, David J

    2014-02-10

    Peptides have the specificity and size required to target the protein-protein interactions involved in many diseases. Some cyclic peptides have been utilised as scaffolds for peptide drugs because of their stability; however, other cyclic peptide scaffolds remain to be explored. θ-Defensins are cyclic peptides from mammals; they are characterised by a cyclic cystine ladder motif and have low haemolytic and cytotoxic activity. Here we demonstrate the potential of the cyclic cystine ladder as a scaffold for peptide drug design by introducing the integrin-binding Arg-Gly-Asp (RGD) motif into the θ-defensin RTD-1. The most active analogue had an IC50 of 18 nM for the αv β3 integrin as well as high serum stability, thus demonstrating that a desired bioactivity can be imparted to the cyclic cystine ladder. This study highlights how θ-defensins can provide a stable and conformationally restrained scaffold for bioactive epitopes in a β-strand or turn conformation. Furthermore, the symmetry of the cyclic cystine ladder presents the opportunity to design peptides with dual bioactive epitopes to increase activity and specificity.

  5. CyclicCO2R: production of cyclic carbonates from CO2 using renewable feedstocks

    NARCIS (Netherlands)

    Kimball, E.; Schuurbiers, C.A.H.; Zevenbergen, J.F.; Håkonsen, S.F.; Heyn, R.; Offermans, W.; Leitner, W.; Ostapowicz, T.; Müller, T. E.; Mul, G.; North, M.; Ngomsik-Fanselow, A.F.; Sarron, E.; Sigurbjörnsson, O.; Schäffner, B.

    2013-01-01

    The consortium behind CyclicCO2R wants to kick-start the implementation of CO2 utilization technologies by converting CO2 into a high value-added product, thus providing a showcase that inspires industry to further develop technologies utilizing CO2 as a sustainable raw material and valorizing CO2

  6. CyclicCO2R: production of cyclic carbonates from CO2 using renewable feedstocks

    NARCIS (Netherlands)

    Kimball, E.; Schuurbiers, C.A.H.; Zevenbergen, J.F.; Håkonsen, S.F.; Heyn, R.; Offermans, W.; Leitner, W.; Ostapowicz, T.; Müller, T. E.; Mul, G.; North, M.; Ngomsik-Fanselow, A.F.; Sarron, E.; Sigurbjörnsson, O.; Schäffner, B.

    2013-01-01

    The consortium behind CyclicCO2R wants to kick-start the implementation of CO2 utilization technologies by converting CO2 into a high value-added product, thus providing a showcase that inspires industry to further develop technologies utilizing CO2 as a sustainable raw material and valorizing CO2 i

  7. Cyclical components of local rainfall data

    Science.gov (United States)

    Mentz, R. P.; D'Urso, M. A.; Jarma, N. M.; Mentz, G. B.

    2000-02-01

    This paper reports on the use of a comparatively simple statistical methodology to study local short time series rainfall data. The objective is to help in agricultural planning, by diminishing the risks associated with some uncertainties affecting this business activity.The analysis starts by assuming a model of unobservable components, trend, cycle, seasonal and irregular, that is well known in many areas of application. When series are in the realm of business and economics, the statistical methods popularized by the US Census Bureau US National Bureau of Economic Research are used for seasonal and cyclical estimation, respectively. The flexibility of these methods makes them good candidates to be applied in the meteorological context, and this is done in this paper for a selection of monthly rainfall time series.Use of the results to help in analysing and forecasting cyclical components is emphasized. The results are interesting. An agricultural entrepreneur, or a group of them located in a single geographical region, will profit by systematically collecting information (monthly in our work) about rainfall, and adopting the scheme of analysis described in this paper.

  8. Evolution of cyclic peptide protease inhibitors.

    Science.gov (United States)

    Young, Travis S; Young, Douglas D; Ahmad, Insha; Louis, John M; Benkovic, Stephen J; Schultz, Peter G

    2011-07-05

    We report a bacterial system for the evolution of cyclic peptides that makes use of an expanded set of amino acid building blocks. Orthogonal aminoacyl-tRNA synthetase/tRNA(CUA) pairs, together with a split intein system were used to biosynthesize a library of ribosomal peptides containing amino acids with unique structures and reactivities. This peptide library was subsequently used to evolve an inhibitor of HIV protease using a selection based on cellular viability. Two of three cyclic peptides isolated after two rounds of selection contained the keto amino acid p-benzoylphenylalanine (pBzF). The most potent peptide (G12: GIXVSL; X=pBzF) inhibited HIV protease through the formation of a covalent Schiff base adduct of the pBzF residue with the ε-amino group of Lys 14 on the protease. This result suggests that an expanded genetic code can confer an evolutionary advantage in response to selective pressure. Moreover, the combination of natural evolutionary processes with chemically biased building blocks provides another strategy for the generation of biologically active peptides using microbial systems.

  9. A cyclically actuated electrolytic drug delivery device

    KAUST Repository

    Yi, Ying

    2015-01-01

    This work, focusing on an implantable drug delivery system, presents the first prototype electrolytic pump that combines a catalytic reformer and a cyclically actuated mode. These features improve the release performance and extend the lifetime of the device. Using our platinum (Pt)-coated carbon fiber mesh that acts as a catalytic reforming element, the cyclical mode is improved because the faster recombination rate allows for a shorter cycling time for drug delivery. Another feature of our device is that it uses a solid-drug-in-reservoir (SDR) approach, which allows small amounts of a solid drug to be dissolved in human fluid, forming a reproducible drug solution for long-term therapies. We have conducted proof-of-principle drug delivery studies using such an electrolytic pump and solvent blue 38 as the drug substitute. These tests demonstrate power-controlled and pulsatile release profiles of the chemical substance, as well as the feasibility of this device. A drug delivery rate of 11.44 ± 0.56 μg min-1 was achieved by using an input power of 4 mW for multiple pulses, which indicates the stability of our system. © The Royal Society of Chemistry 2015.

  10. Cyclic integrals and reduction of rotational relativistic Birkhoffian system

    Institute of Scientific and Technical Information of China (English)

    罗绍凯

    2003-01-01

    The order reduction method of the rotational relativistic Birkhoffian equations is studied. For a rotational relativistic Birkhoffian system, the cyclic integrals can be found by using the perfect differential method. Through these cyclic integrals, the order of the system can be reduced. If the rotational relativistic Birkhoffian system has a cyclic integral, then the Birkhoffian equations can be reduced at least two degrees and the Birkhoffian form can be kept. An example is given to illustrate the application of the results.

  11. Cyclic Voltammetry of Polysulfide (Thiokol) Prepolymers and Related Compounds

    Science.gov (United States)

    1983-12-01

    low scan rates suqges t that A and B are unstable and undergo chesical reactions on the cyclic voltametry time scale. A more detailed examination is...REPOR CYCLIC VOLTAq4ETRY OF POLYSIILF!OE (THIOKOL) PREPOLYMERS AND~ RELATED COMPODWS Waldemar Nazurek ThE UPrEDT STATES NATIONAL. CZTECMNNCAL...DEPARTMENT OF DEFENCE MATERIALS RESEARCH LABORATORIES REPORT MRL-R.911 CYCLIC VOLTAP,4ETRY OF POLYSULFIDE (THIOKOL) PREPOLYMERS AND RELATEn COMPOUNDS 𔃻

  12. Cyclic cocycles on deformation quantizations and higher index theorems

    CERN Document Server

    Pflaum, M; Tang, X

    2008-01-01

    We construct a nontrivial cyclic cocycle on the Weyl algebra of a symplectic vector space. Using this cyclic cocycle we construct an explicit, local, quasi-isomorphism from the complex of differential forms on a symplectic manifold to the complex of cyclic cochains of any formal deformation quantization thereof. We prove an algebraic higher index theorem by computing the pairing between such cyclic cocycles and the $K$-theory of the formal deformation quantization. As an application, we obtain the analytic higher index theorem of Connes--Moscovici.

  13. Cyclic structures in algebraic (co)homology theories

    CERN Document Server

    Kowalzig, Niels

    2010-01-01

    This note discusses the cyclic cohomology of a left Hopf algebroid ($\\times_A$-Hopf algebra) with coefficients in a right module-left comodule, defined using a straightforward generalisation of the original operators given by Connes and Moscovici for Hopf algebras. Lie-Rinehart homology is a special case of this theory. A generalisation of cyclic duality that makes sense for arbitrary para-cyclic objects yields a dual homology theory. The twisted cyclic homology of an associative algebra provides an example of this dual theory that uses coefficients that are not necessarily stable anti Yetter-Drinfel'd modules.

  14. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  15. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2017-03-21

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  16. Use of Galerina marginata genes and proteins for peptide production

    Science.gov (United States)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  17. Cyclic cidofovir (cHPMPC prevents congenital cytomegalovirus infection in a guinea pig model

    Directory of Open Access Journals (Sweden)

    McGregor Alistair

    2006-03-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC, could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test. By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26% were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection.

  18. Ring-opening polymerization of cyclic esters by cyclodextrins.

    Science.gov (United States)

    Harada, Akira; Osaki, Motofumi; Takashima, Yoshinori; Yamaguchi, Hiroyasu

    2008-09-01

    Synthetic polymers, typically prepared by addition polymerization or stepwise polymerization, are used constantly in our daily lives. In recent years, polymer scientists have focused on more environmentally friendly synthetic methods such as mild reaction conditions and biodegradable condensation polymers, including polyesters and polyamides. However, challenges remain in finding greener methods for the synthesis of polymers. Although reactions carried out in water are more environmentally friendly than those in organic solvents, aqueous media can lead to the hydrolysis of condensation polymers. Furthermore, bulk polymerizations are difficult to control. In biological systems, enzymes synthesize most polymers (proteins, DNAs, RNAs, and polysaccharides) in aqueous environments or in condensed phases (membranes). Most enzymes, such as DNA polymerases, RNA polymerases, and ribosomes, form doughnutlike shapes, which encircle the growing polymer chain. As biopolymers form, the active sites and the substrate-combining sites are located at the end of the growing polymer chain and carefully control the polymerization. Therefore, a synthetic catalyst that could insert the monomers between the active site and binding site would create an ideal biomimetic polymerization system. In this Account, we describe cyclodextrins (CDs) as catalysts that can polymerize cyclic esters (lactones and lactides). CDs can initiate polymerizations of cyclic esters in bulk without solvents (even water) to give products in high yields. During our studies on the polymerization of lactones by CDs in bulk, we found that CDs function not only as initiators (catalysts) but also as supporting architectures similar to chaperone proteins. CDs encircle a linear polymer chain so that the chain assumes the proper conformation and avoids coagulation. The CDs can mimic the strategy that living systems use to prepare polymers. Thus, we can obtain polyesters tethered to CDs without employing additional solvents

  19. Beyond Inflation: A Cyclic Universe Scenario

    CERN Document Server

    Turok, N G; Turok, Neil; Seinhardt, Paul J.

    2005-01-01

    Inflation has been the leading early universe scenario for two decades, and has become an accepted element of the successful `cosmic concordance' model. However, there are many puzzling features of the resulting theory. It requires both high energy and low energy inflation, with energy densities differing by a hundred orders of magnitude. The questions of why the universe started out undergoing high energy inflation, and why it will end up in low energy inflation, are unanswered. Rather than resort to anthropic arguments, we have developed an alternative cosmology, the Cyclic universe, in which the universe exists in a very long-lived attractor state determined by the laws of physics. The model shares inflation's phenomenological successes without requiring an epoch of high energy inflation. Instead, the universe is made homogeneous and flat, and scale-invariant adiabatic perturbations are generated during an epoch of low energy acceleration like that seen today, but preceding the last big bang. Unlike inflat...

  20. Corrosive electrochemistry of jamesonite by cyclic voltammetry

    Institute of Scientific and Technical Information of China (English)

    余润兰; 胡岳华; 邱冠周; 覃文庆

    2004-01-01

    The corrosive electrochemistry of jamesonite was studied by cyclic voltammetry. Every peak in voltammograms was identified through thermodynamic calculation. The results show an irreversible electrode process by the strong adsorption of oxidation elemental sulfur on jamesonite. A deficient-metal and sulfur-rich compound is formed under the potential of 80 mV at pH 6.86. The passive action by elemental sulfur occurs from 80 to 470 mV and S2O23- , SO24- are produced at potential over 470 mV. The anodic peak producing SO24- is inhibited due to the deposition of PbSO4 at higher potential in Na2SO4 solution. The corrosive action of jamesonite becomes strong and the redox characterization similar to PbS, FeS and Sb2 S3 appears at pH 9.18.

  1. Bucket foundations under lateral cyclic loading

    DEFF Research Database (Denmark)

    Foglia, Aligi

    -competitive in the energy market. This thesis addresses issues concerning monopod bucket foundations in the hope of providing tools and ideas that could be used to optimize the design of this sub-structure. The work is focussed on the behaviour of bucket foundations under lateral cyclic loading. Other related......To enable a prosperous development of offshore wind energy, economically feasible technologies must be developed. The monopod bucket foundation is likely to become a cost-effective sub-structure for offshore wind turbines and has the potential to make offshore wind more cost...... and propaedeutic topics, such as bucket foundations under transient lateral loading and under monotonic lateral loading, are also investigated. All the scientific work is fundamentally based on small-scale experimental tests of bucket foundations in dense water-saturated sand. The most important scientific...

  2. Extinction in four species cyclic competition

    Science.gov (United States)

    Intoy, Ben; Pleimling, Michel

    2013-08-01

    When four species compete stochastically in a cyclic way, the formation of two teams of mutually neutral partners is observed. In this paper we study through numerical simulations the extinction processes that can take place in this system both in the well mixed case as well as on different types of lattices. The different routes to extinction are revealed by the probability distribution of the domination time, i.e. the time needed for one team to fully occupy the system. If swapping is allowed between neutral partners, then the probability distribution is dominated by very long-lived states where a few very large domains persist, each domain being occupied by a mix of individuals from species that form one of the teams. Many aspects of the possible extinction scenarios are lost when only considering averaged quantities, such as for example the mean domination time.

