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Sample records for ccr point-form quantum

  1. Structure and applications of point form relativistic quantum mechanics

    International Nuclear Information System (INIS)

    Klink, W.H.

    2003-01-01

    The framework of point form relativistic quantum mechanics is used to construct mass and current operators for hadronic systems with finite degree of freedom. For the point form all of the interactions are in the four-momentum operator and, since Lorentz transformations are kinematic, the theory is manifestly covariant. In the Bakamjian-Thomas version of the point form the four-momentum operator is written as a product of the four-velocity operator and mass operator, where the mass operator is the sum of free and interacting mass operators. Interacting mass operators can be constructed from vertices, matrix elements of local field operators evaluated at the space-time point zero, where the states are eigenstates of the four-velocity. Applications include the study of the spectra and widths of vector mesons, viewed as bound states of quark-antiquark pairs. Besides mass operators, current operators are needed to compute form factors. Form factors are matrix elements of current operators on mass operator eigenstates and are often calculated with one-body current operators (in the point form this is called the point form spectator approximation); but in a properly relativistic theory there must also be many-body current operators. Minimal currents needed to satisfy current conservation in the presence of hadronic interactions (called dynamically determined currents) are shown to be easily calculated in the point form. (author)

  2. Point form relativistic quantum mechanics and relativistic SU(6)

    Science.gov (United States)

    Klink, W. H.

    1993-01-01

    The point form is used as a framework for formulating a relativistic quantum mechanics, with the mass operator carrying the interactions of underlying constituents. A symplectic Lie algebra of mass operators is introduced from which a relativistic harmonic oscillator mass operator is formed. Mass splittings within the degenerate harmonic oscillator levels arise from relativistically invariant spin-spin, spin-orbit, and tensor mass operators. Internal flavor (and color) symmetries are introduced which make it possible to formulate a relativistic SU(6) model of baryons (and mesons). Careful attention is paid to the permutation symmetry properties of the hadronic wave functions, which are written as polynomials in Bargmann spaces.

  3. Relativity, Symmetry, and the Structure of Quantum Theory, Volume 2; Point form relativistic quantum mechanics

    Science.gov (United States)

    Klink, William H.; Schweiger, Wolfgang

    2018-03-01

    This book covers relativistic quantum theory from the point of view of a particle theory, based on the irreducible representations of the Poincaré group, the group that expresses the symmetry of Einstein relativity. There are several ways of formulating such a theory; this book develops what is called relativistic point form quantum mechanics, which, unlike quantum field theory, deals with a fixed number of particles in a relativistically invariant way. A chapter is devoted to applications of point form quantum mechanics to nuclear physics.

  4. On relativistic irreducible quantum fields fulfilling CCR

    International Nuclear Information System (INIS)

    Baumann, K.

    1987-01-01

    Let phi be a relativistic scalar field fulfilling canonical commutation relations (CCR). Furthermore it is assumed that the time zero fields and momenta form an irreducible set. Based on estimates given by Herbst [I. W. Herbst, J. Math. Phys. 17, 1210 (1976)], and by methods developed by Powers [R. T. Powers, Commun. Math. Phys. 4, 145 (1967)], it is shown that phi has to be a free field in n>3 space dimensions. For n = 3 (resp. n = 2) restrictions that look similar to the restriction in a formal :phi 4 : 3 /sub +/ 1 (resp. :phi 6 : 2 /sub +/ 1 ) theory are obtained

  5. Quantum continual measurements and a posteriori collapse on CCR

    International Nuclear Information System (INIS)

    Belavkin, V.P.

    1992-01-01

    A quantum stochastic model for the Markovian dynamics of an open system under the nondemolition unsharp observation which is continuous in time, is given. A stochastic equation for the posterior evolution of a quantum continuously observed system is derived and the spontaneous collapse (stochastically continuous reduction of the wave packet) is described. The quantum Langevin evolution equation is solved for the case of a quasi-free Hamiltonian in the initial CCR algebra with a linear output channel, and the posterior dynamics corresponding to an initial Gaussian state is found. It is shown for an example of the posterior dynamics of a quantum oscillator that any mixed state under a complete nondemolition measurement collapses exponentially to a pure Gaussian one. (orig.)

  6. CCR1

    African Journals Online (AJOL)

    inflammatory protein II; Bioinformatics; Protease digestion; HEK293 cells; Radioligand binding. Tropical ... development of many diseases. ... diseases, antagonism of CCR1 has become an ..... importance of molecular conformation in terms of.

  7. Clinical Case Registries (CCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

  8. Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

    OpenAIRE

    Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

    2009-01-01

    There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 a...

  9. Point-form electrodynamics and the construction of conserved current operators

    International Nuclear Information System (INIS)

    Klink, W.H.

    2003-01-01

    A general procedure for constructing conserved electromagnetic current operators in the presence of hadronic interactions is given. The four-momentum operator in point-form relativistic quantum mechanics is written as the sum of hadronic, photon, and electromagnetic four-momentum operators, where the electromagnetic four-momentum operator is generated from a vertex operator, in which a conserved current operator is contracted with the four-vector potential operator. The current operator is the sum of free, dynamically determined and model-dependent operators. The dynamically determined current operator is formed form a free current operator and the interacting hadronic four-momentum operator, in such a way that the sum of free and dynamically determined current operators is conserved with respect to the hadronic interactions. The model-dependent operator is a many-body current operator, formed as the commutator of an antisymmetric operator with the hadronic four-momentum operator. It is shown that such an operator is also conserved with respect to the hadronic interactions and also does not renormalize the charge. Refs. 9 (author)

  10. Regulation of CCR7-dependent cell migration through?CCR7 homodimer formation

    OpenAIRE

    Kobayashi, Daichi; Endo, Masataka; Ochi, Hirotaka; Hojo, Hironobu; Miyasaka, Masayuki; Hayasaka, Haruko

    2017-01-01

    The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers,...

  11. Molekulare Klonierung, stabile Transfektion und funktionelle Expression der murinen Chemokinrezeptoren Ccr2 und Ccr5

    OpenAIRE

    Simonis, Christopher

    2009-01-01

    The two chemokine receptors CCR2 and CCR5 play important roles in the recruitment and activation of monocytes/macrophages and T-lymphocytes at sites of infection and inflammation. To further examine their function, I cloned the two murine chemokine receptors Ccr2 and Ccr5 from genomic mouse DNA by a PCR-based cloning strategy and functionally expressed them in stably transfected CHO-cells. These cells were used to generate the first monoclonal antibodies against Ccr2 and Ccr5.

  12. CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

    Science.gov (United States)

    Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong; Kim, Ju Han

    2014-01-01

    Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

  13. The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

    Directory of Open Access Journals (Sweden)

    Mohammad Zare-Bidaki

    2015-04-01

    Full Text Available Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32 in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  14. CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function.

    Science.gov (United States)

    Mariani, R; Wong, S; Mulder, L C; Wilkinson, D A; Reinhart, A L; LaRosa, G; Nibbs, R; O'Brien, T R; Michael, N L; Connor, R I; Macdonald, M; Busch, M; Koup, R A; Landau, N R

    1999-03-01

    A polymorphism in the gene encoding CCR2 is associated with a delay in progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. The polymorphism, CCR2-64I, changes valine 64 of CCR2 to isoleucine. However, it is not clear whether the effect on AIDS progression results from the amino acid change or whether the polymorphism marks a genetically linked, yet unidentified mutation that mediates the effect. Because the gene encoding CCR5, the major coreceptor for HIV type 1 primary isolates, lies 15 kb 3' to CCR2, linked mutations in the CCR5 promoter or other regulatory sequences could explain the association of CCR2-64I with slowed AIDS pathogenesis. Here, we show that CCR2-64I is efficiently expressed on the cell surface but does not have dominant negative activity on CCR5 coreceptor function. A panel of peripheral blood mononuclear cells (PBMC) from uninfected donors representing the various CCR5/CCR2 genotypes was assembled. Activated primary CD4(+) T cells of CCR2 64I/64I donors expressed cell surface CCR5 at levels comparable to those of CCR2 +/+ donors. A slight reduction in CCR5 expression was noted, although this was not statistically significant. CCR5 and CCR2 mRNA levels were nearly identical for each of the donor PBMC, regardless of genotype. Cell surface CCR5 and CCR2 levels were more variable than mRNA transcript levels, suggesting that an alternative mechanism may influence CCR5 cell surface levels. CCR2-64I is linked to the CCR5 promoter polymorphisms 208G, 303A, 627C, and 676A; however, in transfected promoter reporter constructs, these did not affect transcriptional activity. Taken together, these findings suggest that CCR2-64I does not act by influencing CCR5 transcription or mRNA levels.

  15. CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea.

    Science.gov (United States)

    Mehlotra, Rajeev K; Hall, Noemi B; Bruse, Shannon E; John, Bangan; Zikursh, Melinda J Blood; Stein, Catherine M; Siba, Peter M; Zimmerman, Peter A

    2015-12-01

    Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G >A, CCR5 -2459G >A and Δ32, and CXCL12 801G >A in PNG (n=258), North America (n=184), and five countries in West Africa (n=178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 -2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 -2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-valuesnew insights regarding CCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Human Eosinophils Express Functional CCR7

    Science.gov (United States)

    Ueki, Shigeharu; Estanislau, Jessica; Weller, Peter F.

    2013-01-01

    Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5–primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM–loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5–primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5–primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7. PMID:23449735

  17. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  18. Influence of the CCR2-V64I Polymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4

    OpenAIRE

    Lee, Benhur; Doranz, Benjamin J.; Rana, Shalini; Yi, Yanji; Mellado, Mario; Frade, Jose M. R.; Martinez-A., Carlos; O’Brien, Stephen J.; Dean, Michael; Collman, Ronald G.; Doms, Robert W.

    1998-01-01

    The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor ...

  19. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis

    OpenAIRE

    Lebre, M.C.; Vergunst, C.E.; Choi, I.Y.K.; Aarrass, S.; Oliveira, A.S.F.; Wyant, T.; Horuk, R.; Reedquist, K.A.; Tak, P.P.

    2011-01-01

    BACKGROUND: The aim of this study was to provide more insight into the question as to why blockade of CCR1, CCR2, and CCR5 may have failed in clinical trials in rheumatoid arthritis (RA) patients, using an in vitro monocyte migration system model. METHODOLOGY/PRINCIPAL FINDINGS: Monocytes from healthy donors (HD; n = 8) or from RA patients (for CCR2 and CCR5 antibody n = 8; for CCR1 blockade n = 13) were isolated from peripheral blood and pre-incubated with different concentrations of either ...

  20. Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)

    OpenAIRE

    Fagin, Ursula; Pitann, Silke; Gross, Wolfgang L; Lamprecht, Peter

    2012-01-01

    Introduction Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polari...

  1. CCR Magazines | Center for Cancer Research

    Science.gov (United States)

    The Center for Cancer Research (CCR) has two magazines, MILESTONES and LANDMARKS, that highlight our annual advances and top contributions to the understanding, detection, treatment and prevention of cancer over the years.

  2. CCR7 signaling pathway and retinal neovascularization

    Directory of Open Access Journals (Sweden)

    Lin-Hui Yuan

    2015-11-01

    Full Text Available Retinal neovascularization diseases are the major causes of blindness. C-C chemokine receptor type 7(CCR7can promote the expression of vascular endothelial growth factor(VEGFthrough the extracellular signal regulated kinase(ERKpathway, leading to vascular leakage, proliferation of vascular endothelial cell, neovascularization and etc. The detection of CCR7 can guide the diagnosis and treatments of retinal neovascularization diseases.

  3. CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic rhinitis patients, asymptomatically sensitized and healthy individuals

    DEFF Research Database (Denmark)

    Holse, Mille; Assing, Kristian; Poulsen, Lars K.

    2006-01-01

    Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial....

  4. Extracellular Disulfide Bridges Serve Different Purposes in Two Homologous Chemokine Receptors, CCR1 and CCR5

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Thiele, Stefanie; Hansen, Laerke Smidt

    2013-01-01

    interact with residues in the main binding crevice, we show that the 7TM-conserved bridge is essential for all types of ligand-mediated activation, whereas the chemokine-conserved bridge is dispensable for small-molecule activation in CCR1. However, in striking contrast to previous studies in other...... chemokine receptors, high affinity CCL3 chemokine binding was maintained in the absence of either bridge. In CCR5, the closest homolog to CCR1, a completely different dependency was observed as neither chemokine activation nor binding was retained in the absence of either bridge. In contrast, both bridges...... where dispensable for small-molecule activation. This indicates that CCR5 activity is independent of extracellular regions, whereas in CCR1, preserved folding of ECL2 is necessary for activation. These results indicate that conserved structural features in a receptor subgroup, does not necessarily...

  5. CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5

    OpenAIRE

    Pham, Kien; Luo, Defang; Liu, Che; Harrison, Jeffrey K.

    2012-01-01

    Glioblastoma multiforme (GBM) is the most malignant brain tumor. Microglia/macrophages are found within human GBM where they likely promote tumor progression. We report that CCL5, CCR1, and CCR5 are expressed in glioblastoma. Individual deletion of CCR1 or CCR5 had little to no effect on survival of tumor bearing mice, or numbers of glioblastoma-infiltrated microglia/macrophages or lymphocytes. CCL5 promoted in vitro migration of wild type, CCR1- or CCR5-deficient microglia/macrophages that w...

  6. CCR Interns | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Interns (CRI) Summer Program was inaugurated in 2004 to provide an open door for students looking for an initial training opportunity. The goal is to enhance diversity within the CCR (Center for Cancer Research) training program and we have placed 338 students from 2004 to 2017, in labs and branches across the division.  The CCR and the Center for Cancer Training’s Office of Training and Education provide stipend support, some Service & Supply funds, and travel support for those students who meet the financial eligibility criteria (

  7. Five-point form of the nodal diffusion method and comparison with finite-difference

    International Nuclear Information System (INIS)

    Azmy, Y.Y.

    1988-01-01

    Nodal Methods have been derived, implemented and numerically tested for several problems in physics and engineering. In the field of nuclear engineering, many nodal formalisms have been used for the neutron diffusion equation, all yielding results which were far more computationally efficient than conventional Finite Difference (FD) and Finite Element (FE) methods. However, not much effort has been devoted to theoretically comparing nodal and FD methods in order to explain the very high accuracy of the former. In this summary we outline the derivation of a simple five-point form for the lowest order nodal method and compare it to the traditional five-point, edge-centered FD scheme. The effect of the observed differences on the accuracy of the respective methods is established by considering a simple test problem. It must be emphasized that the nodal five-point scheme derived here is mathematically equivalent to previously derived lowest order nodal methods. 7 refs., 1 tab

  8. Numerical study of multi-point forming of thick sheet using remeshing procedure

    Science.gov (United States)

    Cherouat, A.; Ma, X.; Borouchaki, H.; Zhang, Q.

    2018-05-01

    Multi-point forming MPF is an innovative technology of manufacturing complex thick sheet metal products without the need for solid tools. The central component of this system is a pair of the desired discrete matrices of punches, and die surface constructed by changing the positions of the tools though CAD and a control system. Because reconfigurable discrete tools are used, part-manufacturing costs are reduced and manufacturing time is shorten substantially. Firstly, in this work we develop constitutive equations which couples isotropic ductile damage into various flow stress based on the Continuum Damage Mechanic theory. The modified Johnson-Cook flow model fully coupled with an isotropic ductile damage is established using the quasi-unilateral damage evolution for considering both the open and the close of micro-cracks. During the forming processes severe mesh distortion of elements occur after a few incremental forming steps. Secondly, we introduce 3D adaptive remeshing procedure based on linear tetrahedral element and geometrical/physical errors estimation to optimize the element quality, to refine the mesh size in the whole model and to adapt the deformed mesh to the tools geometry. Simulation of the MPF process (see Fig. 1) and the unloading spring-back are carried out using adaptive remeshing scheme using the commercial finite element package ABAQUS and OPTIFORM mesher. Subsequently, influencing factors of MPF spring-back are researched to investigate the MPF spring-back tendency with the proposed remeshing procedure.

  9. Quantum

    CERN Document Server

    Al-Khalili, Jim

    2003-01-01

    In this lively look at quantum science, a physicist takes you on an entertaining and enlightening journey through the basics of subatomic physics. Along the way, he examines the paradox of quantum mechanics--beautifully mathematical in theory but confoundingly unpredictable in the real world. Marvel at the Dual Slit experiment as a tiny atom passes through two separate openings at the same time. Ponder the peculiar communication of quantum particles, which can remain in touch no matter how far apart. Join the genius jewel thief as he carries out a quantum measurement on a diamond without ever touching the object in question. Baffle yourself with the bizzareness of quantum tunneling, the equivalent of traveling partway up a hill, only to disappear then reappear traveling down the opposite side. With its clean, colorful layout and conversational tone, this text will hook you into the conundrum that is quantum mechanics.

  10. Analysis of Staphylococcal cassette chromosome mec in Staphylococcus haemolyticus and Staphylococcus sciuri: identification of a novel ccr gene complex with a newly identified ccrA allotype (ccrA7).

    Science.gov (United States)

    Urushibara, Noriko; Paul, Shyamal Kumar; Hossain, Mohammad Akram; Kawaguchiya, Mitsuyo; Kobayashi, Nobumichi

    2011-06-01

    Methicillin resistance in staphylococci is conferred by the acquisition in its chromosome of the mecA gene, which is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). Genetic type of SCCmec is defined by combination of mec gene complex class and cassette chromosome recombinase gene (ccr) allotype. In this study, we analyzed genetic diversity of the SCCmec in 11 Staphylococcus haemolyticus strains and a Staphylococcus sciuri strain, which were recently isolated from clinical specimens in Bangladesh. Among these strains, only two S. haemolyticus strains were proved to have the known types of SCCmec, that is, SCCmec V (class C2 mec-ccrC) and VII (class C1 mec-ccrC). Five S. haemolyticus strains were assigned two unique mec-ccr gene complexes combination; that is, class C1 mec-ccrA4B4 (four isolates) and class A mec-ccrC (one isolate). In the remaining four S. haemolyticus strains with class C1 mec, no known ccr allotypes could be detected. A single S. sciuri strain with class A mec complex carried a ccrA gene belonging to a novel allotype designated ccrA7, together with ccrB3. The ccrA7 gene in the S. sciuri strain showed 61.7%-82.7% sequence identity to the ccrA gene sequences published so far, and 75.3% identity to ccrA3, which is a component of the type 3 ccr complex (ccrA3-ccrB3) in methicillin-resistant Staphylococcus aureus. The results of the present study indicated that mec gene complex and ccr genes in coagulase-negative staphylococci are highly divergent, and distinct from those of common methicillin-resistant S. aureus. Identification of the novel ccrA7 allotype combined with ccrB3 suggested an occurrence of recombination between different ccr complexes in nature.

  11. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C

    2011-01-01

    -allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...... preserved, the allosteric enhancement of chemokine binding was disrupted. In summary, the Trojan horse chimera revealed that orthosteric and allosteric sites could be structurally separated and still act together with transmission of agonism and antagonism across the different receptor units....

  12. The ins and outs of ligand binding to CCR2

    NARCIS (Netherlands)

    Zweemer, Annelien Jacomina Maria

    2014-01-01

    This thesis provides novel insights in the molecular mechanism of action of antagonists for the chemokine receptor CCR2. CCR2 belongs to the protein family of G protein-coupled receptors (GPCRs). It is involved in several inflammatory diseases and therefore many small molecule antagonists targeting

  13. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  14. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  15. CCR presentations at AACR - 2018 | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Chicago, IL, between April 14-18, 2018. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  16. CCR presentations at AACR | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Washington, D.C., between April 1-5, 2017. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  17. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    Science.gov (United States)

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in inflammatory…

  18. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  19. Oral CCR5 inhibitors: will they make it through?

    Science.gov (United States)

    Biswas, Priscilla; Nozza, Silvia; Scarlatti, Gabriella; Lazzarin, Adriano; Tambussi, Giuseppe

    2006-05-01

    The therapeutic armamentarium against HIV has recently gained a drug belonging to a novel class of antiretrovirals, the entry inhibitors. The last decade has driven an in-depth knowledge of the HIV entry process, unravelling the multiple engagements of the HIV envelope proteins with the cellular receptorial complex that is composed of a primary receptor (CD4) and a co-receptor (CCR5 or CXCR4). The vast majority of HIV-infected subjects exhibit biological viral variants that use CCR5 as a co-receptor. Individuals with a mutated CCR5 gene, both homo- and heterozygotes, appear to be healthy. For these and other reasons, CCR5 represents an appealing target for treatment intervention, although certain challenges can not be ignored. Promising small-molecule, orally bioavailable CCR5 antagonists are under development for the treatment of HIV-1 infection.

  20. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection

    DEFF Research Database (Denmark)

    Nansen, A; Marker, O; Bartholdy, C

    2000-01-01

    Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic choriomeningi......Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic...... a rapidly lethal, T cell-independent encephalitis, and infection resulted in a dramatic early up-regulation of chemokine gene expression. Similar marked up-regulation of chemokine expression was not seen until late after LCMV infection and required the presence of activated T cells. Cerebral CCR gene...... expression was dominated by CCR1, CCR2 and CCR5. However, despite a stronger initial chemokine signal in VSV-infected mice, only LCMV-induced T cell-dependent inflammation was found to be associated with substantially increased expression of CCR genes. Virus-activated CD8+ T cells were found to express CCR2...

  1. Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

    NARCIS (Netherlands)

    de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

    2010-01-01

    Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

  2. Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice.

    Directory of Open Access Journals (Sweden)

    Rodrigo Guabiraba

    Full Text Available Dengue virus (DENV, a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1⁻/⁻ mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2⁻/⁻ mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4⁻/⁻ mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection.

  3. Roles of CcrA and CcrB in Excision and Integration of Staphylococcal Cassette Chromosome mec, a Staphylococcus aureus Genomic Island▿

    OpenAIRE

    Wang, Lei; Archer, Gordon L.

    2010-01-01

    The gene encoding resistance to methicillin and other β-lactam antibiotics in staphylococci, mecA, is carried on a genomic island, SCCmec (for staphylococcal cassette chromosome mec). The chromosomal excision and integration of types I to IV SCCmec are catalyzed by the site-specific recombinases CcrA and CcrB, the genes for which are encoded on each element. We sought to identify the relative contributions of CcrA and CcrB in the excision and integration of SCCmec. Purified CcrB but not CcrA ...

  4. Cloning and expression analysis of cinnamoyl-CoA reductase (CCR) genes in sorghum.

    Science.gov (United States)

    Li, Jieqin; Fan, Feifei; Wang, Lihua; Zhan, Qiuwen; Wu, Peijin; Du, Junli; Yang, Xiaocui; Liu, Yanlong

    2016-01-01

    Cinnamoyl-CoA reductase (CCR) is the first enzyme in the monolignol-specific branch of the lignin biosynthetic pathway. In this research, three sorghum CCR genes including SbCCR1, SbCCR2-1 and SbCCR2-2 were cloned and characterized. Analyses of the structure and phylogeny of the three CCR genes showed evolutionary conservation of the functional domains and divergence of function. Transient expression assays in Nicotiana benthamiana leaves demonstrated that the three CCR proteins were localized in the cytoplasm. The expression analysis showed that the three CCR genes were induced by drought. But in 48 h, the expression levels of SbCCR1 and SbCCR2-2 did not differ between CK and the drought treatment; while the expression level of SbCCR2-1 in the drought treatment was higher than in CK. The expression of the SbCCR1 and SbCCR2-1 genes was not induced by sorghum aphid [Melanaphis sacchari (Zehntner)] attack, but SbCCR2-2 was significantly induced by sorghum aphid attack. It is suggested that SbCCR2-2 is involved in the process of pest defense. Absolute quantitative real-time PCR revealed that the three CCR genes were mainly expressed in lignin deposition organs. The gene copy number of SbCCR1 was significantly higher than those of SbCCR2-1 and SbCCR2-2 in the tested tissues, especially in stem. The results provide new insight into the functions of the three CCR genes in sorghum.

  5. The chemokine receptor CCR5 in the central nervous system.

    Science.gov (United States)

    Sorce, Silvia; Myburgh, Renier; Krause, Karl-Heinz

    2011-02-01

    The expression and the role of the chemokine receptor CCR5 have been mainly studied in the context of HIV infection. However, this protein is also expressed in the brain, where it can be crucial in determining the outcome in response to different insults. CCR5 expression can be deleterious or protective in controlling the progression of certain infections in the CNS, but it is also emerging that it could play a role in non-infectious diseases. In particular, it appears that, in addition to modulating immune responses, CCR5 can influence neuronal survival. Here, we summarize the present knowledge about the expression of CCR5 in the brain and highlight recent findings suggesting its possible involvement in neuroprotective mechanisms. Copyright © 2011. Published by Elsevier Ltd.

  6. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  7. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen atCCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  8. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    Pardis C Sabeti

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  9. [CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

    Science.gov (United States)

    Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

    2012-01-01

    In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

  10. [The expression of periphery blood leucocyte CCR3 and CCR5 in the children with Epstein-Barr virus associated infectious mononucleosis].

    Science.gov (United States)

    Qi, Tie-xiong; Gao, Guo-hua; Liu, Shi-hua

    2010-10-01

    To explore the expression of periphery blood leucocyte CCR3 and CCR5 and to comprehend T helper cell in the Children with Epstein-Barr virus associated infectious mononucleosis. We defined the children according to the diagnosis criterion through Paul-Bunnell test inspecting the children's periphery blood unusual lymphocyte and detecting their anti-EBV-CA-IgM, anti-EBV-CA-IgG and anti-EBV-NA-IgG by ELISA and counted the ratio of CCR3 + and CCR5 + cells in lymphocytes with flow cytometry. The ratio of unusual lymphocyte in IM was higher than that of the healthy control group (P < 0.05). The ratio of CCR3 + cells in IM group was higher than that of the healthy control group (P < 0.05). The ratio of CCR5 + cells in IM group was significantly lower than that of the healthy control group. CCR3 + had direct interrelation with fever continued time and the ratio of unusual lymphocyte. There was a negative interrelation between CCR5 and fever continued time (P < 0.05). Children infectious of IM expressed higher level of CCR3 + and lower level of CCR5 + and there was a tendency of Th2 polarization with over production of T helper cell divide imbalance. CCR3 + and CCR5 + may be important targets to judge the degree of seriousness of IM.

  11. In-silico guided discovery of novel CCR9 antagonists

    Science.gov (United States)

    Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

    2018-03-01

    Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

  12. The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

    DEFF Research Database (Denmark)

    Cédile, Oriane; Østerby Jørgensen, Line; Frank, Ida

    2017-01-01

    Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α+ Sirpα- DC and Sirpα+ CD8α- cDC. Both pDC and Sirpα+ cDC can take up antigen in periphery and migrate into the thymus in response t...... by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role....

  13. CCR Certification Form for Wyoming or EPA R8 Tribal Community Water Systems

    Science.gov (United States)

    The CCR Certification Form can be used to certify that community water systems in Wyoming or on Tribal Lands in EPA Region 8 have completed and distributed their annual Consumer Confidence Report (CCR) or water quality report.

  14. The discovery of tropane-derived CCR5 receptor antagonists.

    Science.gov (United States)

    Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

    2006-04-01

    The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

  15. Molecular characterization and expression analysis of four fish-specific CC chemokine receptors CCR4La, CCR4Lc1, CCR4Lc2 and CCR11 in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Qi, Zhitao; Holland, Jason W; Jiang, Yousheng; Secombes, Christopher J; Nie, Pin; Wang, Tiehui

    2017-09-01

    The chemokine and chemokine receptor networks regulate leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. Comparative immunological studies have revealed that both chemokines and their receptors have expanded greatly in a species/lineage specific way. Of the 10 human CC chemokine receptors (CCR1-10) that bind CC chemokines, orthologues only to CCR6, 7, 9 and 10 are present in teleost fish. In this study, four fish-specific CCRs, termed as CCR4La, CCR4Lc1, CCR4Lc2 and CCR11, with a close link to human CCR1-5 and 8, in terms of amino acid homology and syntenic conservation, have been identified and characterized in rainbow trout (Oncorhynchus mykiss). These CCRs were found to possess the conserved features of the G protein-linked receptor family, including an extracellular N-terminal, seven TM domains, three extracellular loops and three intracellular loops, and a cytoplasmic carboxyl tail with multiple potential serine/threonine phosphorylation sites. Four cysteine residues known to be involved in forming two disulfide bonds are present in the extracellular domains and a DRY motif is present in the second intracellular loop. Signaling mediated by these receptors might be regulated by N-glycosylation, tyrosine sulfation, S-palmitoylation, a PDZ ligand motif and di-leucine motifs. Studies of intron/exon structure revealed distinct fish-specific CCR gene organization in different fish species/lineages that might contribute to the diversification of the chemokine ligand-receptor networks in different fish lineages. Fish-specific trout CCRs are highly expressed in immune tissues/organs, such as thymus, spleen, head kidney and gills. Their expression can be induced by the pro-inflammatory cytokines, IL-1β, IL-6 and IFNγ, by the pathogen associated molecular patterns, PolyIC and peptidoglycan, and by bacterial infection. These data suggest that fish-specific CCRs are likely to have an important role in immune

  16. Solution Structure of LC4 Transmembrane Segment of CCR5

    OpenAIRE

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescdence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 ...

  17. Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization.

    Science.gov (United States)

    Tejchman, Anna; Lamerant-Fayel, Nathalie; Jacquinet, Jean-Claude; Bielawska-Pohl, Aleksandra; Mleczko-Sanecka, Katarzyna; Grillon, Catherine; Chouaib, Salem; Ugorski, Maciej; Kieda, Claudine

    2017-05-09

    Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression.

  18. 77 FR 5471 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review

    Science.gov (United States)

    2012-02-03

    ... Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review AGENCY... stakeholder input on the Consumer Confidence Report (CCR) Rule as part of the agency's Retrospective Review of... Safe Drinking Water Act (SDWA, section 1414(c)). The Consumer Confidence Report, or CCR, is an annual...

  19. Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Arfelt, K N; Baumann, L

    2012-01-01

    Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative...

  20. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2

    DEFF Research Database (Denmark)

    Zweemer, Annelien J M; Bunnik, Julia; Veenhuizen, Margo

    2014-01-01

    be divided into two groups with most likely two topographically distinct binding sites. The aim of the current study was to identify the binding site of one such group of ligands, exemplified by three allosteric antagonists, CCR2-RA-[R], JNJ-27141491, and SD-24. We first used a chimeric CCR2/CCR5 receptor...

  1. Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.

    Science.gov (United States)

    Cherney, Robert J; Mo, Ruowei; Meyer, Dayton T; Pechulis, Anthony D; Guaciaro, Michael A; Lo, Yvonne C; Yang, Gengjie; Miller, Persymphonie B; Scherle, Peggy A; Zhao, Qihong; Cvijic, Mary Ellen; Barrish, Joel C; Decicco, Carl P; Carter, Percy H

    2012-10-01

    We describe the design, synthesis, and evaluation of benzimidazoles as benzamide replacements within a series of trisubstituted cyclohexane CCR2 antagonists. 7-Trifluoromethylbenzimidazoles displayed potent binding and functional antagonism of CCR2 while being selective over CCR3. These benzimidazoles were also incorporated into lactam-containing antagonists, thus completely eliminating the customary bis-amide. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Central extensions for the Weyl CCR in Curved space

    International Nuclear Information System (INIS)

    Emch, G.G.

    1993-01-01

    For non-necessarily flat homogeneous configuration spaces, we illustrate how the cohomological choices made in the definition a Weyl group of the CCR are reflected in the momentum map for the action of this group on its co-adjoint orbit of maximal dimension. (Author) 8 refs

  3. Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.

    Science.gov (United States)

    Ioannidis, John P A; Contopoulos-Ioannidis, Despina G; Rosenberg, Philip S; Goedert, James J; De Rossi, Anita; Espanol, Teresa; Frenkel, Lisa; Mayaux, Marie-Jeanne; Newell, Marie-Louise; Pahwa, Savita G; Rousseau, Christine; Scarlatti, Gabriella; Sei, Shizuko; Sen, Luisa; O'Brien, Thomas R

    2003-07-25

    Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-delta32 and CCR2-64I in an international meta-analysis. Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P=0.01 for the time-dependent model). For CCR2-64I, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P<0.01 for the time-dependent model). CCR5-delta32 and CCR2-64I offered no clear protection after clinical AIDS had developed. The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

  4. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis

    DEFF Research Database (Denmark)

    Holst, P J; Orskov, C; Qvortrup, K

    2007-01-01

    CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflam...... of CCR5 is associated with the induction of CD8(+) T-cell-mediated immunopathology consisting of marked hepatic microvesicular steatosis....

  5. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L

    2001-01-01

    /G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently......HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A...

  6. An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry

    International Nuclear Information System (INIS)

    Safarian, Diana; Carnec, Xavier; Tsamis, Fotini; Kajumo, Francis; Dragic, Tatjana

    2006-01-01

    HIV-1 coreceptors are attractive targets for novel antivirals. Here, inhibition of entry by two classes of CCR5 antagonists was investigated. We confirmed previous findings that HIV-1 isolates vary greatly in their sensitivity to small molecule inhibitors of CCR5-mediated entry, SCH-C and TAK-779. In contrast, an anti-CCR5 monoclonal antibody (PA14) similarly inhibited entry of diverse viral isolates. Sensitivity to small molecules was V3 loop-dependent and inversely proportional to the level of gp120 binding to CCR5. Moreover, combinations of the MAb and small molecules were highly synergistic in blocking HIV-1 entry, suggesting different mechanisms of action. This was confirmed by time course of inhibition experiments wherein the PA14 MAb and small molecules were shown to inhibit temporally distinct stages of CCR5 usage. We propose that small molecules inhibit V3 binding to the second extracellular loop of CCR5, whereas PA14 preferentially inhibits subsequent events such as CCR5 recruitment into the fusion complex or conformational changes in the gp120-CCR5 complex that trigger fusion. Importantly, our findings suggest that combinations of CCR5 inhibitors with different mechanisms of action will be central to controlling HIV-1 infection and slowing the emergence of resistant strains

  7. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Angelica Martins Batista

    2018-04-01

    Full Text Available Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD, a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC is a fibrogenic inflammation mainly composed of CD8+ and CD4+ T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611 and CCL5 (rs2107538, rs2280788 and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672 and CCR5 (rs1799987 with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n = 110 or cardiopathic (mild, B1, n = 163; severe, C, n = 133. Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 −403 (rs2107538 CT heterozygotes (OR = 0.5, P-value = 0.04 and T carriers (OR = 0.5, P-value = 0.01 were associated with protection against CCC. To gain insight into the participation of the CCL5–CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1+ CD8+ T cells and CD14+ macrophages were decreased, while frequencies of CCR5+ cells were increased. Importantly, CCR1+CD14+ macrophages were mainly IL-10+, while CCR5+ cells were mostly TNF+. CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met-RANTES therapy

  8. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas' Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy.

    Science.gov (United States)

    Batista, Angelica Martins; Alvarado-Arnez, Lucia Elena; Alves, Silvia Marinho; Melo, Gloria; Pereira, Isabela Resende; Ruivo, Leonardo Alexandre de Souza; da Silva, Andrea Alice; Gibaldi, Daniel; da Silva, Thayse do E S Protásio; de Lorena, Virginia Maria Barros; de Melo, Adriene Siqueira; de Araújo Soares, Ana Karine; Barros, Michelle da Silva; Costa, Vláudia Maria Assis; Cardoso, Cynthia C; Pacheco, Antonio G; Carrazzone, Cristina; Oliveira, Wilson; Moraes, Milton Ozório; Lannes-Vieira, Joseli

    2018-01-01

    Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC) is a fibrogenic inflammation mainly composed of CD8 + and CD4 + T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs) in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611) and CCL5 (rs2107538, rs2280788) and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672) and CCR5 (rs1799987) with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n  = 110) or cardiopathic (mild, B1, n  = 163; severe, C, n  = 133). Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 -403 (rs2107538) CT heterozygotes (OR = 0.5, P -value = 0.04) and T carriers (OR = 0.5, P -value = 0.01) were associated with protection against CCC. To gain insight into the participation of the CCL5-CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1 + CD8 + T cells and CD14 + macrophages were decreased, while frequencies of CCR5 + cells were increased. Importantly, CCR1 + CD14 + macrophages were mainly IL-10 + , while CCR5 + cells were mostly TNF + . CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met

  9. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy

    Science.gov (United States)

    Batista, Angelica Martins; Alvarado-Arnez, Lucia Elena; Alves, Silvia Marinho; Melo, Gloria; Pereira, Isabela Resende; Ruivo, Leonardo Alexandre de Souza; da Silva, Andrea Alice; Gibaldi, Daniel; da Silva, Thayse do E. S. Protásio; de Lorena, Virginia Maria Barros; de Melo, Adriene Siqueira; de Araújo Soares, Ana Karine; Barros, Michelle da Silva; Costa, Vláudia Maria Assis; Cardoso, Cynthia C.; Pacheco, Antonio G.; Carrazzone, Cristina; Oliveira, Wilson; Moraes, Milton Ozório; Lannes-Vieira, Joseli

    2018-01-01

    Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC) is a fibrogenic inflammation mainly composed of CD8+ and CD4+ T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs) in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611) and CCL5 (rs2107538, rs2280788) and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672) and CCR5 (rs1799987) with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n = 110) or cardiopathic (mild, B1, n = 163; severe, C, n = 133). Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 −403 (rs2107538) CT heterozygotes (OR = 0.5, P-value = 0.04) and T carriers (OR = 0.5, P-value = 0.01) were associated with protection against CCC. To gain insight into the participation of the CCL5–CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1+ CD8+ T cells and CD14+ macrophages were decreased, while frequencies of CCR5+ cells were increased. Importantly, CCR1+CD14+ macrophages were mainly IL-10+, while CCR5+ cells were mostly TNF+. CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met-RANTES therapy) in

  10. Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

    Science.gov (United States)

    Frossard, Jean Louis; Lenglet, Sébastien; Montecucco, Fabrizio; Steffens, Sabine; Galan, Katia; Pelli, Graziano; Spahr, Laurent; Mach, Francois; Hadengue, Antoine

    2011-05-01

    Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4. The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining. The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates. These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.

  11. Suppression of CCR impacts metabolite profile and cell wall composition in Pinus radiata tracheary elements.

    Science.gov (United States)

    Wagner, Armin; Tobimatsu, Yuki; Goeminne, Geert; Phillips, Lorelle; Flint, Heather; Steward, Diane; Torr, Kirk; Donaldson, Lloyd; Boerjan, Wout; Ralph, John

    2013-01-01

    Suppression of the lignin-related gene cinnamoyl-CoA reductase (CCR) in the Pinus radiata tracheary element (TE) system impacted both the metabolite profile and the cell wall matrix in CCR-RNAi lines. UPLC-MS/MS-based metabolite profiling identified elevated levels of p-coumaroyl hexose, caffeic acid hexoside and ferulic acid hexoside in CCR-RNAi lines, indicating a redirection of metabolite flow within phenylpropanoid metabolism. Dilignols derived from coniferyl alcohol such as G(8-5)G, G(8-O-4)G and isodihydrodehydrodiconiferyl alcohol (IDDDC) were substantially depleted, providing evidence for CCR's involvement in coniferyl alcohol biosynthesis. Severe CCR suppression almost halved lignin content in TEs based on a depletion of both H-type and G-type lignin, providing evidence for CCR's involvement in the biosynthesis of both lignin types. 2D-NMR studies revealed minor changes in the H:G-ratio and consequently a largely unchanged interunit linkage distribution in the lignin polymer. However, unusual cell wall components including ferulate and unsaturated fatty acids were identified in TEs by thioacidolysis, pyrolysis-GC/MS and/or 2D-NMR in CCR-RNAi lines, providing new insights into the consequences of CCR suppression in pine. Interestingly, CCR suppression substantially promoted pyrolytic breakdown of cell wall polysaccharides, a phenotype most likely caused by the incorporation of acidic compounds into the cell wall matrix in CCR-RNAi lines.

  12. Solution structure of LC4 transmembrane segment of CCR5.

    Directory of Open Access Journals (Sweden)

    Kazuhide Miyamoto

    Full Text Available CC-chemokine receptor 5 (CCR5 is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1. The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  13. Solution structure of LC4 transmembrane segment of CCR5.

    Science.gov (United States)

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  14. CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.

    Science.gov (United States)

    Kang, HyunJun; Minder, Petra; Park, Mi Ae; Mesquitta, Walatta-Tseyon; Torbett, Bruce E; Slukvin, Igor I

    2015-12-15

    The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.

  15. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

    Directory of Open Access Journals (Sweden)

    Eric Lefebvre

    Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

  16. Structural refinement and prediction of potential CCR2 antagonists through validated multi-QSAR modeling studies.

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Baidya, Sandip Kumar; Gayen, Shovanlal; Jha, Tarun

    2018-01-03

    Chemokines trigger numerous inflammatory responses and modulate the immune system. The interaction between monocyte chemoattractant protein-1 and chemokine receptor 2 (CCR2) may be the cause of atherosclerosis, obesity, and insulin resistance. However, CCR2 is also implicated in other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma, and neuropathic pain. Therefore, there is a paramount importance of designing potent and selective CCR2 antagonists despite a number of drug candidates failed in clinical trials. In this article, 83 CCR2 antagonists by Jhonson and Jhonson Pharmaceuticals have been considered for robust validated multi-QSAR modeling studies to get an idea about the structural and pharmacophoric requirements for designing more potent CCR2 antagonists. All these QSAR models were validated and statistically reliable. Observations resulted from different modeling studies correlated and validated results of other ones. Finally, depending on these QSAR observations, some new molecules were proposed that may exhibit higher activity against CCR2.

  17. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

    Science.gov (United States)

    Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

    2017-04-01

    We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

  18. CCL2 recruits T cells into the brain in a CCR2-independent manner

    DEFF Research Database (Denmark)

    Cédile, Oriane; Wlodarczyk, Agnieszka; Owens, Trevor

    2017-01-01

    CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2-treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine...

