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Sample records for evades virus-specific igg2

  1. Evader Interdiction and Collateral Damage

    Energy Technology Data Exchange (ETDEWEB)

    Gutfraind, Alexander [Los Alamos National Laboratory

    2011-01-01

    In network interdiction problems, evaders (hostile agents or data packets) are moving through a network towards their targets and we wish to choose sensor placement locations in order to intercept them before they reach their destinations. Sensor locations should be chosen economically, balancing security gains with cost, including the inconvenience sensors inflict upon innocent travelers. We give optimal sensor allocation algorithms for several classes of special graphs and hardness and optimal approximation results for general graphs, including for deterministic or Markov chain-based and oblivious or reactive evaders. In a similar-sounding but much different problem setting posed by [10] where the innocent travelers can also be reactive, we again give optimal algorithms for special cases and hardness and (essentially) optimal approximation results on general graphs.

  2. Detection of FMD virus type specific IgG1, IgG2 and IgA antibodies in milk and serum of buffaloes vaccinated with oil adjuvanted polyvalent FMD vaccine

    Directory of Open Access Journals (Sweden)

    R. Sharma

    2010-02-01

    Full Text Available The present investigation was carried out on 15 randomly selected milch buffaloes divided into three groups on the basis of lactation at an organized farm, to study the foot and mouth disease virus type specific antibodies in milk and serum following FMD vaccination. Milk and serum samples collected before vaccination i.e. 0 day and on 7, 14, 28, 42 and 56 days post vaccination, were analyzed for the detection of FMD virus specific IgG1, IgG2 and IgA antibody response by indirect double antibody sandwich ELISA. Significant FMD virus type specific antibody titres (IgG1, IgG2 and IgA were detected in milk and serum of buffaloes on different days post vaccination, though the levels of antibodies were lower in milk as compared to serum. FMD virus type specific IgG1 was found to be the predominant subclass as compared to IgG2 and IgA both in milk and serum of vaccinated buffaloes. Milk and serum IgG1, IgG2 and IgA antibody titres were positively correlated with values of regression coefficient (R as 0.506, 0.434 and 0.396, respectively.

  3. Virus-Specific T Cells: Broadening Applicability.

    Science.gov (United States)

    Barrett, A John; Prockop, Susan; Bollard, Catherine M

    2018-01-01

    Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease. This review will explore how the VST field has improved outcomes for many patients with life-threatening viral infections after HSCT, and how to broaden applicability beyond the "patient-specific" products, as well as extending to other viral diseases even outside the context of HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.

  4. A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.

    Science.gov (United States)

    Poudrier, J; Graber, P; Herren, S; Gretener, D; Elson, G; Berney, C; Gauchat, J F; Kosco-Vilbois, M H

    1999-08-01

    A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.

  5. Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.

    Science.gov (United States)

    Chan, Anita S Y; Mudhar, Hardeep; Shen, Sunny Yu; Lang, Stephanie S; Fernando, Malee; Hilmy, Maryam Hazly; Guppy, Naomi Jayne; Rennie, Ian; Dunkley, Lisa; Al Jajeh, Issam

    2017-11-01

    To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders. This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed. Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3). Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the 'IgG4-RD' pathogenesis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Optimal interdiction of unreactive Markovian evaders

    Energy Technology Data Exchange (ETDEWEB)

    Gutfraind, Alexander [Los Alamos National Laboratory; Hagberg, Aric [Los Alamos National Laboratory; Pan, Feng [Los Alamos National Laboratory

    2008-01-01

    The network interdiction problem arises in a wide variety of areas including military logistics, infectious disease control and counter-terrorism. In the classical formulation one is given a weighted network G(N, E) and the task is to find b nodes (or edges) whose removal would maximally increase the least-cost path from a source node s to a target node r. In practical applications. G represenLs a transportation or activity network; node/edge removal is done by an agent, the 'interdictor' against another agent the 'evader' who wants to traverse G from s to t along the least-cost route. Our work is motivated by cases in which both agents have bounded rationality: e.g. when the authorities set up road blocks to catch bank robbers, neither party can plot its actions with full information about the other. We introduce a novel model of network interdiction in which the motion of (possibly) several evaders i. described by a Markov pr cess on G.We further suppose that the evaden; do not respond to interdiction decisions because of time, knowledge or computational constraint . We prove that this interdiction problem is NP-hard, like the classical formulation, but unlike the classical problem the objective function is submodular. This implies that the solution could be approximated within 1-lie using a greedy algorithm. Exploiting submodularity again. we demonstrate that a 'priority' (or 'lazy') evaluation algorithm can improve performance by orders of magnitude. Taken together, the results bring closer realistic solutions to the interdiction problem on global-scale networks.

  7. Reprint of: Virus-Specific T Cells: Broadening Applicability.

    Science.gov (United States)

    Barrett, A John; Prockop, Susan; Bollard, Catherine M

    2018-03-01

    Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease. This review will explore how the VST field has improved outcomes for many patients with life-threatening viral infections after HSCT, and how to broaden applicability beyond the "patient-specific" products, as well as extending to other viral diseases even outside the context of HSCT. Copyright © 2018. Published by Elsevier Inc.

  8. Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation.

    Science.gov (United States)

    Parker, Antony; Irure Ventura, Juan; Sims, Dawn; Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; Tricas Aizpún, Lourdes; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Wallis, Gregg; Harding, Stephen

    2017-01-01

    IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.

  9. Quantum Backaction Evading Measurement of Collective Mechanical Modes.

    Science.gov (United States)

    Ockeloen-Korppi, C F; Damskägg, E; Pirkkalainen, J-M; Clerk, A A; Woolley, M J; Sillanpää, M A

    2016-09-30

    The standard quantum limit constrains the precision of an oscillator position measurement. It arises from a balance between the imprecision and the quantum backaction of the measurement. However, a measurement of only a single quadrature of the oscillator can evade the backaction and be made with arbitrary precision. Here we demonstrate quantum backaction evading measurements of a collective quadrature of two mechanical oscillators, both coupled to a common microwave cavity. The work allows for quantum state tomography of two mechanical oscillators, and provides a foundation for macroscopic mechanical entanglement and force sensing beyond conventional quantum limits.

  10. Virus-Specific T Cells for the Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Amy Houghtelin

    2017-10-01

    Full Text Available While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST, which are not only effective but also confer protection in 70–90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo.

  11. Virus-Specific T Cells for the Immunocompromised Patient.

    Science.gov (United States)

    Houghtelin, Amy; Bollard, Catherine M

    2017-01-01

    While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70-90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo .

  12. Täna algavad Eesti Muusika Päevad

    Index Scriptorium Estoniae

    2004-01-01

    Eesti Muusika Päevade raames toimunud üritustest 21. aprillini: ERSO sümfooniakontserdist Estonia kontserdisaalis, Jüri Reinvere radiofoonilise ooperi "Vastaskallas" esiettekandest Tallinna Linnateatri Hobuveski saalis, kontserdist Kunstihoone Vabaduse väljakul (esitusel Urmas Sisaski uus "Tähistaeva tsükkel" - "Eesti rahvataevas"), lastekontserdist "Kodumaine viis" Estonia kontserdisaalis

  13. Ooperipäevad Saaremaal (II) / Tiiu Levald

    Index Scriptorium Estoniae

    Levald, Tiiu, 1940-

    2008-01-01

    21.-27. VII Saaremaa ooperipäevade raames toimunud üritustest - Carmen Tabori lavastatud Aino Kallase ja Tauno Pylkkäneni "Patseba Saaremaal" (esimene osa draama- ja teine ooperilavastus), Gershwini ooperist "Porgy ja Bess" ning 25. VII toimunud galakontserdist

  14. IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis Inmunodeficiencia de IgG2: asociación en pacientes pediátricos con meningoencefalitis bacterianas

    Directory of Open Access Journals (Sweden)

    XIOMARA ESCOBAR-PÉREZ

    2000-03-01

    Full Text Available An IgG subclass deficiency is often associated with bacterial infections. We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b. Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income. The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion. Very low levels of seric IgG2 with non detectable cerebrospinal fluid IgG2 were found in the patients. No intrathecal IgG subclass synthesis was found in two patients. One patient with S. pneumoniae had IgG3 intrathecal synthesis. Intrathecal IgG1, IgG3 and IgG4 synthesis was found in one patient suffering from H. influenzae according with reibergrams. Substitutive therapy with intravenous gammaglobulin was given to the patients as part of the treatment.Las deficiencias por subclases de IgG se asocian frecuentemente con infecciones de origen bacteriano. Se estudian cuatro pacientes en edad pediátrica con meningoencefalitis, dos de ellos a Streptococcus pneumoniae y dos a Haemophilus influenzae tipo b. Se toman muestras simultáneas diagnósticas de suero y líquido cefalorraquídeo en el momento del ingreso. Se cuantificaron las cuatro sublclases de IgG y albúmina en ambos líquidos biológicos por inmunodifusión radial. Se encontró que los pacientes presentaban cifras muy disminuidas de IgG2 sérico y ningun exhibia IgG2 en el líquido cefalorraquídeo. Dos pacientes no sintetizaron ninguna subclase de IgG intratecalmente. Un paciente con S. pneumoniae sintetizó IgG3 intratecal. Uno de los pacientes con meningoencefalitis a H. influenzae sintetizó IgG1, IgG3 e IgG4 intratecalmente de acuerdo com el reibergrama. Estos pacientes recibieron terapia substitutiva com gammaglobulina intravenosa como parte de la medicación.

  15. Virus specific antigens in mammalian cells infected with herpes simplex virus

    Science.gov (United States)

    Watson, D. H.; Shedden, W. I. H.; Elliot, A.; Tetsuka, T.; Wildy, P.; Bourgaux-Ramoisy, D.; Gold, E.

    1966-01-01

    Antisera to specific proteins in herpes simplex infected cells were produced by immunization of rabbits with infected rabbit kidney cells. These antisera were highly virus specific and produced up to twelve lines in immunodiffusion tests against infected cell extracts. Acrylamide electrophoresis and immunoelectrophoresis revealed up to ten virus specific proteins of varying size. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4288648

  16. Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus

    OpenAIRE

    Cromwell, Mandy A.; Veazey, Ronald S.; Altman, John D.; Mansfield, Keith G.; Glickman, Rhona; Allen, Todd M.; Watkins, David I.; Lackner, Andrew A.; Johnson, R. Paul

    2000-01-01

    Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-...

  17. Bacteriophages use hypermodified nucleosides to evade host's defence systems

    DEFF Research Database (Denmark)

    Kot, Witold; Olsen, Nikoline S.; Carstens, Alexander Byth

    developed several strategies to evade these defence mechanisms. Ultimately, this led to the oldest and still running arms race - microorganisms vs. their molecular parasites. We here describe a remarkable new strategy used by the recently isolated Escherichia coli phage CAjan belonging to...... to investigate this mechanism in detail we have used several methods including direct plaque sequencing, restriction endonuclease analysis and CRISPR-Cas genome editing. Through generation of specific mutants, we were able to introduce a restriction sensitive phenotype in the CAjan bacteriophage providing new...

  18. Evading Lyth bound in models of quintessential inflation

    International Nuclear Information System (INIS)

    Hossain, Md. Wali; Myrzakulov, R.; Sami, M.; Saridakis, Emmanuel N.

    2014-01-01

    Quintessential inflation refers to an attempt to unify inflation and late-time cosmic acceleration using a single scalar field. In this letter we consider two different classes of quintessential inflation, one of which is based upon a Lagrangian with non-canonical kinetic term k 2 (ϕ)∂ μ ϕ∂ μ ϕ and a steep exponential potential while the second class uses the concept of steep brane world inflation. We show that in both cases the Lyth bound can be evaded, despite the large tensor-to-scalar ratio of perturbations. The post-inflationary dynamics is consistent with nucleosynthesis constraint in these cases

  19. Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition

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    Mary E. Peek

    2012-01-01

    Full Text Available Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

  20. The new numerology of immunity mediated by virus-specific CD8(+) T cells.

    Science.gov (United States)

    Doherty, P C

    1998-08-01

    Our understanding of virus-specific CD8(+) T cell responses is currently being revolutionized by peptide-based assay systems that allow flow cytometric analysis of effector and memory cytotoxic T lymphocyte populations. These techniques are, for the first time, putting the analysis of T-cell-mediated immunity on a quantitative basis.

  1. Evaluation of six immunoassays for detection of dengue virus-specific immunoglobulin M and G antibodies

    NARCIS (Netherlands)

    J. Groen (Jan); P. Koraka (Penelope); J. Velzing (Jans); C. Copra (Cederick); A.D.M.E. Osterhaus (Albert)

    2000-01-01

    textabstractThe performance of six commercially available immunoassay systems for the detection of dengue virus-specific immunoglobulin M (IgM) and IgG antibodies in serum was evaluated. These included two IgM and IgG enzyme immunoassays (EIA) from MRL Laboratories and PanBio, a rapid

  2. TCR down-regulation controls virus-specific CD8+ T cell responses

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte Menné; Haks, Mariëlle; Nielsen, Bodil

    2008-01-01

    in mice with a mutated CD3gamma di-leucine-based motif. The CD3gamma mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic...

  3. Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system

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    Weissbrich Benedikt

    2007-05-01

    Full Text Available Abstract Background The determination of virus-specific immunoglobulin G (IgG antibodies in cerebrospinal fluid (CSF is useful for the diagnosis of virus associated diseases of the central nervous system (CNS and for the detection of a polyspecific intrathecal immune response in patients with multiple sclerosis. Quantification of virus-specific IgG in the CSF is frequently performed by calculation of a virus-specific antibody index (AI. Determination of the AI is a demanding and labour-intensive technique and therefore automation is desirable. We evaluated the precision and the diagnostic value of a fully automated enzyme immunoassay for the detection of virus-specific IgG in serum and CSF using the analyser BEP2000 (Dade Behring. Methods The AI for measles, rubella, varicella-zoster, and herpes simplex virus IgG was determined from pairs of serum and CSF samples of patients with viral CNS infections, multiple sclerosis and of control patients. CSF and serum samples were tested simultaneously with reference to a standard curve. Starting dilutions were 1:6 and 1:36 for CSF and 1:1386 and 1:8316 for serum samples. Results The interassay coefficient of variation was below 10% for all parameters tested. There was good agreement between AIs obtained with the BEP2000 and AIs derived from the semi-automated reference method. Conclusion Determination of virus-specific IgG in serum-CSF-pairs for calculation of AI has been successfully automated on the BEP2000. Current limitations of the assay layout imposed by the analyser software should be solved in future versions to offer more convenience in comparison to manual or semi-automated methods.

  4. Aggregation and pH-temperature phase behavior for aggregates of an IgG2 antibody.

    Science.gov (United States)

    Sahin, Erinc; Weiss, William F; Kroetsch, Andrew M; King, Kevin R; Kessler, R Kendall; Das, Tapan K; Roberts, Christopher J

    2012-05-01

    Monomer unfolding and thermally accelerated aggregation kinetics to produce soluble oligomers or insoluble macroscopic aggregates were characterized as a function of pH for an IgG2 antibody using differential scanning calorimetry (DSC) and size-exclusion chromatography (SEC). Aggregate size was quantified via laser light scattering, and aggregate solubility via turbidity and visual inspection. Interestingly, nonnative oligomers were soluble at pH 5.5 above approximately 15°C, but converted reversibly to visible/insoluble particles at lower temperatures. Lower pH values yielded only soluble aggregates, whereas higher pH resulted in insoluble aggregates, regardless of the solution temperature. Unlike the growing body of literature that supports the three-endotherm model of IgG1 unfolding in DSC, the results here also illustrate limitations of that model for other monoclonal antibodies. Comparison of DSC with monomer loss (via SEC) from samples during thermal scanning indicates that the least conformationally stable domain is not the most aggregation prone, and that a number of the domains remain intact within the constituent monomers of the resulting aggregates. This highlights continued challenges with predicting a priori which domain(s) or thermal transition(s) is(are) most relevant for product stability with respect to aggregation. Copyright © 2012 Wiley Periodicals, Inc.

  5. Parasitic Cape honeybee workers, Apis mellifera capensis, evade policing

    Science.gov (United States)

    Martin, Stephen J.; Beekman, Madeleine; Wossler, Theresa C.; Ratnieks, Francis L. W.

    2002-01-01

    Relocation of the Cape honeybee, Apis mellifera capensis, by bee-keepers from southern to northern South Africa in 1990 has caused widespread death of managed African honeybee, A. m. scutellata, colonies. Apis mellifera capensis worker bees are able to lay diploid, female eggs without mating by means of automictic thelytoky (meiosis followed by fusion of two meiotic products to restore egg diploidy), whereas workers of other honeybee subspecies are able to lay only haploid, male eggs. The A. m. capensis workers, which are parasitizing and killing A. m. scutellata colonies in northern South Africa, are the asexual offspring of a single, original worker in which the small amount of genetic variation observed is due to crossing over during meiosis (P. Kryger, personal communication). Here we elucidate two principal mechanisms underlying this parasitism. Parasitic A. m. capensis workers activate their ovaries in host colonies that have a queen present (queenright colonies), and they lay eggs that evade being killed by other workers (worker policing)-the normal fate of worker-laid eggs in colonies with a queen. This unique parasitism by workers is an instance in which a society is unable to control the selfish actions of its members.

  6. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans.

    Science.gov (United States)

    Efstathiou, S; Minson, A C; Field, H J; Anderson, J R; Wildy, P

    1986-02-01

    Herpes simplex virus-specific DNA sequences have been detected by Southern hybridization analysis in both central and peripheral nervous system tissues of latently infected mice. We have detected virus-specific sequences corresponding to the junction fragment but not the genomic termini, an observation first made by Rock and Fraser (Nature [London] 302:523-525, 1983). This "endless" herpes simplex virus DNA is both qualitatively and quantitatively stable in mouse neural tissue analyzed over a 4-month period. In addition, examination of DNA extracted from human trigeminal ganglia has shown herpes simplex virus DNA to be present in an "endless" form similar to that found in the mouse model system. Further restriction enzyme analysis of latently infected mouse brainstem and human trigeminal DNA has shown that this "endless" herpes simplex virus DNA is present in all four isomeric configurations.

  7. Accessing complexity: the dynamics of virus-specific T cell responses

    DEFF Research Database (Denmark)

    Doherty, P C; Christensen, Jan Pravsgaard

    2000-01-01

    -specific CD8(+ )T cells. Analysis to date with both naturally acquired and experimentally induced infections has established that the numbers of virus-specific CD8(+) T cells present during both the acute and memory phases of the host response are more than tenfold in excess of previously suspected values....... The levels are such that the virus-specific CD8(+) set is readily detected in the human peripheral blood lymphocyte compartment, particularly during persistent infections. Experimentally, it is now possible to measure the extent of cycling for tetramer (+)CD8(+) T cells during the acute and memory phases...... of the host response to viruses. Dissection of the phenotypic, functional, and molecular diversity of CD8(+) T cell populations has been greatly facilitated. It is hoped it will also soon be possible to analyze CD4(+) T cell populations in this way. Though these are early days and there is an enormous amount...

  8. TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte Menné; Haks, Mariëlle; Nielsen, Bodil

    2008-01-01

    The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8(+) T cells is impaired...... in mice with a mutated CD3gamma di-leucine-based motif. The CD3gamma mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic...... molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8(+) T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3gamma-mediated TCR down-regulation in virus...

  9. Plasma membrane associated, virus-specific polypeptides required for the formation of target antigen complexes recognized by virus-specific cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Domber, E.A.

    1986-01-01

    These studies were undertaken to define some of the poxvirus-specific target antigens which are synthesized in infected cells and recognized by vaccinia virus-specific CTLs (VV-CTLs). Since vaccinia virus infected, unmanipulated target cells express numerous virus-specific antigens on the plasma membrane, attempts were made to manipulate expression of the poxvirus genome after infection so that one or a few defined virus-specified antigens were expressed on the surface of infected cells. In vitro [ 51 Cr]-release assays determined that viral DNA synthesis and expression of late viral proteins were not necessary to form a target cell which was fully competent for lysis by VV-CTLs. Under the conditions employed in these experiments, 90-120 minutes of viral protein synthesis were necessary to produce a competent cell for lysis by VV-CTLs. In order to further inhibit the expression of early viral proteins in infected cells, partially UV-inactivated vaccinia virus was employed to infect target cells. It was determined that L-cells infected with virus preparations which had been UV-irradiated for 90 seconds were fully competent for lysis by VV-CTLs. Cells infected with 90 second UV-irr virus expressed 3 predominant, plasma membrane associated antigens of 36-37K, 27-28K, and 19-17K. These 3 viral antigens represent the predominant membrane-associated viral antigens available for interaction with class I, major histocompatibility antigens and hence are potential target antigens for VV-CTLs

  10. Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

    Science.gov (United States)

    Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

    2015-01-01

    Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689

  11. Pärnus algavad homme Ungari kultuuripäevad / Teet Roossaar

    Index Scriptorium Estoniae

    Roossaar, Teet

    2005-01-01

    Ungari organist Miklos Teleki orelikontsertidest 3. sept. Eliisabeti kirikus ja 4. sept. Pärnu-Jaagupi kirikus ning Pärnu Linnaorkestri hooaja avakontserdist 4. sept. Pärnu kontserdimajas Ungari kultuuripäevade raames

  12. Linear Pursuit Differential Game under Phase Constraint on the State of Evader

    Directory of Open Access Journals (Sweden)

    Askar Rakhmanov

    2016-01-01

    Full Text Available We consider a linear pursuit differential game of one pursuer and one evader. Controls of the pursuer and evader are subjected to integral and geometric constraints, respectively. In addition, phase constraint is imposed on the state of evader, whereas pursuer moves throughout the space. We say that pursuit is completed, if inclusion y(t1-x(t1∈M is satisfied at some t1>0, where x(t and y(t are states of pursuer and evader, respectively, and M is terminal set. Conditions of completion of pursuit in the game from all initial points of players are obtained. Strategy of the pursuer is constructed so that the phase vector of the pursuer first is brought to a given set, and then pursuit is completed.

  13. XX rahvusvahelised trompetipäevad / Valdo Rüütelmaa

    Index Scriptorium Estoniae

    Rüütelmaa, Valdo

    2009-01-01

    17. märtsist kuni 5. aprillini Eesti Muusika- ja Teatriakadeemias toimunud rahvusvahelistest 20. trompetipäevadest, mille raames toimus 5. aprillil konkurss "Trompetitalendid 2009" . Trompetipäevade korraldaja Aavo Otsaga

  14. Tartu Kevadpäevad 2008 : Nädalajagu muusikat igale maitsele / Signe Tamberg

    Index Scriptorium Estoniae

    Tamberg, Signe

    2008-01-01

    Tartu Kevadpäevad 2008 muusikaprogrammis: 34. tudengilaulu võistlusest 29. apr. Tartu Sadamateatris, öölaulupeost 28. apr. Kassitoome orus, kontsertidest "Rokime!" 2. mail ja "Folgime" 3. mail Raekoja platsil

  15. Eesti Suusapäevad Jay Peak´is / Peeter Teedla ; fotod: Peeter Teedla

    Index Scriptorium Estoniae

    Teedla, Peeter

    2006-01-01

    märtsikuu esimesel nädalalõpul idaranniku eestlaste suusapäevad, osavõtjaid 156, paljud perekondade ja väikeste lastega, organiseerijaks Kristin Raamot. Peeti murdmaasuusatamise - ja slaalomivõistlused

  16. IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice.

    Directory of Open Access Journals (Sweden)

    Robert Schwenk

    Full Text Available The availability of a highly purified and well characterized circumsporozoite protein (CSP is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP. A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE of CS/D in combination with the Toll-Like Receptor 4 (TLR4 agonist Glucopyranosyl Lipid A (GLA/SE, or one of two TLR7/8 agonists: R848 (un-conjugated or 3M-051 (covalently conjugated. Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1/T(H2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans.

  17. Acquired transcriptional programming in functional and exhausted virus-specific CD8 T cells.

    Science.gov (United States)

    Youngblood, Ben; Wherry, E John; Ahmed, Rafi

    2012-01-01

    Failure to control viral infections such as HIV results in T-cell receptor (TCR) and inhibitory receptor driven exhaustion of antigen-specific T cells. Persistent signaling by these receptors during chronic viral infection sculpts the transcriptional regulatory programs of virus-specific T cells. The resulting gene expression profile is tailored to temper the potentially damaging effector functions of cytotoxic T cells and adapt them to an antigen-rich and inflammation-rich environment. Here we review recent studies investigating mechanisms of transcriptional regulation of effector, functional memory, and exhausted T-cell functions during acute versus chronic infections. Patterns of gene expression in virus-specific CD8 T cells are a result of a combination of pro and inhibitory signals from antigen presentation (TCR-mediated) and co-inhibitory receptor ligation (PD-1, 2B4). Further, memory-specific transcriptional regulation of 2B4 expression and signaling impose a self-limiting secondary effector response to a prolonged viral infection. Additionally, differentiation of functional memory CD8 T cells is coupled with acquisition of a repressive epigenetic program for PD-1 expression. However, chronic infection provides a signal that blocks the acquisition of these epigenetic modifications reinforcing the suppression of cytotoxic lymphocyte (CTL) functions in exhausted cells. Current findings suggest that the mechanism(s) that delineate functional memory versus exhaustion are coupled with acquisition of transcriptional programs at the effector stage of differentiation, reinforced by cessation or persistence of TCR signaling.

  18. Measuring the diaspora for virus-specific CD8+ T cells

    Science.gov (United States)

    Marshall, Dana R.; Turner, Stephen J.; Belz, Gabrielle T.; Wingo, Suzette; Andreansky, Samita; Sangster, Mark Y.; Riberdy, Janice M.; Liu, Tiebin; Tan, Ming; Doherty, Peter C.

    2001-01-01

    The CD8+ T cell diaspora has been analyzed after secondary challenge with an influenza A virus that replicates only in the respiratory tract. Numbers of DbNP366- and DbPA224-specific CD8+ T cells were measured by tetramer staining at the end of the recall response, then followed sequentially in the lung, lymph nodes, spleen, blood, and other organs. The extent of clonal expansion did not reflect the sizes of the preexisting memory T cell pools. Although the high-frequency CD8+ tetramer+ populations in the pneumonic lung and mediastinal lymph nodes fell rapidly from peak values, the “whole mouse” virus-specific CD8+ T cell counts decreased only 2-fold over the 4 weeks after infection, then subsided at a fairly steady rate to reach a plateau at about 2 months. The largest numbers were found throughout in the spleen, then the bone marrow. The CD8+DbNP366+ and CD8+DbPA224+ sets remained significantly enlarged for at least 4 months, declining at equivalent rates while retaining the nucleoprotein > acid polymerase immunodominance hierarchy characteristic of the earlier antigen-driven phase. Lowest levels of the CD69 “activation marker” were detected consistently on virus-specific CD8+ T cells in the blood, then the spleen. Those in the bone marrow and liver were intermediate, and CD69hi T cells were very prominent in the regional lymph nodes and the nasal-associated lymphoid tissue. Any population of “resting” CD8+ memory T cells is thus phenotypically heterogeneous, widely dispersed, and subject to broad homeostatic and local environmental effects irrespective of epitope specificity or magnitude. PMID:11344265

  19. Increase in serum concentrations of IgG2 and IgG4 by selenium supplementation in children with Down's syndrome.

    Science.gov (United States)

    Annerén, G; Magnusson, C G; Nordvall, S L

    1990-01-01

    In a previous study on children with Down's syndrome a reduced rate of infections was reported by their parents after the children had received six months' treatment with selenium supplements. In the present study the concentrations of the four IgG subclasses were measured in 29 of these children in samples of serum obtained before and immediately after the period of supplementation and one year after it had finished. Selenium had a significant augmentative effect on the serum concentrations of IgG2 and IgG4, but not of IgG1 and IgG3. This effect was not related to age, as among children over the age of 6 years the serum concentrations of IgG2 and IgG4 had decreased significantly one year after the treatment had been stopped. This study suggests that selenium has an immunoregulatory effect, which might be of importance in both basic research and clinical practice. PMID:2148668

  20. Native IgG2a(b) is barely antigenic to major histocompatibility complex class II-restricted T cells owing to inefficient internalization by professional antigen-presenting cells.

    Science.gov (United States)

    Bartnes, K; Hannestad, K

    2000-04-01

    Peptide epitopes derived from immunoglobulin variable regions represent tumour-specific antigens on B-cell neoplasms and can be recognized by syngeneic, major histocompatibility complex (MHC) class II-restricted T cells. Immunoglobulin peptide/MHC class II complexes may also be involved in autoimmunity and CD4+ T-cell-mediated B-cell regulation. Thus, the IgG2a(b) H-chain allopeptide gamma2a(b) 435-451 presented on I-Ad mimics the epitope implicated in herpes simplex virus-induced autoimmune stromal keratitis and is the target of T helper 1 (Th1) clones that suppress IgG2a(b) production in vivo. We here report that spleen and thymus cells constitutively present the autologous gamma2a(b) epitope to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma as a function of the animal housing conditions (specific pathogen-free or not) and the serum levels of IgG2a(b). Constitutive presentation in the spleen was predominantly performed by dendritic cells. Whereas spleen cells poorly presented native IgG2a(b) to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma, IgG2a(b) in the form of immune complexes were presented > 200-fold more efficiently owing to internalization via low-affinity FcgammaR on macrophages. The antigenicity could also be improved by homotypic aggregation and by targeting IgG2a(b) to complement receptors on the A20 B-cell lymphoma. Mice without detectable IgG2a(b)-containing immune complexes typically exhibited minimal constitutive presentation. Nevertheless, native IgG2a(b) can sensitize antigen-presenting cells in vivo, as mice that were devoid of immune complexes and carried an IgG2a(b)-producing tumour did present constitutively, even at physiological IgG2a(b) serum levels. Whereas the amounts of IgG released from most B-cell lymphomas may be too low to allow spontaneous priming of tumour-specific MHC class II-restricted T cells, administration of tumour immunoglobulin in aggregated form might improve the efficacy of idiotype vaccination.

  1. Eesti muusika päevad - üks kord aastas, kõigile / Jelena Gandshu

    Index Scriptorium Estoniae

    Gandshu, Jelena

    2008-01-01

    Muusikateadlased Jelena Gandshu ja Gerhard Lock, heliloojad Age Hirv ja Liis Jürgens 3.-10. aprillini toimunud Eesti muusika päevade kontsertidest: kinos Sõprus "Sensatsioon!!!", Kultuuritehases Polymer "Cellissimo", Estonia kontserdisaalis ERSO "Sümfoonilised hääled", Tallinna raekojas Mihkel Poll ja Oliver Kuusik, Katariina kirikus PaukenfEst, Nigulistes Jüri Reinvere autorikontsert. Järgneb

  2. Eesti Muusika Päevad 2000 : ECPNMi juhatus Tallinnas / Consuelo Diez ; interv. Evelin Kõrvits

    Index Scriptorium Estoniae

    Diez, Consuelo

    2000-01-01

    28.-30. apr. pidas Tallinnas aastakoosolekut ning külastas Eesti Muusika Päevade kontserte ECPNMi (European Conference of Promoters of New Music) juhatus. ECPNMi juhatuse liikmed räägivad uue muusika üritustest oma riikides, muljeid eesti muusika päevadelt

  3. Märtsipäevade valupisaraid peab lastele näitama / Anu Bollverk

    Index Scriptorium Estoniae

    Bollverk, Anu

    2009-01-01

    1949. aasta märtsiküüditamisele pühendatud mälestuspäevast Koeru kultuurimajas ning sealse huviteatri poolt ette kantud Herbert Lasti näidendist "Valupisarais märtsipäevad" (lavastajad Herbert Last ja Uno Aav)

  4. Why Do Firms Evade Taxes? The Role of Information Sharing and Financial Sector Outreach

    NARCIS (Netherlands)

    Beck, T.H.L.; Lin, C.; Ma, Y.

    2010-01-01

    Informality is a wide-spread phenomenon across the globe. We show that firms in countries with better information sharing systems and greater financial sector outreach evade taxes to a lesser degree, an effect that is stronger for smaller firms, firms in smaller cities and towns, and firms in

  5. Nasal-Associated Lymphoid Tissue Is a Mucosal Inductive Site for Virus-Specific Humoral and Cellular Immune Responses

    Czech Academy of Sciences Publication Activity Database

    Zuercher, A. W.; Coffin, S. E.; Thurnheer, M. CH.; Fundová, Petra; Cebra, J. J.

    2002-01-01

    Roč. 168, - (2002), s. 1796-1803 ISSN 0022-1767 Institutional research plan: CEZ:AV0Z5020903 Keywords : lymphoid tissue * virus-specific * humoral Subject RIV: EE - Microbiology, Virology Impact factor: 7.014, year: 2002

  6. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity

    NARCIS (Netherlands)

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E.; Suharti, Catarina; van Gorp, Eric C. M.; Hack, C. E.; Osterhaus, Albert D. M. E.; Groen, Jan

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  7. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity.

    NARCIS (Netherlands)

    Koraka, P.; Murgue, B.; Deparis, X.; Setiati, T.E.; Suharti, C.; Gorp, E. van; Hack, C.E.; Osterhaus, A.D.; Groen, J.

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  8. The Mexican bean beetle (Epilachna varivestis regurgitome and insights into beetle-borne virus specificity.

    Directory of Open Access Journals (Sweden)

    Cassidy R Gedling

    Full Text Available For nearly 400 million years, insects and plants have been embattled in an evolutionary arms race. Insects have developed diverse feeding strategies and behaviors in an effort to circumvent and overcome an extensive collection of plant defense tactics. Sap-sucking insects often inject saliva into hosts plants, which contains a suite of effector proteins and even microbial communities that can alter the plant's defenses. Lacking salivary glands, leaf-feeding beetles represent an interesting group of phytophagous insects. Feeding beetles regurgitate onto leaf surfaces and it is thought that these oral secretions influence insect-plant interactions and even play a role in virus-vector specificity. Since the molecular and biological makeup of the regurgitant is virtually unknown, we carried out RNA sequencing and 16S rDNA analysis on a major soybean pest, Epilachna varivestis, to generate the first ever beetle "regurgitome" and characterize its microbiome. Interestingly, the regurgitant is comprised of a rich molecular assortment of genes encoding putative extracellular proteins involved in digestion, molting, immune defense, and detoxification. By carrying out plant inoculation assays, we reinforced the fundamental role of the regurgitant in beetle-borne virus specificity. Ultimately, these studies begin to characterize the importance of regurgitant in virus transmission and beetle-plant interactions.