  3. Pyroelectric Harvesters for Generating Cyclic Energy

    Directory of Open Access Journals (Sweden)

    Chun-Ching Hsiao

    2015-04-01

    Full Text Available Pyroelectric energy conversion is a novel energy process which directly transforms waste heat energy from cyclic heating into electricity via the pyroelectric effect. Application of a periodic temperature profile to pyroelectric cells is necessary to achieve temperature variation rates for generating an electrical output. The critical consideration in the periodic temperature profile is the frequency or work cycle which is related to the properties and dimensions of the air layer; radiation power and material properties, as well as the dimensions and structure of the pyroelectric cells. This article aims to optimize pyroelectric harvesters by matching all these requirements. The optimal induced charge per period increases about 157% and the efficient period band decreases about 77%, when the thickness of the PZT cell decreases from 200 μm to 50 μm, about a 75% reduction. Moreover, when using the thinner PZT cell for harvesting the pyroelectric energy it is not easy to focus on a narrow band with the efficient period. However, the optimal output voltage and stored energy per period decrease about 50% and 74%, respectively, because the electrical capacitance of the 50 μm thick pyroelectric cell is about four times greater than that of the 200 μm thick pyroelectric cell. In addition, an experiment is used to verify that the work cycle to be able to critically affect the efficiency of PZT pyroelectric harvesters. Periods in the range between 3.6 s and 12.2 s are useful for harvesting thermal cyclic energy by pyroelectricity. The optimal frequency or work cycle can be applied in the design of a rotating shutter in order to control the heated and unheated periods of the pyroelectric cells to further enhance the amount of stored energy.

  4. Classifying Spaces with Virtually Cyclic Stabilisers for Certain Infinite Cyclic Extensions

    CERN Document Server

    Fluch, Martin

    2010-01-01

    Let G be an infinite cyclic extension, 1 -> B -> G -> Z -> 1, of a group B where the action of Z on the set of conjugacy classes of non-trivial elements of B is free. This class of groups includes certain ascending HNN-extensions with abelian or free base groups, certain wreath products by Z and the soluble Baumslag--Solitar groups BS(1,m) with |m|> 1. We construct a model for Evc(G), the classifying space of G for the family of virtually cyclic subgroups of G, and give bounds for the minimum dimension of Evc(G). We construct a 2-dimensional model for Evc(G) where G is a soluble Baumslag-Solitar BS(1,m) group with |m|>1 and we show that this model for Evc(G) is of minimal dimension.

  5. Cyclic mononucleotides modulate potassium and calcium flux responses to H2O2 in Arabidopsis roots

    KAUST Repository

    Ordoñez, Natalia Maria

    2014-02-13

    Cyclic mononucleotides are messengers in plant stress responses. Here we show that hydrogen peroxide (H2O2) induces rapid net K+-efflux and Ca2+-influx in Arabidopsis roots. Pre-treatment with either 10 μM cAMP or cGMP for 1 or 24 h does significantly reduce net K+-leakage and Ca2+-influx, and in the case of the K+-fluxes, the cell permeant cyclic mononucleotides are more effective. We also examined the effect of 10 μM of the cell permeant 8-Br-cGMP on the Arabidopsis microsomal proteome and noted a specific increase in proteins with a role in stress responses and ion transport, suggesting that cGMP is sufficient to directly and/or indirectly induce complex adaptive changes to cellular stresses induced by H2O2. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. CYCLIC VECTORS AND CELLULAR INDECOMPOSABLE OPERATORS ON Qp SPACES

    Institute of Scientific and Technical Information of China (English)

    Ye Shanli; Lou Zengjian

    2011-01-01

    We identify the functions whose polynomial multiples are weak* dense in Qp spaces and prove that if |f(z)|≥|g(z)| and g is cyclic in Qp, then f is cyclic in Qp. We also show that the multiplication operator Mz on Qp spaces is cellular indecomposable.

  7. Cyclic Matching Pursuits with Multiscale Time-frequency Dictionaries

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Christensen, Mads Græsbøll

    2010-01-01

    We generalize cyclic matching pursuit (CMP), propose an orthogonal variant, and examine their performance using multiscale time-frequency dictionaries in the sparse approximation of signals. Overall, we find that the cyclic approach of CMP produces signal models that have a much lower approximati...

  8. Development of Pore Pressure and Material Damping during Cyclic Loading

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo

    1994-01-01

    The behaviour of sand during cyclic loading can be characterized as "stabilization", "instant stabilization". "pore pressure buildup" and "liquefaction". The terminologies can be defined exactly by a simple mathematical formulation based on the existence of a cyclic stable state. By introducing a...

  9. Classifying spaces with virtually cyclic stabilizers for linear groups

    DEFF Research Database (Denmark)

    Degrijse, Dieter Dries; Köhl, Ralf; Petrosyan, Nansen

    2015-01-01

    We show that every discrete subgroup of GL(n, ℝ) admits a finite-dimensional classifying space with virtually cyclic stabilizers. Applying our methods to SL(3, ℤ), we obtain a four-dimensional classifying space with virtually cyclic stabilizers and a decomposition of the algebraic K-theory of its...

  10. Classifying spaces with virtually cyclic stabilizers for linear groups

    DEFF Research Database (Denmark)

    Degrijse, Dieter Dries; Köhl, Ralf; Petrosyan, Nansen

    2015-01-01

    We show that every discrete subgroup of GL(n, ℝ) admits a finite-dimensional classifying space with virtually cyclic stabilizers. Applying our methods to SL(3, ℤ), we obtain a four-dimensional classifying space with virtually cyclic stabilizers and a decomposition of the algebraic K-theory of its...

  11. The redox status of experimental hemorrhagic shock as measured by cyclic voltammetry.

    Science.gov (United States)

    Mittal, Anubhav; Göke, Friederike; Flint, Richard; Loveday, Benjamin P T; Thompson, Nichola; Delahunt, Brett; Kilmartin, Paul A; Cooper, Garth J S; MacDonald, Julia; Hickey, Anthony; Windsor, John A; Phillips, Anthony R J

    2010-05-01

    Hemorrhagic shock (HS) leads to reactive oxygen species production. However, clinicians do not have access to bedside measurements of the redox status during HS. Cyclic voltammetry (CyV) is a simple electrochemical method of measuring redox status. The aims of this study were to 1) report the first application of cyclic voltammetry to measure the acute changes in serum redox status after HS, 2) to contrast it with another severe systemic disease with a different redox pathology (acute pancreatitis [AP]), and 3) to describe the response of CyV over time in a resolving model of AP. In the acute study, 24 male Wistar rats were randomized into three groups: groups 1 (control), 2 (AP), and 3 (HS). In the time-course study, 28 rats were randomized to a sham-control as well as 6 and 24 h post-AP cohorts, respectively.Cyclic voltammetry was performed using a three-electrode system. In the acute study, the first and second voltammetric peaks increased significantly in HS. In contrast, within the AP group, only the first voltammetric peak showed a significant increase. The first voltammetric peak correlated with plasma protein carbonyls (PCs) and with thiobarbituric acid-reactive substances, whereas the second voltammetric peak correlated positively with plasma protein carbonyls. In the second study, the first voltammetric peak correlated with physiological improvements. Here, we showed that serum CyV could respond to the serum redox change in HS and AP. Cyclic voltammetry warrants evaluation as a potential real-time beside measure of a patient's redox status during shock.

  12. Isolation and Partial Characterization of a Cyclic GMP-Dependent Cyclic GMP-Specific Phosphodiesterase from Dictyostelium discoideum

    NARCIS (Netherlands)

    Bulgakov, Roman; Haastert, Peter J.M. van

    1983-01-01

    The cellular slime mold, Dictyostelium discoideum, contains at least two classes of phosphodiesterase activity. One class of enzymes hydrolyses cyclic AMP (cAMP) and cyclic GMP (cGMP) with approximately equal rates. Another enzyme, which is less than 5% of the total activity, specifically hydrolyses

  13. Inter-rater reliability of cyclic and non-cyclic task assessment using the hand activity level in appliance manufacturing.

    Science.gov (United States)

    Paulsen, Robert; Schwatka, Natalie; Gober, Jennifer; Gilkey, David; Anton, Dan; Gerr, Fred; Rosecrance, John

    2014-01-01

    This study evaluated the inter-rater reliability of the American Conference of Governmental Industrial Hygienists (ACGIH(®)) hand activity level (HAL), an observational ergonomic assessment method used to estimate physical exposure to repetitive exertions during task performance. Video recordings of 858 cyclic and non-cyclic appliance manufacturing tasks were assessed by sixteen pairs of raters using the HAL visual-analog scale. A weighted Pearson Product Moment-Correlation Coefficient was used to evaluate the agreement between the HAL scores recorded by each rater pair, and the mean weighted correlation coefficients for cyclic and non-cyclic tasks were calculated. Results indicated that the HAL is a reliable exposure assessment method for cyclic (r̄-bar w = 0.69) and non-cyclic work tasks (r̄-bar w = 0.68). When the two reliability scores were compared using a two-sample Student's t-test, no significant difference in reliability (p = 0.63) between these work task categories was found. This study demonstrated that the HAL may be a useful measure of exposure to repetitive exertions during cyclic and non-cyclic tasks.

  14. NO, nitrotyrosine, and cyclic GMP in signal transduction

    Science.gov (United States)

    Hanafy, K. A.; Krumenacker, J. S.; Murad, F.

    2001-01-01

    Over the past 25 years, the role of nitric oxide (NO) in biology has evolved from being recognized as an environmental pollutant to an endogenously produced substance involved in cell communication and signal transduction. NO is produced by a family of enzymes called nitric oxide synthases (NOSs), which can be stimulated by a variety of factors that mediate responses to various stimuli. NO can initiate its biological effects through activation of the heterodimeric enzyme, soluble guanylyl cyclase (sGC), or through several other chemical reactions. Activation of sGC results in the production of 3',5'-cyclic guanosine monophosphate (cGMP), an intracellular second messenger signaling molecule, which can subsequently mediate such diverse physiological events such as vasodilatation and immunomodulation. Chemically reactive NO can affect physiological changes through modifications to cellular proteins, one of which is tyrosine nitration. The demonstration that NO is involved in so many biological pathways indicates the importance of this endogenously produced substance, and suggests that there is much more to be discovered about its role in biology in years to come.

  15. Escherichia coli exports cyclic AMP via TolC.

    Science.gov (United States)

    Hantke, Klaus; Winkler, Karin; Schultz, Joachim E

    2011-03-01

    In Escherichia coli more than 180 genes are regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. However, more than 90% of cAMP that is made by intracellular adenylyl cyclases is found in the culture medium. How is cAMP exported from E. coli? In a tolC mutant, 0.03 mM IPTG (isopropyl-β-d-thiogalactopyranoside) was sufficient to induce β-galactosidase compared to 0.1 mM IPTG in the parent strain. In a cya mutant unable to produce cAMP about 1 mM extracellular cAMP was required to induce β-galactosidase, whereas in a cya tolC mutant 0.1 mM cAMP was sufficient. When cAMP in E. coli cya was generated intracellularly by a recombinant, weakly active adenylyl cyclase from Corynebacterium glutamicum, the critical level of cAMP necessary for induction of maltose degradation was only achieved in a tolC mutant and not in the parent strain. Deletion of a putative cAMP phosphodiesterase of E. coli, CpdA, resulted in a slightly similar, yet more diffuse phenotype. The data demonstrate that export of cAMP via TolC is a most efficient way of E. coli to lower high concentrations of cAMP in the cell and maintain its sensitivity in changing metabolic environments.