  19. The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome.

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    Nowel Azzouz

    Full Text Available BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation.

  20. Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development.

    Science.gov (United States)

    Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

    2017-11-01

    Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  1. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scand......The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...

  2. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  3. Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development.

    Science.gov (United States)

    Marques, Rafael E; Guabiraba, Rodrigo; Del Sarto, Juliana L; Rocha, Rebeca F; Queiroz, Ana Luiza; Cisalpino, Daniel; Marques, Pedro E; Pacca, Carolina C; Fagundes, Caio T; Menezes, Gustavo B; Nogueira, Maurício L; Souza, Danielle G; Teixeira, Mauro M

    2015-08-01

    Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5. © 2015 John Wiley & Sons Ltd.

  4. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  5. Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

    2012-01-01

    Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

  6. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-12-20

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.

  7. CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity.

    Science.gov (United States)

    Cardaba, Clara Moyano; Kerr, Jason S; Mueller, Anja

    2008-09-01

    The chemokine receptor, CCR5, acts as a co-receptor for human immunodeficiency virus entry into cells. CCR5 has been shown to be targeted to cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts or caveolae. Cholesterol is essential for CCL4 binding to CCR5 and for keeping the conformational integrity of the receptor. Filipin treatment leads to loss of caveolin-1 from the membrane and therefore to a collapse of the caveolae. We have found here that sequestration of membrane cholesterol with filipin did not affect receptor signalling, however a loss of ligand-induced internalisation of CCR5 was observed. Cholesterol extraction with methyl-beta-cyclodextrin (MCD) reduced signalling through CCR5 as measured by release of intracellular Ca(2+) and completely abolished the inhibition of forskolin-stimulated cAMP accumulation with no effect on internalisation. Pertussis toxin (PTX) treatment inhibited the intracellular release of calcium that is transduced via Galphai G-proteins. Depletion of cholesterol destroyed microdomains in the membrane and switched CCR5/G-protein coupling to a PTX-independent G-protein. We conclude that cholesterol in the membrane is essential for CCR5 signalling via the Galphai G-protein subunit, and that integrity of lipid rafts is not essential for effective CCR5 internalisation however it is crucial for proper CCR5 signal transduction via Galphai G-proteins.

  8. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

    DEFF Research Database (Denmark)

    Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt

    2004-01-01

    Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5...... at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did...... not interfere with chemokine-induced Ca(2+) signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca(2+) signaling by itself at concentrations up to 400 microM. In freshly isolated monocytes, AMD3451 inhibited the Ca(2+) flux induced by CXCL12 and CCL4...

  9. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Directory of Open Access Journals (Sweden)

    Michail S Lionakis

    Full Text Available Invasive candidiasis is the 4(th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo to Ccr1(high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+ and Ccr1(-/- donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  10. CCR6(+) Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis.

    Science.gov (United States)

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Davelaar, Nadine; Vroman, Heleen; Hazes, Johanna M W; de Jong, Pascal H P; Lubberts, Erik

    2015-11-30

    Patients with rheumatoid arthritis (RA) can be separated into two major subpopulations based on the absence or presence of serum anti-citrullinated protein antibodies (ACPAs). The more severe disease course in ACPA(+) RA and differences in treatment outcome between these subpopulations suggest that ACPA(+) and ACPA(-) RA are different disease subsets. The identification of T-helper (Th) cells specifically recognizing citrullinated peptides, combined with the strong association between HLA-DRB1 and ACPA positivity, point toward a pathogenic role of Th cells in ACPA(+) RA. In this context we recently identified a potential pathogenic role for CCR6(+) Th cells in RA. Therefore, we examined whether Th cell population distributions differ by ACPA status. We performed a nested matched case-control study including 27 ACPA(+) and 27 ACPA(-) treatment-naive early RA patients matched for disease activity score in 44 joints, presence of rheumatoid factor, sex, age, duration of complaints and presence of erosions. CD4(+)CD45RO(+) (memory) Th cell distribution profiles from these patients were generated based on differential chemokine receptor expression and related with disease duration. ACPA status was not related to differences in total CD4(+) T cell or memory Th cell proportions. However, ACPA(+) patients had significantly higher proportions of Th cells expressing the chemokine receptors CCR6 and CXCR3. Similar proportions of CCR4(+) and CCR10(+) Th cells were found. Within the CCR6(+) cell population, four Th subpopulations were distinguished based on differential chemokine receptor expression: Th17 (CCR4(+)CCR10(-)), Th17.1 (CXCR3(+)), Th22 (CCR4(+)CCR10(+)) and CCR4/CXCR3 double-positive (DP) cells. In particular, higher proportions of Th22 (p = 0.02), Th17.1 (p = 0.03) and CCR4/CXCR3 DP (p = 0.01) cells were present in ACPA(+) patients. In contrast, ACPA status was not associated with differences in Th1 (CCR6(-)CXCR3(+); p = 0.90), Th2 (CCR6(-)CCR4(+); p = 0.27) and T

  11. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Directory of Open Access Journals (Sweden)

    Hiromi Toyoda

    Full Text Available Narcolepsy is caused by the loss of hypocretin (Hcrt neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif receptor 3 (CCR3 as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT littermates. Intraperitoneal injection of lipopolysaccharide (LPS promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  12. Blocking spinal CCR2 with AZ889 reversed hyperalgesia in a model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Vaillancourt François

    2010-12-01

    Full Text Available Abstract Background The CCR2/CCL2 system has been identified as a regulator in the pathogenesis of neuropathy-induced pain. However, CCR2 target validation in analgesia and the mechanism underlying antinociception produced by CCR2 antagonists remains poorly understood. In this study, in vitro and in vivo pharmacological approaches using a novel CCR2 antagonist, AZ889, strengthened the hypothesis of a CCR2 contribution to neuropathic pain and provided confidence over the possibilities to treat neuropathic pain with CCR2 antagonists. Results We provided evidence that dorsal root ganglia (DRG cells harvested from CCI animals responded to stimulation by CCL2 with a concentration-dependent calcium rise involving PLC-dependent internal stores. This response was associated with an increase in evoked neuronal action potentials suggesting these cells were sensitive to CCR2 signalling. Importantly, treatment with AZ889 abolished CCL2-evoked excitation confirming that this activity is CCR2-mediated. Neuronal and non-neuronal cells in the spinal cord were also excited by CCL2 applications indicating an important role of spinal CCR2 in neuropathic pain. We next showed that in vivo spinal intrathecal injection of AZ889 produced dose-dependent analgesia in CCI rats. Additionally, application of AZ889 to the exposed spinal cord inhibited evoked neuronal activity and confirmed that CCR2-mediated analgesia involved predominantly the spinal cord. Furthermore, AZ889 abolished NMDA-dependent wind-up of spinal withdrawal reflex pathway in neuropathic animals giving insight into the spinal mechanism underlying the analgesic properties of AZ889. Conclusions Overall, this study strengthens the important role of CCR2 in neuropathic pain and highlights feasibility that interfering on this mechanism at the spinal level with a selective antagonist can provide new analgesia opportunities.

  13. Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

    Science.gov (United States)

    Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

    2010-01-01

    Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

  14. Study of brain atrophy using X-ray computed tomography. Measurement of CSF space-cranial cavity ratio (CCR)

    Energy Technology Data Exchange (ETDEWEB)

    Kawabata, Masayoshi

    1987-04-01

    Cerebrospinal fluid space-cranial cavity ratio (CCR) of 811 subjects with no brain damage were investigated using X-ray computed tomography. Brain volume of healthy adults aged 20 - 59 years was almost constant and decreased gradually after 60 years. CCR of men aged 20 - 49 years kept constant value and increased with aging after 50 years. CCR of women aged 20 - 59 years kept equal value and CCR increased with aging after 60 years. Brain atrophy with aging was investigated in this study also. In retrospective study, CCR of patients in any age diagnosed brain atrophy in daily CT reports were beyond the normal range of CCR of healthy subjects aged 20 - 49 years. In 48 patients with Parkinson's disease, almost of CCR of them were included within normal range of CCR in age-matched control.

  15. 77 FR 55833 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-11

    ... on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on... potential approaches for providing Consumer Confidence Reports (CCR) via electronic delivery. EPA plans to... meeting to give EPA time to process your request. Background Consumer Confidence Reports are a key part of...

  16. 77 FR 57566 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-18

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OW-2012-0035; FRL-9730-7] Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR; Correction AGENCY: Environmental Protection Agency...

  17. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5

    DEFF Research Database (Denmark)

    Berg, Christian; Spiess, Katja; von Lüttichau, Hans Rudolf

    2016-01-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1...

  18. Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

    Science.gov (United States)

    Xu, Guoyan G.; Guo, Jia; Wu, Yuntao

    2015-01-01

    The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc. PMID:25159165

  19. Profile of State College and Career Readiness Assessments (CCR) Policy. Florida

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Florida's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  20. Profile of State College and Career Readiness Assessments (CCR) Policy. Arkansas

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Arkansas' college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  1. Profile of State College and Career Readiness Assessments (CCR) Policy. Minnesota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Minnesota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  2. Profile of State College and Career Readiness Assessments (CCR) Policy. Alaska

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alaska's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  3. Profile of State College and Career Readiness Assessments (CCR) Policy. South Carolina

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on South Carolina's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  4. Profile of State College and Career Readiness Assessments (CCR) Policy. Kentucky

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Kentucky's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  5. Profile of State College and Career Readiness Assessments (CCR) Policy. Georgia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Georgia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  6. Profile of State College and Career Readiness Assessments (CCR) Policy. North Dakota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on North Dakota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  7. Profile of State College and Career Readiness Assessments (CCR) Policy. Alabama

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alabama's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  8. Profile of State College and Career Readiness Assessments (CCR) Policy. New Mexico

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on New Mexico's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  9. Profile of State College and Career Readiness Assessments (CCR) Policy. Tennessee

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Tennessee's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  10. Profile of State College and Career Readiness Assessments (CCR) Policy. California

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on California's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  11. Profile of State College and Career Readiness Assessments (CCR) Policy. West Virginia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on West Virginia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  12. Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Assenholt, Jannie; Mouaikel, John; Saguez, Cyril

    2011-01-01

    RNPs are exported to the cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae cytoplasmic deadenylase, has recently been implied in nuclear exosome–related processes. Consistent with a possible nuclear function of the complex, the deletion or mutation of Ccr4-Not factors also elicits...

  13. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Qingwen Jin

    Full Text Available Insertion of T4 lysozyme (T4L into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1 infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

  14. Limited protective effect of the CCR5Δ32/CCR5Δ32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)–infected patients with hemophilia. One patient (0.6%) had the CCR5Δ32/CCR5Δ32 genotype (which occurs in ∼2% of the Scandinavian population...

  15. Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio, E-mail: shimada@iw-nmr.f.u-tokyo.ac.jp [The University of Tokyo, Graduate School of Pharmaceutical Sciences (Japan)

    2015-12-15

    C–C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5–MIP-1α interaction affects the progress of autoimmune diseases.

  16. Enriquecimento com calda do CCR para face de barragens

    Directory of Open Access Journals (Sweden)

    A. P. Wendler

    Full Text Available A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferentes relações água/cimento e quantidades de calda e posterior extração de testemunhos, os quais foram submetidos a ensaios mecânicos e de permeabilidade. Os resultados mostraram que para relações água/cimento 0,74, o material resultante atendeu às especificações de projeto, para consumos de cimento notadamente menores (entre 70 e 85% do CCV.

  17. Frequency of CCR5delta32 in Brazilian populations

    Directory of Open Access Journals (Sweden)

    A.E. Vargas

    2006-03-01

    Full Text Available A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59, while blacks and browns (mulattoes were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively, suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

  18. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  19. Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

    Directory of Open Access Journals (Sweden)

    Gupta Arvind

    2007-04-01

    Full Text Available Abstract Background Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI. Transforming growth factor β1 (TGF β1 induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα, chemoattractant protein-1 (MCP-1, and regulated upon activation and normal T cell expressed and secreted (RANTES mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. Methods Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR and 95% confidence intervals (CI. Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. Results SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84. In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035. Conclusion Of the various cytokine gene

  20. Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

    Science.gov (United States)

    Kohno, Hideo; Koso, Hideto; Okano, Kiichiro; Sundermeier, Thomas R; Saito, Saburo; Watanabe, Sumiko; Tsuneoka, Hiroshi; Sakai, Tsutomu

    2015-10-12

    Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1 (GFP/GFP) and Ccr2 (RFP/RFP) mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation. In this study, c-mer proto-oncogene tyrosine kinase (Mertk) (-/-) mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were established by breeding Mertk (-/-) , Cx3cr1 (GFP/GFP) , and Ccr2 (RFP/RFP) mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry. Four-week-old Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. These invading cells were still observed in the

  1. Interaction of small molecule inhibitors of HIV-1 entry with CCR5

    International Nuclear Information System (INIS)

    Seibert, Christoph; Ying Weiwen; Gavrilov, Svetlana; Tsamis, Fotini; Kuhmann, Shawn E.; Palani, Anandan; Tagat, Jayaram R.; Clader, John W.; McCombie, Stuart W.; Baroudy, Bahige M.; Smith, Steven O.; Dragic, Tatjana; Moore, John P.; Sakmar, Thomas P.

    2006-01-01

    The CC-chemokine receptor 5 (CCR5) is the major coreceptor for macrophage-tropic (R5) HIV-1 strains. Several small molecule inhibitors of CCR5 that block chemokine binding and HIV-1 entry are being evaluated as drug candidates. Here we define how CCR5 antagonists TAK-779, AD101 (SCH-350581) and SCH-C (SCH-351125), which inhibit HIV-1 entry, interact with CCR5. Using a mutagenesis approach in combination with a viral entry assay to provide a direct functional read out, we tested predictions based on a homology model of CCR5 and analyzed the functions of more than 30 amino acid residues. We find that a key set of aromatic and aliphatic residues serves as a hydrophobic core for the ligand binding pocket, while E283 is critical for high affinity interaction, most likely by acting as the counterion for a positively charged nitrogen atom common to all three inhibitors. These results provide a structural basis for understanding how specific antagonists interact with CCR5, and may be useful for the rational design of new, improved CCR5 ligands

  2. CCR8 signaling influences Toll-like receptor 4 responses in human macrophages in inflammatory diseases.

    Science.gov (United States)

    Reimer, Martina Kvist; Brange, Charlotte; Rosendahl, Alexander

    2011-12-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients.

  3. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

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    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  4. DISTRIBUTION OF CCR2-64I GENE AMONG THE TRIBES AND CASTE POPULATION OF VIDARBHA, INDIA.

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    Arvind B Chavhan

    2013-08-01

    Results: The genotyping for the CCR2-64I mutation among the selected tribe and a caste reveal that all of the tribes and a caste was found to be heterozygous for the CCR2-64I mutation. Among the tribes Gonds showed highest genotype frequency (29.28% and (11.76% for heterozygous (CCR2/64I and Homozygous (64I/64I respectively, having an allelic frequency (0.233. A pooled allelic frequencies of the wild-type allele CCR2 and CCR2 64I the variant were found to be 0.854 and 0.146, respectively. No significant deviations from the HWE were observed for tribes and a caste population for the CCR2- 64I mutant χ2=2.76. The study reports the presence of mutant CCR2- 64I gene in tribes and caste population from Vidarbha region.

  5. CD4-independent use of the CCR5 receptor by sequential primary SIVsm isolates

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    Thorstensson Rigmor

    2007-07-01

    Full Text Available Abstract Background CD4-independence has been taken as a sign of a more open envelope structure that is more accessible to neutralizing antibodies and may confer altered cell tropism. In the present study, we analyzed SIVsm isolates for CD4-independent use of CCR5, mode of CCR5-use and macrophage tropism. The isolates have been collected sequentially from 13 experimentally infected cynomolgus macaques and have previously been shown to use CCR5 together with CD4. Furthermore, viruses obtained early after infection were neutralization sensitive, while neutralization resistance appeared already three months after infection in monkeys with progressive immunodeficiency. Results Depending whether isolated early or late in infection, two phenotypes of CD4-independent use of CCR5 could be observed. The inoculum virus (SIVsm isolate SMM-3 and reisolates obtained early in infection often showed a pronounced CD4-independence since virus production and/or syncytia induction could be detected directly in NP-2 cells expressing CCR5 but not CD4 (CD4-independent-HIGH. Conversely, late isolates were often more CD4-dependent in that productive infection in NP-2/CCR5 cells was in most cases weak and was revealed only after cocultivation of infected NP-2/CCR5 cells with peripheral blood mononuclear cells (CD4-independent-LOW. Considering neutralization sensitivity of these isolates, newly infected macaques often harbored virus populations with a CD4-independent-HIGH and neutralization sensitive phenotype that changed to a CD4-independent-LOW and neutralization resistant virus population in the course of infection. Phenotype changes occurred faster in progressor than long-term non-progressor macaques. The phenotypes were not reflected by macrophage tropism, since all isolates replicated efficiently in macrophages. Infection of cells expressing CCR5/CXCR4 chimeric receptors revealed that SIVsm used the CCR5 receptor in a different mode than HIV-1. Conclusion Our

  6. Targeting Spare CC Chemokine Receptor 5 (CCR5) as a Principle to Inhibit HIV-1 Entry*

    OpenAIRE

    Jin, Jun; Colin, Philippe; Staropoli, Isabelle; Lima-Fernandes, Evelyne; Ferret, Cécile; Demir, Arzu; Rogée, Sophie; Hartley, Oliver; Randriamampita, Clotilde; Scott, Mark G. H.; Marullo, Stefano; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Lagane, Bernard; Brelot, Anne

    2014-01-01

    International audience; : CCR5 binds the chemokines CCL3, CCL4, and CCL5 and is the major coreceptor for HIV-1 entry into target cells. Chemokines are supposed to form a natural barrier against human immunodeficiency virus, type 1 (HIV-1) infection. However, we showed that their antiviral activity is limited by CCR5 adopting low-chemokine affinity conformations at the cell surface. Here, we investigated whether a pool of CCR5 that is not stabilized by chemokines could represent a target for i...

  7. The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Møller, M; Søndergaard, Helle B; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We...... impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031). CONCLUSIONS: CCR5 Δ32 is not associated with lower disease...

  8. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

    OpenAIRE

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John AL

    2014-01-01

    Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populatio...

  9. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  10. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

    DEFF Research Database (Denmark)

    Motley, Michael P; Madsen, Daniel H; Jürgensen, Henrik J

    2016-01-01

    cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished...... by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin...... subsets of macrophages employing distinct molecular pathways....

  11. Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Strieter, R M

    2004-01-01

    The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied...... the expression of CCR2 on leukocytes in blood and cerebrospinal fluid (CSF) from patients with monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF from these patients. Results were compared with the results in non-inflammatory neurological controls and were correlated with other...... parameters (magnetic resonance imaging and CSF data). Our findings suggest a limited role for CCL2/CCR2 in early active MS....

  12. [Novel echogenic needle for ultrasound-guided peripheral nerve block "Hakko type CCR"].

    Science.gov (United States)

    Takayama, Wataru; Yasumura, Rie; Kaneko, Takehiko; Kobayashi, Yoshiro; Kamada, Takaaki; Yoshikawa, Tamotsu; Aoyama, Yasuhiko

    2009-04-01

    A novel echogenic insulated nerve block needle (CCR-needle: Echogenic Needle Type CCR; Hakko, Japan) is commercially available since 2006 in Japan. This needle has three echogenic dimples, namely corner cube reflectors (CCR) on its tip. The CCR-needle will potentially provide a significant advantage for detecting the needle tip. In this report, we firstly evaluated this new disposable echogenic needle in simulation phantom, and demonstrated improved visibility of the needle tip. Afterwards, an interscalene brachial plexus block was performed on a male patient undergoing shoulder surgery. The needle insertion procedure was the "out of plane" ultrasound-guided technique using simultaneous electrical nerve stimulation. The surgery was successfully conducted without any complications.

  13. Study progress of CCR3 in wet age-related macular degeneration

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    Xian-Wei Wu

    2014-03-01

    Full Text Available According to the study, chemokine receptor 3(CCR3in the eye is mainly distributed in retinal pigment epithelial cells, and also expressed in the choroidal vascular endothelial cells(CECs. The specificity of CCR3's high expression in wet age-related macular degeneration(AMDwas found, and it is proved that in wet-AMD patients, it plays an important role in the formation of choroidal neovascularization(CNV. In this paper, the structure, function, the problem of current research and the future direction of CCR3 were summarized. It is believed that with the further research on CCR3, it will not only help us to find a new method of wet-AMD diagnosis and treatment, but also may provide an important reference for other CNV disease research and new anti-CNV drugs.

  14. Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort.

    Science.gov (United States)

    Vega, Jorge A; Villegas-Ospina, Simón; Aguilar-Jiménez, Wbeimar; Rugeles, María T; Bedoya, Gabriel; Zapata, Wildeman

    2017-06-01

    Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

  15. CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.

    Science.gov (United States)

    Wei, Robert G; Arnaiz, Damian O; Chou, Yuo-Ling; Davey, Dave; Dunning, Laura; Lee, Wheeseong; Lu, Shou-Fu; Onuffer, James; Ye, Bin; Phillips, Gary

    2007-01-01

    High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.

  16. Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury.

    Science.gov (United States)

    Gyoneva, Stefka; Kim, Daniel; Katsumoto, Atsuko; Kokiko-Cochran, O Nicole; Lamb, Bruce T; Ransohoff, Richard M

    2015-12-03

    Millions of people experience traumatic brain injury (TBI) as a result of falls, car accidents, sports injury, and blast. TBI has been associated with the development of neurodegenerative conditions such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). In the initial hours and days, the pathology of TBI comprises neuronal injury, breakdown of the blood-brain barrier, and inflammation. At the cellular level, the inflammatory reaction consists of responses by brain-resident microglia, astrocytes, and vascular elements as well as infiltration of peripheral cells. After TBI, signaling by chemokine (C-C motif) ligand 2 (CCL2) to the chemokine (C-C motif) receptor 2 (CCR2) is a key regulator of brain infiltration by monocytes. We utilized mice with one or both copies of Ccr2 disrupted by red fluorescent protein (RFP, Ccr2 (RFP/+) and Ccr2 (RFP/RFP) ). We subjected these mice to the mild lateral fluid percussion model of TBI and examined several pathological outcomes 3 days later in order to determine the effects of altered monocyte entry into the brain. Ccr2 deletion reduced monocyte infiltration, diminished lesion cavity volume, and lessened axonal damage after mild TBI, but the microglial reaction to the lesion was not affected. We further examined phosphorylation of the microtubule-associated protein tau, which aggregates in brains of people with TBI, AD, and CTE. Surprisingly, Ccr2 deletion was associated with increased tau mislocalization to the cell body in the cortex and hippocampus by tissue staining and increased levels of phosphorylated tau in the hippocampus by Western blot. Disruption of CCR2 enhanced tau pathology and reduced cavity volume in the context of TBI. The data reveal a complex role for CCR2(+) monocytes in TBI, as monitored by cavity volume, axonal damage, and tau phosphorylation.

  17. Frequency of CCR5Δ32 allele in healthy Bosniak population.

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    Grażyna Adler

    2014-08-01

    Full Text Available Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12% and lower in the regions of Southeast Mediterranean (about 5%. Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013.  Mean age of the cohort being 58.8 (±10.7 years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. 

  18. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

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    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

  19. Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

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    Kvien Tore K

    2007-06-01

    Full Text Available Abstract Background The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Δ32 and rheumatoid arthritis (RA has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA, an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5Δ32 polymorphism is associated with RA or JIA in Norwegian cohorts. Methods 853 RA patients, 524 JIA patients and 658 controls were genotyped for the CCR5Δ32 polymorphism. Results The CCR5Δ32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; P = 0.36 and 9.7% in JIA patients (OR = 0.85; P = 0.20. No decreased homozygosity was observed for CCR5Δ32, as previously suggested. Conclusion Our data do not support an association between the CCR5Δ32 allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for CCR5Δ32 in RA, albeit substantially weaker than the effect first reported.

  20. CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.

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    Shih-Wei Wang

    Full Text Available BACKGROUND: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells. CONCLUSIONS/SIGNIFICANCE: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

  1. Functional characterization of CCR in birch (Betula platyphylla × Betula pendula) through overexpression and suppression analysis.

    Science.gov (United States)

    Zhang, Wenbo; Wei, Rui; Chen, Su; Jiang, Jing; Li, Huiyu; Huang, Haijiao; Yang, Guang; Wang, Shuo; Wei, Hairong; Liu, Guifeng

    2015-06-01

    We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and first internode of Betula platyphylla and characterized its functions in lignin biosynthesis, wood formation and tree growth through transgenic approaches. We generated overexpression and suppression transgenic lines and analyzed them in comparison with the wild-type in terms of lignin content, anatomical characteristics, height and biomass. We found that BpCCR1 overexpression could increase lignin content up to 14.6%, and its underexpression decreased lignin content by 6.3%. Surprisingly, modification of BpCCR1 expression led to conspicuous changes in wood characteristics, including xylem vessel number and arrangement, and secondary wall thickness. The growth of transgenic trees in terms of height was also significantly influenced by the modification of BpCCR1 genes. We discuss the functions of BpCCR1 in the context of a phylogenetic tree built with CCR genes from multiple species. © 2014 Scandinavian Plant Physiology Society.

  2. CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer.

    Science.gov (United States)

    Banin-Hirata, Bruna Karina; Losi-Guembarovski, Roberta; Oda, Julie Massayo Maeda; de Oliveira, Carlos Eduardo Coral; Campos, Clodoaldo Zago; Mazzuco, Tânia Longo; Borelli, Sueli Donizete; Ceribelli, Jesus Roberto; Watanabe, Maria Angelica Ehara

    2016-05-01

    Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation.

  3. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

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    Gero Hütter

    2015-07-01

    Full Text Available Allogeneic transplantation with CCR5-delta 32 (CCR5-d32 homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN, clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9, transcription activator-like effectors nuclease (TALEN, short hairpin RNA (shRNA, and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  4. MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8

    DEFF Research Database (Denmark)

    Lüttichau, H R; Gerstoft, J; Schwartz, T W

    2001-01-01

    The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted...... as a high-affinity agonist, whereas vMIP-II acted as a low-affinity antagonist on the murine CCR8 as well as the human CCR8. MC148 was found to bind and block responses through the human CCR8 with high affinity, but surprisingly MC148 was unable to bind and block responses through the murine CCR8. Because...

  5. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.

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    Noah Saederup

    2010-10-01

    Full Text Available Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.We created CCR2-red fluorescent protein (RFP knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi/CCR2(hi monocytes. Surprisingly, neutrophils, not Ly6C(lo monocytes, largely replaced Ly6C(hi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

  6. Distribution of the CCR5delta32 allele (gene variant CCR5) in Rondônia, Western Amazonian region, Brazil

    Science.gov (United States)

    de Farias, Josileide Duarte; Santos, Marlene Guimarães; de França, Andonai Krauze; Delani, Daniel; Tada, Mauro Shugiro; Casseb, Almeida Andrade; Simões, Aguinaldo Luiz; Engracia, Vera

    2012-01-01

    Since around 1723, on the occasion of its initial colonization by Europeans, Rondonia has received successive waves of immigrants. This has been further swelled by individuals from northeastern Brazil, who began entering at the beginning of the twentieth century. The ethnic composition varies across the state according to the various sites of settlement of each wave of immigrants. We analyzed the frequency of the CCR5Δ32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in five sample sets from the population. Four were collected in Porto Velho, the state capital and the site of several waves of migration. Of these, two, from the Hospital de Base were comprised of HB Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%, respectively, a third from the peri-urban neighborhoods of Candelária/Bate-Estaca (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%) came from the inland Quilombola village of Pedras Negras. Two homozygous individuals (CCR5Δ32/CCR5Δ32) were detected among the HB Mother samples. The frequency of this allele was heterogeneous and higher where the European inflow was more pronounced. The presence of the allele in Pedras Negras revealed European miscegenation in a community largely comprising Quilombolas. PMID:22481870

  7. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

    Science.gov (United States)

    Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M

    2012-11-01

    The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. © 2012 John Wiley & Sons A/S.

  8. Exacerbation of Facial Motoneuron Loss after Facial Nerve Axotomy in CCR3-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Derek A Wainwright

    2009-11-01

    Full Text Available We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron survival after facial nerve axotomy that is dependent on CD4+ Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4+ Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type, a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3–/– mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2 –/– (recombination activating gene-2-deficient mice adoptively transferred CD4+ T-cells isolated from CCR3–/– mice, but not in CCR3–/– mice adoptively transferred CD4+ T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4+ T-cell- and CCR3-mediated neuroprotection after FMN injury.

  9. CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.

    Directory of Open Access Journals (Sweden)

    Giuliano Bonfá

    Full Text Available CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/- mice with a sub lethal dose of the parasite by oral route. CCR5(-/- mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/- mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/- infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/- infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.

  10. Quantum optics

    National Research Council Canada - National Science Library

    Agarwal, G. S

    2013-01-01

    .... Focusing on applications of quantum optics, the textbook covers recent developments such as engineering of quantum states, quantum optics on a chip, nano-mechanical mirrors, quantum entanglement...

  11. CCR2 V64I polymorphism in rifampicin resistant tuberculosis patients in Moewardi General Hospital Surakarta, Indonesia

    Science.gov (United States)

    Marwoto; Agung Prasetyo, Afiono; Reviono; Suradi

    2018-05-01

    CC chemokine receptor-2 (CCR2) play important roles in inflammation. The CCR2 V64I polymorphism already reported associated with many diseases; however, the association of CCR2 V64I polymorphism with tuberculosis is still unknown. Also, there is no report about the presentation of CCR2 V64I polymorphisms in Indonesian tuberculosis patients with rifampicin-mono resistant status has ever been published, to the best of our knowledge. This study evaluated the presence of CCR2 V64I polymorphisms in Javanese rifampicin-mono resistant tuberculosis patients. In an ongoing molecular epidemiology study of human genomic polymorphisms and infection, 51 Javanese rifampicin-mono resistant tuberculosis patients in Dr. Moewardi General Hospital in Surakarta were enrolled in the study. The blood samples were aliquoted and fractionated. The nucleic acids were extracted from all blood samples and subjected to the CCR2 V64I polymorphisms detection by a polymerase chain reaction-sequence-specific primer (PCR-SSP) technique. PCR products were analyzed in 3% agarose. CCR2 64V and 64I homozygote were found in 23.5% (12/51) and 23.5% (12/51) blood samples, respectively. The CCR2 VI genotype was found in 52.9% (27/51) blood samples. The CCR2 VI genotype was found predominant in Javanese rifampicin-mono resistant tuberculosis patients and may have anassociation with the clinical progression.

  12. 92R Monoclonal Antibody Inhibits Human CCR9+ Leukemia Cells Growth in NSG Mice Xenografts.

    Science.gov (United States)

    Somovilla-Crespo, Beatriz; Martín Monzón, Maria Teresa; Vela, Maria; Corraliza-Gorjón, Isabel; Santamaria, Silvia; Garcia-Sanz, Jose A; Kremer, Leonor

    2018-01-01

    CCR9 is as an interesting target for the treatment of human CCR9 + -T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding. 92R inhibits human CCR9 + tumor growth in T and B-cell deficient Rag2 -/- mice. In vitro assays suggested complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity as possible in vivo mechanisms of action. Unexpectedly, 92R strongly inhibited tumor growth also in a model with compromised NK and complement activities, suggesting that other mechanisms, including phagocytosis or apoptosis, might also be playing a role on 92R-mediated tumor elimination. Taken together, these data contribute to strengthen the hypothesis of the immune system's opportunistic nature.

  13. Inhibition of HIV-1 infection by synthetic peptides derived CCR5 fragments

    International Nuclear Information System (INIS)

    Imai, Masaki; Baranyi, Lajos; Okada, Noriko; Okada, Hidechika

    2007-01-01

    HIV-1 infection requires interaction of viral envelope protein gp160 with CD4 and a chemokine receptor, CCR5 or CXCR4 as entry coreceptor. We designed HIV-inhibitory peptides targeted to CCR5 using a novel computer program (ANTIS), which searched all possible sense-antisense amino acid pairs between proteins. Seven AHBs were found in CCR5 receptor. All AHB peptides were synthesized and tested for their ability to prevent HIV-1 infection to human T cells. A peptide fragment (LC5) which is a part of the CCR5 receptor corresponding to the loop between the fifth and sixth transmembrane regions (amino acids 222-240) proved to inhibit HIV-1 IIIB infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. LC5 effectively indicated dose-dependent manner, and the suppression was enhanced additively by T20 peptide, which inhibits infection in vitro by disrupting the gp41 conformational changes necessary for membrane fusion. Thus, these results indicate that CCR5-derived AHB peptides could provide a useful tool to define the mechanism(s) of HIV infection, and may provide insight which will contribute to the development of an anti-HIV-1 reagent

  14. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

    Science.gov (United States)

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

    2014-01-09

    Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

  15. Design of a Base Station for MEMS CCR Localization in an Optical Sensor Network

    Directory of Open Access Journals (Sweden)

    Chan Gook Park

    2014-05-01

    Full Text Available This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC. The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR is reflected to the base station, and the Time of Flight (ToF data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  16. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  17. Design of a base station for MEMS CCR localization in an optical sensor network.

    Science.gov (United States)

    Park, Chan Gook; Jeon, Hyun Cheol; Kim, Hyoun Jin; Kim, Jae Yoon

    2014-05-08

    This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC). The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR) is reflected to the base station, and the Time of Flight (ToF) data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS) methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  18. Influence of CCR7 ligand DNA preexposure on the magnitude and duration of immunity

    International Nuclear Information System (INIS)

    Lee, Yunsang; Seong, Kug Eo; Rouse, Richard J.D.; Rouse, Barry T.

    2003-01-01

    The CC chemokine receptor (CCR) 7 ligands CCL21 and CCL19 were recently described as essential elements for establishing the microenvironment needed to initiate optimal immune responses in secondary lymphoid tissues. In the present study we have kinetically investigated the primary responses of naive DO11.10 TCR-transgenic CD4+ T cells (OVA323-339 peptide specific) adoptively transferred into normal BALB/c mice given plasmid DNA encoding CCR7 ligands. The primary responses of CD4+ Tg-T cells in CCR7 ligand DNA recipients occurred more promptly, reaching levels higher than those observed in vector controls. In line with enhanced specific immunity, the T-cell population in CCR7 ligand recipients underwent more in vivo cell division following Ag stimulation, and a higher percentage of Ag-specific T cells expressed an activation phenotype. Moreover, the enhanced primary responses of naive CD4+ T cells appeared to act via affects on migration and maturation of CD11c+ dendritic cells in the draining lymph nodes. In addition following mucosal challenge of herpes simplex virus-immune mice with virus, those that had received CCL21 or CCL19 during priming contained a higher frequency of responding CD4 T cells in lymph nodes and the site of infection. Moreover, CCL21- and CCL19-treated mice showed less severe disease and better survival following challenge. Our results are discussed in terms of the relevance of CCR7 ligand preimmunization to improve vaccine

  19. Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2016-02-01

    C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.

  20. CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells

    International Nuclear Information System (INIS)

    Latinovic, Olga; Reitz, Marvin; Le, Nhut M.; Foulke, James S.; Faetkenheuer, Gerd; Lehmann, Clara; Redfield, Robert R.; Heredia, Alonso

    2011-01-01

    R5 HIV-1 strains resistant to the CCR5 antagonist Maraviroc (MVC) can use drug-bound CCR5. We demonstrate that MVC-resistant HIV-1 exhibits delayed kinetics of coreceptor engagement and fusion during drug-bound versus free CCR5 infection of cell lines. Antibodies directed against the second extracellular loop (ECL2) of CCR5 had greater antiviral activity against MVC-bound compared to MVC-free CCR5 infection. However, in PBMCs, only ECL2 CCR5 antibodies HGS004 and HGS101, but not 2D7, inhibited infection by MVC resistant HIV-1 more potently with MVC-bound than with free CCR5. In addition, HGS004 and HGS101, but not 2D7, restored the antiviral activity of MVC against resistant virus in PBMCs. In flow cytometric studies, CCR5 binding by the HGS mAbs, but not by 2D7, was increased when PBMCs were treated with MVC, suggesting MVC increases exposure of the relevant epitope. Thus, HGS004 and HGS101 have antiviral mechanisms distinct from 2D7 and could help overcome MVC resistance.

  1. Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8

    DEFF Research Database (Denmark)

    Jensen, Pia C; Nygaard, Rie; Thiele, Stefanie

    2007-01-01

    Most nonpeptide antagonists for CC-chemokine receptors share a common pharmacophore with a centrally located, positively charged amine that interacts with the highly conserved glutamic acid (Glu) located in position 6 of transmembrane helix VII (VII:06). We present a novel CCR8 nonpeptide agonist......, 8-[3-(2-methoxyphenoxy)benzyl]-1-phenethyl-1,3,8-triaza-spiro[4.5]decan-4-one (LMD-009), that also contains a centrally located, positively charged amine. LMD-009 selectively stimulated CCR8 among the 20 identified human chemokine receptors. It mediated chemotaxis, inositol phosphate accumulation......-binding pockets of CCR8 uncovered that the binding of LMD-009 and of four analogs [2-(1-(3-(2-methoxyphenoxy)benzyl)-4-hydroxypiperidin-4-yl)benzoic acid (LMD-584), N-ethyl-2-4-methoxybenzenesulfonamide (LMD-902), N-(1-(3-(2-methoxyphenoxy)benzyl)piperidin-4-yl)-2-phenyl-4-(pyrrolidin-1yl)butanamide (LMD-268...

  2. The prognostic significance and relationship with body composition of CCR7-positive cells in colorectal cancer.

    Science.gov (United States)

    Malietzis, George; Lee, Gui Han; Bernardo, David; Blakemore, Alexandra I F; Knight, Stella C; Moorghen, Morgan; Al-Hassi, Hafid O; Jenkins, John T

    2015-07-01

    The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker. © 2015 Wiley Periodicals, Inc.

  3. Characterization of developmental and stress mediated expression of cinnamoyl-CoA reductase (CCR) in kenaf (Hibiscus cannabinus L.)

    Science.gov (United States)

    Cinnamoyl-CoA reductase (CCR) is an important enzyme for lignin biosynthesis as it catalyzes the first specific committed step in monolignol biosynthesis. We have cloned a full length coding sequence of CCR from kenaf (Hibiscus cannabinus L.), which contains a 1,020-bp open reading frame (ORF), enco...

  4. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S; Ortiz, Carla; O'Connell, Samuel; Hess, Henry; Lord, Graham M; Noelle, Randolph

    2015-01-15

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B(mem)) are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area. Copyright © 2015 by The American Association of Immunologists, Inc.

  5. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S.; Ortiz, Carla; O’Connell, Samuel; Hess, Henry; Lord, Graham M.; Noelle, Randolph

    2014-01-01

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to insure successful cognate interactions. While cognate interactions between T cells and memory B cells (Bmem)5 are essential for the secondary humoral immune responses, the chemokine response patterns of Bmem cells are largely unknown. In contrast to naïve B cells, this study shows that antigen-specific Bmem cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. While CCR6 appears be non-essential for the initial clonal expansion and maintenance of Bmem, CCR6 is essential for the ability of Bmem to respond to a recall response to their cognate antigen. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone-marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient Bmem was revealed by immunohistological analysis with an altered distribution of CCR6-deficient Bmem from the marginal and perifollicular to the follicular/germinal center area. PMID:25505290

  6. Exploring a model of human chemokine receptor CCR2 in presence of TAK779: A membrane based molecular dynamics study

    Science.gov (United States)

    Balupuri, Anand; Sobhia, M. Elizabeth

    2014-04-01

    Chemokine receptor 2 (CCR2) is a G-protein coupled receptor (GPCR) and a crucial target for various inflammation-driven diseases. In the present study, molecular docking and molecular dynamics simulations were performed on a CCR2 homology model. This work includes the comparative MD simulations of uncomplexed and ‘antagonist-complexed’ CCR2 models. These simulations yield insights into the binding mechanism of antagonist TAK779 and improve the understanding of various structural changes induced by the ligand in the CCR2 protein. Here, one 20 ns MD simulation was carried out on the uncomplexed CCR2 model in lipid bilayer to explore the effects of lipid membrane on the protein. Another 20 ns MD simulation was performed under the similar conditions on the docked CCR2-TAK779 complex. An alteration in the position and orientation of the ligand in binding site was observed after the simulation. Examination of protein-ligand complex suggested that TAK779 produced a greater structural change on the TM-III, TM-IV, TM-V and TM-VI than TM-I, TM-II and TM-VII. Interaction networks involving the conserved residues of uncomplexed and ‘antagonist-complexed’ CCR2 models were also examined. The major difference was observed to be the role of conserved residues of the DRY motif of TM-III and the NPxxY motif of TM-VII of CCR2.

  7. Evidence favoring the involvement of CC chemokine receptor (CCR) 5 in T-lymphocyte accumulation in optic neuritis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Jensen, J

    2003-01-01

    To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON).......To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON)....