  9. A Potent Virus-Specific Antibody-Secreting Cell Response to Acute Enterovirus 71 Infection in Children.

    Science.gov (United States)

    Huang, Kuan-Ying Arthur; Lin, Jainn-Jim; Chiu, Cheng-Hsun; Yang, Shuan; Tsao, Kuo-Chien; Huang, Yhu-Chering; Lin, Tzou-Yien

    2015-09-01

    Enterovirus 71 (EV71) remains a leading pathogen for acute infectious diseases in children, especially in Asia. The cellular basis for establishing a virus-specific antibody response to acute EV71 infections is unclear in children. We studied the magnitude of virus-specific antibody-secreting B cells (ASCs) and its relationship with serological response, clinical parameters, and virological parameters among children with laboratory-confirmed EV71 infection. A potent EV71 genogroup B- and virus-specific ASC response was detected in the first week of illness among genotype B5 EV71-infected children. The cross-reactive EV71-specific ASC response to genogroup C viral antigens composed about 10% of the response. The EV71-specific ASC response in children aged ≥3 years produced immunoglobulin G predominantly, but immunoglobulin M was predominant in younger children. Proliferation marker was expressed by the majority of circulating ASCs in the acute phase of EV71 infection. Virus-specific ASC responses significantly correlated with throat viral load, fever duration, and serological genogroup-specific neutralization titer. The presence of a virus-specific ASC response serves an early cellular marker of an EV71-specific antibody response. Further detailed study of EV71-specific ASCs at the monoclonal level is crucial to delineate the specificity and function of antibody immunity in children. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.

    Directory of Open Access Journals (Sweden)

    Michaela Lucas

    2007-07-01

    Full Text Available CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays.Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C.During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

  11. Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.

    Science.gov (United States)

    Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A; Leen, Ann M; Hanley, Patrick J; Gottschalk, Steven M; Rooney, Cliona M; Hanson, I Celine; Krance, Robert A; Shpall, Elizabeth J; Cruz, Conrad R; Amrolia, Persis; Lucchini, Giovanna; Bunin, Nancy; Heimall, Jennifer; Klein, Orly R; Gennery, Andrew R; Slatter, Mary A; Vickers, Mark A; Orange, Jordan S; Heslop, Helen E; Bollard, Catherine M; Keller, Michael D

    2016-05-01

    Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers. We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs. Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared. Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive. VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. evad : [luuletused] / Philip Larkin ; inglise keelest tlk. Maarja Kangro

    Index Scriptorium Estoniae

    Larkin, Philip

    2007-01-01

    Sisu: Päevad ; Mitte midagi öelda ; See olgu värss ; Uurimus lugemisharjumustest ; Hommage valitsusele ; Vesi ; Vajakud ; Viige üks koju lastele ; Jutt voodis ; Kõrged aknad ; Sa jätkad elu ; Kui. Orig.: Days ; Nothing to be said ; This be the verse ; A study of reading habits ; Homage to a government ; Water ; Wants ; Take one home for the kiddies ; Talking in bed ; High windows ; Continuing to live ; If

  13. DO PENALTIES AND ENFORCEMENT MEASURES MAKE TAXPAYERS MORE COMPLIANT? THE VIEW OF AUSTRALIAN TAX EVADERS

    OpenAIRE

    Dr Ken Devos

    2013-01-01

    The tax compliance literature indicates that many factors, including, economic, social, psychological and demographic, impact upon the compliance behaviour of individual taxpayers. This study explores the relationship, if any, that exists between selected tax compliance and demographic variables and the compliance behaviour of Australian individual tax evaders. The study employed a mixed method research approach comprising both a survey and interviews. The findings revealed that tax law enfor...

  14. Polyomavirus specific cellular immunity: from BK-virus-specific cellular immunity to BK-virus-associated nephropathy ?

    Directory of Open Access Journals (Sweden)

    manon edekeyser

    2015-06-01

    Full Text Available In renal transplantation, BK-virus-associated nephropathy has emerged as a major complication, with a prevalence of 5–10% and graft loss in >50% of cases. BK-virus is a member of the Polyomavirus family and rarely induces apparent clinical disease in the general population. However, replication of polyomaviruses, associated with significant organ disease, is observed in patients with acquired immunosuppression, which suggests a critical role for virus-specific cellular immunity to control virus replication and prevent chronic disease. Monitoring of specific immunity combined with viral load could be used to individually assess the risk of viral reactivation and virus control. We review the current knowledge on BK-virus specific cellular immunity and, more specifically, in immunocompromised patients. In the future, immune-based therapies could allow us to treat and prevent BK-virus-associated nephropathy.

  15. Muusika : Jeremija nutulaulud palmipuudepühal. Jätkub "Musica Grande". Lihavõttetervitus Barcelonast. Rannap "Selges eesti helikeeles". Juba XIII trompetipäevad. III klavessiinipäevad / Jaan-Eik Tulve

    Index Scriptorium Estoniae

    Tulve, Jaan-Eik, 1967-

    2002-01-01

    Vox Clamantise kontsertidest Tartus ja Tallinnas. Jätkub sari "Musica Grande" kontsertidega Tartus ja Tallinnas pealkirjaga "Kontsertlik". Eestisse sõidab esinema üks Hispaania tippkoore Coral Cantiga Barcelonast. Rein Rannapi tänavusest suurprojektist, klaveriõhtust "Selges eesti helikeeles". 1. - 7. aprillini toimuvad EMA rahvusvahelised trompetipäevad. 4. - 7. aprillini korraldab Eesti Klavessiinisõprade Tsunft III klavessiinipäevad

  16. Multinuclear NMR study of the structure of the Fv fragment of anti-dansyl mouse IgG2a antibody

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hideo; Odaka, Asano; Matsunaga, Chigusa; Kato, Koichi; Shimada, Ichio; Arata, Yoji (Univ. of Tokyo (Japan)); Kawaminami, Shunro (Kao Corp., Tochigi (Japan))

    1991-07-02

    A multinuclear NMR study is reported of Fv, which is a minimum antigen-binding unit of immunoglobulin. Fv has been prepared by clostripain digestion of a mouse anti-dansyl IgG2a monoclonal antibody that lacks the entire C{sub H}1 domain. A variety of Fv analogues labeled with {sup 2}H in the aromatic rings and with {sup 13}C and/or {sup 15}N in the peptide bonds have been prepared and used for multinuclear NMR analyses of Fv spectra of Fv sensitively reflect the antigen binding and can be used along with {sup 1}H and {sup 13}C spectral data for the structural analyses of antigen-antibody interactions. Hydrogen-deuterium exchange of the amide protons has been folowed in the absence and presence of DNS-Lys by using the {sup 1}H-{sup 15}N shift correlation spectra. Use of the {beta}-shift observed for the carbonyl carbon resonances has also been helpful in following the hydrogen-deuterium exchange. On the basis of the NMR data obtained, the static and dynamic structure of the Fv fragment in the absence and presence of DNS-Lys has been discussed.

  17. Multinuclear NMR study of the structure of the Fv fragment of anti-dansyl mouse IgG2a antibody

    International Nuclear Information System (INIS)

    Takahashi, Hideo; Odaka, Asano; Matsunaga, Chigusa; Kato, Koichi; Shimada, Ichio; Arata, Yoji; Kawaminami, Shunro

    1991-01-01

    A multinuclear NMR study is reported of Fv, which is a minimum antigen-binding unit of immunoglobulin. Fv has been prepared by clostripain digestion of a mouse anti-dansyl IgG2a monoclonal antibody that lacks the entire C H 1 domain. A variety of Fv analogues labeled with 2 H in the aromatic rings and with 13 C and/or 15 N in the peptide bonds have been prepared and used for multinuclear NMR analyses of Fv spectra of Fv sensitively reflect the antigen binding and can be used along with 1 H and 13 C spectral data for the structural analyses of antigen-antibody interactions. Hydrogen-deuterium exchange of the amide protons has been folowed in the absence and presence of DNS-Lys by using the 1 H- 15 N shift correlation spectra. Use of the β-shift observed for the carbonyl carbon resonances has also been helpful in following the hydrogen-deuterium exchange. On the basis of the NMR data obtained, the static and dynamic structure of the Fv fragment in the absence and presence of DNS-Lys has been discussed

  18. A perfusion culture system using a stirred ceramic membrane reactor for hyperproduction of IgG2a monoclonal antibody by hybridoma cells.

    Science.gov (United States)

    Dong, Haodi; Tang, Ya-Jie; Ohashi, Ryo; Hamel, Jean-François P

    2005-01-01

    A novel perfusion culture system for efficient production of IgG2a monoclonal antibody (mAb) by hybridoma cells was developed. A ceramic membrane module was constructed and used as a cell retention device installed in a conventional stirred-tank reactor during the perfusion culture. Furthermore, the significance of the control strategy of perfusion rate (volume of fresh medium/working volume of reactor/day, vvd) was investigated. With the highest increasing rate (deltaD, vvd per day, vvdd) of perfusion rate, the maximal viable cell density of 3.5 x 10(7) cells/mL was obtained within 6 days without any limitation and the cell viability was maintained above 95%. At lower deltaD's, the cell growth became limited. Under nutrient-limited condition, the specific cell growth rate (mu) was regulated by deltaD. During the nonlimited growth phase, the specific mAb production rate (qmAb) remained constant at 0.26 +/- 0.02 pg/cell x h in all runs. During the cell growth-limited phase, qmAb was regulated by deltaD within the range of 0.25-0.65 vvdd. Under optimal conditions, qmAb of 0.80 and 2.15 pg/cell x h was obtained during the growth-limited phase and stationary phase, respectively. The overall productivity and yield were 690 mg/L x day and 340 mg/L x medium, respectively. This study demonstrated that this novel perfusion culture system for suspension mammalian cells can support high cell density and efficient mAb production and that deltaD is an important control parameter to regulate and achieve high mAb production.

  19. Virus-specific proteins in cells infected with tomato black ring nepovirus: evidence for proteolytic processing in vivo.

    OpenAIRE

    Demangeat, Gerard; Hemmer, O; Reinbolt, J; Mayo, M A; Fritsch, Coralie

    1992-01-01

    The synthesis of proteins encoded by the RNA of tomato black ring virus (TBRV) in vivo was studied in protoplasts by direct labelling with [35S]methionine, and in protoplasts and plants by immunoblotting experiments with specific antisera. Comparison of the proteins synthesized in infected and mock-inoculated protoplasts suggested that proteins of M(r) 120K, 90K, 80K, 57K and 46K were virus-specific. The proteins derived from the RNA-1-encoded polyprotein detected by immunoblotting were a sta...

  20. How type 1 fimbriae help Escherichia coli to evade extracellular antibiotics.

    Science.gov (United States)

    Avalos Vizcarra, Ima; Hosseini, Vahid; Kollmannsberger, Philip; Meier, Stefanie; Weber, Stefan S; Arnoldini, Markus; Ackermann, Martin; Vogel, Viola

    2016-01-05

    To survive antibiotics, bacteria use two different strategies: counteracting antibiotic effects by expression of resistance genes or evading their effects e.g. by persisting inside host cells. Since bacterial adhesins provide access to the shielded, intracellular niche and the adhesin type 1 fimbriae increases bacterial survival chances inside macrophages, we asked if fimbriae also influenced survival by antibiotic evasion. Combined gentamicin survival assays, flow cytometry, single cell microscopy and kinetic modeling of dose response curves showed that type 1 fimbriae increased the adhesion and internalization by macrophages. This was caused by strongly decreased off-rates and affected the number of intracellular bacteria but not the macrophage viability and morphology. Fimbriae thus promote antibiotic evasion which is particularly relevant in the context of chronic infections.

  1. The atherogenic bacterium Porphyromonas gingivalis evades circulating phagocytes by adhering to erythrocytes

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Holmstrup, Palle; Damgaard, Christian

    2011-01-01

    A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows...... the bacterium to adhere to human red blood cells (RBCs) and thereby evade attack by circulating phagocytes. On incubation with normal human serum, the P. gingivalis strain efficiently fixed complement component 3 (C3). Incubation of bacteria with washed whole blood cells suspended in autologous serum resulted...... in a dose- and time-dependent adherence to RBCs. The adherence required functionally intact complement receptor 1 (CR1; also called CD35) on the RBCs and significantly inhibited the uptake of P. gingivalis by neutrophils and B cells within 1 min of incubation (by 64% and 51%, respectively...

  2. Evading the pulsar constraints on the cosmic string tension in supergravity inflation

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Kohei [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Miyamoto, Yuhei [Tokyo Univ. (Japan). Dept. of Physics; Tokyo Univ. (JP). Research Center for the Early Universe (RESCEU); Yokoyama, Jun' ichi [Tokyo Univ. (JP). Research Center for the Early Universe (RESCEU); Tokyo Univ., Kashiwa, Chiba (JP). Inst. for the Physics and Mathematics of the Universe (IPMU)

    2012-04-15

    The cosmic string is a useful probe of the early Universe and may give us a clue to physics at high energy scales where any artificial particle accelerators cannot reach. Although one of the most promising tools is the cosmic microwave background, the constraint from gravitational waves is becoming so stringent that one may not hope to detect its signatures in the cosmic microwave background. In this paper, we construct a scenario that contains cosmic strings observable in the cosmic microwave background while evading the constraint imposed by the recent pulsar timing data. We argue that cosmic strings with relatively large tension are allowed by delaying the onset of the scaling regime. We also show that this scenario is naturally realized in the context of chaotic inflation in supergravity, where the phase transition is governed by the Hubble induced mass.

  3. Evading the pulsar constraints on the cosmic string tension in supergravity inflation

    International Nuclear Information System (INIS)

    Kamada, Kohei; Miyamoto, Yuhei; Yokoyama, Jun'ichi

    2012-04-01

    The cosmic string is a useful probe of the early Universe and may give us a clue to physics at high energy scales where any artificial particle accelerators cannot reach. Although one of the most promising tools is the cosmic microwave background, the constraint from gravitational waves is becoming so stringent that one may not hope to detect its signatures in the cosmic microwave background. In this paper, we construct a scenario that contains cosmic strings observable in the cosmic microwave background while evading the constraint imposed by the recent pulsar timing data. We argue that cosmic strings with relatively large tension are allowed by delaying the onset of the scaling regime. We also show that this scenario is naturally realized in the context of chaotic inflation in supergravity, where the phase transition is governed by the Hubble induced mass.

  4. Plasmablasts During Acute Dengue Infection Represent a Small Subset of a Broader Virus-specific Memory B Cell Pool

    Directory of Open Access Journals (Sweden)

    Ramapraba Appanna

    2016-10-01

    Full Text Available Dengue is endemic in tropical countries worldwide and the four dengue virus serotypes often co-circulate. Infection with one serotype results in high titers of cross-reactive antibodies produced by plasmablasts, protecting temporarily against all serotypes, but impairing protective immunity in subsequent infections. To understand the development of these plasmablasts, we analyzed virus-specific B cell properties in patients during acute disease and at convalescence. Plasmablasts were unrelated to classical memory cells expanding in the blood during early recovery. We propose that only a small subset of memory B cells is activated as plasmablasts during repeat infection and that plasmablast responses are not representative of the memory B cell repertoire after dengue infection.

  5. Lübecki filmipäevad 1999 ja Thomas Manni ekraniseering 1923 / Lauri Kärk

    Index Scriptorium Estoniae

    Kärk, Lauri, 1954-

    1999-01-01

    4.-7. novembrini Lübeckis toimunud Põhjamaade filmipäevade 41. Nordische Filmtage huvitavamatest filmidest, nagu Thomas Manni "Buddenbrookide" ekraniseering 1923. aastast (režissöör Gerhard Lamprecht) ja Rasmus Gerlachi dokumentaal "Operaator Kaufman" Dziga Vertovist ja tema kahest, samuti kino alal tegutsenud vennast

  6. The Small Rho GTPases Rac1 and Rac2 Are Important for T-Cell Independent Antigen Responses and for Suppressing Switching to IgG2b in Mice.

    Science.gov (United States)

    Gerasimčik, Natalija; He, Minghui; Dahlberg, Carin I M; Kuznetsov, Nikolai V; Severinson, Eva; Westerberg, Lisa S

    2017-01-01

    The Rho GTPases Cdc42, Rac1, and Rac2 coordinate receptor signaling to cell adhesion, migration, and proliferation. Deletion of Rac1 and Rac2 early during B cell development leads to failure in B cell entry into the splenic white pulp. Here, we sought to understand the role of Rac1 and Rac2 in B cell functionality and during the humoral antibody response. To circumvent the migratory deficiency of B cells lacking both Rac1 and Rac2, we took the approach to inducibly delete Rac1 in Rac2 -/- B cells in the spleen (Rac1 B Rac2 -/- B cells). Rac1 B Rac2 -/- mice had normal differentiation of splenic B cell populations, except for a reduction in marginal zone B cells. Rac1 B Rac2 -/- B cells showed normal spreading response on antibody-coated layers, while both Rac2 -/- and Rac1 B Rac2 -/- B cells had reduced homotypic adhesion and decreased proliferative response when compared to wild-type B cells. Upon challenge with the T-cell-independent antigen TNP-conjugated lipopolysaccharide, Rac1 B Rac2 -/- mice showed reduced antibody response. In contrast, in response to the T-cell-dependent antigen sheep red blood cells, Rac1 B Rac2 -/- mice had increased serum titers of IgG1 and IgG2b. During in vitro Ig class switching, Rac1 B Rac2 -/- B cells had elevated germline γ2b transcripts leading to increased Ig class switching to IgG2b. Our data suggest that Rac1 and Rac2 serve an important role in regulation of the B cell humoral immune response and in suppressing Ig class switching to IgG2b.

  7. Henipaviruses Employ a Multifaceted Approach to Evade the Antiviral Interferon Response

    Directory of Open Access Journals (Sweden)

    Megan L. Shaw

    2009-12-01

    Full Text Available Hendra and Nipah virus, which constitute the genus Henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. Similar to other paramyxoviruses, their ability to evade the host interferon (IFN response is conferred by the P gene. The henipavirus P gene encodes four proteins; the P, V, W and C proteins, which have all been described to inhibit the antiviral response. Further studies have revealed that these proteins have overlapping but unique properties which enable the virus to block multiple signaling pathways in the IFN response. The best characterized of these is the JAK-STAT signaling pathway which is targeted by the P, V and W proteins via an interaction with the transcription factor STAT1. In addition the V and W proteins can both limit virus-induced induction of IFN but they appear to do this via distinct mechanisms that rely on unique sequences in their C-terminal domains. The ability to generate recombinant Nipah viruses now gives us the opportunity to determine the precise role for each of these proteins and address their contribution to pathogenicity. Additionally, the question of whether these multiple anti-IFN strategies are all active in the different mammalian hosts for henipaviruses, particularly the fruit bat reservoir, warrants further exploration.

  8. Quantum back-action-evading measurement of motion in a negative mass reference frame

    Science.gov (United States)

    Møller, Christoffer B.; Thomas, Rodrigo A.; Vasilakis, Georgios; Zeuthen, Emil; Tsaturyan, Yeghishe; Balabas, Mikhail; Jensen, Kasper; Schliesser, Albert; Hammerer, Klemens; Polzik, Eugene S.

    2017-07-01

    Quantum mechanics dictates that a continuous measurement of the position of an object imposes a random quantum back-action (QBA) perturbation on its momentum. This randomness translates with time into position uncertainty, thus leading to the well known uncertainty on the measurement of motion. As a consequence of this randomness, and in accordance with the Heisenberg uncertainty principle, the QBA puts a limitation—the so-called standard quantum limit—on the precision of sensing of position, velocity and acceleration. Here we show that QBA on a macroscopic mechanical oscillator can be evaded if the measurement of motion is conducted in the reference frame of an atomic spin oscillator. The collective quantum measurement on this hybrid system of two distant and disparate oscillators is performed with light. The mechanical oscillator is a vibrational ‘drum’ mode of a millimetre-sized dielectric membrane, and the spin oscillator is an atomic ensemble in a magnetic field. The spin oriented along the field corresponds to an energetically inverted spin population and realizes a negative-effective-mass oscillator, while the opposite orientation corresponds to an oscillator with positive effective mass. The QBA is suppressed by -1.8 decibels in the negative-mass setting and enhanced by 2.4 decibels in the positive-mass case. This hybrid quantum system paves the way to entanglement generation and distant quantum communication between mechanical and spin systems and to sensing of force, motion and gravity beyond the standard quantum limit.

  9. Quantum back-action-evading measurement of motion in a negative mass reference frame.

    Science.gov (United States)

    Møller, Christoffer B; Thomas, Rodrigo A; Vasilakis, Georgios; Zeuthen, Emil; Tsaturyan, Yeghishe; Balabas, Mikhail; Jensen, Kasper; Schliesser, Albert; Hammerer, Klemens; Polzik, Eugene S

    2017-07-12

    Quantum mechanics dictates that a continuous measurement of the position of an object imposes a random quantum back-action (QBA) perturbation on its momentum. This randomness translates with time into position uncertainty, thus leading to the well known uncertainty on the measurement of motion. As a consequence of this randomness, and in accordance with the Heisenberg uncertainty principle, the QBA puts a limitation-the so-called standard quantum limit-on the precision of sensing of position, velocity and acceleration. Here we show that QBA on a macroscopic mechanical oscillator can be evaded if the measurement of motion is conducted in the reference frame of an atomic spin oscillator. The collective quantum measurement on this hybrid system of two distant and disparate oscillators is performed with light. The mechanical oscillator is a vibrational 'drum' mode of a millimetre-sized dielectric membrane, and the spin oscillator is an atomic ensemble in a magnetic field. The spin oriented along the field corresponds to an energetically inverted spin population and realizes a negative-effective-mass oscillator, while the opposite orientation corresponds to an oscillator with positive effective mass. The QBA is suppressed by -1.8 decibels in the negative-mass setting and enhanced by 2.4 decibels in the positive-mass case. This hybrid quantum system paves the way to entanglement generation and distant quantum communication between mechanical and spin systems and to sensing of force, motion and gravity beyond the standard quantum limit.

  10. Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

    Science.gov (United States)

    Kotagiri, Nalinikanth; Kim, Jin-Woo

    2014-01-01

    Carbon nanotubes (CNTs) have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such “stealth” CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid-based nanotheranostic agents for multiplex, multimodal molecular imaging and therapy, as well as in other applications, such as drug delivery and tissue engineering. PMID:24872705

  11. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice.

    Science.gov (United States)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S; Pushko, Peter

    2014-11-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Virus-specific regulatory T cells ameliorate encephalitis by repressing effector T cell functions from priming to effector stages.

    Directory of Open Access Journals (Sweden)

    Jingxian Zhao

    2014-08-01

    Full Text Available Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg and conventional CD4 T cells (M133 Tconv in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN. Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.

  13. Quantification of the IgG2/4 kappa Monoclonal Therapeutic Eculizumab from Serum Using Isotype Specific Affinity Purification and Microflow LC-ESI-Q-TOF Mass Spectrometry.

    Science.gov (United States)

    Ladwig, Paula M; Barnidge, David R; Willrich, Maria A V

    2017-05-01

    As therapeutic monoclonal antibodies (mAbs) become more humanized, traditional tryptic peptide approaches used to measure biologics in serum become more challenging since unique clonotypic peptides used for quantifying the mAb may also be found in the normal serum polyclonal background. An alternative approach is to monitor the unique molecular mass of the intact light chain portion of the mAbs using liquid chromatography-mass spectrometry (LC-MS). Distinguishing a therapeutic mAb from a patient's normal polyclonal immunoglobulin (Ig) repertoire is the primary limiting factor when determining the limit of quantitation (LOQ) in serum. The ability to selectively extract subclass specific Igs from serum reduces the polyclonal background in a sample. We present here the development of an LC-MS method to quantify eculizumab in serum. Eculizumab is a complement component 5 (C5) binding mAb that is fully humanized and contains portions of both IgG2 and IgG4 subclasses. Our group developed a method that uses Life Technologies CaptureSelect IgG4 (Hu) affinity matrix. We show here the ability to quantitate eculizumab with a LOQ of 5 mcg/mL by removing the higher abundance IgG1, IgG2, and IgG3 from the polyclonal background, making this approach a simple and efficient procedure. Graphical Abstract ᅟ.

  14. Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

    Directory of Open Access Journals (Sweden)

    Kotagiri N

    2014-05-01

    Full Text Available Nalinikanth Kotagiri,1–4 Jin-Woo Kim1–31Bio/Nano Technology Laboratory, Institute for Nanoscience and Engineering, 2Department of Biological and Agricultural Engineering, 3Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, AR, USA; 4Optical Radiology Laboratory, Department of Radiology, Washington University School of Medicine, St Louis, MO, USAAbstract: Carbon nanotubes (CNTs have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such "stealth" CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid

  15. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    International Nuclear Information System (INIS)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S.; Pushko, Peter

    2014-01-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA ® platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice

  16. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Jokinen, Jenny; Lukashevich, Igor S. [Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States)

    2014-11-15

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA{sup ®} platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice.

  17. Virus-specific proteins in cells infected with tomato black ring nepovirus: evidence for proteolytic processing in vivo.

    Science.gov (United States)

    Demangeat, G; Hemmer, O; Reinbolt, J; Mayo, M A; Fritsch, C

    1992-07-01

    The synthesis of proteins encoded by the RNA of tomato black ring virus (TBRV) in vivo was studied in protoplasts by direct labelling with [35S]methionine, and in protoplasts and plants by immunoblotting experiments with specific antisera. Comparison of the proteins synthesized in infected and mock-inoculated protoplasts suggested that proteins of M(r) 120K, 90K, 80K, 57K and 46K were virus-specific. The proteins derived from the RNA-1-encoded polyprotein detected by immunoblotting were a stable 120K protein and, only in protoplasts, small amounts of a 90K protein which contains the C-terminal part of the 120K protein and the polymerase domain. The results suggest that the polymerase and the adjacent protease function in vivo largely or solely when combined in a 120K protein. The proteins derived from the RNA-2-encoded polyprotein detected by immunoblotting were 59K and 57K proteins, which reacted with antiserum to TBRV particles, and a 46K protein. In extracts of infected Nicotiana clevelandii and Chenopodium quinoa made soon after inoculation, the 59K protein was more abundant than the 57K protein; later samples contained similar quantities of each protein. The 57K protein comigrated with protein extracted from virus particles. The results of amino acid sequencing suggested that the 57K protein is derived from the 59K protein by the loss of nine C-terminal amino acids. Antiserum to a peptide adjacent to the 57K protein in the 150K polyprotein detected a 46K protein in protoplasts and plant tissue. The results support the processing scheme for TBRV polyproteins proposed after analysis of the products of in vitro translation.

  18. Simple and efficient generation of virus-specific T cells for adoptive therapy using anti-4-1BB antibody.

    Science.gov (United States)

    Imahashi, Nobuhiko; Nishida, Tetsuya; Goto, Tatsunori; Terakura, Seitaro; Watanabe, Keisuke; Hanajiri, Ryo; Sakemura, Reona; Imai, Misa; Kiyoi, Hitoshi; Naoe, Tomoki; Murata, Makoto

    2015-01-01

    Although recent studies of virus-specific T-cell (VST) therapy for viral infections after allogeneic hematopoietic stem cell transplantation have shown promising results, simple and less time-intensive and labor-intensive methods are required to generate VSTs for the wider application of VST therapy. We investigated the efficacy of anti-CD28 and anti-4-1BB antibodies, which can provide T cells with costimulatory signals similar in strength to those of antigen-presenting cells, in generating VSTs. When peripheral blood mononuclear cells were stimulated with viral peptides together with isotype control, anti-CD28, or anti-4-1BB antibodies, anti-4-1BB antibodies yielded the highest numbers of VSTs, which were on an average 7.9 times higher than those generated with isotype control antibody. The combination of anti-CD28 and anti-4-1BB antibodies did not result in increased numbers of VSTs compared with anti-4-1BB antibody alone. Importantly, the positive effect of anti-4-1BB antibody was observed regardless of the epitopes of the VSTs. In contrast, the capacity of dendritic cells (DCs) to generate VSTs differed considerably depending on the epitopes of the VSTs. Furthermore, the numbers of VSTs generated with DCs were at most similar to those generated with the anti-4-1BB antibody. Generation of VSTs with anti-4-1BB antibody did not result in excessive differentiation or deteriorated function of the generated VSTs compared with those generated with control antibody or DCs. In conclusion, VSTs can be generated rapidly and efficiently by simply stimulating peripheral blood mononuclear cells with viral peptide and anti-4-1BB antibody without using antigen-presenting cells. We propose using anti-4-1BB antibody as a novel strategy to generate VSTs for adoptive therapy.

  19. Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Reis, Bernardo S.; Goes, Alfredo M.

    2007-01-01

    Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

  20. Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)]. E-mail: estefaniabio@yahoo.com.br; antero@cdtn.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia]. E-mail: brsgarbi@mono.icb.ufmg.br; goes@mono.icb.ufmg.br

    2007-07-01

    Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

  1. Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function

    Directory of Open Access Journals (Sweden)

    Brendan E. Russ

    2017-12-01

    Full Text Available Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs, we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+ chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation.

  2. Evading the top-quark mass bound at the Fermilab Tevatron: New signals for the top quark

    International Nuclear Information System (INIS)

    Mukhopadhyaya, B.; Nandi, S.

    1991-01-01

    If an SU(2)-singlet charge-2/3 quark exists, current data allow a wide range for the parameters of the 4x4 mixing matrix in which the usual ''hard-lepton'' signal of the top quark is suppressed. For a light Higgs boson, the top quark decays predominantly via the flavor-changing Yukawa interaction, thus evading the Fermilab Tevatron bounds on its mass. For a heavier Higgs boson, flavor-changing neutral-current decays become important, giving rise to anomalous Z-pair production, testable at the upgraded Tevetron, at the CERN Large Hardon Collider, and at the Superconducting Super Collider

  3. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Torpey, D.J. III

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

  4. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Torpey, D.J. III.

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with 51 Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant

  5. Testing the ability of viral haemorrhagic septicaemia virus to evade the protective immune response induced in rainbow trout by DNA vaccination

    DEFF Research Database (Denmark)

    Sepulveda, Dagoberto; Lorenzen, Niels

    2013-01-01

    , this work aims to evaluate whether VHSV is able to evade the protective immune response induced by the DNA vaccination. Earlier studies have demonstrated that VHSV can evade the neutralizing effect of monoclonal antibodies by mutations in the glycoprotein gene. One approach of the present study is therefore...... to try to isolate VHSV variants which can escape the neutralizing activity of serum from fish immunized with the DNA vaccine. To do so, a highly pathogenic VHSV isolate (DK3592B) will be repeatedly passaged in fish cell cultures in the presence of neutralizing fish serum. Another approach comprises...

  6. 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

  7. 47-mG2a: A Mouse IgG2a-Type of PcMab-47 Useful for Detecting Podocalyxin in Esophageal Cancers by Immunohistochemistry.

    Science.gov (United States)

    Kaneko, Mika K; Itai, Shunsuke; Yamada, Shinji; Kato, Yukinari

    2018-04-09

    Esophageal cancer is one of the highly malignant cancers. It comprises two of the most common histological tumor types: squamous cell carcinoma (SCC) and adenocarcinoma. SCC accounts for about 90% of esophageal cancers. Despite developments in treatment strategies, the prognosis and survival rate remain poor. Podocalyxin (PODXL) is a highly glycosylated type-I transmembrane protein. It is expressed in normal tissues such as kidney, heart, breast, and pancreas. Upregulation of PODXL correlates with tumor progression, invasion, and metastasis. Therefore, this glycoprotein could be a potential biomarker for predicting the prognosis of some cancers, for instance, brain, colorectal, oral, lung, bladder, prostate, and ovarian cancers. We previously developed a specific and sensitive anti-PODXL monoclonal antibody (mAb), PcMab-47 (mouse IgG 1 , kappa) and its mouse IgG 2a -type (47-mG 2a ). We showed their utility in immunohistochemical analysis of oral cancers. Herein, we demonstrate that PcMab-47 and 47-mG 2a can also be used to detect esophageal squamous cell carcinoma (ESCC) with this technique. These two antibodies, respectively, stained 123/130 (94.6%) and 127/130 (97.7%) ESCC cases, indicating that they can detect PODXL with high sensitivity in this carcinoma. Of more than 3+ cases, 47-mG 2a was more effective than PcMab-47, respectively, staining 56/127 (44.1%) and 41/123 (33.3%). Therefore, 47-mG 2a can be used for the detection of PODXL in ESCC using immunohistochemical analysis.

  8. Muusikamaailm : Arvo Pärdi uus teos. Telemanni päevad Magdeburgis. Uus orkester Soomes. Ingvar Lidholm 80. Auhindu ja preemiaid / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2001-01-01

    21. veebr. tuli Oxfordis maailmaesiettekandele A. Pärdi teos "Littlemore Tractus". Telemanni päevade raames toimuvast rahvusvahelisest kammeransamblite konkursist Magdeburgis. O. Mustonen asutas Helsingis uue orkestri. Lühidalt I.Lidholmi tegevusest ja loomingust. P. Norgaardile ja H. von Manen'ile antud autasust ja preemiast

  9. Muusikamaailm : Festivalil Schwetzingenis. Ellingtoni sajandi tähistamine. Linz saab uue ooperimaja. Isaac Stern viiulita Saksamaal. Muusikapäevad Luksemburgis / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    30. apr.-7. juunini toimuvast muusikafestivalist Schwetzingenis. D. Ellingtoni 100. sünniaastapäeva tähistamisest maailmas. Valmis Linzi uue ooperimaja planeering. I. Stern juhatas kümnepäevast seminari Kölni Kõrgema Muusikakooli juures. Rahvusvahelise Nüüdismuusika Ühingu (ISCM) iga-aastased maailma muusikapäevad toimuvad 2000. aastal Luksemburgis

  10. Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2014-01-01

    Full Text Available Hepatitis B virus (HBV persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1. Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1 interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV, therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients.

  11. Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells

    International Nuclear Information System (INIS)

    Zinkernagel, R.M.

    1982-01-01

    The proposal was tested that (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras expressed predominantly P1-restricted T cells because donor derived stem cells were exposed to recipient derived antigen-presenting cells in the thymus. Because P1 recipient-derived antigen-presenting cells are replaced only slowly after 6-8 wk by (P1 X P2) donor-derived antigen-presenting cells in the thymus and because replenished pools of mature T cells may by then prevent substantial numbers of P2-restricted T cells to be generated, a large portion of thymus cells and mature T cells were eliminated using the following treatments of 12-20-wk-old (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras: (a) cortisone plus antilymphocyte serum, (b) Cytoxan, (c) three doses of sublethal irradiation (300 rad) 2d apart, and (d) lethal irradiation (850 rad) and reconstitution with T cell-depleted (P1 X P2) F1 stem cells. 12-20 wk after this second treatment, (P1 X P2) leads to P1 chimeras were infected with vaccinia-virus. Virus-specific cytotoxic T cell reactivity was expressed by chimeric T cells of (P1 X P[2) F1 origin and was restricted predominantly to P1. Virus-specific cytotoxic T cells, therefore, do not seem to be selected to measurable extent by the immigrating donor-derived antigen-presenting cells in the thymus; their selection depends apparently from the recipient-derived radioresistant thymus cells

  12. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Leen, Ann M; Bollard, Catherine M; Mendizabal, Adam M; Shpall, Elizabeth J; Szabolcs, Paul; Antin, Joseph H; Kapoor, Neena; Pai, Sung-Yun; Rowley, Scott D; Kebriaei, Partow; Dey, Bimalangshu R; Grilley, Bambi J; Gee, Adrian P; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E

    2013-06-27

    Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2% -96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-related adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035.