  16. Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia

    Science.gov (United States)

    Perez, Dominique R.; Smagley, Yelena; Garcia, Matthew; Carter, Mark B.; Evangelisti, Annette; Matlawska-Wasowska, Ksenia; Winter, Stuart S.; Sklar, Larry A.; Chigaev, Alexandre

    2016-01-01

    Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3′-5′-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing. PMID:27129155

  17. Cyclic stretch enhances the expression of Toll-like Receptor 4 gene in cultured cardiomyocytes via p38 MAP kinase and NF-κB pathway

    Directory of Open Access Journals (Sweden)

    Wang Bao-Wei

    2010-03-01

    Full Text Available Abstract Background Toll-like receptor 4 (TLR4 plays an important role in innate immunity. The role of TLR4 in stretched cardiomyocytes is not known. We sought to investigate whether mechanical stretch could regulate TLR4 expression, as well as the possible molecular mechanisms and signal pathways mediating the expression of TLR4 by cyclic mechanical stretch in cardiomyocytes. Methods Neonatal Wistar rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. Western blot, real-time polymerase chain reaction, and promoter activity assay were performed. In vitro monocyte adhesion to stretched myocyte was detected. Results Cyclic stretch significantly increased TLR4 protein and mRNA expression after 2 h to 24 h of stretch. Addition of SB203580, TNF-α antibody, and p38α MAP kinase siRNA 30 min before stretch inhibited the induction of TLR4 protein. Cyclic stretch increased, while SB203580 abolished the phosphorylated p38 protein. Gel shifting assay showed significant increase of DNA-protein binding activity of NF-κB after stretch and SB203580 abolished the DNA-protein binding activity induced by cyclic stretch. DNA-binding complexes induced by cyclic stretch could be supershifted by p65 monoclonal antibody. Cyclic stretch increased TLR4 promoter activity while SB203580 and NF-κB siRNA decreased TLR4 promoter activity. Cyclic stretch increased adhesion of monocyte to cardiomyocytes while SB203580, TNF-α antibody, and TLR4 siRNA attenuated the adherence of monocyte. TNF-α and Ang II significantly increased TLR4 protein expression. Addition of losartan, TNF-α antibody, or p38α siRNA 30 min before Ang II and TNF-α stimulation significantly blocked the increase of TLR4 protein by AngII and TNF-α. Conclusions Cyclic mechanical stretch enhances TLR4 expression in cultured rat neonatal cardiomyocytes. The stretch-induced TLR4 is mediated through activation of p38 MAP kinase and NF

  18. Cyclic nucleotide specific phosphodiesterases of Leishmania major

    Directory of Open Access Journals (Sweden)

    Linder Markus

    2006-03-01

    Full Text Available Abstract Background Leishmania represent a complex of important human pathogens that belong to the systematic order of the kinetoplastida. They are transmitted between their human and mammalian hosts by different bloodsucking sandfly vectors. In their hosts, the Leishmania undergo several differentiation steps, and their coordination and optimization crucially depend on numerous interactions between the parasites and the physiological environment presented by the fly and human hosts. Little is still known about the signalling networks involved in these functions. In an attempt to better understand the role of cyclic nucleotide signalling in Leishmania differentiation and host-parasite interaction, we here present an initial study on the cyclic nucleotide-specific phosphodiesterases of Leishmania major. Results This paper presents the identification of three class I cyclic-nucleotide-specific phosphodiesterases (PDEs from L. major, PDEs whose catalytic domains exhibit considerable sequence conservation with, among other, all eleven human PDE families. In contrast to other protozoa such as Dictyostelium, or fungi such as Saccharomyces cerevisiae, Candida ssp or Neurospora, no genes for class II PDEs were found in the Leishmania genomes. LmjPDEA contains a class I catalytic domain at the C-terminus of the polypeptide, with no other discernible functional domains elsewhere. LmjPDEB1 and LmjPDEB2 are coded for by closely related, tandemly linked genes on chromosome 15. Both PDEs contain two GAF domains in their N-terminal region, and their almost identical catalytic domains are located at the C-terminus of the polypeptide. LmjPDEA, LmjPDEB1 and LmjPDEB2 were further characterized by functional complementation in a PDE-deficient S. cerevisiae strain. All three enzymes conferred complementation, demonstrating that all three can hydrolyze cAMP. Recombinant LmjPDEB1 and LmjPDEB2 were shown to be cAMP-specific, with Km values in the low micromolar range

  19. ATP and noradrenaline activate CREB in astrocytes via noncanonical Ca(2+) and cyclic AMP independent pathways.

    Science.gov (United States)

    Carriba, Paulina; Pardo, Luis; Parra-Damas, Arnaldo; Lichtenstein, Mathieu P; Saura, Carlos A; Pujol, Aurora; Masgrau, Roser; Galea, Elena

    2012-09-01

    In neurons, it is well established that CREB contributes to learning and memory by orchestrating the translation of experience into the activity-dependent (i.e., driven by neurotransmitters) transcription of plasticity-related genes. The activity-dependent CREB-triggered transcription requires the concerted action of cyclic AMP/protein kinase A and Ca(2+) /calcineurin via the CREB-regulated transcription co-activator (CRTC). It is not known, however, whether a comparable molecular sequence occurs in astrocytes, despite the unquestionable contribution of these cells to brain plasticity. Here we sought to determine whether and how ATP and noradrenaline cause CREB-dependent transcription in rat cortical astrocyte cultures. Both transmitters induced CREB phosphorylation (Western Blots), CREB-dependent transcription (CRE-luciferase reporter assays), and the transcription of Bdnf, a canonical regulator of synaptic plasticity (quantitative RT-PCR). We indentified a Ca(2+) and diacylglycerol-independent protein kinase C at the uppermost position of the cascade leading to CREB-dependent transcription. Notably, CREB-dependent transcription was partially dependent on ERK1/2 and CRTC, but independent of cyclic AMP/protein kinase A or Ca(2+) /calcineurin. We conclude that ATP and noradrenaline activate CREB-dependent transcription in cortical astrocytes via an atypical protein kinase C. It is of relevance that the signaling involved be starkly different to the one described in neurons since there is no convergence of Ca(2+) and cyclic AMP-dependent pathways on CRTC, which, moreover, exerts a modulatory rather than a central role. Our data thus point to the existence of an alternative, non-neuronal, glia-based role of CREB in plasticity.

  20. Evaluation and Control of Cyclic Variation in Spark Ignited Engines by a Thermodynic Model

    Institute of Scientific and Technical Information of China (English)

    纪常伟; 张红光

    2004-01-01

    An evaluation method of engine cyclic variation is proposed based on fuzzy mathematics concept. The degree of engine cyclic variation is divided into 4 levels: stable, slight variation, moderate variation and serious variation based on the statistic standard deviation of residual gas temperatures within the specified simulation cycles and the function of cyclic variation is also inducted for the cyclic variation control. Because the degree of engine cyclic variation can be estimated qualitatively, the effective control means can be applied to appease the undesired cyclic variation. Simulation result shows that for a very serious cyclic variation through the proper adjustment of the spark angle and the cyclic variation will disappear.

  1. Beyond Inflation:. A Cyclic Universe Scenario

    Science.gov (United States)

    Turok, Neil; Steinhardt, Paul J.

    2005-08-01

    Inflation has been the leading early universe scenario for two decades, and has become an accepted element of the successful 'cosmic concordance' model. However, there are many puzzling features of the resulting theory. It requires both high energy and low energy inflation, with energy densities differing by a hundred orders of magnitude. The questions of why the universe started out undergoing high energy inflation, and why it will end up in low energy inflation, are unanswered. Rather than resort to anthropic arguments, we have developed an alternative cosmology, the cyclic universe [1], in which the universe exists in a very long-lived attractor state determined by the laws of physics. The model shares inflation's phenomenological successes without requiring an epoch of high energy inflation. Instead, the universe is made homogeneous and flat, and scale-invariant adiabatic perturbations are generated during an epoch of low energy acceleration like that seen today, but preceding the last big bang. Unlike inflation, the model requires low energy acceleration in order for a periodic attractor state to exist. The key challenge facing the scenario is that of passing through the cosmic singularity at t = 0. Substantial progress has been made at the level of linearised gravity, which is reviewed here. The challenge of extending this to nonlinear gravity and string theory remains.

  2. Thermophoresis of cyclic oligosaccharides in polar solvents.

    Science.gov (United States)

    Eguchi, Kazuya; Niether, Doreen; Wiegand, Simone; Kita, Rio

    2016-09-01

    Cyclodextrins are cyclic oligosaccharides which are interesting as drug delivery systems, because they can be used as containers for pharmaceutical substances. We studied the Ludwig-Soret effect of [Formula: see text]-, [Formula: see text]-, [Formula: see text]- and methyl-[Formula: see text]-cyclodextrin in water and formamide by infrared thermal diffusion forced Rayleigh scattering (IR-TDFRS). In water the Soret coefficient, S T, of [Formula: see text]-, [Formula: see text]- and [Formula: see text]-cyclodextrin increases with increasing temperature and shows a sign change from negative to positive around T = 35 (°) C, while S T of methyl-[Formula: see text]-cyclodextrin is positive in the entire investigated temperature. In formamide S T-values of all cyclodextrins coincide and show a slight decrease with temperature. We discuss the obtained results and relate the S T-values to the different hydrogen bonding capabilities of the cyclodextrins and the used solvents. It turns out that the change of S T with temperature correlates with the partition coefficient, logP, which indicates that more hydrophilic substances show a more pronounced temperature sensitivity of S T. Additionally we obtained a surprising result measuring the refractive index contrast factor with temperature, [Formula: see text] of cyclodextrins in formamide, which might be explained by a complex formation between cyclodextrins and formamide.

  3. Cyclic voltammetry of fast conducting electrocatalytic films.

    Science.gov (United States)

    Costentin, Cyrille; Savéant, Jean-Michel

    2015-07-15

    In the framework of contemporary energy challenges, cyclic voltammetry is a particularly useful tool for deciphering the kinetics of catalytic films. The case of fast conducting films is analyzed, whether conduction is of the ohmic type or proceeds through rapid electron hopping. The rate-limiting factors are then the diffusion of the substrate in solution and through the film as well as the catalytic reaction itself. The dimensionless combination of the characteristics of these factors allows reducing the number of actual parameters to a maximum of two. The kinetics of the system may then be fully analyzed with the help of a kinetic zone diagram. Observing the variations of the current-potential responses with operational parameters such as film thickness, the potential scan rate and substrate concentration allows a precise assessment of the interplay between these factors and of the values of the rate controlling factors. A series of thought experiments is described in order to render the kinetic analysis more palpable.

  4. Noise-guided evolution within cyclical interactions

    CERN Document Server

    Perc, Matjaz

    2007-01-01

    We study a stochastic predator-prey model on a square lattice, where each of the six species has two superior and two inferior partners. The invasion probabilities between species depend on the predator-prey pair and are supplemented by Gaussian noise. Conditions are identified that warrant the largest impact of noise on the evolutionary process, and the results of Monte Carlo simulations are qualitatively reproduced by a four-point cluster dynamical mean-field approximation. The observed noise-guided evolution is deeply routed in short-range spatial correlations, which is supported by simulations on other host lattice topologies. Our findings are conceptually related to the coherence resonance phenomenon in dynamical systems via the mechanism of threshold duality. We also show that the introduced concept of noise-guided evolution via the exploitation of threshold duality is not limited to predator-prey cyclical interactions, but may apply to models of evolutionary game theory as well, thus indicating its app...

  5. Property Testing for Cyclic Groups and Beyond

    CERN Document Server

    Gall, Francois Le

    2011-01-01

    This paper studies the problem of testing if an input (Gamma,*), where Gamma is a finite set of unknown size and * is a binary operation over Gamma given as an oracle, is close to a specified class of groups. Friedl et al. [Efficient testing of groups, STOC'05] have constructed an efficient tester using poly(log|Gamma|) queries for the class of abelian groups. We focus in this paper on subclasses of abelian groups, and show that these problems are much harder: Omega(|Gamma|^{1/6}) queries are necessary to test if the input is close to a cyclic group, and Omega(|Gamma|^c) queries for some constant c are necessary to test more generally if the input is close to an abelian group generated by k elements, for any fixed integer k>0. We also show that knowledge of the size of the ground set Gamma helps only for k=1, in which case we construct an efficient tester using poly(log|Gamma|) queries; for any other value k>1 the query complexity remains Omega(|Gamma|^c). All our upper and lower bounds hold for both the edit...

  6. Coarsening and biodiversity in cyclically competing species

    Science.gov (United States)

    Intoy, Ben; Pleimling, Michel

    2014-03-01

    When four species compete stochastically in a cyclic way, the formation of two teams of mutually neutral partners is observed. We study through numerical simulations the extinction processes that can take place in this system both in the well mixed case as well as on different types of lattices. The different routes to extinction are revealed by the probability distribution of the domination time, i.e. the time needed for one team to fully occupy the system. If swapping is allowed between neutral partners, then the probability distribution is dominated by very long-lived states where a few very large domains persist, each domain being occupied by a mix of individuals from species that form one of the teams. Many aspects of the possible extinction scenarios are lost when only considering averaged quantities as for example the mean domination time. We also discuss some results for a model where species, that compete in Rock-Paper-Scissor fashion, have mixed strategies rather than pure strategies. We compare the case with mixed strategy to the pure strategy case and look at similarities and differences. This work is supported by the US National Science Foundation through grant DMR-1205309.

  7. The mycotoxin definition reconsidered towards fungal cyclic depsipeptides.

    Science.gov (United States)

    Taevernier, Lien; Wynendaele, Evelien; De Vreese, Leen; Burvenich, Christian; De Spiegeleer, Bart

    2016-04-01

    Currently, next to the major classes, cyclic depsipeptides beauvericin and enniatins are also positioned as mycotoxins. However, as there are hundreds more fungal cyclic depsipeptides already identified, should these not be considered as mycotoxins as well? The current status of the mycotoxin definition revealed a lack of consistency, leading to confusion about what compounds should be called mycotoxins. Because this is of pivotal importance in risk assessment prioritization, a clear and quantitatively expressed mycotoxin definition is proposed, based on data of widely accepted mycotoxins. Finally, this definition is applied to a set of fungal cyclic depsipeptides, revealing that some of these should indeed be considered as mycotoxins.

  8. Constacyclic and cyclic codes over finite chain rings

    Institute of Scientific and Technical Information of China (English)

    QIAN Jian-fa; MA Wen-ping

    2009-01-01

    The problem of Gray image of constacyclic code over finite chain ring is studied. A Gray map between codes over a finite chain ring and a finite field is defined. The Gray image of a linear constacyclic code over the finite chain ring is proved to be a distance invariant quasi-cyclic code over the finite field. It is shown that every code over the finite field, which is the Gray image of a cyclic code over the finite chain ring, is equivalent to a quasi-cyclic code.

  9. Laterally cyclic loading of monopile in dense sand

    DEFF Research Database (Denmark)

    Klinkvort, Rasmus Tofte; Hededal, Ole; Svensson, M.

    2011-01-01

    the loading conditions. In these tests the load conditions are controlled by two load characteristics, one controlling the level of the cyclic loading and one controlling the characteristic of the cyclic loading. The centrifuge tests were performed in dense dry sand on a pile with prototype dimensions......In order to investigate the response from laterally cyclic loading of monopiles a large centrifuge tests series is ongoing at the Technical University of Denmark (DTU). This paper will present some of the tests carried out with a focus on the influence of accumulation of rotation when changing...