  8. Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate

    NARCIS (Netherlands)

    Gerlag, Daniëlle M.; Hollis, Sally; Layton, Mark; Vencovský, Jiří; Szekanecz, Zoltán; Braddock, Martin; Tak, Paul P.; Oparanov, Boycho; Stoilov, Rumen; Yaneva, Tanya; Batalov, Anastas; Arteaga, Edgardo Tobias; Escalante, William Otero; Velez, Patricia; Restrepo, Jose Molina; Augustinova, Sevda; Blahova, Anna; Dvorak, Zdenek; Novosad, Libor; Rosa, Jan; Stehlikova, Helena; Vitek, Petr; Balazs, Tibor; Seregely, Katalin; Szombati, Istvan; Tarjan, Katalin; Csengei, Gabor; Galeazzi, Mauro; Saleniece, Sarmite; Saulite-Kandevica, Daina; Coleiro, Bernard; Badurski, Janusz; Brzosko, Marek; Chudzik, Dariusz; Gruszecka-Marczynska, Katarzyna; Hensel, Joanna; Pokrzywnicka-Gajek, Ines; Korpanty-Danda, Joanna; Sochocka-Bykowska, Malgorzata; Tlustochowicz, Witold; Stopinska-Polaszewska, Maria; Gluszko, Piotr; Nedelcovici, Corina; Radulescu, Florin; Gavrila, Mirea; Tanasescu, Coman; Korshunov, Nikolay; Matsievskaia, Galina; Damjanov, Nemanja; Dimic, Aleksandar

    2010-01-01

    To investigate both the preclinical effects of blocking the chemokine receptor CCR5 and the clinical effects of this approach on the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease. Preclinical evaluations of AZD5672, a small-molecule antagonist of CCR5, were

  9. Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients...

  10. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

    2003-01-01

    The chemokine-like, secreted protein product of the U83 gene from human herpesvirus 6, here named vCCL4, was chemically synthesized to be characterized in a complete library of the 18 known human chemokine receptors expressed individually in stably transfected cell lines. vCCL4 was found to cause...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

  11. Differential evolution of a CXCR4-using HIV-1 strain in CCR5wt/wt and CCR5∆32/∆32 hosts revealed by longitudinal deep sequencing and phylogenetic reconstruction.

    Science.gov (United States)

    Le, Anh Q; Taylor, Jeremy; Dong, Winnie; McCloskey, Rosemary; Woods, Conan; Danroth, Ryan; Hayashi, Kanna; Milloy, M-J; Poon, Art F Y; Brumme, Zabrina L

    2015-12-03

    Rare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using ("R5") HIV-1 strains but remain susceptible to less common CXCR4-using ("X4") strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4.5-5 log10 HIV-1 RNA copies/ml), CD4 counts in the CCR5wt/wt individual reached a nadir of 250 cells/mm(3) in the CCR5∆32/∆32 individual. Ancestral phylogenetic reconstructions using longitudinal envelope-V3 deep sequences suggested that both individuals were infected by a single transmitted/founder (T/F) X4 virus that differed at only one V3 site (codon 24). While substantial within-host HIV-1 V3 diversification was observed in plasma and PBMC in both individuals, the CCR5wt/wt individual's HIV-1 population gradually reverted from 100% X4 to ~60% R5 over ~4 years whereas the CCR5∆32/∆32 individual's remained consistently X4. Our observations illuminate early dynamics of X4 HIV-1 infections and underscore the influence of CCR5 genotype on HIV-1 V3 evolution.

  12. Medicinal chemistry of small molecule CCR5 antagonists for blocking HIV-1 entry: a review of structural evolution.

    Science.gov (United States)

    Tian, Ye; Zhang, Dujuan; Zhan, Peng; Liu, Xinyong

    2014-01-01

    CCR5, a member of G protein-coupled receptors superfamily, plays an important role in the HIV-1 entry process. Antagonism of this receptor finally leads to the inhibition of R5 strains of HIV entry into the human cells. The identification of CCR5 antagonists as antiviral agents will provide more option for HAART. Now, more than a decade after the first small molecule CCR5 inhibitor was discovered, great achievements have been made. In this article, we will give a brief introduction of several series of small molecule CCR5 antagonists, focused on their appealing structure evolution, essential SAR information and thereof the enlightenment of strategies on CCR5 inhibitors design.

  13. Quantum Erasure: Quantum Interference Revisited

    OpenAIRE

    Walborn, Stephen P.; Cunha, Marcelo O. Terra; Pádua, Sebastião; Monken, Carlos H.

    2005-01-01

    Recent experiments in quantum optics have shed light on the foundations of quantum physics. Quantum erasers - modified quantum interference experiments - show that quantum entanglement is responsible for the complementarity principle.

  14. CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

    Science.gov (United States)

    Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

    2014-01-01

    CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

  15. Structure-Activity Relationships and Identification of Optmized CC-Chemokine Receptor CCR1, 5, and 8 Metal-Ion Chelators

    DEFF Research Database (Denmark)

    Chalikiopoulos, Alexander; Thiele, Stefanie; Malmgaard-Clausen, Mikkel

    2013-01-01

    Chemokine receptors are involved in trafficking of leukocytes and represent targets for autoimmune conditions, inflammatory diseases, viral infections, and cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive modulators based on a three metal-ion chelator series: 2,2'-bipyridi...

  16. Elucidating a Key Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2014-06-01

    CCL5 (RANTES) is an inflammatory chemokine which binds to chemokine receptor CCR5 and induces signaling. The CCL5:CCR5 associated chemotactic signaling is of critical biological importance and is a potential HIV-1 therapeutic axis. Several studies provided growing evidence for the expression of CCL5 and CCR5 in non-hematological malignancies. Therefore, the delineation of the CCL5:CCR5 complex structure can pave the way for novel CCR5-targeted drugs. We employed a computational protocol which is primarily based on free energy calculations and molecular dynamics simulations, and report, what is to our knowledge, the first computationally derived CCL5:CCR5 complex structure which is in excellent agreement with experimental findings and clarifies the functional role of CCL5 and CCR5 residues which are associated with binding and signaling. A wealth of polar and non-polar interactions contributes to the tight CCL5:CCR5 binding. The structure of an HIV-1 gp120 V3 loop in complex with CCR5 has recently been derived through a similar computational protocol. A comparison between the CCL5 : CCR5 and the HIV-1 gp120 V3 loop : CCR5 complex structures depicts that both the chemokine and the virus primarily interact with the same CCR5 residues. The present work provides insights into the blocking mechanism of HIV-1 by CCL5.

  17. Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors

    International Nuclear Information System (INIS)

    Pugach, Pavel; Ketas, Thomas J.; Michael, Elizabeth; Moore, John P.

    2008-01-01

    The small molecule CCR5 inhibitors are a new class of drugs for treating infection by human immunodeficiency virus type 1 (HIV-1). They act by binding to the CCR5 co-receptor and preventing its use during HIV-1-cell fusion. Escape mutants can be raised against CCR5 inhibitors in vitro and will arise when these drugs are used clinically. Here, we have assessed the responses of CCR5 inhibitor-resistant viruses to other anti-retroviral drugs that act by different mechanisms, and their sensitivities to neutralizing antibodies (NAbs). The rationale for the latter study is that the resistance pathway for CCR5 inhibitors involves changes in the HIV-1 envelope glycoproteins (Env), which are also targets for NAbs. The escape mutants CC101.19 and D1/85.16 were selected for resistance to AD101 and vicriviroc (VVC), respectively, from the primary R5 HIV-1 isolate CC1/85. Each escape mutant was cross-resistant to other small molecule CCR5 inhibitors (aplaviroc, maraviroc, VVC, AD101 and CMPD 167), but sensitive to protein ligands of CCR5: the modified chemokine PSC-RANTES and the humanized MAb PRO-140. The resistant viruses also retained wild-type sensitivity to the nucleoside reverse transcriptase inhibitor (RTI) zidovudine, the non-nucleoside RTI nevirapine, the protease inhibitor atazanavir and other attachment and fusion inhibitors that act independently of CCR5 (BMS-806, PRO-542 and enfuvirtide). Of note is that the escape mutants were more sensitive than the parental CC1/85 isolate to a subset of neutralizing monoclonal antibodies and to some sera from HIV-1-infected people, implying that sequence changes in Env that confer resistance to CCR5 inhibitors can increase the accessibility of some NAb epitopes. The need to preserve NAb resistance may therefore be a constraint upon how escape from CCR5 inhibitors occurs in vivo

  18. Orphan chemokine receptors in neuroimmunology : functional and pharmacological analysis of L-CCR and HCR

    NARCIS (Netherlands)

    Zuurman, Michael Wilhelmer

    2003-01-01

    In this thesis we have investigated the expression and biological activity of the orphan chemokine receptors L-CCR/HCR in astrocytes and microglia. Several lines of evidence indicate that the chemokines CCL2, CCL5, CCL7 and CCL8 are agonists for these receptors. Although a variety of biological

  19. Why CCR: A conversation with Physician Assistant Julia Friend | Center for Cancer Research

    Science.gov (United States)

    "Where else can you make such a profound difference not only for the individual now, but for those who come in the future? It is hard work, good work and worth doing well.” Physician Assistant Julia Friend answers our questions about why she loves working for CCR. Read more...

  20. Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

    DEFF Research Database (Denmark)

    Hjorto, Gertrud M.; Larsen, Olav; Steen, Anne

    2016-01-01

    The CCR7 ligands CCL19 and CCL21 are increasingly recognized as functionally different (biased). Using mature human dendritic cells (DCs), we show that CCL19 is more potent than CCL21 in inducing 3D chemotaxis. Intriguingly, CCL21 induces prolonged and more efficient ERK1/2 activation compared...

  1. Impact of CCR5 Delta32/+ deletion on herpes zoster among HIV-1-infected homosexual men

    NARCIS (Netherlands)

    Krol, Anneke; Lensen, Ruud; Veenstra, Jan; Prins, Maria; Schuitemaker, Hanneke; Coutinho, Roel A.

    2006-01-01

    The association between the presence of CCR5 Delta32 heterozygosity and incidence of clinical herpes zoster was studied among 296 homosexual men from the Amsterdam cohort study (ACS) infected with human immunodeficiency virus type I (HIV-1) with an estimated date of seroconversion. Of them 63 were

  2. Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos.

    Science.gov (United States)

    Raisch, Tobias; Bhandari, Dipankar; Sabath, Kevin; Helms, Sigrun; Valkov, Eugene; Weichenrieder, Oliver; Izaurralde, Elisa

    2016-05-02

    Nanos proteins repress the expression of target mRNAs by recruiting effector complexes through non-conserved N-terminal regions. In vertebrates, Nanos proteins interact with the NOT1 subunit of the CCR4-NOT effector complex through a NOT1 interacting motif (NIM), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR4-NOT deadenylase complex in invertebrates. Here, we identify an effector domain (NED) that is necessary for the Drosophila melanogaster (Dm) Nanos to repress mRNA targets. The NED recruits the CCR4-NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C-terminal domains of NOT1-3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT1 and NOT3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N-terminal regions of Nanos proteins recruit CCR4-NOT to assemble analogous repressive complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  3. TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

    Science.gov (United States)

    Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

    2018-05-08

    The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

  4. Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

    Science.gov (United States)

    Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

    2000-01-01

    A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

  5. Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver transplant recipients.

    Science.gov (United States)

    Li, Hong; Xie, Hai-Yang; Zhou, Lin; Wang, Wei-Lin; Liang, Ting-Bo; Zhang, Min; Zheng, Shu-Sen

    2011-12-01

    The genetic diversity of chemokines and chemokine receptors has been associated with the outcome of hepatitis B virus infection. The aim of this study was to evaluate whether the copy number variation in the CCL3L1 gene and the polymorphisms of CCR5Δ32 and CCR5-2459A→G (rs1799987) are associated with recurrent hepatitis B in liver transplantation for hepatitis B virus infection-related end-stage liver disease. A total of 185 transplant recipients were enrolled in this study. The genomic DNA was extracted from whole blood, the copy number of the CCL3L1 gene was determined by a quantitative real-time PCR based assay, CCR5Δ32 was detected by a sizing PCR method, and a single-nucleotide polymorphism in CCR5-2459 was detected by restriction fragment length polymorphism PCR. No CCR5Δ32 mutation was detected in any of the individuals from China. Neither copy number variation nor polymorphism in CCR5-2459 was associated with post-transplant re-infection with hepatitis B virus. However, patients with fewer copies (CCR5 genes might be more likely to have recurrence of hepatitis B after transplantation.

  6. Relationship between CCR and NT-proBNP in Chinese HF patients, and their correlations with severity of HF.

    Science.gov (United States)

    Lu, Zhigang; Wang, Bo; Wang, Yunliang; Qian, Xueqing; Zheng, Wei; Wei, Meng

    2014-01-01

    To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF.

  7. The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

    Directory of Open Access Journals (Sweden)

    Hütter Gero

    2011-10-01

    Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

  8. CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

    Science.gov (United States)

    Zhong, Wei; Jiang, Zhenyu; Wu, Jiang; Jiang, Yanfang; Zhao, Ling

    2018-01-01

    Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA + SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6 + Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. We recruited 25 anti-DNA + and 25 anti-DNA - treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6 + Th cells and their additional subsets were analyzed in each patient by flow cytometry. Anti-DNA + SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6 + Th cell subsets showed that anti-DNA + SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6 - Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6 + Th subsets and clinical indicators, specifically in anti-DNA + SLE patients. Our data indicated that CCR6 + Th cells and their subsets were elevated and correlated with disease activity in anti-DNA + SLE patients. We speculated that CCR6 + Th cells may contribute to distinct disease severity in anti-DNA + SLE patients.

  9. CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases ▿

    Science.gov (United States)

    Kvist Reimer, Martina; Brange, Charlotte; Rosendahl, Alexander

    2011-01-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients. PMID:21976223

  10. CCR-2 neutralization augments murine fresh BMC activation by Staphylococcus aureus via two distinct mechanisms: at the level of ROS production and cytokine response.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2017-05-01

    CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the bloodstream and then to sites of infection. We sought to determine whether CCL-2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)-NF-κB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to determine whether neutralization of CCR-2 augments the response of murine fresh BMCs (FBMCs) after S. aureus infection. It was observed that anti-CCR-2 Ab-treated FBMCs released fewer ROS on encountering S. aureus infection than CCR-2 non-neutralized FBMCs, also correlating with reduced killing of S. aureus in CCR-2 neutralized FBMCs. Staphylococcal catalase and SOD were also found to play a role in protecting S. aureus from the ROS-mediated killing of FBMC. S. aureus infection of CCR-2 intact FBMCs pre-treated with either NF-κB or p-38-MAPK blocker induced less CCL-2, suggesting that NF-κB or p-38-MAPK is required for CCL-2 production by FBMCs. Moreover, blocking of CCR-2 along with NF-κB or p-38-MAPK resulted in elevated CCL-2 production and reduced CCR-2 expression. Inhibition of CCR-2 impairs the response of murine BMCs to S. aureus infection by attenuation ROS production and modulating the cytokine response.

  11. Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis.

    Science.gov (United States)

    Cavallari, Fransérgio Emílio; Valera, Fabiana Cardoso Pereira; Gallego, Aline Jorge; Malinsky, Rafael Rossell; Küpper, Daniel Salgado; Milanezi, Cristiane; Silva, João Santana da; Tamashiro, Edwin; Anselmo-Lima, Wilma Terezinha

    2012-09-01

    To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.

  12. Quantum optics

    National Research Council Canada - National Science Library

    Agarwal, G. S

    2013-01-01

    ..., quantum metrology, spin squeezing, control of decoherence and many other key topics. Readers are guided through the principles of quantum optics and their uses in a wide variety of areas including quantum information science and quantum mechanics...

  13. Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice.

    Science.gov (United States)

    Menasria, Rafik; Canivet, Coraline; Piret, Jocelyne; Gosselin, Jean; Boivin, Guy

    2016-01-01

    CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6Chi» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2-/- BM-derived cells in CCR2-/- (WT→CCR2-/-) and WT (CCR2-/-→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x106 plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2-/- (71.4%) and CCR2-/-→WT (57.1%) mice were significantly higher than that of WT (15.3%; Pdeficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.

  14. Quantum Instantons and Quantum Chaos

    OpenAIRE

    Jirari, H.; Kröger, H.; Luo, X. Q.; Moriarty, K. J. M.; Rubin, S. G.

    1999-01-01

    Based on a closed form expression for the path integral of quantum transition amplitudes, we suggest rigorous definitions of both, quantum instantons and quantum chaos. As an example we compute the quantum instanton of the double well potential.

  15. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

    Directory of Open Access Journals (Sweden)

    Kazuko Ino

    Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

  16. Quantum metrology

    International Nuclear Information System (INIS)

    Xiang Guo-Yong; Guo Guang-Can

    2013-01-01

    The statistical error is ineluctable in any measurement. Quantum techniques, especially with the development of quantum information, can help us squeeze the statistical error and enhance the precision of measurement. In a quantum system, there are some quantum parameters, such as the quantum state, quantum operator, and quantum dimension, which have no classical counterparts. So quantum metrology deals with not only the traditional parameters, but also the quantum parameters. Quantum metrology includes two important parts: measuring the physical parameters with a precision beating the classical physics limit and measuring the quantum parameters precisely. In this review, we will introduce how quantum characters (e.g., squeezed state and quantum entanglement) yield a higher precision, what the research areas are scientists most interesting in, and what the development status of quantum metrology and its perspectives are. (topical review - quantum information)

  17. HIV-infected individuals with the CCR delta32/CCR5 genotype have lower HIV RNA levels and higher CD4 cell counts in the early years of the infection than do patients with the wild type. Copenhagen AIDS Cohort Study Group

    DEFF Research Database (Denmark)

    Katzenstein, T L; Eugen-Olsen, J; Hofmann, B

    1997-01-01

    The relations among serum HIV RNA levels, CD4 cell counts, presence of the mutant CCR5-allele in heterozygous form, and clinical outcome was analyzed in 96 patients from the Copenhagen AIDS Cohort. In the early years of the infection, patients with the CCR5 delta32/CCR5 genotype had significantly...

  18. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  19. The impact of CCR5-Δ32 deletion on C-reactive protein levels and cardiovascular disease

    DEFF Research Database (Denmark)

    Dinh, Khoa Manh; Pedersen, Ole B; Petersen, Mikkel S

    2015-01-01

    BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Δ32 deletion (CCR5-Δ32) has been associated with lower levels of C-reactive protein (CRP), but the effect on cardiovascular diseases is uncertain. This study addresses the impact of CCR5-Δ32 on the risk of low-grade inflammation...... and hospitalization with cardiovascular diseases in a large cohort of blood donors. METHODS: Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for CCR5-Δ32 was performed and combined with CRP measurements and questionnaire data. Cardiovascular disease diagnoses were identified by ICD-10......: In this cohort, carriers of the CCR5-Δ32 deletion had normal CRP levels but a borderline significant increased risk of cardiovascular diseases....

  20. CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function.

    Science.gov (United States)

    Rivino, Laura; Gruarin, Paola; Häringer, Barbara; Steinfelder, Svenja; Lozza, Laura; Steckel, Bodo; Weick, Anja; Sugliano, Elisa; Jarrossay, David; Kühl, Anja A; Loddenkemper, Christoph; Abrignani, Sergio; Sallusto, Federica; Lanzavecchia, Antonio; Geginat, Jens

    2010-03-15

    Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10-producing memory T cells. Human CD4(+)CCR6(+) memory T cells contained comparable numbers of IL-17- and IL-10-producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)-beta. In normal human spleens, the majority of CCR6(+) memory T cells were in the close vicinity of CCR6(+) myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6(+) memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6(+) T cells induced expression of IL-2, interferon-gamma, CCL20, and CD40L, and autoreactive CCR6(+) T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6(+) T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions.

  1. Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

    Directory of Open Access Journals (Sweden)

    Cauda Roberto

    2006-09-01

    Full Text Available Abstract Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN. The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s, for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04 among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort.

  2. A rhodanine derivative CCR-11 inhibits bacterial proliferation by inhibiting the assembly and GTPase activity of FtsZ.

    Science.gov (United States)

    Singh, Parminder; Jindal, Bhavya; Surolia, Avadhesha; Panda, Dulal

    2012-07-10

    A perturbation of FtsZ assembly dynamics has been shown to inhibit bacterial cytokinesis. In this study, the antibacterial activity of 151 rhodanine compounds was assayed using Bacillus subtilis cells. Of 151 compounds, eight strongly inhibited bacterial proliferation at 2 μM. Subsequently, we used the elongation of B. subtilis cells as a secondary screen to identify potential FtsZ-targeted antibacterial agents. We found that three compounds significantly increased bacterial cell length. One of the three compounds, namely, CCR-11 [(E)-2-thioxo-5-({[3-(trifluoromethyl)phenyl]furan-2-yl}methylene)thiazolidin-4-one], inhibited the assembly and GTPase activity of FtsZ in vitro. CCR-11 bound to FtsZ with a dissociation constant of 1.5 ± 0.3 μM. A docking analysis indicated that CCR-11 may bind to FtsZ in a cavity adjacent to the T7 loop and that short halogen-oxygen, H-bonding, and hydrophobic interactions might be important for the binding of CCR-11 with FtsZ. CCR-11 inhibited the proliferation of B. subtilis cells with a half-maximal inhibitory concentration (IC(50)) of 1.2 ± 0.2 μM and a minimal inhibitory concentration of 3 μM. It also potently inhibited proliferation of Mycobacterium smegmatis cells. Further, CCR-11 perturbed Z-ring formation in B. subtilis cells; however, it neither visibly affected nucleoid segregation nor altered the membrane integrity of the cells. CCR-11 inhibited HeLa cell proliferation with an IC(50) value of 18.1 ± 0.2 μM (∼15 × IC(50) of B. subtilis cell proliferation). The results suggested that CCR-11 inhibits bacterial cytokinesis by inhibiting FtsZ assembly, and it can be used as a lead molecule to develop FtsZ-targeted antibacterial agents.

  3. Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

    DEFF Research Database (Denmark)

    Kerstjens, Huib A; Bjermer, Leif; Eriksson, Leif

    2010-01-01

    OBJECTIVE: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. METHODS: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler....... These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas....

  4. Interaction between NANOS2 and the CCR4-NOT Deadenylation Complex Is Essential for Male Germ Cell Development in Mouse

    OpenAIRE

    Suzuki, Atsushi; Saba, Rie; Miyoshi, Kei; Morita, Yoshinori; Saga, Yumiko

    2012-01-01

    Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the f...

  5. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.

    Science.gov (United States)

    Bolus, W Reid; Gutierrez, Dario A; Kennedy, Arion J; Anderson-Baucum, Emily K; Hasty, Alyssa H

    2015-10-01

    Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation. © Society for Leukocyte Biology.

  6. Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex

    Directory of Open Access Journals (Sweden)

    Ishaan Gupta

    2016-05-01

    Full Text Available The current understanding of gene expression considers transcription and translation to be independent processes. Challenging this notion, we found that translation efficiency is determined during transcription elongation through the imprinting of mRNAs with Not1, the central scaffold of the Ccr4-Not complex. We determined that another subunit of the complex, Not5, defines Not1 binding to specific mRNAs, particularly those produced from ribosomal protein genes. This imprinting mechanism specifically regulates ribosomal protein gene expression, which in turn determines the translational capacity of cells. We validate our model by SILAC and polysome profiling experiments. As a proof of concept, we demonstrate that enhanced translation compensates for transcriptional elongation stress. Taken together, our data indicate that in addition to defining mRNA stability, components of the Ccr4-Not imprinting complex regulate RNA translatability, thus ensuring global gene expression homeostasis.

  7. Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration.

    Science.gov (United States)

    Choi, Dong-Young; Lee, Myung Koo; Hong, Jin Tae

    2013-01-01

    Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg×4 times, 2hr interval)-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model.

    Directory of Open Access Journals (Sweden)

    Charlotte E Egan

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR or susceptible (BALB/c and C57BL/6 to hepatitis followed by molecular and flow cytometric analysis. Following this, a similar approach was taken in congenic mice with specific mutations in immunological genes. The initial study identified a significant and profound increase in multiple ligands for the chemokine receptor CCR2 and an increase in CD44 expression in susceptible C57BL/6 (B6 but not resistant AKR mice. Ccr2(-/- mice were completely protected from hepatitis and Cd44(-/- mice were partially protected. Despite protection from inflammation, both strains displayed similar histological steatosis scores and significant increases in serum liver enzymes. CD45(+CD44(+ cells bound to hyaluronic acid (HA in diet fed B6 mice but not Cd44(-/- or Ccr2(-/- mice. Ccr2(-/- mice displayed a diminished HA binding phenotype most notably in monocytes, and CD8(+ T-cells. In conclusion, this study demonstrates that absence of CCR2 completely and CD44 partially reduces hepatic leukocyte recruitment. These data also provide evidence that there are multiple redundant CCR2 ligands produced during hepatic lipid accumulation and describes the induction of a strong HA binding phenotype in response to LD feeding in some subsets of leukocytes from susceptible strains.

  9. Interleukin 4 increases CCR9 expression and homing of lymphocytes to gut-associated lymphoid tissue in chickens.

    Science.gov (United States)

    Annamalai, Thavamathi; Selvaraj, Ramesh K

    2012-01-15

    The effects of in vitro and in vivo IL-4 supplementation on thymocyte and splenocyte CCR9 mRNA amount and migration were studied. Thymocytes, splenocytes, splenocytes+thymocytes (2:1), and splenocytes+bursocyte cells (2:1) were supplemented with either 0 or 5 ng/ml IL-4 for 5d. CCR9 mRNA was undetectable in all experimental groups supplemented with 0 ng/ml IL-4. IL-4 treatment (5 ng/ml) upregulated (P=0.01) CCR9 mRNA only in the splenocyte+thymocyte cell culture. IL-4-mediated CCR9 mRNA induction in the splenocyte+thymocyte cell culture was dependent on the in vitro dose of IL-4 supplementation. IL-4-treated splenocyte+thymocyte cells when injected in vivo preferentially migrated to cecal tonsils. In vivo supplementation of IL-4 was achieved through in ovo injection of recombinant chicken IL-4 plasmid. Cecal tonsils in chicks hatched from IL-4-plasmid-injected eggs weighed more, had a higher amount of CCR9 mRNA, and had a higher percentage of CD8(+) cells than cecal tonsils from chicks hatched from PBS-injected eggs. It could be concluded that IL-4 induces CCR9 mRNA in thymocytes and splenocytes and directs the migration of cells to gut-associated lymphoid tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. The Increased Expression of CCL20 and CCR6 in Rectal Mucosa Correlated to Severe Inflammation in Pediatric Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Keiichi Uchida

    2015-01-01

    Full Text Available Background/Aims. The aim of this study is to clarify the differences of CCL20 and CCR6 expression, chemokine correlated to intestinal homeostasis, between pediatric and adult ulcerative colitis (UC patients. Methods. Onehundred forty-one patients who underwent proctocolectomy were divided to two groups including childhood-onset UC (CUC, <16 years old, n=24 and adult-onset UC (AUC, ≧16 years old, n=117. A total of 141 formalin-fixed, paraffin-embedded tissue samples of rectum were obtained from these patients. Histological inflammation of rectum in resected specimen was evaluated by using Geboes histological assessment. In immunohistochemistry study, the CCL20 expression was evaluated by intensity and the stained area, and the CCR6 expression was evaluated by lymphocytes infiltration pattern. Results. CCL20 score and CCR6 positive lymphocytes infiltration pattern were statistically significantly correlated with histological inflammation severity of UC in all patients (P<0.05. CCL20 and CCR6 expression in CUC were statistically significantly higher than that in AUC in all or pathologically severe cases (P<0.05. Conclusions. CCL20 and CCR6 may play a significant role in local damage and pathological changes in UC especially pediatric patients. In the future, our understanding of the differences in CCL-CCR6 interaction between adults and children may lead to the pathogenesis of IBD.

  11. Inflammatory monocytes promote progression of Duchenne muscular dystrophy and can be therapeutically targeted via CCR2

    OpenAIRE

    Mojumdar, Kamalika; Liang, Feng; Giordano, Christian; Lemaire, Christian; Danialou, Gawiyou; Okazaki, Tatsuma; Bourdon, Johanne; Rafei, Moutih; Galipeau, Jacques; Divangahi, Maziar; Petrof, Basil J

    2014-01-01

    Myofiber necrosis and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), leading to lethal weakness of the diaphragm. Macrophages (MPs) are required for successful muscle regeneration, but the role of inflammatory monocyte (MO)-derived MPs in either promoting or mitigating DMD is unclear. We show that DMD (mdx) mouse diaphragms exhibit greatly increased expression of CCR2 and its chemokine ligands, along with inflammatory (Ly6Chigh) MO recruitment and accumulation of CD11bhigh MO-de...

  12. HIV-1 tropism testing and clinical management of CCR5 antagonists: Quebec review and recommendations.

    Science.gov (United States)

    Tremblay, Cécile; Hardy, Isabelle; Lalonde, Richard; Trottier, Benoit; Tsarevsky, Irina; Vézina, Louis-Philippe; Roger, Michel; Wainberg, Mark; Baril, Jean-Guy

    2013-01-01

    HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

  13. Screening of chemokine receptor CCR4 antagonists by capillary zone electrophoresis

    Directory of Open Access Journals (Sweden)

    Zhe Sun

    2011-11-01

    Full Text Available CC chemokine receptor 4 (CCR4 is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-(2-(4-chloro-phenyl-5-{[(naphthalen-1-ylmethyl-carbamoyl]-methyl}-4-oxo-thiazolidin-3-yl-N-(3-morpholin-4-yl-propyl-acetamide (S009 and the N-terminal extracellular tail (ML40 of CCR4 has been validated to be high affinity by capillary zone electrophoresis (CZE. The S009 is a known CCR4 antagonist. Now, a series of new thiourea derivatives have been synthesized. Compared with positive control S009, they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases. The synthesized compounds XJH-5, XJH-4, XJH-17 and XJH-1 displayed the interaction with ML40, but XJH-9, XJH-10, XJH-11, XJH-12, XJH-13, XJH-14, XJH-3, XJH-8, XJH-6, XJH-7, XJH-15, XJH-16 and XJH-2 did not bind to ML40. Both qualification and quantification characterizations of the binding were determined. The affinity of the four compounds was valued by the binding constant, which was similar with the results of chemotactic experiments. The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases. Keywords: Capillary zone electrophoresis, CCR4 antagonist, 2-(2-(4-chloro-phenyl-5-{[(naphthalen-1-ylmethyl-carbamoyl]-methyl}-4-oxo-thiazolidin-3-yl-N-(3-morpholin-4-yl-propyl-acetamide, Interactions, Structural modification

  14. Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.

    Science.gov (United States)

    Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Ţieranu, Eugen Nicolae; Popa, Caterina; Mănuc, Mircea; Preda, Carmen Monica; Ţieranu, Ioana; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

    2017-01-01

    A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.

  15. Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility.

    Science.gov (United States)

    Lin, Hsiu-Ling; Ueng, Kwo-Chang; Hsieh, Yih-Shou; Chiang, Whei-Ling; Yang, Shun-Fa; Chu, Shu-Chen

    2012-09-01

    Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.

  16. CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

    OpenAIRE

    Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.

    2000-01-01

    The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...

  17. $200,000 Grants Awarded to CCR Researchers for HIV/AIDS Studies | Poster

    Science.gov (United States)

    By Nancy Parrish, Staff Writer Earlier this year, the Office of AIDS Research (OAR) awarded two, two-year grants of $200,000 each to Anu Puri, Ph.D., and Robert Blumenthal, Ph.D., both of the Center for Cancer Research (CCR) Nanobiology Program, and to Eric Freed, Ph.D., of the HIV Drug Resistance Program, for their research on potential new treatments for HIV.

  18. Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Thakur Gurjeet

    2012-10-01

    The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Current discharge management of acute coronary syndromes: data from the Rijnmond Collective Cardiology Research (CCR) study.

    Science.gov (United States)

    Yetgin, T; van der Linden, M M J M; de Vries, A G; Smits, P C; van Mechelen, R; Yap, S C; Boersma, E; Zijlstra, F; van Geuns, R-J M

    2014-01-01

    Medical discharge management of acute coronary syndromes (ACS) remains suboptimal outside randomised trials and constitutes an essential quality benchmark for ACS. We sought to evaluate the rates of key guideline-recommended pharmacological agents after ACS and characteristics associated with optimal treatment at discharge. The Rijnmond Collective Cardiology Research (CCR) registry is an ongoing prospective, observational study in the Netherlands that aims to enrol 4000 patients with ACS. We examined discharge and 1-month follow-up medication use among the first 1000 patients enrolled in the CCR registry. Logistic regression was performed to identify patient and hospital characteristics associated with collective guideline-recommended pharmacotherapy at hospital discharge. At discharge, 94 % of patients received aspirin, 100 % thienopyridines, 80 % angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers, 87 % β-blockers, 96 % statins, and 65 % the combination of all 5 agents. ST-segment elevation myocardial infarction, hypertension, hypercholesterolaemia, and enrolment in an interventional centre were positive independent predictors of 5-drug combination therapy at discharge. Negative independent predictors were unstable angina and advanced age. Current data from the CCR registry reflect a high quality of care for ACS discharge management in the Rotterdam-Rijnmond region. However, potential still remains for further optimisation.

  20. Quantum walks, quantum gates, and quantum computers

    International Nuclear Information System (INIS)

    Hines, Andrew P.; Stamp, P. C. E.

    2007-01-01

    The physics of quantum walks on graphs is formulated in Hamiltonian language, both for simple quantum walks and for composite walks, where extra discrete degrees of freedom live at each node of the graph. It is shown how to map between quantum walk Hamiltonians and Hamiltonians for qubit systems and quantum circuits; this is done for both single-excitation and multiexcitation encodings. Specific examples of spin chains, as well as static and dynamic systems of qubits, are mapped to quantum walks, and walks on hyperlattices and hypercubes are mapped to various gate systems. We also show how to map a quantum circuit performing the quantum Fourier transform, the key element of Shor's algorithm, to a quantum walk system doing the same. The results herein are an essential preliminary to a Hamiltonian formulation of quantum walks in which coupling to a dynamic quantum environment is included

  1. Frequencies of CCR5-D32, CCR2-64I and SDF1-3’A mutations in Human Immunodeficiency Virus (HIV seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia

    Directory of Open Access Journals (Sweden)

    Fernanda Andreza de Pinho Lott Carvalhaes

    2005-12-01

    Full Text Available The distribution of genetic polymorphisms of chemokine receptors CCR5-delta32, CCR2-64I and chemokine (SDF1-3’A mutations were studied in 110 Human Immunodeficiency Virus type 1 (HIV-1 seropositive individuals (seropositive group and 139 seronegative individuals (seronegative group from the population of the northern Brazilian city of Belém which is the capital of the state of Pará in the Brazilian Amazon. The CCR5-delta32 mutation was found in the two groups at similar frequencies, i.e. 2.2% for the seronegative group and 2.7% for the seropositive group. The frequencies of the SDF1-3’A mutation were 21.0% for the seronegative group and 15.4% for the seropositive group, and the CCR2-64I allele was found at frequencies of 12.5% for the seronegative group and 5.4% for the seropositive group. Genotype distributions were consistent with Hardy-Weinberg expectations in both groups, suggesting that none of the three mutations has a detectable selective effect. Difference in the allelic and genotypic frequencies was statistically significant for the CCR2 locus, the frequency in the seronegative group being twice that found in the seropositive group. This finding may indicate a protective effect of the CCR2-64I mutation in relation to HIV transmission. However, considering that the CCR2-64I mutation has been more strongly associated with a decreased risk for progression for AIDS than to the resistance to the HIV infection, this could reflect an aspect of population structure or a Type I error.

  2. Quantum memory Quantum memory

    Science.gov (United States)

    Le Gouët, Jean-Louis; Moiseev, Sergey

    2012-06-01

    Interaction of quantum radiation with multi-particle ensembles has sparked off intense research efforts during the past decade. Emblematic of this field is the quantum memory scheme, where a quantum state of light is mapped onto an ensemble of atoms and then recovered in its original shape. While opening new access to the basics of light-atom interaction, quantum memory also appears as a key element for information processing applications, such as linear optics quantum computation and long-distance quantum communication via quantum repeaters. Not surprisingly, it is far from trivial to practically recover a stored quantum state of light and, although impressive progress has already been accomplished, researchers are still struggling to reach this ambitious objective. This special issue provides an account of the state-of-the-art in a fast-moving research area that makes physicists, engineers and chemists work together at the forefront of their discipline, involving quantum fields and atoms in different media, magnetic resonance techniques and material science. Various strategies have been considered to store and retrieve quantum light. The explored designs belong to three main—while still overlapping—classes. In architectures derived from photon echo, information is mapped over the spectral components of inhomogeneously broadened absorption bands, such as those encountered in rare earth ion doped crystals and atomic gases in external gradient magnetic field. Protocols based on electromagnetic induced transparency also rely on resonant excitation and are ideally suited to the homogeneous absorption lines offered by laser cooled atomic clouds or ion Coulomb crystals. Finally off-resonance approaches are illustrated by Faraday and Raman processes. Coupling with an optical cavity may enhance the storage process, even for negligibly small atom number. Multiple scattering is also proposed as a way to enlarge the quantum interaction distance of light with matter. The

  3. Evaluation of the effect of the specific CCR1 antagonist CP-481715 on the clinical and cellular responses observed following epicutaneous nickel challenge in human subjects

    DEFF Research Database (Denmark)

    Borregaard, Jeanett; Skov, Lone; Wang, Lisy

    2008-01-01

    BACKGROUND: The CC-chemokine receptor-1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP-481715 is a specific antagonist of CCR1. OBJECTIVES: To determine the inhibitory effects of CP-418 715 in ACD by evaluating the clinical signs....... CONCLUSIONS: Blocking of CCR1 only partly inhibited clinical manifestations of ACD. Several chemokine receptors are likely relevant for the cellular influx observed in ACD lesions....

  4. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    Science.gov (United States)

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  5. Quantum stochastics

    CERN Document Server

    Chang, Mou-Hsiung

    2015-01-01

    The classical probability theory initiated by Kolmogorov and its quantum counterpart, pioneered by von Neumann, were created at about the same time in the 1930s, but development of the quantum theory has trailed far behind. Although highly appealing, the quantum theory has a steep learning curve, requiring tools from both probability and analysis and a facility for combining the two viewpoints. This book is a systematic, self-contained account of the core of quantum probability and quantum stochastic processes for graduate students and researchers. The only assumed background is knowledge of the basic theory of Hilbert spaces, bounded linear operators, and classical Markov processes. From there, the book introduces additional tools from analysis, and then builds the quantum probability framework needed to support applications to quantum control and quantum information and communication. These include quantum noise, quantum stochastic calculus, stochastic quantum differential equations, quantum Markov semigrou...

  6. Quantum Computing

    OpenAIRE

    Scarani, Valerio

    1998-01-01

    The aim of this thesis was to explain what quantum computing is. The information for the thesis was gathered from books, scientific publications, and news articles. The analysis of the information revealed that quantum computing can be broken down to three areas: theories behind quantum computing explaining the structure of a quantum computer, known quantum algorithms, and the actual physical realizations of a quantum computer. The thesis reveals that moving from classical memor...

  7. Quantum Malware

    OpenAIRE

    Wu, Lian-Ao; Lidar, Daniel A.

    2005-01-01

    When quantum communication networks proliferate they will likely be subject to a new type of attack: by hackers, virus makers, and other malicious intruders. Here we introduce the concept of "quantum malware" to describe such human-made intrusions. We offer a simple solution for storage of quantum information in a manner which protects quantum networks from quantum malware. This solution involves swapping the quantum information at random times between the network and isolated, distributed an...

  8. Similarity transformed coupled cluster response (ST-CCR) theory--a time-dependent similarity transformed equation-of-motion coupled cluster (STEOM-CC) approach.

    Science.gov (United States)

    Landau, Arie

    2013-07-07

    This paper presents a new method for calculating spectroscopic properties in the framework of response theory utilizing a sequence of similarity transformations (STs). The STs are preformed using the coupled cluster (CC) and Fock-space coupled cluster operators. The linear and quadratic response functions of the new similarity transformed CC response (ST-CCR) method are derived. The poles of the linear response yield excitation-energy (EE) expressions identical to the ones in the similarity transformed equation-of-motion coupled cluster (STEOM-CC) approach. ST-CCR and STEOM-CC complement each other, in analogy to the complementarity of CC response (CCR) and equation-of-motion coupled cluster (EOM-CC). ST-CCR/STEOM-CC and CCR/EOM-CC yield size-extensive and size-intensive EEs, respectively. Other electronic-properties, e.g., transition dipole strengths, are also size-extensive within ST-CCR, in contrast to STEOM-CC. Moreover, analysis suggests that in comparison with CCR, the ST-CCR expressions may be confined to a smaller subspace, however, the precise scope of the truncation can only be determined numerically. In addition, reformulation of the time-independent STEOM-CC using the same parameterization as in ST-CCR, as well as an efficient truncation scheme, is presented. The shown convergence of the time-dependent and time-independent expressions displays the completeness of the presented formalism.

  9. Upregulation of the Chemokine Receptor CCR2B in Epstein‒Barr Virus-Positive Burkitt Lymphoma Cell Lines with the Latency III Program

    Directory of Open Access Journals (Sweden)

    Svetlana Kozireva

    2018-05-01

    Full Text Available CCR2 is the cognate receptor to the chemokine CCL2. CCR2–CCL2 signaling mediates cancer progression and metastasis dissemination. However, the role of CCR2–CCL2 signaling in pathogenesis of B-cell malignancies is not clear. Previously, we showed that CCR2B was upregulated in ex vivo peripheral blood B cells upon Epstein‒Barr virus (EBV infection and in established lymphoblastoid cell lines with the EBV latency III program. EBV latency III is associated with B-cell lymphomas in immunosuppressed patients. The majority of EBV-positive Burkitt lymphoma (BL tumors are characterized by latency I, but the BL cell lines drift towards latency III during in vitro culture. In this study, the CCR2A and CCR2B expression was assessed in the isogenic EBV-positive BL cell lines with latency I and III using RT-PCR, immunoblotting, and immunostaining analyses. We found that CCR2B is upregulated in the EBV-positive BL cells with latency III. Consequently, we detected the migration of latency III cells toward CCL2. Notably, the G190A mutation, corresponding to SNP CCR2-V64I, was found in one latency III cell line with a reduced migratory response to CCL2. The upregulation of CCR2B may contribute to the enhanced migration of malignant B cells into CCL2-rich compartments.