  13. The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

    Energy Technology Data Exchange (ETDEWEB)

    Hoenen, Antje [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Gillespie, Leah [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia); Morgan, Garry; Heide, Peter van der [Institute for Molecular Bioscience, University of Queensland, Brisbane (Australia); Khromykh, Alexander [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Australian Infectious Diseases Research Centre, University of Queensland, Brisbane (Australia); Mackenzie, Jason, E-mail: jason.mackenzie@unimelb.edu.au [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia)

    2014-01-05

    Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition.

  14. Cooperative option of pursuit game with two pursuers and one evader. A strong stability of division variety

    Directory of Open Access Journals (Sweden)

    Viktor D. Shiryayev

    2017-06-01

    Full Text Available Introduction: The article deals with a simple differential game on the plane of pursuit with two consistently active players and one evader E; the game is considered in the form of the characteristic function. Materials and Methods: The geometric constructions and methods are used for solving the problem. The security zone of the escapee is bounded by the Apollonius circle, the pursuit team uses a strategy of parallel approach. Results: A method of finding the optimal players strategies and the optimal players’ trajectory is proposed. The way of forming the characteristic function is provided. All the variety of division is considered as a solution. However, the use of the results of cooperative theory of differential games is impossible without solving the problems associated with the specifics of differential equations of motion. Foremost, it is the problem of dynamic stability of optimality principles. The article introduces an auxiliary function of making the redistribution of winnings in time, keeping his total winnings throughout the game. The dynamic stability of the cooperative solution is determined with the help of this function. Strong dynamic stability of the entire set of solutions is shown. Discussion and Conclusions: The obtained results are consistent with similar research of other authors. Further research in this field can be used in the development of methods for “regularization” of optimality principles, for which the condition of dynamic stability is always fulfilled.

  15. Pasteurella pneumotropica evades the human complement system by acquisition of the complement regulators factor H and C4BP.

    Directory of Open Access Journals (Sweden)

    Alfredo Sahagún-Ruiz

    Full Text Available Pasteurella pneumotropica is an opportunist Gram negative bacterium responsible for rodent pasteurellosis that affects upper respiratory, reproductive and digestive tracts of mammals. In animal care facilities the presence of P. pneumotropica causes severe to lethal infection in immunodeficient mice, being also a potential source for human contamination. Indeed, occupational exposure is one of the main causes of human infection by P. pneumotropica. The clinical presentation of the disease includes subcutaneous abscesses, respiratory tract colonization and systemic infections. Given the ability of P. pneumotropica to fully disseminate in the organism, it is quite relevant to study the role of the complement system to control the infection as well as the possible evasion mechanisms involved in bacterial survival. Here, we show for the first time that P. pneumotropica is able to survive the bactericidal activity of the human complement system. We observed that host regulatory complement C4BP and Factor H bind to the surface of P. pneumotropica, controlling the activation pathways regulating the formation and maintenance of C3-convertases. These results show that P. pneumotropica has evolved mechanisms to evade the human complement system that may increase the efficiency by which this pathogen is able to gain access to and colonize inner tissues where it may cause severe infections.

  16. Escape and evade control policies for ensuring the physical security of nonholonomic, ground-based, unattended mobile sensor nodes

    Science.gov (United States)

    Mascarenas, David; Stull, Christopher; Farrar, Charles

    2011-06-01

    In order to realize the wide-scale deployment of high-endurance, unattended mobile sensing technologies, it is vital to ensure the self-preservation of the sensing assets. Deployed mobile sensor nodes face a variety of physical security threats including theft, vandalism and physical damage. Unattended mobile sensor nodes must be able to respond to these threats with control policies that facilitate escape and evasion to a low-risk state. In this work the Precision Immobilization Technique (PIT) problem has been considered. The PIT maneuver is a technique that a pursuing, car-like vehicle can use to force a fleeing vehicle to abruptly turn ninety degrees to the direction of travel. The abrupt change in direction generally causes the fleeing driver to lose control and stop. The PIT maneuver was originally developed by law enforcement to end vehicular pursuits in a manner that minimizes damage to the persons and property involved. It is easy to imagine that unattended autonomous convoys could be targets of this type of action by adversarial agents. This effort focused on developing control policies unattended mobile sensor nodes could employ to escape, evade and recover from PIT-maneuver-like attacks. The development of these control policies involved both simulation as well as small-scale experimental testing. The goal of this work is to be a step toward ensuring the physical security of unattended sensor node assets.

  17. The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release

    Science.gov (United States)

    Escudero, Claudia A.; Lazo, Oscal M.; Galleguillos, Carolina; Parraguez, Jose I.; Lopez-Verrilli, Maria A.; Cabeza, Carolina; Leon, Luisa; Saeed, Uzma; Retamal, Claudio; Gonzalez, Alfonso; Marzolo, Maria-Paz; Carter, Bruce D.; Court, Felipe A.; Bronfman, Francisca C.

    2014-01-01

    ABSTRACT The p75 neurotrophin receptor (p75, also known as NGFR) is a multifaceted signalling receptor that regulates neuronal physiology, including neurite outgrowth, and survival and death decisions. A key cellular aspect regulating neurotrophin signalling is the intracellular trafficking of their receptors; however, the post-endocytic trafficking of p75 is poorly defined. We used sympathetic neurons and rat PC12 cells to study the mechanism of internalisation and post-endocytic trafficking of p75. We found that p75 internalisation depended on the clathrin adaptor protein AP2 and on dynamin. More surprisingly, p75 evaded the lysosomal route at the level of the early endosome, instead accumulating in two different types of endosomes, Rab11-positive endosomes and multivesicular bodies (MVBs) positive for CD63, a marker of the exosomal pathway. Consistently, depolarisation by KCl induced the liberation of previously endocytosed full-length p75 into the extracellular medium in exosomes. Thus, p75 defines a subpopulation of MVBs that does not mature to lysosomes and is available for exosomal release by neuronal cells. PMID:24569882

  18. Uudised : Üheteistkümnendad trompetipäevad. Eesti Muusikanõukogus. Tüüri "Motus I" Londonis / Kadri Ruudi

    Index Scriptorium Estoniae

    Ruudi, Kadri

    2000-01-01

    4.-15. apr. toimuvad EMA XI trompetipäevad. 14.-19. märtsil viibis Eestis IMC asepresident F. Müller-Heuser, 22. märtsil toimus EMN juhatuse koosolek. 19. märtsil andis Londoni South Bank Centre'is kontserdi P. Carneiro, kes tõi Inglismaal esiettekandele ka E.-S. Tüüri teose "Motus I"

  19. The elicitin-like glycoprotein, ELI025, is secreted by the pathogenic oomycete Pythium insidiosum and evades host antibody responses.

    Directory of Open Access Journals (Sweden)

    Tassanee Lerksuthirat

    Full Text Available Pythium insidiosum is a unique oomycete that can infect humans and animals. Patients with a P. insidiosum infection (pythiosis have high rates of morbidity and mortality. The pathogen resists conventional antifungal drugs. Information on the biology and pathogenesis of P. insidiosum is limited. Many pathogens secrete proteins, known as effectors, which can affect the host response and promote the infection process. Elicitins are secretory proteins and are found only in the oomycetes, primarily in Phytophthora and Pythium species. In plant-pathogenic oomycetes, elicitins function as pathogen-associated molecular pattern molecules, sterol carriers, and plant defense stimulators. Recently, we reported a number of elicitin-encoding genes from the P. insidiosum transcriptome. The function of elicitins during human infections is unknown. One of the P. insidiosum elicitin-encoding genes, ELI025, is highly expressed and up-regulated at body temperature. This study aims to characterize the biochemical, immunological, and genetic properties of the elicitin protein, ELI025. A 12.4-kDa recombinant ELI025 protein (rELI025 was expressed in Escherichia coli. Rabbit anti-rELI025 antibodies reacted strongly with the native ELI025 in P. insidiosum's culture medium. The detected ELI025 had two isoforms: glycosylated and non-glycosylated. ELI025 was not immunoreactive with sera from pythiosis patients. The region near the transcriptional start site of ELI025 contained conserved oomycete core promoter elements. In conclusion, ELI025 is a small, abundant, secreted glycoprotein that evades host antibody responses. ELI025 is a promising candidate for development of diagnostic and therapeutic targets for pythiosis.

  20. A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro

    NARCIS (Netherlands)

    E.G.M. Berkhoff (Eufemia); A.C.M. Boon (Adrianus); N.J. Nieuwkoop; R.A.M. Fouchier (Ron); K. Sintnicolaas (Krijn); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2004-01-01

    textabstractViruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus

  1. EST: Evading Scientific Text.

    Science.gov (United States)

    Ward, Jeremy

    2001-01-01

    Examines chemical engineering students' attitudes to text and other parts of English language textbooks. A questionnaire was administered to a group of undergraduates. Results reveal one way students get around the problem of textbook reading. (Author/VWL)

  2. Evading the Boomerang Effect

    DEFF Research Database (Denmark)

    Laursen, Keld; Moreira, Solon; Reichstein, Toke

    2017-01-01

    Technology licensing agreements potentially can create future appropriability problems. Drawing on the appropriability literature, we argue that the inclusion of a grant-back clause in technology licensing agreements is an attempt to balance the gains from and protection of the focal firms’ techn...

  3. Evading the CKM Hierarchy

    International Nuclear Information System (INIS)

    Brodsky, Stanley J.

    2001-01-01

    We show that the presence of intrinsic charm in the hadrons' light-cone wave functions, even at a few percent level, provides new, competitive decay mechanisms for B decays which are nominally CKM-suppressed. For example, the weak decays of the B-meson to two-body exclusive states consisting of strange plus light hadrons, such as B → π K, are expected to be dominated by penguin contributions since the tree-level b → s u bar u decay is CKM suppressed However, higher Fock states in the B wave function containing charm quark pairs can mediate the decay via a CKM-favored b → s cbar c tree-level transition. Such intrinsic charm contributions can be phenomenologically significant. Since they mimic the amplitude structure of ''charming'' penguin contributions, charming penguins need not be penguins at all

  4. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

    Science.gov (United States)

    Cruz, Conrad Russell Y; Micklethwaite, Kenneth P; Savoldo, Barbara; Ramos, Carlos A; Lam, Sharon; Ku, Stephanie; Diouf, Oumar; Liu, Enli; Barrett, A John; Ito, Sawa; Shpall, Elizabeth J; Krance, Robert A; Kamble, Rammurti T; Carrum, George; Hosing, Chitra M; Gee, Adrian P; Mei, Zhuyong; Grilley, Bambi J; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Bollard, Catherine M; Dotti, Gianpietro

    2013-10-24

    Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

  5. Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study

    Directory of Open Access Journals (Sweden)

    Washington Parks Robyn

    2001-07-01

    Full Text Available Abstract Background HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. Methods For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. Results Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. Conclusions These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development.

  6. Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium

    Science.gov (United States)

    Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

    2016-01-01

    Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01–24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

  7. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells.

    Science.gov (United States)

    Withers, Barbara; Blyth, Emily; Clancy, Leighton E; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J; Micklethwaite, Kenneth P; Gottlieb, David J

    2017-11-14

    Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8 + terminal effector cells. PD-1 expression was elevated on CD8 + lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8 + effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

  8. Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application

    OpenAIRE

    Sun, Jiali; Huye, Leslie E; Lapteva, Natalia; Mamonkin, Maksim; Hiregange, Manasa; Ballard, Brandon; Dakhova, Olga; Raghavan, Darshana; Durett, April G; Perna, Serena K; Omer, Bilal; Rollins, Lisa A; Leen, Ann M; Vera, Juan F; Dotti, Gianpietro

    2015-01-01

    Background Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al. in a previous clinical trial with CD19.CAR-modified VSTs, but there was ...

  9. HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.

    Science.gov (United States)

    Ahmed, Nabil; Brawley, Vita; Hegde, Meenakshi; Bielamowicz, Kevin; Kalra, Mamta; Landi, Daniel; Robertson, Catherine; Gray, Tara L; Diouf, Oumar; Wakefield, Amanda; Ghazi, Alexia; Gerken, Claudia; Yi, Zhongzhen; Ashoori, Aidin; Wu, Meng-Fen; Liu, Hao; Rooney, Cliona; Dotti, Gianpietro; Gee, Adrian; Su, Jack; Kew, Yvonne; Baskin, David; Zhang, Yi Jonathan; New, Pamela; Grilley, Bambi; Stojakovic, Milica; Hicks, John; Powell, Suzanne Z; Brenner, Malcolm K; Heslop, Helen E; Grossman, Robert; Wels, Winfried S; Gottschalk, Stephen

    2017-08-01

    Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients VSTs (1 × 106/m2 to 1 × 108/m2) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma

  10. Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Kállay, Krisztián; Kassa, Csaba; Réti, Marienn; Karászi, Éva; Sinkó, János; Goda, Vera; Stréhn, Anita; Csordás, Katalin; Horváth, Orsolya; Szederjesi, Attila; Tasnády, Szabolcs; Hardi, Apor; Kriván, Gergely

    2018-04-01

    Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

  11. Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

    Directory of Open Access Journals (Sweden)

    K.P. Nickerson

    2018-05-01

    Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer

  12. Cross-border reproductive care for law evasion: should physicians be allowed to help infertility patients evade the law of their own country?

    Science.gov (United States)

    Van Hoof, Wannes; Pennings, Guido; De Sutter, Petra

    2016-07-01

    There are fundamental differences between countries with regard to legislation on assisted reproduction. Many infertility patients are looking to evade the law of their own country and make use of reproductive services abroad. The role of the local physician in cross-border reproductive care for law evasion has been characterized as "channeling local patients to foreign medical establishments" and "against the spirit and essence of the law". The logical view is that by supporting CBRC for law evasion, physicians are essentially supporting immoral behavior. We will tackle this position on two levels. First, we will argue that governments should generally be tolerant toward people with different positions on assisted reproduction. Second, we will show that contributing to cross-border reproductive care for law evasion is not necessarily immoral, because the prima facie wrongness of complicity in law evasion can be outweighed by the fact that physicians should act in the best interest of the patient. Several countries have tried to prevent local physicians from helping patients to make use of reproductive services abroad, but they should rather leave it up to the individual physicians to decide whether or not to support a particular patient. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Hõimupäevad 2004

    Index Scriptorium Estoniae

    2004-01-01

    Näitusi: Tallinna Pedagoogikaülikooli Akadeemilises Raamatukogus Eesti Kunstiakadeemia ekspeditsiooninäitus "Seto' täämbä" 12. X-13. XI. Obinitsas kontor-galeriis "Hal'as kunn" Vladimir Nagovitsõni näitus "Põhja-Udmurdi jumalad" 12. X-1. XI. E. Vilde ja A. H. Tammsaare memoriaalmuuseumis Valt Ernshtreidi ja Zane Graudina fotonäitus "Inter/rational" 13. X-1. XI. Eesti Rahva Muuseumi Näitustemajas näitus "Pruudi-vara" (kuraator Svetlana Karm, kujundaja Jane Liiv)15. X-31. XII

  14. Evading the joint decision trap

    DEFF Research Database (Denmark)

    Stenbæk, Jørgen; Jensen, Mads Christian Dagnis

    2016-01-01

    spending level. In addition, the external environment with the fiscal and economic crisis created a momentum for reduced expenditures. Those against the reduction, the member states in favour of agriculture and cohesion, were not able to avoid cutbacks. Member states in favour of the cohesion policy faced...

  15. Preparation of the Fv fragment from a short-chain mouse IgG2a anti-dansyl monoclonal antibody and use of selectively deuterated Fv analogues for two-dimensional 1H NMR analyses fo the antigen-antibody interactions

    International Nuclear Information System (INIS)

    Takahashi, Hideo; Igarashi, Takako; Shimada, Ichio; Arata, Yoji

    1991-01-01

    The Fv fragment, a univalent antigen-binding unit with a molecular weight of 25,000, has successfully been prepared in high yield by limited proteolysis with clostripain of a short-chain mouse IgG2a anti-dansyl monoclonal antibody in which the entire C H 1 domain is deleted. The Fv fragment obtained is stable at room temperature and retains its full antigen-binding capability. It has been shown that selective deuterium labeling of the Fv fragment, which is half the size of the Fab fragment, provides 1 H NMR spectral data at a sufficient resolution for a detailed structural analysis of the antigen-combining site. NOESY spectra of an Fv analogue, in which all aromatic protons except for His C2'-H and Tyr C3',5'-H had been deuterated, were measured in the presence of varying amounts of dansyl-L-lysine. On the basis of the NOESY data obtained, it was possible to assign all the ring proton resonances for the dansly group that is bound to the Fv fragment. It was also possible to obtain information about His and Tyr residues of the Fv fragment in the absence and presence of the antigen. On the basis of the NMR data obtained, the authors have shown that at least two Tyr residues along with one of the amide groups are directly involved in antigen binding. The mode of interaction of the dansyl ring with these residues in the Fv fragment has briefly been discussed

  16. Preparation of the Fv fragment from a short-chain mouse IgG2a anti-dansyl monoclonal antibody and use of selectively deuterated Fv analogues for two-dimensional sup 1 H NMR analyses fo the antigen-antibody interactions

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hideo; Igarashi, Takako; Shimada, Ichio; Arata, Yoji (Univ. of Tokyo (Japan))

    1991-03-19

    The Fv fragment, a univalent antigen-binding unit with a molecular weight of 25,000, has successfully been prepared in high yield by limited proteolysis with clostripain of a short-chain mouse IgG2a anti-dansyl monoclonal antibody in which the entire C{sub H}1 domain is deleted. The Fv fragment obtained is stable at room temperature and retains its full antigen-binding capability. It has been shown that selective deuterium labeling of the Fv fragment, which is half the size of the Fab fragment, provides {sup 1}H NMR spectral data at a sufficient resolution for a detailed structural analysis of the antigen-combining site. NOESY spectra of an Fv analogue, in which all aromatic protons except for His C2{prime}-H and Tyr C3{prime},5{prime}-H had been deuterated, were measured in the presence of varying amounts of dansyl-L-lysine. On the basis of the NOESY data obtained, it was possible to assign all the ring proton resonances for the dansly group that is bound to the Fv fragment. It was also possible to obtain information about His and Tyr residues of the Fv fragment in the absence and presence of the antigen. On the basis of the NMR data obtained, the authors have shown that at least two Tyr residues along with one of the amide groups are directly involved in antigen binding. The mode of interaction of the dansyl ring with these residues in the Fv fragment has briefly been discussed.

  17. Burkholderia pseudomallei Evades Nramp1 (Slc11a1- and NADPH Oxidase-Mediated Killing in Macrophages and Exhibits Nramp1-Dependent Virulence Gene Expression

    Directory of Open Access Journals (Sweden)

    Veerachat Muangsombut

    2017-08-01

    Full Text Available Bacterial survival in macrophages can be affected by the natural resistance-associated macrophage protein 1 (Nramp1; also known as solute carrier family 11 member a1 or Slc11a1 which localizes to phagosome membranes and transports divalent cations, including iron. Little is known about the role of Nramp1 in Burkholderia infection, in particular whether this differs for pathogenic species like Burkholderia pseudomallei causing melioidosis or non-pathogenic species like Burkholderia thailandensis. Here we show that transfected macrophages stably expressing wild-type Nramp1 (Nramp1+ control the net replication of B. thailandensis, but not B. pseudomallei. Control of B. thailandensis was associated with increased cytokine responses, and could be abrogated by blocking NADPH oxidase-mediated production of reactive oxygen species but not by blocking generation of reactive nitrogen species. The inability of Nramp1+ macrophages to control B. pseudomallei was associated with rapid escape of bacteria from phagosomes, as indicated by decreased co-localization with LAMP1 compared to B. thailandensis. A B. pseudomallei bipB mutant impaired in escape from phagosomes was controlled to a greater extent than the parent strain in Nramp1+ macrophages, but was also attenuated in Nramp1− cells. Consistent with reduced escape from phagosomes, B. thailandensis formed fewer multinucleated giant cells in Nramp1+ macrophages at later time points compared to B. pseudomallei. B. pseudomallei exhibited elevated transcription of virulence-associated genes of Type VI Secretion System cluster 1 (T6SS-1, the Bsa Type III Secretion System (T3SS-3 and the bimA gene required for actin-based motility in Nramp1+ macrophages. Nramp1+ macrophages were found to contain decreased iron levels that may impact on expression of such genes. Our data show that B. pseudomallei is able to evade Nramp1- and NADPH oxidase-mediated killing in macrophages and that expression of virulence

  18. Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

    Directory of Open Access Journals (Sweden)

    Galia Ramírez-Toloza

    2017-09-01

    Full Text Available American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68, T. cruzi complement regulatory protein (TcCRP, trypomastigote decay-accelerating factor (T-DAF, C2 receptor inhibitor trispanning (CRIT and T. cruzi calreticulin (TcCRT. Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH and plasma membrane-derived vesicles (PMVs. All these proteins inhibit different steps of the classical (CP, alternative (AP or lectin pathways (LP. Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host

  19. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.

    Science.gov (United States)

    Tzannou, Ifigeneia; Papadopoulou, Anastasia; Naik, Swati; Leung, Kathryn; Martinez, Caridad A; Ramos, Carlos A; Carrum, George; Sasa, Ghadir; Lulla, Premal; Watanabe, Ayumi; Kuvalekar, Manik; Gee, Adrian P; Wu, Meng-Fen; Liu, Hao; Grilley, Bambi J; Krance, Robert A; Gottschalk, Stephen; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E; Leen, Ann M; Omer, Bilal

    2017-11-01

    Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.

  20. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections

    OpenAIRE

    Hua, Rong-Hong; Chen, Na-Sha; Qin, Cheng-Feng; Deng, Yong-Qiang; Ge, Jin-Ying; Wang, Xi-Jun; Qiao, Zu-Jian; Chen, Wei-Ye; Wen, Zhi-Yuan; Liu, Wen-Xin; Hu, Sen; Bu, Zhi-Gao

    2010-01-01

    Abstract Background Differential diagnose of Japanese encephalitis virus (JEV) infection from other flavivirus especially West Nile virus (WNV) and Dengue virus (DV) infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. Results To map the epitopes on the P...

  1. Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application.

    Science.gov (United States)

    Sun, Jiali; Huye, Leslie E; Lapteva, Natalia; Mamonkin, Maksim; Hiregange, Manasa; Ballard, Brandon; Dakhova, Olga; Raghavan, Darshana; Durett, April G; Perna, Serena K; Omer, Bilal; Rollins, Lisa A; Leen, Ann M; Vera, Juan F; Dotti, Gianpietro; Gee, Adrian P; Brenner, Malcolm K; Myers, Douglas G; Rooney, Cliona M

    2015-01-01

    Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al. in a previous clinical trial with CD19.CAR-modified VSTs, but there was little apparent expansion of these cells in patients. In that study, VSTs were gene-modified on day 19 of culture and we hypothesized that by this time, sufficient T-cell differentiation may have occurred to limit the subsequent proliferative capacity of the transduced T-cells. To facilitate the clinical testing of this hypothesis in a project supported by the NHLBI-PACT mechanism, we developed and optimized a good manufacturing practices (GMP) compliant method for the early transduction of VSTs directed to Epstein-Barr virus (EBV), Adenovirus (AdV) and cytomegalovirus (CMV) using a CAR directed to the tumor-associated antigen disialoganglioside (GD2). Ad-CMVpp65-transduced EBV-LCLs effectively stimulated VSTs directed to all three viruses (triVSTs). Transduction efficiency on day three was increased in the presence of cytokines and high-speed centrifugation of retroviral supernatant onto retronectin-coated plates, so that under optimal conditions up to 88% of tetramer-positive VSTs expressed the GD2.CAR. The average transduction efficiency of early-and late transduced VSTs was 55 ± 4% and 22 ± 5% respectively, and early-transduced VSTs maintained higher frequencies of T cells with central memory or intermediate memory phenotypes. Early-transduced VSTs also had higher proliferative capacity and produced higher levels of TH1 cytokines IL-2, TNF-α, IFN-γ, MIP-1α, MIP-1β and other cytokines in vitro. We developed a rapid and GMP compliant method for the early transduction of

  2. Evolution of Soybean mosaic virus-G7 molecularly cloned genome in Rsv1-genotype soybean results in emergence of a mutant capable of evading Rsv1-mediated recognition

    International Nuclear Information System (INIS)

    Hajimorad, M.R.; Eggenberger, A.L.; Hill, J.H.

    2003-01-01

    Plant resistance (R) genes direct recognition of pathogens harboring matching avirluent signals leading to activation of defense responses. It has long been hypothesized that under selection pressure the infidelity of RNA virus replication together with large population size and short generation times results in emergence of mutants capable of evading R-mediated recognition. In this study, the Rsv1/Soybean mosaic virus (SMV) pathosystem was used to investigate this hypothesis. In soybean line PI 96983 (Rsv1), the progeny of molecularly cloned SMV strain G7 (pSMV-G7) provokes a lethal systemic hypersensitive response (LSHR) with up regulation of a defense-associated gene transcript (PR-1). Serial passages of a large population of the progeny in PI 96983 resulted in emergence of a mutant population (vSMV-G7d), incapable of provoking either Rsv1-mediated LSHR or PR-1 protein gene transcript up regulation. An infectious clone of the mutant (pSMV-G7d) was synthesized whose sequences were very similar but not identical to the vSMV-G7d population; however, it displayed a similar phenotype. The genome of pSMV-G7d differs from parental pSMV-G7 by 17 substitutions, of which 10 are translationally silent. The seven amino acid substitutions in deduced sequences of pSMV-G7d differ from that of pSMV-G7 by one each in P1 proteinase, helper component-proteinase, and coat protein, respectively, and by four in P3. To the best of our knowledge, this is the first demonstration in which experimental evolution of a molecularly cloned plant RNA virus resulted in emergence of a mutant capable of evading an R-mediated recognition

  3. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections

    Directory of Open Access Journals (Sweden)

    Liu Wen-Xin

    2010-09-01

    Full Text Available Abstract Background Differential diagnose of Japanese encephalitis virus (JEV infection from other flavivirus especially West Nile virus (WNV and Dengue virus (DV infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. Results To map the epitopes on the PrM/M protein, we designed a set of 20 partially overlapping fragments spanning the whole PrM, fused them with GST, and expressed them in an expression vector. Linear epitope M14 (105VNKKEAWLDSTKATRY120 was detected by enzyme-linked immunosorbent assay (ELISA. By removing amino acid residues individually from the carboxy and amino terminal of peptide M14, we confirmed that the minimal unit of the linear epitope of PrM/M was M14-13 (108KEAWLDSTKAT118. This epitope was highly conserved across different JEV strains. Moreover, this epitope did not cross-react with WNV-positive and DENV-positive sera. Conclusion Epitope M14-13 was a JEV specific lineal B-cell epitpe. The results may provide a useful basis for the development of epitope-based virus specific diagnostic clinical techniques.

  4. how to evade the immune system?

    Indian Academy of Sciences (India)

    HCV usually induces robust immune responses, but it frequently escapes the immune defense to establish persistent infection. The fact that HCV exists as an evolving quasispecies plays an important role in the selection of escape mutants. Furthermore, several viral proteins interfere with cellular functions, in particular, ...

  5. Maipäevad Dessaus / Maimu Berg

    Index Scriptorium Estoniae

    Berg, Maimu, 1945-

    1989-01-01

    Moekunstnike loomingulisest seminarist, mida juhendas professor ja vabakutseline kunstnik Bodo Müller, Dessaus Bauhausi hoones (Tallinnast osalesid Maimu Berg ja kunstnik Kristel Leedjärv); Bauhausi ajaloost

  6. Tallinna Merepäevade turismikonverents

    Index Scriptorium Estoniae

    2012-01-01

    13. juulil Lennusadama angaarides toimunud turismikonverentsist "Lennukad ideed Lennusadamas", kus esinesid Tallinna abilinnapea Taavi Aas, Tallinna Sadama ärisuunajuht Ahto Ader, müügijuht Aare Maurer, EHTE arenduse ja uuringute osakonna juhataja Ain Hinsberg, kes rääkis projektist "Cultural Tourism 2011", Tallinna Lennujaama juhatuse esimees Rein Loik, Lennusadama tegevjuht Ott Sarapuu

  7. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  8. 134 original article prevalence of rubella virus-specific ...

    African Journals Online (AJOL)

    boaz

    ABSTRACT. Background: Rubella is a self-limiting disease that causes congenital rubella syndrome (CRS) when rubella virus (RV) infects women in the first trimester of pregnancy. Objective: To assess a population of pregnant women attending antenatal clinics in two tertiary hospitals in southwestern. Nigeria for anti-RV ...

  9. Evading the Lyth bound in hybrid natural inflation

    International Nuclear Information System (INIS)

    Hebecker, A.; Kraus, S.C.; Westphal, Alexander

    2013-05-01

    Generically, the gravitational-wave or tensor-mode contribution to the primordial curvature spectrum of inflation is tiny if the field-range of the inflaton is much smaller than the Planck scale. We show that this pessimistic conclusion is naturally avoided in a rather broad class of small-field models. More specifically, we consider models where an axion-like shift symmetry keeps the inflaton potential flat (up to non-perturbative cosine-shaped modulations), but inflation nevertheless ends in a waterfall-regime, as is typical for hybrid inflation. In such hybrid natural inflation scenarios (examples are provided by Wilson line inflation and fluxbrane inflation), the slow-roll parameter ε can be sizable during an early period (relevant for the CMB spectrum). Subsequently, ε quickly becomes very small before the tachyonic instability eventually terminates the slow-roll regime. In this scenario, one naturally generates a considerable tensor-mode contribution in the curvature spectrum, collecting nevertheless the required amount of e-foldings during the final period of inflation. While non-observation of tensors by Planck is certainly not a problem, a discovery in the medium to long term future is realistic.

  10. Evading the Lyth bound in hybrid natural inflation

    Science.gov (United States)

    Hebecker, A.; Kraus, S. C.; Westphal, A.

    2013-12-01

    Generically, the gravitational-wave or tensor-mode contribution to the primordial curvature spectrum of inflation is tiny if the field range of the inflaton is much smaller than the Planck scale. We show that this pessimistic conclusion is naturally avoided in a rather broad class of small-field models. More specifically, we consider models where an axionlike shift symmetry keeps the inflaton potential flat (up to nonperturbative cosine-shaped modulations), but inflation nevertheless ends in a waterfall regime, as is typical for hybrid inflation. In such hybrid natural inflation scenarios (examples are provided by Wilson line inflation and fluxbrane inflation), the slow-roll parameter ɛ can be sizable during an early period (relevant for the cosmic microwave background spectrum). Subsequently, ɛ quickly becomes very small before the tachyonic instability eventually terminates the slow-roll regime. In this scenario, one naturally generates a considerable tensor-mode contribution in the curvature spectrum, collecting nevertheless the required amount of e-foldings during the final period of inflation. While nonobservation of tensors by Planck is certainly not a problem, a discovery in the medium- to long-term future is realistic.

  11. Ungari päevad vabaõhumuuseumis / Tõnu Kalvet

    Index Scriptorium Estoniae

    Kalvet, Tõnu

    2002-01-01

    Kuie koolimajas avati Ibolya Bereczki ja Mária Káldy koostatud näitus "Laste maailm Ungaris". Väljas on fotod, mänguasjad jm., tutvustati ungari mänguasju. Sassi-Jaani talu õues õpetati looduslikest materjalidest lelude tegemist jm

  12. Piiskop Platoni viimased päevad / Anton Laar

    Index Scriptorium Estoniae

    Laar, Anton, 1885-1933

    2009-01-01

    Taastrükk EAÕK häälekandja Uus Elu 1919. aasta teises numbris avaldatud piiskop Platoni lähema kaasteenija preester Anton Laari sissevaatest Püha Platoni viimastesse päevadesse, tema vangistusse ja hukkamisse

  13. Single Trial Probability Applications: Can Subjectivity Evade Frequency Limitations?

    Directory of Open Access Journals (Sweden)

    David Howden

    2009-10-01

    Full Text Available Frequency probability theorists define an event’s probability distribution as the limit of a repeated set of trials belonging to a homogeneous collective. The subsets of this collective are events which we have deficient knowledge about on an individual level, although for the larger collective we have knowledge its aggregate behavior. Hence, probabilities can only be achieved through repeated trials of these subsets arriving at the established frequencies that define the probabilities. Crovelli (2009 argues that this is a mistaken approach, and that a subjective assessment of individual trials should be used instead. Bifurcating between the two concepts of risk and uncertainty, Crovelli first asserts that probability is the tool used to manage uncertain situations, and then attempts to rebuild a definition of probability theory with this in mind. We show that such an attempt has little to gain, and results in an indeterminate application of entrepreneurial forecasting to uncertain decisions—a process far-removed from any application of probability theory.

  14. Filmipäevad lõpetas "Magnus" / Kristiina Davidjants

    Index Scriptorium Estoniae

    Davidjants, Kristiina, 1974-

    2008-01-01

    Eesti filmipäevadel Kinomajas autasustas Eesti Kinoliit aastapreemiaga Sulev Keeduse dokumentaalfilmi "Jonathan Austraaliast" ja noorte- ja tudengifilmi auhinna sai Vanalinna hariduskolleegiumi teatriklassi noorte film "Pablo ja Tiiu". Näidati ka kohtutõkendi alust Kadri Kõusaare filmi "Magnus"

  15. Rewarding quality teaching in higher education: the evading dream ...

    African Journals Online (AJOL)

    Teaching, and specifically quality teaching, has for many centuries been the defining characteristic of the academic profession. However, since the dawning of the 20th century, it seems that the very basis of the global higher education institutional reward system is the belief that working with, contributing to, and pursuing ...

  16. CovertCast: Using Live Streaming to Evade Internet Censorship

    Directory of Open Access Journals (Sweden)

    McPherson Richard

    2016-07-01

    Full Text Available We design, implement, and evaluate CovertCast, a censorship circumvention system that broadcasts the content of popular websites in real-time, encrypted video streams on common live-streaming services such as YouTube. CovertCast does not require any modifications to the streaming service and employs the same protocols, servers, and streaming software as any other user of the service. Therefore, CovertCast cannot be distinguished from other live streams by IP address filtering or protocol fingerprinting, raising the bar for censors.

  17. Climate Policy: Stop Wanting to Pay to Evade Our Responsibilities

    International Nuclear Information System (INIS)

    Billette de Villemeur, Etienne; Leroux, Justin

    2016-01-01

    We explore an alternative to existing economic instruments to tackle climate change: carbon liabilities. Such liabilities would hold countries responsible for future climate damage to the tune of their emissions over time. The prospect of having to repay this carbon debt over time is enough to discipline emitters, leading to the efficient emissions level. Contrary to existing instruments, our scheme does not rest on a consensus regarding the discount factor nor about climate forecasts; this, together with its reliance on observed damage, allows for better international participation and leads to a fairer division of costs and risks

  18. Valge klaasi päevad Haapsalus / Merle Kannus

    Index Scriptorium Estoniae

    Kannus, Merle

    2005-01-01

    III rahvusvaheline kuuma klaasi sümpoosion 16.-23. VII ja näitus kuni 14. VIII Evald Okase muuseumis. Sümpoosioni kõrval korraldati 14. VII klaasimaali päev lastele, Rait Prääts avas isikunäituse "Klaasist majad" Viie Risti galeriis, bulgaarlased Lachezar Dochev ja Ventseslav Danev esinesid paarisnäitusega kultuurikeskuses, leedulane Remigius Kriukas esitas klaasist paberipresse Kuke galeriis, Erki ja Merle Kannus seadsid interaktiivse heliinstallatsiooni "Ood reisijatele" raudteejaama perroonile

  19. eVADE: Volcanic Ash Detection Raman LIDAR, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Volcanic ash is a significant hazard to aircraft engine and electronics and has caused damage to unwary aircraft and disrupted air travel for thousands of travelers,...