  10. Centrifuge modelling of a laterally cyclic loaded pile

    DEFF Research Database (Denmark)

    Klinkvort, Rasmus Tofte; Leth, Caspar Thrane; Hededal, Ole

    2010-01-01

    A total number of 9 static and 6 cyclic centrifuge tests on laterally loaded piles in very dense, dry sand was erformed. The prototype dimensions of the piles were 1 meter in diameter and penetration depths varying from 6 to 10 meters. The static tests were used to investigate the initial subgrade...... reaction modulus and as a reference for cyclic tests. For the cyclic tests the accumulation of deflections and the change in secant stiffness of the soil from repetitive loading were investigated. From all the tests carried out accumulations of deflections were seen. rom the centrifuge tests it was seen...

  11. CRP-Cyclic AMP Regulates the Expression of Type 3 Fimbriae via Cyclic di-GMP in Klebsiella pneumoniae.

    Science.gov (United States)

    Lin, Ching-Ting; Lin, Tien-Huang; Wu, Chien-Chen; Wan, Lei; Huang, Chun-Fa; Peng, Hwei-Ling

    2016-01-01

    Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP) signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of PmrkA were increased in Δcrp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP)-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of PmrkHI and PmrkJ were decreased in ΔlacZΔcrp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Δcrp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of PmrkHI in the ΔlacZΔcrp strain was diminished in ΔlacZΔcrpΔmrkHI, but increased in the ΔlacZΔcrpΔmrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Δcrp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP-cAMP and c

  12. Structural Flexibility and Conformation Features of Cyclic Dinucleotides in Aqueous Solutions.

    Science.gov (United States)

    Che, Xing; Zhang, Jun; Zhu, Yanyu; Yang, Lijiang; Quan, Hui; Gao, Yi Qin

    2016-03-17

    Cyclic dinucleotides are able to trigger the innate immune system by activating STING. It was found that the binding affinity of asymmetric 2'3'-cGAMP to symmetric dimer of STING is 3 orders of magnitude higher than that of the symmetric 3'3'-cyclic dinucleotides. Such a phenomenon has not been understood yet. Here we show that the subtle changes in phosphodiester linkage of CDNs lead to their distinct structural properties which correspond to the varied binding affinities. 2'-5' and/or 3'-5' linked CDNs adopt specific while different types of ribose puckers and backbone conformations. That ribose conformations and base types have different propensities for anti or syn glycosidic conformations further affects the overall flexibility of CDNs. The counterbalance between backbone ring tension and electrostatic repulsion, both affected by the ring size, also contributes to the different flexibility of CDNs. Our calculations reveal that the free energy cost for 2'3'-cGAMP to adopt the STING-bound structure is smaller than that for 3'3'-cGAMP and cyclic-di-GMP. These findings may serve as a reference for design of CDN-analogues as vaccine adjuvants. Moreover, the cyclization pattern of CDNs closely related to their physiological roles suggests the importance of understanding structural properties in the study of protein-ligand interactions.

  13. Pneumatic pressure bioreactor for cyclic hydrostatic stress application: mechanobiology effects on periodontal ligament cells.

    Science.gov (United States)

    Wenger, Karl H; El-Awady, Ahmed R; Messer, Regina L W; Sharawy, Mohamed M; White, Greg; Lapp, Carol A

    2011-10-01

    A bioreactor system was developed to provide high-amplitude cyclic hydrostatic compressive stress (cHSC) using compressed air mixed commercially as needed to create partial pressures of oxygen and carbon dioxide appropriate for the cells under investigation. Operating pressures as high as 300 psi are achievable in this system at cyclic speeds of up to 0.2 Hz. In this study, ligamentous fibroblasts from human periodontal ligaments (n = 6) were compressed on two consecutive days at 150 psi for 3 h each day, and the mRNA for families of extracellular matrix protein and protease isoforms was evaluated by real-time PCR array. Several integrins were significantly upregulated, most notably alpha-3 (6.4-fold), as was SPG7 (12.1-fold). Among the collagens, Col8a1 was highly upregulated at 53.5-fold, with Col6a1, Col6a2, and Col7a1 also significantly upregulated 4.4- to 8.5-fold. MMP-1 was the most affected at 122.9-fold upregulation. MMP-14 likewise increased 17.8-fold with slight reductions for the gelatinases and a significant increase of TIMP-2 at 5.8-fold. The development of this bioreactor system and its utility in characterizing periodontal ligament fibroblast mechanobiology in intermediate-term testing hold promise for better simulating the conditions of the musculoskeletal system and the large cyclic compressive stresses joints may experience in gait, exertion, and mastication.

  14. Early endosomal escape of a cyclic cell-penetrating peptide allows effective cytosolic cargo delivery.

    Science.gov (United States)

    Qian, Ziqing; LaRochelle, Jonathan R; Jiang, Bisheng; Lian, Wenlong; Hard, Ryan L; Selner, Nicholas G; Luechapanichkul, Rinrada; Barrios, Amy M; Pei, Dehua

    2014-06-24

    Cyclic heptapeptide cyclo(FΦRRRRQ) (cFΦR4, where Φ is l-2-naphthylalanine) was recently found to be efficiently internalized by mammalian cells. In this study, its mechanism of internalization was investigated by perturbing various endocytic events through the introduction of pharmacologic agents and genetic mutations. The results show that cFΦR4 binds directly to membrane phospholipids, is internalized into human cancer cells through endocytosis, and escapes from early endosomes into the cytoplasm. Its cargo capacity was examined with a wide variety of molecules, including small-molecule dyes, linear and cyclic peptides of various charged states, and proteins. Depending on the nature of the cargos, they may be delivered by endocyclic (insertion of cargo into the cFΦR4 ring), exocyclic (attachment of cargo to the Gln side chain), or bicyclic approaches (fusion of cFΦR4 and cyclic cargo rings). The overall delivery efficiency (i.e., delivery of cargo into the cytoplasm and nucleus) of cFΦR4 was 4-12-fold higher than those of nonaarginine, HIV Tat-derived peptide, or penetratin. The higher delivery efficiency, coupled with superior serum stability, minimal toxicity, and synthetic accessibility, renders cFΦR4 a useful transporter for intracellular cargo delivery and a suitable system for investigating the mechanism of endosomal escape.

  15. Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium.

    Science.gov (United States)

    Altenhofen, W; Ludwig, J; Eismann, E; Kraus, W; Bönigk, W; Kaupp, U B

    1991-11-01

    Cyclic nucleotide-gated ionic channels in photoreceptors and olfactory sensory neurons are activated by binding of cGMP or cAMP to a receptor site on the channel polypeptide. By site-directed mutagenesis and functional expression of bovine wild-type and mutant channels in Xenopus oocytes, we have tested the hypothesis that an alanine/threonine difference in the cyclic nucleotide-binding site determines the specificity of ligand binding, as has been proposed for cyclic nucleotide-dependent protein kinases [Weber, I.T., Shabb, J.B. & Corbin, J.D. (1989) Biochemistry 28, 6122-6127]. The wild-type olfactory channel is approximately 25-fold more sensitive to both cAMP and cGMP than the wild-type rod photoreceptor channel, and both channels are 30- to 40-fold more sensitive to cGMP than to cAMP. Substitution of the respective threonine by alanine in the rod photoreceptor and olfactory channels decreases the cGMP sensitivity of channel activation 30-fold but little affects activation by cAMP. Substitution of threonine by serine, an amino acid that also carries a hydroxyl group, even improves cGMP sensitivity of the wild-type channels 2- to 5-fold. We conclude that the hydroxyl group of Thr-560 (rod) and Thr-537 (olfactory) forms an additional hydrogen bond with cGMP, but not cAMP, and thereby provides the structural basis for ligand discrimination in cyclic nucleotide-gated channels.

  16. Synthesis and Catalytic Activity of Two New Cyclic Tetraaza Ligands

    Directory of Open Access Journals (Sweden)

    Burkhard König

    2003-05-01

    Full Text Available Two new chiral cyclic tetraaza ligands were synthesized and characterized. Their catalytic activity was tested in the asymmetric addition of diethylzinc to benzaldehyde. The expected secondary alcohol was obtained in moderate yields, but with very low enantioselectivity.

  17. Cyclical mastalgia: Prevalence and associated determinants in Hamadan City, Iran

    Directory of Open Access Journals (Sweden)

    Fatemeh Shobeiri

    2016-03-01

    Conclusions: Most of women with breast discomfort suffered cyclical mastalgia which severity can be determined by advanced age, age of marriage, history of abortion and history of premenstrual syndrome, but inversely by oral contraceptive use and exercise activity.

  18. A constitutive model for unsaturated cemented soils under cyclic loading

    CERN Document Server

    Yang, C; Pereira, Jean-Michel; Huang, M S

    2008-01-01

    On the basis of plastic bounding surface model, the damage theory for structured soils and unsaturated soil mechanics, an elastoplastic model for unsaturated loessic soils under cyclic loading has been elaborated. Firstly, the description of bond degradation in a damage framework is given, linking the damage of soil's structure to the accumulated strain. The Barcelona Basic Model (BBM) was considered for the suction effects. The elastoplastic model is then integrated into a bounding surface plasticity framework in order to model strain accumulation along cyclic loading, even under small stress levels. The validation of the proposed model is conducted by comparing its predictions with the experimental results from multi-level cyclic triaxial tests performed on a natural loess sampled beside the Northern French railway for high speed train and about 140 km far from Paris. The comparisons show the capabilities of the model to describe the behaviour of unsaturated cemented soils under cyclic loading.

  19. A Novel Cyclic Catalytic Reformer for Hydrocarbon Fuels Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposed Small Business Innovative Research (SBIR) Phase I addresses development of a compact reformer system based on a cyclic partial oxidation (POx)...

  20. Association of Marijuana Use and Cyclic Vomiting Syndrome

    Directory of Open Access Journals (Sweden)

    Mithun B. Pattathan

    2012-06-01

    Full Text Available Cannabis use has become one of the most commonly abused drugs in the world. It is estimated that each year 2.6 million individuals in the USA become new users and most are younger than 19 years of age. Reports describe marijuana use as high as 40–50% in male Cyclic Vomiting Syndrome patients. It is this interest in cannabis in the World, coupled with recognition of a cyclic vomiting illness associated with its chronic use that beckons a review of the most current articles, as well as a contribution from our own experiences in this area. The similarities we have demonstrated for both cannibinoid hyperemesis syndrome and cyclic vomiting make the case that cannibinoid hyperemesis syndrome is a subset of patients who have the diagnoses of cyclic vomiting syndrome and the role of marijuana should always be considered in the diagnosis of CVS, particularly in males.

  1. Resistance to cyclic loading of teeth restored with posts

    DEFF Research Database (Denmark)

    Sahafi, A; Peutzfeldt, A; Ravnholt, G

    2005-01-01

    This in vitro study evaluated the effect of presence of post, presence of core, and of shape, type, and surface treatment of posts on resistance to cyclic loading of crowned human teeth. For all teeth, crowns designed without ferrule were cast in sterling silver and luted with resin cement (Panavia...... F). Each tooth underwent cyclic loading of 600 N at two loads per second until failure. Teeth that had only been crowned showed significantly higher resistance to cyclic loading than teeth with cores or with post and cores. No significant differences were found between teeth restored with cores only...... or with post and cores, irrespective of surface-treatment of the posts. Teeth restored with parallel-sided cast post (ParaPost XP) and cores showed significantly higher resistance to cyclic loading than teeth with either tapered cast posts or untreated prefabricated posts of titanium alloy (ParaPost XH...

  2. Cyclic Family Symmetry and Lepton Hierarchy in Supersymmetry

    OpenAIRE

    Du, Dongsheng; Chun LIU

    1995-01-01

    A cyclic symmetry among the left-handed doublets of the three families is proposed. This symmetry can naturally result in a realistic hierarchical pattern of the fermion masses within the framework of supersymmetry with nonvanishing sneutrino vacuum expectation values.

  3. Cyclic Voltammetric Responses of Nitrate Reductase on Chemical Modified Electrodes

    Institute of Scientific and Technical Information of China (English)

    YaRuSONG; HuiBoSHAO; 等

    2002-01-01

    Electrochemistry of nitrate reductases (NR) incorporated into 2-aminoethanethiol self-assembled on the gold electrode and polyacrylamide cast on the pyrolytic graphite electrode was examined. NR on chemical modified electrode showed electrochemical cyclic voltammetric responses in phosphate buffers.

  4. Cyclical Cohabitation Among Unmarried Parents in Fragile Families.

    Science.gov (United States)

    Nepomnyaschy, Lenna; Teitler, Julien

    2013-10-01

    Building on past research suggesting that cohabitation is an ambiguous family form, the authors examined an understudied residential pattern among unmarried parents: cyclical cohabitation, in which parents have multiple cohabitation spells with each other. Using 9 years of panel data from the Fragile Families and Child Wellbeing Study (N = 2,084), they found that 10% of all parents with nonmarital births, and nearly a quarter of those living together when the child is 9 years old, are cyclical cohabitors. Cyclically cohabiting mothers reported more material hardships than mothers in most other relationship patterns but also reported more father involvement with children. On all measures of child well-being, except grade retention, children of cyclically cohabiting parents fared no worse than children of stably cohabiting biological parents and did not differ significantly from any other group.

  5. The antimycin A-sensitive pathway of cyclic electron flow

    DEFF Research Database (Denmark)

    Labs, Mathias; Rühle, Thilo; Leister, Dario Michael

    2016-01-01

    severe effects on plant growth. One of the two pathways mediating cyclic electron flow can be inhibited by antimycin A, a chemical that has also widely been used to characterize the mitochondrial respiratory chain. For the characterization of cyclic electron flow, antimycin A has been used since 1963......Cyclic electron flow has puzzled and divided the field of photosynthesis researchers for decades. This mainly concerns the proportion of its overall contribution to photosynthesis, as well as its components and molecular mechanism. Yet, it is irrefutable that the absence of cyclic electron flow has......, when ferredoxin was found to be the electron donor of the pathway. In 2013, antimycin A was used to identify the PGRL1/PGR5 complex as the ferredoxin:plastoquinone reductase completing the last puzzle piece of this pathway. The controversy has not ended, and here, we review the history of research...