  10. Quantumness beyond quantum mechanics

    International Nuclear Information System (INIS)

    Sanz, Ángel S

    2012-01-01

    Bohmian mechanics allows us to understand quantum systems in the light of other quantum traits than the well-known ones (coherence, diffraction, interference, tunnelling, discreteness, entanglement, etc.). Here the discussion focusses precisely on two of these interesting aspects, which arise when quantum mechanics is thought within this theoretical framework: the non-crossing property, which allows for distinguishability without erasing interference patterns, and the possibility to define quantum probability tubes, along which the probability remains constant all the way. Furthermore, taking into account this hydrodynamic-like description as a link, it is also shown how this knowledge (concepts and ideas) can be straightforwardly transferred to other fields of physics (for example, the transmission of light along waveguides).

  11. Nonlinear Dynamics In Quantum Physics -- Quantum Chaos and Quantum Instantons

    OpenAIRE

    Kröger, H.

    2003-01-01

    We discuss the recently proposed quantum action - its interpretation, its motivation, its mathematical properties and its use in physics: quantum mechanical tunneling, quantum instantons and quantum chaos.

  12. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  13. Downregulation of mouse CCR3 by lentiviral shRNA inhibits proliferation and induces apoptosis of mouse eosinophils.

    Science.gov (United States)

    Zhu, Xin-Hua; Liao, Bing; Xu, Yi; Liu, Ke; Huang, Yun; Huang, Quan-Long; Liu, Yue-Hui

    2017-02-01

    RNA interference has been considered as an effective gene silencing method in basic and preclinical investigations. The aims of the present study were to construct a lentiviral vector expressing a short hairpin RNA (shRNA) targeting the murine CC chemokine receptor 3 (mCCR3), and to investigate its effects on the proliferation and apoptosis of mouse eosinophils. A recombinant lentiviral vector expressing four fragments of mouse CCR3 shRNA (pLVX‑mCCR3‑1+2+3+4‑shRNA) was constructed using subcloning techniques. This novel lentivirus was then packaged into 293T cells by co‑transduction with plasmids, including Baculo p35, pCMV R8.2 and VSV. The interference effects of the vector were verified using polymerase chain reaction (PCR) and western blot analyses. The effects of the interference on the proliferation and apoptosis of mouse eosinophils were investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxymethoxyphenyl)‑2‑(4‑sulfophenyl)‑2H‑tetrazolium and terminal deoxynucleotidyl transferase dUTP nick end labeling methods, respectively. The results of the PCR and western blot analyses confirmed that the novel recombinant vector, pLVX‑mCCR3‑1+2+3+4‑shRNA, had high efficiency in inhibiting the mRNA and protein expression levels of mCCR3 in mouse eosinophils. The downregulation of mCCR3 significantly inhibited proliferation of the eosinophils. Furthermore, the present study found that the downregulation of mCCR3 significantly promoted apoptosis of the eosinophils. Therefore, the downregulation of mCCR3 led to the inhibition of proliferation and induction of apoptosis in mouse eosinophils. The predominant characteristics of allergic rhinitis are eosinophil infiltration and release of inflammatory mediators, which appear in a variety of clinical manifestations. The results of the present study indicate that mCCR3 silencing may serve as a putative approach for the treatment of allergic rhinitis.

  14. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

    Directory of Open Access Journals (Sweden)

    Aric L Gregson

    2010-06-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-, and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+ and CD103(- and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+ Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+ Treg frequency and inversely with BOS. Higher frequencies of CCR7(+ CD3(+CD4(+CD25(hiFoxp3(+CD45RA(- lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.

  15. Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

    Science.gov (United States)

    Chávez, Juliana H; França, Rafael F O; Oliveira, Carlo J F; de Aquino, Maria T P; Farias, Kleber J S; Machado, Paula R L; de Oliveira, Thelma F M; Yokosawa, Jonny; Soares, Edson G; da Silva, João S; da Fonseca, Benedito A L; Figueiredo, Luiz T M

    2013-11-01

    Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 α-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

  16. CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

    DEFF Research Database (Denmark)

    Jinquan, Tan; Jacobi, Henrik H; Jing, Chen

    2003-01-01

    We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19......-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant....... Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests...

  17. Investigation of Chemokine Receptor CCR2V64Il Gene Polymorphism and Migraine without Aura in the Iranian Population

    Directory of Open Access Journals (Sweden)

    Alireza Zandifar

    2013-01-01

    Full Text Available Background and Objectives. Migraine is a multifactorial common neurovascular disease with a polygenic inheritance. Inflammation plays an important part in migraine pathophysiology. C-C chemokine receptor 2 (CCR2 is an important chemokine for monocyte aggregation and transendothelial monocyte migration. The aim of our study was to investigate the association of migraine with CCR2V64Il polymorphism in the Iranian population. Methods. We assessed 103 patients with newly diagnosed migraine and 100 healthy subjects. Genomic DNA samples were extracted from peripheral blood and genotypes of CCR2V64Il gene polymorphism were determined. For measuring the severity of headache, every patient filled out the MIGSEV questionnaire. Results. There were no significant differences in the distribution of both 64Il allele and heterozygote (GA genotype of CCR2 gene polymorphism (P=0.396; OR=0.92, 95% CI = 0.50–1.67 and P=0.388; OR=0.91, 95% CI = 0.47–1.73, resp. between case and control groups. There was no significant difference of alleles frequency between three grades of MIGSEV (P=0.922. Conclusions. In conclusion our results revealed no association between CCR2V64Il polymorphism and susceptibility to migraine and also headache severity in the Iranian population.

  18. High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    J.A.B. Chies

    2003-01-01

    Full Text Available Homozygous sickle cell disease (SCD has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1% of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3% with the same ethnic background (Afro-Brazilians. Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

  19. The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yuan-kun Xu

    Full Text Available BACKGROUND: Osteoarthritis (OA is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1 and receptor chemokine (C-C motif receptor 2 (CCR2 in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001 and the expression of MMP-13 also increased (P < 0.05. MCP-1 stimulation also induced (or enhanced the apoptosis of OA chondrocytes (P < 0.05. Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13 in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA model CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis

  20. CCL2 binding is CCR2 independent in primary adult human astrocytes.

    Science.gov (United States)

    Fouillet, A; Mawson, J; Suliman, O; Sharrack, B; Romero, I A; Woodroofe, M N

    2012-02-09

    Chemokines are low relative molecular mass proteins, which have chemoattractant actions on many cell types. The chemokine, CCL2, has been shown to play a major role in the recruitment of monocytes in central nervous system (CNS) lesions in multiple sclerosis (MS). Since resident astrocytes constitute a major source of chemokine synthesis including CCL2, we were interested to assess the regulation of CCL2 by astrocytes. We showed that CCL2 bound to the cell surface of astrocytes and binding was not modulated by inflammatory conditions. However, CCR2 protein was not detected nor was activation of the classical CCR2 downstream signaling pathways. Recent studies have shown that non-signaling decoy chemokine receptors bind and modulate the expression of chemokines at site of inflammation. Here, we show that the D6 chemokine decoy receptor is constitutively expressed by primary human adult astrocytes at both mRNA and protein level. In addition, CCL3, which binds to D6, but not CCL19, which does not bind to D6, displaced CCL2 binding to astrocytes; indicating that CCL2 may bind to this cell type via the D6 receptor. Our results suggest that CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy chemokine receptor. Therefore we propose that astrocytes are implicated in both the establishment of chemokine gradients for the migration of leukocytes into and within the CNS and in the regulation of CCL2 levels at inflammatory sites in the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. De-novo Collateral Formation Following Acute Myocardial Infarction: Dependence on CCR2+ Bone Marrow Cells

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-01-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form (“neo-collaterals”) versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤ 7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume−1, and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1−/− and CCR2−/− mice. Bone-marrow transplant rescued collateral formation in CCR2−/− mice. Involvement of fractalkine→CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neocollaterals form rapidly after coronary occlusion, and finds that MCP→CCR2-mediated recruitment of myeloid cells is required for this process. PMID:26254180

  2. Consequences of ChemR23 heteromerization with the chemokine receptors CXCR4 and CCR7.

    Directory of Open Access Journals (Sweden)

    Cédric de Poorter

    Full Text Available Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed.

  3. Consequences of ChemR23 heteromerization with the chemokine receptors CXCR4 and CCR7.

    Science.gov (United States)

    de Poorter, Cédric; Baertsoen, Kevin; Lannoy, Vincent; Parmentier, Marc; Springael, Jean-Yves

    2013-01-01

    Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed.

  4. The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

    Science.gov (United States)

    Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

    2018-01-01

    Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses.

  5. Expression analysis of cinnamoyl-CoA reductase (CCR) gene in developing seedlings of Leucaena leucocephala: a pulp yielding tree species.

    Science.gov (United States)

    Srivastava, Sameer; Gupta, Ranadheer K; Arha, Manish; Vishwakarma, Rishi K; Rawal, Shuban K; Kavi Kishor, P B; Khan, Bashir M

    2011-02-01

    Removal of lignin is a major hurdle for obtaining good quality pulp. Leucaena leucocephala (subabul) is extensively used in paper industry in India; therefore, as a first step to generate transgenic plants with low lignin content, cDNA and genomic clones of CCR gene were isolated and characterized. The cDNA encoding CCR (EC 1.2.1.44) was designated as Ll-CCR; the sequence analysis revealed an Open Reading Frame (ORF) of 1005 bp. Phylogenetic analysis showed that Ll-CCR sequence is highly homologous to CCRs from other dicot plants. The 2992 bp genomic clone of Leucaena CCR consists of 5 exons and 4 introns. The haploid genome of L. leucocephala contains two copies as revealed by DNA blot hybridization. Ll-CCR gene was over-expressed in Escherichia coli, which showed a molecular mass of approximately 38 kDa. Protein blot analysis revealed that Ll-CCR protein is expressed at higher levels in root and in stem, but undetectable in leaf tissues. Expression of CCR gene in Leucaena increased up to 15 d in case of roots and stem as revealed by QRT-PCR studies in 0-15 d old seedlings. ELISA based studies of extractable CCR protein corroborated with QRT-PCR data. CCR protein was immuno-cytolocalized around xylem tissue. Lignin estimation and expression studies of 5, 10 and 15 d old stem and root suggest that CCR expression correlates with quantity of lignin produced, which makes it a good target for antisense down regulation for producing designer species for paper industry. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  6. HIV-1 Tropism Testing and Clinical Management of CCR5 Antagonists: Quebec Review and Recommendations

    Directory of Open Access Journals (Sweden)

    Cécile Tremblay

    2013-01-01

    Full Text Available HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

  7. Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective

    DEFF Research Database (Denmark)

    Jørgensen, Astrid Sissel; Rosenkilde, Mette M; Hjortø, Gertrud M

    2018-01-01

    of CCL21 displays an extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role in coordinating the meeting between mature antigen presenting DCs and naïve T-cells which normally takes place in the lymph nodes (LNs). This process is a prerequisite for the initiation of an antigen...... the cell-based immune system is controlled. Bias comes in three forms; ligand-, receptor- and tissue-bias. Biased signaling is increasingly being recognized as playing an important role in contributing to the fine-tuned coordination of immune cell chemotaxis. In the current review we discuss the recent...

  8. Quantum mechanics

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The book is on quantum mechanics. The emphasis is on the basic concepts and the methodology. The chapters include: Breakdown of classical concepts; Quantum mechanical concepts; Basic postulates of quantum mechanics; solution of problems in quantum mechanics; Simple harmonic oscillator; and Angular Momentum

  9. Quantum matter

    International Nuclear Information System (INIS)

    Buechler, Hans Peter; Calcarco, Tommaso; Dressel, Martin

    2008-01-01

    The following topics are dealt with: Artificial atoms and molecules, tailored from solids, fractional flux quanta, molecular magnets, controlled interaction in quantum gases, the theory of quantum correlations in mott matter, cold gases, and mesoscopic systems, Bose-Einstein condensates on the chip, on the route to the quantum computer, a quantum computer in diamond. (HSI)

  10. Quantum fluctuations

    International Nuclear Information System (INIS)

    Reynaud, S.; Giacobino, S.; Zinn-Justin, J.

    1997-01-01

    This course is dedicated to present in a pedagogical manner the recent developments in peculiar fields concerned by quantum fluctuations: quantum noise in optics, light propagation through dielectric media, sub-Poissonian light generated by lasers and masers, quantum non-demolition measurements, quantum electrodynamics applied to cavities and electrical circuits involving superconducting tunnel junctions. (A.C.)

  11. Quantum radar

    CERN Document Server

    Lanzagorta, Marco

    2011-01-01

    This book offers a concise review of quantum radar theory. Our approach is pedagogical, making emphasis on the physics behind the operation of a hypothetical quantum radar. We concentrate our discussion on the two major models proposed to date: interferometric quantum radar and quantum illumination. In addition, this book offers some new results, including an analytical study of quantum interferometry in the X-band radar region with a variety of atmospheric conditions, a derivation of a quantum radar equation, and a discussion of quantum radar jamming.This book assumes the reader is familiar w

  12. CCR2+ Monocyte-Derived Infiltrating Macrophages Are Required for Adverse Cardiac Remodeling During Pressure Overload

    Directory of Open Access Journals (Sweden)

    Bindiya Patel, PhD

    2018-04-01

    Full Text Available Summary: Although chronic inflammation is a central feature of heart failure (HF, the immune cell profiles differ with different underlying causes. This suggests that for immunomodulatory therapy in HF to be successful, it needs to be tailored to the specific etiology. Here, the authors demonstrate that monocyte-derived C-C chemokine receptor 2 (CCR2+ macrophages infiltrate the heart early during pressure overload in mice, and that blocking this response either pharmacologically or with antibody-mediated CCR2+ monocyte depletion alleviates late pathological left ventricular remodeling and dysfunction, T-cell expansion, and cardiac fibrosis. Hence, suppression of CCR2+ monocytes/macrophages may be an important immunomodulatory therapeutic target to ameliorate pressure-overload HF. Key Words: cardiac remodeling, heart failure, inflammation, macrophages, T cells

  13. Quantum information

    International Nuclear Information System (INIS)

    Kilin, Sergei Ya

    1999-01-01

    A new research direction known as quantum information is a multidisciplinary subject which involves quantum mechanics, optics, information theory, programming, discrete mathematics, laser physics and spectroscopy, and depends heavily on contributions from such areas as quantum computing, quantum teleportation and quantum cryptography, decoherence studies, and single-molecule and impurity spectroscopy. Some new results achieved in this rapidly growing field are discussed. (reviews of topical problems)

  14. Quantum information

    Energy Technology Data Exchange (ETDEWEB)

    Kilin, Sergei Ya [B.I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk (Belarus)

    1999-05-31

    A new research direction known as quantum information is a multidisciplinary subject which involves quantum mechanics, optics, information theory, programming, discrete mathematics, laser physics and spectroscopy, and depends heavily on contributions from such areas as quantum computing, quantum teleportation and quantum cryptography, decoherence studies, and single-molecule and impurity spectroscopy. Some new results achieved in this rapidly growing field are discussed. (reviews of topical problems)

  15. Quantum ontologies

    International Nuclear Information System (INIS)

    Stapp, H.P.

    1988-12-01

    Quantum ontologies are conceptions of the constitution of the universe that are compatible with quantum theory. The ontological orientation is contrasted to the pragmatic orientation of science, and reasons are given for considering quantum ontologies both within science, and in broader contexts. The principal quantum ontologies are described and evaluated. Invited paper at conference: Bell's Theorem, Quantum Theory, and Conceptions of the Universe, George Mason University, October 20-21, 1988. 16 refs

  16. Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells.

    Science.gov (United States)

    Elgueta, Raul; Sepulveda, Fernando E; Vilches, Felipe; Vargas, Leonardo; Mora, J Rodrigo; Bono, Maria Rosa; Rosemblatt, Mario

    2008-05-15

    It has recently been shown that IL-4 can educate dendritic cells (DC) to differentially affect T cell effector activity. In this study, we show that IL-4 can also act upon DC to instruct naive T cells to express the gut-associated homing receptor CCR9. Thus, effector T cells generated after coculture with mesenteric lymph node (MLN)-DC show a higher expression of CCR9 when activated in the presence of IL-4. In contrast, IL-4 had no effect on CCR9 expression when naive T cells were polyclonally activated in the absence of MLN-DC, suggesting that the effect of IL-4 on CCR9 expression passed through DC. Indeed, T cells activated by MLN-DC from IL-4Ralpha(-/-) mice showed a much lower CCR9 expression and a greatly reduced migration to the small intestine than T cells activated by wild-type MLN-DC even in the presence of IL-4. Consistent with the finding that the vitamin A metabolite retinoic acid (RA) induces gut-homing molecules on T cells, we further demonstrate that IL-4 up-regulated retinaldehyde dehydrogenase 2 mRNA on MLN-DC, a critical enzyme involved in the synthesis of RA. Moreover, LE135, a RA receptor antagonist, blocked the increased expression of CCR9 driven by IL-4-treated MLN-DC. Thus, besides the direct effect of RA on T cell gut tropism, our results show that the induction of a gut-homing phenotype on CD4(+) T cells is also influenced by the effect of IL-4 on gut-associated DC.

  17. Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis.

    Science.gov (United States)

    Laurance, Sandrine; Bertin, François-René; Ebrahimian, Talin; Kassim, Yusra; Rys, Ryan N; Lehoux, Stéphanie; Lemarié, Catherine A; Blostein, Mark D

    2017-07-01

    Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl 3 and flow reduction in the inferior vena cava. Total monocyte depletion was achieved by injection of clodronate before deep venous thrombosis. Inflammatory monocytes were depleted using an anti-C-C chemokine receptor type 2 (CCR2) antibody. Similarly, injection of an anti-chemokine ligand 2 (CCL2) antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6 was associated with a reduction of monocyte recruitment in both deep venous thrombosis models. Global monocyte depletion by clodronate leads to smaller thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6 -/- mice contain less inflammatory (CCR2 hi CX 3 CR1 lo ) monocytes, consistent with a Gas6-dependent recruitment of this monocyte subset. Correspondingly, selective depletion of CCR2 hi CX 3 CR1 lo monocytes reduced the formation of venous thrombi in wild-type mice demonstrating a predominant role of the inflammatory monocytes in thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in monocytes and endothelial cells, respectively, impacting monocyte migration. Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase). This study demonstrates that Gas6 specifically promotes the recruitment of inflammatory CCR2 hi CX 3 CR1 lo monocytes through the regulation of both CCR2 and CCL2 during deep venous thrombosis. © 2017 American Heart Association, Inc.

  18. Quantum Computer Games: Quantum Minesweeper

    Science.gov (United States)

    Gordon, Michal; Gordon, Goren

    2010-01-01

    The computer game of quantum minesweeper is introduced as a quantum extension of the well-known classical minesweeper. Its main objective is to teach the unique concepts of quantum mechanics in a fun way. Quantum minesweeper demonstrates the effects of superposition, entanglement and their non-local characteristics. While in the classical…

  19. The CC-chemokine receptor 5 (CCR5) is a marker of, but not essential for the development of human Th1 cells

    DEFF Research Database (Denmark)

    Odum, Niels; Bregenholt, S; Eriksen, K W

    1999-01-01

    The CC-chemokine receptor 5 (CCR5) has recently been described as a surface marker of human T cells producing type 1 (Th1) cytokines. Here we confirm that CCR5 is expressed on human Th1 but not on Th2 T-cell clones. Using intracellular cytokine staining, we show that alloantigen specific CD4+ T...

  20. Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8+ T cells following coronavirus infection of the central nervous system

    International Nuclear Information System (INIS)

    Glass, William G.; Lane, Thomas E.

    2003-01-01

    Intracranial infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a demyelinating disease similar in pathology to the human disease multiple sclerosis (MS). T cells participate in both defense and disease progression following MHV infection. Expression of chemokine receptors on activated T cells is important in allowing these cells to traffic into and accumulate within the central nervous system (CNS) of MHV-infected mice. The present study evaluated the contributions of CCR5 to the activation and trafficking of virus-specific CD8 + T cells into the MHV-infected CNS mice. Comparable numbers of virus-specific CD8 + T cells derived from immunized CCR5 +/+ or CCR5 -/- mice were present within the CNS of MHV-infected RAG1 -/- mice following adoptive transfer, indicating that CCR5 is not required for trafficking of these cells into the CNS. RAG1 -/- recipients of CCR5 -/- -derived CD8 + T cells exhibited a modest, yet significant (P ≤ 0.05), reduction in viral burden within the brain which correlated with increased CTL activity and IFN-γ expression. Histological analysis of RAG1 -/- recipients of either CCR5 +/+ or CCR5 -/- -derived CD8 + T cells revealed only focal areas of demyelination with no significant differences in white matter destruction. These data indicate that CCR5 signaling on CD8 + T cells modulates antiviral activities but is not essential for entry into the CNS

  1. Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity state of the CC-chemokine receptor 5 (CCR5)

    DEFF Research Database (Denmark)

    Steen, A; Sparre-Ulrich, A H; Thiele, Stefanie

    2014-01-01

    TM receptors - it is a leucine indicating an altered function. Here, we describe the significance of this position and its possible interaction with TM-3 for CCR5 activity. EXPERIMENTAL APPROACH: The effects of [L203F]-CCR5 in TM-5 (position V:13/5.47), [I116A]-CCR5 in TM-3 (III:16/3.40) and [L203F...... ) with a threefold increase in agonist potency. In silico, [I116A]-CCR5 switched χ1-angle in [L203F]-CCR5. Furthermore, [I116A]-CCR5 was constitutively active to a similar degree as [L203F]-CCR5. Tyr(244) in TM-6 (VI:09/6.44) moved towards TM-5 in silico, consistent with its previously shown function for CCR5...... in the active state, a mechanism proposed previously for the β2 -adrenoceptor. The results provide an understanding of chemokine receptor function and thereby information for the development of biased and non-biased antagonists and inverse agonists....

  2. The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

    Science.gov (United States)

    Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai

    2013-01-01

    Abstract Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening strategy by using cells that co-express GFP and CCR5, along with an excess of control cells that do not express these proteins (and are otherwise identical to the CCR5-expressing cells). These control cells are intended to remove most of the phages that bind the cells nonspecifically; thus leading to an enrichment of the phages presenting anti-CCR5-specific antibodies. Subsequently, the CCR5-presenting cells were quantitatively sorted by flow cytometry, and the bound phages were eluted, amplified, and used for further successive selection rounds. Several different clones of human single-chain Fv antibodies that interact with CCR5-expressing cells were identified. The most specific monoclonal antibody was converted to a full-length IgG and bound the second extracellular loop of CCR5. The experimental approach presented herein for screening for CCR5-specific antibodies can be applicable to screen antibody-presenting phage libraries against any cell-surface expressed protein of interest. PMID:23941674

  3. The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor

    DEFF Research Database (Denmark)

    Lüttichau, H R; Lewis, I C; Gerstoft, J

    2001-01-01

    The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had the highest identity to MC148 and because both...

  4. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

    Science.gov (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

    2014-01-01

    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  5. CCR1

    African Journals Online (AJOL)

    inflammatory protein II; Bioinformatics; Protease digestion; HEK293 cells; Radioligand binding. Tropical .... Cell membranes ... binding was counted using a scintillation counter. ... any remaining red blood cells. .... *Denotes the most stable peptide, C18P; amount presents .... korthalsii methanol extract on human peripheral.

  6. Cyclooxygenase-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 in breast cancer cells.

    Science.gov (United States)

    Chuang, Chun-Wei; Pan, Mei-Ren; Hou, Ming-Feng; Hung, Wen-Chun

    2013-02-01

    Up-regulation of cyclooxygenase-2 (COX-2) is frequently found in human cancers and is significantly associated with tumor metastasis. Our previous results demonstrate that COX-2 and its metabolite prostaglandin E2 (PGE2) stimulate the expression of CCR7 chemokine receptor via EP2/EP4 receptors to promote lymphatic invasion in breast cancer cells. In this study, we address the underlying mechanism of COX-2/PGE2-induced CCR7 expression. We find that COX-2/PGE2 increase CCR7 expression via the AKT signaling pathway in breast cancer cells. Promoter deletion and mutation assays identify the Sp1 site located at the -60/-57 region of CCR7 gene promoter is critical for stimulation. Chromatin immunoprecipitation (ChIP) assay confirms that in vivo binding of Sp1 to human CCR7 promoter is increased by COX-2 and PGE2. Knockdown of Sp1 by shRNA reduces the induction of CCR7 by PGE2. We demonstrate for the first time that AKT may directly phosphorylate Sp1 at S42, T679, and S698. Phosphorylation-mimic Sp1 protein harboring S42D, T679D, and S698D mutation strongly activates CCR7 expression. In contrast, change of these three residues to alanine completely blocks the induction of CCR7 by PGE2. Pathological investigation demonstrates that CCR7 expression is strongly associated with phospho-AKT and Sp1 in 120 breast cancer tissues. Collectively, our results demonstrate that COX-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 and this pathway is highly activated in metastatic breast cancer. Copyright © 2012 Wiley Periodicals, Inc.

  7. Quantum optics

    Energy Technology Data Exchange (ETDEWEB)

    Drummond, P D [University of Queensland, St. Lucia, QLD (Australia).Physics Department

    1999-07-01

    Full text: Quantum optics in Australia has been an active research field for some years. I shall focus on recent developments in quantum and atom optics. Generally, the field as a whole is becoming more and more diverse, as technological developments drive experiments into new areas, and theorists either attempt to explain the new features, or else develop models for even more exotic ideas. The recent developments include quantum solitons, quantum computing, Bose-Einstein condensation, atom lasers, quantum cryptography, and novel tests of quantum mechanics. The talk will briefly cover current progress and outstanding problems in each of these areas. Copyright (1999) Australian Optical Society.

  8. Quantum entanglement and quantum teleportation

    International Nuclear Information System (INIS)

    Shih, Y.H.

    2001-01-01

    One of the most surprising consequences of quantum mechanics is the entanglement of two or more distance particles. The ''ghost'' interference and the ''ghost'' image experiments demonstrated the astonishing nonlocal behavior of an entangled photon pair. Even though we still have questions in regard to fundamental issues of the entangled quantum systems, quantum entanglement has started to play important roles in quantum information and quantum computation. Quantum teleportation is one of the hot topics. We have demonstrated a quantum teleportation experiment recently. The experimental results proved the working principle of irreversibly teleporting an unknown arbitrary quantum state from one system to another distant system by disassembling into and then later reconstructing from purely classical information and nonclassical EPR correlations. The distinct feature of this experiment is that the complete set of Bell states can be distinguished in the Bell state measurement. Teleportation of a quantum state can thus occur with certainty in principle. (orig.)

  9. Upregulation of the Chemokine Receptor CCR7 expression by HIF-1αand HIF-2α in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yang LI

    2008-10-01

    Full Text Available Background and objective CCR7 is closely related with the lymph node metastasis of non-small cell lung cancer. The objective of this work is to investigate the expressions of chemokine receptor CCR7, hypoxiainducible factor 1α (HIF-1α and hypoxia inducible factor 2α (HIF-2α protein in non small cell lung cancer and the relationships of their expression, and to study the mechanism of CCR7 upregulation in NSCLC. Methods T he levels of expressions of CCR7, HIF-1α and HIF-2α protein were detected in 94 specimens of human primary non small cell lung cancer by immunohistochemical S-P method. Human lung adenocarcinoma cell line A549 cells were transfected by lipofection with HIF-1α siRNA、HIF-2α siRNA, the change of CCR7 was observed by RT-PCR and immunofluorescence staining. Correlations between the expression of CCR7 and HIF-1α, HIF-2α were respectively analyzed. Results Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells, HIF-1α, HIF-2α was distributed in nucleus and/or cytoplasm of tumor cells. The levels of expressions of CCR7, HIF-1α and HIF-2α protein were found to be 75.53% (71/94, 54.25% (51/ 94 and 70.21% (66/94 in non small celllung cancer, respectively. the levels of expression of CCR7 protein were closely related to the clinical stages (P 0.05. Furthermore, A significant correlation were found among CCR7, Hif-1α and HIF-2α (r =0.272, P <0.01 (r=0.225, P <0.05. In addition, the expression of CCR7 mRNA and protein levels were decreased in the transfected specificHIF-1α, HIF-2αsiRNA group (P <0.05. Conclusion CCR7 expression is significantly associated with non small cell lung cancer invasion and metastasis. The upregulation of CCR7 is regulated by HIF-1α and HIF-2α in non small cell lung cancer.

  10. Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians

    Directory of Open Access Journals (Sweden)

    Angelica B.W. Boldt

    2009-01-01

    Full Text Available The CC chemokine receptor 5 (CCR5 molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%, which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%. This allele is uncommon in Afro-Brazilians (2.0%, rare in the Guarani Amerindians (0.4% and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7% and R60S in the Afro-Brazilians (5.0%. A29S and L55Q present an impaired response to b-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T in Guarani (1.4% and Y68C (g.2964A > G in Kaingang (10.3%. The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations.

  11. Quantum robots and quantum computers

    Energy Technology Data Exchange (ETDEWEB)

    Benioff, P.

    1998-07-01

    Validation of a presumably universal theory, such as quantum mechanics, requires a quantum mechanical description of systems that carry out theoretical calculations and systems that carry out experiments. The description of quantum computers is under active development. No description of systems to carry out experiments has been given. A small step in this direction is taken here by giving a description of quantum robots as mobile systems with on board quantum computers that interact with different environments. Some properties of these systems are discussed. A specific model based on the literature descriptions of quantum Turing machines is presented.

  12. Quantum computers and quantum computations

    International Nuclear Information System (INIS)

    Valiev, Kamil' A

    2005-01-01

    This review outlines the principles of operation of quantum computers and their elements. The theory of ideal computers that do not interact with the environment and are immune to quantum decohering processes is presented. Decohering processes in quantum computers are investigated. The review considers methods for correcting quantum computing errors arising from the decoherence of the state of the quantum computer, as well as possible methods for the suppression of the decohering processes. A brief enumeration of proposed quantum computer realizations concludes the review. (reviews of topical problems)

  13. Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis

    NARCIS (Netherlands)

    Klein, Matthias; Brouwer, Matthijs C.; Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter; van de Beek, Diederik; Koedel, Uwe

    2014-01-01

    We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels

  14. CCR1, an enzyme required for lignin biosynthesis in Arabidopsis, mediates cell proliferation exit for leaf development

    DEFF Research Database (Denmark)

    Xue, Jingshi; Luo, Dexian; Xu, Deyang

    2015-01-01

    A level was dramatically reduced. Cell proliferation in comt ccoaomt leaves was decreased, accompanied by elevated ROS levels, and the mutant phenotypes were partially rescued by treatment with FeA or another antioxidant (N-acetyl-L-cysteine). Taken together, our results suggest that CCR1, FeA and ROS...

  15. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-01-01

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  16. A Linear Epitope in the N-Terminal Domain of CCR5 and Its Interaction with Antibody.

    Directory of Open Access Journals (Sweden)

    Benny Chain

    Full Text Available The CCR5 receptor plays a role in several key physiological and pathological processes and is an important therapeutic target. Inhibition of the CCR5 axis by passive or active immunisation offers one very selective strategy for intervention. In this study we define a new linear epitope within the extracellular domain of CCR5 recognised by two independently produced monoclonal antibodies. A short peptide encoding the linear epitope can induce antibodies which recognise the intact receptor when administered colinear with a tetanus toxoid helper T cell epitope. The monoclonal antibody RoAb 13 is shown to bind to both cells and peptide with moderate to high affinity (6x10^8 and 1.2x107 M-1 respectively, and binding to the peptide is enhanced by sulfation of tyrosines at positions 10 and 14. RoAb13, which has previously been shown to block HIV infection, also blocks migration of monocytes in response to CCR5 binding chemokines and to inflammatory macrophage conditioned medium. A Fab fragment of RoAb13 has been crystallised and a structure of the antibody is reported to 2.1 angstrom resolution.

  17. OSCAR Is a Receptor for Surfactant Protein D That Activates TNF-α Release from Human CCR2+ Inflammatory Monocytes

    DEFF Research Database (Denmark)

    Barrow, Alexander D; Palarasah, Yaseelan; Bugatti, Mattia

    2015-01-01

    of recombinant SP-D and captured native SP-D from human bronchoalveolar lavage. OSCAR localized in an intracellular compartment of alveolar macrophages together with SP-D. Moreover, we found OSCAR on the surface of interstitial lung and blood CCR2(+) inflammatory monocytes, which secreted TNF-α when exposed...

  18. Differential between Protein and mRNA Expression of CCR7 and SSTR5 Receptors in Crohn's Disease Patients

    Directory of Open Access Journals (Sweden)

    Nathalie Taquet

    2009-01-01

    Full Text Available Crohn's disease (CD is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417 ± 71 times in CD peripheral blood mononuclear cells (PBMCs. Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10 ± 3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.

  19. Interaction between NANOS2 and the CCR4-NOT deadenylation complex is essential for male germ cell development in mouse.

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki

    Full Text Available Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the first 10 amino acids (AAs of NANOS2 are required for this binding. We further observe that a NANOS2 mutant lacking these first 10 AAs (NANOS2-ΔN10 fails to rescue defects in the Nanos2-null mouse. Our current data thus indicate that the interaction with the CCR4-NOT deadenylation complex is essential for NANOS2 function. In addition, we further demonstrate that NANOS2-ΔN10 can associate with specific mRNAs as well as wild-type NANOS2, suggesting the existence of other NANOS2-associated factor(s that determine the specificity of RNA-binding independently of the CCR4-NOT deadenylation complex.

  20. Quantum mystery

    CERN Document Server

    Chanda, Rajat

    1997-01-01

    The book discusses the laws of quantum mechanics, several amazing quantum phenomena and some recent progress in understanding the connection between the quantum and the classical worlds. We show how paradoxes arise and how to resolve them. The significance of Bell's theorem and the remarkable experimental results on particle correlations are described in some detail. Finally, the current status of our understanding of quantum theory is summerised.

  1. Quantum criticality.

    Science.gov (United States)

    Coleman, Piers; Schofield, Andrew J

    2005-01-20

    As we mark the centenary of Albert Einstein's seminal contribution to both quantum mechanics and special relativity, we approach another anniversary--that of Einstein's foundation of the quantum theory of solids. But 100 years on, the same experimental measurement that puzzled Einstein and his contemporaries is forcing us to question our understanding of how quantum matter transforms at ultra-low temperatures.

  2. Quantum Computing

    Indian Academy of Sciences (India)

    In the first part of this article, we had looked at how quantum physics can be harnessed to make the building blocks of a quantum computer. In this concluding part, we look at algorithms which can exploit the power of this computational device, and some practical difficulties in building such a device. Quantum Algorithms.

  3. I, Quantum Robot: Quantum Mind control on a Quantum Computer

    OpenAIRE

    Zizzi, Paola

    2008-01-01

    The logic which describes quantum robots is not orthodox quantum logic, but a deductive calculus which reproduces the quantum tasks (computational processes, and actions) taking into account quantum superposition and quantum entanglement. A way toward the realization of intelligent quantum robots is to adopt a quantum metalanguage to control quantum robots. A physical implementation of a quantum metalanguage might be the use of coherent states in brain signals.

  4. Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding

    Directory of Open Access Journals (Sweden)

    Corbo Laura

    2001-11-01

    Full Text Available Abstract Background The yeast yCCR4 factor belongs to the CCR4-NOT transcriptional regulatory complex, in which it interacts, through its leucine-rich repeat (LRR motif with yPOP2. Recently, yCCR4 was shown to be a component of the major cytoplasmic mRNA deadenylase complex, and to contain a fold related to the Mg2+-dependent endonuclease core. Results Here, we report the identification of nineteen yCCR4-related proteins in eukaryotes (including yeast, plants and animals, which all contain the yCCR4 endonuclease-like fold, with highly conserved CCR4-specific residues. Phylogenetic and genomic analyses show that they form four distinct families, one of which contains the yCCR4 orthologs. The orthologs in animals possess a leucine-rich repeat domain. We show, using two-hybrid and far-Western assays, that the human member binds to the human yPOP2 homologs, i.e. hCAF1 and hPOP2, in a LRR-dependent manner. Conclusions We have identified the mammalian orthologs of yCCR4 and have shown that the human member binds to the human yPOP2 homologs, thus strongly suggesting conservation of the CCR4-NOT complex from yeast to human. All members of the four identified yCCR4-related protein families show stricking conservation of the endonuclease-like catalytic motifs of the yCCR4 C-terminal domain and therefore constitute a new family of potential deadenylases in mammals.

  5. Characterization of the virus-cell interactions by HIV-1 subtype C variants from an antiretroviral therapy-naïve subject with baseline resistance to the CCR5 inhibitor maraviroc

    DEFF Research Database (Denmark)

    Jakobsen, Martin Roelsgaard

    The CCR5 inhibitor maraviroc (MVC) exerts its antiviral activity by binding to- and altering the conformation of the CCR5 extracellular loops such that HIV-1 gp120 no longer recognizes CCR5. Viruses that have become resistant to MVC through long-term in vitro culture, or from treatment failure...... in vivo, can use the MVCbound form of CCR5 for HIV-1 entry via adaptive alterations in gp120. Partial baseline resistance to another CCR5 inhibitor through this mechanism, AD101, has been noted recently in one subject (1). Here, we identified and characterized envelope (Env) clones with baseline...

  6. Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils.

    Science.gov (United States)

    Fu, Chia-Hsiang; Tsai, Wan-Chun; Lee, Ta-Jen; Huang, Chi-Che; Chang, Po-Hung; Su Pang, Jong-Hwei

    2016-01-01

    IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis.

  7. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

    Science.gov (United States)

    de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

    2015-01-01

    The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

  8. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

    Directory of Open Access Journals (Sweden)

    Amanda Priscila de Oliveira

    Full Text Available The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333 and CCR5 59029 A/G (promoter region--rs1799987 polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD. The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

  9. Characterization and analysis of CCR and CAD gene families at the whole-genome level for lignin synthesis of stone cells in pear (Pyrus bretschneideri) fruit.

    Science.gov (United States)

    Cheng, Xi; Li, Manli; Li, Dahui; Zhang, Jinyun; Jin, Qing; Sheng, Lingling; Cai, Yongping; Lin, Yi

    2017-11-15

    The content of stone cells has significant effects on the flavour and quality of pear fruit. Previous research suggested that lignin deposition is closely related to stone cell formation. In the lignin biosynthetic pathway, cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD), dehydrogenase/reductase family members, catalyse the last two steps in monolignol synthesis. However, there is little knowledge of the characteristics of the CCR and CAD families in pear and their involvement in lignin synthesis of stone cells. In this study, 31 CCR s and 26 CAD s were identified in the pear genome. Phylogenetic trees for CCR s and CAD s were constructed; key amino acid residues were analysed, and three-dimensional structures were predicted. Using quantitative real-time polymerase chain reaction (qRT-PCR), PbCAD2 , PbCCR1 , -2 and - 3 were identified as participating in lignin synthesis of stone cells in pear fruit. Subcellular localization analysis showed that the expressed proteins (PbCAD2, PbCCR1, -2 and -3) are found in the cytoplasm or at the cell membrane. These results reveal the evolutionary features of the CCR and CAD families in pear as well as the genes responsible for regulation of lignin synthesis and stone cell development in pear fruit. © 2017. Published by The Company of Biologists Ltd.

  10. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...

  11. Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists.

    Science.gov (United States)

    Miah, Afjal H; Champigny, Aurelie C; Graves, Rebecca H; Hodgson, Simon T; Percy, Jonathan M; Procopiou, Panayiotis A

    2017-10-15

    A novel 4-aminoindazole sulfonamide hit (13) was identified as a human CCR4 antagonists from testing a focussed library of compounds in the primary GTPγS assay. Replacing the indazole core with a pyrazolopyrimidine, and introduction of a methoxy group adjacent to the sulfonamide substituent, resulted in the identification of pyrazolopyrimidine 37a, which exhibited good binding affinity in the GTPγS assay (pIC 50 =7.2), low lipophilicity (clogP=2.2, chromlogD 7.4 =2.4), high LE (0.41), high solubility (CLND solubility ≥581µM), and an excellent PK profile in both the rat (F=62%) and the dog (F=100%). Further SAR investigation of the pyrazolopyrimidine suggested that substitution at N1 is tolerated, providing a suitable vector to modulate the properties, and increase the potency in a lead optimisation campaign. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Quantum Logic and Quantum Reconstruction

    OpenAIRE

    Stairs, Allen

    2015-01-01

    Quantum logic understood as a reconstruction program had real successes and genuine limitations. This paper offers a synopsis of both and suggests a way of seeing quantum logic in a larger, still thriving context.

  13. Quantum dynamics of quantum bits

    International Nuclear Information System (INIS)

    Nguyen, Bich Ha

    2011-01-01

    The theory of coherent oscillations of the matrix elements of the density matrix of the two-state system as a quantum bit is presented. Different calculation methods are elaborated in the case of a free quantum bit. Then the most appropriate methods are applied to the study of the density matrices of the quantum bits interacting with a classical pumping radiation field as well as with the quantum electromagnetic field in a single-mode microcavity. The theory of decoherence of a quantum bit in Markovian approximation is presented. The decoherence of a quantum bit interacting with monoenergetic photons in a microcavity is also discussed. The content of the present work can be considered as an introduction to the study of the quantum dynamics of quantum bits. (review)

  14. The geographic spread of the CCR5 Delta32 HIV-resistance allele.

    Directory of Open Access Journals (Sweden)

    John Novembre

    2005-11-01

    Full Text Available The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10% for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation. When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

  15. Effects of treatment with Maraviroc a CCR5 inhibitor on a human hepatic stellate cell line.

    Science.gov (United States)

    Coppola, Nicola; Perna, Angelica; Lucariello, Angela; Martini, Salvatore; Macera, Margherita; Carleo, Maria A; Guerra, Germano; Esposito, Vincenzo; De Luca, Antonio

    2018-08-01

    After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated following several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis. Drawing from these background we decided to evaluate the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while the expression of p53 was reduced. Treatment with Maraviroc was also able to block the accumulation of fibrillar collagens and extracellular matrix proteins (ECM), as demonstrated by the decrease of specific markers as Collagen type I, α-SMA, and TGF-β1. In addition we observed a down regulation of both metalloproteins (MMP-2, MMP-9), used for the degradation of the extracellular matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound that may modulate the dynamic of liver fibrosis could be crucial in all chronic liver diseases. Maraviroc could play an important role because, in addition to its own anti-HIV activity, it could reduce the release of pro-inflammatory citokynes implicated in liver fibrogenesis. © 2018 Wiley Periodicals, Inc.