  20. Mechanisms by which Porphyromonas gingivalis evades innate immunity.

    Directory of Open Access Journals (Sweden)

    Kaveh Abdi

    Full Text Available The oral cavity is home to unique resident microbial communities whose interactions with host immunity are less frequently studied than those of the intestinal microbiome. We examined the stimulatory capacity and the interactions of two oral bacteria, Porphyromonas gingivalis (P. gingivalis and Fusobacterium nucleatum (F. nucleatum, on Dendritic Cell (DC activation, comparing them to the effects of the well-studied intestinal microbe Escherichia coli (E. coli. Unlike F. nucleatum and E. coli, P. gingivalis failed to activate DCs, and in fact silenced DC responses induced by F. nucleatum or E. coli. We identified a variant strain of P. gingivalis (W50 that lacked this immunomodulatory activity. Using biochemical approaches and whole genome sequencing to compare the two substrains, we found a point mutation in the hagA gene. This protein is though to be involved in the alteration of the PorSS/gingipain pathway, which regulates protein secretion into the extracellular environment. A proteomic comparison of the secreted products of the two substrains revealed enzymatic differences corresponding to this phenotype. We found that P. gingivalis secretes gingipain(s that inactivate several key proinflammatory mediators made by DCs and/or T cells, but spare Interleukin-1 (IL-1 and GM-CSF, which can cause capillary leaks that serve as a source of the heme that P. gingivalis requires for its survival, and GM-CSF, which can cause epithelial-cell growth. Taken together, our results suggest that P. gingivalis has evolved potent mechanisms to modulate its virulence factors and dampen the innate immune response by selectively inactivating most proinflammatory cytokines.

  1. Premium Motorsi priimad päevad / Raigo Neudorf

    Index Scriptorium Estoniae

    Neudorf, Raigo

    2007-01-01

    Automüüja Premium Motors on edu saavutanud luksusmaasturi Hummer ning teiste USA eksklusiivsete automarkide müügiõigusega. Tabel: Rentaabel äri. Vt. samas: Palun kaks roosat Hummerit; Premium Motors hakkab sügisel Hiina maastureid müüma.

  2. Demokraatliku fundamentalismi rasked päevad / Mele Pesti

    Index Scriptorium Estoniae

    Pesti, Mele, 1979-

    2006-01-01

    Autor uuris Kopenhaagenis ja Arhusis taanlaste ja Taanis elavate moslemite arusaamu Muhamedist, sõnavabadusest ja elust Taanis. Intervjuu Taani moslemite tähtsaima juhi imaam Ahmed Abu Labaniga, kes autori sõnul on nn. Muhamedi-loo rahvusvahelisele tasemele viimise taga

  3. How Current Android Malware Seeks to Evade Automated Code Analysis

    OpenAIRE

    Rasthofer , Siegfried; Asrar , Irfan; Huber , Stephan; Bodden , Eric

    2015-01-01

    Part 4: Challenges of Security and Reliability; International audience; First we report on a new threat campaign, underway in Korea, which infected around 20,000 Android users within two months. The campaign attacked mobile users with malicious applications spread via different channels, such as email attachments or SMS spam. A detailed investigation of the Android malware resulted in the identification of a new Android malware family Android/BadAccents. The family represents current state-of...

  4. Evading the Lyth bound in hybrid natural inflation

    Energy Technology Data Exchange (ETDEWEB)

    Hebecker, A.; Kraus, S.C. [Heidelberg Univ. (Germany). Inst. fuer Theoretische Physik; Westphal, Alexander [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany). Theory Group

    2013-05-15

    Generically, the gravitational-wave or tensor-mode contribution to the primordial curvature spectrum of inflation is tiny if the field-range of the inflaton is much smaller than the Planck scale. We show that this pessimistic conclusion is naturally avoided in a rather broad class of small-field models. More specifically, we consider models where an axion-like shift symmetry keeps the inflaton potential flat (up to non-perturbative cosine-shaped modulations), but inflation nevertheless ends in a waterfall-regime, as is typical for hybrid inflation. In such hybrid natural inflation scenarios (examples are provided by Wilson line inflation and fluxbrane inflation), the slow-roll parameter {epsilon} can be sizable during an early period (relevant for the CMB spectrum). Subsequently, {epsilon} quickly becomes very small before the tachyonic instability eventually terminates the slow-roll regime. In this scenario, one naturally generates a considerable tensor-mode contribution in the curvature spectrum, collecting nevertheless the required amount of e-foldings during the final period of inflation. While non-observation of tensors by Planck is certainly not a problem, a discovery in the medium to long term future is realistic.

  5. Birma vaiksed päevad / Vaclav Havel

    Index Scriptorium Estoniae

    Havel, Václav, 1936-2011

    2007-01-01

    Endine Tšehhi president heidab seoses Birmas kujunenud olukorraga rahvusvahelisele üldsusele ette tegutsematust ning küsib: kuidas on võimalik, et rahvusvaheline üldsus on võimetu veenma Birma sõjaväelisi juhte, et nood ei eskaleeriks jõudu, mille nad on Yangonis valla päästnud?

  6. Evading direct dark matter detection in Higgs portal models

    Energy Technology Data Exchange (ETDEWEB)

    Arcadi, Giorgio [Max Planck Institut für Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany); Gross, Christian, E-mail: christian.gross@helsinki.fi [Department of Physics and Helsinki Institute of Physics, Gustaf Hällströmin katu 2, FI-00014 Helsinki (Finland); Lebedev, Oleg [Department of Physics and Helsinki Institute of Physics, Gustaf Hällströmin katu 2, FI-00014 Helsinki (Finland); Pokorski, Stefan [Institute of Theoretical Physics, University of Warsaw, Pasteura 5, PL-02-093 Warsaw (Poland); Toma, Takashi [Physik-Department T30d, Technische Universität München, James-Franck-Straße, D-85748 Garching (Germany)

    2017-06-10

    Many models of Higgs portal Dark Matter (DM) find themselves under pressure from increasingly tight direct detection constraints. In the framework of gauge field DM, we study how such bounds can be relaxed while retaining the thermal WIMP paradigm. When the hidden sector gauge symmetry is broken via the Higgs mechanism, the hidden sector generally contains unstable states which are lighter than dark matter. These states provide DM with an efficient annihilation channel. As a result, the DM relic abundance and the direct detection limits are controlled by different parameters, and the two can easily be reconciled. This simple setup realizes the idea of “secluded” dark matter naturally.

  7. Maailma parimad näevad vaeva motiveerimisega / Harry Tuul

    Index Scriptorium Estoniae

    Tuul, Harry

    2011-01-01

    Rahvusvahelises juhtimiskonsultatsiooni ettevõttes Hay Group ja majandusajakirjas Fortune töötavad Tom McMullen, Mel Stark ning Mark Royal jõudsid oma artiklis Rewards-program effectiveness: What makes the world's Most Admired Companies great? järeldusele, et oluline pole niivõrd tasustamispõhimõtete ülesehitus, kuivõrd nende rakendamine ja tööshoidmine. Diagrammid

  8. Marine biofilm bacteria evade eukaryotic predation by targeted chemical defense.

    Directory of Open Access Journals (Sweden)

    Carsten Matz

    Full Text Available Many plants and animals are defended from predation or herbivory by inhibitory secondary metabolites, which in the marine environment are very common among sessile organisms. Among bacteria, where there is the greatest metabolic potential, little is known about chemical defenses against bacterivorous consumers. An emerging hypothesis is that sessile bacterial communities organized as biofilms serve as bacterial refuge from predation. By testing growth and survival of two common bacterivorous nanoflagellates, we find evidence that chemically mediated resistance against protozoan predators is common among biofilm populations in a diverse set of marine bacteria. Using bioassay-guided chemical and genetic analysis, we identified one of the most effective antiprotozoal compounds as violacein, an alkaloid that we demonstrate is produced predominately within biofilm cells. Nanomolar concentrations of violacein inhibit protozoan feeding by inducing a conserved eukaryotic cell death program. Such biofilm-specific chemical defenses could contribute to the successful persistence of biofilm bacteria in various environments and provide the ecological and evolutionary context for a number of eukaryote-targeting bacterial metabolites.

  9. Epigenetic age analysis of children who seem to evade aging.

    Science.gov (United States)

    Walker, Richard F; Liu, Jia Sophie; Peters, Brock A; Ritz, Beate R; Wu, Timothy; Ophoff, Roel A; Horvath, Steve

    2015-05-01

    We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other such cases exist, and if so, whether aging is actually slowed. Of seven children characterized by dramatically slow developmental rates, five also had associated disorders displayed by the first case. All of the identified subjects were female. To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as "epigenetic clock" based on DNA methylation levels. No statistically significant differences in chronological and epigenetic ages were detected in any of the newly discovered cases.

  10. Strategies of the protozoan parasite Entamoeba histolytica to evade ...

    Indian Academy of Sciences (India)

    Unknown

    the innate immune responses of intestinal epithelial cells ... metabolically active eukaryotic cells and display anti- bacterial activity ..... and TLR4 in inflammatory bowel disease; Infect. Immun. .... which contains a beta2 integrin motif; Mol. Biol.

  11. Strategies of the protozoan parasite Entamoeba histolytica to evade ...

    Indian Academy of Sciences (India)

    Unknown

    and the subsequent migration of the amoeba to the liver where abscesses are formed (Espinosa-Cantellano and. Martinez-Paloma 2000; Stanley 2001). ..... activity of bacterial peroxiredoxins; Nature (London) 407. 211–215. Cario E and Podolsky D K 2000 Differential alteration in intes- tinal epithelial cell expression of ...

  12. Louis Kahni Päevad Kuressaares / Ingrid Mald-Villand

    Index Scriptorium Estoniae

    Mald-Villand, Ingrid

    2006-01-01

    6.-7. oktoobril toimunud üritustest, millega tähistati arhitekt Louis Kahni 105. sünniaastapäeva ja eesti inseneri August Komendanti 100. sünniaastapäeva. 6. oktoobril alustati arhitekti portree avamisega, mille oli maalinud tütar Alexandra Tyng, sama päeva õhtul avati näitus Kahni loomingust Kuressaare lossis ja linnateatris esitleti Nathaniel Kahni dokumentaalfilmi "My architect". 7. oktoobril peeti rahvusvaheline arhitektuurikonverents

  13. Opalescence of an IgG2 monoclonal antibody solution as it relates to liquid-liquid phase separation.

    Science.gov (United States)

    Mason, Bruce D; Zhang, Le; Remmele, Richard L; Zhang, Jifeng

    2011-11-01

    Opalescence for a monoclonal antibody solution was systematically studied with respect to temperature, protein concentration, ionic strength (using KCl), and pH conditions. Multiple techniques, including measurement of light scattering at 90° and transmission, Tyndall test, and microscopy, were deployed to examine the opalescence behavior. Near the vicinity of the critical point on the liquid-liquid coexistence curve in the temperature-protein concentration phase diagram, the enhanced concentration fluctuations significantly contributed to the critical opalescence evidently by formation of small liquid droplets. Furthermore, our data confirm that away from the critical point, the opalescence behavior is related to the antibody self-association (agglomeration) caused by the attractive antibody-antibody interactions. As expected, at a pH near the pI of the antibody, the solution became less opalescent as the ionic strength increased. However, at a pH below the pI, the opalescence of the solution became stronger, reached a maximum, and then began to drop as the ionic strength further increased. The change in the opalescence correlated well with the trends of protein-protein interactions revealed by the critical temperature from the liquid-liquid phase separation. Copyright © 2011 Wiley-Liss, Inc.

  14. Opção e evasão de um curso de graduação em enfermagem: percepção de estudantes evadidos Opción y evasión de un curso de grado en enfermería: percepción de estudiantes evadidos Option and evasion of a bachelor's degree programme in nursing: evaded students' perception

    Directory of Open Access Journals (Sweden)

    Jamila Geri Tomaschewski Barlem

    2012-06-01

    demostrado la necesidad de un mayor énfasis en la difusión de conocimientos sobre el trabajo de enfermería, áreas de práctica y sus atribuciones.Qualitative study, developed in a Federal University in southern Brazil, aiming to know the motives for choosing and evading a Bachelor's degree programme in Nursing, in the evaded students´ perception. The data were collected through a questionnaire sent by e-mail to 19 evaded students. The 9 questionnaires that returned were submitted to Qualitative Textual Analysis, and two categories emerged: motives to opt for the nursing programme and motives to evade from the nursing programme. The results showed that the option for the programme is associated to personal vocation, perception of Nursing as a profession of care, and its closeness to the health area. Evasion seems to be related to passing the first option of undergraduate programme, ignorance about the profession, financial difficulties, and professional depreciation. We demonstrated that greater emphasis should be put on promoting knowledge about the nursing work, areas of activity and attributions.

  15. Dengue Virus Specific Immune Response: Implications for laboratory diagnosis and vaccine development

    NARCIS (Netherlands)

    P. Koraka (Penelope)

    2007-01-01

    textabstractDengue viruses (DENV 1-4) belong to the family Flaviviridae, genus Flavivirus. They are transmitted to humans through the bite of infected mosquitoes of the Aedes species. An estimated 100 million people are annually infected with DENV and over two billion people are at risk in

  16. Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease.

    Science.gov (United States)

    Middeldorp, Jaap M

    2015-01-01

    Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

  17. Radioimmunoassay for the detection of virus-specific IgA antibodies in saliva

    International Nuclear Information System (INIS)

    Friedman, M.G.

    1982-01-01

    The use of a sensitive and versatile radioimmunoassay (RIA) for detection of mumps-specific IgA and measles-specific IgA in unconcentrated saliva samples is described. The samples were obtained either by expectoration or by swabbing of the oral cavity, with or without stimulation of secretion, and were inactivated and clarified before testing. Mumps-specific IgA antibodies were detected as early as one day after onset of illness and peaked at 1-2 weeks after onset. Measles-specific salivary IgA antibodies were detected in 15-month old children 2-3 weeks after immunization. These results suggest that the RIA technique may be useful for early diagnosis of viral infections and for confirmation of response to immunization without the need for a blood sample, as well as for the study of the secretory immune response in very young and older subjects. (Auth.)

  18. Virus-specific cytotoxic T cells in chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Shibayama, Haruna; Imadome, Ken-Ichi; Onozawa, Erika; Tsuzura, Akiho; Miura, Osamu; Koyama, Takatoshi; Arai, Ayako

    2017-01-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a disease characterized by clonally proliferating and activated EBV-infected T or NK cells accompanied by chronic inflammation and T- or NK-cell neoplasms. However, the mechanism for developing CAEBV has not been clarified to date. Because the decreased number or inactivation of EBV-specific cytotoxic T lymphocytes (CTLs) resulted in the development of EBV-positive B-cell neoplasms, we investigated the number of CTLs in CAEBV patients using the tetrameric complexes of HLA-restricted EBV-specific peptides. Among the seven patients examined, EBV-specific CTLs were detected in the peripheral blood mononuclear cells (PBMCs) of four cases but were not detected in three cases. The ratio of EBV-specific CTLs in PBMCs tended to be higher in the patients with active disease than in those with inactive disease. In two patients in whom EBV-specific CTLs had not been detected, CTLs appeared after the eradication of EBV-infected T cells by allogeneic bone marrow transplantation. These results suggested that the failure of CTLs had a role in developing CAEBV, although the induction number and function of EBV-specific CTLs might vary in each patient.

  19. Virus-Specific Differences in Rates of Disease during the 2010 Dengue Epidemic in Puerto Rico

    Science.gov (United States)

    Sharp, Tyler M.; Hunsperger, Elizabeth; Santiago, Gilberto A.; Muñoz-Jordan, Jorge L.; Santiago, Luis M.; Rivera, Aidsa; Rodríguez-Acosta, Rosa L.; Gonzalez Feliciano, Lorenzo; Margolis, Harold S.; Tomashek, Kay M.

    2013-01-01

    Background Dengue is a potentially fatal acute febrile illness (AFI) caused by four mosquito-transmitted dengue viruses (DENV-1–4) that are endemic in Puerto Rico. In January 2010, the number of suspected dengue cases reported to the passive dengue surveillance system exceeded the epidemic threshold and an epidemic was declared soon after. Methodology/Principal Findings To characterize the epidemic, surveillance and laboratory diagnostic data were compiled. A suspected case was a dengue-like AFI in a person reported by a health care provider with or without a specimen submitted for diagnostic testing. Laboratory-positive cases had: (i) DENV nucleic acid detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in an acute serum specimen; (ii) anti-DENV IgM antibody detected by ELISA in any serum specimen; or (iii) DENV antigen or nucleic acid detected in an autopsy-tissue specimen. In 2010, a total of 26,766 suspected dengue cases (7.2 per 1,000 residents) were identified, of which 46.6% were laboratory-positive. Of 7,426 RT-PCR-positive specimens, DENV-1 (69.0%) and DENV-4 (23.6%) were detected more frequently than DENV-2 (7.3%) and DENV-3 (Puerto Rico in the late 1960's. This epidemic re-emphasizes the need for more effective primary prevention interventions to reduce the morbidity and mortality of dengue. PMID:23593526

  20. Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

    Directory of Open Access Journals (Sweden)

    Adiba Isa

    2005-12-01

    Full Text Available Human parvovirus B19 (B19 is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously.The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low.This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

  1. Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Human parvovirus B19 (B19 is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS: The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low. CONCLUSION: This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

  2. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

    Science.gov (United States)

    Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

    2018-06-01

    The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Establishment and characterization of Epstein-Barr virus-specific human CD4+ T lymphocyte clones

    International Nuclear Information System (INIS)

    Honda, S.; Okuno, K.; Yasutomi, M.; Takasaki, T.; Kurane, I.

    1998-01-01

    We developed a simple method for establishing Epstein-Barr virus (EBV)-specific, human CD4+ T cell clones. The method originates from our experience that the regression of cell growth in in vitro EBV transformation of B cells occurs when round lymphoid cells appear in the culture. Peripheral blood mononuclear cells were cultured with EBV; and IL-2 (20 U/ml) was added to the culture on day 17 after the virus addition. The phenotype of the growing cells was CD3+ , CD4+ , and CD8-. The cells were cytotoxic for autologous lymphoblastoid B cell line (LCL) and EBV-super-infected autologous LCL. The cytotoxic T lymphocytes (CTLs) were confirmed to be CD4+ T cells but not CD8+ T cells in the culture. CTL clones were established by a limiting dilution method. All the CTL clones had the phenotype of CD3+ , CD4+ and CD8-, and proliferated in response to autologous LCL. They produced interferon (IFN)-gamma, interleukin 2 (IL-2) and tumour necrosis factor (TNF)-beta but not IL-4. All but one clone responded to both autologous, EBV-super-infected and non-super-infected LCLs. Proliferative and cytotoxic responses to allogeneic LCLs were heterogeneous. These results suggest that this method induces heterogeneous, EBV-specific CD4+ CTL clones and is useful for analysis of CD4+ T cells in EBV infections. (authors)

  4. Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

    DEFF Research Database (Denmark)

    Patch, J.R.; Pedersen, Lasse Eggers; Toka, F.N.

    2011-01-01

    Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus (FMDV), which infects cloven-hoofed animals including large and small ruminants and swine. Current vaccine...... cytopathic virus. Here, we have used recombinant human adenovirus vectors as a means of delivering FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that impaired processing of the FMDV capsid would enhance cytolytic activity, presumably by targeting all proteins for degradation...... and effectively increasing the class I MHC/FMDV peptide concentration for stimulation of a CTL response. We compared such a T cell targeting vaccine with the parental vaccine, previously shown to effectively induce a neutralizing antibody response. Our results show induction of FMDV-specific CD8(+) CTL killing...

  5. Prolonged activation of virus-specific CD8+T cells after acute B19 infection

    DEFF Research Database (Denmark)

    Isa, Adiba; Kasprowicz, Victoria; Norbeck, Oscar

    2005-01-01

    BACKGROUND: Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS......: The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia......, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function...

  6. Antiviral effects of herpes simplex virus specific anti-sense nucleic acids.

    Science.gov (United States)

    Cantin, E M; Podsakoff, G; Willey, D E; Openshaw, H

    1992-01-01

    We have targeted mRNA sequences encompassing the translation initiation codon of the essential herpes simplex virus type 1 (HSV-1) IE3 gene with three kinds of anti-sense molecule. Addition of a 15mer oligodeoxyribonucleoside methylphosphonate to tissue culture cells resulted in suppression of viral replication. HSV-1 replication was also inhibited in cultured cells containing anti-sense vectors expressing transcripts complementary to the IE3 mRNA. We have also constructed a ribozyme which upon base pairing with the target IE3 mRNA induces cleavage at the predicted GUC site. A major obstacle to anti-sense studies in animals is drug delivery of preformed antisense molecules to ganglionic neurons, the site of HSV latency and reactivation. We speculate as to how this may be accomplished through carrier compounds which are taken up by nerve terminals and transported by retrograde axoplasmic flow. By the same route, HSV itself may be used as an anti-sense vector.

  7. Virus genetic variations and evade from immune system, the present influenza challenges: review article

    Directory of Open Access Journals (Sweden)

    Shahla Shahsavandi

    2015-10-01

    Full Text Available The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to viral vaccine can be achieved by using adjuvant. The ability of biological molecular adjuvant such as cytokines, interlukines, and bacterial derivatives to improve the immunogenicity of vaccines as a novel strategy is under evaluation, however, and immune system regulator proteins have additional considerations.

  8. The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.

    Directory of Open Access Journals (Sweden)

    Tamding Wangdi

    2014-08-01

    Full Text Available Salmonella enterica serovar Typhi (S. Typhi causes typhoid fever, a disseminated infection, while the closely related pathogen S. enterica serovar Typhimurium (S. Typhimurium is associated with a localized gastroenteritis in humans. Here we investigated whether both pathogens differ in the chemotactic response they induce in neutrophils using a single-cell experimental approach. Surprisingly, neutrophils extended chemotactic pseudopodia toward Escherichia coli and S. Typhimurium, but not toward S. Typhi. Bacterial-guided chemotaxis was dependent on the presence of complement component 5a (C5a and C5a receptor (C5aR. Deletion of S. Typhi capsule biosynthesis genes markedly enhanced the chemotactic response of neutrophils in vitro. Furthermore, deletion of capsule biosynthesis genes heightened the association of S. Typhi with neutrophils in vivo through a C5aR-dependent mechanism. Collectively, these data suggest that expression of the virulence-associated (Vi capsular polysaccharide of S. Typhi obstructs bacterial-guided neutrophil chemotaxis.

  9. Pseudomonas Evades Immune Recognition of Flagellin in Both Mammals and Plants

    Science.gov (United States)

    Bardoel, Bart W.; van der Ent, Sjoerd; Pel, Michiel J. C.; Tommassen, Jan; Pieterse, Corné M. J.; van Kessel, Kok P. M.; van Strijp, Jos A. G.

    2011-01-01

    The building blocks of bacterial flagella, flagellin monomers, are potent stimulators of host innate immune systems. Recognition of flagellin monomers occurs by flagellin-specific pattern-recognition receptors, such as Toll-like receptor 5 (TLR5) in mammals and flagellin-sensitive 2 (FLS2) in plants. Activation of these immune systems via flagellin leads eventually to elimination of the bacterium from the host. In order to prevent immune activation and thus favor survival in the host, bacteria secrete many proteins that hamper such recognition. In our search for Toll like receptor (TLR) antagonists, we screened bacterial supernatants and identified alkaline protease (AprA) of Pseudomonas aeruginosa as a TLR5 signaling inhibitor as evidenced by a marked reduction in IL-8 production and NF-κB activation. AprA effectively degrades the TLR5 ligand monomeric flagellin, while polymeric flagellin (involved in bacterial motility) and TLR5 itself resist degradation. The natural occurring alkaline protease inhibitor AprI of P. aeruginosa blocked flagellin degradation by AprA. P. aeruginosa aprA mutants induced an over 100-fold enhanced activation of TLR5 signaling, because they fail to degrade excess monomeric flagellin in their environment. Interestingly, AprA also prevents flagellin-mediated immune responses (such as growth inhibition and callose deposition) in Arabidopsis thaliana plants. This was due to decreased activation of the receptor FLS2 and clearly demonstrated by delayed stomatal closure with live bacteria in plants. Thus, by degrading the ligand for TLR5 and FLS2, P. aeruginosa escapes recognition by the innate immune systems of both mammals and plants. PMID:21901099

  10. Pseudomonas syringae evades host immunity by degrading flagellin monomers with alkaline protease AprA

    NARCIS (Netherlands)

    Pel, Michiel J C; van Dijken, Anja J H; Bardoel, Bart W; Seidl, Michael F; van der Ent, Sjoerd; van Strijp, Jos A G; Pieterse, Corné M J

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of

  11. Pseudomonas evades immune recognition of flagellin in both mammals and plants.

    Directory of Open Access Journals (Sweden)

    Bart W Bardoel

    2011-08-01

    Full Text Available The building blocks of bacterial flagella, flagellin monomers, are potent stimulators of host innate immune systems. Recognition of flagellin monomers occurs by flagellin-specific pattern-recognition receptors, such as Toll-like receptor 5 (TLR5 in mammals and flagellin-sensitive 2 (FLS2 in plants. Activation of these immune systems via flagellin leads eventually to elimination of the bacterium from the host. In order to prevent immune activation and thus favor survival in the host, bacteria secrete many proteins that hamper such recognition. In our search for Toll like receptor (TLR antagonists, we screened bacterial supernatants and identified alkaline protease (AprA of Pseudomonas aeruginosa as a TLR5 signaling inhibitor as evidenced by a marked reduction in IL-8 production and NF-κB activation. AprA effectively degrades the TLR5 ligand monomeric flagellin, while polymeric flagellin (involved in bacterial motility and TLR5 itself resist degradation. The natural occurring alkaline protease inhibitor AprI of P. aeruginosa blocked flagellin degradation by AprA. P. aeruginosa aprA mutants induced an over 100-fold enhanced activation of TLR5 signaling, because they fail to degrade excess monomeric flagellin in their environment. Interestingly, AprA also prevents flagellin-mediated immune responses (such as growth inhibition and callose deposition in Arabidopsis thaliana plants. This was due to decreased activation of the receptor FLS2 and clearly demonstrated by delayed stomatal closure with live bacteria in plants. Thus, by degrading the ligand for TLR5 and FLS2, P. aeruginosa escapes recognition by the innate immune systems of both mammals and plants.

  12. Pseudomonas syringae evades host immunity by degrading flagellin monomers with alkaline protease AprA.

    Science.gov (United States)

    Pel, Michiel J C; van Dijken, Anja J H; Bardoel, Bart W; Seidl, Michael F; van der Ent, Sjoerd; van Strijp, Jos A G; Pieterse, Corné M J

    2014-07-01

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of bacterial species. In addition, we investigated the role of AprA in virulence of the bacterial plant pathogen P. syringae pv. tomato DC3000. The AprA-deficient DC3000 ΔaprA knockout mutant was significantly less virulent on both tomato and Arabidopsis thaliana. Moreover, infiltration of A. thaliana Col-0 leaves with DC3000 ΔaprA evoked a significantly higher level of expression of the defense-related genes FRK1 and PR-1 than did wild-type DC3000. In the flagellin receptor mutant fls2, pathogen virulence and defense-related gene activation did not differ between DC3000 and DC3000 ΔaprA. Together, these results suggest that AprA of DC3000 is important for evasion of recognition by the FLS2 receptor, allowing wild-type DC3000 to be more virulent on its host plant than AprA-deficient DC3000 ΔaprA. To provide further evidence for the role of DC3000 AprA in host immune evasion, we overexpressed the AprA inhibitory peptide AprI of DC3000 in A. thaliana to counteract the immune evasive capacity of DC3000 AprA. Ectopic expression of aprI in A. thaliana resulted in an enhanced level of resistance against wild-type DC3000, while the already elevated level of resistance against DC3000 ΔaprA remained unchanged. Together, these results indicate that evasion of host immunity by the alkaline protease AprA is important for full virulence of strain DC3000 and likely acts by preventing flagellin monomers from being recognized by its cognate immune receptor.

  13. Pseudomonas syringae evades host Immunity by degrading flagellin monomers with alkaline protease AprA

    NARCIS (Netherlands)

    Pel, M.J.C.; Van Dijken, A.J.H.; Bardoel, B.W.; Seidl, M.F; Van der Ent, S.; Van Strijp, J.A.G.

    2014-01-01

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of

  14. Pseudomonas syringae evades host Immunity by degrading flagellin monomers with alkaline protease AprA

    OpenAIRE

    Pel, M.J.C.; Van Dijken, A.J.H.; Bardoel, B.W.; Seidl, M.F; Van der Ent, S.; Van Strijp, J.A.G.

    2014-01-01

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of bacterial species. In addition, we investigated the role of AprA in virulence of the bacterial plant athogen P. syringae pv. tomato DC3000. The AprA-deficient DC3000 ΔaprA knockout mutant was significantl...

  15. Pseudomonas evades immune recognition of flagellin in both mammals and plants

    NARCIS (Netherlands)

    Bardoel, B.W.; Ent, S. van der; Pel, M.J.C.; Tommassen, J.; Pieterse, C.M.J.; Kessel, K.P.M. van; Strijp, J.A.G. van

    2011-01-01

    The building blocks of bacterial flagella, flagellin monomers, are potent stimulators of host innate immune systems. Recognition of flagellin monomers occurs by flagellin-specific pattern-recognition receptors, such as Toll-like receptor 5 (TLR5) in mammals and flagellin-sensitive 2 (FLS2) in

  16. Moskvalased näevad eesti nüüdiskunsti / Johannes Saar

    Index Scriptorium Estoniae

    Saar, Johannes, 1965-

    2007-01-01

    Moskvas nüüdiskunsti keskuses avatakse 19.09.2007 eesti kunstnike grupinäitus "Tagurpidi bluus". Anna Hints, Laura Kuusk, Neeme Külm, Kristina Norman, Jüri Ojaver, Jaan Paavle, Jaan Toomik ja Paul Rodgers pakuvad videos, fotos ja installatsioonides mõtlemisainet kultuurilise konsensuse üle. Näituse korraldaja on Kaasaegse Kunsti Eesti Keskus

  17. Kikilipsu pidused päevad / Mari Hiiemäe

    Index Scriptorium Estoniae

    Hiiemäe, Mari

    2008-01-01

    Ansamblist Rock Hotel, tema 30. sünnipäeva tähistamise juubelikontsertidest 14. okt. Pärnu Endla teatris, 15. okt. Rakvere Teatris, 16. okt. Viljandi Pärimusmuusika Aidas, 17. okt. Paide kultuurikeskuses, 18. okt. Võru kultuurimajas Kannel, 19. okt. Vanemuise väikeses majas ja 20. okt. Vene Teatris

  18. Riigikogu liikmed ja sotsiaalteadlased näevad Eestit erinevalt / Tõnis Saarts

    Index Scriptorium Estoniae

    Saarts, Tõnis

    2006-01-01

    8.-16. veebruarini 2006. a. Riigikogu liikmete ja sotsiaalteadlaste seas läbiviidud ekspertküsitluse tulemuste analüüs. Poliitikute ning sotsioloogide vastuste sarnasusest ja erinevustest. Rootsi demokraatiaauditi mudelist. Tabelid

  19. Phi photoproduction near threshold with Okubo-Zweig-Iizuka evading phi NN interactions

    CERN Document Server

    William, R A

    1998-01-01

    Existing intermediate and high energy phi-photoproduction data is consistent with purely diffractive production (i.e., Pomeron exchange). However, near threshold (1.574 GeV K sup + K sup - decay angular distribution. We stress the importance of measurements with linearly polarized photons near the phi threshold to separate natural and unnatural parity exchange mechanisms. Approved and planned phi photoproduction and electroproduction experiments at Jefferson Lab will help establish the relative dynamical contributions near threshold and clarify outstanding theoretical issues related to apparent Okubo-Zweig-Iizuka violations.

  20. Demodex canis targets TLRs to evade host immunity and induce canine demodicosis.

    Science.gov (United States)

    Kumari, P; Nigam, R; Choudhury, S; Singh, S K; Yadav, B; Kumar, D; Garg, S K

    2018-03-01

    Widespread incidence of Demodex mites throughout the mammalian class and occasional serious and fatal outcomes in dogs warrant an insight into the host-parasite interface especially. Therefore, this study was aimed to unravel the interplay between innate immune response and canine demodicosis. The dogs diagnosed to have natural clinical demodicosis were allocated into two groups; dogs with localized demodicosis (LD) and with generalized demodicosis (GD). The expression of toll-like receptors (TLRs) 2, 4 and 6 genes in peripheral blood mononuclear cells of these dogs was quantified by real-time PCR. Significantly increased TLR2 gene expression, while significantly diminished TLR4 and TLR6 gene expressions were observed in demodicosed dogs (LD and GD) as compared with the healthy ones. Even the expression of TLR2 gene was found to differ significantly between the dogs with LD and GD. Therefore, it can be inferred that clinical demodicosis in dogs is coupled with an up-regulation of TLR2 and down-regulation of TLR4 and TLR6 gene expressions. Overexpression of TLR2 gene might be responsible for Demodex-induced clinical manifestations, while TLR4 and TLR6 gene down-regulations could be the paramount strategy of Demodex mites to elude the host-immune interface. © 2017 John Wiley & Sons Ltd.

  1. Jaapanlased näevad Eestis uut turgu / Kazuhisa Sano ; interv. Riina Luik

    Index Scriptorium Estoniae

    Sano, Kazuhisa

    2005-01-01

    Jaapani suurima turismifirma Japan Travel Bureau tegevjuht vastab küsimustele, mis puudutavad Ettevõtluse Sihtasutusega sõlmitud koostöölepet, turismikoostöö arendamist Eestiga, jaapani turistide huvi Soome vastu, muljeid Eestist. Lisa: Jaapanlased Eestis

  2. Anneli Remme soovitab : Eesti Muusika Päevad 2005 / Anneli Remme

    Index Scriptorium Estoniae

    Remme, Anneli, 1968-

    2005-01-01

    Eesti Muusika Päevadest 2005: 7.-14. apr. Estonia kontserdisaalis, Viru Keskuses, Eesti Teatri- ja Muusikamuuseumis, Rahvusooperis Estonia, Õpetajate majas, Eesti Muusikaakadeemias, vanalinna tänavatel, Kinomajas, Stereo Lounge'is, Kanuti Gildi saalis, Eesti Kunstiakadeemias ja Metodisti kirikus (festivali peaheliloojaks valiti Arvo Pärt, autorikontsert tuleb Eino Tambergilt). Festivali kava: www.helilooja.ee

  3. Models of f(R) cosmic acceleration that evade solar system tests

    International Nuclear Information System (INIS)

    Hu, Wayne; Sawicki, Ignacy

    2007-01-01

    We study a class of metric-variation f(R) models that accelerates the expansion without a cosmological constant and satisfies both cosmological and solar-system tests in the small-field limit of the parameter space. Solar-system tests alone place only weak bounds on these models, since the additional scalar degree of freedom is locked to the high-curvature general-relativistic prediction across more than 25 orders of magnitude in density, out through the solar corona. This agreement requires that the galactic halo be of sufficient extent to maintain the galaxy at high curvature in the presence of the low-curvature cosmological background. If the galactic halo and local environment in f(R) models do not have substantially deeper potentials than expected in ΛCDM, then cosmological field amplitudes |f R | > or approx.10 -6 will cause the galactic interior to evolve to low curvature during the acceleration epoch. Viability of large-deviation models therefore rests on the structure and evolution of the galactic halo, requiring cosmological simulations of f(R) models, and not directly on solar-system tests. Even small deviations that conservatively satisfy both galactic and solar-system constraints can still be tested by future, percent-level measurements of the linear power spectrum, while they remain undetectable to cosmological-distance measures. Although we illustrate these effects in a specific class of models, the requirements on f(R) are phrased in a nearly model-independent manner

  4. Lattice QCD with chemical potential: Evading the fermion-sign problem

    Indian Academy of Sciences (India)

    Department of Theoretical Physics, Tata Institute of Fundamental Research, .... baryon and electric charge remain conserved, and only these two chemical potentials ..... of the equation of state also shows a power law behaviour for small n/T 3. In QCD with .... talk of C Schmidt in SEWM 2004 (Helsinki) for more on this topic.