  6. Cyclical Cushing's syndrome due to an atypical thymic carcinoid

    NARCIS (Netherlands)

    Meinardi, [No Value; van den Berg, G; Wolffenbuttel, BHR; Kema, IP; Dullaart, RPF

    A 43-year-old man presented with fluctuating symptoms of weight gain, shortness of breath, pretibial oedema, associated with anxiety and memory disturbances. Laboratory investigation revealed an adrenocorticotropin (ACTH)-dependent cyclical Cushing's syndrome characterised by remarkable variations

  7. Cyclic Redundancy Checking (CRC) Accelerator for Embedded Processor Datapaths

    National Research Council Canada - National Science Library

    Abdul Rehman Buzdar; Liguo Sun; Rao Kashif; Muhammad Waqar Azhar; Muhammad Imran Khan

    2017-01-01

    We present the integration of a multimode Cyclic Redundancy Checking (CRC) accelerator unit with an embedded processor datapath to enhance the processor performance in terms of execution time and energy efficiency...

  8. Gauss Sum of Index 4: (2) Non-cyclic Case

    Institute of Scientific and Technical Information of China (English)

    Jing YANG; Shi Xin LUO; Ke Qin FENG

    2006-01-01

    Assume that m≥2,p is a prime number,(m,p(p-1))=1,-1(∈)(∈)((Z)/m(Z))* and [((z)/m(Z)*:]=4.In this paper,we calculate the value of Gauss sum G(χ)=∑x(F)*qχ(x)ζTp(x) over (F)q,where q=pf,(f)=(ψ)(m)/4,χ is a multiplicative character of (F)q and T is the trace map from (F)q to (F)p.Under our assumptions,C(χ) belongs to the decomposition field K of p in (Q)(ζm) and K is an imaginary quartic abelian number field.When the Galois group Gal(K/(Q)) is cyclic,we have studied this cyclic case in another paper:"Gauss sums of index four:(1) cyclic case" (accepted by Acta Mathematica Sinica,2003).In this paper we deal with the non-cyclic case.

  9. Properties of Surface Cyclic Oligomers Present on Polyester Fiber

    Institute of Scientific and Technical Information of China (English)

    郑敏; 宋心远

    2003-01-01

    The effects of different treatments, such as dry heat,wet heat, solvent vapor and ultrasonic, on properties of the cyclic oligomers on the surface of polyester fiber are studied. The components of surface oligomers are analyzed through Thin-Layer Chromatograph. The result shows that: all of the treatments, especially solvent vapor treatment, can significantly increase the content of surface cyclic oligomers. The content of cyclic trimer is increased more considerably than other oligomers. Moreover, the morphology and the distribution of surface cyclic oligomers are also different from different treatments: Dry heat and wet heat cause larger polygonal solids distributed evenly on the surface of fiber; solvent vapor makes fiber surface exhibit irregular rodlike crystal shapes randomly; ultrasonic treatment induces some obscure and smaller deposits on the surface of fiber.

  10. The Cyclical Relationship Approach in Teaching Basic Accounting Principles.

    Science.gov (United States)

    Golen, Steven

    1981-01-01

    Shows how teachers can provide a more meaningful presentation of various accounting principles by illustrating them through a cyclical relationship approach. Thus, the students see the entire accounting relationship as a result of doing business. (CT)

  11. Cyclic viscoelasticity and viscoplasticity of polypropylene/clay nanocomposites

    DEFF Research Database (Denmark)

    Drozdov, Aleksey; Christiansen, Jesper de Claville; Hog Lejre, Anne-Lise

    2012-01-01

    Observations are reported in tensile relaxation tests under stretching and retraction on poly-propylene/clay nanocomposites with various contents of filler. A two-phase constitutive model is developed in cyclic viscoelasticity and viscoplasticity of hybrid nanocomposites. Adjustable parameters...

  12. Safety Discrete Event Models for Holonic Cyclic Manufacturing Systems

    Science.gov (United States)

    Ciufudean, Calin; Filote, Constantin

    In this paper the expression “holonic cyclic manufacturing systems” refers to complex assembly/disassembly systems or fork/join systems, kanban systems, and in general, to any discrete event system that transforms raw material and/or components into products. Such a system is said to be cyclic if it provides the same sequence of products indefinitely. This paper considers the scheduling of holonic cyclic manufacturing systems and describes a new approach using Petri nets formalism. We propose an approach to frame the optimum schedule of holonic cyclic manufacturing systems in order to maximize the throughput while minimize the work in process. We also propose an algorithm to verify the optimum schedule.

  13. Coping with cyclic oxygen availability: evolutionary aspects.

    Science.gov (United States)

    Flück, Martin; Webster, Keith A; Graham, Jeffrey; Giomi, Folco; Gerlach, Frank; Schmitz, Anke

    2007-10-01

    Both the gradual rise in atmospheric oxygen over the Proterozoic Eon as well as episodic fluctuations in oxygen over several million-year time spans during the Phanerozoic Era, have arguably exerted strong selective forces on cellular and organismic respiratory specialization and evolution. The rise in atmospheric oxygen, some 2 billion years after the origin of life, dramatically altered cell biology and set the stage for the appearance of multicelluar life forms in the Vendian (Ediacaran) Period of the Neoproterozoic Era. Over much of the Paleozoic, the level of oxygen in the atmosphere was near the present atmospheric level (21%). In the Late Paleozoic, however, there were extended times during which the level of atmospheric oxygen was either markedly lower or markedly higher than 21%. That these Paleozoic shifts in atmospheric oxygen affected the biota is suggested by the correlations between: (1) Reduced oxygen and the occurrences of extinctions, a lowered biodiversity and shifts in phyletic succession, and (2) During hyperoxia, the corresponding occurrence of phenomena such as arthropod gigantism, the origin of insect flight, and the evolution of vertebrate terrestriality. Basic similarities in features of adaptation to hyopoxia, manifest in living organisms at levels ranging from genetic and cellular to physiological and behavioral, suggest the common and early origin of a suite of adaptive mechanisms responsive to fluctuations in ambient oxygen. Comparative integrative approaches addressing the molecular bases of phenotypic adjustments to cyclic oxygen fluctuation provide broad insight into the incremental steps leading to the early evolution of homeostatic respiratory mechanisms and to the specialization of organismic respiratory function.

  14. Cyclic Benzimidazole Derivatives and Their Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Karminski-Zamola, G.

    2008-06-01

    Full Text Available Over the past years benzimidazole derivatives are one of the most extensively studied classes of heterocyclic compounds, and have received much attention from synthetic organic as well as medicinal chemists, because of their well known biological activities and their applications in several areas as materials in electronics, in electrochemistry as anticorrosive agents, as polymers or optical materials and fluorescent tags in DNA sequencing. The structure of vitamin B12, as an example, contains a benzimidazole group. Compounds containing benzimidazole nuclei show anticancer, antineoplastic, antiinfective, antibacterial, antifungal and many others activities. Due to the structural similarity of benzimidazole nuclei with some naturally occurring compounds such as purine, they can easily interact with biomolecules of the living systems. The introduction of an additional substituent on the benzimidazole nuclei has been increasing attention in the expectation that such changes could potentially affect the interaction of the molecules with biological targets. Fused cyclic benzimidazole derivatives, as benzimidazo[1,2-a]quinolines,benzimidazo[1,2-c]quinazolines, benzimidazo[2,1-b]isoquinolines and many others, have also interesting biological activities and most of them are very good anticancer agents.DNA is the molecular target of many anticancer drugs in clinical use and development. Compounds which can bind to DNA with intercalative or non-intercalative mechanism play a major role in biological processes such as gene transcription or DNA replication. Benzoannulated benzimidazole analogues contain a planar chromophore and have the ability to become inserted between adjacent base pairs of DNA double helix. Intercalators are recognized as one of the most important classes of anticancer agents. So an understanding of the drug-DNA interactions is a promising approach to developing novel reagents and plays a key role in pharmacology today.

  15. Mechanical control of cyclic AMP signalling and gene transcription through integrins

    Science.gov (United States)

    Meyer, C. J.; Alenghat, F. J.; Rim, P.; Fong, J. H.; Fabry, B.; Ingber, D. E.

    2000-01-01

    This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

  16. Deformation localization and cyclic strength in polycrystalline molybdenum

    Energy Technology Data Exchange (ETDEWEB)

    Sidorov, O.T.; Rakshin, A.F.; Fenyuk, M.I.

    1983-06-01

    Conditions of deformation localization and its interrelation with cyclic strength in polycrystalline molybdenum were investigated. A fatigue failure of polycrystalline molybdenum after rolling and in an embrittled state reached by recrystallization annealing under cyclic bending at room temperature takes place under nonuniform distribution of microplastic strain resulting in a temperature rise in separate sections of more than 314 K. More intensive structural changes take place in molybdenum after rolling than in recrystallized state.

  17. Defect agglomeration in ferroelectric ceramics under cyclic electric field

    Institute of Scientific and Technical Information of China (English)

    GENG LiMing; YANG Wei

    2008-01-01

    The agglomeration of point defects in ferroelectric ceramics could be driven by repeated domain switching under cyclic electric field. The evolution equation of pore concentration under cyclic electric field is derived, with the help of a relation between the pore concentration and the extent of pore agglomeration. The results of the simulation agree quantitatively with the experimental data. An integrated framework about the mechanisms of electrically induced fatigue is proposed, which links the mechanisms at different scales.

  18. Cyclical Long-term Unemployment, Skill Loss, and Monetary Policy

    OpenAIRE

    2012-01-01

    Movements in long-term unemployment (LTU) exhibit a substantial cyclical component. I develop a business cycle model featuring labor market frictions and skill loss during unemployment to capture various stylized facts about the cyclical behavior of long-term unemployment. I find that the skill loss mechanism helps reproduce negative duration dependence, high persistence in unemployment and output, volatility patterns across macroeconomic variables and the behavior of the incidence of LTU aro...

  19. Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

    LENUS (Irish Health Repository)

    Noctor, E

    2015-06-01

    Cushing\\'s disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing\\'s syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing\\'s disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia.

  20. Recovery of Compressively Sampled Sparse Signals using Cyclic Matching Pursuit

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Christensen, Mads Græsbøll; Gribonval, Rémi

    We empirically show how applying a pure greedy algorithm cyclically can recover compressively sampled sparse signals as well as other more computationally complex approaches, such as orthogonal greedy algorithms, iterative thresholding, and $\\ell_1$-minimization.......We empirically show how applying a pure greedy algorithm cyclically can recover compressively sampled sparse signals as well as other more computationally complex approaches, such as orthogonal greedy algorithms, iterative thresholding, and $\\ell_1$-minimization....

  1. CYCLIC CODES OVER THE RING Zp2 OF LENGTH pe

    Institute of Scientific and Technical Information of China (English)

    Shi Minjia; Zhu Shixin

    2008-01-01

    The study of cyclic codes over rings has generated a lot of public interest. In this paper,we study cyclic codes and their dual codes over the ring Zp2 of length pe,and find a set of generators for these codes. The ranks and minimal generator sets of these codes are studied as well,which play an important role in decoding and determining the distance distribution of codes.

  2. Towards an incremental maintenance of cyclic association rules

    CERN Document Server

    Ahmed, Eya ben

    2010-01-01

    Recently, the cyclic association rules have been introduced in order to discover rules from items characterized by their regular variation over time. In real life situations, temporal databases are often appended or updated. Rescanning the whole database every time is highly expensive while existing incremental mining techniques can efficiently solve such a problem. In this paper, we propose an incremental algorithm for cyclic association rules maintenance. The carried out experiments of our proposal stress on its efficiency and performance.

  3. Distributed consensus on minimum time rendezvous via cyclic alternating projection

    OpenAIRE

    Hu, Chunhe; Chen, Zongji

    2014-01-01

    In this paper, we propose a distributed algorithm to solve planar minimum time multi-vehicle rendezvous problem with non-identical velocity constraints on cyclic digraph (topology). Motivated by the cyclic alternating projection method that can compute a point's projection on the intersection of some convex sets, we transform the minimum time rendezvous problem into finding the distance between the position plane and the intersection of several second-order cones in position-time space. The d...

  4. An affinity pull-down approach to identify the plant cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth

    2013-09-03

    Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.

  5. Asymmetric synthesis of gem-diaryl substituted cyclic sulfamidates and sulfamides by rhodium-catalyzed arylation of cyclic ketimines.

    Science.gov (United States)

    Nishimura, Takahiro; Ebe, Yusuke; Fujimoto, Hiroto; Hayashi, Tamio

    2013-06-18

    Asymmetric addition of arylboronates to aryl-substituted cyclic ketimines proceeded in the presence of a rhodium catalyst coordinated with a chiral diene ligand to give high yields of sulfamidates and sulfamides with high enantioselectivity (up to 99% ee).

  6. Effect of cyclic torsional preloading on cyclic fatigue resistance of ProTaper Next and Mtwo nickel–titanium instruments

    Directory of Open Access Journals (Sweden)

    Eugenio Pedullà

    2015-06-01

    Conclusions: Torsional preloads reduced the cyclic fatigue resistance of M-wire and conventional (as ProTaper Next and Mtwo NiTi rotary instruments except for Mtwo with 25% or 50% of torsional preloading.

  7. On the resolutions of cyclic Steiner triple systems with small parameters

    Directory of Open Access Journals (Sweden)

    Svetlana Topalova

    2016-09-01

    Full Text Available The paper presents useful invariants of resolutions of cyclic $STS(v$ with $v\\le 39$, namely of all resolutions of cyclic $STS(15$, $STS(21$ and $STS(27$, of the resolutions with nontrivial automorphisms of cyclic $STS(33$ and of resolutions with automorphisms of order $13$  of cyclic $STS(39$.