  16. The simultaneous repression of CCR and CAD, two enzymes of the lignin biosynthetic pathway, results in sterility and dwarfism in Arabidopsis thaliana.

    Science.gov (United States)

    Thévenin, Johanne; Pollet, Brigitte; Letarnec, Bruno; Saulnier, Luc; Gissot, Lionel; Maia-Grondard, Alessandra; Lapierre, Catherine; Jouanin, Lise

    2011-01-01

    Cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the last steps of monolignol biosynthesis. In Arabidopsis, one CCR gene (CCR1, At1g15950) and two CAD genes (CAD C At3g19450 and CAD D At4g34230) are involved in this pathway. A triple cad c cad d ccr1 mutant, named ccc, was obtained. This mutant displays a severe dwarf phenotype and male sterility. The lignin content in ccc mature stems is reduced to 50% of the wild-type level. In addition, stem lignin structure is severely affected, as shown by the dramatic enrichment in resistant inter-unit bonds and incorporation into the polymer of monolignol precursors such as coniferaldehyde, sinapaldehyde, and ferulic acid. Male sterility is due to the lack of lignification in the anther endothecium, which causes the failure of anther dehiscence and of pollen release. The ccc hypolignified stems accumulate higher amounts of flavonol glycosides, sinapoyl malate and feruloyl malate, which suggests a redirection of the phenolic pathway. Therefore, the absence of CAD and CCR, key enzymes of the monolignol pathway, has more severe consequences on the phenotype than the individual absence of each of them. Induction of another CCR (CCR2, At1g80820) and another CAD (CAD1, At4g39330) does not compensate the absence of the main CCR and CAD activities. This lack of CCR and CAD activities not only impacts lignification, but also severely affects the development of the plants. These consequences must be carefully considered when trying to reduce the lignin content of plants in order to facilitate the lignocellulose-to-bioethanol conversion process.

  17. CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Johnson Erica L

    2010-06-01

    Full Text Available Abstract Background Cisplatin is more often used to treat ovarian cancer (OvCa, which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9. Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells. Methods Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival. Results Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion. Conclusions Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.

  18. Quantum frames

    Science.gov (United States)

    Brown, Matthew J.

    2014-02-01

    The framework of quantum frames can help unravel some of the interpretive difficulties i the foundation of quantum mechanics. In this paper, I begin by tracing the origins of this concept in Bohr's discussion of quantum theory and his theory of complementarity. Engaging with various interpreters and followers of Bohr, I argue that the correct account of quantum frames must be extended beyond literal space-time reference frames to frames defined by relations between a quantum system and the exosystem or external physical frame, of which measurement contexts are a particularly important example. This approach provides superior solutions to key EPR-type measurement and locality paradoxes.

  19. Quantum Darwinism

    Science.gov (United States)

    Zurek, Wojciech Hubert

    2009-03-01

    Quantum Darwinism describes the proliferation, in the environment, of multiple records of selected states of a quantum system. It explains how the quantum fragility of a state of a single quantum system can lead to the classical robustness of states in their correlated multitude; shows how effective `wave-packet collapse' arises as a result of the proliferation throughout the environment of imprints of the state of the system; and provides a framework for the derivation of Born's rule, which relates the probabilities of detecting states to their amplitudes. Taken together, these three advances mark considerable progress towards settling the quantum measurement problem.

  20. Quantum dots

    International Nuclear Information System (INIS)

    Kouwenhoven, L.; Marcus, C.

    1998-01-01

    Quantum dots are man-made ''droplets'' of charge that can contain anything from a single electron to a collection of several thousand. Their typical dimensions range from nanometres to a few microns, and their size, shape and interactions can be precisely controlled through the use of advanced nanofabrication technology. The physics of quantum dots shows many parallels with the behaviour of naturally occurring quantum systems in atomic and nuclear physics. Indeed, quantum dots exemplify an important trend in condensed-matter physics in which researchers study man-made objects rather than real atoms or nuclei. As in an atom, the energy levels in a quantum dot become quantized due to the confinement of electrons. With quantum dots, however, an experimentalist can scan through the entire periodic table by simply changing a voltage. In this article the authors describe how quantum dots make it possible to explore new physics in regimes that cannot otherwise be accessed in the laboratory. (UK)

  1. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

    OpenAIRE

    de Oliveira, Amanda Priscila; Bernardo, C?ssia Rubia; Camargo, Ana Vit?ria da Silveira; Ronchi, Luiz S?rgio; Borim, Aldenis Albaneze; Brand?o de Mattos, Cinara C?ssia; de Campos J?nior, Eumildo; Castiglioni, L?lian; Netinho, Jo?o Gomes; Cavasini, Carlos Eug?nio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

    2015-01-01

    The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic C...

  2. Chemokine CCL2–CCR2 Signaling Induces Neuronal Cell Death via STAT3 Activation and IL-1β Production after Status Epilepticus

    Science.gov (United States)

    Tian, Dai-Shi; Feng, Li-Jie; Liu, Jun-Li

    2017-01-01

    Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2–CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1 d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1GFP/+:CCR2RFP/+ double-transgenic mice, we demonstrated that CCL2–CCR2 signaling has a role in resident microglial activation and blood-derived monocyte infiltration. Moreover, seizure-induced degeneration of neurons in the hippocampal CA3 region was attenuated in mice lacking CCL2 or CCR2. We further showed that CCR2 activation induced STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL-1β production, which are critical for promoting neuronal cell death after status epilepticus. Consistently, pharmacological inhibition of STAT3 by WP1066 reduced seizure-induced IL-1β production and subsequent neuronal death. Two weeks after KA-induced seizures, CCR2 deficiency not only reduced neuronal loss, but also attenuated seizure-induced behavioral impairments, including anxiety, memory decline, and recurrent seizure severity. Together, we demonstrated that CCL2–CCR2 signaling contributes to neurodegeneration via STAT3 activation and IL-1β production after status epilepticus, providing potential therapeutic targets for the treatment of epilepsy. SIGNIFICANCE STATEMENT Epilepsy is a global concern and epileptic seizures occur in many neurological conditions. Neuroinflammation associated with microglial activation and monocyte infiltration are characteristic of epileptic brains. However, molecular mechanisms underlying neuroinflammation in neuronal death following epilepsy remain to be elucidated. Here we demonstrate that CCL2–CCR2 signaling is

  3. Quantum information. Teleporation - cryptography - quantum computer

    International Nuclear Information System (INIS)

    Breuer, Reinhard

    2010-01-01

    The following topics are dealt with: Reality in the test house, quantum teleportation, 100 years of quantum theory, the reality of quanta, interactionless quantum measurement, rules for quantum computers, quantum computers with ions, spintronics with diamond, the limits of the quantum computers, a view into the future of quantum optics. (HSI)

  4. Quantum symmetry in quantum theory

    International Nuclear Information System (INIS)

    Schomerus, V.

    1993-02-01

    Symmetry concepts have always been of great importance for physical problems like explicit calculations, classification or model building. More recently, new 'quantum symmetries' ((quasi) quantum groups) attracted much interest in quantum theory. It is shown that all these quantum symmetries permit a conventional formulation as symmetry in quantum mechanics. Symmetry transformations can act on the Hilbert space H of physical states such that the ground state is invariant and field operators transform covariantly. Models show that one must allow for 'truncation' in the tensor product of representations of a quantum symmetry. This means that the dimension of the tensor product of two representations of dimension σ 1 and σ 2 may be strictly smaller than σ 1 σ 2 . Consistency of the transformation law of field operators local braid relations leads us to expect, that (weak) quasi quantum groups are the most general symmetries in local quantum theory. The elements of the R-matrix which appears in these local braid relations turn out to be operators on H in general. It will be explained in detail how examples of field algebras with weak quasi quantum group symmetry can be obtained. Given a set of observable field with a finite number of superselection sectors, a quantum symmetry together with a complete set of covariant field operators which obey local braid relations are constructed. A covariant transformation law for adjoint fields is not automatic but will follow when the existence of an appropriate antipode is assumed. At the example of the chiral critical Ising model, non-uniqueness of the quantum symmetry will be demonstrated. Generalized quantum symmetries yield examples of gauge symmetries in non-commutative geometry. Quasi-quantum planes are introduced as the simplest examples of quasi-associative differential geometry. (Weak) quasi quantum groups can act on them by generalized derivations much as quantum groups do in non-commutative (differential-) geometry

  5. Quantum games as quantum types

    Science.gov (United States)

    Delbecque, Yannick

    In this thesis, we present a new model for higher-order quantum programming languages. The proposed model is an adaptation of the probabilistic game semantics developed by Danos and Harmer [DH02]: we expand it with quantum strategies which enable one to represent quantum states and quantum operations. Some of the basic properties of these strategies are established and then used to construct denotational semantics for three quantum programming languages. The first of these languages is a formalisation of the measurement calculus proposed by Danos et al. [DKP07]. The other two are new: they are higher-order quantum programming languages. Previous attempts to define a denotational semantics for higher-order quantum programming languages have failed. We identify some of the key reasons for this and base the design of our higher-order languages on these observations. The game semantics proposed in this thesis is the first denotational semantics for a lambda-calculus equipped with quantum types and with extra operations which allow one to program quantum algorithms. The results presented validate the two different approaches used in the design of these two new higher-order languages: a first one where quantum states are used through references and a second one where they are introduced as constants in the language. The quantum strategies presented in this thesis allow one to understand the constraints that must be imposed on quantum type systems with higher-order types. The most significant constraint is the fact that abstraction over part of the tensor product of many unknown quantum states must not be allowed. Quantum strategies are a new mathematical model which describes the interaction between classical and quantum data using system-environment dialogues. The interactions between the different parts of a quantum system are described using the rich structure generated by composition of strategies. This approach has enough generality to be put in relation with other

  6. CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.

    Science.gov (United States)

    Kulkarni, Hemant; Agan, Brian K; Marconi, Vincent C; O'Connell, Robert J; Camargo, Jose F; He, Weijing; Delmar, Judith; Phelps, Kenneth R; Crawford, George; Clark, Robert A; Dolan, Matthew J; Ahuja, Sunil K

    2008-09-08

    Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management

  7. Quantum measurement

    CERN Document Server

    Busch, Paul; Pellonpää, Juha-Pekka; Ylinen, Kari

    2016-01-01

    This is a book about the Hilbert space formulation of quantum mechanics and its measurement theory. It contains a synopsis of what became of the Mathematical Foundations of Quantum Mechanics since von Neumann’s classic treatise with this title. Fundamental non-classical features of quantum mechanics—indeterminacy and incompatibility of observables, unavoidable measurement disturbance, entanglement, nonlocality—are explicated and analysed using the tools of operational quantum theory. The book is divided into four parts: 1. Mathematics provides a systematic exposition of the Hilbert space and operator theoretic tools and relevant measure and integration theory leading to the Naimark and Stinespring dilation theorems; 2. Elements develops the basic concepts of quantum mechanics and measurement theory with a focus on the notion of approximate joint measurability; 3. Realisations offers in-depth studies of the fundamental observables of quantum mechanics and some of their measurement implementations; and 4....

  8. Quantum Optics

    CERN Document Server

    Walls, D F

    2007-01-01

    Quantum Optics gives a comprehensive coverage of developments in quantum optics over the past years. In the early chapters the formalism of quantum optics is elucidated and the main techniques are introduced. These are applied in the later chapters to problems such as squeezed states of light, resonance fluorescence, laser theory, quantum theory of four-wave mixing, quantum non-demolition measurements, Bell's inequalities, and atom optics. Experimental results are used to illustrate the theory throughout. This yields the most comprehensive and up-to-date coverage of experiment and theory in quantum optics in any textbook. More than 40 exercises helps readers test their understanding and provide practice in quantitative problem solving.

  9. Quantum gravity

    International Nuclear Information System (INIS)

    Markov, M.A.; West, P.C.

    1984-01-01

    This book discusses the state of the art of quantum gravity, quantum effects in cosmology, quantum black-hole physics, recent developments in supergravity, and quantum gauge theories. Topics considered include the problems of general relativity, pregeometry, complete cosmological theories, quantum fluctuations in cosmology and galaxy formation, a new inflationary universe scenario, grand unified phase transitions and the early Universe, the generalized second law of thermodynamics, vacuum polarization near black holes, the relativity of vacuum, black hole evaporations and their cosmological consequences, currents in supersymmetric theories, the Kaluza-Klein theories, gauge algebra and quantization, and twistor theory. This volume constitutes the proceedings of the Second Seminar on Quantum Gravity held in Moscow in 1981

  10. Opposing effects of CXCR3 and CCR5 deficiency on CD8+ T cell-mediated inflammation in the central nervous system of virus-infected mice

    DEFF Research Database (Denmark)

    de Lemos, Carina; Christensen, Jeanette Erbo; Nansen, Anneline

    2005-01-01

    and therefore protect mice against the otherwise fatal CD8+ T cell-mediated immune attack. Contrary to expectations, the accumulation of mononuclear cells in cerebrospinal fluid was only slightly delayed compared with mice with normal expression of both receptors. Even more surprising, CXCR3/CCR5 double-deficient......T cells play a key role in the control of viral infection in the CNS but may also contribute to immune-mediated cell damage. To study the redundancy of the chemokine receptors CXCR3 and CCR5 in regulating virus-induced CD8+ T cell-mediated inflammation in the brain, CXCR3/CCR5 double-deficient mice...... mice were more susceptible to intracerebral infection than CXCR3-deficient mice. Analysis of effector T cell generation revealed an accelerated antiviral CD8+ T cell response in CXCR3/CCR5 double-deficient mice. Furthermore, while the accumulation of CD8+ T cells in the neural parenchyma...

  11. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor

    DEFF Research Database (Denmark)

    Tran, E H; Kuziel, W A; Owens, T

    2000-01-01

    -type mice in Th1 cytokine gene expression, the kinetics and severity of disease, and infiltration of the central nervous system by lymphocytes, macrophages and granulocytes. RNase protection assays showed comparable accumulation of mRNA for the chemokines interferon-inducible protein-10, RANTES, macrophage...... and its CCR5 receptor in the induction of EAE by immunizing C57BL / 6 mice deficient in either MIP-1alpha or CCR5 with myelin oligodendrocyte glycoprotein (MOG). We found that MIP-1alpha-deficient mice were fully susceptible to MOG-induced EAE. These knockout animals were indistinguishable from wild...... chemoattractant protein-1, MIP-1beta, MIP-2, lymphotactin and T cell activation gene-3 during the course of the disease. CCR5-deficient mice were also susceptible to disease induction by MOG. The dispensability of MIP-1alpha and CCR5 for MOG-induced EAE in C57BL / 6 mice supports the idea that differential...

  12. A paternally transmitted complex chromosomal rearrangement (CCR) involving chromosomes 2, 6, and 18 includes eight breakpoints and five insertional translocations (ITs) through three generations.

    Science.gov (United States)

    Gruchy, Nicolas; Barreau, Morgane; Kessler, Ketty; Gourdier, Dominique; Leporrier, Nathalie

    2010-01-01

    Complex chromosomal rearrangements (CCRs) are uncommon and mainly occur de novo. We report here on a familial CCR involving chromosomes 2, 6, and 18. The propositus is a boy first referred because of growth delays, hypotonia, and facial anomalies, suggestive of deletion 18q syndrome. However, a cytogenetic family study disclosed a balanced CCR in three generations, which was detailed by FISH using BAC clones, and consisted of eight breakpoints with five insertional translocations (ITs). The propositus had a cryptic 18q deletion and a 6p duplication. Paternal transmission of this CCR was observed through three generations without meiotic recombination. Our investigation allowed us to provide porosities counseling and management of prenatal diagnosis for propositus cousin who carries this particular CCR.

  13. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Kaas, A.; Hansen, L.

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated...... longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated...... of CCR5 by therapeutic agents such as maraviroc may provide a new therapeutic target to ameliorate disease progression in type 1 diabetes. (C) 2008 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/7...

  14. Quantum Locality?

    OpenAIRE

    Stapp, Henry P.

    2011-01-01

    Robert Griffiths has recently addressed, within the framework of a 'consistent quantum theory' that he has developed, the issue of whether, as is often claimed, quantum mechanics entails a need for faster-than-light transfers of information over long distances. He argues that the putative proofs of this property that involve hidden variables include in their premises some essentially classical-physics-type assumptions that are fundamentally incompatible with the precepts of quantum physics. O...

  15. Quantum ratchets

    OpenAIRE

    Grifoni, Milena

    1997-01-01

    In this thesis, ratchet systems operating in the quantum regime are investigated. Ratchet systems, also known as Brownian motors, are periodic systems presenting an intrinsic asymmetry which can be exploited to extract work out of unbiased forces. As a model for ratchet systems, we consider the motion of a particle in a one-dimensional periodic and asymmetric potential, interacting with a thermal environment, and subject to an unbiased driving force. In quantum ratchets, intrinsic quantum flu...

  16. Quantum space and quantum completeness

    Science.gov (United States)

    Jurić, Tajron

    2018-05-01

    Motivated by the question whether quantum gravity can "smear out" the classical singularity we analyze a certain quantum space and its quantum-mechanical completeness. Classical singularity is understood as a geodesic incompleteness, while quantum completeness requires a unique unitary time evolution for test fields propagating on an underlying background. Here the crucial point is that quantum completeness renders the Hamiltonian (or spatial part of the wave operator) to be essentially self-adjoint in order to generate a unique time evolution. We examine a model of quantum space which consists of a noncommutative BTZ black hole probed by a test scalar field. We show that the quantum gravity (noncommutative) effect is to enlarge the domain of BTZ parameters for which the relevant wave operator is essentially self-adjoint. This means that the corresponding quantum space is quantum complete for a larger range of BTZ parameters rendering the conclusion that in the quantum space one observes the effect of "smearing out" the singularity.

  17. Quantum mechanics

    International Nuclear Information System (INIS)

    Basdevant, J.L.; Dalibard, J.; Joffre, M.

    2008-01-01

    All physics is quantum from elementary particles to stars and to the big-bang via semi-conductors and chemistry. This theory is very subtle and we are not able to explain it without the help of mathematic tools. This book presents the principles of quantum mechanics and describes its mathematical formalism (wave function, Schroedinger equation, quantum operators, spin, Hamiltonians, collisions,..). We find numerous applications in the fields of new technologies (maser, quantum computer, cryptography,..) and in astrophysics. A series of about 90 exercises with their answers is included. This book is based on a physics course at a graduate level. (A.C.)

  18. Quantum information

    International Nuclear Information System (INIS)

    Rodgers, P.

    1998-01-01

    There is more to information than a string of ones and zeroes the ability of ''quantum bits'' to be in two states at the same time could revolutionize information technology. In the mid-1930s two influential but seemingly unrelated papers were published. In 1935 Einstein, Podolsky and Rosen proposed the famous EPR paradox that has come to symbolize the mysteries of quantum mechanics. Two years later, Alan Turing introduced the universal Turing machine in an enigmatically titled paper, On computable numbers, and laid the foundations of the computer industry one of the biggest industries in the world today. Although quantum physics is essential to understand the operation of transistors and other solid-state devices in computers, computation itself has remained a resolutely classical process. Indeed it seems only natural that computation and quantum theory should be kept as far apart as possible surely the uncertainty associated with quantum theory is anathema to the reliability expected from computers? Wrong. In 1985 David Deutsch introduced the universal quantum computer and showed that quantum theory can actually allow computers to do more rather than less. The ability of particles to be in a superposition of more than one quantum state naturally introduces a form of parallelism that can, in principle, perform some traditional computing tasks faster than is possible with classical computers. Moreover, quantum computers are capable of other tasks that are not conceivable with their classical counterparts. Similar breakthroughs in cryptography and communication followed. (author)

  19. Quantum information

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, P

    1998-03-01

    There is more to information than a string of ones and zeroes the ability of ''quantum bits'' to be in two states at the same time could revolutionize information technology. In the mid-1930s two influential but seemingly unrelated papers were published. In 1935 Einstein, Podolsky and Rosen proposed the famous EPR paradox that has come to symbolize the mysteries of quantum mechanics. Two years later, Alan Turing introduced the universal Turing machine in an enigmatically titled paper, On computable numbers, and laid the foundations of the computer industry one of the biggest industries in the world today. Although quantum physics is essential to understand the operation of transistors and other solid-state devices in computers, computation itself has remained a resolutely classical process. Indeed it seems only natural that computation and quantum theory should be kept as far apart as possible surely the uncertainty associated with quantum theory is anathema to the reliability expected from computers? Wrong. In 1985 David Deutsch introduced the universal quantum computer and showed that quantum theory can actually allow computers to do more rather than less. The ability of particles to be in a superposition of more than one quantum state naturally introduces a form of parallelism that can, in principle, perform some traditional computing tasks faster than is possible with classical computers. Moreover, quantum computers are capable of other tasks that are not conceivable with their classical counterparts. Similar breakthroughs in cryptography and communication followed. (author)

  20. Quantum Integers

    International Nuclear Information System (INIS)

    Khrennikov, Andrei; Klein, Moshe; Mor, Tal

    2010-01-01

    In number theory, a partition of a positive integer n is a way of writing n as a sum of positive integers. The number of partitions of n is given by the partition function p(n). Inspired by quantum information processing, we extend the concept of partitions in number theory as follows: for an integer n, we treat each partition as a basis state of a quantum system representing that number n, so that the Hilbert-space that corresponds to that integer n is of dimension p(n); the 'classical integer' n can thus be generalized into a (pure) quantum state ||ψ(n) > which is a superposition of the partitions of n, in the same way that a quantum bit (qubit) is a generalization of a classical bit. More generally, ρ(n) is a density matrix in that same Hilbert-space (a probability distribution over pure states). Inspired by the notion of quantum numbers in quantum theory (such as in Bohr's model of the atom), we then try to go beyond the partitions, by defining (via recursion) the notion of 'sub-partitions' in number theory. Combining the two notions mentioned above, sub-partitions and quantum integers, we finally provide an alternative definition of the quantum integers [the pure-state |ψ'(n)> and the mixed-state ρ'(n),] this time using the sub-partitions as the basis states instead of the partitions, for describing the quantum number that corresponds to the integer n.

  1. Quantum computation

    International Nuclear Information System (INIS)

    Deutsch, D.

    1992-01-01

    As computers become ever more complex, they inevitably become smaller. This leads to a need for components which are fabricated and operate on increasingly smaller size scales. Quantum theory is already taken into account in microelectronics design. This article explores how quantum theory will need to be incorporated into computers in future in order to give them their components functionality. Computation tasks which depend on quantum effects will become possible. Physicists may have to reconsider their perspective on computation in the light of understanding developed in connection with universal quantum computers. (UK)

  2. Quantum information

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, P

    1998-03-01

    There is more to information than a string of ones and zeroes the ability of ''quantum bits'' to be in two states at the same time could revolutionize information technology. In the mid-1930s two influential but seemingly unrelated papers were published. In 1935 Einstein, Podolsky and Rosen proposed the famous EPR paradox that has come to symbolize the mysteries of quantum mechanics. Two years later, Alan Turing introduced the universal Turing machine in an enigmatically titled paper, On computable numbers, and laid the foundations of the computer industry one of the biggest industries in the world today. Although quantum physics is essential to understand the operation of transistors and other solid-state devices in computers, computation itself has remained a resolutely classical process. Indeed it seems only natural that computation and quantum theory should be kept as far apart as possible surely the uncertainty associated with quantum theory is anathema to the reliability expected from computers? Wrong. In 1985 David Deutsch introduced the universal quantum computer and showed that quantum theory can actually allow computers to do more rather than less. The ability of particles to be in a superposition of more than one quantum state naturally introduces a form of parallelism that can, in principle, perform some traditional computing tasks faster than is possible with classical computers. Moreover, quantum computers are capable of other tasks that are not conceivable with their classical counterparts. Similar breakthroughs in cryptography and communication followed. (author)

  3. Quantum Dots

    Science.gov (United States)

    Tartakovskii, Alexander

    2012-07-01

    Part I. Nanostructure Design and Structural Properties of Epitaxially Grown Quantum Dots and Nanowires: 1. Growth of III/V semiconductor quantum dots C. Schneider, S. Hofling and A. Forchel; 2. Single semiconductor quantum dots in nanowires: growth, optics, and devices M. E. Reimer, N. Akopian, M. Barkelid, G. Bulgarini, R. Heeres, M. Hocevar, B. J. Witek, E. Bakkers and V. Zwiller; 3. Atomic scale analysis of self-assembled quantum dots by cross-sectional scanning tunneling microscopy and atom probe tomography J. G. Keizer and P. M. Koenraad; Part II. Manipulation of Individual Quantum States in Quantum Dots Using Optical Techniques: 4. Studies of the hole spin in self-assembled quantum dots using optical techniques B. D. Gerardot and R. J. Warburton; 5. Resonance fluorescence from a single quantum dot A. N. Vamivakas, C. Matthiesen, Y. Zhao, C.-Y. Lu and M. Atature; 6. Coherent control of quantum dot excitons using ultra-fast optical techniques A. J. Ramsay and A. M. Fox; 7. Optical probing of holes in quantum dot molecules: structure, symmetry, and spin M. F. Doty and J. I. Climente; Part III. Optical Properties of Quantum Dots in Photonic Cavities and Plasmon-Coupled Dots: 8. Deterministic light-matter coupling using single quantum dots P. Senellart; 9. Quantum dots in photonic crystal cavities A. Faraon, D. Englund, I. Fushman, A. Majumdar and J. Vukovic; 10. Photon statistics in quantum dot micropillar emission M. Asmann and M. Bayer; 11. Nanoplasmonics with colloidal quantum dots V. Temnov and U. Woggon; Part IV. Quantum Dot Nano-Laboratory: Magnetic Ions and Nuclear Spins in a Dot: 12. Dynamics and optical control of an individual Mn spin in a quantum dot L. Besombes, C. Le Gall, H. Boukari and H. Mariette; 13. Optical spectroscopy of InAs/GaAs quantum dots doped with a single Mn atom O. Krebs and A. Lemaitre; 14. Nuclear spin effects in quantum dot optics B. Urbaszek, B. Eble, T. Amand and X. Marie; Part V. Electron Transport in Quantum Dots Fabricated by

  4. MCP-1/CCR-2-double-deficiency severely impairs the migration of hematogenous inflammatory cells following transient cerebral ischemia in mice.

    Science.gov (United States)

    Schuette-Nuetgen, Katharina; Strecker, Jan-Kolja; Minnerup, Jens; Ringelstein, E Bernd; Schilling, Matthias

    2012-02-01

    Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR-2 are known to play a major role in inflammatory responses after cerebral ischemia. Mice deficient in either MCP-1 or CCR-2 have been reported to develop smaller infarct sizes and show decreased numbers of infiltrating inflammatory cells. In the present study we used green fluorescent protein (GFP) transgenic mice to investigate the effect of MCP-1/CCR-2-double deficiency on the recruitment of inflammatory cells in a model of both, mild and severe cerebral ischemia. We show that MCP-1/CCR-2-double deficiency virtually entirely abrogates the recruitment of hematogenous macrophages and significantly reduces neutrophil migration to the ischemic brain 4 and 7 days following focal cerebral ischemia. This argues for a predominant role of the MCP-1/CCR-2 axis in chemotaxis of monocytes despite a wide redundancy in the chemokine-receptor-system. Chemokine analysis revealed that even candidates known to be involved in monocyte and neutrophil recruitment like MIP-1α, CXCL-1, C5a, G-CSF and GM-CSF showed a reduced and delayed or even a lack of relevant compensatory response in MCP-1(-/-)/CCR-2(-/-)-mice. Solely, chemokine receptor 5 (CCR-5) increased early in both, but rose above wildtype levels at day 7 in MCP-1(-/-)/CCR-2(-/-)-animals, which might explain the higher number of activated microglial cells compared to control mice. Our study was, however, not powered to investigate infarct volumes. Further studies are needed to clarify whether these mechanisms of inflammatory cell recruitment might be essential for early infarct development and final infarct size and to evaluate potential therapeutic implications. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

    Directory of Open Access Journals (Sweden)

    Charo Israel F

    2004-09-01

    Full Text Available Abstract Background Asthma is characterized by type 2 T-helper cell (Th2 inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2 and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.

  6. The positive correlation of the CCL2-CCR2 axis with the disease activity may indicate the fundamental role in the pathogenesis of oral lichen planus.

    Science.gov (United States)

    Yin, Jingfang; Yang, Xi; Zeng, Qi; Yang, Linglan; Cheng, Bin; Tao, Xiaoan

    2016-01-01

    The important roles of CCL2 and its receptor CCR2 had been reported in a series of inflammatory disorders. However, few studies investigated the potential role of CCL2/CCR2 axis in oral lichen planus (OLP). Therefore, this study aimed to detect the expression of CCL2 and CCR2 in OLP lesions and compare their changes before and after treatment. CCL2 and CCR2 expression was investigated using immunohistochemical staining and real-time RT-PCR in 32 patients with OLP and eight controls. Moreover, changes in their expression after treatment with triamcinolone acetonide were assessed in lesions from three patients. CCL2+ and CCR2+ cells were few in the controls and remarkably increased in the epithelial and subepithelial layers of lesions (n = 32, all P < 0.001). However, the densities of CCL2+ and CCR2+ cells were not significantly different between reticular (n = 12) and erythematous/erosive lesions (n = 20), although they significantly decreased after treatment (627.7 ± 108.2 vs. 258.3 ± 148.3, P = 0.017; 1034.7 ± 74.6 vs. 648 ± 77.6, P = 0.003, respectively). CCL2+/CCR2+ cell numbers were positively correlated with disease activity (correlation coefficient, 0.588; P < 0.001; correlation coefficient, 0.409; P = 0.02, respectively). The results of this study indicated that the CCL2-CCR2 axis was involved in the pathogenesis of OLP and was positively correlated with disease activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Comparison of different boost transformations for the calculation of form factors in relativistic quantum mechanics

    International Nuclear Information System (INIS)

    Theussl, L.; Noguera, S.; Amghar, A.; Desplanques, B.

    2003-01-01

    The effect of different boost expressions, pertinent to the instant, front and point forms of relativistic quantum mechanics, is considered for the calculation of the ground-state form factor of a two-body system in simple scalar models. Results with a Galilean boost as well as an explicitly covariant calculation based on the Bethe-Salpeter approach are given for comparison. It is found that the present so-called point-form calculations of form factors strongly deviate from all the other ones. This suggests that the formalism which underlies them requires further elaboration. A proposition in this sense is made. (author)

  8. Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5)

    DEFF Research Database (Denmark)

    Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav

    2016-01-01

    The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn(2+) (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site......Terp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248(VI:13/6.48) microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism...

  9. HIV-1 entry inhibition by small-molecule CCR5 antagonists: A combined molecular modeling and mutant study using a high-throughput assay

    International Nuclear Information System (INIS)

    Labrecque, Jean; Metz, Markus; Lau, Gloria; Darkes, Marilyn C.; Wong, Rebecca S.Y.; Bogucki, David; Carpenter, Bryon; Chen Gang; Li Tongshuang; Nan, Susan; Schols, Dominique; Bridger, Gary J.; Fricker, Simon P.; Skerlj, Renato T.

    2011-01-01

    Based on the attrition rate of CCR5 small molecule antagonists in the clinic the discovery and development of next generation antagonists with an improved pharmacology and safety profile is necessary. Herein, we describe a combined molecular modeling, CCR5-mediated cell fusion, and receptor site-directed mutagenesis approach to study the molecular interactions of six structurally diverse compounds (aplaviroc, maraviroc, vicriviroc, TAK-779, SCH-C and a benzyloxycarbonyl-aminopiperidin-1-yl-butane derivative) with CCR5, a coreceptor for CCR5-tropic HIV-1 strains. This is the first study using an antifusogenic assay, a model of the interaction of the gp120 envelope protein with CCR5. This assay avoids the use of radioactivity and HIV infection assays, and can be used in a high throughput mode. The assay was validated by comparison with other established CCR5 assays. Given the hydrophobic nature of the binding pocket several binding models are suggested which could prove useful in the rational drug design of new lead compounds.

  10. Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.

    Science.gov (United States)

    Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

    2010-06-11

    Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium 3 days after MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks after MI. Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium.

  11. CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs.

    Science.gov (United States)

    Diao, Ruiying; Wei, Weixia; Zhao, Jinghui; Tian, Fuying; Cai, Xueyong; Duan, Yong-Gang

    2017-11-01

    The level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown. ELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Expressions of Bcl2, MMP2, MMP9, and p-AKT/AKT were analyzed by Western blot. Peritoneal fluid concentration of CCL19 in patients with endometriosis was higher than that in controls. Those patients with moderate/severe endometriosis had significantly higher peritoneal fluid concentrations of CCL19 compared to those with minimal/mild endometriosis. Higher CCL19 and CCR7 were found in the endometrium with endometriosis compared to control. CCL19 significantly enhanced ESC proliferation and invasion through CCR7 via activating PI3K/Akt signal pathways. CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, Bcl2, MMP2, and MMP9 in ESCs. These data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

    2014-01-01

    Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

  13. Human anti-CCR4 minibody gene transfer for the treatment of cutaneous T-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Thomas Han

    Full Text Available Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL, no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4.In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8 vector expressing a humanized single-chain variable fragment (scFv-Fc fusion (scFvFc or "minibody" of anti-CCR4 monoclonal antibody (mAb h1567 was evaluated for curative treatment. Human CCR4+ tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567 minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G+ FcγRIIIa(CD16A+ murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice. Furthermore, in CCR4+ tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs, marked tumor infiltration of human CD16A+ CD56+ NK cells was observed. The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells.Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A+ immune effector cell ADCC mechanisms. These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.

  14. Determination of thermodynamic parameters of benzylpenicillin hydrolysis by metallo-β-lactamase CcrA from Bacteroides fragilis

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Le; Zhou, Li-Sheng; Liu, Cheng-Cheng; Shi, Ying; Zhou, Ya-Jun [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an 710069 (China); Yang, Ke-Wu, E-mail: kwyang@nwu.edu.cn [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an 710069 (China)

    2013-03-20

    Highlights: ► First report the thermokinetic parameters of benzylpenicillin hydrolysis with CcrA. ► The hydrolysis is a spontaneous and exothermic reaction with order of 1.4. ► Summarized that CcrA prefer to hydrolyze penicillins among β-lactam antibiotics. - Abstract: One of the most common way that bacteria become resistant to antibiotics is by the production of metallo-β-lactamases (MβLs) to hydrolyze the β-lactam-containing antibiotics. In this paper, the thermodynamic parameters of benzylpenicillin hydrolysis with B1 subclasses MβL CcrA (carbapenem and cephamycin resistance) from Bacteroides fragilis were determined by microcalorimetry. The activation free energy ΔG{sub ≠}{sup θ} is 87.90 ± 0.03, 88.99 ± 0.01, 89.93 ± 0.04 and 90.93 ± 0.05 kJ mol{sup −1} at 293.15, 298.15, 303.15 and 308.15 K, activation enthalpy ΔH{sub ≠}{sup θ} is 29.21 ± 0.03 kJ mol{sup −1}, activation entropy ΔS{sub ≠}{sup θ} is −200.34 ± 0.08 J mol{sup −1} K{sup −1}, the reaction order is 1.4, and the apparent activation energy E is 31.71 kJ mol{sup −1}. The thermodynamic characterization indicated that CcrA prefer to hydrolyze penicillins among three kinds of β-lactam-containing antibiotics.

  15. Determination of thermodynamic parameters of benzylpenicillin hydrolysis by metallo-β-lactamase CcrA from Bacteroides fragilis

    International Nuclear Information System (INIS)

    Zhai, Le; Zhou, Li-Sheng; Liu, Cheng-Cheng; Shi, Ying; Zhou, Ya-Jun; Yang, Ke-Wu

    2013-01-01

    Highlights: ► First report the thermokinetic parameters of benzylpenicillin hydrolysis with CcrA. ► The hydrolysis is a spontaneous and exothermic reaction with order of 1.4. ► Summarized that CcrA prefer to hydrolyze penicillins among β-lactam antibiotics. - Abstract: One of the most common way that bacteria become resistant to antibiotics is by the production of metallo-β-lactamases (MβLs) to hydrolyze the β-lactam-containing antibiotics. In this paper, the thermodynamic parameters of benzylpenicillin hydrolysis with B1 subclasses MβL CcrA (carbapenem and cephamycin resistance) from Bacteroides fragilis were determined by microcalorimetry. The activation free energy ΔG ≠ θ is 87.90 ± 0.03, 88.99 ± 0.01, 89.93 ± 0.04 and 90.93 ± 0.05 kJ mol −1 at 293.15, 298.15, 303.15 and 308.15 K, activation enthalpy ΔH ≠ θ is 29.21 ± 0.03 kJ mol −1 , activation entropy ΔS ≠ θ is −200.34 ± 0.08 J mol −1 K −1 , the reaction order is 1.4, and the apparent activation energy E is 31.71 kJ mol −1 . The thermodynamic characterization indicated that CcrA prefer to hydrolyze penicillins among three kinds of β-lactam-containing antibiotics

  16. Influence of Acyclic Nucleoside Phosphonate Antivirals on Gene Expression of Chemokine Receptors CCR5 and CXCR4

    Czech Academy of Sciences Publication Activity Database

    Potměšil, P.; Holý, Antonín; Zídek, Zdeněk

    2015-01-01

    Roč. 61, č. 1 (2015), s. 1-7 ISSN 0015-5500 R&D Projects: GA ČR GA305/03/1470; GA MŠk 1M0508 Institutional support: RVO:61388963 ; RVO:68378041 Keywords : acyclic nucleoside phosphonate * HIV * CCR5 * CXCR4 * cytokine * RT-PCR Subject RIV: CC - Organic Chemistry; FR - Pharmacology ; Medidal Chemistry (UEM-P) Impact factor: 0.833, year: 2015

  17. CCR investigators use liquid biopsies to uncover cancer in the blood of lymphoma patients | Center for Cancer Research

    Science.gov (United States)

    CCR investigators are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin

  18. Quantum group and quantum symmetry

    International Nuclear Information System (INIS)

    Chang Zhe.

    1994-05-01

    This is a self-contained review on the theory of quantum group and its applications to modern physics. A brief introduction is given to the Yang-Baxter equation in integrable quantum field theory and lattice statistical physics. The quantum group is primarily introduced as a systematic method for solving the Yang-Baxter equation. Quantum group theory is presented within the framework of quantum double through quantizing Lie bi-algebra. Both the highest weight and the cyclic representations are investigated for the quantum group and emphasis is laid on the new features of representations for q being a root of unity. Quantum symmetries are explored in selected topics of modern physics. For a Hamiltonian system the quantum symmetry is an enlarged symmetry that maintains invariance of equations of motion and allows a deformation of the Hamiltonian and symplectic form. The configuration space of the integrable lattice model is analyzed in terms of the representation theory of quantum group. By means of constructing the Young operators of quantum group, the Schroedinger equation of the model is transformed to be a set of coupled linear equations that can be solved by the standard method. Quantum symmetry of the minimal model and the WZNW model in conformal field theory is a hidden symmetry expressed in terms of screened vertex operators, and has a deep interplay with the Virasoro algebra. In quantum group approach a complete description for vibrating and rotating diatomic molecules is given. The exact selection rules and wave functions are obtained. The Taylor expansion of the analytic formulas of the approach reproduces the famous Dunham expansion. (author). 133 refs, 20 figs

  19. β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.

    Science.gov (United States)

    Lin, Rui; Choi, Yeon Ho; Zidar, David A; Walker, Julia K L

    2018-06-01

    Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4 + T-helper cell type 2 (Th2) cells are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of β-arrestin (β-arr)-2 and that CD4 + T cells from these mice displayed significantly reduced CCL22-mediated chemotaxis. Because CCL22-mediated activation of CCR4 plays a role in Th2 cell regulation in asthmatic inflammation, we hypothesized that CCR4-mediated migration of CD4 + Th2 cells to the lung in asthma may use β-arr-dependent signaling. To test this hypothesis, we assessed the effect of various signaling inhibitors on CCL22-induced chemotaxis using in vitro-polarized primary CD4 + Th2 cells from β-arr2-knockout and wild-type mice. Our results show, for the first time, that CCL22-induced, CCR4-mediated Th2 cell chemotaxis is dependent, in part, on a β-arr2-dependent signaling pathway. In addition, we show that this chemotactic signaling mechanism involves activation of P-p38 and Rho-associated protein kinase. These findings point to a proinflammatory role for β-arr2-dependent signaling and support β-arr2 as a novel therapeutic target in asthma.

  20. Structural basis for the Nanos-mediated recruitment of the CCR4–NOT complex and translational repression

    Science.gov (United States)

    Bhandari, Dipankar; Raisch, Tobias; Weichenrieder, Oliver; Jonas, Stefanie; Izaurralde, Elisa

    2014-01-01

    The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4–NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1–3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1–3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1–3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4–NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4–NOT complex as the main effector complex for Nanos function. PMID:24736845

  1. Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.

    Science.gov (United States)

    Bhandari, Dipankar; Raisch, Tobias; Weichenrieder, Oliver; Jonas, Stefanie; Izaurralde, Elisa

    2014-04-15

    The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function.