  5. Structure-based redesign of lysostaphin yields potent antistaphylococcal enzymes that evade immune cell surveillance

    Directory of Open Access Journals (Sweden)

    Kristina Blazanovic

    Full Text Available Staphylococcus aureus infections exert a tremendous burden on the health-care system, and the threat of drug-resistant strains continues to grow. The bacteriolytic enzyme lysostaphin is a potent antistaphylococcal agent with proven efficacy against both drug-sensitive and drug-resistant strains; however, the enzyme's own bacterial origins cause undesirable immunogenicity and pose a barrier to clinical translation. Here, we deimmunized lysostaphin using a computationally guided process that optimizes sets of mutations to delete immunogenic T cell epitopes without disrupting protein function. In vitro analyses showed the methods to be both efficient and effective, producing seven different deimmunized designs exhibiting high function and reduced immunogenic potential. Two deimmunized candidates elicited greatly suppressed proliferative responses in splenocytes from humanized mice, while at the same time the variants maintained wild-type efficacy in a staphylococcal pneumonia model. Overall, the deimmunized enzymes represent promising leads in the battle against S. aureus.

  6. Põhja-Ameerika Eesti Päevad kui eestlaste esimene suurkogunemine / Kaire Tensuda

    Index Scriptorium Estoniae

    Tensuda, Kaire

    2007-01-01

    tagasivaade Robert Kreemi raamatu "Uus algus" ning Mai Kreemi mälestuste ja materjalide põhjal ESTOde eelkäijale, esimesele eestlaste suurüritusele Ameerika mandril - I Põhja-Ameerika Eesti Päevadele, mis toimusid 30. maist 2. juunini 1957. a. Torontos ja millest tänavu möödus 50. aastat. Robert Kreemi tegevusest ürituse peakomitee esimehe ja suurorganiseerijana. Ülevaade ka II, III, IV Põhja-Ameerika Eesti Päevadest ja Rootsi Eesti Päevadest 1968. a.

  7. TAX EVASION AND MONEY LAUNDERING – WAYS OF EVADING THE PAYMENT OF THE STATE BUDGET LIABILITIES

    Directory of Open Access Journals (Sweden)

    Constantin AFANASE

    2005-01-01

    Full Text Available Tax evasion is an antisocial phenomenon to be fight against with all forces. By reducing collection oftaxes, this phenomenon abridges society of significant public resources which could be used forachieving some social and economic goals used by the whole society. It is known that since the oldtimes tax payers were looking for means of reducing tax liabilities through various and ingeniousmethods. Basis of tax evasion phenomenon are in the deep structures of human cerebration, in theselfish spirit of human being, which always tend to bring specific interest before overall interest.

  8. Bussijuhtide kindrali rasked päevad / Peep Peterson ; interv. Tanel Raig

    Index Scriptorium Estoniae

    Peterson, Peep, 1975-

    2007-01-01

    Eesti Transpordi- ja Teetöötajate Ametiühingu esimees Peep Peterson vastab bussijuhtide ja tööandjate vahelisi lahkhelisid, ametiühinguliikumist ning kokkuleppe sõlmimist puudutavatele küsimustele. Kommenteerivad: Villem Tori. Streikija iseloomuga raske vastane; Henn Pärn. Peterson saavutas maksimumide maksimumi; Harri Taliga. Ametiühingu liidritel erinevad arusaamad. Lisa: Fakte eluloost

  9. Trompetipäevade pidulikud hetked / Valdu Rüütelmaa

    Index Scriptorium Estoniae

    Rüütelmaa, Valdo

    2009-01-01

    17. märtsist kuni 5. aprillini Eesti Muusika- ja Teatriakadeemias toimunud rahvusvahelistest 20. trompetipäevadest, mille raames toimusid mitmed koolitused ja konkurss "Trompetitalendid 2009". Muljeid konkursist jagavad žürii liige trompetist Adan Delgado Illada ja Sibeliuse Akadeemia magistrand Anni Jääskeläinen

  10. The hepatitis C virus persistence: how to evade the immune system?

    Indian Academy of Sciences (India)

    Unknown

    1.1b HCV proteins and functions: The first structural protein, from the N-terminus of ... sera of the patients are associated with lipids and lipopro- teins, the nonspecific ...... Classification of hepatitis C virus into six major genotypes and a series of ...

  11. Aromatic claw: A new fold with high aromatic content that evades structural prediction: Aromatic Claw

    Energy Technology Data Exchange (ETDEWEB)

    Sachleben, Joseph R. [Biomolecular NMR Core Facility, University of Chicago, Chicago Illinois; Adhikari, Aashish N. [Department of Chemistry, University of Chicago, Chicago Illinois; Gawlak, Grzegorz [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Hoey, Robert J. [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Liu, Gaohua [Northeast Structural Genomics Consortium (NESG), Department of Molecular Biology and Biochemistry, School of Arts and Sciences, and Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, and Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey; Joachimiak, Andrzej [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Biological Sciences Division, Argonne National Laboratory, Argonne Illinois; Montelione, Gaetano T. [Northeast Structural Genomics Consortium (NESG), Department of Molecular Biology and Biochemistry, School of Arts and Sciences, and Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, and Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey; Sosnick, Tobin R. [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Koide, Shohei [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Department of Biochemistry and Molecular Pharmacology and the Perlmutter Cancer Center, New York University School of Medicine, New York New York

    2016-11-10

    We determined the NMR structure of a highly aromatic (13%) protein of unknown function, Aq1974 from Aquifex aeolicus (PDB ID: 5SYQ). The unusual sequence of this protein has a tryptophan content five times the normal (six tryptophan residues of 114 or 5.2% while the average tryptophan content is 1.0%) with the tryptophans occurring in a WXW motif. It has no detectable sequence homology with known protein structures. Although its NMR spectrum suggested that the protein was rich in β-sheet, upon resonance assignment and solution structure determination, the protein was found to be primarily α-helical with a small two-stranded β-sheet with a novel fold that we have termed an Aromatic Claw. As this fold was previously unknown and the sequence unique, we submitted the sequence to CASP10 as a target for blind structural prediction. At the end of the competition, the sequence was classified a hard template based model; the structural relationship between the template and the experimental structure was small and the predictions all failed to predict the structure. CSRosetta was found to predict the secondary structure and its packing; however, it was found that there was little correlation between CSRosetta score and the RMSD between the CSRosetta structure and the NMR determined one. This work demonstrates that even in relatively small proteins, we do not yet have the capacity to accurately predict the fold for all primary sequences. The experimental discovery of new folds helps guide the improvement of structural prediction methods.

  12. Leishmania infantum and Leishmania braziliensis: differences and similarities to evade the innate immune system

    Directory of Open Access Journals (Sweden)

    Sarah Athayde Couto Falcão

    2016-08-01

    Full Text Available Visceral Leishmaniasis is a severe form of the disease, caused by Leishmania infantum in the New World. Patients present an anergic immune response that favors parasite establishment and spreading through tissues like bone marrow and liver. On the other hand, Leishmania braziliensis causes localized cutaneous lesions, which can be self healing in some individuals. Interactions between host and parasite are essential to understand disease pathogenesis and progression. In this context, dendritic cells (DCs act as essential bridges that connect innate and adaptive immune responses. In this way, the aim of this study was to compare the effects of these two Leishmania species, in some aspects of human dendritic cells biology to better understanding of the evasion mechanisms of Leishmania from host innate immune response. To do so, DCs were obtained from monocytes from whole peripheral blood’s healthy volunteers donors and infected with L. infantum or L. braziliensis for 24 hours. We observed similar rates of infection (around 40% as well as parasite burden for both Leishmania species. Concerning surface molecules, we observed that both parasites induced CD86 expression when DCs were infected for 24h. On the other hand, we detected a lower surface expression of CD209 in the presence of both L. braziliensis and L. infantum, but only the last one promoted the survival of dendritic cells after 24 hours. Therefore, DCs infected by both Leishmania species showed a higher expression of CD86 and a decrease of CD209 expression, suggesting that both enter DCs through CD209 molecule. However, only L. infantum had the ability to inhibit DC apoptotic death, as an evasion mechanism that enables its spreading to organs like bone marrow and liver. Lastly, L. braziliensis was more silent parasite, once it did not inhibit DC apoptosis in our in vitro model.

  13. Evading the Burden of Proof in European Union Soft Law Instruments : The Case of Commission Recommendations

    NARCIS (Netherlands)

    Andone, C.; Greco, S.

    2018-01-01

    The European Union is making increased efforts to find simpler and more effective ways to function adequately in the eyes of its citizens by using ‘soft law’ instruments such as recommendations. Although they have no legally binding force, recommendations have practical and legal effects occurring

  14. Winding out of the Swamp: Evading the weak gravity conjecture with F-term winding inflation?

    Directory of Open Access Journals (Sweden)

    Arthur Hebecker

    2015-09-01

    Full Text Available We present a new model of large field inflation along a winding trajectory in the field space of two axionic fields, where the “axions” originate from the complex structure moduli sector of a Calabi–Yau 3-fold at large complex structure. The winding trajectory arises from fixing one combination of axions by bulk fluxes and allows for a transplanckian effective field range. The inflaton potential arises from small “instantonic” corrections to the geometry and realises natural inflation. By working in a regime of large complex structure for two complex structure moduli the inflaton potential can be made subdominant without severe tuning. We also discuss the impact of the recent ‘no-go theorems’ for transplanckian axion periodicities on our work. Interestingly, our setup seems to realise a loophole pointed out in arXiv:1503.00795 and arXiv:1503.04783: our construction is a candidate for a string theory model of large field inflation which is consistent with the mild form of the weak gravity conjecture for axions.

  15. Hydrogel-embedded endothelial progenitor cells evade LPS and mitigate endotoxemia.

    Science.gov (United States)

    Ghaly, Tammer; Rabadi, May M; Weber, Mia; Rabadi, Seham M; Bank, Michael; Grom, John M; Fallon, John T; Goligorsky, Michael S; Ratliff, Brian B

    2011-10-01

    Sepsis and its complications are associated with poor clinical outcomes. The circulatory system is a well-known target of lipopolysaccharide (LPS). Recently, several clinical studies documented mobilization of endothelial progenitor cells (EPCs) during endotoxemia, with the probability of patients' survival correlating with the rise in circulating EPCs. This fact combined with endotoxemia-induced vascular injury led us to hypothesize that the developing functional EPC incompetence could impede vascular repair and that adoptive transfer of EPCs could improve hemodynamics in endotoxemia. We used LPS injection to model endotoxemia. EPCs isolated from endotoxemic mice exhibited impaired clonogenic potential and LPS exerted Toll-like receptor 4-mediated cytotoxic effects toward EPCs, which was mitigated by embedding them in hyaluronic acid (HA) hydrogels. Therefore, intact EPCs were either delivered intravenously or embedded within pronectin-coated HA hydrogels. Adoptive transfer of EPCs in LPS-injected mice improved control of blood pressure and reduced hepatocellular and renal dysfunction. Specifically, EPC treatment was associated with the restoration of renal microcirculation and improved renal function. EPC therapy was most efficient when cells were delivered embedded in HA hydrogel. These findings establish major therapeutic benefits of adoptive transfer of EPCs, especially when embedded in HA hydrogels, in mice with LPS-induced endotoxemia, and they argue that hemodynamic and renal abnormalities of endotoxemia are in significant part due to developing incompetence of endogenous EPCs.

  16. Evading Equity: Principal Autonomy under the Bloomberg-Klein Market Regime

    Science.gov (United States)

    Lewis-Durham, Tiffanie C.

    2015-01-01

    Using New York City schools as a case study, this study draws on interview data from principals, district consultants and administrators, and principal's union representatives to explore the relationship between market-based reform and colorblindness in educational policy. The study is informed by colorblindness theory, which explores the subtle…

  17. Ester Tuiksoo. Proua Suhkru kibedad päevad / Ester Tuiksoo ; interv. Piret Tali

    Index Scriptorium Estoniae

    Tuiksoo, Ester, 1965-

    2005-01-01

    Põllumajandusminister Ester Tuiksoo, kellel peagi täitub ministri ametis aasta Euroopa Liidu suhkrutrahvist, maaettevõtlusest, põllumajandusest, Euroopa Liidu toetustest, ministri elu- ja teenistuskäigust. Lisa: Ester Tuiksoo

  18. Marburg virus evades interferon responses by a mechanism distinct from ebola virus.

    Directory of Open Access Journals (Sweden)

    Charalampos Valmas

    2010-01-01

    Full Text Available Previous studies have demonstrated that Marburg viruses (MARV and Ebola viruses (EBOV inhibit interferon (IFN-alpha/beta signaling but utilize different mechanisms. EBOV inhibits IFN signaling via its VP24 protein which blocks the nuclear accumulation of tyrosine phosphorylated STAT1. In contrast, MARV infection inhibits IFNalpha/beta induced tyrosine phosphorylation of STAT1 and STAT2. MARV infection is now demonstrated to inhibit not only IFNalpha/beta but also IFNgamma-induced STAT phosphorylation and to inhibit the IFNalpha/beta and IFNgamma-induced tyrosine phosphorylation of upstream Janus (Jak family kinases. Surprisingly, the MARV matrix protein VP40, not the MARV VP24 protein, has been identified to antagonize Jak and STAT tyrosine phosphorylation, to inhibit IFNalpha/beta or IFNgamma-induced gene expression and to inhibit the induction of an antiviral state by IFNalpha/beta. Global loss of STAT and Jak tyrosine phosphorylation in response to both IFNalpha/beta and IFNgamma is reminiscent of the phenotype seen in Jak1-null cells. Consistent with this model, MARV infection and MARV VP40 expression also inhibit the Jak1-dependent, IL-6-induced tyrosine phosphorylation of STAT1 and STAT3. Finally, expression of MARV VP40 is able to prevent the tyrosine phosphorylation of Jak1, STAT1, STAT2 or STAT3 which occurs following over-expression of the Jak1 kinase. In contrast, MARV VP40 does not detectably inhibit the tyrosine phosphorylation of STAT2 or Tyk2 when Tyk2 is over-expressed. Mutation of the VP40 late domain, essential for efficient VP40 budding, has no detectable impact on inhibition of IFN signaling. This study shows that MARV inhibits IFN signaling by a mechanism different from that employed by the related EBOV. It identifies a novel function for the MARV VP40 protein and suggests that MARV may globally inhibit Jak1-dependent cytokine signaling.

  19. Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

    Science.gov (United States)

    Enderling, Heiko; Hahnfeldt, Philip

    2011-08-01

    Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Dynamic Atomic Reconstruction: How Fe_{3}O_{4} Thin Films Evade Polar Catastrophe for Epitaxy

    Directory of Open Access Journals (Sweden)

    C. F. Chang

    2016-10-01

    Full Text Available Polar catastrophe at the interface of oxide materials with strongly correlated electrons has triggered a flurry of new research activities. The expectations are that the design of such advanced interfaces will become a powerful route to engineer devices with novel functionalities. Here, we investigate the initial stages of growth and the electronic structure of the spintronic Fe_{3}O_{4}/MgO(001 interface. Using soft x-ray absorption spectroscopy, we have discovered that the so-called A-sites are completely missing in the first Fe_{3}O_{4} monolayer. This discovery allows us to develop an unexpected but elegant growth principle in which, during deposition, the Fe atoms are constantly on the move to solve the divergent electrostatic potential problem, thereby ensuring epitaxy and stoichiometry at the same time. This growth principle provides a new perspective for the design of interfaces.

  1. Sügiskaamose puhul tõttavad appi kolmed moepäevad / Mari Rebane

    Index Scriptorium Estoniae

    Rebane, Mari

    2007-01-01

    4.10.2007 alanud Tallinna moenädal Tallinn Fashion Week Estonia teatri kammersaalis toob vaatajateni kodumaiste moedisainerite loomingut. Moenädala raames toimub Viru keskuses ka sügisene FIBIT ning Montoni kauplustes Tallinnas ja Tartus antakse tasuta stiilinõuandeid

  2. Candida albicans Biofilms Do Not Trigger Reactive Oxygen Species and Evade Neutrophil Killing

    Science.gov (United States)

    Xie, Zhihong; Thompson, Angela; Sobue, Takanori; Kashleva, Helena; Xu, Hongbin; Vasilakos, John; Dongari-Bagtzoglou, Anna

    2012-01-01

    Neutrophils are found within Candida albicans biofilms in vivo and could play a crucial role in clearing the pathogen from biofilms forming on catheters and mucosal surfaces. Our goal was to compare the antimicrobial activity of neutrophils against developing and mature C. albicans biofilms and identify biofilm-specific properties mediating resistance to immune cells. Antibiofilm activity was measured with the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)2H-tetrazolium-5-carboxanilide assay and a molecular Candida viability assay. Reactive oxygen species generation was assessed by measuring fluorescence of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester in preloaded neutrophils. We found that mature biofilms were resistant to leukocytic killing and did not trigger reactive oxygen species, even though neutrophils retained their viability and functional activation potential. Beta-glucans found in the extracellular matrix negatively affected antibiofilm activities. We conclude that these polymers act as a decoy mechanism to prevent neutrophil activation and that this represents an important innate immune evasion mechanism of C. albicans biofilms. PMID:23033146

  3. Can butterflies evade fire? Pupa location and heat tolerance in fire prone habitats of Florida.

    Science.gov (United States)

    Thom, Matthew D; Daniels, Jaret C; Kobziar, Leda N; Colburn, Jonathan R

    2015-01-01

    Butterflies such as the atala hairstreak, Eumaeus atala Poey, and the frosted elfin, Callophrys irus Godart, are restricted to frequently disturbed habitats where their larval host plants occur. Pupae of these butterflies are noted to reside at the base of host plants or in the leaf litter and soil, which may allow them to escape direct mortality by fire, a prominent disturbance in many areas they inhabit. The capacity of these species to cope with fire is a critical consideration for land management and conservation strategies in the locations where they are found. Survival of E. atala pupae in relation to temperature and duration of heat pulse was tested using controlled water bath experiments and a series of prescribed fire field experiments. Survival of E. atala pupae was correlated to peak temperature and heat exposure in both laboratory and field trials. In addition, E. atala survival following field trials was correlated to depth of burial; complete mortality was observed for pupae at the soil surface. Fifty percent of E. atala survived the heat generated by prescribed fire when experimentally placed at depths ≥ 1.75 cm, suggesting that pupation of butterflies in the soil at depth can protect from fatal temperatures caused by fire. For a species such as E. atala that pupates above ground, a population reduction from a burn event is a significant loss, and so decreasing the impact of prescribed fire on populations is critical.

  4. Viral Pseudo Enzymes Activate RIG-I via Deamidation to Evade Cytokine Production

    Science.gov (United States)

    He, Shanping; Zhao, Jun; Song, Shanshan; He, Xiaojing; Minassian, Arlet; Zhou, Yu; Zhang, Junjie; Brulois, Kevin; Wang, Yuqi; Cabo, Jackson; Zandi, Ebrahim; Liang, Chengyu; Jung, Jae U; Zhang, Xuewu; Feng, Pinghui

    2015-01-01

    SUMMARY RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologues of phosphoribosylformyglycinamide synthase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homologue thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme. PMID:25752576

  5. Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

    Science.gov (United States)

    Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

    2015-01-01

    Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

  6. Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.

    Directory of Open Access Journals (Sweden)

    Ayman Khattab

    2015-02-01

    Full Text Available Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.

  7. Geeniuste tagasitulek : Louis Kahni päevad Kuressaares / Toivo Tammik

    Index Scriptorium Estoniae

    Tammik, Toivo

    2006-01-01

    6. X avatakse Louis Kahni portree Kuressaare raekojas ja näitus Kuressaare linnuses, Kuressaare Linnateatris linastub arhitekti poja Nathaniel Kahni film "My architect. Son's journey" (2003). 7. X toimuva rahvusvahelise arhitektuurikonverentsi kava. 1956. a. Philadelphias kohtunud Saaremaal sündinud Louis Isadore Kahnist ja Järvamaal sündinud August Eduard Komendandist

  8. Can butterflies evade fire? Pupa location and heat tolerance in fire prone habitats of Florida

    Science.gov (United States)

    The imperiled frosted elfin butterfly, Callophrys irus Godart, is restricted to frequently disturbed habitats where its larval host plants, Lupinus perennis L. and Baptisia tinctoria (L.) R. Br. occur. C. irus pupae are noted to reside in both leaf litter and soil, which may allow them to escape dir...

  9. 73. hõimupäevade avamisel / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2008-01-01

    Presidendi kõne 15. oktoobril 2001 Tallinnas. President leiab, et just kultuuride paljususes peitub maailma tugevus ja kui räägitakse kultuuride konfliktist, siis tegelikult räägitakse selle varjus majanduslikest ja poliitilistest ambitsioonidest ning privileegidest

  10. Phenotypes and functions of persistent Sendai virus-induced antibody forming cells and CD8+ T cells in diffuse nasal-associated lymphoid tissue typify lymphocyte responses of the gut.

    Science.gov (United States)

    Rudraraju, Rajeev; Surman, Sherri; Jones, Bart; Sealy, Robert; Woodland, David L; Hurwitz, Julia L

    2011-02-20

    Lymphocytes of the diffuse nasal-associated lymphoid tissue (d-NALT) are uniquely positioned to tackle respiratory pathogens at their point-of-entry, yet are rarely examined after intranasal (i.n.) vaccinations or infections. Here we evaluate an i.n. inoculation with Sendai virus (SeV) for elicitation of virus-specific antibody forming cells (AFCs) and CD8(+) T cells in the d-NALT. Virus-specific AFCs and CD8(+) T cells each appeared by day 7 after SeV inoculation and persisted for 8 months, explaining the long-sustained protection against respiratory virus challenge conferred by this vaccine. AFCs produced IgM, IgG1, IgG2a, IgG2b and IgA, while CD8+ T cells were cytolytic and produced low levels of cytokines. Phenotypic analyses of virus-specific T cells revealed striking similarities with pathogen-specific immune responses in the intestine, highlighting some key features of adaptive immunity at a mucosal site. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner.

    Directory of Open Access Journals (Sweden)

    Josef Köck

    Full Text Available Persistence of hepatitis B virus (HBV infection requires covalently closed circular (cccDNA formation and amplification, which can occur via intracellular recycling of the viral polymerase-linked relaxed circular (rc DNA genomes present in virions. Here we reveal a fundamental difference between HBV and the related duck hepatitis B virus (DHBV in the recycling mechanism. Direct comparison of HBV and DHBV cccDNA amplification in cross-species transfection experiments showed that, in the same human cell background, DHBV but not HBV rcDNA converts efficiently into cccDNA. By characterizing the distinct forms of HBV and DHBV rcDNA accumulating in the cells we find that nuclear import, complete versus partial release from the capsid and complete versus partial removal of the covalently bound polymerase contribute to limiting HBV cccDNA formation; particularly, we identify genome region-selectively opened nuclear capsids as a putative novel HBV uncoating intermediate. However, the presence in the nucleus of around 40% of completely uncoated rcDNA that lacks most if not all of the covalently bound protein strongly suggests a major block further downstream that operates in the HBV but not DHBV recycling pathway. In summary, our results uncover an unexpected contribution of the virus to cccDNA formation that might help to better understand the persistence of HBV infection. Moreover, efficient DHBV cccDNA formation in human hepatoma cells should greatly facilitate experimental identification, and possibly inhibition, of the human cell factors involved in the process.

  12. ROLE OF PREEXISTING VIRUS-SPECIFIC IgG IN PRIMARY DISEASE AND IN REINFECTION WITH RESPIRATORY SYNCYTIAL VIRUS

    Directory of Open Access Journals (Sweden)

    V. Z. Krivitskaya

    2012-01-01

    Full Text Available Abstract. The aim of the study is evaluation of links between presence in blood of specific pre-existing IgG to respiratory-syncytial virus (RSV, clinical course of RSV infection and character specific to RSV humoral immune response in patients of different ages. The antibodies were detected by ELISA using whole RS virus or synthetic peptides corresponded to the selected determinants of the envelope RSV proteins. It was shown that RS specific maternal IgG antibodies passively transferred to babies in utero can circulate in the blood up to 10 months of life. The analysis of paired sera of 45 babies in the age of 1–10 months revealed firstly that presence of maternal IgG specific antibodies to the conservative B-cell immunogenic determinants of the F-protein (amino acids 221–232 and/or the G-protein (amino acids 152–164 and 184–198 is coupled with more high morbidity of primary RSV infection (89% versus 56%, p = 0.023, and also with more high frequency of complicated by bronchus obstruction course of the disease (81% versus 20%, р = 0.001 in compare with babies who were serologically negative to the maternal determinants specific antibodies. The correlation analysis has shown that the high presence of maternal determinant-specific IgG in the blood in babies till 10 months of life is associated in the case of primary infection with disbalance of humoral anti-viral immune response: intensive synthesis of serum RSV IgA. This is evidence of complicated course of infection with simultaneous suppression of response to RSV specific IgG. As opposed to the primary RSV infection in patients older than 3 years (n = 121 it was not detected links between anamnestic determinant-specific IgG synthesized by own immune system as the results of previous disease episodes and synthesis of anti-RSV IgG, IgM, IgE and IgA in RSV re-infections. In the contrast to babies in more older patients the feedback connection between level of pre-existing determinant-specific “memory IgG” and diagnostics of RSV infection has been established.

  13. Routine detection of Epstein-Barr virus specific T-cells in the peripheral blood by flow cytometry

    Science.gov (United States)

    Crucian, B. E.; Stowe, R. P.; Pierson, D. L.; Sams, C. F.

    2001-01-01

    The ability to detect cytomegalovirus-specific T-cells (CD4(+)) in the peripheral blood by flow cytometry has been recently described by Picker et al. In this method, cells are incubated with viral antigen and responding (cytokine producing) T-cells are then identified by flow cytometry. To date, this technique has not been reliably used to detect Epstein-Barr virus (EBV)-specific T-cells primarily due to the superantigen/mitogenic properties of the virus which non-specifically activate T-cells. By modifying culture conditions under which the antigens are presented, we have overcome this limitation and developed an assay to detect and quantitate EBV-specific T-cells. The detection of cytokine producing T-cells by flow cytometry requires an extremely strong signal (such as culture in the presence of PMA and ionomycin). Our data indicate that in modified culture conditions (early removal of viral antigen) the non-specific activation of T-cells by EBV is reduced, but antigen presentation will continue uninhibited. Using this method, EBV-specific T-cells may be legitimately detected using flow cytometry. No reduction in the numbers of antigen-specific T-cells was observed by the early removal of target antigen when verified using cytomegalovirus antigen (a virus with no non-specific T-cell activation properties). In EBV-seropositive individuals, the phenotype of the EBV-specific cytokine producing T-cells was evaluated using four-color flow cytometry and found to be CD45(+), CD3(+), CD4(+), CD45RA(-), CD69(+), CD25(-). This phenotype indicates the stimulation of circulating previously unactivated memory T-cells. No cytokine production was observed in CD4(+) T-cells from EBV-seronegative individuals, confirming the specificity of this assay. In addition, the use of four color cytometry (CD45, CD3, CD69, IFNgamma/IL-2) allows the total quantitative assessment of EBV-specific T-cells while monitoring the interference of EBV non-specific mitogenic activity. This method may have significant utility for the monitoring of the immune response to latent virus infection/reactivation.

  14. The coat protein of prunus necrotic ringspot virus specifically binds to and regulates the conformation of its genomic RNA.

    Science.gov (United States)

    Aparicio, Frederic; Vilar, Marçal; Perez-Payá, Enrique; Pallás, Vicente

    2003-08-15

    Binding of coat protein (CP) to the 3' nontranslated region (3'-NTR) of viral RNAs is a crucial requirement to establish the infection of Alfamo- and Ilarviruses. In vitro binding properties of the Prunus necrotic ringspot ilarvirus (PNRSV) CP to the 3'-NTR of its genomic RNA using purified E. coli- expressed CP and different synthetic peptides corresponding to a 26-residue sequence near the N-terminus were investigated by electrophoretic mobility shift assays. PNRSV CP bound to, at least, three different sites existing on the 3'-NTR. Moreover, the N-terminal region between amino acid residues 25 to 50 of the protein could function as an independent RNA-binding domain. Single exchange of some arginine residues by alanine eliminated the RNA-interaction capacity of the synthetic peptides, consistent with a crucial role for Arg residues common to many RNA-binding proteins possessing Arg-rich domains. Circular dichroism spectroscopy revealed that the RNA conformation is altered when amino-terminal CP peptides bind to the viral RNA. Finally, mutational analysis of the 3'-NTR suggested the presence of a pseudoknotted structure at this region on the PNRSV RNA that, when stabilized by the presence of Mg(2+), lost its capability to bind the coat protein. The existence of two mutually exclusive conformations for the 3'-NTR of PNRSV strongly suggests a similar regulatory mechanism at the 3'-NTR level in Alfamo- and Ilarvirus genera.

  15. Detailed analysis of Epstein–Barr virus-specific CD4+ and CD8+ T cell responses during infectious mononucleosis

    Science.gov (United States)

    Scherrenburg, J; Piriou, E R W A N; Nanlohy, N M; van Baarle, D

    2008-01-01

    We studied simultaneously Epstein–Barr virus (EBV)-specific CD4+ and CD8+ T cell responses during and after infectious mononucleosis (IM), using a previously described 12-day stimulation protocol with EBNA1 or BZLF1 peptide pools. Effector function of EBV-specific T cells was determined after restimulation by measuring intracellular interferon-γ production. During IM, BZLF1-specifc CD4+ T cell responses were dominant compared with CD8+ T cell responses. EBNA1-specific CD4+ and CD8+ T cell responses were low and remained similar for 6 months. However, 6 months after IM, BZLF1-specific CD4+ T cell responses had declined, but CD8+ T cell responses had increased. At diagnosis, EBV-specific CD8+ T cells as studied by human leucocyte antigen class I tetramer staining comprised a tetramerbrightCD8bright population consisting mainly of CD27+ memory T cells and a tetramerdimCD8dim population consisting primarily of CD27- effector T cells. The remaining EBV-specific CD8+ T cell population 6 months after the diagnosis of IM consisted mainly of tetramerbrightCD8bright CD27+ T cells, suggesting preferential preservation of memory T cells after contraction of the EBV-specific T cell pool. PMID:18549439

  16. Generation of Recombinant Schmallenberg Virus Nucleocapsid Protein in Yeast and Development of Virus-Specific Monoclonal Antibodies

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    Justas Lazutka

    2014-01-01

    Full Text Available Schmallenberg virus (SBV, discovered in continental Europe in late 2011, causes mild clinical signs in adult ruminants, including diarrhoea and reduced milk yield. However, fetal infection can lead to severe malformation in newborn offspring. To develop improved reagents for SBV serology, a high-level yeast expression system was employed to produce recombinant SBV nucleocapsid (N protein. Recombinant SBV N protein was investigated as an antigen in SBV-specific IgG enzyme immunoassay and used for generation of monoclonal antibodies (MAbs. Yeast-expressed SBV N protein was reactive with anti-SBV IgG-positive cow serum specimens collected from different farms of Lithuania. After immunization of mice with recombinant SBV N protein, four MAbs were generated. The MAbs raised against recombinant SBV N protein reacted with native viral nucleocapsids in SBV-infected BHK cells by immunofluorescence assay. The reactivity of recombinant N protein with SBV-positive cow serum specimens and the ability of the MAbs to recognize virus-infected cells confirm the antigenic similarity between yeast-expressed SBV N protein and native viral nucleocapsids. Our study demonstrates that yeast expression system is suitable for high-level production of recombinant SBV N protein and provides the first evidence on the presence of SBV-specific antibodies in cow serum specimens collected in Lithuania.

  17. Analysis of mumps vaccine failure by means of avidity testing for mumps virus-specific immunoglobulin G.

    Science.gov (United States)

    Narita, M; Matsuzono, Y; Takekoshi, Y; Yamada, S; Itakura, O; Kubota, M; Kikuta, H; Togashi, T

    1998-11-01

    To characterize patients with mumps vaccine failure, avidity testing was performed with the Enzygnost Anti-Parotitis Virus/IgG kit using a single-dilution-6 M urea denaturation method. Five groups of patients were tested. Group 1 consisted of 29 patients with primary mumps infections; group 2 was 20 children and adults with a definite history of natural infection; group 3 was 7 patients with a recent mumps vaccination, 1 of whom developed parotid gland swelling and aseptic meningitis; group 4 was 14 patients with mumps vaccine failure; and group 5 was 6 patients with recurrent episodes of parotitis in addition to a history of vaccination. On the basis of the results of groups 1 and 2, an avidity of /=32% was determined to be high. Avidity maturation from low to high appears to occur around 180 days after the acute illness. The results of group 3 showed that the vaccine-induced immunoglobulin G (IgG) had very low avidity. Among the 14 patients in group 4, 12 patients, including 7 with a positive IgM response, were diagnosed as having secondary vaccine failures. The results of group 5 suggested the possibility that the avidity of the mumps vaccine-induced IgG remains low or borderline. These results showed that secondary mumps vaccine failure occurs not infrequently, even among school age children under condition in which the vaccine coverage is low (i.e., 33% in our study population), and therefore, vaccinees are prone to be exposed to wild-type viruses. Avidity testing should provide information useful for the analysis of mumps virus infections.

  18. Effects of long-term low dose radiation. Epstein-Barr virus-specific antibodies in radiological technologists

    Energy Technology Data Exchange (ETDEWEB)

    Kumagai, Etsuko; Higashida, Yoshiharu; Onomichi, Mitsukazu; Nakamura, Ikuo; Tanoue, Shozo; Tanaka, Ryuji; Kumagai, Takashi; Katsuki, Takato; Sawada, Shozo.