  8. Effect of Surgical Removal of Endometriomas on Cyclic and Non-cyclic Pelvic Pain

    Directory of Open Access Journals (Sweden)

    Murat Api

    2015-07-01

    Full Text Available Background: Endometriosis is a complex disease with a spectrum of pain symptoms from mild dysmenorrhea to debilitating pelvic pain. There is no concrete evidence in the literature whether endometriotic cyst per se, causes pain spectrum related to the disease. The aim of the present study was to evaluate the effect of surgical removal of endometriomas on pain symptoms. Materials and Methods: In this prospective, observational, before-after study, which was conducted between March 2012 and January 2013 in Training and Research Hospital,Adana, Turkey, a total of 23 patients including 16 sexually active and 7 virgin symptomatic women were questioned for non-cyclic pelvic pain (NCPP, intensity of the NCPP, presence of cyclic dysmenorrhea, and dyspareunia before and after the endometrioma operation. Participants who were sonographically diagnosed and later pathologically confirmed as having endometrioma without sign and symptoms of deep infiltrative endometriosis (DIE were also questioned for pain symptoms before and after the laparoscopic removal of cyst wall. Patients with intraabdominal adhesions, history of pelvic inflammatory disease, and pathological diagnosis other than endometrioma were excluded. No ancillary procedures were applied for pain management, but if pain was present, pelvic peritoneal endometriotic lesions were ablated beside the removal of ovarian endometriotic cysts. Results: Out of 23 cases with endometrioma, 91 and 78% reported to have NCPP and dysmenorrhea, respectively, before the operation, while 60 and 48%, respectively, after the operation (McNemar’s test, P=0.016 for both figures. Among the sexually active cases, 31% (5/16 had dyspareunia before the operation and only 1 case reported the pain relief after the operation (McNemar’s test, P=1. Intensity of NCPP were reported to be none (8.7%, moderate (21.7%, severe (56.5% and unbearable (13% before the operation and decreased to none (43.5%, mild (43.5%, moderate (4

  9. 8-Bromo-cyclic inosine diphosphoribose: towards a selective cyclic ADP-ribose agonist

    Science.gov (United States)

    Kirchberger, Tanja; Moreau, Christelle; Wagner, Gerd K.; Fliegert, Ralf; Siebrands, Cornelia C.; Nebel, Merle; Schmid, Frederike; Harneit, Angelika; Odoardi, Francesca; Flügel, Alexander; Potter, Barry V. L.; Guse, Andreas H.

    2009-01-01

    cADPR (cyclic ADP-ribose) is a universal Ca2+ mobilizing second messenger. In T-cells cADPR is involved in sustained Ca2+ release and also in Ca2+ entry. Potential mechanisms for the latter include either capacitative Ca2+ entry, secondary to store depletion by cADPR, or direct activation of the non-selective cation channel TRPM2 (transient receptor potential cation channel, subfamily melastatin, member 2). Here we characterize the molecular target of the newly-described membrane-permeant cADPR agonist 8-Br-N1-cIDPR (8-bromo-cyclic IDP-ribose). 8-Br-N1-cIDPR evoked Ca2+ signalling in the human T-lymphoma cell line Jurkat and in primary rat T-lymphocytes. Ca2+ signalling induced by 8-Br-N1-cIDPR consisted of Ca2+ release and Ca2+ entry. Whereas Ca2+ release was sensitive to both the RyR (ryanodine receptor) blocker RuRed (Ruthenium Red) and the cADPR antagonist 8-Br-cADPR (8-bromo-cyclic ADP-ribose), Ca2+ entry was inhibited by the Ca2+ entry blockers Gd3+ (gadolinium ion) and SKF-96365, as well as by 8-Br-cADPR. To unravel a potential role for TRPM2 in sustained Ca2+ entry evoked by 8-Br-N1-cIDPR, TRPM2 was overexpressed in HEK (human embryonic kidney)-293 cells. However, though activation by H2O2 was enhanced dramatically in those cells, Ca2+ signalling induced by 8-Br-N1-cIDPR was almost unaffected. Similarly, direct analysis of TRPM2 currents did not reveal activation or co-activation of TRPM2 by 8-Br-N1-cIDPR. In summary, the sensitivity to the Ca2+ entry blockers Gd3+ and SKF-96365 is in favour of the concept of capacitative Ca2+ entry, secondary to store depletion by 8-Br-N1-cIDPR. Taken together, 8-Br-N1-cIDPR appears to be the first cADPR agonist affecting Ca2+ release and secondary Ca2+ entry, but without effect on TRPM2. PMID:19492987

  10. Co-crystal structures of PKG Iβ (92-227 with cGMP and cAMP reveal the molecular details of cyclic-nucleotide binding.

    Directory of Open Access Journals (Sweden)

    Jeong Joo Kim

    Full Text Available Cyclic GMP-dependent protein kinases (PKGs are central mediators of the NO-cGMP signaling pathway and phosphorylate downstream substrates that are crucial for regulating smooth muscle tone, platelet activation, nociception and memory formation. As one of the main receptors for cGMP, PKGs mediate most of the effects of cGMP elevating drugs, such as nitric oxide-releasing agents and phosphodiesterase inhibitors which are used for the treatment of angina pectoris and erectile dysfunction, respectively.We have investigated the mechanism of cyclic nucleotide binding to PKG by determining crystal structures of the amino-terminal cyclic nucleotide-binding domain (CNBD-A of human PKG I bound to either cGMP or cAMP. We also determined the structure of CNBD-A in the absence of bound nucleotide. The crystal structures of CNBD-A with bound cAMP or cGMP reveal that cAMP binds in either syn or anti configurations whereas cGMP binds only in a syn configuration, with a conserved threonine residue anchoring both cyclic phosphate and guanine moieties. The structure of CNBD-A in the absence of bound cyclic nucleotide was similar to that of the cyclic nucleotide bound structures. Surprisingly, isothermal titration calorimetry experiments demonstrated that CNBD-A binds both cGMP and cAMP with a relatively high affinity, showing an approximately two-fold preference for cGMP.Our findings suggest that CNBD-A binds cGMP in the syn conformation through its interaction with Thr193 and an unusual cis-peptide forming residues Leu172 and Cys173. Although these studies provide the first structural insights into cyclic nucleotide binding to PKG, our ITC results show only a two-fold preference for cGMP, indicating that other domains are required for the previously reported cyclic nucleotide selectivity.

  11. Cannabinoid receptor type 1- and 2-mediated increase in cyclic AMP inhibits T cell receptor-triggered signaling.

    Science.gov (United States)

    Börner, Christine; Smida, Michal; Höllt, Volker; Schraven, Burkhart; Kraus, Jürgen

    2009-12-18

    The aim of this study was to characterize inhibitory mechanisms on T cell receptor signaling mediated by the cannabinoid receptors CB1 and CB2. Both receptors are coupled to G(i/o) proteins, which are associated with inhibition of cyclic AMP formation. In human primary and Jurkat T lymphocytes, activation of CB1 by R(+)-methanandamide, CB2 by JWH015, and both by Delta9-tetrahydrocannabinol induced a short decrease in cyclic AMP lasting less than 1 h. However, this decrease was followed by a massive (up to 10-fold) and sustained (at least up to 48 h) increase in cyclic AMP. Mediated by the cyclic AMP-activated protein kinase A and C-terminal Src kinase, the cannabinoids induced a stable phosphorylation of the inhibitory Tyr-505 of the leukocyte-specific protein tyrosine kinase (Lck). By thus arresting Lck in its inhibited form, the cannabinoids prevented the dephosphorylation of Lck at Tyr-505 in response to T cell receptor activation, which is necessary for the subsequent initiation of T cell receptor signaling. In this way the cannabinoids inhibited the T cell receptor-triggered signaling, i.e. the activation of the zeta-chain-associated protein kinase of 70 kDa, the linker for activation of T cells, MAPK, the induction of interleukin-2, and T cell proliferation. All of the effects of the cannabinoids were blocked by the CB1 and CB2 antagonists AM281 and AM630. These findings help to better understand the immunosuppressive effects of cannabinoids and explain the beneficial effects of these drugs in the treatment of T cell-mediated autoimmune disorders like multiple sclerosis.

  12. Adjuvant radiation therapy compared with cyclic chemotherapy in patients with mammary carcinoma. II. Changes of mitogen responses of blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Strender, L.E.; Blomgren, H.; Wasserman, J.; Petrini, B.; Baral, E. (Karolinska Sjukhuset, Stockholm (Sweden))

    1981-01-01

    Blood lymphocyte reactivity to purified protein derivative of tuberculin (PPD) and phytohaemagglutinin (PHA) was examined in 62 patients with breast carcinoma who received postoperative adjuvant radiation therapy or cyclic chemotherapy with chlorambucil, methotrexate and 5-fluorouracil. Both treatments impaired the immunologic reactivity of blood lymphocytes as measured by PPD and PHA stimulation in vitro. Radiation therapy seemed to cause more profound and protracted suppression of the PPD response than chemotherapy.

  13. The Role of Cyclic Nucleotide Signaling Pathways in Cancer: Targets for Prevention and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Fajardo, Alexandra M.; Piazza, Gary A. [Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave, Suite 3029, Mobile, AL 36604 (United States); Tinsley, Heather N., E-mail: htinsley@montevallo.edu [Department of Biology, Chemistry, and Mathematics, University of Montevallo, Station 6480, Montevallo, AL 35115 (United States)

    2014-02-26

    For more than four decades, the cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) have been recognized as important signaling molecules within cells. Under normal physiological conditions, cyclic nucleotides regulate a myriad of biological processes such as cell growth and adhesion, energy homeostasis, neuronal signaling, and muscle relaxation. In addition, altered cyclic nucleotide signaling has been observed in a number of pathophysiological conditions, including cancer. While the distinct molecular alterations responsible for these effects vary depending on the specific cancer type, several studies have demonstrated that activation of cyclic nucleotide signaling through one of three mechanisms—induction of cyclic nucleotide synthesis, inhibition of cyclic nucleotide degradation, or activation of cyclic nucleotide receptors—is sufficient to inhibit proliferation and activate apoptosis in many types of cancer cells. These findings suggest that targeting cyclic nucleotide signaling can provide a strategy for the discovery of novel agents for the prevention and/or treatment of selected cancers.

  14. A random search algorithm for cyclic delivery synchronization problem

    Directory of Open Access Journals (Sweden)

    Katarzyna Gdowska

    2017-09-01

    Full Text Available Background: The paper is devoted to the cyclic delivery synchronization problem with vehicles serving fixed routes. Each vehicle is assigned to a fixed route: the series of supplier’s and logistic centers to be visited one after another. For each route the service frequency is fixed and known in advance. A vehicle loads at a supplier’s, then it delivers goods to a logistic center and either loads other goods there and delivers them to the next logistic center along the route or goes to another logistic center. Each logistic center can belong to several routes, so goods are delivered there with one vehicle and then they departure for the further journey with another truck. The objective of this cyclic delivery synchronization problem is to maximize the total number of synchronizations of vehicles arrivals in logistic centers and their load times, so that it is possible to organize their arrivals in repeatable blocks. Methods: Basing on the previously developed mathematical model for the cyclic delivery synchronization problem we built a random search algorithm for cyclic delivery synchronization problem. The random heuristic search utilizes objective-oriented randomizing. In the paper the newly-developed random search algorithm for cyclic delivery synchronization problem is presented. Results: A computational experiment consisted of employing the newly-developed random search algorithm for solving a series of cyclic delivery synchronization problems. Results obtained with the algorithm were compared with solutions computed with the exact method. Conclusions: The newly-developed random search algorithm for cyclic delivery synchronization problem gives results which are considerably close to the ones obtained with mixed-integer programming. The main advantage of the algorithm is reduction of computing time; it is relevant for utilization of this method in practice, especially for large-sized problems.

  15. Combined effects of interleukin-1β and cyclic stretching on metalloproteinase expression in corneal fibroblasts in vitro.

    Science.gov (United States)

    Feng, Pengfei; Li, Xiaona; Chen, Weiyi; Liu, Chengxing; Rong, Shuo; Wang, Xiaojun; Du, Genlai

    2016-06-10

    Corneal tensile strain increases if the cornea becomes thin or if intraocular pressure increases. However, the effects of mechanical stress on extracellular matrix (ECM) remodelling in the corneal repair process and the corneal anomalies are unknown. In this study, the combined effects of interleukin-1β (IL-1β) on matrix metalloproteinases (MMPs) in corneal fibroblasts under cyclic stretching were investigated in vitro. Cultured rabbit corneal fibroblasts were subjected to 5, 10 or 15 % cyclic equibiaxial stretching at 0.1 Hz for 36 h in the presence of IL-1β. Conditioned medium was harvested for the analysis of MMP2 and MMP9 protein production using the gelatin zymography and western blot techniques. Cyclic equibiaxial stretching changed the cell morphology by increasing the contractility of F-actin fibres. IL-1β alone induced the expression of MMP9 and increased the production of MMP2, and 5 % stretching alone decreased the production of MMP2, which indicates that a low stretching magnitude can reduce ECM degradation. In the presence of IL-1β, 5 and 10 % stretching increased the production of MMP2, whereas 15 % stretching increased the production of MMP9. These results indicate that MMP expression is enhanced by cyclic mechanical stimulation in the presence of IL-1β, which is expected to contribute to corneal ECM degradation, leading to the development of post-refractive surgery keratectasia.