  2. Quantum information. Teleportation - cryptography - quantum computer

    International Nuclear Information System (INIS)

    Koenneker, Carsten

    2012-01-01

    The following topics are dealt with: Reality in the test facility, quantum teleportation, the reality of quanta, interaction-free quantum measurement, rules for quantum computers, quantum computers with ions, spintronics with diamond, the limits of the quantum computers, a view in the future of quantum optics. (HSI)

  3. Quantum ensembles of quantum classifiers.

    Science.gov (United States)

    Schuld, Maria; Petruccione, Francesco

    2018-02-09

    Quantum machine learning witnesses an increasing amount of quantum algorithms for data-driven decision making, a problem with potential applications ranging from automated image recognition to medical diagnosis. Many of those algorithms are implementations of quantum classifiers, or models for the classification of data inputs with a quantum computer. Following the success of collective decision making with ensembles in classical machine learning, this paper introduces the concept of quantum ensembles of quantum classifiers. Creating the ensemble corresponds to a state preparation routine, after which the quantum classifiers are evaluated in parallel and their combined decision is accessed by a single-qubit measurement. This framework naturally allows for exponentially large ensembles in which - similar to Bayesian learning - the individual classifiers do not have to be trained. As an example, we analyse an exponentially large quantum ensemble in which each classifier is weighed according to its performance in classifying the training data, leading to new results for quantum as well as classical machine learning.

  4. Quantum computer games: quantum minesweeper

    Science.gov (United States)

    Gordon, Michal; Gordon, Goren

    2010-07-01

    The computer game of quantum minesweeper is introduced as a quantum extension of the well-known classical minesweeper. Its main objective is to teach the unique concepts of quantum mechanics in a fun way. Quantum minesweeper demonstrates the effects of superposition, entanglement and their non-local characteristics. While in the classical minesweeper the goal of the game is to discover all the mines laid out on a board without triggering them, in the quantum version there are several classical boards in superposition. The goal is to know the exact quantum state, i.e. the precise layout of all the mines in all the superposed classical boards. The player can perform three types of measurement: a classical measurement that probabilistically collapses the superposition; a quantum interaction-free measurement that can detect a mine without triggering it; and an entanglement measurement that provides non-local information. The application of the concepts taught by quantum minesweeper to one-way quantum computing are also presented.

  5. Quantum Physics Without Quantum Philosophy

    CERN Document Server

    Dürr, Detlef; Zanghì, Nino

    2013-01-01

    It has often been claimed that without drastic conceptual innovations a genuine explanation of quantum interference effects and quantum randomness is impossible. This book concerns Bohmian mechanics, a simple particle theory that is a counterexample to such claims. The gentle introduction and other contributions collected here show how the phenomena of non-relativistic quantum mechanics, from Heisenberg's uncertainty principle to non-commuting observables, emerge from the Bohmian motion of particles, the natural particle motion associated with Schrödinger's equation. This book will be of value to all students and researchers in physics with an interest in the meaning of quantum theory as well as to philosophers of science.

  6. Quantum measurement in quantum optics

    International Nuclear Information System (INIS)

    Kimble, H.J.

    1993-01-01

    Recent progress in the generation and application of manifestly quantum or nonclassical states of the electromagnetic field is reviewed with emphasis on the research of the Quantum Optics Group at Caltech. In particular, the possibilities for spectroscopy with non-classical light are discussed both in terms of improved quantitative measurement capabilities and for the fundamental alteration of atomic radiative processes. Quantum correlations for spatially extended systems are investigated in a variety of experiments which utilize nondegenerate parametric down conversion. Finally, the prospects for measurement of the position of a free mass with precision beyond the standard quantum limit are briefly considered. (author). 38 refs., 1 fig

  7. Quantum Computing

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Quantum Computing - Building Blocks of a Quantum Computer. C S Vijay Vishal Gupta. General Article Volume 5 Issue 9 September 2000 pp 69-81. Fulltext. Click here to view fulltext PDF. Permanent link:

  8. Quantum spacetime

    International Nuclear Information System (INIS)

    Doplicher, S.

    1996-01-01

    We review some recent result and work in progress on the quantum structure of spacetime at scales comparable with the Planck length; the models discussed here are operationally motivated by the limitations in the accuracy of localization of events in spacetime imposed by the interplay between quantum mechanics and classical general relativity. (orig.)

  9. Quantum photonics

    CERN Document Server

    Pearsall, Thomas P

    2017-01-01

    This textbook employs a pedagogical approach that facilitates access to the fundamentals of Quantum Photonics. It contains an introductory description of the quantum properties of photons through the second quantization of the electromagnetic field, introducing stimulated and spontaneous emission of photons at the quantum level. Schrödinger’s equation is used to describe the behavior of electrons in a one-dimensional potential. Tunneling through a barrier is used to introduce the concept of non­locality of an electron at the quantum level, which is closely-related to quantum confinement tunneling, resonant tunneling, and the origin of energy bands in both periodic (crystalline) and aperiodic (non-crystalline) materials. Introducing the concepts of reciprocal space, Brillouin zones, and Bloch’s theorem, the determination of electronic band structure using the pseudopotential method is presented, allowing direct computation of the band structures of most group IV, group III-V, and group II-VI semiconducto...

  10. Quantum cosmology

    International Nuclear Information System (INIS)

    Hawking, S.W.

    1984-01-01

    The subject of these lectures is quantum effects in cosmology. The author deals first with situations in which the gravitational field can be treated as a classical, unquantized background on which the quantum matter fields propagate. This is the case with inflation at the GUT era. Nevertheless the curvature of spacetime can have important effects on the behaviour of the quantum fields and on the development of long-range correlations. He then turns to the question of the quantization of the gravitational field itself. The plan of these lectures is as follows: Euclidean approach to quantum field theory in flat space; the extension of techniques to quantum fields on a curved background with the four-sphere, the Euclidean version of De Sitter space as a particular example; the GUT era; quantization of the gravitational field by Euclidean path integrals; mini superspace model. (Auth.)

  11. Quantum mechanics

    CERN Document Server

    Rae, Alastair I M

    2016-01-01

    A Thorough Update of One of the Most Highly Regarded Textbooks on Quantum Mechanics Continuing to offer an exceptionally clear, up-to-date treatment of the subject, Quantum Mechanics, Sixth Edition explains the concepts of quantum mechanics for undergraduate students in physics and related disciplines and provides the foundation necessary for other specialized courses. This sixth edition builds on its highly praised predecessors to make the text even more accessible to a wider audience. It is now divided into five parts that separately cover broad topics suitable for any general course on quantum mechanics. New to the Sixth Edition * Three chapters that review prerequisite physics and mathematics, laying out the notation, formalism, and physical basis necessary for the rest of the book * Short descriptions of numerous applications relevant to the physics discussed, giving students a brief look at what quantum mechanics has made possible industrially and scientifically * Additional end-of-chapter problems with...

  12. Quantum magnetism

    CERN Document Server

    Richter, Johannes; Farnell, Damian; Bishop, Raymod

    2004-01-01

    The investigation of magnetic systems where quantum effects play a dominant role has become a very active branch of solid-state-physics research in its own right. The first three chapters of the "Quantum Magnetism" survey conceptual problems and provide insights into the classes of systems considered, namely one-dimensional, two-dimensional and molecular magnets. The following chapters introduce the methods used in the field of quantum magnetism, including spin wave analysis, exact diagonalization, quantum field theory, coupled cluster methods and the Bethe ansatz. The book closes with a chapter on quantum phase transitions and a contribution that puts the wealth of phenomena into the context of experimental solid-state physics. Closing a gap in the literature, this volume is intended both as an introductory text at postgraduate level and as a modern, comprehensive reference for researchers in the field.

  13. Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists.

    Science.gov (United States)

    Miah, Afjal H; Abas, Hossay; Begg, Malcolm; Marsh, Benjamin J; O'Flynn, Daniel E; Ford, Alison J; Percy, Jonathan M; Procopiou, Panayiotis A; Richards, Steve A; Rumley, Sally-Anne

    2014-08-01

    A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (clogP 116 μg/mL), and be stable to acid and light. The benzimidazol-2-one core was identified as a hit suitable for further investigation. Substitution at N1 with small alkyl groups was tolerated; however, these analogues were inactive in the whole blood assay (pA₂ <5). Azabenzimidazolone analogues were all found to be active, with compound 38 exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom logD₇.₄ (2.4), high LE (0.43), and solubility (152 μg/mL). In addition, 38 had human serum albumin binding of around 93% and met all the criteria for progression to lead optimisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. The applications of PCA in QSAR studies: A case study on CCR5 antagonists.

    Science.gov (United States)

    Yoo, ChangKyoo; Shahlaei, Mohsen

    2018-01-01

    Principal component analysis (PCA), as a well-known multivariate data analysis and data reduction technique, is an important and useful algebraic tool in drug design and discovery. PCA, in a typical quantitative structure-activity relationship (QSAR) study, analyzes an original data matrix in which molecules are described by several intercorrelated quantitative dependent variables (molecular descriptors). Although extensively applied, there is disparity in the literature with respect to the applications of PCA in the QSAR studies. This study investigates the different applications of PCA in QSAR studies using a dataset including CCR5 inhibitors. The different types of preprocessing are used to compare the PCA performances. The use of PC plots in the exploratory investigation of matrix of descriptors is described. This work is also proved PCA analysis to be a powerful technique for exploring complex datasets in QSAR studies for identification of outliers. This study shows that PCA is able to easily apply to the pool of calculated structural descriptors and also the extracted information can be used to help decide upon an appropriate harder model for further analysis. © 2017 John Wiley & Sons A/S.

  15. [A case of breast cancer postoperative metastases to the liver obtained cCR].

    Science.gov (United States)

    Enomoto, Katsuhisa; Sakurai, Kenichi

    2011-11-01

    A case is a 55-year-old woman. We noticed the right breast lump in May 2006. It was papillotubular carcinoma, ER(-), PgR -), HER2 (3+) by needle biopsy. The patient was introduced to our department in November 2006 for a close inspection and treatment. The palpation showed a mass without a firm flexibility, which was a border indistinctness of about 2 cm in size in the right AB area. We did not find a distant metastasis either. We operated for Bt+Ax (level II) in December. It was T2N0M0, stage IIA papillotubular carcinoma, ER(-), PgR(-), HER2 (3+) with histopathology. We recommended an adjuvant therapy but the patient refused. Since then we followed her up. After two years from the operation, multiple metastases were observed to the liver, FEC therapy was started. CT revealed that metastasized tumors were disappeared after six courses of treatment. Echography obtained cCR. Generally speaking, chemotherapy was effective for breast cancer as we compared it to endemic cancer of other organs. Meanwhile, it has been reported that many kinds of newly developed medicines for the treatment are available and effective. On the other hand, a selection of therapeutic drugs could be a problem for metastasized organs.

  16. Quantum computing

    International Nuclear Information System (INIS)

    Steane, Andrew

    1998-01-01

    The subject of quantum computing brings together ideas from classical information theory, computer science, and quantum physics. This review aims to summarize not just quantum computing, but the whole subject of quantum information theory. Information can be identified as the most general thing which must propagate from a cause to an effect. It therefore has a fundamentally important role in the science of physics. However, the mathematical treatment of information, especially information processing, is quite recent, dating from the mid-20th century. This has meant that the full significance of information as a basic concept in physics is only now being discovered. This is especially true in quantum mechanics. The theory of quantum information and computing puts this significance on a firm footing, and has led to some profound and exciting new insights into the natural world. Among these are the use of quantum states to permit the secure transmission of classical information (quantum cryptography), the use of quantum entanglement to permit reliable transmission of quantum states (teleportation), the possibility of preserving quantum coherence in the presence of irreversible noise processes (quantum error correction), and the use of controlled quantum evolution for efficient computation (quantum computation). The common theme of all these insights is the use of quantum entanglement as a computational resource. It turns out that information theory and quantum mechanics fit together very well. In order to explain their relationship, this review begins with an introduction to classical information theory and computer science, including Shannon's theorem, error correcting codes, Turing machines and computational complexity. The principles of quantum mechanics are then outlined, and the Einstein, Podolsky and Rosen (EPR) experiment described. The EPR-Bell correlations, and quantum entanglement in general, form the essential new ingredient which distinguishes quantum from

  17. Quantum computing

    Energy Technology Data Exchange (ETDEWEB)

    Steane, Andrew [Department of Atomic and Laser Physics, University of Oxford, Clarendon Laboratory, Oxford (United Kingdom)

    1998-02-01

    The subject of quantum computing brings together ideas from classical information theory, computer science, and quantum physics. This review aims to summarize not just quantum computing, but the whole subject of quantum information theory. Information can be identified as the most general thing which must propagate from a cause to an effect. It therefore has a fundamentally important role in the science of physics. However, the mathematical treatment of information, especially information processing, is quite recent, dating from the mid-20th century. This has meant that the full significance of information as a basic concept in physics is only now being discovered. This is especially true in quantum mechanics. The theory of quantum information and computing puts this significance on a firm footing, and has led to some profound and exciting new insights into the natural world. Among these are the use of quantum states to permit the secure transmission of classical information (quantum cryptography), the use of quantum entanglement to permit reliable transmission of quantum states (teleportation), the possibility of preserving quantum coherence in the presence of irreversible noise processes (quantum error correction), and the use of controlled quantum evolution for efficient computation (quantum computation). The common theme of all these insights is the use of quantum entanglement as a computational resource. It turns out that information theory and quantum mechanics fit together very well. In order to explain their relationship, this review begins with an introduction to classical information theory and computer science, including Shannon's theorem, error correcting codes, Turing machines and computational complexity. The principles of quantum mechanics are then outlined, and the Einstein, Podolsky and Rosen (EPR) experiment described. The EPR-Bell correlations, and quantum entanglement in general, form the essential new ingredient which distinguishes quantum from

  18. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2017-04-01

    Full Text Available BackgroundT follicular helper (Tfh cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.MethodologyTfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.ResultsPhylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils.ConclusionThe major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population

  19. Quantum mechanics with quantum time

    International Nuclear Information System (INIS)

    Kapuscik, E.

    1984-01-01

    Using a non-canonical Lie structure of classical mechanics a new algebra of quantum mechanical observables is constructed. The new algebra, in addition to the notion of classical time, makes it possible to introduce the notion of quantum time. A new type of uncertainty relation is derived. (author)

  20. Proceedings of quantum field theory, quantum mechanics, and quantum optics

    International Nuclear Information System (INIS)

    Dodonov, V.V.; Man; ko, V.I.

    1991-01-01

    This book contains papers presented at the XVIII International Colloquium on Group Theoretical Methods in Physics held in Moscow on June 4-9, 1990. Topics covered include; applications of algebraic methods in quantum field theory, quantum mechanics, quantum optics, spectrum generating groups, quantum algebras, symmetries of equations, quantum physics, coherent states, group representations and space groups

  1. Quantum physics

    International Nuclear Information System (INIS)

    Basdevant, J.L.; Dalibart, J.

    1997-01-01

    This pedagogical book gives an initiation to the principles and practice of quantum mechanics. A large part is devoted to experimental facts and to their analysis: concrete facts, phenomena and applications related to fundamental physics, elementary particles, astrophysics, high-technology, semi-conductors, micro-electronics and lasers. The book is divided in 22 chapters dealing with: quantum phenomena, wave function and Schroedinger equation, physical units and measurements, energy quantification of some simple systems, Hilbert space, Dirac formalism and quantum mechanics postulates, two-state systems and ammonia Maser principle, bands theory and crystals conductibility, commutation of observables, Stern and Gerlach experiment, approximation methods, kinetic momentum in quantum mechanics, first description of atoms, 1/2 spin formalism and magnetic resonance, Lagrangian, Hamiltonian and Lorentz force in quantum mechanics, addition of kinetic momenta and fine and hyper-fine structure of atomic lines, identical particle systems and Pauli principle, qualitative physics and scale of size of some microscopic and macroscopic phenomena, systems evolution, collisions and cross sections, invariance and conservation laws, quantum mechanics and astrophysics, and historical aspects of quantum mechanics. (J.S.)

  2. Quantum communications

    CERN Document Server

    Cariolaro, Gianfranco

    2015-01-01

    This book demonstrates that a quantum communication system using the coherent light of a laser can achieve performance orders of magnitude superior to classical optical communications Quantum Communications provides the Masters and PhD signals or communications student with a complete basics-to-applications course in using the principles of quantum mechanics to provide cutting-edge telecommunications. Assuming only knowledge of elementary probability, complex analysis and optics, the book guides its reader through the fundamentals of vector and Hilbert spaces and the necessary quantum-mechanical ideas, simply formulated in four postulates. A turn to practical matters begins with and is then developed by: ·         development of the concept of quantum decision, emphasizing the optimization of measurements to extract useful information from a quantum system; ·         general formulation of a transmitter–receiver system ·         particular treatment of the most popular quantum co...

  3. Quantum Criticality

    Science.gov (United States)

    Drummond, P. D.; Chaturvedi, S.; Dechoum, K.; Comey, J.

    2001-02-01

    We investigate the theory of quantum fluctuations in non-equilibrium systems having large crit­ical fluctuations. This allows us to treat the limits imposed by nonlinearities to quantum squeezing and noise reduction, and also to envisage future tests of quantum theory in regions of macroscopic quantum fluctuations. A long-term objective of this research is to identify suitable physical sys­tems in which macroscopic 'Schrödinger cat'-like behaviour may be observed. We investigate two systems in particular of much current experimental interest, namely the degenerate parametric oscillator near threshold, and the evaporatively cooled (BEC). We compare the results obtained in the positive-P representation, as a fully quantum mechanical calculation, with the truncated Wigner phase space equation, also known as semi-classical theory. We show when these results agree and differ in calculations taken beyond the linearized approximation. In the region where the largest quantum fluctuations and Schrödinger cat-like behaviour might be expected, we find that the quantum predictions correspond very closely to the semi-classical theory. Nature abhors observing a Schrödinger cat. -Pacs: 03.65.Bz

  4. Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity

    OpenAIRE

    Dorr, Patrick; Westby, Mike; Dobbs, Susan; Griffin, Paul; Irvine, Becky; Macartney, Malcolm; Mori, Julie; Rickett, Graham; Smith-Burchnell, Caroline; Napier, Carolyn; Webster, Rob; Armour, Duncan; Price, David; Stammen, Blanda; Wood, Anthony

    2005-01-01

    Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades a...

  5. Quantum Computers and Quantum Computer Languages: Quantum Assembly Language and Quantum C Language

    OpenAIRE

    Blaha, Stephen

    2002-01-01

    We show a representation of Quantum Computers defines Quantum Turing Machines with associated Quantum Grammars. We then create examples of Quantum Grammars. Lastly we develop an algebraic approach to high level Quantum Languages using Quantum Assembly language and Quantum C language as examples.

  6. Quantum Computers and Quantum Computer Languages: Quantum Assembly Language and Quantum C

    OpenAIRE

    Blaha, Stephen

    2002-01-01

    We show a representation of Quantum Computers defines Quantum Turing Machines with associated Quantum Grammars. We then create examples of Quantum Grammars. Lastly we develop an algebraic approach to high level Quantum Languages using Quantum Assembly language and Quantum C language as examples.

  7. Cascade quantum teleportation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Nan-run; GONG Li-hua; LIU Ye

    2006-01-01

    In this letter a cascade quantum teleportation scheme is proposed. The proposed scheme needs less local quantum operations than those of quantum multi-teleportation. A quantum teleportation scheme based on entanglement swapping is presented and compared with the cascade quantum teleportation scheme. Those two schemes can effectively teleport quantum information and extend the distance of quantum communication.

  8. Quantum mechanics

    CERN Document Server

    Powell, John L

    2015-01-01

    Suitable for advanced undergraduates, this thorough text focuses on the role of symmetry operations and the essentially algebraic structure of quantum-mechanical theory. Based on courses in quantum mechanics taught by the authors, the treatment provides numerous problems that require applications of theory and serve to supplement the textual material.Starting with a historical introduction to the origins of quantum theory, the book advances to discussions of the foundations of wave mechanics, wave packets and the uncertainty principle, and an examination of the Schrödinger equation that includ

  9. Quantum mechanics

    International Nuclear Information System (INIS)

    Rae, A.I.M.

    1981-01-01

    This book, based on a thirty lecture course given to students at the beginning of their second year, covers the quantum mechanics required by physics undergraduates. Early chapters deal with wave mechanics, including a discussion of the energy states of the hydrogen atom. These are followed by a more formal development of the theory, leading to a discussion of some advanced applications and an introduction to the conceptual problems associated with quantum measurement theory. Emphasis is placed on the fundamentals of quantum mechanics. Problems are included at the end of each chapter. (U.K.)

  10. Quantum chaos

    International Nuclear Information System (INIS)

    Steiner, F.

    1994-01-01

    A short historical overview is given on the development of our knowledge of complex dynamical systems with special emphasis on ergodicity and chaos, and on the semiclassical quantization of integrable and chaotic systems. The general trace formular is discussed as a sound mathematical basis for the semiclassical quantization of chaos. Two conjectures are presented on the basis of which it is argued that there are unique fluctuation properties in quantum mechanics which are universal and, in a well defined sense, maximally random if the corresponding classical system is strongly chaotic. These properties constitute the quantum mechanical analogue of the phenomenon of chaos in classical mechanics. Thus quantum chaos has been found. (orig.)

  11. Quantum thermodynamics

    International Nuclear Information System (INIS)

    Beretta, G.P.; Gyftopoulos, E.P.; Park, J.L.

    1985-01-01

    A novel nonlinear equation of motion is proposed for a general quantum system consisting of more than one distinguishable elementary constituent of matter. In the domain of idempotent quantum-mechanical state operators, it is satisfied by all unitary evolutions generated by the Schroedinger equation. But in the broader domain of nonidempotent state operators not contemplated by conventional quantum mechanics, it generates a generally nonunitary evolution, it keeps the energy invariant and causes the entropy to increase with time until the system reaches a state of equilibrium or a limit cycle

  12. Quantum chemistry

    CERN Document Server

    Lowe, John P

    1993-01-01

    Praised for its appealing writing style and clear pedagogy, Lowe's Quantum Chemistry is now available in its Second Edition as a text for senior undergraduate- and graduate-level chemistry students. The book assumes little mathematical or physical sophistication and emphasizes an understanding of the techniques and results of quantum chemistry, thus enabling students to comprehend much of the current chemical literature in which quantum chemical methods or concepts are used as tools. The book begins with a six-chapter introduction of standard one-dimensional systems, the hydrogen atom,

  13. Investigation of the Binding Site of CCR2 using 4-Azetidinyl-1-aryl-cyclohexane Derivatives: A Membrane Modeling and Molecular Dynamics Study

    Energy Technology Data Exchange (ETDEWEB)

    Kothandan, Gugan; Gadhe, Changdev G.; Cho, Seung Joo [Chosun Univ., Gwangju (Korea, Republic of)

    2013-11-15

    Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

  14. Ancient DNA Investigation of a Medieval German Cemetery Confirms Long-Term Stability of CCR5-Δ32 Allele Frequencies in Central Europe.

    Science.gov (United States)

    Bouwman, Abigail; Shved, Natallia; Akgül, Gülfirde; Rühli, Frank; Warinner, Christina

    2017-04-01

    The CCR5-Δ32 mutation present in European populations is among the most prominently debated cases of recent positive selection in humans. This allele, a 32-bp deletion that renders the T-cell CCR5 receptor nonfunctional, has important epidemiological and public health significance, as homozygous carriers are resistant to several HIV strains. However, although the function of this allele in preventing HIV infection is now well described, its human evolutionary origin is poorly understood. Initial attempts to determine the emergence of the CCR5-Δ32 allele pointed to selection during the 14th-century Black Death pandemic; however, subsequent analyses suggest that the allele rose in frequency more than 5,000 years ago, possibly through drift. Recently, three studies have identified populations predating the 14th century CE that are positive for the CCR5-Δ32 allele, supporting the claim for a more ancient origin. However, these studies also suggest poorly understood regional differences in the recent evolutionary history of the CCR5-Δ32 allele. Here a new hydrolysis-probe-based real-time PCR assay was designed to ascertain CCR5 allele frequency in 53 individuals from a 10th- to 12th-century CE church and convent complex in central Germany that predates outbreaks of the Black Death pandemic. High-confidence genotypes were obtained for 32 individuals, and results show that CCR5-Δ32 allele frequency has remained unchanged in this region of Central Europe over the last millennium, suggesting that there has been no strong positive selective pressure over this time period and confirming a more ancient origin for the allele.

  15. Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?

    Science.gov (United States)

    Faure, Eric

    2008-01-01

    Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of

  16. A novel CCR-2/TLR-2 triggered signaling in murine peritoneal macrophages intensifies bacterial (Staphylococcus aureus) killing by reactive oxygen species through TNF-R1.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2017-10-01

    Macrophages are remarkably versatile in their ability to recognize and respond to a wide range of stimuli by expressing a variety of surface and intracellular receptors and triggering multiple signal transduction pathways. The onset of microbial infection is primarily determined by the initial contacts made by the microbes with the host macrophages. Although there prevail a relationship between the chemokine receptor and Toll like receptors during disease, particularly TLR-2 and CCR-2 signaling interdependence on each other has not been yet investigated during acute staphylococcal infection. Thus, the present study was aimed to trace possible interaction between CCR-2 and TLR-2 in peritoneal macrophages during acute Staphylococcus aureus infection. We found that neutralization of CCR-2 attenuates TLR-2 expression and restricts S. aureus burden but TLR-2 neutralization augments CCR-2 expression in macrophages, along with compromised host-derived reactive oxygen species production. S. aureus infection to CCR-2 intact but TLR-2 neutralized macrophages triggered production of IL-1β, TNF-α, IL-6, IFN-γ, MCP-1 and expression of iNOS, TNFR-1 and GPx with concomitant decrease in IL-10 production. Further, study with NG-monomethyl-l-arginine (L-NMMA) [iNOS blocker] and buthionine sulfoximine (BSO) [GPx blocker] revealed that S. aureus infection enhanced TLR-2 expression in CCR-2 intact and TLR-2 neutralized macrophages possibly via iNOS and TNFR-1 up regulation and GPx down regulation. Overall, our data indicate that targeting CCR-2 with neutralizing antibody in the early phase of S. aureus infection could restrict excessive inflammation with less compromised bacterial killing. It certainly would be a therapeutic strategy in S. aureus induced inflammatory and infective diseases. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  17. Development of an inflammation imaging tracer, 111In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE-/- atherosclerosis mouse model.

    Science.gov (United States)

    Wei, Lihui; Petryk, Julia; Gaudet, Chantal; Kamkar, Maryam; Gan, Wei; Duan, Yin; Ruddy, Terrence D

    2018-02-07

    Chemokine receptor 5 (CCR5) plays an important role in atherosclerosis. Our objective was to develop a SPECT tracer targeting CCR5 for imaging plaque inflammation by radiolabeling D-Ala-peptide T-amide (DAPTA), a CCR5 antagonist, with 111 In. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with 111 In. Cell uptake studies were conducted in U87-CD4-CCR5 and U87-MG cells. Biodistribution was determined in C57BL/6 mice. Autoradiography, en face and Oil Red O (ORO) imaging studies were performed in ApoE -/- mice. DOTA-DAPTA was radiolabeled with 111 In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). 111 In-DOTA-DAPTA exhibited fast blood and renal clearance and high spleen uptake. The U87-CD4-CCR5 cells had significantly higher uptake in comparison to the U87-MG cells. The cell uptake was reduced by three times with DAPTA, indicating the receptor specificity of the uptake. Autoradiographic images showed significantly higher lesion uptake of 111 In-DOTA-DAPTA in ApoE -/- mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE -/- high fat diet (HFD) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the CCR5 receptor. 111 In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.

  18. Quantum Noise

    International Nuclear Information System (INIS)

    Beenakker, C W J

    2005-01-01

    Quantum Noise is advertised as a handbook, and this is indeed how it functions for me these days: it is a book that I keep within hand's reach, ready to be consulted on the proper use of quantum stochastic methods in the course of my research on quantum dots. I should point out that quantum optics, the target field for this book, is not my field by training. So I have much to learn, and find this handbook to be a reliable and helpful guide. Crispin Gardiner previously wrote the Handbook of Stochastic Methods (also published by Springer), which provides an overview of methods in classical statistical physics. Quantum Noise, written jointly with Peter Zoller, is the counterpart for quantum statistical physics, and indeed the two books rely on each other by frequent cross referencing. The fundamental problem addressed by Quantum Noise is how the quantum dynamics of an open system can be described statistically by treating the environment as a source of noise. This is a general problem in condensed matter physics (in particular in the context of Josephson junctions) and in quantum optics. The emphasis in this book in on the optical applications (for condensed matter applications one could consult Quantum Dissipative Systems by Ulrich Weiss, published by World Scientific). The optical applications centre around the interaction of light with atoms, where the atoms represent the open system and the light is the noisy environment. A complete description of the production and detection of non-classical states of radiation (such as squeezed states) can be obtained using one of the equivalent quantum stochastic formulations: the quantum Langevin equation for the field operators (in either the Ito or the Stratonovich form), the Master equation for the density matrix, or the stochastic Schroedinger equation for the wave functions. Each formulation is fully developed here (as one would expect from a handbook), with detailed instructions on how to go from one to the other. The

  19. Quantum exam

    International Nuclear Information System (INIS)

    Nguyen, Ba An

    2006-01-01

    Absolutely and asymptotically secure protocols for organizing an exam in a quantum way are proposed basing judiciously on multipartite entanglement. The protocols are shown to stand against common types of eavesdropping attack

  20. Quantum cryptography

    International Nuclear Information System (INIS)

    Tittel, W.; Brendel, J.; Gissin, N.; Ribordy, G.; Zbinden, H.

    1999-01-01

    The principles of quantum cryptography based on non-local correlations of entanglement photons are outlined. The method of coding and decoding of information and experiments is also described. The prospects of the technique are briefly discussed. (Z.J.)

  1. Quantum chaos

    International Nuclear Information System (INIS)

    Cejnar, P.

    2007-01-01

    Chaos is a name given in physics to a branch which, within classical mechanics, studies the consequences of sensitive dependences of the behavior of physical systems on the starting conditions, i.e., the 'butterfly wing effect'. However, how to describe chaotic behavior in the world of quantum particles? It appears that quantum mechanics does not admit the sensitive dependence on the starting conditions, and moreover, predicts a substantial suppression of chaos also at the macroscopic level. Still, the quantum properties of systems that are chaotic in terms of classical mechanics differ basically from the properties of classically arranged systems. This topic is studied by a field of physics referred to as quantum chaos. (author)

  2. Quantum transformations

    International Nuclear Information System (INIS)

    Faraggi, A.E.; Matone, M.

    1998-01-01

    We show that the quantum Hamilton-Jacobi equation can be written in the classical form with the spatial derivative ∂ q replaced by ∂ q with dq = dq/√1-β 2 (q), where β 2 (q) is strictly related to the quantum potential. This can be seen as the opposite of the problem of finding the wave function representation of classical mechanics as formulated by Schiller and Rosen. The structure of the above open-quotes quantum transformationclose quotes, related to the recently formulated equivalence principle, indicates that the potential deforms space geometry. In particular, a result by Flanders implies that both W(q) = V(q) - E and the quantum potential Q are proportional to the curvatures κ W and κ Q which arise as natural invariants in an equivalence problem for curves in the projective line. In this formulation the Schroedinger equation takes the geometrical form (∂ q 2 + κ W )ψ = 0

  3. Quantum Correlations Evolution Asymmetry in Quantum Channels

    International Nuclear Information System (INIS)

    Li Meng; Huang Yun-Feng; Guo Guang-Can

    2017-01-01

    It was demonstrated that the entanglement evolution of a specially designed quantum state in the bistochastic channel is asymmetric. In this work, we generalize the study of the quantum correlations, including entanglement and quantum discord, evolution asymmetry to various quantum channels. We found that the asymmetry of entanglement and quantum discord only occurs in some special quantum channels, and the behavior of the entanglement evolution may be quite different from the behavior of the quantum discord evolution. To quantum entanglement, in some channels it decreases monotonously with the increase of the quantum channel intensity. In some other channels, when we increase the intensity of the quantum channel, it decreases at first, then keeps zero for some time, and then rises up. To quantum discord, the evolution becomes more complex and you may find that it evolutes unsmoothly at some points. These results illustrate the strong dependence of the quantum correlations evolution on the property of the quantum channels. (paper)

  4. Duality Quantum Information and Duality Quantum Communication

    International Nuclear Information System (INIS)

    Li, C. Y.; Wang, W. Y.; Wang, C.; Song, S. Y.; Long, G. L.

    2011-01-01

    Quantum mechanical systems exhibit particle wave duality property. This duality property has been exploited for information processing. A duality quantum computer is a quantum computer on the move and passing through a multi-slits. It offers quantum wave divider and quantum wave combiner operations in addition to those allowed in an ordinary quantum computer. It has been shown that all linear bounded operators can be realized in a duality quantum computer, and a duality quantum computer with n qubits and d-slits can be realized in an ordinary quantum computer with n qubits and a qudit in the so-called duality quantum computing mode. The quantum particle-wave duality can be used in providing secure communication. In this paper, we will review duality quantum computing and duality quantum key distribution.

  5. The Not5 subunit of the ccr4-not complex connects transcription and translation.

    Directory of Open Access Journals (Sweden)

    Zoltan Villanyi

    2014-10-01

    Full Text Available Recent studies have suggested that a sub-complex of RNA polymerase II composed of Rpb4 and Rpb7 couples the nuclear and cytoplasmic stages of gene expression by associating with newly made mRNAs in the nucleus, and contributing to their translation and degradation in the cytoplasm. Here we show by yeast two hybrid and co-immunoprecipitation experiments, followed by ribosome fractionation and fluorescent microscopy, that a subunit of the Ccr4-Not complex, Not5, is essential in the nucleus for the cytoplasmic functions of Rpb4. Not5 interacts with Rpb4; it is required for the presence of Rpb4 in polysomes, for interaction of Rpb4 with the translation initiation factor eIF3 and for association of Rpb4 with mRNAs. We find that Rpb7 presence in the cytoplasm and polysomes is much less significant than that of Rpb4, and that it does not depend upon Not5. Hence Not5-dependence unlinks the cytoplasmic functions of Rpb4 and Rpb7. We additionally determine with RNA immunoprecipitation and native gel analysis that Not5 is needed in the cytoplasm for the co-translational assembly of RNA polymerase II. This stems from the importance of Not5 for the association of the R2TP Hsp90 co-chaperone with polysomes translating RPB1 mRNA to protect newly synthesized Rpb1 from aggregation. Hence taken together our results show that Not5 interconnects translation and transcription.

  6. Quantum correlations and distinguishability of quantum states

    Energy Technology Data Exchange (ETDEWEB)

    Spehner, Dominique [Université Grenoble Alpes and CNRS, Institut Fourier, F-38000 Grenoble, France and Laboratoire de Physique et Modélisation des Milieux Condensés, F-38000 Grenoble (France)

    2014-07-15

    A survey of various concepts in quantum information is given, with a main emphasis on the distinguishability of quantum states and quantum correlations. Covered topics include generalized and least square measurements, state discrimination, quantum relative entropies, the Bures distance on the set of quantum states, the quantum Fisher information, the quantum Chernoff bound, bipartite entanglement, the quantum discord, and geometrical measures of quantum correlations. The article is intended both for physicists interested not only by collections of results but also by the mathematical methods justifying them, and for mathematicians looking for an up-to-date introductory course on these subjects, which are mainly developed in the physics literature.

  7. Quantum correlations and distinguishability of quantum states

    International Nuclear Information System (INIS)

    Spehner, Dominique

    2014-01-01

    A survey of various concepts in quantum information is given, with a main emphasis on the distinguishability of quantum states and quantum correlations. Covered topics include generalized and least square measurements, state discrimination, quantum relative entropies, the Bures distance on the set of quantum states, the quantum Fisher information, the quantum Chernoff bound, bipartite entanglement, the quantum discord, and geometrical measures of quantum correlations. The article is intended both for physicists interested not only by collections of results but also by the mathematical methods justifying them, and for mathematicians looking for an up-to-date introductory course on these subjects, which are mainly developed in the physics literature

  8. Quantum Locality?

    Science.gov (United States)

    Stapp, Henry P.

    2012-05-01

    Robert Griffiths has recently addressed, within the framework of a `consistent quantum theory' that he has developed, the issue of whether, as is often claimed, quantum mechanics entails a need for faster-than-light transfers of information over long distances. He argues that the putative proofs of this property that involve hidden variables include in their premises some essentially classical-physics-type assumptions that are not entailed by the precepts of quantum mechanics. Thus whatever is proved is not a feature of quantum mechanics, but is a property of a theory that tries to combine quantum theory with quasi-classical features that go beyond what is entailed by quantum theory itself. One cannot logically prove properties of a system by establishing, instead, properties of a system modified by adding properties alien to the original system. Hence Griffiths' rejection of hidden-variable-based proofs is logically warranted. Griffiths mentions the existence of a certain alternative proof that does not involve hidden variables, and that uses only macroscopically described observable properties. He notes that he had examined in his book proofs of this general kind, and concluded that they provide no evidence for nonlocal influences. But he did not examine the particular proof that he cites. An examination of that particular proof by the method specified by his `consistent quantum theory' shows that the cited proof is valid within that restrictive version of quantum theory. An added section responds to Griffiths' reply, which cites general possibilities of ambiguities that might make what is to be proved ill-defined, and hence render the pertinent `consistent framework' ill defined. But the vagaries that he cites do not upset the proof in question, which, both by its physical formulation and by explicit identification, specify the framework to be used. Griffiths confirms the validity of the proof insofar as that pertinent framework is used. The section also shows

  9. Quantum lottery

    CERN Multimedia

    CERN Bulletin

    2013-01-01

    On April Fools' Day, CERN Quantum Diaries blogger Pauline Gagnon held a giveaway of microscopic proportion. Up for grabs? Ten Higgs bosons, courtesy of CERN. Pauline announced the winners last week; let's see what they'll really be getting in the mail...   Custom-made Particle Zoo Higgs bosons were sent out to the winners. Read more about the prize in the Quantum Diaries post "Higgs boson lottery: when CERN plays April Fools' jokes".

  10. Quantum optics

    DEFF Research Database (Denmark)

    Andersen, Ulrik Lund

    2013-01-01

    Further sensitivity improvements are required before advanced optical interferometers will be able to measure gravitational waves. A team has now shown that introducing quantum squeezing of light may help to detect these elusive waves.......Further sensitivity improvements are required before advanced optical interferometers will be able to measure gravitational waves. A team has now shown that introducing quantum squeezing of light may help to detect these elusive waves....

  11. Quantum torsors

    OpenAIRE

    Grunspan, C.

    2003-01-01

    This text gives some results about quantum torsors. Our starting point is an old reformulation of torsors recalled recently by Kontsevich. We propose an unification of the definitions of torsors in algebraic geometry and in Poisson geometry. Any quantum torsor is equipped with two comodule-algebra structures over Hopf algebras and these structures commute with each other. In the finite dimensional case, these two Hopf algebras share the same finite dimension. We show that any Galois extension...

  12. Quantum conversion

    OpenAIRE

    Mazilu, Michael

    2015-01-01

    ICOAM 2015 The electromagnetic momentum transferred transferred to scattering particles is proportional to the intensity of the incident fields, however, the momentum of single photons ℏk does not naturally appear in these classical expressions. Here, we discuss an alternative to Maxwell's stress tensor that renders the classical electromagnetic field momentum compatible to the quantum mechanical one. This is achieved through the introduction of the quantum conversion which allows the tran...

  13. Quantum entanglement

    International Nuclear Information System (INIS)

    Hadjiivanov, L.; Todorov, I.