    1988-09-01

    To clarify the long-term effects of occupational exposure to low doses of radiation, Epstein-Barr virus (EBV)-specific antibody titers in sera from 104 radiological technologists (R.T.) and 118 controls in Kumamoto prefecture were measured by the immunofluorescence method. Antibody titers to viral capsid antigen (VCA)-IgG increased with the years of experience as R.T., and the prevalence of abnormal antibody titers to both VCA-IgG and early antigen (EA)-IgG were significantly higher in R.T. with over 15 years of experience or 30 rads of cumulative radiation dose than in the controls. However, there was no correlation between exposure and the frequency of abnormal EBV-associated nuclear antigen (EBNA) antibody titers. The EBV-specific antibody titers of 24 Hiroshima atomic-bomb survivors were also measured. They were similar to those of the R.T. with over 30 years of experience. The EBV-specific antibody titers of R.T. suggest that there may be an impairment of immunologic competence after continuous long-term exposure to low doses of radiation. Also, the correlation of EBV-specific antibody titers and frequency of cells with chromosome aberrations in 53 R.T. was studied. Some correlations were found between the antibody titers to both of the VCA-IgG and EBNA and the frequency of cells with chromosome aberrations.

  19. A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice.

    Science.gov (United States)

    Gummow, Jason; Li, Yanrui; Yu, Wenbo; Garrod, Tamsin; Wijesundara, Danushka; Brennan, Amelia J; Mullick, Ranajoy; Voskoboinik, Ilia; Grubor-Bauk, Branka; Gowans, Eric J

    2015-08-01

    There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising "multiantigen" vaccine that elicits robust CMI. Since their development, vaccines have reduced the global burden of disease. One strategy for vaccine development is to use commercially viable DNA technology, which has the potential to generate robust immune responses. Hepatitis C virus causes chronic liver infection and is a leading cause of liver cancer. To date, no vaccine is currently available, and treatment is costly and often results in side effects, limiting the number of patients who are treated. Despite recent advances in treatment, prevention remains the key to efficient control and elimination of this virus. Here, we describe a novel DNA vaccine against hepatitis C virus that is capable of inducing robust cell-mediated immune responses in mice and is a promising vaccine candidate for humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Generation of Recombinant Porcine Parvovirus Virus-Like Particles in Saccharomyces cerevisiae and Development of Virus-Specific Monoclonal Antibodies

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    Paulius Lukas Tamošiūnas

    2014-01-01

    Full Text Available Porcine parvovirus (PPV is a widespread infectious virus that causes serious reproductive diseases of swine and death of piglets. The gene coding for the major capsid protein VP2 of PPV was amplified using viral nucleic acid extract from swine serum and inserted into yeast Saccharomyces cerevisiae expression plasmid. Recombinant PPV VP2 protein was efficiently expressed in yeast and purified using density gradient centrifugation. Electron microscopy analysis of purified PPV VP2 protein revealed the self-assembly of virus-like particles (VLPs. Nine monoclonal antibodies (MAbs against the recombinant PPV VP2 protein were generated. The specificity of the newly generated MAbs was proven by immunofluorescence analysis of PPV-infected cells. Indirect IgG ELISA based on the recombinant VLPs for detection of PPV-specific antibodies in swine sera was developed and evaluated. The sensitivity and specificity of the new assay were found to be 93.4% and 97.4%, respectively. In conclusion, yeast S. cerevisiae represents a promising expression system for generating recombinant PPV VP2 protein VLPs of diagnostic relevance.

  1. Kinetics of Epstein-Barr virus load and virus-specific CD8+ T cells in acute infectious mononucleosis.

    Science.gov (United States)

    Hoshino, Yo; Nishikawa, Kazuo; Ito, Yoshinori; Kuzushima, Kiyotaka; Kimura, Hiroshi

    2011-03-01

    During the convalescent phase of acute infectious mononucleosis (AIM), Epstein-Barr virus (EBV) load shrinks rapidly in association with a rapid decline in the number of EBV-specific CD8(+) T cells. The actual contribution of EBV-specific CD8(+) T cells in reducing EBV load, however, is not known. To clarify the impact of EBV-specific CD8(+) T cells on the contraction of EBV load in AIM, we estimated half-lives of both EBV load and EBV-specific CD8(+) T cells. Blood was serially taken from five pediatric patients with AIM during the convalescent period, including the very early phase, and both EBV load and EBV-specific CD8(+) T cell numbers were assayed. EBV load declined rapidly (half-life 1.5 d) during the first 2 weeks after onset of symptoms. This half-life was seven-fold shorter than that reported for CD27(+) memory B cells. Subsequently, the EBV load declined much more slowly, with a half-life of 38.7 d. EBV-specific CD8(+) T cell numbers also declined concomitantly with the decrease in EBV load. The half-life of EBV-specific CD8(+) T cells during first 2 weeks was 2.9 d. The number of EBV-specific CD8(+) T cells and the rate of change of viral load correlated significantly (R(2) ≥ 0.8; p ≤ 0.02). The short half-life of EBV load, together with the strong correlation between the number of EBV-specific CD8(+) T cells and the rate of change of viral load indicates an active role for EBV-specific CD8(+) T cells in elimination of EBV in AIM. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV

    Science.gov (United States)

    Bu, Wei; Hayes, Gregory M.; Liu, Hui; Gemmell, Lorraine; Schmeling, David O.; Radecki, Pierce; Aguilar, Fiona; Burbelo, Peter D.; Woo, Jennifer; Balfour, Henry H.

    2016-01-01

    Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV. PMID:26888186

  3. Partial reconstitution of virus-specific memory CD8+ T cells following whole body γ-irradiation

    International Nuclear Information System (INIS)

    Grayson, Jason M.; Laniewski, Nathan G.; Holbrook, Beth C.

    2006-01-01

    CD8 + memory T cells are critical in providing immunity to viral infection. Previous studies documented that antigen-specific CD8 + memory T cells are more resistant to radiation-induced apoptosis than naive T cells. Here, we determined the number and in vivo function of memory CD8 + T cells as immune reconstitution progressed following irradiation. Immediately following irradiation, the number of memory CD8 + T cells declined 80%. As reconstitution progressed, the number of memory cells reached a zenith at 33% of pre-irradiation levels, and was maintained for 120 days post-irradiation. In vitro, memory CD8 + T cells were able to produce cytokines at all times post-irradiation, but when adoptively transferred, they were not able to expand upon rechallenge immediately following irradiation, but regained this ability as reconstitution progressed. When proliferation was examined in vitro, irradiated memory CD8 + T cells were able to respond to mitogenic growth but were unable to divide

  4. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host.

    Science.gov (United States)

    Schurich, Anna; Pallett, Laura J; Jajbhay, Danyal; Wijngaarden, Jessica; Otano, Itziar; Gill, Upkar S; Hansi, Navjyot; Kennedy, Patrick T; Nastouli, Eleni; Gilson, Richard; Frezza, Christian; Henson, Sian M; Maini, Mala K

    2016-08-02

    T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1(hi) T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1(hi) HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV)-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL)-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8+ T cell response.

    Science.gov (United States)

    Culshaw, Abigail; Ladell, Kristin; Gras, Stephanie; McLaren, James E; Miners, Kelly L; Farenc, Carine; van den Heuvel, Heleen; Gostick, Emma; Dejnirattisai, Wanwisa; Wangteeraprasert, Apirath; Duangchinda, Thaneeya; Chotiyarnwong, Pojchong; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida; Dong, Tao; Rossjohn, Jamie; Mongkolsapaya, Juthathip; Price, David A; Screaton, Gavin R

    2017-11-01

    Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8 + T cell populations specific for variants of the nonstructural protein epitope NS3 133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3 133 -DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2 + TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second β-chain complementarity-determining region (CDR2β). Extensive mutagenesis studies of three distinct TRBV11-2 + TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.

  6. Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2 infection in guinea pigs.

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    Jingya Xia

    Full Text Available Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.

  7. Virus-specific DNA sequences present in cells which carry the herpes simplex virus thymidine kinase gene.

    Science.gov (United States)

    Minson, A C; Darby, G K; Wildy, P

    1979-11-01

    Two independently derived cell lines which carry the herpes simplex type 2 thymidine kinase gene have been examined for the presence of HSV-2-specific DNA sequences. Both cell lines contained 1 to 3 copies per cell of a sequence lying within map co-ordinates 0.2 to 0.4 of the HSV-2 genome. Revertant cells, which contained no detectable thymidine kinase, did not contain this DNA sequence. The failure of EcoR1-restricted HSV-2 DNA to act as a donor of the thymidine kinase gene in transformation experiments suggests that the gene lies close to the EcoR1 restriction site within this sequence at a map position of approx. 0.3. The HSV-2 kinase gene is therefore approximately co-linear with the HSV-1 gene.

  8. Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

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    Alba Grifoni

    2017-10-01

    Full Text Available BackgroundDengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV. To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua.MethodsHLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays.ResultsWe detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005. This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles.ConclusionThe DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.

  9. Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells.

    Science.gov (United States)

    Pizzolla, Angela; Wang, Zhongfang; Groom, Joanna R; Kedzierska, Katherine; Brooks, Andrew G; Reading, Patrick C; Wakim, Linda M

    2017-05-16

    The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8 + T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8 + T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8 + T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3 + memory CD8 + T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.

  10. Hepatitis B virus-specific miRNAs and Argonaute2 play a role in the viral life cycle.

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    C Nelson Hayes

    Full Text Available UNLABELLED: Disease-specific serum miRNA profiles may serve as biomarkers and might reveal potential new avenues for therapy. An HBV-specific serum miRNA profile associated with HBV surface antigen (HBsAg particles has recently been reported, and AGO2 and miRNAs have been shown to be stably associated with HBsAg in serum. We identified HBV-associated serum miRNAs using the Toray 3D array system in 10 healthy controls and 10 patients with chronic hepatitis B virus (HBV infection. 19 selected miRNAs were then measured by quantitative RT-PCR in 248 chronic HBV patients and 22 healthy controls. MiRNA expression in serum versus liver tissue was also compared using biopsy samples. To examine the role of AGO2 during the HBV life cycle, we analyzed intracellular co-localization of AGO2 and HBV core (HBcAg and surface (HBsAg antigens using immunocytochemistry and proximity ligation assays in stably transfected HepG2 cells. The effect of AGO2 ablation on viral replication was assessed using siRNA. Several miRNAs, including miR-122, miR-22, and miR-99a, were up-regulated at least 1.5 fold (P<2E-08 in serum of HBV-infected patients. AGO2 and HBcAg were found to physically interact and co-localize in the ER and other subcellular compartments. HBs was also found to co-localize with AGO2 and was detected in multiple subcellular compartments. Conversely, HBx localized non-specifically in the nucleus and cytoplasm, and no interaction between AGO2 and HBx was detected. SiRNA ablation of AGO2 suppressed production of HBV DNA and HBs antigen in the supernatant. CONCLUSION: These results suggest that AGO2 and HBV-specific miRNAs might play a role in the HBV life cycle.

  11. Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs.

    Science.gov (United States)

    Xia, Jingya; Veselenak, Ronald L; Gorder, Summer R; Bourne, Nigel; Milligan, Gregg N

    2014-01-01

    Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.

  12. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host

    Directory of Open Access Journals (Sweden)

    Anna Schurich

    2016-08-01

    Full Text Available T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1hi T cell response against hepatitis B virus (HBV had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1hi HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.

  13. Herpes Simplex Virus-2 Glycoprotein Interaction with HVEM Influences Virus-Specific Recall Cellular Responses at the Mucosa

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    Sarah J. Kopp

    2012-01-01

    Full Text Available Infection of susceptible cells by herpes simplex virus (HSV requires the interaction of the HSV gD glycoprotein with one of two principal entry receptors, herpes virus entry mediator (HVEM or nectins. HVEM naturally functions in immune signaling, and the gD-HVEM interaction alters innate signaling early after mucosal infection. We investigated whether the gD-HVEM interaction during priming changes lymphocyte recall responses in the murine intravaginal model. Mice were primed with attenuated HSV-2 expressing wild-type gD or mutant gD unable to engage HVEM and challenged 32 days later with virulent HSV-2 expressing wild-type gD. HSV-specific CD8+ T cells were decreased at the genital mucosa during the recall response after priming with virus unable to engage HVEM but did not differ in draining lymph nodes. CD4+ T cells, which are critical for entry of HSV-specific CD8+ T cells into mucosa in acute infection, did not differ between the two groups in either tissue. An inverse association between Foxp3+ CD4+ regulatory T cells and CD8+ infiltration into the mucosa was not statistically significant. CXCR3 surface expression was not significantly different among different lymphocyte subsets. We conclude that engagement of HVEM during the acute phase of HSV infection influences the antiviral CD8+ recall response by an unexplained mechanism.

  14. Selective expansion of influenza a virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques

    NARCIS (Netherlands)

    Keller, Tymen T.; van der Meer, Jelger J.; Teeling, Peter; van der Sluijs, Koen; Idu, Mirza M.; Rimmelzwaan, Guus F.; Levi, Marcel; van der Wal, Allard C.; de Boer, Onno J.

    2008-01-01

    Background and Purpose-Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the hypothesis that

  15. Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

    Science.gov (United States)

    Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

    2017-07-15

    The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4 + and CD8 + T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8 + CD57 + senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4 + CD69 + CD57 + PD1 + and CD8 + CD69 + CD57 + PD1 + T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8 + effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4 + and CD8 + proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. The coat protein of prunus necrotic ringspot virus specifically binds to and regulates the conformation of its genomic RNA

    International Nuclear Information System (INIS)

    Aparicio, Frederic; Vilar, Marcal; Perez-Paya, Enrique; Pallas, Vicente

    2003-01-01

    Binding of coat protein (CP) to the 3' nontranslated region (3'-NTR) of viral RNAs is a crucial requirement to establish the infection of Alfamo- and Ilarviruses. In vitro binding properties of the Prunus necrotic ringspot ilarvirus (PNRSV) CP to the 3'-NTR of its genomic RNA using purified E. coli- expressed CP and different synthetic peptides corresponding to a 26-residue sequence near the N-terminus were investigated by electrophoretic mobility shift assays. PNRSV CP bound to, at least, three different sites existing on the 3'-NTR. Moreover, the N-terminal region between amino acid residues 25 to 50 of the protein could function as an independent RNA-binding domain. Single exchange of some arginine residues by alanine eliminated the RNA-interaction capacity of the synthetic peptides, consistent with a crucial role for Arg residues common to many RNA-binding proteins possessing Arg-rich domains. Circular dichroism spectroscopy revealed that the RNA conformation is altered when amino-terminal CP peptides bind to the viral RNA. Finally, mutational analysis of the 3'-NTR suggested the presence of a pseudoknotted structure at this region on the PNRSV RNA that, when stabilized by the presence of Mg 2+ , lost its capability to bind the coat protein. The existence of two mutually exclusive conformations for the 3'-NTR of PNRSV strongly suggests a similar regulatory mechanism at the 3'-NTR level in Alfamo- and Ilarvirus genera

  17. Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Christensen, Jan P; Kristensen, Nanna N

    2002-01-01

    Efficient induction of T cell responses is normally assumed to require both TCR-mediated signaling and engagement of co-stimulatory molecules, in particular CD28. However, the importance of CD28 co-stimulation in induction and maintenance of antiviral T cell responses is not clearly established....... For this reason antiviral CD4(+) and CD8(+) T cell responses in CD28-deficient mice were studied using two different viruses [vesicular stomatitis virus and lymphocytic choriomeningitis virus (LCMV)]. Intracellular cytokine staining and/or MHC-peptide tetramers were used to enumerate antigen-specific T cells...

  18. Induction of feline immunodeficiency virus specific antibodies in cats with an attenuated Salmonella strain expressing the Gag protein.

    NARCIS (Netherlands)

    E.J. Tijhaar (Edwin); C.H.J. Siebelink (Kees); J.A. Karlas (Jos); M.C. Burger; F.R. Mooi (Frits); A.D.M.E. Osterhaus (Albert)

    1997-01-01

    textabstractSalmonella typhimurium aroA strains (SL3261), expressing high levels of the Gag protein of feline immunodeficiency virus (FIV) fused with maltose binding protein (SL3261-MFG), were constructed using an invertible promoter system that allows the stable expression of heterologous antigens

  19. Diminished primary and secondary influenza virus-specific CD8(+) T-cell responses in CD4-depleted Ig(-/-) mice

    DEFF Research Database (Denmark)

    Riberdy, J M; Christensen, Jan Pravsgaard; Branum, K

    2000-01-01

    Optimal expansion of influenza virus nucleoprotein (D(b)NP(366))-specific CD8(+) T cells following respiratory challenge of naive Ig(-/-) microMT mice was found to require CD4(+) T-cell help, and this effect was also observed in primed animals. Absence of the CD4(+) population was consistently...

  20. Meningitis, spondylodiscitis, pneumonia and septic shock with Streptococcus pneumoniae in a previously healthy woman with isolated IgG2-, IgG3-, IgA-deficiency and monoclonal gammopathy of undetermined significance

    DEFF Research Database (Denmark)

    Gaini, Shahin; Gudnason, David; Steig, Bjarni

    2018-01-01

    A 66 years old Caucasian woman with pneumococcal meningitis was treated and discharged after an uncomplicated course. Five months later she was readmitted with fever and right side abdominal pain and diagnosed with pneumococcal spondylodiscitis. One year later she was treated for a severe chest X...... not respond serologically on vaccination with 13-valent conjugate and 23-valent polysaccharide pneumococcal vaccines. Further evaluations revealed a positive M-component in her blood and a bone marrow biopsy diagnosed her to have monoclonal gammopathy of undetermined significance. To protect her against...... significance in an apparently healthy woman with at least three life threatening documented pneumococcal infections in a two-year period and poor pneumococcal vaccine response....

  1. Differential antibody isotype reactivity to specific antigens in human lymphatic filariasis: gp15/400 preferentially induces immunoglobulin E (IgE), IgG4, and IgG2

    NARCIS (Netherlands)

    Yazdanbakhsh, M.; Paxton, W. A.; Brandenburg, A.; van Ree, R.; Lens, M.; Partono, F.; Maizels, R. M.; Selkirk, M. E.

    1995-01-01

    Lymphatic filarial infection in humans is associated with a strong skewing of the immune response towards the TH2 arm, with prominent interleukin 4-producing cells and elevated levels of immunoglobulin G4 (IgG4) and IgE antibodies in peripheral blood. To determine how such a generalized TH2

  2. Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2010-01-01

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained ...

  3. Muusikamaailm : "Let the Peoples Sing 1999". Bruckneri päevad Viinis. Festival Huddersfieldis. Kolmelt pianistide konkursilt / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    Rahvusvahelise raadiokonkursi "Let the Peoples Sing" võitjatest. A. Bruckneri 175. sünniaastapäeva puhul toimunud Bruckneri päevadest Viinis. Kaasaegse muusika festivalist Huddersfieldist. Pianistide konkurssidest - Dino Ciani nim. konkursist Milanos, 7. Schuberti-nim. konkursist Dortmundis ja Ferruccio Busoni nim. konkursist Itaalias Bolzanos

  4. Evading plant defence: Infestation of poisonous milkweed fruits (Asclepiadaceae) by the fruit fly Dacus siliqualactis (Diptera: Tephritidae).

    Science.gov (United States)

    Schneider, Michael; Wunder, Cora; Reuss, Esther; Toennes, Stefan W; Mebs, Dietrich

    2017-12-01

    To cope with toxic metabolites plants use for defence, herbivorous insects employ various adaptive strategies. For oviposition, the fruit fly Dacus siliqualactis (Tephritidae) uses milkweed plants of the genus Gomphocarpus (Asclepiadaceae) by circumventing the plant's physical (gluey latex) and chemical (toxic cadenolides) defence. With its long, telescope-like ovipositor, the fly penetrates the exo- and endocarp of the fruit and places the eggs on the unripe seeds located in the centre of the fruit. Whereas most plant parts contain high concentrations of cardenolides such as gomphoside, calotropin/calacatin and gomphogenin, only the seeds exhibit low cardenolide levels. By surmounting physical barriers (fruit membranes, latex), the fly secures a safe environment and a latex-free food source of low toxicity for the developing larvae. One amino acid substitution (Q111V) at the cardenolide binding site of the fly's Na + , K + -ATPase was detected, but the significance of that substitution: reducing cardenolide sensitivity or not, is unclear. However, poisoning of the larvae by low levels of cardenolides is assumed to be prevented by non-resorption and excretion of the polar cardenolides, which cannot passively permeate the midgut membrane. This example of an insect-plant interaction demonstrates that by morphological and behavioural adaptation, a fruit fly manages to overcome even highly effective defence mechanisms of its host plant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Helicobacter pylori Outer Membrane Protein 18 (Hp1125 Is Involved in Persistent Colonization by Evading Interferon-γ Signaling

    Directory of Open Access Journals (Sweden)

    Yuqun Shan

    2015-01-01

    Full Text Available Outer membrane proteins (OMPs can induce an immune response. Omp18 (HP1125 of H. pylori is a powerful antigen that can induce significant interferon-γ (IFN-γ levels. Previous studies have suggested that IFN-γ plays an important role in H. pylori clearance. However, H. pylori has multiple mechanisms to avoid host immune surveillance for persistent colonization. We generated an omp18 mutant (H. pylori 26695 and H. pylori SS1 strain to examine whether Omp18 interacts with IFN-γ and is involved in H. pylori colonization. qRT-PCR revealed that IFN-γ induced Omp18 expression. qRT-PCR and western blot analysis revealed reduced expressions of virulence factors CagA and NapA in H. pylori 26695 with IFN-γ treatment, but they were induced in the Δomp18 strain. In C57BL/6 mice infected with H. pylori SS1 and the Δomp18 strain, the Δomp18 strain conferred defective colonization and activated a stronger inflammatory response. Signal transducer phosphorylation and transcription 1 (STAT1 activator was downregulated by the wild-type strain but not the Δomp18 strain in IFN-γ-treated macrophages. Furthermore, Δomp18 strain survival rates were poor in macrophages compared to the wild-type strain. We concluded that H. pylori Omp18 has an important function influencing IFN-γ-mediated immune response to participate in persistent colonization.

  6. Evading obsolescence: a strategic growth analysis for a small business unit that currently exists within a large corporation

    OpenAIRE

    Joseph, Ian Darryl; Wu, Qingbo

    2006-01-01

    Group X is a new strategic group of a well-known telecommunications corporation in Canada that is introducing a suite of employee performance evaluation and enhancement software to the Web-based e-HR industry. This analysis aims to assist Group X in understanding their competitive environment and to identify, analyze and compare key strategies for the company as they attempt to enter and ultimately sustain themselves in the Web-based e-HR industry. To this end, this paper includes a detailed ...

  7. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies.

    Directory of Open Access Journals (Sweden)

    Anna Olivieri

    2011-12-01

    Full Text Available The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1 is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1, and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However - in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins.

  8. Evading Colonial Authority. Rebels and Outlaws in the Borderlands of Dutch West Borneo 1850s–1920s

    DEFF Research Database (Denmark)

    Eilenberg, Michael

    2014-01-01

    inhabiting these edges of states further seem especially resistant towards officialdom through their engagement in law bending practices and a heightened sense of autonomy. This paper examines these dynamics as they unravel on the island of Borneo during the Dutch colonial administration in the mid...

  9. Smuggling across the border: how arthropod-borne pathogens evade and exploit the host defense system of the skin.

    Science.gov (United States)

    Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie

    2014-05-01

    The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.

  10. The Design, Synthesis, and Biological Evaluation of New Paclitaxel Analogs With the Ability to Evade Efflux by P-Glycoprotein

    National Research Council Canada - National Science Library

    Turunen, Brandon

    2004-01-01

    ... often results in the development of drug resistance. Furthermore, few current chemotherapeutics are able to cross the blood brain barrier leaving victims of brain cancer few viable treatment alternatives...

  11. Muusikamaailm : Weimari Riigikapell 400. Korngoldi mälestuspäevad Brnos. Ooperietendus taas Indias. Uusooperid laval Euroopas / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2002-01-01

    Weimari Riigikapell tähistab oma 400. aastapäeva. Brnos tähistatakse mitmete muusikasündmustega helilooja Erich Wolfgang Korngoldi mälestuspäevasid. New Delhi Siri Forti auditooriumis kõlab üle hulga aja ooper. Euroopa eri linnades toimuvatest ooperite uusalvastustest

  12. Firewalls and flat mirrors: An alternative to the AMPS experiment which evades the Harlow-Hayden obstacle

    Science.gov (United States)

    Oppenheim, Jonathan; Unruh, Bill

    2014-03-01

    If quantum gravity does not lead to a breakdown of predictability, then Almheiri-Marolf-Polchinski-Sully (AMPS) have argued that an observer falling into a black hole can perform an experiment which verifies a violation of entanglement monogamy — that late time Hawking radiation is maximally entangled with early time Hawking radiation and also with in-falling radiation — something impossible in quantum field theory. However, as pointed out by Hayden and Harlow, this experiment is infeasible, as the time required to perform the experiment is almost certainly longer than the lifetime of the black hole. Here we propose an alternative firewall experiment which could actually be performed within the black hole's lifetime. The alternative experiment involves forming an entangled black hole in which the unscrambling of information is precomputed on a quantum memory prior to the creation of the black hole and without acting on the matter which forms the black hole or emerges from it. This would allow an observer near a black hole to signal faster than light. As another application of our precomputing strategy, we show how one can produce entangled black holes which acts like "flat mirrors", in the sense that information comes out almost instantly (as in the Hayden-Preskill scenario), but also emerge unscrambled, so that it can actually be observed instantly as well. Finally, we prove that a black hole in thermal equilibrium with its own radiation, is uncorrelated with this radiation.

  13. Evading the Endgame in an Insurgency Undertaking: The Case of the Lord’s Resistance Army and Beyond

    Science.gov (United States)

    2015-06-01

    the argument, see Michelle Hale Williams, “Grappling with Ethnic Difference in Multicultural Societies,” in The Multicultural Dilemma: Migration...Michelle Hale. “Grappling with Ethnic Difference in Multicultural Societies.” In The Multicultural Dilemma: Migration, Ethnic Politics, and State...Center Ft. Belvoir, Virginia 2. Dudley Knox Library Naval Postgraduate School Monterey, California

  14. Enesessetõmbumine ehk Ungari välispoliitika argipäevad / Anita Orban ; tõlk. Ivar Sinimets

    Index Scriptorium Estoniae

    Orban, Anita

    2006-01-01

    Autor leiab, et Ungari välispoliitika on toodud sisepoliitikale ohvriks ja seetõttu suudetakse saavutada ainult murdosake sellest, mida tegelikult tuleks ja saaks teha. Ungari diplomaatia pole võimeline pärast liitumisläbirääkimisi ELiga välja töötama või ellu viima Ungari huve hõlmavat kontseptsiooni. Ülevaade riigi poliitilisest olukorrast

  15. The plant pathogen Pseudomonas syringae pv. tomato is genetically monomorphic and under strong selection to evade tomato immunity.

    Directory of Open Access Journals (Sweden)

    Rongman Cai

    2011-08-01

    Full Text Available Recently, genome sequencing of many isolates of genetically monomorphic bacterial human pathogens has given new insights into pathogen microevolution and phylogeography. Here, we report a genome-based micro-evolutionary study of a bacterial plant pathogen, Pseudomonas syringae pv. tomato. Only 267 mutations were identified between five sequenced isolates in 3,543,009 nt of analyzed genome sequence, which suggests a recent evolutionary origin of this pathogen. Further analysis with genome-derived markers of 89 world-wide isolates showed that several genotypes exist in North America and in Europe indicating frequent pathogen movement between these world regions. Genome-derived markers and molecular analyses of key pathogen loci important for virulence and motility both suggest ongoing adaptation to the tomato host. A mutational hotspot was found in the type III-secreted effector gene hopM1. These mutations abolish the cell death triggering activity of the full-length protein indicating strong selection for loss of function of this effector, which was previously considered a virulence factor. Two non-synonymous mutations in the flagellin-encoding gene fliC allowed identifying a new microbe associated molecular pattern (MAMP in a region distinct from the known MAMP flg22. Interestingly, the ancestral allele of this MAMP induces a stronger tomato immune response than the derived alleles. The ancestral allele has largely disappeared from today's Pto populations suggesting that flagellin-triggered immunity limits pathogen fitness even in highly virulent pathogens. An additional non-synonymous mutation was identified in flg22 in South American isolates. Therefore, MAMPs are more variable than expected differing even between otherwise almost identical isolates of the same pathogen strain.

  16. Firewalls and flat mirrors: An alternative to the AMPS experiment which evades the Harlow-Hayden obstacle

    International Nuclear Information System (INIS)

    Oppenheim, Jonathan; Unruh, Bill

    2014-01-01

    If quantum gravity does not lead to a breakdown of predictability, then Almheiri-Marolf-Polchinski-Sully (AMPS) have argued that an observer falling into a black hole can perform an experiment which verifies a violation of entanglement monogamy — that late time Hawking radiation is maximally entangled with early time Hawking radiation and also with in-falling radiation — something impossible in quantum field theory. However, as pointed out by Hayden and Harlow, this experiment is infeasible, as the time required to perform the experiment is almost certainly longer than the lifetime of the black hole. Here we propose an alternative firewall experiment which could actually be performed within the black hole’s lifetime. The alternative experiment involves forming an entangled black hole in which the unscrambling of information is precomputed on a quantum memory prior to the creation of the black hole and without acting on the matter which forms the black hole or emerges from it. This would allow an observer near a black hole to signal faster than light. As another application of our precomputing strategy, we show how one can produce entangled black holes which acts like “flat mirrors”, in the sense that information comes out almost instantly (as in the Hayden-Preskill scenario), but also emerge unscrambled, so that it can actually be observed instantly as well. Finally, we prove that a black hole in thermal equilibrium with its own radiation, is uncorrelated with this radiation

  17. HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G.

    Directory of Open Access Journals (Sweden)

    Terumasa Ikeda

    2018-04-01

    Full Text Available HIV-1 replication normally requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies were leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to restrictive levels of APOBEC3G. Several resistant viruses were recovered with multiple amino acid substitutions in Env, and these changes alone are sufficient to protect Vif-null viruses from APOBEC3G-dependent restriction in T cell lines. Env adaptations cause decreased fusogenicity, which results in higher levels of Gag-Pol packaging. Increased concentrations of packaged Pol in turn enable faster virus DNA replication and protection from APOBEC3G-mediated hypermutation of viral replication intermediates. Taken together, these studies reveal that a moderate decrease in one essential viral activity, namely Env-mediated fusogenicity, enables the virus to change other activities, here, Gag-Pol packaging during particle production, and thereby escape restriction by the antiviral factor APOBEC3G. We propose a new paradigm in which alterations in viral homeostasis, through compensatory small changes, constitute a general mechanism used by HIV-1 and other viral pathogens to escape innate antiviral responses and other inhibitions including antiviral drugs.

  18. Spitting Image: Tick Saliva Assists the Causative Agent of Lyme Disease in Evading Host Skin's Innate Immune Response

    NARCIS (Netherlands)

    Hovius, Joppe W. R.

    2009-01-01

    Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted through ticks. Inhibition of host skin's innate immune response might be instrumental to both tick feeding and B. burgdorferi transmission. The article by Marchal et al. describes how tick saliva suppresses B.

  19. "Your Whole Effort Has Been to Create Desire": Reproducing Knowledge and Evading Censorship in the Nineteenth- Century Subscription Press.

    Science.gov (United States)

    Puglionesi, Alicia

    2015-01-01

    Historians once regarded the passage of the Comstock Laws in 1873 as a death knell for the public discourse on gender, sex, and reproduction that thrived in the early nineteenth-century United States, but this view has given way to a more complex appreciation of the strategies available to actors seeking knowledge about the body. I examine some of these strategies in late-century health and hygiene manuals. Although certain discourses about sex became closed off, others persisted and evolved in the interstices of Comstock's regulatory state. Readers' demand for information did not abate in 1873; savvy publishers found different ways to meet it, utilizing suggestion, allusion, and nontextual cues from which active readers could extract useful knowledge. A once-public debate about the morality, effectiveness, and appropriate use of contraception had become coded in the pages of health and hygiene manuals, pointing readers to the burgeoning mass market for contraceptive devices as a locus of reproductive control.

  20. Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization.

    Science.gov (United States)

    Haller, Samantha; Franchet, Adrien; Hakkim, Abdul; Chen, Jing; Drenkard, Eliana; Yu, Shen; Schirmeier, Stefanie; Li, Zi; Martins, Nelson; Ausubel, Frederick M; Liégeois, Samuel; Ferrandon, Dominique

    2018-03-09

    When Drosophila melanogaster feeds on Pseudomonas aeruginosa , some bacteria cross the intestinal barrier and eventually proliferate in the hemocoel. This process is limited by hemocytes through phagocytosis. P. aeruginosa requires the quorum-sensing regulator RhlR to elude the cellular immune response of the fly. RhlI synthesizes the autoinducer signal that activates RhlR. Here, we show that rhlI mutants are unexpectedly more virulent than rhlR mutants, both in fly and in nematode intestinal infection models, suggesting that RhlR has RhlI-independent functions. We also report that RhlR protects P. aeruginosa from opsonization mediated by the Drosophila thioester-containing protein 4 (Tep4). RhlR mutant bacteria show higher levels of Tep4- mediated opsonization, as compared to rhlI mutants, which prevents lethal bacteremia in the Drosophila hemocoel. In contrast, in a septic model of infection, in which bacteria are introduced directly into the hemocoel, Tep4 mutant flies are more resistant to wild-type P. aeruginosa, but not to the rhlR mutant. Thus, depending on the infection route, the Tep4 opsonin can either be protective or detrimental to host defense. © 2018 The Authors.

  1. Jaani kirik seljatas aasta teo konkursil hansapäevad / Mari-Liis Hüvato, Martin Shmutov

    Index Scriptorium Estoniae

    Hüvato, Mari-Liis

    2005-01-01

    Tartlased ja Postimehe lugejad tunnistasid Tartu 2005. aasta väärikaimaks teoks Jaani kiriku taastamise, kommenteerivad Juhani Jaeger, Toomas Peterson, Reet Mägi. Loetletud konkursil osalenud Tartu aasta teod 2005 ja varasemad aasta teod

  2. Tantsiva lauljana tuntud Lowry üllitas uue singli. Tulekul on järjekordsed kitarrimuusikapäevad

    Index Scriptorium Estoniae

    2007-01-01

    Lowry (Lauri Pihlapi) singlist "Come back" ja tema detsembris ilmuvast heliplaadist "Split personality". 6. rahvusvahelistest kitarrimuusikapäevadest "Fiesta de la guitarra" 7.-11. nov. Tallinnas ja Tartus

  3. Indication of viruses and virus-specific antibodies by ELISA using conjugates based on β-lactamase obtained by genetic engineering

    International Nuclear Information System (INIS)

    Kharitonenkov, I.G.; Kordym, V.A.; Khristova, M.L.; Leonov, S.V.; Kirillova, V.S.; Chernykh, S.I.