  16. Cyclic stretch of Embryonic Cardiomyocytes Increases Proliferation, Growth, and Expression While Repressing Tgf-β Signaling

    Science.gov (United States)

    Banerjee, Indroneal; Carrion, Katrina; Serrano, Ricardo; Dyo, Jeffrey; Sasik, Roman; Lund, Sean; Willems, Erik; Aceves, Seema; Meili, Rudolph; Mercola, Mark; Chen, Ju; Zambon, Alexander; Hardiman, Gary; Doherty, Taylor A; Lange, Stephan; del Álamo, Juan C.; Nigam, Vishal

    2014-01-01

    Perturbed biomechanical stimuli are thought to be critical for the pathogenesis of a number of congenital heart defects, including Hypoplastic Left Heart Syndrome (HLHS). While embryonic cardiomyocytes experience biomechanical stretch every heart beat, their molecular responses to biomechanical stimuli during heart development are poorly understood. We hypothesized that biomechanical stimuli activate specific signaling pathways that impact proliferation, gene expression and myocyte contraction. The objective of this study was to expose embryonic mouse cardiomyocytes (EMCM) to cyclic stretch and examine key molecular and phenotypic responses. Analysis of RNA-Sequencing data demonstrated that gene ontology groups associated with myofibril and cardiac development were significantly modulated. Stretch increased EMCM proliferation, size, cardiac gene expression, and myofibril protein levels. Stretch also repressed several components belonging to the Transforming Growth Factor-β (Tgf-β) signaling pathway. EMCMs undergoing cyclic stretch had decreased Tgf-β expression, protein levels, and signaling. Furthermore, treatment of EMCMs with a Tgf-β inhibitor resulted in increased EMCM size. Functionally, Tgf-β signaling repressed EMCM proliferation and contractile function, as assayed via dynamic monolayer force microscopy (DMFM). Taken together, these data support the hypothesis that biomechanical stimuli play a vital role in normal cardiac development and for cardiac pathology, including HLHS. PMID:25446186

  17. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

    Directory of Open Access Journals (Sweden)

    Robert W Moon

    2009-09-01

    Full Text Available The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta, unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta, showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.

  18. Topological chaos, braiding and bifurcation of almost-cyclic sets

    Science.gov (United States)

    Grover, Piyush; Ross, Shane D.; Stremler, Mark A.; Kumar, Pankaj

    2012-12-01

    In certain two-dimensional time-dependent flows, the braiding of periodic orbits provides a way to analyze chaos in the system through application of the Thurston-Nielsen classification theorem (TNCT). We expand upon earlier work that introduced the application of the TNCT to braiding of almost-cyclic sets, which are individual components of almost-invariant sets [Stremler et al., "Topological chaos and periodic braiding of almost-cyclic sets," Phys. Rev. Lett. 106, 114101 (2011)]. In this context, almost-cyclic sets are periodic regions in the flow with high local residence time that act as stirrers or "ghost rods" around which the surrounding fluid appears to be stretched and folded. In the present work, we discuss the bifurcation of the almost-cyclic sets as a system parameter is varied, which results in a sequence of topologically distinct braids. We show that, for Stokes' flow in a lid-driven cavity, these various braids give good lower bounds on the topological entropy over the respective parameter regimes in which they exist. We make the case that a topological analysis based on spatiotemporal braiding of almost-cyclic sets can be used for analyzing chaos in fluid flows. Hence, we further develop a connection between set-oriented statistical methods and topological methods, which promises to be an important analysis tool in the study of complex systems.

  19. Numerical modeling of centrifuge cyclic lateral pile load experiments

    Institute of Scientific and Technical Information of China (English)

    Nikos Gerolymos; Sandra Escoffer; George Gazetas; Jacques Gamier

    2009-01-01

    To gain insight into the inelastic behavior of piles, the response of a vertical pile embedded in dry sand and subjected to cyclic lateral loading was studied experimentally in centrifuge tests conducted in Laboratoire Central des Ponts et Chaussees. Three types of cyclic loading were applied, two asymmetric and one symmetric with respect to the unloaded pile. An approximately square-root variation of soil stiffness with depth was obtained from indirect in-flight density measurements, laboratory tests on reconstituted samples, and well-established empirical correlations. The tests were simulated using a cyclic nonlinear Winkler spring model, which describes the full range of inelastic phenomena, including separation and re-attachment of the pile from and to the soil. The model consists of three mathematical expressions capable of reproducing a wide variety of monotonic and cyclic experimental p-y curves. The physical meaning of key model parameters is graphically explained and related to soil behavior. Comparisons with the centrifuge test results demonstrate the general validity of the model and its ability to capture several features of pile-soil interaction, including: soil plastification at an early stage of loading, "pinching" behavior due to the formation of a relaxation zone around the upper part of the pile, and stiffness and strength changes due to cyclic loading. A comparison of the p-y curves derived from the test results and the proposed model, as well as those from the classical curves of Reese et al. (1974) for sand, is also presented.

  20. Degradation forecast for PEMFC cathode-catalysts under cyclic loads

    Science.gov (United States)

    Moein-Jahromi, M.; Kermani, M. J.; Movahed, S.

    2017-08-01

    Degradation of Fuel Cell (FC) components under cyclic loads is one of the biggest bottlenecks in FC commercialization. In this paper, a novel experimental based algorithm is presented to predict the Catalyst Layer (CL) performance loss during cyclic load. The algorithm consists of two models namely Models 1 and 2. The Model 1 calculates the Electro-Chemical Surface Area (ECSA) and agglomerate size (e.g. agglomerate radius, rt,agg) for the catalyst layer under cyclic load. The Model 2 is the already-existing model from our earlier studies that computes catalyst performance with fixed structural parameters. Combinations of these two Models predict the CL performance under an arbitrary cyclic load. A set of parametric/sensitivity studies is performed to investigate the effects of operating parameters on the percentage of Voltage Degradation Rate (VDR%) with rank 1 for the most influential one. Amongst the considered parameters (such as: temperature, relative humidity, pressure, minimum and maximum voltage of the cyclic load), the results show that temperature and pressure have the most and the least influences on the VDR%, respectively. So that, increase of temperature from 60 °C to 80 °C leads to over 20% VDR intensification, the VDR will also reduce 1.41% by increasing pressure from 2 atm to 4 atm.

  1. Low severity coal liquefaction promoted by cyclic olefins

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, C.W.

    1992-01-01

    Low severity coal liquefaction promoted by cyclic olefins offers a means of liquefying coal at low severity conditions. Lower temperature, 350[degrees]C, and lower hydrogen pressure, 500 psi, have been used to perform liquefaction reactions. The presence of the cyclic olefin, hexahydroanthracene, made a substantial difference in the conversion of Illinois No. 6 coal at these low severity conditions. The Researchperformed this quarter was a parametric evaluation of the effect of different parameters on the coal conversion and product distribution from coal. The effect of the parameters on product distribution from hexahydroanthracene was also determined. The work planned for next quarter includes combining the most effective parametric conditions for the low severity reactions and determining their effect. The second part ofthe research performed this quarter involved performing Fourier transform infrared (FTIR) spectroscopy using cyclic olefins. The objective of this study was to determine the feasibility of using FTIR and a heated cell to determine the reaction pathway that occurs in the hydrogen donation reactions from cyclic olefins. The progress made to date includes evaluating the FTIR spectra of cyclic olefins and their expected reaction products. This work is included in this progress report.

  2. Temperature Dependent Cyclic Deformation Mechanisms in Haynes 188 Superalloy

    Science.gov (United States)

    Rao, K. Bhanu Sankara; Castelli, Michael G.; Allen, Gorden P.; Ellis, John R.

    1995-01-01

    The cyclic deformation behavior of a wrought cobalt-base superalloy, Haynes 188, has been investigated over a range of temperatures between 25 and 1000 C under isothermal and in-phase thermomechanical fatigue (TMF) conditions. Constant mechanical strain rates (epsilon-dot) of 10(exp -3)/s and 10(exp -4)/s were examined with a fully reversed strain range of 0.8%. Particular attention was given to the effects of dynamic strain aging (DSA) on the stress-strain response and low cycle fatigue life. A correlation between cyclic deformation behavior and microstructural substructure was made through detailed transmission electron microscopy. Although DSA was found to occur over a wide temperature range between approximately 300 and 750 C the microstructural characteristics and the deformation mechanisms responsible for DSA varied considerably and were dependent upon temperature. In general, the operation of DSA processes led to a maximum of the cyclic stress amplitude at 650 C and was accompanied by pronounced planar slip, relatively high dislocation density, and the generation of stacking faults. DSA was evidenced through a combination of phenomena, including serrated yielding, an inverse dependence of the maximum cyclic hardening with epsilon-dot, and an instantaneous inverse epsilon-dot sensitivity verified by specialized epsilon-dot -change tests. The TMF cyclic hardening behavior of the alloy appeared to be dictated by the substructural changes occuring at the maximum temperature in the TMF cycle.

  3. Cyclical mastalgia: Prevalence and associated determinants in Hamadan City, Iran

    Institute of Scientific and Technical Information of China (English)

    Fatemeh Shobeiri; Khodayar Oshvandi; Mansour Nazari

    2016-01-01

    Objective: To assess prevalence of cyclical mastalgia and its main determinants in women who attended in health centers of Hamadan City, Iran.Methods: This case–control study was conducted on 400 women(case: cyclical mastalgia, n = 240; control: without cyclical mastalgia, n = 160) who attended family planning clinic for routine follow-up in health centers. The cluster sampling was used.Information was collected by interviewing and using a standardized validated questionnaire. Severity of mastalgia was assessed through using visual analog scaling. Data processing and statistical analysis were performed by using SPSS 19.0.Results: The results revealed that majority of women(60.0%) experienced cyclical mastalgia.Out of these, 22.5% and 37.5% were mild and moderate-to-severe mastalgia, respectively. No association was revealed in experience of depression and anxiety in mastalgia group. In a multivariable logistic regression model, the increasing age, age of marriage, history of abortion and history of premenstrual syndrome were main determinants of mastalgia, while use of oral contraceptive and regular exercise was associated with lower incidence of mastalgia.Conclusions: Most of women with breast discomfort suffered cyclical mastalgia which severity can be determined by advanced age, age of marriage, history of abortion and history of premenstrual syndrome, but inversely by oral contraceptive use and exercise activity.

  4. Influences of cyclic loading on martensite transformation of TRIP steels

    Science.gov (United States)

    Dan, W. J.; Hu, Z. G.; Zhang, W. G.

    2013-03-01

    While austenite transformation into martensite induces increasing of the crack initiation life and restraining of the growth of fatigue cracks in cyclic-loading processes, TRIP-assisted steels have a better fatigue life than the AHSS (Advance High Strength Steels). As two key parameters in the cyclic loading process, strain amplitude and cyclic frequency are used in a kinetic transformation model to reasonably evaluate the phase transformation from austenite into martensite with the shear-band intersections theory, in which strain amplitude and cyclic frequency are related to the rate of shear-band intersection formation and the driving force of phase transformation. The results revealed that the martensite volume fraction increased and the rate of phase transformation decrease while the number of cycles increased, and the martensite volume fraction was almost constant after the number of cycles was more than 2000 times. Higher strain amplitude promotes martensite transformation and higher cyclic frequency impedes phase transformation, which are interpreted by temperature increment, the driving force of phase transformation and the rate of shearband intersection formation.

  5. Cyclic electron flow around photosystem I is essential for photosynthesis.

    Science.gov (United States)

    Munekage, Yuri; Hashimoto, Mihoko; Miyake, Chikahiro; Tomizawa, Ken-ichi; Endo, Tsuyoshi; Tasaka, Masao; Shikanai, Toshiharu

    2004-06-03

    Photosynthesis provides at least two routes through which light energy can be used to generate a proton gradient across the thylakoid membrane of chloroplasts, which is subsequently used to synthesize ATP. In the first route, electrons released from water in photosystem II (PSII) are eventually transferred to NADP+ by way of photosystem I (PSI). This linear electron flow is driven by two photochemical reactions that function in series. The cytochrome b6f complex mediates electron transport between the two photosystems and generates the proton gradient (DeltapH). In the second route, driven solely by PSI, electrons can be recycled from either reduced ferredoxin or NADPH to plastoquinone, and subsequently to the cytochrome b6f complex. Such cyclic flow generates DeltapH and thus ATP without the accumulation of reduced species. Whereas linear flow from water to NADP+ is commonly used to explain the function of the light-dependent reactions of photosynthesis, the role of cyclic flow is less clear. In higher plants cyclic flow consists of two partially redundant pathways. Here we have constructed mutants in Arabidopsis thaliana in which both PSI cyclic pathways are impaired, and present evidence that cyclic flow is essential for efficient photosynthesis.

  6. Interaction between integrin a Ⅱbβ 3 and synthesized cyclic hexapeptide containing RGD

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The RGD sequence generally exists in the extracellular matrix proteins and can be recognized by many integrin proteins. The binding ability of immobilized biotinylated cyclic hexapeptide [cyclo(-Arg-Gly-Asp-D-Phe-Lys-Gly-)] containing RGD to integrin a ab β3 was tested by the methods of ELISA and SPR. Results showed that a spacer of 1.48-2.2 nm between the peptide and the biotin residue was long enough to send the RGD sequence into the binding center embedded within a Ⅱbβ 3, and the equilibrium dissociation constant was 1.1 μm. The work provides an ideal model system for the research of cell adhesion on solid surfaces.

  7. [Biosynthesis of cyclic GMP in plant cells - new insight into guanylate cyclases].

    Science.gov (United States)

    Świeżawska, Brygida; Marciniak, Katarzyna; Szmidt-Jaworska, Adriana

    2015-01-01

    Cyclic 3',5'-guanosine monophosphate (cGMP) is involved in many physiological processes in plants. Concentration of this second messenger in plant cell is determined by guanylyl cyclases (GCs) responsible for cGMP synthesis and phosphodiesterases (PDEs) involved in cGMP inactivation. First discovered plant GCs were localized in cytosol, but few years ago a new family of plasma membrane proteins with guanylyl cyclase activity was identified in Arabidopsis thaliana. These proteins belong to the family of a leucine-rich repeat receptor-like kinases (LRR-RLK) with extracellular leucine-rich repeat domain, a transmembrane-spanning domain, and an intracellular kinase domain. A novel class of guanylyl cyclases contain the GC catalytic center encapsulated within the intracellular kinase domain. These molecules are different to animal GCs in that the GC catalytic center is nested within the kinase domain. In presented paper we summarized the most recent data concerning plant guanylyl cyclases.