    2015-01-01

    Expository paper providing a historical survey of the gradual transformation of the 'philosophical discussions' between Bohr, Einstein and Schrödinger on foundational issues in quantum mechanics into a quantitative prediction of a new quantum effect, its experimental verification and its proposed (and loudly advertised) applications. The basic idea of the 1935 paper of Einstein-Podolsky-Rosen (EPR) was reformulated by David Bohm for a finite dimensional spin system. This allowed John Bell to derive his inequalities that separate the prediction of quantum entanglement from its possible classical interpretation. We reproduce here their later (1971) version, reviewing on the way the generalization (and mathematical derivation) of Heisenberg's uncertainty relations (due to Weyl and Schrödinger) needed for the passage from EPR to Bell. We also provide an improved derivation of the quantum theoretic violation of Bell's inequalities. Soon after the experimental confirmation of the quantum entanglement (culminating with the work of Alain Aspect) it was Feynman who made public the idea of a quantum computer based on the observed effect

  14. Quantum Computation and Quantum Spin Dynamics

    NARCIS (Netherlands)

    Raedt, Hans De; Michielsen, Kristel; Hams, Anthony; Miyashita, Seiji; Saito, Keiji

    2001-01-01

    We analyze the stability of quantum computations on physically realizable quantum computers by simulating quantum spin models representing quantum computer hardware. Examples of logically identical implementations of the controlled-NOT operation are used to demonstrate that the results of a quantum

  15. 27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun-Mi, E-mail: lala1647@hanmail.net [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Bo-Young, E-mail: kimboyoung@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Sae-A, E-mail: saeah486@nate.com [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Eo, Seong-Kug, E-mail: vetvirus@chonbuk.ac.kr [Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Yun, Yungdae, E-mail: yunyung@ewha.ac.kr [Department of Life Science, Ewha Womans University, Seoul 120-750 (Korea, Republic of); Kim, Chi-Dae, E-mail: chidkim@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Koanhoi, E-mail: koanhoi@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of)

    2014-02-01

    Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1 lymphocyte recruitment in a cholesterol-rich milieu. A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE{sup −/−} mice. 27-Hydroxycholesterol and 7α-hydroxycholesterol, cholesterol oxides (oxysterols) detected in abundance in atherosclerotic lesions, greatly induced the transcription of CCL3 and CCL4 genes in addition to enhancing secretion of corresponding proteins by THP-1 monocytic cells. However, an identical or even higher concentration of cholesterol, 7β-hydroxycholesterol, and 7-ketocholsterol did not influence expression of these chemokines. Conditioned media containing the CCR5 ligands secreted from THP-1 cells induced migration of Jurkat T cells expressing CCR5, a characteristic chemokine receptor of Th1 cells, but not of Jurkat T cells that do not express CCR5. The migration of CCR5-expressing Jurkat T cells was abrogated in the presence of a CCR5-neutralizing antibody. 27-Hydroxycholesterol and 7α-hydroxycholesterol enhanced phosphorylation of Akt. Pharmacological inhibitors of phosphoinositide-3-kinase/Akt pathways blocked transcription as well as secretion of CCL3 and CCL4 in conjunction with attenuated migration of CCR5-expressing Jurkat T cells. This is the first report on the involvement of cholesterol oxides in migration of distinct subtype of T cells. We propose that 27-hydroxycholesterol and 7α-hydroxycholesterol can trigger a sequence of events that leads to recruitment of Th1 lymphocytes and phosphoinositide-3-kinase/Akt pathways play a major role in the process. - Graphical abstract: Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of

  16. 27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes

    International Nuclear Information System (INIS)

    Kim, Sun-Mi; Kim, Bo-Young; Lee, Sae-A; Eo, Seong-Kug; Yun, Yungdae; Kim, Chi-Dae; Kim, Koanhoi

    2014-01-01

    Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1 lymphocyte recruitment in a cholesterol-rich milieu. A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE −/− mice. 27-Hydroxycholesterol and 7α-hydroxycholesterol, cholesterol oxides (oxysterols) detected in abundance in atherosclerotic lesions, greatly induced the transcription of CCL3 and CCL4 genes in addition to enhancing secretion of corresponding proteins by THP-1 monocytic cells. However, an identical or even higher concentration of cholesterol, 7β-hydroxycholesterol, and 7-ketocholsterol did not influence expression of these chemokines. Conditioned media containing the CCR5 ligands secreted from THP-1 cells induced migration of Jurkat T cells expressing CCR5, a characteristic chemokine receptor of Th1 cells, but not of Jurkat T cells that do not express CCR5. The migration of CCR5-expressing Jurkat T cells was abrogated in the presence of a CCR5-neutralizing antibody. 27-Hydroxycholesterol and 7α-hydroxycholesterol enhanced phosphorylation of Akt. Pharmacological inhibitors of phosphoinositide-3-kinase/Akt pathways blocked transcription as well as secretion of CCL3 and CCL4 in conjunction with attenuated migration of CCR5-expressing Jurkat T cells. This is the first report on the involvement of cholesterol oxides in migration of distinct subtype of T cells. We propose that 27-hydroxycholesterol and 7α-hydroxycholesterol can trigger a sequence of events that leads to recruitment of Th1 lymphocytes and phosphoinositide-3-kinase/Akt pathways play a major role in the process. - Graphical abstract: Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1

  17. CCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women

    International Nuclear Information System (INIS)

    Chatterjee, Koushik; Dandara, Collet; Hoffman, Margaret; Williamson, Anna-Lise

    2010-01-01

    Cervical cancer, caused by specific oncogenic types of human papillomavirus (HPV), is the second most common cancer in women worldwide. A large number of young sexually active women get infected by HPV but only a small fraction of them have persistent infection and develop cervical cancer pointing to co- factors including host genetics that might play a role in outcome of the HPV infection. This study investigated the role of CCR2-V64I polymorphism in cervical cancer, pre-cancers and HPV infection in South African women resident in Western Cape. CCR2-V64I polymorphism has been previously reported to influence the progression to cervical cancer in some populations and has also been associated with decreased progression from HIV infection to AIDS. Genotyping for CCR2-V64I was done by PCR-SSP in a case-control study of 446 women (106 black African and 340 mixed-ancestry) with histologically confirmed invasive cervical cancer and 1432 controls (322 black African and 1110 mixed-ancestry) group-matched (1:3) by age, ethnicity and domicile status. In the control women HPV was detected using the Digene Hybrid Capture II test and cervical disease was detected by cervical cytology. The CCR2-64I variant was significantly associated with cervical cancer when cases were compared to the control group (P = 0.001). Further analysis comparing selected groups within the controls showed that individuals with abnormal cytology and high grade squamous intraepitleial neoplasia (HSIL) did not have this association when compared to women with normal cytology. HPV infection also showed no association with CCR2-64I variant. Comparing SIL positive controls with the cases showed a significant association of CCR2-64I variant (P = 0.001) with cervical cancer. This is the first study of the role of CCR2-V64I polymorphism in cervical cancer in an African population. Our results show that CCR2-64I variant is associated with the risk of cervical cancer but does not affect the susceptibility to HPV

  18. CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1–infected individuals

    Science.gov (United States)

    Ahuja, Sunil K; Kulkarni, Hemant; Catano, Gabriel; Agan, Brian K; Camargo, Jose F; He, Weijing; O'Connell, Robert J; Marconi, Vincent C; Delmar, Judith; Eron, Joseph; Clark, Robert A; Frost, Simon; Martin, Jeffrey; Ahuja, Seema S; Deeks, Steven G; Little, Susan; Richman, Douglas; Hecht, Frederick M; Dolan, Matthew J

    2008-01-01

    The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. PMID:18376407

  19. Abiotic stress induces change in Cinnamoyl CoA Reductase (CCR) protein abundance and lignin deposition in developing seedlings of Leucaena leucocephala.

    Science.gov (United States)

    Srivastava, Sameer; Vishwakarma, Rishi K; Arafat, Yasir Ali; Gupta, Sushim K; Khan, Bashir M

    2015-04-01

    Aboitic stress such as drought and salinity are class of major threats, which plants undergo through their lifetime. Lignin deposition is one of the responses to such abiotic stresses. The gene encoding Cinnamoyl CoA Reductase (CCR) is a key gene for lignin biosynthesis, which has been shown to be over-expressed under stress conditions. In the present study, developing seedlings of Leucaena leucocephala (Vernacular name: Subabul, White popinac) were treated with 1 % mannitol and 200 mM NaCl to mimic drought and salinity stress conditions, respectively. Enzyme linked immunosorbant assay (ELISA) based expression pattern of CCR protein was monitored coupled with Phlorogucinol/HCl activity staining of lignin in transverse sections of developing L. leucocephala seedlings under stress. Our result suggests a differential lignification pattern in developing root and stem under stress conditions. Increase in lignification was observed in mannitol treated stems and corresponding CCR protein accumulation was also higher than control and salt stress treated samples. On the contrary CCR protein was lower in NaCl treated stems and corresponding lignin deposition was also low. Developing root tissue showed a high level of CCR content and lignin deposition than stem samples under all conditions tested. Overall result suggested that lignin accumulation was not affected much in case of developing root however developing stems were significantly affected under drought and salinity stress condition.

  20. Characterization and analysis of CCR and CAD gene families at the whole-genome level for lignin synthesis of stone cells in pear (Pyrus bretschneideri fruit

    Directory of Open Access Journals (Sweden)

    Xi Cheng

    2017-11-01

    Full Text Available The content of stone cells has significant effects on the flavour and quality of pear fruit. Previous research suggested that lignin deposition is closely related to stone cell formation. In the lignin biosynthetic pathway, cinnamoyl-CoA reductase (CCR and cinnamyl alcohol dehydrogenase (CAD, dehydrogenase/reductase family members, catalyse the last two steps in monolignol synthesis. However, there is little knowledge of the characteristics of the CCR and CAD families in pear and their involvement in lignin synthesis of stone cells. In this study, 31 CCRs and 26 CADs were identified in the pear genome. Phylogenetic trees for CCRs and CADs were constructed; key amino acid residues were analysed, and three-dimensional structures were predicted. Using quantitative real-time polymerase chain reaction (qRT-PCR, PbCAD2, PbCCR1, -2 and -3 were identified as participating in lignin synthesis of stone cells in pear fruit. Subcellular localization analysis showed that the expressed proteins (PbCAD2, PbCCR1, -2 and -3 are found in the cytoplasm or at the cell membrane. These results reveal the evolutionary features of the CCR and CAD families in pear as well as the genes responsible for regulation of lignin synthesis and stone cell development in pear fruit.

  1. Investigating the association of chemokine receptor 5 (CCR5 polymorphism with cervical cancer in human papillomavirus (HPV positive patients - DOI: 10.4025/actascihealthsci.v30i2.944 Investigating association of chemokine receptor 5 (CCR5 polymorphism with cervical cancer in human papillomavirus (HPV suggestive patients - DOI: 10.4025/actascihealthsci.v30i2.944

    Directory of Open Access Journals (Sweden)

    Sueli Donizete Borelli

    2008-12-01

    Full Text Available HPV is one of the most frequent causes for the development of cervical cancer. It is known that chemokines are important determinants of early inflammatory responses. The CC chemokine receptor 5 (CCR5 gene is involved in the chemotaxis of leukocytes toward inflammation sites. In the present study, polymerase chain reactions (PCR in genomic DNA samples, using specific CCR5 oligonucleotide primers surrounding the breakpoint deletion, detected a 225 bp product from the normal CCR5 allele and a 193 bp product from the 32 bp deletion allele. The wild type genotype was prevalent in both group, but it was not statistically significant, with χ2 = 1.519 (2 degrees of freedom; p > 0.05. As there are a small number of 32 allele carriers, further studies are needed to clarify the role of CCR5 in the cervical cancer.HPV is the most responsible of cervical cancer. It is known that chemokines are important determinants of the early inflammatory response. The CC chemokine receptor 5 (CCR5 gene is involved in the chemotaxis of leukocytes toward inflammation sites. In the present study, polymerase chain reactions (PCR in genomic DNA samples, using specific CCR5 oligonucleotide primers surrounding the breakpoint deletion, detected a 225bp product from the normal CCR5 allele and a 193bp product from the 32bp deletion allele. The wild type genotype was prevalent in both group, but it wasn’t statistically significant with χ² =1,519 (2 degrees of freedom; p>0.05. Once there is a small number of 32 allele carriers, further studies are needed to clarify the role of CCR5 in the cervical cancer.

  2. Quantum computing: Quantum advantage deferred

    Science.gov (United States)

    Childs, Andrew M.

    2017-12-01

    A type of optics experiment called a boson sampler could be among the easiest routes to demonstrating the power of quantum computers. But recent work shows that super-classical boson sampling may be a long way off.

  3. Hypoxia preconditioning of mesenchymal stromal cells enhances PC3 cell lymphatic metastasis accompanied by VEGFR-3/CCR7 activation.

    Science.gov (United States)

    Huang, Xin; Su, Kunkai; Zhou, Limin; Shen, Guofang; Dong, Qi; Lou, Yijia; Zheng, Shu

    2013-12-01

    Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastases through the secretion of chemokines. MSCs have been reported to home toward the hypoxic tumor microenvironment in vivo. In this study, we investigated prostate cancer PC3 cell behavior under the influence of hypoxia preconditioned MSCs and explored the related mechanism of prostate cancer lymphatic metastases in mice. Transwell assays revealed that VEGF-C receptor, VEGFR-3, as well as chemokine CCL21 receptor, CC chemokine receptor 7 (CCR7), were responsible for the migration of PC3 cells toward hypoxia preconditioned MSCs. Knock-in Ccr7 in PC3 cells also improved cell migration in vitro. Furthermore, when PC3 cells were labeled using the hrGfp-lentiviral vector, and were combined with hypoxia preconditioned MSCs for xenografting, it resulted in an enhancement of lymph node metastases accompanied by up-regulation of VEGFR-3 and CCR7 in primary tumors. Both PI3K/Akt/IκBα and JAK2/STAT3 signaling pathways were activated in xenografts in the presence of hypoxia-preconditioned MSCs. Unexpectedly, the p-VEGFR-2/VEGFR-2 ratio was attenuated accompanied by decreased JAK1 expression, indicating a switching-off of potential vascular signal within xenografts in the presence of hypoxia-preconditioned MSCs. Unlike results from other studies, VEGF-C maintained a stable expression in both conditions, which indicated that hypoxia preconditioning of MSCs did not influence VEGF-C secretion. Our results provide the new insights into the functional molecular events and signalings influencing prostate tumor metastases, suggesting a hopeful diagnosis and treatment in new approaches. © 2013 Wiley Periodicals, Inc.

  4. De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-10-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form ("neo-collaterals") versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume(-1), and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1(-/-) and CCR2(-/-) mice. Bone-marrow transplant rescued collateral formation in CCR2(-/-) mice. Involvement of fractalkine➔CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neo-collaterals form rapidly after coronary occlusion, and finds that MCP➔CCR2-mediated recruitment of myeloid cells is required for this process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression

    Directory of Open Access Journals (Sweden)

    Adam J. Wells

    2016-07-01

    Full Text Available The recruitment and infiltration of classical monocytes into damaged muscle is critical for optimal tissue remodeling. This study examined the effects of an amino acid supplement on classical monocyte recruitment following an acute bout of lower body resistance exercise. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm ingested supplement (SUPP or placebo (PL immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL, immediately (IP, 30-min (30P, 1-h (1H, 2-h (2H, and 5-h (5H post-exercise to assess plasma concentrations of monocyte chemoattractant protein 1 (MCP-1, myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2, and macrophage-1 antigen (CD11b on classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Changes in myoglobin, cortisol, and insulin concentrations were similar between treatments. Compared to PL, plasma MCP-1 was “very likely greater” (98.1% likelihood effect in SUPP at 2H. CCR2 expression was “likely greater” at IP (84.9% likelihood effect, “likely greater” at 1H (87.7% likelihood effect, “very likely greater” at 2H (97.0% likelihood effect, and “likely greater” at 5H (90.1% likelihood effect in SUPP, compared to PL. Ingestion of SUPP did not influence CD11b expression. Ingestion of an amino acid supplement immediately post-exercise appears to help maintain plasma MCP-1 concentrations and augment CCR2 expression in resistance trained men.

  6. Quantum Physics for Beginners.

    Science.gov (United States)

    Strand, J.

    1981-01-01

    Suggests a new approach for teaching secondary school quantum physics. Reviews traditional approaches and presents some characteristics of the three-part "Quantum Physics for Beginners" project, including: quantum physics, quantum mechanics, and a short historical survey. (SK)

  7. Quantum Transmemetic Intelligence

    Science.gov (United States)

    Piotrowski, Edward W.; Sładkowski, Jan

    The following sections are included: * Introduction * A Quantum Model of Free Will * Quantum Acquisition of Knowledge * Thinking as a Quantum Algorithm * Counterfactual Measurement as a Model of Intuition * Quantum Modification of Freud's Model of Consciousness * Conclusion * Acknowledgements * References

  8. Quantum correlations in multipartite quantum systems

    Science.gov (United States)

    Jafarizadeh, M. A.; Heshmati, A.; Karimi, N.; Yahyavi, M.

    2018-03-01

    Quantum entanglement is the most famous type of quantum correlation between elements of a quantum system that has a basic role in quantum communication protocols like quantum cryptography, teleportation and Bell inequality detection. However, it has already been shown that various applications in quantum information theory do not require entanglement. Quantum discord as a new kind of quantum correlations beyond entanglement, is the most popular candidate for general quantum correlations. In this paper, first we find the entanglement witness in a particular multipartite quantum system which consists of a N-partite system in 2 n -dimensional space. Then we give an exact analytical formula for the quantum discord of this system. At the end of the paper, we investigate the additivity relation of the quantum correlation and show that this relation is satisfied for a N-partite system with 2 n -dimensional space.

  9. [Single nucleotide polymorphisms of HIV coreceptor CCR5 gene in Chinese Yi ethnic group and its association with HIV infection].

    Science.gov (United States)

    Ma, Li-ying; Hong, Kun-xue; Lu, Xiao-zhi; Qin, Guang-ming; Chen, Jian-ping; Chen, Kang-lin; Ruan, Yu-hua; Xing, Hui; Zhu, Jia-hong; Shao, Yi-ming

    2005-11-30

    To investigate the single nucleotide polymorphism (SNP) of HIV-1 coreceptor CCR5 gene in Chinese Yi ethnic group and the association between these SNPs and HIV/AIDS. Peripheral blood samples of 102 HIV negative persons of Chinese Yi nationality, 87 males amd 15 females, aged 23 (12-37), and 68 HIV carriers, 61 males and 7 females, aged 27 (17-51). The regulatory and structural regions of the HIV coreceptor CCR5 gene were amplified from the genomic DNA by nested PCR, each of the two regions was divided into three gene fragments which were overlapped. High throughput DHPLC was used for screening of unknown mutations in each gene fragment. The PCR products showing different peak traces from wild types in DHPLC were sequenced by forward and reverse primers respectively. The sequences were analyzed with the help of Sequence Navigator software to search for SNP loci. Statistical analysis by SPSS and PPAP softwares were made to study the association between these SNPs and HIV infection. Five SNPs (A77G, G316A, T532C, C921T, and G668A) and a AGA deletion of the 686-688 nucleotides were discovered in the coding region of this gene in Chinese Yi ethnic group. C921T mutation was a nonsense mutation, and the other SNPs (A77G, G316A, T532C, and G668A) are sense mutation, with the amino acid changes of K26R, G106R, C178R, and R223Q. Only the frequency of R223Q allelic gene was high (0.08) but those of the others were low (less than 0.01). There was no significant difference in the allele frequency between the HIV negative and HIV positive groups (all P > 0.05). Five SNP loci (T58934G, G59029A, T59353C, G59402A, and C59653T) were found in the regulatory region of CCR5 gene with high allelic frequencies of 0.1912-0.2941. Between the HIV negative and HIV positive groups, there were no differences in the SNP loc (all P > 0.05). Statistical analysis of the association between the linkage of mutation loci with HIV infection suggested a significant difference in the haplotype frequency

  10. MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.

    Directory of Open Access Journals (Sweden)

    Masahiro Ishikawa

    Full Text Available OBJECTIVE: The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models. METHODS: The expression profiles of chemokines were examined during fracture healing in wild-type (WT mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1 on primary mouse bone marrow stromal cells (mBMSCs was evaluated using an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2-/- mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT. RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1-/- mice and were evaluated by histological staining and micro-CT. RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and CCR2-/- mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1-/- mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely, transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing.

  11. Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5).

    Science.gov (United States)

    Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav; Daugvilaite, Viktorija; Steen, Anne; Brvar, Matjaž; Pui, Aurel; Frimurer, Thomas Michael; Ulven, Trond; Rosenkilde, Mette Marie

    2016-12-23

    The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn 2+ (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site using computational modeling, binding, and functional studies on WT and mutated CCR5. The metal ion Zn 2+ is anchored to the chemokine receptor-conserved Glu-283 VII:06/7.39 Both chelators interact with aromatic residues in the transmembrane receptor domain. The additional pyridine ring of ZnTerp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248 VI:13/6.48 microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism but maintained positive allosteric modulation of CCL3 binding. Despite a similar overall binding mode of all three metal ion chelator complexes, the pyridine ring of ZnClTerp blocks the conformational switch of Trp-248 required for receptor activation, thereby explaining its lack of activity. Importantly, ZnClTerp becomes agonist to the same extent as ZnTerp upon Ala mutation of Ile-116 III:16/3.40 , a residue that constrains the Trp-248 microswitch in its inactive conformation. Binding studies with 125 I-CCL3 revealed an allosteric interface between the chemokine and the small molecule binding site, including residues Tyr-37 I:07/1.39 , Trp-86 II:20/2.60 , and Phe-109 III:09/3.33 The small molecules and CCL3 approach this interface from opposite directions, with some residues being mutually exploited. This study provides new insight into the molecular mechanism of CCR5 activation and paves the way for future allosteric drugs for chemokine receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b

    Directory of Open Access Journals (Sweden)

    Lee Robert E

    2006-01-01

    Full Text Available Abstract Background There have been indications that common Angiotensin Receptor Blockers (ARBs may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone and the Parathyroid Hormone (PTH. Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma, which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b, which recruits monocytes to the site of inflammatory immune challenge. Results Telmisartan was predicted to strongly antagonize (Ki≈0.04nmol the VDR. The ARBs Olmesartan, Irbesartan and Valsartan (Ki≈10 nmol are likely to be useful VDR antagonists at typical in-vivo concentrations. Candesartan (Ki≈30 nmol and Losartan (Ki≈70 nmol may also usefully inhibit the VDR. Telmisartan is a strong modulator of PPARgamma (Ki≈0.3 nmol, while Losartan (Ki≈3 nmol, Irbesartan (Ki≈6 nmol, Olmesartan and Valsartan (Ki≈12 nmol also seem likely to have significant PPAR modulatory activity. Olmesartan andIrbesartan (Ki≈9 nmol additionally act as antagonists of a theoretical modelof CCR2b. Initial validation of this CCR2b model was performed, and a proposed model for the AngiotensinII Type1 receptor (AT2R1 has been presented. Conclusion Molecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design. ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b. However, this study also found evidence that ARBs modulate the

  13. Long distance quantum teleportation

    Science.gov (United States)

    Xia, Xiu-Xiu; Sun, Qi-Chao; Zhang, Qiang; Pan, Jian-Wei

    2018-01-01

    Quantum teleportation is a core protocol in quantum information science. Besides revealing the fascinating feature of quantum entanglement, quantum teleportation provides an ultimate way to distribute quantum state over extremely long distance, which is crucial for global quantum communication and future quantum networks. In this review, we focus on the long distance quantum teleportation experiments, especially those employing photonic qubits. From the viewpoint of real-world application, both the technical advantages and disadvantages of these experiments are discussed.

  14. Electron quantum optics as quantum signal processing

    OpenAIRE

    Roussel, B.; Cabart, C.; Fève, G.; Thibierge, E.; Degiovanni, P.

    2016-01-01

    The recent developments of electron quantum optics in quantum Hall edge channels have given us new ways to probe the behavior of electrons in quantum conductors. It has brought new quantities called electronic coherences under the spotlight. In this paper, we explore the relations between electron quantum optics and signal processing through a global review of the various methods for accessing single- and two-electron coherences in electron quantum optics. We interpret electron quantum optics...

  15. Quantum solitons

    Energy Technology Data Exchange (ETDEWEB)

    Abram, I [Centre National d' Etudes des Telecommunications (CNET), 196 Avenue Henri Ravera, F-92220 Bagneux (France)

    1999-02-01

    Two of the most remarkable properties of light - squeezing and solitons - are being combined in a new generation of experiments that could revolutionize optics and communications. One area of application concerns the transmission and processing of classical (binary) information, in which the presence or absence of a soliton in a time-window corresponds to a ''1'' or ''0'', as in traditional optical-fibre communications. However, since solitons occur at fixed power levels, we do not have the luxury of being able to crank up the input power to improve the signal-to-noise ratio at the receiving end. Nevertheless, the exploitation of quantum effects such as squeezing could help to reduce noise and improve fidelity. In long-distance communications, where the signal is amplified every 50-100 kilometres or so, the soliton pulse is strongest just after the amplifier. Luckily this is where the bulk of the nonlinear interaction needed to maintain the soliton shape occurs. However, the pulse gets weaker as it propagates along the fibre, so the nonlinear interaction also becomes weakerand weaker. This means that dispersive effects become dominant until the next stage of amplification, where the nonlinearity takes over again. One problem is that quantum fluctuations in the amplifiers lead to random jumps in the central wavelength of the individual solitons, and this results in a random variation of the speed of individual solitons in the fibre. Several schemes have been devised to remove this excess noise and bring the train of solitons back to the orderly behaviour characteristic of a stable coherent state (e.g. the solitons could be passed through a spectral filter). Photon-number squeezing could also play a key role in solving this problem. For example, if the solitons are number-squeezed immediately after amplification, there will be a smaller uncertainty in the nonlinearity that keeps the soliton in shape and, therefore, there will also be less noise in the soliton. This

  16. Quantum Physics

    Science.gov (United States)

    Le Bellac, Michel

    2006-03-01

    Quantum physics allows us to understand the nature of the physical phenomena which govern the behavior of solids, semi-conductors, lasers, atoms, nuclei, subnuclear particles and light. In Quantum Physics, Le Bellac provides a thoroughly modern approach to this fundamental theory. Throughout the book, Le Bellac teaches the fundamentals of quantum physics using an original approach which relies primarily on an algebraic treatment and on the systematic use of symmetry principles. In addition to the standard topics such as one-dimensional potentials, angular momentum and scattering theory, the reader is introduced to more recent developments at an early stage. These include a detailed account of entangled states and their applications, the optical Bloch equations, the theory of laser cooling and of magneto-optical traps, vacuum Rabi oscillations, and an introduction to open quantum systems. This is a textbook for a modern course on quantum physics, written for advanced undergraduate and graduate students. Completely original and contemporary approach, using algebra and symmetry principles Introduces recent developments at an early stage, including many topics that cannot be found in standard textbooks. Contains 130 physically relevant exercises

  17. Quantum minigolf

    Energy Technology Data Exchange (ETDEWEB)

    Reinhard, Friedemann [Universitaet Stuttgart (Germany). 3. Physikalisches Institut

    2010-07-01

    Quantum minigolf is a virtual-reality computer game visualizing quantum mechanics. The rules are the same as for the classical game minigolf, the goal being to kick a ball such that it crosses an obstacle course and runs into a hole. The ball, however, follows the laws of quantum mechanics: It can be at several places at once or tunnel through obstacles. To know whether the ball has reached the goal, the player has to perform a position measurement, which converts the ball into a classical object and fixes its position. But quantum mechanics is indeterministic: There is always a chance to lose, even for Tiger Woods. Technically, the obstacle course and the ball are projected onto the floor by a video projector. The position of the club is tracked by an infrared marker, similar as in Nintendo's Wii console. The whole setup is portable and the software has been published under the GPL license on www.quantum-minigolf.org.

  18. Pushing it back. Dating the CCR5–32 bp deletion to the Mesolithic in Sweden and its implications for the Meso\\Neo transition

    Directory of Open Access Journals (Sweden)

    Kerstin Lidén

    2006-12-01

    Full Text Available Genetic variation in the chemokine receptor gene CCR5 has received considerable scientific interest during the last few years. Protection against HIV-infection and AIDS, together with specific geographic distribution are the major reasons for the great interest in CCR5 32bp deletion. The event for the occurrence of this mutation has been postulated by coalescence dating to the 14th century, or 5000 BP. In our prehistoric Swedish samples we show that the frequency of 32pb deletion in CCR5 in the Neolithic population does not deviate from the frequency in a modern Swedish population, and that the deletion existed in Sweden already during the Mesolithic period.

  19. The CCL3L1-CCR5 genotype influences the development of AIDS, but not HIV susceptibility or the response to HAART

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Tanmoy [Los Alamos National Laboratory; Stanton, Jennifer [NORTHWESTERN UNIV; Kim, Eun - Young [NORTHWESTERN UNIV; Kunstman, Kevin [NORTHWESTERN UNIV; Phair, John [NORTHWESTERN UNIV; Jacobson, Lisa P [JOHNS HOPKINS UNIV; Wolinsky, Steven M [NORTHWESTERN UNIV

    2008-01-01

    A selective advantage against infectious diseases such as HIV/AIDS is associated with differences in the genes relevant to immunity and virus replication. The CC chemokine receptor 5 (CCR5), the principal coreceptor for HIV, and its chemokine ligands, including CCL3L1, influences the CD4+ target cells susceptibility to infection. The CCL3L1 gene is in a region of segmental duplication on the q-arm of human chromosome 17. Increased numbers of CCL3L1 gene copies that affect the gene expression phenotype might have substantial protective effects. Here we show that the population-specific CCL3L1 gene copy number and the CCR5 {Delta}32 protein-inactivating deletion that categorizes the CCL3L1-CCR5 genotype do not influence HIV/AIDS susceptibility or the robustness of immune recovery after the initiation of highly active antiretroviral therapy (HAART).

  20. Quantum walk computation

    International Nuclear Information System (INIS)

    Kendon, Viv

    2014-01-01

    Quantum versions of random walks have diverse applications that are motivating experimental implementations as well as theoretical studies. Recent results showing quantum walks are “universal for quantum computation” relate to algorithms, to be run on quantum computers. We consider whether an experimental implementation of a quantum walk could provide useful computation before we have a universal quantum computer

  1. Quantum group gauge theory on quantum spaces

    International Nuclear Information System (INIS)

    Brzezinski, T.; Majid, S.

    1993-01-01

    We construct quantum group-valued canonical connections on quantum homogeneous spaces, including a q-deformed Dirac monopole on the quantum sphere of Podles quantum differential coming from the 3-D calculus of Woronowicz on SU q (2). The construction is presented within the setting of a general theory of quantum principal bundles with quantum group (Hopf algebra) fiber, associated quantum vector bundles and connection one-forms. Both the base space (spacetime) and the total space are non-commutative algebras (quantum spaces). (orig.)

  2. Efficient quantum circuit implementation of quantum walks

    International Nuclear Information System (INIS)

    Douglas, B. L.; Wang, J. B.

    2009-01-01

    Quantum walks, being the quantum analog of classical random walks, are expected to provide a fruitful source of quantum algorithms. A few such algorithms have already been developed, including the 'glued trees' algorithm, which provides an exponential speedup over classical methods, relative to a particular quantum oracle. Here, we discuss the possibility of a quantum walk algorithm yielding such an exponential speedup over possible classical algorithms, without the use of an oracle. We provide examples of some highly symmetric graphs on which efficient quantum circuits implementing quantum walks can be constructed and discuss potential applications to quantum search for marked vertices along these graphs.

  3. Renormalisation in Quantum Mechanics, Quantum Instantons and Quantum Chaos

    OpenAIRE

    Jirari, H.; Kröger, H.; Luo, X. Q.; Moriarty, K. J. M.

    2001-01-01

    We suggest how to construct non-perturbatively a renormalized action in quantum mechanics. We discuss similarties and differences with the standard effective action. We propose that the new quantum action is suitable to define and compute quantum instantons and quantum chaos.

  4. Synthesis and characterization of Ge–Cr-based intermetallic compounds: GeCr3, GeCCr3, and GeNCr3

    International Nuclear Information System (INIS)

    Lin, S.; Tong, P.; Wang, B.S.; Huang, Y.N.; Song, W.H.; Sun, Y.P.

    2014-01-01

    Highlights: • Polycrystalline samples of GeCr 3 , GeCCr 3 , and GeNCr 3 are synthesized by using solid state reaction method. • A good quality of our samples is verified by the Rietveld refinement and electrical transport measurement. • We present a comprehensive understanding of physical properties of GeCr 3 , GeCCr 3 , and GeNCr 3 . -- Abstract: We report the synthesis of GeCr 3 , GeCCr 3 , and GeNCr 3 polycrystalline compounds, and present a systematic study of this series by the measurements of X-ray diffraction (XRD), magnetism, electrical/thermal transport, specific heat, and Hall coefficient. Good quality of our samples is verified by quite small value of residual resistivity and considerably large residual resistivity ratio. Based on the Rietveld refinement of XRD data, the crystallographic parameters are obtained, and, correspondingly, the sketches of crystal structure are plotted for all the samples. The ground states of GeCr 3 , GeCCr 3 , and GeNCr 3 are paramagnetic/antiferromagnetic metal, and even a Fermi-liquid behavior is observed in electrical transport at low temperatures. Furthermore, the analysis of the thermal conductivity data suggests the electron thermal conductivity plays a major role in total thermal conductivity for GeCr 3 at low temperatures, while the phonon thermal conductivity is dominant for GeCCr 3 and GeNCr 3 at high temperatures. The negative value of Seebeck coefficient and Hall coefficient indicate that the charge carriers are electron-type for GeCr 3 , GeCCr 3 , and GeNCr 3

  5. CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells.

    Science.gov (United States)

    Haas, Jan D; González, Frano H Malinarich; Schmitz, Susanne; Chennupati, Vijaykumar; Föhse, Lisa; Kremmer, Elisabeth; Förster, Reinhold; Prinz, Immo

    2009-12-01

    Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.

  6. Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways.

    Science.gov (United States)

    Gan, Lu; Zhou, Qiaoling; Li, Xiaozhao; Chen, Chen; Meng, Ting; Pu, Jiaxi; Zhu, Mengyuan; Xiao, Chenggen

    2018-04-01

    IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7-CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

  7. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Lillard James W

    2011-05-01

    Full Text Available Abstract Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β and forkhead in human rhabdomyosarcoma (FKHR inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  8. Quantum mechanics

    CERN Document Server

    Fitzpatrick, Richard

    2015-01-01

    Quantum mechanics was developed during the first few decades of the twentieth century via a series of inspired guesses made by various physicists, including Planck, Einstein, Bohr, Schroedinger, Heisenberg, Pauli, and Dirac. All these scientists were trying to construct a self-consistent theory of microscopic dynamics that was compatible with experimental observations. The purpose of this book is to present quantum mechanics in a clear, concise, and systematic fashion, starting from the fundamental postulates, and developing the theory in as logical manner as possible. Topics covered in the book include the fundamental postulates of quantum mechanics, angular momentum, time-dependent and time-dependent perturbation theory, scattering theory, identical particles, and relativistic electron theory.

  9. Quantum Worlds

    Directory of Open Access Journals (Sweden)

    Jeffrey A. Barrett

    2016-09-01

    Full Text Available http://dx.doi.org/10.5007/1808-1711.2016v20n1p45 Because of the conceptual difficulties it faces, quantum mechanics provides a salient example of how alternative metaphysical commitments may clarify our understanding of a physical theory and the explanations it provides. Here we will consider how postulating alternative quantum worlds in the context of Hugh Everett III’s pure wave mechanics may serve to explain determinate measurement records and the standard quantum statistics. We will focus on the properties of such worlds, then briefly consider other metaphysical options available for interpreting pure wave mechanics. These reflections will serve to illustrate both the nature and the limits of naturalized metaphysics.

  10. Quantum weirdness

    CERN Document Server

    Mullin, William J

    2017-01-01

    Quantum mechanics allows a remarkably accurate description of nature and powerful predictive capabilities. The analyses of quantum systems and their interpretation lead to many surprises, for example, the ability to detect the characteristics of an object without ever touching it in any way, via "interaction-free measurement," or the teleportation of an atomic state over large distances. The results can become downright bizarre. Quantum mechanics is a subtle subject that usually involves complicated mathematics -- calculus, partial differential equations, etc., for complete understanding. Most texts for general audiences avoid all mathematics. The result is that the reader misses almost all deep understanding of the subject, much of which can be probed with just high-school level algebra and trigonometry. Thus, readers with that level of mathematics can learn so much more about this fundamental science. The book starts with a discussion of the basic physics of waves (an appendix reviews some necessary class...

  11. Quantum gravity

    International Nuclear Information System (INIS)

    Isham, C.

    1989-01-01

    Gravitational effects are seen as arising from a curvature in spacetime. This must be reconciled with gravity's apparently passive role in quantum theory to achieve a satisfactory quantum theory of gravity. The development of grand unified theories has spurred the search, with forces being of equal strength at a unification energy of 10 15 - 10 18 GeV, with the ''Plank length'', Lp ≅ 10 -35 m. Fundamental principles of general relativity and quantum mechanics are outlined. Gravitons are shown to have spin-0, as mediators of gravitation force in the classical sense or spin-2 which are related to the quantisation of general relativity. Applying the ideas of supersymmetry to gravitation implies partners for the graviton, especially the massless spin 3/2 fermion called a gravitino. The concept of supersymmetric strings is introduced and discussed. (U.K.)

  12. Quantum mechanics

    CERN Document Server

    Ghosh, P K

    2014-01-01

    Quantum mechanics, designed for advanced undergraduate and graduate students of physics, mathematics and chemistry, provides a concise yet self-contained introduction to the formal framework of quantum mechanics, its application to physical problems and the interpretation of the theory. Starting with a review of some of the necessary mathematics, the basic concepts are carefully developed in the text. After building a general formalism, detailed treatment of the standard material - the harmonic oscillator, the hydrogen atom, angular momentum theory, symmetry transformations, approximation methods, identical particle and many-particle systems, and scattering theory - is presented. The concluding chapter discusses the interpretation of quantum mechanics. Some of the important topics discussed in the book are the rigged Hilbert space, deformation quantization, path integrals, coherent states, geometric phases, decoherene, etc. This book is characterized by clarity and coherence of presentation.

  13. Quantum waveguides

    CERN Document Server

    Exner, Pavel

    2015-01-01

    This monograph explains the theory of quantum waveguides, that is, dynamics of quantum particles confined to regions in the form of tubes, layers, networks, etc. The focus is on relations between the confinement geometry on the one hand and the spectral and scattering properties of the corresponding quantum Hamiltonians on the other. Perturbations of such operators, in particular, by external fields are also considered. The volume provides a unique summary of twenty five years of research activity in this area and indicates ways in which the theory can develop further. The book is fairly self-contained. While it requires some broader mathematical physics background, all the basic concepts are properly explained and proofs of most theorems are given in detail, so there is no need for additional sources. Without a parallel in the literature, the monograph by Exner and Kovarik guides the reader through this new and exciting field.

  14. Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.

    Science.gov (United States)

    He, Jing; Tsai, Louis M; Leong, Yew Ann; Hu, Xin; Ma, Cindy S; Chevalier, Nina; Sun, Xiaolin; Vandenberg, Kirsten; Rockman, Steve; Ding, Yan; Zhu, Lei; Wei, Wei; Wang, Changqi; Karnowski, Alexander; Belz, Gabrielle T; Ghali, Joanna R; Cook, Matthew C; Riminton, D Sean; Veillette, André; Schwartzberg, Pamela L; Mackay, Fabienne; Brink, Robert; Tangye, Stuart G; Vinuesa, Carola G; Mackay, Charles R; Li, Zhanguo; Yu, Di

    2013-10-17

    Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Quantum mechanics

    CERN Document Server

    Rae, Alastair I M

    2007-01-01

    PREFACESINTRODUCTION The Photoelectric Effect The Compton Effect Line Spectra and Atomic Structure De Broglie Waves Wave-Particle Duality The Rest of This Book THE ONE-DIMENSIONAL SCHRÖDINGER EQUATIONS The Time-Dependent Schrödinger Equation The Time-Independent Schrödinger Equation Boundary ConditionsThe Infinite Square Well The Finite Square Well Quantum Mechanical Tunneling The Harmonic Oscillator THE THREE-DIMENSIONAL SCHRÖDINGER EQUATIONS The Wave Equations Separation in Cartesian Coordinates Separation in Spherical Polar Coordinates The Hydrogenic Atom THE BASIC POSTULATES OF QUANTUM MEC

  16. Quantum Chaos

    Energy Technology Data Exchange (ETDEWEB)

    Bohigas, Oriol [Laboratoire de Physique Theorique et Modeles Statistiques, Orsay (France)

    2005-04-18

    Are there quantum signatures, for instance in the spectral properties, of the underlying regular or chaotic nature of the corresponding classical motion? Are there universality classes? Within this framework the merging of two at first sight seemingly disconnected fields, namely random matrix theories (RMT) and quantum chaos (QC), is briefly described. Periodic orbit theory (POT) plays a prominent role. Emphasis is given to compound nucleus resonances and binding energies, whose shell effects are examined from this perspective. Several aspects are illustrated with Riemann's {zeta}-function, which has become a testing ground for RMT, QC, POT, and their relationship.

  17. Quantum Chaos

    International Nuclear Information System (INIS)

    Bohigas, Oriol

    2005-01-01

    Are there quantum signatures, for instance in the spectral properties, of the underlying regular or chaotic nature of the corresponding classical motion? Are there universality classes? Within this framework the merging of two at first sight seemingly disconnected fields, namely random matrix theories (RMT) and quantum chaos (QC), is briefly described. Periodic orbit theory (POT) plays a prominent role. Emphasis is given to compound nucleus resonances and binding energies, whose shell effects are examined from this perspective. Several aspects are illustrated with Riemann's ζ-function, which has become a testing ground for RMT, QC, POT, and their relationship

  18. Quantum Cosmology

    OpenAIRE

    Page, Don N.

    2006-01-01

    A complete model of the universe needs at least three parts: (1) a complete set of physical variables and dynamical laws for them, (2) the correct solution of the dynamical laws, and (3) the connection with conscious experience. In quantum cosmology, item (2) is the quantum state of the cosmos. Hartle and Hawking have made the `no-boundary' proposal, that the wavefunction of the universe is given by a path integral over all compact Euclidean 4-dimensional geometries and matter fields that hav...

  19. Quantum diffusion

    International Nuclear Information System (INIS)

    Habib, S.

    1994-01-01

    We consider a simple quantum system subjected to a classical random force. Under certain conditions it is shown that the noise-averaged Wigner function of the system follows an integro-differential stochastic Liouville equation. In the simple case of polynomial noise-couplings this equation reduces to a generalized Fokker-Planck form. With nonlinear noise injection new ''quantum diffusion'' terms rise that have no counterpart in the classical case. Two special examples that are not of a Fokker-Planck form are discussed: the first with a localized noise source and the other with a spatially modulated noise source

  20. Blind Quantum Signature with Blind Quantum Computation

    Science.gov (United States)

    Li, Wei; Shi, Ronghua; Guo, Ying

    2017-04-01

    Blind quantum computation allows a client without quantum abilities to interact with a quantum server to perform a unconditional secure computing protocol, while protecting client's privacy. Motivated by confidentiality of blind quantum computation, a blind quantum signature scheme is designed with laconic structure. Different from the traditional signature schemes, the signing and verifying operations are performed through measurement-based quantum computation. Inputs of blind quantum computation are securely controlled with multi-qubit entangled states. The unique signature of the transmitted message is generated by the signer without leaking information in imperfect channels. Whereas, the receiver can verify the validity of the signature using the quantum matching algorithm. The security is guaranteed by entanglement of quantum system for blind quantum computation. It provides a potential practical application for e-commerce in the cloud computing and first-generation quantum computation.

  1. Quantum control limited by quantum decoherence

    International Nuclear Information System (INIS)

    Xue, Fei; Sun, C. P.; Yu, S. X.