    1987-01-01

    The method of enzyme-linked immunosorbent assay (ELISA), by means of which antigens and antibodies of different origin can be detected with high sensitivity and specificity, is an immunoenzymatic technique based on the use of conjugates, or macromolecular complexes formed by covalent attachment of enzyme molecules to antigen or antibody molecules. Conjugates based on peroxidase, alkaline phosphatase, and beta-galactosidase are most frequently used to construct immunoenzymatic test systems. The use of these enzymes in ELISA, however, is complicated by the fact that they are often present in free or bound form in the biological material under study, and that their substrates either possess low stability, are difficult to synthesize, or are toxic. In this paper, in order to avoid these shortcomings, the authors develop a method for the biosynthesis of lactamase conjugates which is based on genetic engineering, and demonstrate the viability and stability of these conjugates in radioimmunoenzymatic assay of viruses

  4. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Bates, John T. [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Keefer, Christopher J. [The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Slaughter, James C. [The Vanderbilt Vaccine Center, Departments of Biostatistics and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Kulp, Daniel W. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Schief, William R. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA (United States); Crowe, James E., E-mail: james.crowe@vanderbilt.edu [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2014-04-15

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

  5. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Directory of Open Access Journals (Sweden)

    Ashley L Fink

    2017-07-01

    Full Text Available Dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4. At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE by binding to viral antigens and then Fcγ receptors (FcγR on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

  6. Augmentation of alphavirus vector-induced human papilloma virus-specific immune and anti-tumour responses by co-expression of interleukin-12

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Regts, Joke; Chen, Margaret; Wilschut, Jan; Daemen, Toos

    2009-01-01

    To enhance the efficacy of a therapeutic immunisition strategy against human papillomavirus-induced cervical cancer we evaluated the adjuvant effect of interleukin-12 (IL12) expressed by a Semliki Forest virus vector (SFV) in mice. Depending on the dose and schedule. SFV-IL12 Stimulated

  7. Comparison of Bovine coronavirus-specific and Bovine respiratory syncytial virus-specific antibodies in serum versus milk samples detected by enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Ohlson, Anna; Blanco-Penedo, Isabel; Fall, Nils

    2014-01-01

    Bovine coronavirus (BCV; Betacoronavirus 1) and Bovine respiratory syncytial virus (BRSV) are significant causes of enteric and respiratory disease in beef and dairy cattle throughout the world. Indirect enzyme-linked immunosorbent assays are widely used to detect serum antibodies for herd monitoring and prevalence studies. In dairy herds, milk is more readily collected than serum. Hence, in order to investigate the test agreement between serum and milk, both serum and milk samples from 105 cows in 27 dairy herds were analyzed in parallel for presence of immunoglobulin G antibodies to BCV and BRSV. The Bland-Altman analyses of data demonstrated good agreement between serum and milk antibody titers for both viruses. The results indicate milk samples are sufficient for surveillance of antibodies to BCV and BRSV.

  8. Detection of West Nile virus-specific antibodies and nucleic acid in horses and mosquitoes, respectively, in Nuevo Leon State, northern Mexico, 2006-2007.

    Science.gov (United States)

    Ibarra-Juarez, L; Eisen, L; Bolling, B G; Beaty, B J; Blitvich, B J; Sanchez-Casas, R M; Ayala-Sulca, Y O; Fernandez-Salas, I

    2012-09-01

    In the last 5 years, there has been only one reported human case of West Nile virus (WNV) disease in northern Mexico. To determine if the virus was still circulating in this region, equine and entomological surveillance for WNV was conducted in the state of Nuevo Leon in northern Mexico in 2006 and 2007. A total of 203 horses were serologically assayed for antibodies to WNV using an epitope-blocking enzyme-linked immunosorbent assay (bELISA). Seroprevalences for WNV in horses sampled in 2006 and 2007 were 26% and 45%, respectively. Mosquito collections in 2007 produced 7365 specimens representing 15 species. Culex mosquitoes were screened for WNV RNA and other genera (Mansonia, Anopheles, Aedes, Psorophora and Uranotaenia) were screened for flaviviruses using reverse-transcription (RT)-PCR. Two pools consisting of Culex spp. mosquitoes contained WNV RNA. Molecular species identification revealed that neither pool included Culex quinquefasciatus (Say) (Diptera:Culicidae) complex mosquitoes. No evidence of flaviviruses was found in the other mosquito genera examined. These data provide evidence that WNV is currently circulating in northern Mexico and that non-Cx. quinquefasciatus spp. mosquitoes may be participating in the WNV transmission cycle in this region. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  9. Perforin and IFN-gamma do not significantly regulate the virus-specific CD8+ T cell response in the absence of antiviral effector activity

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Wodarz, Dominik; Christensen, Jan P

    2004-01-01

    Using gene-targeted mice we have investigated whether perforin and/or interferon-gamma exert a direct regulatory effect on the expansion and contraction of antigen-specific CD8(+) T cells following infection with a virus (vesicular stomatitis virus) which is not controlled through these molecular...

  10. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    International Nuclear Information System (INIS)

    Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schief, William R.; Crowe, James E.

    2014-01-01

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K on ) for binding to RSV F protein, while alteration of dissociation rate (K off ) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K on with reduced potency mirrored the effect of increased K on found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K on ) correlated well with the potency of neutralization

  11. First Evidence for the Disease-Stage, Cell-Type, and Virus Specificity of microRNAs during Human Immunodeficiency Virus Type-1 Infection

    Directory of Open Access Journals (Sweden)

    Lauren Fowler

    2016-05-01

    Full Text Available The potential involvement of host microRNAs (miRNAs in HIV infection is well documented, and evidence suggests that HIV modulates and also dysregulates host miRNAs involved in maintaining the host innate immune system. Moreover, the dysregulation of host miRNAs by HIV also effectively interferes directly with the host gene expression. In this study, we have simultaneously evaluated the expression of host miRNAs in both CD4+ and CD8+ T-cells derived from HIV-positive (HIV+ individuals (viremic and aviremic individuals while receiving highly active antiretroviral therapy (HAART, therapy-naïve long-term non-progressors (LTNP, and HIV-negative (HIV– healthy controls. miRNAs were run on Affymetrix V2 chips, and the differential expression between HIV+ and HIV− samples, along with intergroup comparisons, was derived using PARTEK software, using an FDR of 5% and an adjusted p-value < 0.05. The miR-199a-5p was found to be HIV-specific and expressed in all HIV+ groups as opposed to HIV– controls. Moreover, these are the first studies to reveal clearly the highly discriminatory miRNAs at the level of the disease state, cell type, and HIV-specific miRNAs.

  12. Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction.

    Science.gov (United States)

    Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

    2015-09-01

    Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Tick-borne encephalitis virus-specific RT-PCR - a rapid test for detection of the pathogen without viral RNA purification

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Cihlářová, Věra; Grubhoffer, Libor

    2004-01-01

    Roč. 48, č. 3 (2004), s. 167-171 ISSN 0001-723X R&D Projects: GA ČR GA524/03/1326 Institutional research plan: CEZ:AV0Z6022909 Keywords : Ixodes ricinus * tick-borne encephalitis virus * RT-PCR Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 0.605, year: 2004

  14. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Science.gov (United States)

    Fink, Ashley L; Williams, Katherine L; Harris, Eva; Alvine, Travis D; Henderson, Thomas; Schiltz, James; Nilles, Matthew L; Bradley, David S

    2017-07-01

    Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

  15. Demonstration of the serum antibody to Epstein-Barr virus specific DNA polymerased (EBV-DP) from patients with nasopharyngeal carcinoma (NPC)

    Energy Technology Data Exchange (ETDEWEB)

    Tan, R.S.; Li, J.S.; Grill, S.; Nutter, L.M.; Cheng, Y.C.

    1986-03-05

    Raji cells, an EBV genome carrying and nonproducer cell line, treated with tetradecanoyl-phorbol-13-acetate (TPA) and n-butyrate could induce a special DNA polymerase which has properties that are similar to the EBV-DP induced by TPA in P/sub 3/HR-I cells, an EBV producer cell line. Since EBV was found to have a strong association with NPC, and antibodies against EBV proteins or enzymes were found in high levels in sera from these patients, the possible presence of serum antibody against EBV-DP was examined. The serum titer of antibody to EBV-DP was found to have 190 +/- 84 units/ml serum (mean +/- S.D.) in 48 sera from patients with NPC. The titer in 52 healthy donors was 31.4 +/- 28 unit/ml serum (p < 0.01). The antibody was found to be associated with the IgG but not the IgA fraction. The antibody titers against EBV-DP were not correlated with the titer against EBV-DNase or VCA-IgA. Whether the antibody observed is against an EBV-DP core protein or its stimulating protein, as demonstrated by this laboratory previously, is still being investigated. This study demonstrated the high frequency and high titer of antibody against EBV-DP in serum from patients with NPC, and suggested the potential of utilizing this antibody titer to compliment other methods for the early diagnosis or prognosis of NPC.

  16. How much of Virus-Specific CD8 T Cell Reactivity is Detected with a Peptide Pool when Compared to Individual Peptides?

    Directory of Open Access Journals (Sweden)

    Ramu A. Subbramanian

    2012-10-01

    Full Text Available Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides, when restricted by the same HLA allele, and presented from within the same peptide pool, can compete for HLA binding sites. What impact such competition has on functional T cell stimulation, however, is not clear. Using a model peptide pool that is comprised of 32 well-defined viral epitopes from Cytomegalovirus, Epstein-Barr virus, and Influenza viruses (CEF peptide pool, we assessed peptide competition in PBMC from 42 human subjects. The magnitude of the peptide pool-elicited CD8 T cell responses was a mean 79% and a median 77% of the sum of the CD8 T cell responses elicited by the individual peptides. Therefore, while the effect of peptide competition was evident, it was of a relatively minor magnitude. By studying the dose-response curves for individual CEF peptides, we show that several of these peptides are present in the CEF-pool at concentrations that are orders of magnitude in excess of what is needed for the activation threshold of the CD8 T cells. The presence of such T cells with very high functional avidity for the viral antigens can explain why the effect of peptide competition is relatively minor within the CEF-pool.

  17. CD8+ T lymphocytes of patients with AIDS maintain normal broad cytolytic function despite the loss of human immunodeficiency virus-specific cytotoxicity

    International Nuclear Information System (INIS)

    Pantaleo, G.; De Maria, A.; Koenig, S.; Butini, L.; Moss, B.; Lane, H.C.; Fauci, A.S.; Baseler, M.

    1990-01-01

    In this study, the authors have investigated the potential mechanisms responsible for the loss of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic activity in the advanced stages of HIV-1 infection. They have demonstrated that HIV-1-specific cytotoxic T lymphocytes are predominantly contained within the CD8 + DR + subset. Furthermore, they have shown by a redirected killing assay that there is a dichotomy between HIV-1-specific cytolytic activity and broad cytolytic potential since the cytolytic machinery of CD8 + DR + cells is still functioning even in patients with AIDS who have lost their HIV-1-specific cytolytic activity. In addition, by comparative analysis of these two types of cytolytic activity over time they have demonstrated a progressive loss of HIV-1-specific cytolytic activity in the advanced stages of the disease, whereas the cytolytic potential remained unchanged regardless of the clinical stage. On the basis of these results, they propose that the loss of HIV-1-specific cytolytic activity in HIV-1-infected individuals may result at least in part from a progressive decrease in the pool of HIV-1-specific cytotoxic T lymphocytes belonging to the CD8 + DR + subset whose ability to expand has been impaired

  18. Rabies virus-specific human T cell clones provide help for an in vitro antibody response against neutralizing antibody-inducing determinants of the viral glycoprotein.

    NARCIS (Netherlands)

    H. Bunschoten; R.J. Klapmuts; I.J.Th.M. Claassen (Ivo); S.D. Reijneveld; A.D.M.E. Osterhaus (Albert); F.G.C.M. Uytdehaag (Fons)

    1989-01-01

    textabstractHuman T cell clones were prepared from peripheral blood mononuclear cells from a vaccinated human donor and kept in culture in the presence of rabies virus antigen and growth factors. Phenotypic analysis of the T cell clones revealed expression of the CD3 and CD4 cell surface markers,

  19. Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element

    NARCIS (Netherlands)

    Piersma, Sytse J.; Welters, Marij J. P.; van der Hulst, Jeanette M.; Kloth, Judith N.; Kwappenberg, Kitty M. C.; Trimbos, Baptist J.; Melief, Cornelis J. M.; Hellebrekers, Bart W.; Fleuren, Gert Jan; Kenter, Gemma G.; Offringa, Rienk; van der Burg, Sjoerd H.

    2008-01-01

    Human papillomavirus (HPV)-induced malignancies are frequently infiltrated by lymphocytes. To comprehend the contribution of HPV-specific T cells in this anti-tumor response we developed a method that allowed the analysis of the presence and specificity of cervix-infiltrating and draining lymph node

  20. Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response

    DEFF Research Database (Denmark)

    Embregts, Carmen W. E.; Rigaudeau, Dimitri; Veselý, Tomas

    2017-01-01

    Although spring viremia of carp virus (SVCV) can cause high mortalities in common carp, a commercial vaccine is not available for worldwide use. Here, we report a DNA vaccine based on the expression of the SVCV glycoprotein (G) which, when injected in the muscle even at a single low dose of 0.1 μg...... DNA/g of fish, confers up to 100% protection against a subsequent bath challenge with SVCV. Importantly, to best validate vaccine efficacy, we also optimized a reliable bath challenge model closely mimicking a natural infection, based on a prolonged exposure of carp to SVCV at 15°C. Using...... this optimized bath challenge, we showed a strong age-dependent susceptibility of carp to SVCV, with high susceptibility at young age (3 months) and a full resistance at 9 months. We visualized local expression of the G protein and associated early inflammatory response by immunohistochemistry and described...

  1. Cytokine production by virus-specific CD8(+) T cells varies with activation state and localization, but not with TCR avidity

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Madsen, Andreas Nygaard; Thomsen, Allan Randrup

    2004-01-01

    produce a similar range of cytokines (IFN-gamma, TNF-alpha, IL-2, GM-CSF, RANTES, MIP-1alpha and MIP-1beta) as CD4(+) T cells, but the relative distribution of cytokine-producing subsets is different. Moreover, cytokine-producing CD8(+) T cells were found to dominate numerically at all time-points tested...... (peritoneum) and generally increased with transition into the memory phase; however, GM-CSF producing cells were only present transiently. Concerning factors predicted to influence the distribution of cytokine-producing subsets, IFN-gamma and IL-12 did not play a role, nor was extensive virus replication...

  2. Programmed Death-1 expression on Epstein Barr virus specific CD8+ T cells varies by stage of infection, epitope specificity, and T-cell receptor usage.

    Directory of Open Access Journals (Sweden)

    Thomas C Greenough

    Full Text Available BACKGROUND: Programmed Death-1 (PD-1 is an inhibitory member of the CD28 family of molecules expressed on CD8+ T cells in response to antigenic stimulation. To better understand the role of PD-1 in antiviral immunity we examined the expression of PD-1 on Epstein-Barr virus (EBV epitope-specific CD8+ T cells during acute infectious mononucleosis (AIM and convalescence. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we observed higher frequencies of EBV-specific CD8+ T cells and higher intensity of PD-1 expression on EBV-specific CD8+ T cells during AIM than during convalescence. PD-1 expression during AIM directly correlated with viral load and with the subsequent degree of CD8+ T cell contraction in convalescence. Consistent differences in PD-1 expression were observed between CD8+ T cells with specificity for two different EBV lytic antigen epitopes. Similar differences were observed in the degree to which PD-1 was upregulated on these epitope-specific CD8+ T cells following peptide stimulation in vitro. EBV epitope-specific CD8+ T cell proliferative responses to peptide stimulation were diminished during AIM regardless of PD-1 expression and were unaffected by blocking PD-1 interactions with PD-L1. Significant variability in PD-1 expression was observed on EBV epitope-specific CD8+ T cell subsets defined by V-beta usage. CONCLUSIONS/SIGNIFICANCE: These observations suggest that PD-1 expression is not only dependent on the degree of antigen presentation, but also on undefined characteristics of the responding cell that segregate with epitope specificity and V-beta usage.

  3. Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome.

    Science.gov (United States)

    Ferraro, Diana; Galli, Veronica; Simone, Anna Maria; Bedin, Roberta; Vitetta, Francesca; Merelli, Elisa; Nichelli, Paolo Frigio; Sola, Patrizia

    2017-04-01

    Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years.

  4. Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels.

    Directory of Open Access Journals (Sweden)

    Elisabetta Loggi

    Full Text Available BACKGROUND AIMS: The immune impairment characterizing chronic hepatitis B (cHBV infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV. METHODS: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay. RESULTS: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients. CONCLUSIONS: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

  5. The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype

    NARCIS (Netherlands)

    A.C.M. Boon (Adrianus); G. de Mutsert (Gerrie); Y.M.F. Graus; R.A.M. Fouchier (Ron); K. Sintnicolaas (Krijn); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2002-01-01

    textabstractThe repertoire of human cytotoxic T-lymphocytes (CTL) in response to influenza A viruses has been shown to be directed towards multiple epitopes, with a dominant response to the HLA-A2-restricted M1(58-66) epitope. These studies, however, were performed with peripheral blood mononuclear

  6. Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.

    Science.gov (United States)

    Franzen-Röhl, Elisabeth; Schepis, Danika; Atterfelt, Fredrik; Franck, Kristina; Wikström, Arne; Liljeqvist, Jan-Åke; Bergström, Tomas; Aurelius, Elisabeth; Kärre, Klas; Berg, Louise; Gaines, Hans

    2017-05-01

    During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. HSV-specific interleukin(Il)-4 and Il-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. In vitro generation of Epstein-Barr virus-specific cytotoxic T cells in patients receiving haplo-identical allogeneic stem cell transplantation.

    Science.gov (United States)

    Musk, P; Szmania, S; Galloway, A T; Johnson, K; Scott, A; Guttman, S; Bridges, K; Bruorton, M; Gatlin, J; Garcia, J V; Lamb, L; Chiang, K Y; Spencer, T; Henslee-Downey, J; van Rhee, F

    2001-01-01

    Use of a partially mismatched related donor (PMRD) is an option for patients who require allogeneic transplantation but do not have a matched sibling or unrelated donor. Epstein-Barr virus (EBV)-induced lymphoma is a major cause of mortality after PMRD transplantation. In this study, we present a clinical grade culture system for donor-derived EBV-specific cytotoxic T cells (CTLs) that do not recognize haplo-identical recipient cells. The EBV-specific CTLs were tested for cytolytic specificity and other functional properties, including ability to transgress into tissues, propensity for apoptosis, degree of clonality, stability of dominant T-cell clones, and Tc and Th phenotypes. The EBV-specific CTLs were routinely expanded to greater than 80 x 10(6) over a period of 5 weeks, which is sufficient for clinical application. A CD8+ phenotype predominated, and the CTLs were highly specific for donor lymphoblastoid cell lines (LCLs) without killing of recipient targets or K562. Vbeta spectratyping showed an oligoclonal population that was stable on prolonged culture. The EBV-specific CTLs were activated (D-related human leukocyte antigen [HLA-DR+], L-selectin+/-) and of memory phenotype (CD45RO+). Expression of the integrin VLA-4 suggested that these CTLs could adhere to endothelium and migrate into tissues. The Bcl-2 message was upregulated, which may protect the CTLs from the apoptosis. The first demonstration of overexpression of bcl-2 in human memory CTLs. In addition, we show that lymphoblastoid cell lines used to generate CTLs are readily genetically modified with recombinant lentivirus, indicating that genetically engineered antigen presentation is feasible.

  8. The role of CD80/CD86 in generation and maintenance of functional virus-specific CD8+ T cells in mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Bartholdy, Christina; Remy, Melissa

    2010-01-01

    Lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cell responses are considered to be independent of CD28-B7 costimulation. However, the LCMV-specific response has never been evaluated in B7.1/B7.2(-/-) mice. For this reason, we decided to study the T cell response in B7.1/B7.2(-/-) mice......, but no chronic infection. Taken together, these results indicate that B7 costimulation is required for induction and maintenance of LCMV-specific CD8(+) T cell memory, irrespective of the LCMV strain used for priming. However, the erosion of CD8(+) T cell memory in B7.1/B7.2(-/-) mice was more pronounced...

  9. Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

    Directory of Open Access Journals (Sweden)

    Samantha J Westrop

    Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

  10. Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice

    Science.gov (United States)

    Jaiswal, Smita; Pazoles, Pamela; Woda, Marcia; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2012-01-01

    Dengue is a mosquito-borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD-scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co-transplantation of human fetal thymus and liver tissues into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell-engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice secreted interferon-γ in response to overlapping DENV peptide pools and HLA-A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections. PMID:22384859

  11. Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

    Science.gov (United States)

    Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

    2015-01-01

    Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

  12. Friend and Moloney murine leukemia viruses specifically recombine with different endogenous retroviral sequences to generate mink cell focus-forming viruses.

    Science.gov (United States)

    Evans, L H; Cloyd, M W

    1985-01-01

    A group of mink cell focus-forming (MCF) viruses was derived by inoculation of NFS/N mice with Moloney murine leukemia virus (Mo-MuLV 1387) and was compared to a similarly derived group of MCF viruses from mice inoculated with Friend MuLV (Fr-MuLV 57). Antigenic analyses using monoclonal antibodies specific for MCF virus and xenotropic MuLV envelope proteins and genomic structural analyses by RNase T1-resistant oligonucleotide finger-printing indicated that the Moloney and Friend MCF viruses arose by recombination of the respective ecotropic MuLVs with different endogenous retrovirus sequences of NFS mice.

  13. Muusikamaailm : Kammermuusikapäevad Wittenis. Ligeti ooper heliplaadil. Firenze maifestival. Poola tagastab käsikirjad Saksamaale. Mirjam Helini nimeline konkurss / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    Aprilli viimasel nädalavahetusel toimuvast Witteni uue kammermuusika päevadest Saksamaal. Ligeti ooperi "Le grand macabre" äsja ilmunud plaadistusest. Firenzes avati 15.aprillil iga-aastane festival Maggio Musicale Fiorentino. Poola tagastabSaksamaale nn. Berliini raamatukogu muusikakäsikirjad, mis natsid toimetasid Poolasse 1939.a. Põhjamaade mainekamaid lauljate konkursse selgitas eelvaliku põhjal konkursile pääsejad

  14. Validation of the general test for the evaluation of development for children and adolescents aged 6 to 14 years old (EVADE

    Directory of Open Access Journals (Sweden)

    Ana María Quezada Ugalde

    2015-07-01

    Full Text Available Introduction. In this paper the results of the validation of the General Test Development Evaluation children and adolescents are presented (CIRCUMVENT, consistent with the growth needs, interests and development of the Costa Rican population between the ages of 6 and 14 years. Methodology. The methodology was qualitative, transversal and exploratory. For this purpose, conducted a validation process that included: technical expert judgment type aggregates individual; in the first phase results analysis, triangulation was used, resulting in the modified CIRCUMVENT. Subsequently, a pilot with 300 children and adolescents aged 6 to 14 years old, schools and colleges both public and private Metropolitan Area, San Jose, Costa Rica was made; using an observation guide for the collection of the data provided in this test. In the second phase, the results obtained with the theoretical triangulation, a new version of CIRCUMVENT was structured. Results. There is limited literature regarding developmental screening tests in middle childhood and adolescence; technical expert judgment confirmed the inconsistency of some items of CIRCUMVENT; was necessary to create standardized instructional materials for the application of the test. Conclusion. This research provides two significant inputs: a book with instructions for the interpretation and application of CIRCUMVENT, and standardized materials for implementation

  15. Uudised : Don Juan jõuab Estonia lavale. VII Rudolf Tobiase päevad Hiiumaal. Esineb Laine Leichteri koolkond / Liina Teder

    Index Scriptorium Estoniae

    Teder, Liina

    1999-01-01

    3.juunil Estonias esietenduvast Mozarti ooperist "Don Giovanni". 28.-29.05 toimuvatest VII R. Tobiase päevadest, mis on pühendatud helilooja 126. sünniaastapäevale. 3.06 Mustpeade Majas toimuvast L. Leichteri juubelikontserdist

  16. Uudised : Sumera VI sümfoonia Saksamaa esiettekanne. Mati Palm Peterburis. Globaliseerumine ja identiteet. Muusikapäevad Oleviste Maarja kabelis / Merike Utt

    Index Scriptorium Estoniae

    Utt, Merike

    2001-01-01

    5. ja 6. apr. toimus Frankfurdis L.Sumera 6. sümfoonia ettekanne. M.Palm andis soolokontserdi 15. mail Peterburis. Euroopa Koolimuusika Assotsiatsiooni konverentsist "Globaliseerumine ja identiteet" 10.-13. maini Riias. 22. mail alanud Oleviste Maarja kabeli muusikapäevadest

  17. 2. ja 3. mail kella 10-19 on Tallinna kultuurirahvaülikoolis (TKRÜ) lahtiste uste päevad

    Index Scriptorium Estoniae

    2002-01-01

    TKRÜ kunsti- ja käsitöökursustel valminud tööde näitusel on väljas Heino Kivihalli kalligraafiakeskuse õpilaste, Jüri Sillarti fotokursuslaste, kunstistuudio, klaasikunsti, nahakunsti ja siidimaali õpilaste tööd, lapitööd. Vastuvõtust 2002/03. a. kursustele, õppejõududest. Avatakse Ülle Marksi laste kunstikursus. 3. V origami kursuse esitlus (Niina Juganson)

  18. The Effect of a Vegan versus AHA DiEt in Coronary Artery Disease (EVADE CAD) trial: study design and rationale.

    Science.gov (United States)

    Shah, Binita; Ganguzza, Lisa; Slater, James; Newman, Jonathan D; Allen, Nicole; Fisher, Edward; Larigakis, John; Ujueta, Francisco; Gianos, Eugenia; Guo, Yu; Woolf, Kathleen

    2017-12-01

    Multiple studies demonstrate the benefit of a vegan diet on cardiovascular risk factors when compared to no intervention or usual dietary patterns. The aim of this study is to evaluate the effect of a vegan diet versus the American Heart Association (AHA)-recommended diet on inflammatory and glucometabolic profiles in patients with angiographically defined coronary artery disease (CAD). This study is a randomized, open label, blinded end-point trial of 100 patients with CAD as defined by ≥50% diameter stenosis in a coronary artery ≥2 mm in diameter on invasive angiography. Participants are randomized to 8 weeks of either a vegan or AHA-recommended diet (March 2014 and February 2017). Participants are provided weekly groceries that adhere to the guidelines of their diet. The primary endpoint is high sensitivity C-reactive concentrations. Secondary endpoints include anthropometric data, other markers of inflammation, lipid parameters, glycemic markers, endothelial function, quality of life data, and assessment of physical activity. Endpoints are measured at each visit (baseline, 4 weeks, and 8 weeks). Dietary adherence is measured by two weekly 24-hour dietary recalls, a 4-day food record during the week prior to each visit, and both plasma and urine levels of trimethylamine- N -oxide at each visit. This study is the first to comprehensively assess multiple indices of inflammation and glucometabolic profile in a rigorously conducted randomized trial of patients with CAD on a vegan versus AHA-recommended diet.

  19. Muusikamaailm : Praemium Imperiale kätteandmine. Vanamuusika päevad Hernes. Uus ooper Don Quijotest. Soome muusikud Münchenis / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    Jaapani kunstide auhinna "Praemium Imperiale" laureaatidest. Lääne-Saksa Raadio festivalist "Herne", tänavu pealkirja all "Spiel auf, Europa!". C. Halffteri uudisooper "Don Quijote" tuleb maailmaesiettekandele Madridis 2000. a. veebruaris. Soome muusikute kontsertidest sügishooajal Baierimaal ja Münchenis

  20. Muusikamaailm : Hong Kong Arts Festival. "Haydni päevad" Viinis. "Ars Musica" Brüsselis. Martha Mödli mälestuseks / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2002-01-01

    22. II - 19. III toimuvast Hong Kong Arts Festivalist. Viinis toimuvast muusikaüritusest "Haydn-Tage". 7. - 24.III Brüsselis toimuvast uue muusika festivalist"Ars Musica". Meenutatakse saksa ooperisopranit Martha Mödli

  1. Ene-Liis Semper: selle aasta puhkepäevad võib ühe käe sõrmedel kokku lugeda

    Index Scriptorium Estoniae

    Semper, Ene-Liis, 1969-

    2011-01-01

    Tallinna kultuuripealinna projekti panustanud Ene-Liis Semper võtab 2011. aasta sündmused kokku ja selgitab, kuidas jõudsid publiku ette suurlavastused "The Rise and Fall of Estonia", "Three Kingdoms", Põhuteater ning isikunäitus Kumus

  2. The effect of a vegan versus AHA DiEt in coronary artery disease (EVADE CAD trial: Study design and rationale

    Directory of Open Access Journals (Sweden)

    Binita Shah

    2017-12-01

    Conclusion: This study is the first to comprehensively assess multiple indices of inflammation and glucometabolic profile in a rigorously conducted randomized trial of patients with CAD on a vegan versus AHA-recommended diet.

  3. Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.

    Directory of Open Access Journals (Sweden)

    Shi Qun Zhang

    2016-05-01

    Full Text Available The cell wall is a dynamic structure that is important for the pathogenicity of Candida albicans. Mannan, which is located in the outermost layer of the cell wall, has been shown to contribute to the pathogenesis of C. albicans, however, the molecular mechanism by which this occurs remains unclear. Here we identified a novel α-1,6-mannosyltransferase encoded by MNN10 in C. albicans. We found that Mnn10 is required for cell wall α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion of MNN10 resulted in significant attenuation of the pathogenesis of C. albicans in a murine systemic candidiasis model. Inhibition of α-1,6-mannose backbone extension did not, however, impact the invasive ability of C. albicans in vitro. Notably, mnn10 mutant restored the invasive capacity in athymic nude mice, which further supports the notion of an enhanced host antifungal defense related to this backbone change. Mnn10 mutant induced enhanced Th1 and Th17 cell mediated antifungal immunity, and resulted in enhanced recruitment of neutrophils and monocytes for pathogen clearance in vivo. We also demonstrated that MNN10 could unmask the surface β-(1,3-glucan, a crucial pathogen-associated molecular pattern (PAMP of C. albicans recognized by host Dectin-1. Our results demonstrate that mnn10 mutant could stimulate an enhanced Dectin-1 dependent immune response of macrophages in vitro, including the activation of nuclear factor-κB, mitogen-activated protein kinase pathways, and secretion of specific cytokines such as TNF-α, IL-6, IL-1β and IL-12p40. In summary, our study indicated that α-1,6-mannose backbone is critical for the pathogenesis of C. albicans via shielding β-glucan from recognition by host Dectin-1 mediated immune recognition. Moreover, our work suggests that inhibition of α-1,6-mannose extension by Mnn10 may represent a novel modality to reduce the pathogenicity of C. albicans.

  4. Teater : Tänavused balletipreemiad. "Prima la Donna". Kontsertetendus "Sina ja mina". Rahvakultuur : Laste murdelaulu ja -luulepäevad tänavu Hageris / Vesta Uuetoa

    Index Scriptorium Estoniae

    Uuetoa, Vesta

    2002-01-01

    Rahvusooperis laulab "Boheemis" külaline Soomest - Ari Grönthal. Kadrioru lossis antakse üle traditsioonilised balletiauhinnad. 20.-26. V toimub rahvusooperis Estonia ooperi ja balletifestival "Prima la Donna", mille teemaks on saatuslikud, tähelepanuväärsed ja jõulised naised. Kurt Weilli ja Lotte Lenya elu draamas ja muusikas on lavastanud Mart Kampus. 18. ja 19. mail saavad Hageris kokku murdelaulu ja -luulega tegelevad lapsed

  5. HIV-specific CD8+ T cells: serial killers condemned to die?

    Science.gov (United States)

    Petrovas, Constantinos; Mueller, Yvonne M; Katsikis, Peter D

    2004-04-01

    An increasing body of evidence supports a key role for cytotoxic CD8+ T cells (CTL) in controlling HIV infection. Although a vigorous HIV-specific CD8+ T cell response is raised during the primary infection, these cells ultimately fail to control virus and prevent disease progression. The failure of CTL to control HIV infection has been attributed to a number of strategies HIV employs to evade the immune system. Recently, intrinsic defects in the CTL themselves have been proposed to contribute to the failure of CTL to control HIV. HIV-specific CD8+ T cells differ in their effector/memory phenotype from other virus-specific CD8+ T cells indicating that their differentiation status differs. This altered differentiation may affect effector functions as well as homing properties of these cells. Other studies have indicated that activation of HIV-specific CTL may be impaired and this contributes to their dysfunction. The effector function of these CTL may also be affected. There are conflicting reports about their ability to kill, whereas IFNgamma production does not appear to be impaired in these cells. In this review we focus on recent work indicating that apoptosis may be an important mechanism through which HIV evades the CTL response. In particular, HIV-specific CD8+ T cells are highly susceptible to CD95/Fas-induced apoptosis. This leads to the hypothesis that virus-specific cytotoxic T cells can be eliminated upon binding CD95L/FasL on HIV-infected cells. Understanding the intrinsic defects of CTL in HIV infection could lead to new therapeutic strategies and optimized vaccination protocols that enhance the HIV-specific cytotoxic response.

  6. Successful generation of primary virus-specific and anti-tumor T-cell responses from the naive donor T-cell repertoire is determined by the balance between antigen-specific precursor T cells and regulatory T cells.

    NARCIS (Netherlands)

    Jedema, I.; Meent, M. van de; Pots, J.M.; Kester, M.G.; Beek, M.T. van der; Falkenburg, J.H.F.

    2011-01-01

    BACKGROUND: One of the major challenges in allogeneic stem cell transplantation is to find a balance between the harmful induction of graft-versus-host disease and the beneficial graft-versus-leukemia and pathogen-specific immune responses. Adoptive transfer of in-vitro generated donor T cells with

  7. Development of a combined canine distemper virus specific RT-PCR protocol for the differentiation of infected and vaccinated animals (DIVA) and genetic characterization of the hemagglutinin gene of seven Chinese strains demonstrated in dogs.