  8. The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control

    Science.gov (United States)

    Lindenberg, Sandra; Klauck, Gisela; Pesavento, Christina; Klauck, Eberhard; Hengge, Regine

    2013-01-01

    C-di-GMP—which is produced by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases (PDEs)—is a ubiquitous second messenger in bacterial biofilm formation. In Escherichia coli, several DGCs (YegE, YdaM) and PDEs (YhjH, YciR) and the MerR-like transcription factor MlrA regulate the transcription of csgD, which encodes a biofilm regulator essential for producing amyloid curli fibres of the biofilm matrix. Here, we demonstrate that this system operates as a signalling cascade, in which c-di-GMP controlled by the DGC/PDE pair YegE/YhjH (module I) regulates the activity of the YdaM/YciR pair (module II). Via multiple direct interactions, the two module II proteins form a signalling complex with MlrA. YciR acts as a connector between modules I and II and functions as a trigger enzyme: its direct inhibition of the DGC YdaM is relieved when it binds and degrades c-di-GMP generated by module I. As a consequence, YdaM then generates c-di-GMP and—by direct and specific interaction—activates MlrA to stimulate csgD transcription. Trigger enzymes may represent a general principle in local c-di-GMP signalling. PMID:23708798

  9. Cyclic mechanical load causes global translational arrest in articular chondrocytes: a process which is partially dependent upon PKR phosphorylation

    Directory of Open Access Journals (Sweden)

    C Lomas

    2011-09-01

    Full Text Available he cellular mechanisms by which articular cartilage responds to load are poorly understood, but such responses may involve regulation at the level of protein translation rather than synthesis of mRNA. We investigated the role of translational control in cyclically (0.5 Hz, 0.1 Hz and 0.05 Hz and statically loaded porcine articular cartilage explants. Messenger RNA was extracted for real time polymerase chain reaction (RT-PCR and newly synthesised proteins were measured by their incorporation of radiolabelled 35S[methionine/cysteine] or 35SO4. Some medium from loaded and unloaded explants was immunoblotted for type II collagen, CTGF and TIMP3. The pathways that control protein translation were investigated by immunoblotting explant lysates for PKR, PERK (PKR like endoplasmic reticulum kinase, eIF2a (eukaryotic initiation factor 2a, eEFs (eukaryotic elongation factors, and AMP-dependent kinase. Explants were also loaded in the presence of inhibitors of PKR, the fibroblast growth factor (FGF receptor and PI3 kinase. Cyclic loading caused complete global translational arrest as evidenced by a total suppression of new protein synthesis whilst maintaining mRNA levels. Translational arrest did not occur following static loading and was partly dependent upon the load frequency. There was a rebound increase in protein synthesis when labelling was performed after load had been withdrawn. Phosphorylation of PKR occurred in explants following cyclic load and inhibition of PKR modestly reversed suppression of newly synthesised proteins suggesting that PKR, at least in part, was responsible for loading induced translational arrest. These results show that translational control provides a rapid and potentially important mechanism for controlling the synthetic responses of articular chondrocytes in response to different types of mechanical load.

  10. Laterally cyclic loading of monopile in dense sand

    DEFF Research Database (Denmark)

    Klinkvort, Rasmus Tofte; Hededal, Ole; Svensson, M.

    2011-01-01

    In order to investigate the response from laterally cyclic loading of monopiles a large centrifuge tests series is ongoing at the Technical University of Denmark (DTU). This paper will present some of the tests carried out with a focus on the influence of accumulation of rotation when changing...... the loading conditions. In these tests the load conditions are controlled by two load characteristics, one controlling the level of the cyclic loading and one controlling the characteristic of the cyclic loading. The centrifuge tests were performed in dense dry sand on a pile with prototype dimensions...... used for wind turbine foundation. This is important in order to get the right failure mechanism in the sand. The load frame is controlled with a feedback system which enables force controlled load series. A total number of 8 tests have been carried. In all of the tests, the pile was loaded with 500...

  11. Concretion cyclicity of oil- and gas-bearing formations

    Energy Technology Data Exchange (ETDEWEB)

    Vysotskiy, V.N.; Sidorenkov, A.I.

    1987-02-01

    The authors find that analysis of the occurrence and abundance of concretions can be used as a method of correlating, subdividing and studying the cyclic and lithofacies makeup of sedimentary oil- and gas-bearing sequences. The cyclicity of Mesozoic sedimentogenesis in West Siberia have been examined. Two indices are used to describe the distribution of concretions: concretion saturation, the number of concentrations per meter of section; and concretion content, the percentage content of concretions in a selected interval of section. On the basis of 550 wells, the authors plotted graphs showing the mean statistical distribution of carbonate concretions in the producing horizons of individual fields. The analysis shows that their distribution is very complicated, but in general the cyclic nature is controlled by the microstructural features of the host rocks. Results are discussed. 15 references, 3 figures.

  12. Lipolymphedema Associated with Idiopathic Cyclic Edema: A Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jose Maria Pereira de Godoy

    2017-01-01

    Full Text Available Idiopathic cyclic edema is a type of generalized edema that mainly affects women. Diagnosis is made by the patient’s clinical history and an evaluation of the accumulation of weight during the day. The objective of this study is to report the clinical control of lymphedema associated with idiopathic cyclic edema using calcium dobesilate. A 55-year-old female patient reported generalized edema for years in that she woke up in the morning with her legs swollen and the edema worsened during the day. The physical examination revealed generalized edema. After four days of treatment with calcium dobesilate, the patient returned to the Clínica Godoy, Brazil, with less edema and reductions in body weight and the amount of extracellular and intracellular fluid. With further treatment, there was a total reduction of the edema. It is concluded that calcium dobesilate helps to control lymphedema secondary to idiopathic cyclic edema.

  13. Durability of Modified Expanded Polystyrene Concrete after Dynamic Cyclic Loading

    Directory of Open Access Journals (Sweden)

    Wenbo Shi

    2016-01-01

    Full Text Available EPS concrete was produced by mixing the expanded polystyrene spheres (EPS and polymer emulsion and thickener to the matrix concrete, and this concrete had good vibration energy absorption characteristics. Based on the experimental data obtained on EPS volume ratio of 0%, 20%, 30%, and 40% by replacing matrix or coarse aggregate, the two design styles had nearly the same compressive strength. By applying frequency of 5 Hz, 50000 or 100000 times, 40 KN, 50 KN, and 60 KN cyclic loading, it is shown that the higher the inclusion size was, the lower the compressive strength of the EPS concrete would be; the larger the applying dynamic cyclic load was, the more obvious the compressive strength changing would be. Meanwhile, the strength of EPS concrete had no evident change after durability test. The results of this research had practical significance on using EPS concrete in some long-term cyclic dynamic load engineering.

  14. Cyclic AMP system in muscle tissue during prolonged hypokinesia

    Science.gov (United States)

    Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

    1980-01-01

    Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

  15. Theoretical characterisation of the SSO, cyclic SOS and SOS isomers

    Science.gov (United States)

    Denis, Pablo A.

    2010-01-01

    The SSO, cyclic SOS and open SOS isomers have been investigated, employing the CCSD(T) methodology and the cc-pV(X + d)Z X = 3, 4, 5, 6 basis sets. The anharmonic force fields have been calculated to predict the fundamental vibrational frequencies, rotational constants, vibration-rotation corrections, anharmonic corrections to zero-point energies, and structural parameters. At the CCSD(T)/CBS limit and including corrections for scalar relativistic effects, complete quadruple excitations, spin-orbit and core-valence correlation effects, the estimated enthalpies of formation are -13.9 ± 1, 32.1 ± 1, and -51.2 ± 1 kcal/mol, for SSO, cyclic-SOS and open-SOS, respectively. Finally, it was found that the asymmetric SO stretch of the open and cyclic SOS isomers are located in a nearly identical position and it is likely that SOS also maybe present in the surface of Io.

  16. Low Severity Coal Liquefaction Promoted by Cyclic Olefins

    Energy Technology Data Exchange (ETDEWEB)

    Christine W. Curtis

    1998-04-09

    The development of the donor solvent technology for coal liquefaction has drawn a good deal of attention over the last three decades. The search for better hydrogen donors led investigators to a class of compounds known as cyclic olefins. Cyclic olefins are analogues of the conventional hydroaromatic donor species but do not contain aromatic rings. The cyclic olefins are highly reactive compounds which readily release their hydrogen at temperatures of 200 C or higher. Considerable effort has been o expended toward understanding the process of hydrogen donation. Most of this work was conducted in bomb reactors, with product analysis being carried out after the reaction was complete. Efforts directed towards fundamental studies of these reactions in situ are rare. The current work employs a high temperature and high pressure infrared cell to monitor in situ the concentrations of reactants and products during hydrogen release from hydrogen donor compounds.

  17. Cyclic operation of power plant; Cyklisk drift av kraftvaermeverk

    Energy Technology Data Exchange (ETDEWEB)

    Storesund, Jan

    2007-12-15

    The great majority of power plants are designed for base load operation with a relatively small number of starts and stops per year. Therefore, there has been no need to consider fatigue at design. Over the last few years operation with more frequent starts and stops exists as a consequence of swinging electricity prices that has become common. This involves significantly higher frequency of damages; not least fatigue relates damages, and the number of severe failures in components that never before have had damage problems may increase as well. In the present work the different types of component that may suffer from cyclic operation related damage are gathered by a literature survey and described as follows: - where and how the damages comes up, - constructions that should be avoided, - non-destructive testing (NDT) for damage that may come up under cyclic operation, - calculation and assessment of integrity of critical components - areas where continued research would be valuable. Recommendations have been put together to be used to prevent cyclic operation related damage and to detect it in time. The target group for this study is i) plant owners of plants where cyclic operation is or may be present, ii) researchers in the area, and, iii) inspectors and NDT-operators. There are quite a number of components where cyclic operation has been found to significantly influence the lift time. Some of these components are described in many papers whereas occasional papers have been found for others. The amount of information that is possible to get for a certain component is likely related to its significance for cyclic operation damage. The most frequently reported problem is ligament cracking of high temperature headers. Other components where extensive studies have been done are: wall panels, creep-fatigue loaded welds and turbine components

  18. Influence of material's cyclic deformation behaviour on fatigue crack growth threshold

    Institute of Scientific and Technical Information of China (English)

    ZHANG Rui; SUN Yi; WANG zhen-qing

    2008-01-01

    To investigate the relation between material's cyclic plastic behaviour and fatigue crack growth, a new model is proposed. The model incorporated the two intrinsic properties of material' s cyclic plastic and crack tip' s deformation dislocation to interpret fatigue crack threshold. The relation between material's cyclic hardening parameters (cyclic hardening amplitude and cyclic hardening rate) and fatigue threshold is studied. Fatigue threshold is determined based on the dislocation-free zone (DFZ) model, the theory of cohesive zone and the cyclic deformation behaviour. The results show that fatigue threshold increases with the decrease of the amplitude of cyclic hardening and is independent of cyclic hardening rate, but fatigue crack growth rate increa-ses with the increase of cyclic hardening rate.

  19. Laboratory Testing of Cyclic Laterally Loaded Pile in Cohesionless Soil

    DEFF Research Database (Denmark)

    Roesen, Hanne Ravn; Ibsen, Lars Bo; Hansen, Mette;

    2013-01-01

    Offshore wind turbines are normally founded with large diameter monopiles and placed in rough environments subjected to variable lateral loads from wind and waves. A long-term lateral loading may create rotation (tilt) of the pile by change in the pile-soil system which is critical...... in the serviceability limit state. In this paper small-scale testing of a pile subjected to cyclic, lateral loading is treated in order to investigate the effect of cyclic loading. The test setup, which is an improvement of a previous setup, is described and the first results of testing are compared with previous...

  20. Controls on Precambrian sea level change and sedimentary cyclicity

    Science.gov (United States)

    Eriksson, P. G.; Catuneanu, O.; Nelson, D. R.; Popa, M.

    2005-04-01

    Although uniformitarianism applies in a general sense to the controls on relative and global sea level change, some influences thereon were more prominent in the Precambrian. Short-term base level change due to waves and tides may have been enhanced due to possibly more uniform circulation systems on wide, low gradient Precambrian shelves. The lack of evidence for global glacial events in the Precambrian record implies that intraplate stresses and cyclic changes to Earth's geoid were more likely explanations for third-order sea level change than glacio-eustasy. Higher heat flow in the earlier Precambrian may have led to more rapid tectonic plate formation, transport and destruction, along with an increased role for hot spots, aseismic ridges and mantle plumes (superplumes), all of which may have influenced cyclic sedimentation within the ocean basins. A weak cyclicity in the occurrence of plume events has an approximate duration comparable to that of first-order (supercontinental cycle) sea level change. Second-order cyclicity in the Precambrian largely reflects the influences of thermal epeirogeny, changes to mid-ocean ridge volume as well as to ridge growth and decay rates, and cratonic marginal downwarping concomitant with either sediment loading or extensional tectonism. Third-order cycles of sea level change in the Precambrian also reflected cyclic loading/unloading within flexural foreland basin settings, and filling/deflation of magma chambers associated with island arc evolution. The relatively limited number of studies of Precambrian sequence stratigraphy allows some preliminary conclusions to be drawn on duration of the first three orders of cyclicity. Archaean greenstone basins appear to have had first- and second-order cycle durations analogous to Phanerozoic equivalents, supporting steady state tectonics throughout Earth history. In direct contrast, however, preserved basin-fills from Neoarchaean-Palaeoproterozoic cratonic terranes have first- and