    2006-01-01

    We describe quantum controllability under the influences of the quantum decoherence induced by the quantum control itself. It is shown that, when the controller is considered as a quantum system, it will entangle with its controlled system and then cause quantum decoherence in the controlled system. In competition with this induced decoherence, the controllability will be limited by some uncertainty relation in a well-armed quantum control process. In association with the phase uncertainty and the standard quantum limit, a general model is studied to demonstrate the possibility of realizing a decoherence-free quantum control with a finite energy within a finite time. It is also shown that if the operations of quantum control are to be determined by the initial state of the controller, then due to the decoherence which results from the quantum control itself, there exists a low bound for quantum controllability

  2. Quantum memory for images: A quantum hologram

    International Nuclear Information System (INIS)

    Vasilyev, Denis V.; Sokolov, Ivan V.; Polzik, Eugene S.

    2008-01-01

    Matter-light quantum interface and quantum memory for light are important ingredients of quantum information protocols, such as quantum networks, distributed quantum computation, etc. [P. Zoller et al., Eur. Phys. J. D 36, 203 (2005)]. In this paper we present a spatially multimode scheme for quantum memory for light, which we call a quantum hologram. Our approach uses a multiatom ensemble which has been shown to be efficient for a single spatial mode quantum memory. Due to the multiatom nature of the ensemble and to the optical parallelism it is capable of storing many spatial modes, a feature critical for the present proposal. A quantum hologram with the fidelity exceeding that of classical hologram will be able to store quantum features of an image, such as multimode superposition and entangled quantum states, something that a standard hologram is unable to achieve

  3. Quantum machine learning for quantum anomaly detection

    Science.gov (United States)

    Liu, Nana; Rebentrost, Patrick

    2018-04-01

    Anomaly detection is used for identifying data that deviate from "normal" data patterns. Its usage on classical data finds diverse applications in many important areas such as finance, fraud detection, medical diagnoses, data cleaning, and surveillance. With the advent of quantum technologies, anomaly detection of quantum data, in the form of quantum states, may become an important component of quantum applications. Machine-learning algorithms are playing pivotal roles in anomaly detection using classical data. Two widely used algorithms are the kernel principal component analysis and the one-class support vector machine. We find corresponding quantum algorithms to detect anomalies in quantum states. We show that these two quantum algorithms can be performed using resources that are logarithmic in the dimensionality of quantum states. For pure quantum states, these resources can also be logarithmic in the number of quantum states used for training the machine-learning algorithm. This makes these algorithms potentially applicable to big quantum data applications.

  4. More about the Viking hypothesis of origin of the delta32 mutation in the CCR5 gene conferring resistance to HIV-1 infection.

    Science.gov (United States)

    Lucotte, Gérard; Dieterlen, Florent

    2003-11-01

    The chemokine receptor CCR5 constitutes the major coreceptor for the HIV-1, because a mutant allele of the CCR5 gene named delta32 was shown to provide to homozygotes a strong resistance against infection. In the present study the frequency of the delta32 allele was collected in 36 European populations and in Cyprus, and the highest allele frequencies were found in Nordic countries. We constructed an allele map of delta32 frequencies in Europe; the map is in accordance to the Vikings hypothesis of the origin of the mutation and his dissemination during the eighth to the tenth centuries.

  5. Role of Conserved Disulfide Bridges and Aromatic Residues in Extracellular Loop 2 of Chemokine Receptor CCR8 for Chemokine and Small Molecule Binding

    DEFF Research Database (Denmark)

    Barington, Line; Rummel, Pia C; Lückmann, Michael

    2016-01-01

    and aromatic residues in extracellular loop 2 (ECL2) for ligand binding and activation in the chemokine receptor CCR8. We used IP3 accumulation and radioligand binding experiments to determine the impact of receptor mutagenesis on both chemokine and small molecule agonist and antagonist binding and action...... in CCR8. We find that the 7 transmembrane (7TM) receptor conserved disulfide bridge (7TM bridge) linking transmembrane helix (TM)III and ECL2 is crucial for chemokine and small molecule action, whereas the chemokine receptor conserved disulfide bridge between the N terminus and TMVII is needed only...

  6. Stable gene transfer of CCR5 and CXCR4 siRNAs by sleeping beauty transposon system to confer HIV-1 resistance

    Directory of Open Access Journals (Sweden)

    Akkina Ramesh

    2008-07-01

    Full Text Available Abstract Background Thus far gene therapy strategies for HIV/AIDS have used either conventional retroviral vectors or lentiviral vectors for gene transfer. Although highly efficient, their use poses a certain degree of risk in terms of viral mediated oncogenesis. Sleeping Beauty (SB transposon system offers a non-viral method of gene transfer to avoid this possible risk. With respect to conferring HIV resistance, stable knock down of HIV-1 coreceptors CCR5 and CXCR4 by the use of lentiviral vector delivered siRNAs has proved to be a promising strategy to protect cells from HIV-1 infection. In the current studies our aim is to evaluate the utility of SB system for stable gene transfer of CCR5 and CXCR4 siRNA genes to derive HIV resistant cells as a first step towards using this system for gene therapy. Results Two well characterized siRNAs against the HIV-1 coreceptors CCR5 and CXCR4 were chosen based on their previous efficacy for the SB transposon gene delivery. The siRNA transgenes were incorporated individually into a modified SB transfer plasmid containing a FACS sortable red fluorescence protein (RFP reporter and a drug selectable neomycin resistance gene. Gene transfer was achieved by co-delivery with a construct expressing a hyperactive transposase (HSB5 into the GHOST-R3/X4/R5 cell line, which expresses the major HIV receptor CD4 and and the co-receptors CCR5 and CXCR4. SB constructs expressing CCR5 or CXCR4 siRNAs were also transfected into MAGI-CCR5 or MAGI-CXCR4 cell lines, respectively. Near complete downregulation of CCR5 and CXCR4 surface expression was observed in transfected cells. During viral challenge with X4-tropic (NL4.3 or R5-tropic (BaL HIV-1 strains, the respective transposed cells showed marked viral resistance. Conclusion SB transposon system can be used to deliver siRNA genes for stable gene transfer. The siRNA genes against HIV-1 coreceptors CCR5 and CXCR4 are able to downregulate the respective cell surface proteins

  7. Overcoming hERG affinity in the discovery of maraviroc; a CCR5 antagonist for the treatment of HIV.

    Science.gov (United States)

    Price, David A; Armour, Duncan; de Groot, Marcel; Leishman, Derek; Napier, Carolyn; Perros, Manos; Stammen, Blanda L; Wood, Anthony

    2008-01-01

    Avoiding cardiac liability associated with blockade of hERG (human ether a go-go) is key for successful drug discovery and development. This paper describes the work undertaken in the discovery of a potent CCR5 antagonist, maraviroc 34, for the treatment of HIV. In particular the use of a pharmacophore model of the hERG channel and a high throughput binding assay for the hERG channel are described that were critical to elucidate SAR to overcome hERG liabilities. The key SAR involves the introduction of polar substituents into regions of the molecule where it is postulated to undergo hydrophobic interactions with the ion channel. Within the CCR5 project there appeared to be no strong correlation between hERG affinity and physiochemical parameters such as pKa or lipophilicity. It is believed that chemists could apply these same strategies early in drug discovery to remove hERG interactions associated with lead compounds while retaining potency at the primary target.

  8. Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice.

    Science.gov (United States)

    Kim, Jongkil; Chung, Kunho; Choi, Changseon; Beloor, Jagadish; Ullah, Irfan; Kim, Nahyeon; Lee, Kuen Yong; Lee, Sang-Kyung; Kumar, Priti

    2016-01-26

    Adipose tissue macrophage (ATM)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT) can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival.

  9. Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice

    Directory of Open Access Journals (Sweden)

    Jongkil Kim

    2016-01-01

    Full Text Available Adipose tissue macrophage (ATM-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1, which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival.

  10. [A Case of an Older Patient with Metastatic Breast Cancer Effectively Treated with Capecitabine, with Achievement of cCR].

    Science.gov (United States)

    Ono, Yoko; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2015-11-01

    A case: An 82-year-old woman underwent Bp plus Ax enforcement for carcinoma of the right breast (T2N1M0, StageⅡB) about 5 years previously. Letrozole was administered, but right pleura tuberculum and pleural dissemination was noted in the fifth postoperative year. The hormone therapy was changed, but mediastinal lymph node metastases were observed with tumor marker elevation and bilateral metastases in the lung and right pleural fluid retention. Capecitabine 1,800 mg/day for 3 weeks was started in the sixth postoperative year. The response to treatment was classified as cCR and no side effects were noted. For approximately 1 year and 6 months, no recurrence or metastasis has been observed. Consecutive therapy such as onset of the side effect or an injection method change, dosage weight loss is difficult though chemotherapies is performed for the recurrence metastasis breast cancer case of the older patient. Because capecitabine is isolated, and a continuous administration is had without a side effect, and it was with cCR for this case, in addition, discussion of the literature is reported because it seemed that it may be in effective therapy for an older patient breast cancer case in future.

  11. A Rare De novo Complex Chromosomal Rearrangement (CCR) Involving Four Chromosomes in An Oligo-asthenosperm Infertile Man.

    Science.gov (United States)

    Asia, Saba; Vaziri Nasab, Hamed; Sabbaghian, Marjan; Kalantari, Hamid; Zari Moradi, Shabnam; Gourabi, Hamid; Mohseni Meybodi, Anahita

    2014-01-01

    Complex chromosomal rearrangements (CCRs) are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization (FISH) procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms.

  12. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

    Science.gov (United States)

    Wunderlich, Claudia M; Ackermann, P Justus; Ostermann, Anna Lena; Adams-Quack, Petra; Vogt, Merly C; Tran, My-Ly; Nikolajev, Alexei; Waisman, Ari; Garbers, Christoph; Theurich, Sebastian; Mauer, Jan; Hövelmeyer, Nadine; Wunderlich, F Thomas

    2018-04-25

    Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.

  13. Eosinophils subvert host resistance to an intracellular pathogen by instigating non-protective IL-4 in CCR2-/- mice.

    Science.gov (United States)

    Verma, A H; Bueter, C L; Rothenberg, M E; Deepe, G S

    2017-01-01

    Eosinophils contribute to type II immune responses in helminth infections and allergic diseases; however, their influence on intracellular pathogens is less clear. We previously reported that CCR2 -/- mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated interleukin (IL)-4 response. We sought to identify the cellular source promulgating IL-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2 -/- animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity.

  14. CCR9 Is Not Required for the Homing of Pro-inflammatory Effector T cells, but Is Crucial for Recruitment and Expansion of FoxP3+ CD8+ Tregs in the Small Intestine

    DEFF Research Database (Denmark)

    Gomez-Casado, Cristina; Joeris, Thorsten; Holmkvist, Petra

    Chemokine receptor 9 (CCR9) is required for the homeostatic recruitment of T cells to the mucosa of the small intestine. Accordingly, CCR9 has been suggested as a potential target to inhibit the recruitment of proinflammatory effector T cells (Teff) in inflammatory bowel disease (IBD). Since...... the contribution of CCR9 to the recruitment of Teff in inflammation is not entirely clear, we aimed to address this question using IFABPtOva mice. These mice express Ovalbumin (Ova) specifically in small intestinal epithelial cells, which allows triggering of acute inflammation following transfer of Ova......-specific CD8+ T cells (OT-I cells) and adjuvant treatment. Strikingly, intestinal inflammation in IFABP-tOva mice could also be triggered following transfer of CCR9-deficient OT-I cells, demonstrating that CCR9 is not required for homing of Teff cells. Interestingly, OTI cells transferred to IFABP-tOva mice...

  15. Quantum gravity and quantum cosmology

    CERN Document Server

    Papantonopoulos, Lefteris; Siopsis, George; Tsamis, Nikos

    2013-01-01

    Quantum gravity has developed into a fast-growing subject in physics and it is expected that probing the high-energy and high-curvature regimes of gravitating systems will shed some light on how to eventually achieve an ultraviolet complete quantum theory of gravity. Such a theory would provide the much needed information about fundamental problems of classical gravity, such as the initial big-bang singularity, the cosmological constant problem, Planck scale physics and the early-time inflationary evolution of our Universe.   While in the first part of this book concepts of quantum gravity are introduced and approached from different angles, the second part discusses these theories in connection with cosmological models and observations, thereby exploring which types of signatures of modern and mathematically rigorous frameworks can be detected by experiments. The third and final part briefly reviews the observational status of dark matter and dark energy, and introduces alternative cosmological models.   ...

  16. Quantum biological information theory

    CERN Document Server

    Djordjevic, Ivan B

    2016-01-01

    This book is a self-contained, tutorial-based introduction to quantum information theory and quantum biology. It serves as a single-source reference to the topic for researchers in bioengineering, communications engineering, electrical engineering, applied mathematics, biology, computer science, and physics. The book provides all the essential principles of the quantum biological information theory required to describe the quantum information transfer from DNA to proteins, the sources of genetic noise and genetic errors as well as their effects. Integrates quantum information and quantum biology concepts; Assumes only knowledge of basic concepts of vector algebra at undergraduate level; Provides a thorough introduction to basic concepts of quantum information processing, quantum information theory, and quantum biology; Includes in-depth discussion of the quantum biological channel modelling, quantum biological channel capacity calculation, quantum models of aging, quantum models of evolution, quantum models o...

  17. Quantum Computation

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 9. Quantum Computation - Particle and Wave Aspects of Algorithms. Apoorva Patel. General Article Volume 16 Issue 9 September 2011 pp 821-835. Fulltext. Click here to view fulltext PDF. Permanent link:

  18. Quantum Computing

    Indian Academy of Sciences (India)

    performance driven optimization ofVLSI ... start-up company at lIT. Mumbai. ... 1 The best known algorithms for factorization ... make a measurement the quantum state continues to be ... cally in this way: if there is a source producing identical.

  19. Quantum Biology

    Directory of Open Access Journals (Sweden)

    Alessandro Sergi

    2009-06-01

    Full Text Available A critical assessment of the recent developmentsof molecular biology is presented.The thesis that they do not lead to a conceptualunderstanding of life and biological systems is defended.Maturana and Varela's concept of autopoiesis is briefly sketchedand its logical circularity avoided by postulatingthe existence of underlying living processes,entailing amplification from the microscopic to the macroscopic scale,with increasing complexity in the passage from one scale to the other.Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces,is criticized. It is suggested that the correct interpretationof quantum dispersion forces (van der Waals, hydrogen bonding, and so onas quantum coherence effects hints at the necessity of includinglong-ranged forces (or mechanisms for them incondensed matter theories of biological processes.Some quantum effects in biology are reviewedand quantum mechanics is acknowledged as conceptually important to biology since withoutit most (if not all of the biological structuresand signalling processes would not even exist. Moreover, it is suggested that long-rangequantum coherent dynamics, including electron polarization,may be invoked to explain signal amplificationprocess in biological systems in general.

  20. Quantum logic

    International Nuclear Information System (INIS)

    Mittelstaedt, P.

    1979-01-01

    The subspaces of Hilbert space constitute an orthocomplemented quasimodular lattice Lsub(q) for which neither a two-valued function nor generalized truth function exist. A generalisation of the dialogic method can be used as an interpretation of a lattice Lsub(qi), which may be considered as the intuitionistic part of Lsub(q). Some obvious modifications of the dialogic method are introduced which come from the possible incommensurability of propositions about quantum mechanical systems. With the aid of this generalized dialogic method a propositional calculus Qsub(eff) is derived which is similar to the calculus of effective (intuitionistic) logic, but contains a few restrictions which are based on the incommensurability of quantum mechanical propositions. It can be shown within the framework of the calculus Qsub(eff) that the value-definiteness of the elementary propositions which are proved by quantum mechanical propositions is inherited by all finite compund propositions. In this way one arrives at the calculus Q of full quantum logic which incorporates the principle of excluded middle for all propositions and which is a model for the lattice Lsub(q). (Auth.)

  1. Quantum computing

    OpenAIRE

    Burba, M.; Lapitskaya, T.

    2017-01-01

    This article gives an elementary introduction to quantum computing. It is a draft for a book chapter of the "Handbook of Nature-Inspired and Innovative Computing", Eds. A. Zomaya, G.J. Milburn, J. Dongarra, D. Bader, R. Brent, M. Eshaghian-Wilner, F. Seredynski (Springer, Berlin Heidelberg New York, 2006).

  2. Quantum Theory

    NARCIS (Netherlands)

    Raedt, Hans De; Binder, K; Ciccotti, G

    1996-01-01

    The purpose of this set of lectures is to introduce the general concepts that are at the basis of the computer simulation algorithms that are used to study the behavior of condensed matter quantum systems. The emphasis is on the underlying concepts rather than on specific applications. Topics

  3. Quantum chromodynamics

    International Nuclear Information System (INIS)

    Mosher, A.

    1980-01-01

    The symposium included lectures covering both the elements and the experimental tests of the theory of quantum chromdynamics. A three day topical conference was included which included the first results from PETRA as well as the latest reports from CERN, Fermilab, and SPEAR experiments. Twenty-one items from the symposium were prepared separately for the data base

  4. Quantum Statistical Mechanics on a Quantum Computer

    NARCIS (Netherlands)

    Raedt, H. De; Hams, A.H.; Michielsen, K.; Miyashita, S.; Saito, K.; Saito, E.

    2000-01-01

    We describe a simulation method for a quantum spin model of a generic, general purpose quantum computer. The use of this quantum computer simulator is illustrated through several implementations of Grover’s database search algorithm. Some preliminary results on the stability of quantum algorithms

  5. Quantum arithmetic with the Quantum Fourier Transform

    OpenAIRE

    Ruiz-Perez, Lidia; Garcia-Escartin, Juan Carlos

    2014-01-01

    The Quantum Fourier Transform offers an interesting way to perform arithmetic operations on a quantum computer. We review existing Quantum Fourier Transform adders and multipliers and propose some modifications that extend their capabilities. Among the new circuits, we propose a quantum method to compute the weighted average of a series of inputs in the transform domain.

  6. Quantum Chaos via the Quantum Action

    OpenAIRE

    Kröger, H.

    2002-01-01

    We discuss the concept of the quantum action with the purpose to characterize and quantitatively compute quantum chaos. As an example we consider in quantum mechanics a 2-D Hamiltonian system - harmonic oscillators with anharmonic coupling - which is classically a chaotic system. We compare Poincar\\'e sections obtained from the quantum action with those from the classical action.

  7. Quantum optics and fundamentals of quantum theory

    International Nuclear Information System (INIS)

    Dusek, M.

    1997-01-01

    Quantum optics has opened up new opportunities for experimental verification of the basic principles of quantum mechanics, particularly in the field of quantum interference and so-called non-local phenomena. The results of the experiments described provide unambiguous support to quantum mechanics. (Z.J.)

  8. Quantum cryptography beyond quantum key distribution

    NARCIS (Netherlands)

    Broadbent, A.; Schaffner, C.

    2016-01-01

    Quantum cryptography is the art and science of exploiting quantum mechanical effects in order to perform cryptographic tasks. While the most well-known example of this discipline is quantum key distribution (QKD), there exist many other applications such as quantum money, randomness generation,

  9. Quantum Computing: a Quantum Group Approach

    OpenAIRE

    Wang, Zhenghan

    2013-01-01

    There is compelling theoretical evidence that quantum physics will change the face of information science. Exciting progress has been made during the last two decades towards the building of a large scale quantum computer. A quantum group approach stands out as a promising route to this holy grail, and provides hope that we may have quantum computers in our future.

  10. Quantum net dynamics

    International Nuclear Information System (INIS)

    Finkelstein, D.

    1989-01-01

    The quantum net unifies the basic principles of quantum theory and relativity in a quantum spacetime having no ultraviolet infinities, supporting the Dirac equation, and having the usual vacuum as a quantum condensation. A correspondence principle connects nets to Schwinger sources and further unifies the vertical structure of the theory, so that the functions of the many hierarchic levels of quantum field theory (predicate algebra, set theory, topology,hor-ellipsis, quantum dynamics) are served by one in quantum net dynamics

  11. Quantum Gravity

    International Nuclear Information System (INIS)

    Giribet, G E

    2005-01-01

    Claus Kiefer presents his book, Quantum Gravity, with his hope that '[the] book will convince readers of [the] outstanding problem [of unification and quantum gravity] and encourage them to work on its solution'. With this aim, the author presents a clear exposition of the fundamental concepts of gravity and the steps towards the understanding of its quantum aspects. The main part of the text is dedicated to the analysis of standard topics in the formulation of general relativity. An analysis of the Hamiltonian formulation of general relativity and the canonical quantization of gravity is performed in detail. Chapters four, five and eight provide a pedagogical introduction to the basic concepts of gravitational physics. In particular, aspects such as the quantization of constrained systems, the role played by the quadratic constraint, the ADM decomposition, the Wheeler-de Witt equation and the problem of time are treated in an expert and concise way. Moreover, other specific topics, such as the minisuperspace approach and the feasibility of defining extrinsic times for certain models, are discussed as well. The ninth chapter of the book is dedicated to the quantum gravitational aspects of string theory. Here, a minimalistic but clear introduction to string theory is presented, and this is actually done with emphasis on gravity. It is worth mentioning that no hard (nor explicit) computations are presented, even though the exposition covers the main features of the topic. For instance, black hole statistical physics (within the framework of string theory) is developed in a pedagogical and concise way by means of heuristical arguments. As the author asserts in the epilogue, the hope of the book is to give 'some impressions from progress' made in the study of quantum gravity since its beginning, i.e., since the end of 1920s. In my opinion, Kiefer's book does actually achieve this goal and gives an extensive review of the subject. (book review)

  12. Quantum optics with single quantum dot devices

    International Nuclear Information System (INIS)

    Zwiller, Valery; Aichele, Thomas; Benson, Oliver

    2004-01-01

    A single radiative transition in a single-quantum emitter results in the emission of a single photon. Single quantum dots are single-quantum emitters with all the requirements to generate single photons at visible and near-infrared wavelengths. It is also possible to generate more than single photons with single quantum dots. In this paper we show that single quantum dots can be used to generate non-classical states of light, from single photons to photon triplets. Advanced solid state structures can be fabricated with single quantum dots as their active region. We also show results obtained on devices based on single quantum dots

  13. Efficient quantum walk on a quantum processor

    Science.gov (United States)

    Qiang, Xiaogang; Loke, Thomas; Montanaro, Ashley; Aungskunsiri, Kanin; Zhou, Xiaoqi; O'Brien, Jeremy L.; Wang, Jingbo B.; Matthews, Jonathan C. F.

    2016-01-01

    The random walk formalism is used across a wide range of applications, from modelling share prices to predicting population genetics. Likewise, quantum walks have shown much potential as a framework for developing new quantum algorithms. Here we present explicit efficient quantum circuits for implementing continuous-time quantum walks on the circulant class of graphs. These circuits allow us to sample from the output probability distributions of quantum walks on circulant graphs efficiently. We also show that solving the same sampling problem for arbitrary circulant quantum circuits is intractable for a classical computer, assuming conjectures from computational complexity theory. This is a new link between continuous-time quantum walks and computational complexity theory and it indicates a family of tasks that could ultimately demonstrate quantum supremacy over classical computers. As a proof of principle, we experimentally implement the proposed quantum circuit on an example circulant graph using a two-qubit photonics quantum processor. PMID:27146471

  14. Quantum Secure Dialogue with Quantum Encryption

    International Nuclear Information System (INIS)

    Ye Tian-Yu

    2014-01-01

    How to solve the information leakage problem has become the research focus of quantum dialogue. In this paper, in order to overcome the information leakage problem in quantum dialogue, a novel approach for sharing the initial quantum state privately between communicators, i.e., quantum encryption sharing, is proposed by utilizing the idea of quantum encryption. The proposed protocol uses EPR pairs as the private quantum key to encrypt and decrypt the traveling photons, which can be repeatedly used after rotation. Due to quantum encryption sharing, the public announcement on the state of the initial quantum state is omitted, thus the information leakage problem is overcome. The information-theoretical efficiency of the proposed protocol is nearly 100%, much higher than previous information leakage resistant quantum dialogue protocols. Moreover, the proposed protocol only needs single-photon measurements and nearly uses single photons as quantum resource so that it is convenient to implement in practice. (general)

  15. Quantum key distribution via quantum encryption

    CERN Document Server

    Yong Sheng Zhang; Guang Can Guo

    2001-01-01

    A quantum key distribution protocol based on quantum encryption is presented in this Brief Report. In this protocol, the previously shared Einstein-Podolsky-Rosen pairs act as the quantum key to encode and decode the classical cryptography key. The quantum key is reusable and the eavesdropper cannot elicit any information from the particle Alice sends to Bob. The concept of quantum encryption is also discussed. (21 refs).

  16. Quantum random walks using quantum accelerator modes

    International Nuclear Information System (INIS)

    Ma, Z.-Y.; Burnett, K.; D'Arcy, M. B.; Gardiner, S. A.

    2006-01-01

    We discuss the use of high-order quantum accelerator modes to achieve an atom optical realization of a biased quantum random walk. We first discuss how one can create coexistent quantum accelerator modes, and hence how momentum transfer that depends on the atoms' internal state can be achieved. When combined with microwave driving of the transition between the states, a different type of atomic beam splitter results. This permits the realization of a biased quantum random walk through quantum accelerator modes

  17. Quantum chemistry on a superconducting quantum processor

    Energy Technology Data Exchange (ETDEWEB)

    Kaicher, Michael P.; Wilhelm, Frank K. [Theoretical Physics, Saarland University, 66123 Saarbruecken (Germany); Love, Peter J. [Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States)

    2016-07-01

    Quantum chemistry is the most promising civilian application for quantum processors to date. We study its adaptation to superconducting (sc) quantum systems, computing the ground state energy of LiH through a variational hybrid quantum classical algorithm. We demonstrate how interactions native to sc qubits further reduce the amount of quantum resources needed, pushing sc architectures as a near-term candidate for simulations of more complex atoms/molecules.

  18. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C; Kaas, A; Hansen, L

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated lo...

  19. Impact of CCR5delta32 Host Genetic Background and Disease Progression on HIV-1 Intrahost Evolutionary Processes: Efficient Hypothesis Testing through Hierarchical Phylogenetic Models

    NARCIS (Netherlands)

    Edo-Matas, Diana; Lemey, Philippe; Tom, Jennifer A.; Serna-Bolea, Cèlia; van den Blink, Agnes E.; van 't Wout, Angélique B.; Schuitemaker, Hanneke; Suchard, Marc A.

    2011-01-01

    The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically

  20. Biased and Constitutive Signaling in the CC-Chemokine Receptor CCR5 by manipulating the Interface between Transmembrane Helix 6 and 7

    DEFF Research Database (Denmark)

    Steen, Anne; Thiele, Stefanie; Guo, Dong

    2013-01-01

    The equilibrium state of CCR5 is manipulated here toward either activation or inactivation by introduction of single amino acid substitutions in the transmembrane domains (TMs) 6 and 7. Insertion of a steric hindrance mutation in the center of TM7 (G286F in position VII:09/7.42) resulted in biase...

  1. Modulators of the human CCR5 receptor. Part 1: Discovery and initial SAR of 1-(3,3-diphenylpropyl)-piperidinyl amides and ureas.

    Science.gov (United States)

    Burrows, Jeremy N; Cumming, John G; Fillery, Shaun M; Hamlin, Gordon A; Hudson, Julian A; Jackson, Ruth J; McLaughlin, Sharon; Shaw, John S

    2005-01-03

    Investigation of weak screening hits led to the identification of N-alkyl-N-[1-(3,3-diphenylpropyl)piperidin-4-yl]-2-phenylacetamides and N-alkyl-N-[1-(3,3-diphenylpropyl)piperidin-4-yl]-N'-benzylureas as potent, selective ligands for the human CCR5 chemokine receptor.

  2. The CCR4 Deadenylase Acts with Nanos and Pumilio in the Fine-Tuning of Mei-P26 Expression to Promote Germline Stem Cell Self-Renewal

    Science.gov (United States)

    Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

    2013-01-01

    Summary Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation. PMID:24286029

  3. A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn's disease

    DEFF Research Database (Denmark)

    Keshav, Satish; Vaňásek, Tomáš; Niv, Yaron

    2013-01-01

    CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436...

  4. A closed-tube assay for genotyping of the 32-bp deletion polymorphism in the chemokine receptor 5 (CCR5) gene

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Werge, Thomas

    2007-01-01

    We have developed a closed-tube assay for determination of the chemokine receptor type 5 (CCR5) 32-bp deletion allele, which protects against infections with HIV and modulates susceptibility to a variety of inflammatory diseases. This assay utilizes dissociation analysis of amplified products...

  5. LPS-induced expression of a novel chemokine receptor (L-CCR) in mouse glial cells in vitro and in vivo

    NARCIS (Netherlands)

    Zuurman, MW; Heeroma, J; Brouwer, N; Boddeke, HWGM; Biber, K

    There is increasing evidence that chemokines, specialized regulators of the peripheral immune system, are also involved in the physiology and pathology of the CNS. It is known that glial cells (astrocytes and microglia) express various chemokine receptors like CCR1, -3, -5, and CXCR4. We have

  6. CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine/Chemokine Receptor Complex in Patients with AMD

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    PURPOSE: The chemokine receptors CX3CR1 and CCR2 have been implicated in the development of age-related macular degeneration (AMD). The evidence is mainly derived from experimental cell studies and murine models of AMD. The purpose of this study was to investigate the association between expression...... of CX3CR1 and CCR2 on different leukocyte subsets and AMD. Furthermore we measured the plasma levels of ligands CX3CL1 and CCL2. METHODS: Patients attending our department were asked to participate in the study. The diagnosis of AMD was based on clinical examination and multimodal imaging techniques...... positive correlation between CCR2 and CX3CR1 expression on CD8+ cells (r = 0.727, p = 0.0001). We found no difference in plasma levels of CX3CL1 and CCL2 among the groups. CONCLUSIONS: Our results show a down regulation of CX3CR1 on CD8+ cells; this correlated to a low expression of CCR2 on CD8+ cells...

  7. Memory CD4(+)CCR5(+) T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1

    NARCIS (Netherlands)

    Bunders, Madeleine J.; van der Loos, Chris M.; Klarenbeek, Paul L.; van Hamme, John L.; Boer, Kees; Wilde, Jim C. H.; de Vries, Niek; van Lier, Rene A. W.; Kootstra, Neeltje; Pals, Steven T.; Kuijpers, Taco W.

    2012-01-01

    Despite potential clinical importance, target cells for mother-to-child transmission of HIV-1 have not yet been identified. Cord blood-derived CD4(+) T cells are largely naive and do not express CCR5, the mandatory coreceptor for transmitted HIV-1 R5 strains in infants. In the present study, we

  8. The CCR4 deadenylase acts with Nanos and Pumilio in the fine-tuning of Mei-P26 expression to promote germline stem cell self-renewal.

    Science.gov (United States)

    Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

    2013-01-01

    Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation.

  9. Unconventional Quantum Computing Devices

    OpenAIRE

    Lloyd, Seth

    2000-01-01

    This paper investigates a variety of unconventional quantum computation devices, including fermionic quantum computers and computers that exploit nonlinear quantum mechanics. It is shown that unconventional quantum computing devices can in principle compute some quantities more rapidly than `conventional' quantum computers.

  10. Physics of quantum computation

    International Nuclear Information System (INIS)

    Belokurov, V.V.; Khrustalev, O.A.; Sadovnichij, V.A.; Timofeevskaya, O.D.

    2003-01-01

    In the paper, the modern status of the theory of quantum computation is considered. The fundamental principles of quantum computers and their basic notions such as quantum processors and computational basis states of the quantum Turing machine as well as the quantum Fourier transform are discussed. Some possible experimental realizations on the basis of NMR methods are given

  11. The Classroom Communication Resource (CCR) intervention to change peer's attitudes towards children who stutter (CWS): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Mallick, Rizwana; Kathard, Harsha; Thabane, Lehana; Pillay, Mershen

    2018-01-17

    Children who stutter (CWS) are at a high-risk of being teased and bullied in primary school because of negative peer attitudes and perceptions towards stuttering. There is little evidence to determine if classroom-based interventions are effective in changing peer attitudes towards stuttering. The primary objective is to determine the effect of the Classroom Communication Resource (CCR) intervention versus usual practice, measured using the Stuttering Resource Outcomes Measure (SROM) 6-months post-intervention among grade 7 students. The secondary objective is to investigate attitude changes towards stuttering among grade participants on the SROM subscales. A cluster randomised controlled trial (RCT) will be conducted with schools as the unit of randomization. Schools will be stratified into quintile groups, and then randomized to receive the CCR intervention or usual practice. Quintile stratification will be conducted in accordance to the Western Cape Department of Education classification of schools according to geographical location, fee per school and allocation of resources and funding. Participants will include primary schools in the lower (second and third) and higher (fourth and fifth) quintiles and children aged 11 years or older in grade 7 will be included. The study will consist of the CCR intervention program or usual practice as a no-CCR control. The CCR is a classroom-based, teacher led intervention tool including a story, role-play and discussion. The grade 7 teachers allocated to the CCR intervention, will be trained and will administer the intervention. The analysis will follow intention-to-treat (ITT) principle and generalized estimating equations (GEE) to compare groups on the global SROM and its subscales to account for possible clustering within schools. The subgroup hypothesis will be tested by adding an interaction term of quintile group x intervention. This study is designed to assess whether the CCR intervention versus usual practice in

  12. Quantum electrodynamics

    International Nuclear Information System (INIS)

    Akhiezer, A.I.

    1983-01-01

    Basic ideas of quantum electrodynamics history of its origination and its importance are outlined. It is shown low the notion of the field for each kind of particles and the notion of vacuum for such field had originated and been affirmed how a new language of the Feynman diagrams had appeared without which it is quite impossible to described complex processes of particle scattering and mutual transformation. The main problem of the quantum electrodynamics is to find a scattering matrix, which solution comes to the determination of the Green electrodynamic functions. A review is given of papers on clarifying the asymptotic behaviour of the Green electrodynamic functions in the range of high pulses, on studying the Compton effect, bremsstrahlung irradiation Raman light scattering elastic scattering during channeling of charged particles in a crystal

  13. Quantum electrodynamics

    CERN Document Server

    Greiner, Walter

    2009-01-01

    This textbook on Quantum Electrodynamics is a thorough introductory text providing all necessary mathematical tools together with many examples and worked problems. In their presentation of the subject the authors adopt a heuristic approach based on the propagator formalism. The latter is introduced in the first two chapters in both its nonrelativistic and relativistic versions. Subsequently, a large number of scattering and radiation processes involving electrons, positrons, and photons are introduced and their theoretical treatment is presented in great detail. Higher order processes and renormalization are also included. The book concludes with a discussion of two-particle states and the interaction of spinless bosons. This completely revised and corrected new edition provides several additions to enable deeper insight in formalism and application of quantum electrodynamics.

  14. Quantum psyche

    CERN Document Server

    Baaquie, Belal E; Demongeot, J; Galli-Carminati, Giuliana; Martin, F; Teodorani, Massimo

    2015-01-01

    At the end of the 19th century Sigmund Freud discovered that our acts and choices are not only decisions of our consciousness, but that they are also deeply determined by our unconscious (the so-called "Freudian unconscious"). During a long correspondence between them (1932-1958) Wolfgang Pauli and Carl Gustav Jung speculated that the unconscious could be a quantum system. This book is addressed both to all those interested in the new developments of the age-old enquiry in the relations between mind and matter, and also to the experts in quantum physics that are interested in a formalisation of this new approach. The description of the "Bilbao experiment" adds a very interesting experimental inquiry into the synchronicity effect in a group situation, linking theory to a quantifiable verification of these subtle effects. Cover design: "Entangled Minds". Riccardo Carminati Galli, 2014.

  15. Quantum Squeezing

    International Nuclear Information System (INIS)

    Zubairy, Suhail

    2005-01-01

    Quantum squeezed states are a consequence of uncertainty relations; a state is squeezed when the noise in one variable is reduced below the symmetric limit at the expense of the increased noise in the conjugate variable such that the Heisenberg uncertainty relation is not violated. Such states have been known since the earliest days of quantum mechanics. The realization in the early 80's that quantum squeezed states of the radiation field can have important applications in high precision Michelson interferometry for detecting gravitational waves led to a tremendous amount of activity, both in theoretical and experimental quantum optics. The present volume, edited by two eminent scientists, is a collection of papers by leading experts in the field of squeezed states on different aspects of the field as it stands today. The book is divided into three parts. In the first part, there are three articles that review the fundamentals. The first paper by Knight and Buzek presents an introductory account of squeezed states and their properties. The chapter, which opens with the quantization of the radiation field, goes on to discuss the quantum optical properties of single mode and multimode squeezed states. The second article by Hillery provides a detailed description of field quantization in the presence of a nonlinear dielectric medium, thus providing a rigorous treatment of squeezing in nonlinear media. The third article by Yurke presents a comprehensive discussion of the input-output theory of the squeezed radiation at the dielectric boundaries. The second part of the book, comprising of three articles, deals with the generation of squeezed states. In the first article, Drummond reviews the squeezing properties of light in nonlinear systems such as parametric oscillators. He also discusses squeezed light propagation through waveguides and optical fibers. In the second article, Ralph concentrates on active laser sources of squeezing and presents an analysis based on the

  16. C*-algebraic scattering theory and explicitly solvable quantum field theories

    International Nuclear Information System (INIS)

    Warchall, H.A.

    1985-01-01

    A general theoretical framework is developed for the treatment of a class of quantum field theories that are explicitly exactly solvable, but require the use of C*-algebraic techniques because time-dependent scattering theory cannot be constructed in any one natural representation of the observable algebra. The purpose is to exhibit mechanisms by which inequivalent representations of the observable algebra can arise in quantum field theory, in a setting free of other complications commonly associated with the specification of dynamics. One of two major results is the development of necessary and sufficient conditions for the concurrent unitary implementation of two automorphism groups in a class of quasifree representations of the algebra of the canonical commutation relations (CCR). The automorphism groups considered are induced by one-parameter groups of symplectic transformations on the classical phase space over which the Weyl algebra of the CCR is built; each symplectic group is conjugate by a fixed symplectic transformation to a one-parameter unitary group. The second result, an analog to the Birman--Belopol'skii theorem in two-Hilbert-space scattering theory, gives sufficient conditions for the existence of Moller wave morphisms in theories with time-development automorphism groups of the above type. In a paper which follows, this framework is used to analyze a particular model system for which wave operators fail to exist in any natural representation of the observable algebra, but for which wave morphisms and an associated S matrix are easily constructed

  17. Quantum hadrodynamics

    International Nuclear Information System (INIS)

    Serot, B.D.

    1992-01-01

    It is therefore essential to develop reliable nuclear models that go beyond the traditional non-relativistic many-body framework. The arguments for renormalizable models based on hadronic degrees of freedom (quantum hadrodynamics) are presented, and the assumptions underlying this framework are discussed. The Walecka model, which contains neutrons, protons, and neutral scalar and vector mesons, is considered first as a simple example. The development is based on the relativistic mean-field and Hartree approximations, and their application to infinite matter and atomic nuclei. Some successes of this model are discussed, such as the nuclear equation of state, the derivation of the shell model, the prediction of nuclear properties throughout the periodic table, and the inclusion of zero-point vacuum corrections. The important concepts of Lorentz covariance and self-consistency are emphasized and the new dynamical features that arise in a relativistic many-body framework are highlighted. The computation of isoscalar magnetic moments is presented as an illustrative example. Calculations beyond the relativistic mean-field and Hartree approximations (for example, Dirac-Hartree-Fock and Dirac-Brueckner) are considered next, as well as recent efforts to incorporate the full role of the quantum vacuum in a consistent fashion. An extended model containing isovector pi and rho mesons is then developed; the dynamics is based on the chirally invariant linear sigma model. The difficulties in constructing realistic chiral descriptions of nuclear matter and nuclei are analysed, and the connection between the sigma model and the Walecka model is established. Finally, the relationship between quantum hadrodynamics and quantum chromodynamics is briefly addressed. (Author)

  18. Quantum Physics

    OpenAIRE

    Haroche, Serge

    2013-01-01

    From the infinitely small to the infinitely big, covering over 60 spatial orders of magnitude, quantum theory is used as much to describe the still largely mysterious vibrations of the microscopic strings that could be the basic constituents of the Universe, as to explain the fluctuations of the microwave radiation reaching us from the depths of outer space. Serge Haroche tells us about the scientific theory that revolutionised our understanding of nature and made an extraordinary contributio...

  19. Quantum Finance

    OpenAIRE

    Martin Schaden

    2002-01-01

    Quantum theory is used to model secondary financial markets. Contrary to stochastic descriptions, the formalism emphasizes the importance of trading in determining the value of a security. All possible realizations of investors holding securities and cash is taken as the basis of the Hilbert space of market states. The temporal evolution of an isolated market is unitary in this space. Linear operators representing basic financial transactions such as cash transfer and the buying or selling of...

  20. Quantum Secure Direct Communication with Quantum Memory.

    Science.gov (United States)

    Zhang, Wei; Ding, Dong-Sheng; Sheng, Yu-Bo; Zhou, Lan; Shi, Bao-Sen; Guo, Guang-Can

    2017-06-02

    Quantum communication provides an absolute security advantage, and it has been widely developed over the past 30 years. As an important branch of quantum communication, quantum secure direct communication (QSDC) promotes high security and instantaneousness in communication through directly transmitting messages over a quantum channel. The full implementation of a quantum protocol always requires the ability to control the transfer of a message effectively in the time domain; thus, it is essential to combine QSDC with quantum memory to accomplish the communication task. In this Letter, we report the experimental demonstration of QSDC with state-of-the-art atomic quantum memory for the first time in principle. We use the polarization degrees of freedom of photons as the information carrier, and the fidelity of entanglement decoding is verified as approximately 90%. Our work completes a fundamental step toward practical QSDC and demonstrates a potential application for long-distance quantum communication in a quantum network.