    Science.gov (United States)

    Yi, Li; Cheng, Shipeng; Xu, Hongli; Wang, Jianke; Cheng, Yuening; Yang, Shen; Luo, Bin

    2012-01-01

    A combined reverse-transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of the canine distemper virus (CDV). A pair of primers (P1/P2) was used to detect both CDV wild-type strains and vaccines. Another pair (P3/P4) was used to detect only CDV wild-type strains. A 335bp fragment was amplified from the genomic RNA of the vaccine and wild-type strains. A 555bp fragment was amplified specifically from the genomic RNA of the wild-type strains. No amplification was achieved for the uninfected cells, cells infected with canine parvovirus, canine coronavirus, or canine adenovirus. The combined RT-PCR method detected effectively and differentiated the CDV wild-type and vaccine strains by two separate RT-PCRs. The method can be used for clinical detection and epidemiological surveillance. The phylogenetic analysis of the hemagglutinin gene of the local wild-type CDV strains revealed that the seven local isolates all belonged to the Asia-1 lineage, and were clustered closely with one another at the same location. These results suggested that the CDV genotype Asia-1 is circulating currently in domestic dogs in China. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. A Multi-Agent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

    Science.gov (United States)

    2016-07-26

    expression 128 of the structural proteins by adapting the gene sequence to reflect the codon bias of highly-129 expressed Homo sapiens genes...optimized expression in Homo sapiens followed by synthesis of the codon-167 optimized genes (Geneart). VEEV, WEEV, and EEEV DNA vaccine plasmids were...735 to biological warfare agents. Clin Lab Med 21:435-473. 736 9. Hanson RP, Sulkin SE, Beuscher EL , Hammon WM, McKinney RW, Work TH. 1967. Arbovirus

  9. Development of a Novel, Ultra-rapid Biosensor for the Qualitative Detection of Hepatitis B Virus-associated Antigens and Anti-HBV, Based on “Membrane-engineered” Fibroblast Cells with Virus-Specific Antibodies and Antigens

    Directory of Open Access Journals (Sweden)

    Antonios Perdikaris

    2009-03-01

    Full Text Available A novel miniature cell biosensor detection system for the detection of Hepatis B virus (HBV-associated antigens and anti-HBV is described. The biosensor is based on “membrane-engineered” Vero fibroblast cells immobilized in an alginate matrix. The membrane-engineering process involved the electroinsertion of anti-HBV specific antibodies (anti-HBs, anti-HBe or antigens (HBsAg in the membranes of the Vero cells. The attachment of a homologous antigen to the electroinserted antibody (or, respectively, of the antibody to the electroinserted antigen triggered specific changes to the cell membrane potential that were measured by appropriate microelectrodes, according to the principle of the Bioelectric Recognition Assay (BERA. The sensor was used for screening 133 clinical blood serum samples according to a double-blind protocol. Considerably higher sensor responses were observed against HBV-positive samples, compared with responses against negative samples or samples positive for heterologous hepatitis viruses such as Hepatitis C (HCV virus. Detection of anti-HBs antibodies was made possible by using a biosensor based on immobilized Vero cells bearing the respective antigen (HBsAg. The observed response was rapid (45 sec and quite reproducible. Fluorescence microscopy observations showed that attachment of HBV particles to cells membrane-engineered with anti-HBs was associated with a decrease of [Ca2+]cyt. The perspectives for using the novel biosensor as a qualitative, rapid screening, high throughput assay for HBV antigens and anti-HBs in clinical samples is discussed.

  10. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay

    International Nuclear Information System (INIS)

    Zinkernagel, R.M.; Haenseler, E.; Leist, T.; Cerny, A.; Hengartner, H.; Althage, A.

    1986-01-01

    A model for immunologically T cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (LCMV). The severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP). Kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic T cell activities in livers and spleens all correlated and were dependent upon several parameters: LCMV-isolate; LCMV-WE caused extensive hepatitis, LCMV-Armstrong virtually none. Virus dose. Route of infection; i.v. or i.p. infection caused hepatitis, whereas infection into the footpad did not. The general genetic background of the murine host; of the strains tested, Swiss mice and A-strain mice were more susceptible than C57BL or CBA mice; BALB/c and DBA/2 mice were least susceptible. The degree of immunocompetence of the murine host; T cell deficient nu/nu mice never developed hepatitis, whereas nu/+ or +/+ mice always did. B cell-depleted anti-IgM-treated mice developed immune-mediated hepatitis comparably or even more extensively than control mice. Local cytotoxic T cell activity; mononuclear cells isolated from livers during the period of overt hepatitis were two to five times more active than equal numbers of spleen cells. Adoptive transfer of nylon wool-nonadherent anti-Thy-1.2 and anti-Lyt-2 plus C-sensitive, anti-L3T4 plus C-resistant lymphocytes into irradiated mice preinfected with LCMV-WE caused a rapid time- and dose-dependent linear increase of serum enzyme levels. This increase was caused by adoptive transfer of lymphocytes if immune cell donors and recipient mice shared class I, but not when they shared class II histocompatibility antigens

  11. Old and New World arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by Lassa virus-specific human CD4+ T-cell clones

    International Nuclear Information System (INIS)

    Meulen, Jan ter; Badusche, Marlis; Satoguina, Judith; Strecker, Thomas; Lenz, Oliver; Loeliger, Cornelius; Sakho, Mohamed; Koulemou, Kekoura; Koivogui, Lamine; Hoerauf, Achim

    2004-01-01

    Data from human studies and animal experiments indicate a dominant role of T-cells over antibodies in controlling acute Lassa virus infection and providing immunity to reinfection. Knowledge of the epitopes recognized by T-cells may therefore be crucial to the development of a recombinant Lassa virus vaccine. In order to study human T-cell reactivity to the most conserved structural protein of Lassa virus, the glycoprotein 2 (GP2), seven GP2-specific CD4+ T-cell clones (TCCs) were generated from the lymphocytes of a Lassa antibody positive individual. All TCC displayed high specific proliferation, showed DR-restriction, and produced IFN-γ upon stimulation with recombinant GP2. The epitope of four of the clones was localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (aa 289-301, numbering according to sequence of GPC). This epitope is conserved in all strains of Lassa virus and lymphocytic choriomeningitis virus (LCMV), shows >90% similarity in all New World arenaviruses of clade B, and overlaps with the proposed fusion domain of GP2. Peptides with conservative aa exchanges, as they naturally occur in the epitope 289-301 of the Old World arenavirus Mopeia and some New World arenaviruses, continued to effectively stimulate the Lassa-GP2-specific T-cell clones tested. The finding of a human T-helper cell epitope, which is highly conserved between Old and New World arenaviruses, is of importance for the design of arenavirus vaccines

  12. An Adjuvanted A(H5N1) Subvirion Vaccine Elicits Virus-Specific Antibody Response and Improves Protection Against Lethal Influenza Viral Challenge in Mouse Model of Protein Energy Malnutrition.

    Science.gov (United States)

    Jones, Enitra N; Amoah, Samuel; Cao, Weiping; Sambhara, Suryaprakash; Gangappa, Shivaprakash

    2017-09-15

    Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination. We demonstrated that mice maintained on a VLP diet succumb to lethal challenge at greater rates than mice maintained on an AP diet, despite comparable immunization regimens. Importantly, there was no virus-induced mortality in both VLP and AP groups of mice when either group was immunized with adjuvanted low-dose A(H5N1) subvirion vaccine. Our results suggest that adjuvanted vaccination in populations where PEM is endemic may be one strategy to boost vaccination-promoted immunity and improve outcomes associated with highly pathogenic A(H5N1). Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8+ TEM and CD8+ TRM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.

    Science.gov (United States)

    Srivastava, Ruchi; Khan, Arif A; Chilukuri, Sravya; Syed, Sabrina A; Tran, Tien T; Furness, Julie; Bahraoui, Elmostafa; BenMohamed, Lbachir

    2017-07-15

    Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 + T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 + T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 + T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 + CD8 + T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 -/- or CXCR3 -/- deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 -/- mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 + T cells (T EM ) and tissue-resident memory CD8 + T cells (T RM ), but not of central memory CD8 + T cells (T CM ), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 -/- deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 + T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. IMPORTANCE We determined how the CXCL10/CXCR3 pathway affects CD8 + T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8 + T EM and CD8 + T RM cells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8 + T EM and CD8 + T RM cells associated with protection against recurrent ocular herpes. Based on these findings, a novel "prime/pull" therapeutic ocular herpes vaccine strategy is proposed and discussed. Copyright © 2017 American Society for Microbiology.

  14. Use of recombinant nucleoproteins in enzyme-linked immunosorbent assays for detection of virus-specific immunoglobulin A (IgA) and IgG antibodies in influenza virus A- or B-infected patients

    NARCIS (Netherlands)

    J. Groen (Jan); D. van Alphen; E.C.J. Claas (Eric); R. de Groot (Ronald); G.F. Rimmelzwaan (Guus); J.T.M. Voeten; A.D.M.E. Osterhaus (Albert)

    1998-01-01

    textabstractThe nucleoprotein genes of influenza virus A/Netherlands/018/94 (H3N2) and influenza virus B/Harbin/7/94 were cloned into the bacterial expression vector pMalC to yield highly purified recombinant influenza virus A and B nucleoproteins. With these recombinant influenza

  15. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

    Science.gov (United States)

    Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

    2015-01-01

    Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

  16. Evade, Corrupt, or Confront? Organized Crime and the State in Brazil and Mexico ¿Evadir, corromper o confrontar? El crimen organizado y el Estado en Brasil y México

    Directory of Open Access Journals (Sweden)

    Matthew M. Taylor

    2009-07-01

    Full Text Available Government and organized criminal groups co-exist in uneasy equilibrium. Criminal groups adjust their behavior as a function of their own goals and resources in relation to inter-group cooperation and conflict, dynamic markets, and public policies; governments adjust their behavior according to shifting perceptions of the benefits offered, threats posed, and strategies adopted by criminal groups. When governments attempt to control or repress their activities, criminal groups employ various tools and instruments that might be grouped into three categories: evasion, corruption, and confrontation. The paper draws on recent cases from Brazil and Mexico with respect to tactical and strategic choices by governments and criminal groups, seeking to address three broad questions. What factors disrupt the state-criminal group equilibrium? Under what circumstances do disruptions produce significant levels of violence (as opposed to evasion or corruption? What are the implications for the quality of democracy as criminal groups violently confront the state? El crimen organizado y el gobierno coexisten en un equilibrio sumamente delicado. En función de sus recursos y objetivos, los grupos criminales ajustan su comportamiento en base a las dinámicas del mercado, las políticas públicas y el grado de cooperación o conflicto con otros grupos delictivos. El gobierno, por su parte, actúa de acuerdo al cambio en la percepción de amenazas, beneficios y estrategias adoptadas por el crimen organizado. De tal forma, cuando el gobierno intenta controlar o reprimir actividades ilícitas, los grupos criminales emplean diversos mecanismos que pueden catalogarse en las siguientes categorías: evasión, corrupción y confrontación. El artículo se basa en las tácticas y estrategias adoptadas por el gobierno y los grupos criminales durante casos recientes en Brasil y México, a fin de responder las siguientes tres preguntas ¿Qué factores interrumpen el equilibrio entre gobierno y crimen organizado? ¿Bajo qué circunstancias incrementa la violencia significativamente (a diferencia de la corrupción o la evasión? ¿Cuáles son las implicaciones para la calidad de la democracia una vez que los grupos criminales se enfrentan violentamente al Estado?

  17. Keeping your armour intact: how HIV-1 evades detection by the innate immune system: HIV-1 capsid controls detection of reverse transcription products by the cytosolic DNA sensor cGAS.

    Science.gov (United States)

    Maelfait, Jonathan; Seiradake, Elena; Rehwinkel, Jan

    2014-07-01

    HIV-1 infects dendritic cells (DCs) without triggering an effective innate antiviral immune response. As a consequence, the induction of adaptive immune responses controlling virus spread is limited. In a recent issue of Immunity, Lahaye and colleagues show that intricate interactions of HIV capsid with the cellular cofactor cyclophilin A (CypA) control infection and innate immune activation in DCs. Manipulation of HIV-1 capsid to increase its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA sensor cGAS to reverse transcribed DNA. This in turn induces a strong host response. Here, we discuss these findings in the context of recent developments in innate immunity and consider the implications for disease control and vaccine design. © 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.

  18. Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity.

    Science.gov (United States)

    Spaulding, Andrew; Takrouri, Khuloud; Mahalingam, Pornachandran; Cleary, Dillon C; Cooper, Harold D; Zucchi, Paola; Tear, Westley; Koleva, Bilyana; Beuning, Penny J; Hirsch, Elizabeth B; Aggen, James B

    2017-12-01

    Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (<400), ii) high polarity (clogD 7.4 <1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts. Copyright © 2017. Published by Elsevier Ltd.

  19. The SAATELLITE and EVADE Clinical Studies Within the COMBACTE Consortium: A Public-Private Collaborative Effort in Designing and Performing Clinical Trials for Novel Antibacterial Drugs to Prevent Nosocomial Pneumonia.

    Science.gov (United States)

    François, Bruno; Chastre, Jean; Eggiman, Philippe; Laterre, Pierre-François; Torres, Antoni; Sanchez, Miguel; Esser, Mark T; Bishop, Brian; Bonten, Marc; Goosens, Herman; Jafri, Hasan S

    2016-08-15

    The Innovative Medicines Initiative-funded COMBACTE consortium fosters academic-industry partnership in pioneering studies to combat serious bacterial infections. We describe how this partnership is advancing the development of 2 monoclonal antibodies, MEDI4893 and MEDI3902, for the prevention of nosocomial pneumonia. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. Prevalência de anticorpos antivírus da arterite dos eqüinos em cavalos criados no Estado de São Paulo Prevalence of equine arteritis virus specific antibodies in horses of São Paulo State, Brazil

    OpenAIRE

    M.C.C.S.H. Lara; W.R. Fernandes; P.J. Timoney; E.H. Birgel

    2002-01-01

    Utilizou-se a prova de soroneutralização em microplacas para detecção de anticorpos antivírus da arterite dos eqüinos em 659 amostras de soro sangüíneo de animais criados no Estado de São Paulo. A prevalência de anticorpos na população estudada foi igual a 18,2%. A raça Mangalarga foi a que apresentou maior taxa de prevalência, 33,3%. Animais na faixa etária de 6 a 24 meses de idade apresentaram a maior taxa de prevalência, 30,4%, e as fêmeas apresentaram prevalência de 22, 9%, mais alta do q...

  1. Prevalência de anticorpos antivírus da arterite dos eqüinos em cavalos criados no Estado de São Paulo Prevalence of equine arteritis virus specific antibodies in horses of São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    M.C.C.S.H. Lara

    2002-06-01

    Full Text Available Utilizou-se a prova de soroneutralização em microplacas para detecção de anticorpos antivírus da arterite dos eqüinos em 659 amostras de soro sangüíneo de animais criados no Estado de São Paulo. A prevalência de anticorpos na população estudada foi igual a 18,2%. A raça Mangalarga foi a que apresentou maior taxa de prevalência, 33,3%. Animais na faixa etária de 6 a 24 meses de idade apresentaram a maior taxa de prevalência, 30,4%, e as fêmeas apresentaram prevalência de 22, 9%, mais alta do que nos machos.With the purpose of studying the prevalence of equine viral arteritis in horses raised in São Paulo State, Brazil, by the standard microtiter serum neutralization test, 659 serum samples were investigated. The prevalence of antibodies in the horse population was 18.2%, which was significantly higher in Mangalarga horses (33.3% than in any other breed (Thoroughbred, Arab, Quarter Horse, mixed breeds and others. The distribuition of horses by age showed that horses between 6 to 24 months of age (30.4% had a higher prevalence (30.4% rate than others. The female horses prevalence rate of 22.9% was significantly higher than in male horses.

  2. Evaluation of a recombinant p24 antigen for the detection of Feline Immunodeficiency Virus-specific antibodies Avaliação do antígeno recombinante p24 para a detecção de anticorpos específicos do Vírus da Imunodeficiência Felina

    Directory of Open Access Journals (Sweden)

    Carlos Mazur

    2010-10-01

    Full Text Available Feline Immunodeficiency Virus is a worldwide infection and is considered a significant pathogen. The diagnosis of FIV infections is mainly based on commercially available rapid tests that are highly expensive in Brazil, hence it is rarely performed in the country. Furthermore, lentiviruses grow slowly and poorly in tissue cultures, making the production of viral antigen by classic means and thus the establishment of FIV immunodiagnosis impracticable. In order to deal with this, recombinant DNA techniques were adopted to produce the protein p24, a viral capsid antigen. The protein's reactivity evaluation analyzed by Western blot indicated that this recombinant antigen can be a useful tool for the immunodiagnostic of FIV infections.O vírus da imunodeficiência felina tem distribuição mundial e é considerado um patógeno significativo. No Brasil, a prática diagnóstica é baseada principalmente em teste rápidos, importados e de custo elevado, disponíveis comercialmente. Devido ao seu custo proibitivo em nosso país, o diagnóstico da infecção pelo FIV é raramente realizado. Ademais, os lentivírus se multiplicam lenta e pobremente em cultura de células, o que torna a produção de antígeno por meios clássicos e o estabelecimento do imunodiagnóstico impraticável. Com o objetivo de lidar com esta questão, técnicas de DNA recombinante foram utilizadas para produção de um antígeno do capsídeo viral, a proteína p24. A avaliação da reatividade realizada por Western blot indicou que este antígeno recombinante pode ser útil para o imunodiagnóstico de infecções pelo FIV.

  3. Human Asymptomatic Epitope Peptide/CXCL10-Based Prime/Pull Vaccine Induces Herpes Simplex Virus-Specific Gamma Interferon-Positive CD107+ CD8+ T Cells That Infiltrate the Cornea and Trigeminal Ganglia of Humanized HLA Transgenic Rabbits and Protect against Ocular Herpes Challenge.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Vahed, Hawa; Roy, Soumyabrata; Walia, Sager S; Kim, Grace J; Fouladi, Mona A; Yamada, Taikun; Ly, Vincent T; Lam, Cynthia; Lou, Anthony; Nguyen, Vivianna; Boldbaatar, Undariya; Geertsema, Roger; Fraser, Nigel W; BenMohamed, Lbachir

    2018-06-13

    Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in Human Leukocyte Antigen- (HLA-) transgenic rabbit model of ocular herpes (HLA Tg rabbit). Three asymptomatic (ASYMP) peptide epitopes were selected from the HSV-1 membrane glycoprotein C (UL44 400-408 ), the DNA replication binding helicase (UL9 196-204 ), and the tegument protein (UL25 572-580 ), all preferentially recognized by CD8 + T cells from "naturally protected" HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were immunized with a mixture of these three ASYMP CD8 + T cell peptide epitopes (UL44 400-408 , UL9 196-204 and UL25 572-580 ), delivered subcutaneously with CpG 2007 adjuvant (prime). Fifteen days later, half of the rabbits received a topical ocular treatment with a recombinant neurotropic AAV8 vector, expressing the T cell-attracting CXCL10 chemokine (pull). The frequency, function of HSV-specific CD8 + T cells induced by the prime/pull vaccine were assessed in peripheral blood, cornea, and trigeminal ganglia (TG). Compared to peptides alone, the peptides/CXCL10 prime/pull vaccine generated frequent polyfunctional gamma interferon-positive (IFN-γ + ) CD107 + CD8 + T cells that infiltrated both the cornea and TG. CD8 + T cells mobilization into cornea and TG of prime/pull- vaccinated rabbits was associated with a significant reduction in corneal herpes infection and disease following an ocular HSV-1 challenge (McKrae). These findings draw attention to the novel prime/pull vaccine strategy to mobilize anti-viral CD8 + T cells into tissues protecting them against herpes infection and disease. IMPORTANCE There is an urgent need for a vaccine against widespread herpes simplex virus infections. The present study demonstrates that immunization of HLA transgenic rabbits with a peptide/CXCL10 prime/pull vaccine triggered mobilization of HSV-specific CD8 + T cells locally in the cornea and TG, the sites of acute and latent herpes infections. Mobilization of antiviral CD8 + T cells into cornea and TG of rabbits that received the prime/pull vaccine was associated with protection against ocular herpes infection and disease following an ocular HSV-1 challenge. These results highlight the importance of the prime/pull vaccine strategy to bolster the number and function of protective CD8 + T cells within infected tissues. Copyright © 2018 American Society for Microbiology.

  4. Suvi tulvil festivale

    Index Scriptorium Estoniae

    2005-01-01

    Suvel toimuvate musikafestivalide tutvustus: Eduard Tubin ja tema aeg (muusikafestival), Pärnu rahvusvaheline ooperimuusika festival 2005, Juu Jääb 2005 (retromuusikafestival), Suure-Jaani muusikapäevad 2005, Mravinski Festival 2005, Seitsme linna muusika 2005, Hiiumaa kammermuusikapäevad 2005, Saaremaa suvemuusikafestival 2005, David Oistrahhi festival 2005, Klaaspärlimäng (festival) 2005, Rapla kirikumuusika XIII festival 2005, Kuressaare ooperipäevad 2005, Pärnu ooperipäevad 2005, Tallinna XIX orelifestival, Haapsalu XII viiulimängud 2005, Viljandi vanamuusikafestival 2005, Kuressaare kammermuusikapäevad 2005, Haapsalu vanamuusikafestival 2005, Võru Muusikapäevad 2005

  5. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

    Science.gov (United States)

    Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

    2018-01-01

    Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and

  6. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2018-03-01

    Full Text Available Respiratory syncytial virus (RSV and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell

  7. 27 Estonian Music Festivals 2002

    Index Scriptorium Estoniae

    2003-01-01

    2002. aastal Eestis toimunud muusikafestivalidest: opeNBaroque 2002 (muusikafestival),Akadeemilised Trompetipäevad, Klavessiinimuusika Päevad, Eesti muusika päevad 2002,Mravinski Festival, Rudolf Tobiase muusikafestival, Eduard Tubin ja tema aeg (muusikafestival), Suure-Jaani muusikapäevad 2002,Regiöö (muusikafestival), David Oistrahhi festival, Haapsalu vanamuusikafestival 2002, Viljandi vanamuusikafestival 2002, Hiiumaa kammermuusikapäevad 2002, Klaaspärlimäng (festival),Mustjala Festival, Haapsalu viiulimuusika Päevad 2002, Kuressaare ooperipäevad 2002, Leigo järvemuusika 2002, Tallinna Orelifestival, Rapla kirikumuusika X festival 2002, Kuressaare kammermuusikapäevad 2002, Mart Saare muusikafestival, Credo 2002, Tartu vanamuusika IX festival, Trialogos 2002 (kultuurifestival), Fiesta de la guitarra (kitarrimuusika festival), Klaver 2002

  8. 1. XII kell 13 avatakse Pärnu uue kunsti muuseumis...

    Index Scriptorium Estoniae

    2002-01-01

    Jõulunäitus "Kunst kuulub lastele!" kunstnike ja laste töödest. 6.-8. XII tekstiilipäevad (Anu Raud, Hilja Kulles); 13.-15. XII piparkoogipäevad; 20.-21. XII inglipäevad (kutsutud Ilon Wikland); 27-29. XII unenäopäevad (Enn Tegova). Saab vaadata Lasse Naukarise filmi "Kunstniku elu"

  9. Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

    International Nuclear Information System (INIS)

    Ganusov, Vitaly V; Neher, Richard A; Perelson, Alan S

    2013-01-01

    Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2–3 weeks postinfection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in the face of a strong immune response remains poorly understood. It has been shown that HIV is able to rapidly change its proteins via mutation to evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an HIV-infected patient will generate 4–12 CTL responses specific for parts of viral proteins called epitopes. Such CTL responses lead to strong selective pressure to change the viral sequences encoding these epitopes so as to avoid CTL recognition. Indeed, the viral population ‘escapes’ from about half of the CTL responses by mutation in the first year. Here we review experimental data on HIV evolution in response to CTL pressure, mathematical models developed to explain this evolution, and highlight problems associated with the data and previous modeling efforts. We show that estimates of the strength of the epitope-specific CTL response depend on the method used to fit models to experimental data and on the assumptions made regarding how mutants are generated during infection. We illustrate that allowing CTL responses to decay over time may improve the model fit to experimental data and provides higher estimates of the killing efficacy of HIV-specific CTLs. We also propose a novel method for simultaneously estimating the killing efficacy of multiple CTL populations specific for different epitopes of HIV using stochastic simulations. Lastly, we show that current estimates of the efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by more frequent sampling of viral sequences and by combining data on sequence evolution with

  10. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  11. FEATURES OF THE IMMUNE RESPONSE DURING INFECTION AND PROSPECTS FOR THE VACCINES CREATION

    Directory of Open Access Journals (Sweden)

    Davidova T.V.

    2015-12-01

    Full Text Available The influenza virus belongs to the family Orthomyxoviridae and is a major cause of respiratory infections in humans. Each year, influenza viruses cause, according to experts, 3-5 million severe course of the disease and 250 000-500 000 deaths. Influenza A viruses are divided into serotypes based on their surface glycoproteins - known currently 17 subtypes of HA and NA subtypes ten. Upon infection with an influenza virus, both innate and adaptive immune responses are inducing. In recent years the annual seasonal epidemics were causing strains of the virus A (H1N1 and H3N2 and virus B. This may be due to their ability to be unrecognizable virus specific antibodies due to antigenic drift (Figure 1. Seasonal flu vaccine, to be effective, must be updated almost annually, according to new epidemic strains. In this work will discuss various strategies used by influenza viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells.The primary targets for influenza viruses are the epithelial cells that line the respiratory tract and which initiate an antiviral immune response upon detection of the virus. The first line of defense is formed by the innate immune system, which is quick but lacks specificity and memory. Innate immunity is formed by physical barriers and innate cellular immune responses. Here, we outline several of the innate defense mechanisms directed against influenza infections. During homeostasis, alveolar macrophages exhibit a relatively quiescent state, producing only low levels of cytokines, and suppress the induction of innate and adaptive immunity. Activated macrophages enhance their pro-inflammatory cytokine response, including IL-6 and TNF-α. Alveolar macrophages have a direct role in limiting viral spread by phagocytosis of apoptotic infected cells and by phagocyte

  12. Characterization of a vraG Mutant in a Genetically Stable Staphylococcus aureus Small-Colony Variant and Preliminary Assessment for Use as a Live-Attenuated Vaccine against Intrammamary Infections.

    Directory of Open Access Journals (Sweden)

    Julie Côté-Gravel

    Full Text Available Staphylococcus aureus is a leading cause of bovine intramammary infections (IMIs that can evolve into difficult-to-treat chronic mastitis. To date, no vaccine formulation has shown high protective efficacy against S. aureus IMI, partly because this bacterium can efficiently evade the immune system. For instance, S. aureus small colony variants (SCVs have intracellular abilities and can persist without producing invasive infections. As a first step towards the development of a live vaccine, this study describes the elaboration of a novel attenuated mutant of S. aureus taking advantage of the SCV phenotype. A genetically stable SCV was created through the deletion of the hemB gene, impairing its ability to adapt and revert to the invasive phenotype. Further attenuation was obtained through inactivation of gene vraG (SACOL0720 which we previously showed to be important for full virulence during bovine IMIs. After infection of bovine mammary epithelial cells (MAC-T, the double mutant (ΔvraGΔhemB was less internalized and caused less cell destruction than that seen with ΔhemB and ΔvraG, respectively. In a murine IMI model, the ΔvraGΔhemB mutant was strongly attenuated, with a reduction of viable counts of up to 5-log10 CFU/g of mammary gland when compared to the parental strain. A complete clearance of ΔvraGΔhemB from glands was observed whereas mortality rapidly (48h occurred with the wild-type strain. Immunization of mice using subcutaneous injections of live ΔvraGΔhemB raised a strong immune response as judged by the high total IgG titers measured against bacterial cell extracts and by the high IgG2a/IgG1 ratio observed against the IsdH protein. Also, ΔvraGΔhemB had sufficient common features with bovine mastitis strains so that the antibody response also strongly recognized strains from a variety of mastitis associated spa types. This double mutant could serve as a live-attenuated component in vaccines to improve cell-mediated immune

  13. Intramammary Immunization of Pregnant Mice with Staphylococcal Protein A Reduces the Post-Challenge Mammary Gland Bacterial Load but Not Pathology.

    Directory of Open Access Journals (Sweden)

    Jully Gogoi-Tiwari

    Full Text Available Protein A, encoded by the spa gene, is one of the major immune evading MSCRAMM of S. aureus, demonstrated to be prevalent in a significant percentage of clinical bovine mastitis isolates in Australia. Given its' reported significance in biofilm formation and the superior performance of S. aureus biofilm versus planktonic vaccine in the mouse mastitis model, it was of interest to determine the immunogenicity and protective potential of Protein A as a potential vaccine candidate against bovine mastitis using the mouse mastitis model. Pregnant Balb/c mice were immunised with Protein A emulsified in an alum-based adjuvant by subcutaneous (s/c or intramammary (i/mam routes. While humoral immune response of mice post-immunization were determined using indirect ELISA, cell-mediated immune response was assessed by estimation of interferon-gamma (IFN-γ produced by protein A-stimulated splenocyte supernatants. Protective potential of Protein A against experimental mastitis was determined by challenge of immunized versus sham-vaccinated mice by i/mam route, based upon manifestation of clinical symptoms, total bacterial load and histopathological damage to mammary glands. Significantly (p<0.05 higher levels of IgG1 isotype were produced in mice immunized by the s/c route. In contrast, significantly higher levels of the antibody isotype IgG2a were produced in mice immunized by the i/mam route (p<0.05. There was significant reduction (p<0.05 in bacterial loads of the mammary glands of mice immunized by Protein A regardless of the route of immunization, with medium level of clinical symptoms observed up to day 3 post-challenge. However, Protein A vaccine failed to protect immunized mice post-challenge with biofilm producing encapsulated S. aureus via i/mam route, regardless of the route of immunization, as measured by the level of mammary tissue damage. It was concluded that, Protein A in its' native state was apparently not a suitable candidate for inclusion

  14. Structure of a mouse immunoglobulin G that lacks the entire CH1 domain: Protein sequencing and small-angle X-ray scattering studies

    International Nuclear Information System (INIS)

    Igarashi, Takako; Tanaka, Toshiyuki; Nakanishi, Mamoru; Arata, Yoji; Sato, Mamoru; Katsube, Yukiteru; Takio, Koji

    1990-01-01

    The structure of a short-chain IgG2a antibody, which is a member of the family of mouse anti-dansyl switch variant antibodies with identical variable regions but different heavy-chain constant regions, is reported. Amino acid sequencing analyses have demonstrated that in the short-chain IgG2a antibody the entire C H 1 domain is deleted whereas the hinge region remains intact. Small-angle X-ray scattering data were collected for the short-chain IgG2a antibody and compared with those for the switch variant IgG1, IgG2a, and IgG2b antibodies with the normal heavy chain. It has been concluded that deletion of the C H 1 domain results in a large structural change and the short-chain IgG2a antibody possesses an elongated molecular shape with a much smaller hinge angle as compared with the normal IgG2a antibody that is a Y-shaped molecule

  15. Structure of a mouse immunoglobulin G that lacks the entire C sub H 1 domain: Protein sequencing and small-angle X-ray scattering studies

    Energy Technology Data Exchange (ETDEWEB)

    Igarashi, Takako; Tanaka, Toshiyuki; Nakanishi, Mamoru; Arata, Yoji (Univ. of Tokyo (Japan)); Sato, Mamoru; Katsube, Yukiteru (Osaka Univ. (Japan)); Takio, Koji (Institute of Physical and Chemical Research, Saitama (Japan))

    1990-06-19

    The structure of a short-chain IgG2a antibody, which is a member of the family of mouse anti-dansyl switch variant antibodies with identical variable regions but different heavy-chain constant regions, is reported. Amino acid sequencing analyses have demonstrated that in the short-chain IgG2a antibody the entire C{sub H}1 domain is deleted whereas the hinge region remains intact. Small-angle X-ray scattering data were collected for the short-chain IgG2a antibody and compared with those for the switch variant IgG1, IgG2a, and IgG2b antibodies with the normal heavy chain. It has been concluded that deletion of the C{sub H}1 domain results in a large structural change and the short-chain IgG2a antibody possesses an elongated molecular shape with a much smaller hinge angle as compared with the normal IgG2a antibody that is a Y-shaped molecule.

  16. Rüütel kutsus Ansipi, Savisaare js Reiljani Kadriorgu

    Index Scriptorium Estoniae

    2005-01-01

    President Arnold Rüütel kutsus Kadriorgu kolm erakonnajuhti, kes teatasid valmisolekust moodustada uus koalitsioon. Uue koalitsiooni peaministrikandidaadina näevad nad Reformierakonna esimeest Andrus Ansipit

  17. Rotermanni kvartalit päästetakse nüüd juba pendlimehe abil / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2009-01-01

    Tallinna Rotermanni kvartali reanimeerimisest. Planeerimisprobleeme aitab lahendada arhitekt-geobioloog Rein Weber. Kvartali peaarhitektiks on Andres Alver. Festivali Tallinna Uue Linna Päevad üritustest

  18. Fixed Duration Pursuit-Evasion Differential Game with Integral Constraints

    International Nuclear Information System (INIS)

    Ibragimov G I; Kuchkarov A Sh

    2013-01-01

    We investigate a pursuit-evasion differential game of countably many pursuers and one evader. Integral constraints are imposed on control functions of the players. Duration of the game is fixed and the payoff of the game is infimum of the distances between the evader and pursuers when the game is completed. Purpose of the pursuers is to minimize the payoff and that of the evader is to maximize it. Optimal strategies of the players are constructed, and the value of the game is found. It should be noted that energy resource of any pursuer may be less than that of the evader.

  19. Determination of Interrogating Frequencies to Maximize Electromagnetic Backscatter from Objects with Material Coatings

    National Research Council Canada - National Science Library

    Banks, H. T; Ito, K; Toivanen, J

    2005-01-01

    .... Based on the radar cross section and a reflection coefficient, optimization problems are formulated for evaders and interrogators leading to optimal material parameters for the coating and optimal...

  20. Suvefestivalid

    Index Scriptorium Estoniae

    2006-01-01

    2006. aasta suvel toimuvatest muusikaüritustest: Heliloojatele Kappidele pühendatud IX Suure-Jaani Muusikafestival, Nissi suvemuusika, Seitsme Linna muusika, Klaaspärlimäng, Pärnu ooperipäevad 2006, Tallinna XX orelifestival, Mravinski Festival 2006, Andrew Lloyd Webberi galaõhtu, Juu Jääb 2006 (retromuusikafestival), David Oistrahhi festival 2006, Hiiumaa VIII kammermuusikapäevad 2006, Viljandi vanamuusikafestival 2006, Rapla kirikumuusika XIV festival 2006, Haapsalu XIII keelpillimuusika festival, Kuressaare ooperipäevad 2006, Birgitta festival 2006, Võru Vaskpillipäevad 2006, Tallinna Kammermuusika festival 2006

  1. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway

    Directory of Open Access Journals (Sweden)

    Gompels Ursula A

    2009-07-01

    . Conclusion U83A diverts human chemokines from signalling, but not regulatory or scavenger, receptors facilitating their clearance, while occupying signalling receptors at the cell surface. This can enhance virus specific inflammation, facilitating dissemination to replication sensitive leukocytes while evading clearance; this has implications for linked neuro-inflammatory pathologies.

  2. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway.

    Science.gov (United States)

    Catusse, Julie; Clark, David J; Gompels, Ursula A

    2009-07-30

    regulatory or scavenger, receptors facilitating their clearance, while occupying signalling receptors at the cell surface. This can enhance virus specific inflammation, facilitating dissemination to replication sensitive leukocytes while evading clearance; this has implications for linked neuro-inflammatory pathologies.

  3. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide.

    Science.gov (United States)

    Schlageter, A M; Kozel, T R

    1990-06-01

    A family of immunoglobulin isotype-switch variants was isolated by sib selection from a murine hybridoma which produced an immunoglobulin G subclass 1 (IgG1) antibody specific for the capsular polysaccharide of Cryptococcus neoformans. Antibodies of the IgG1, IgG2a, and IgG2b isotypes had similar serotype specificity patterns in double immunodiffusion assays which used polysaccharides of the four cryptococcal serotypes as antigens. A quantitative difference in the ability of the isotypes to form a precipitate with the polysaccharide was observed in a double immunodiffusion assay and confirmed in a quantitative precipitin assay. The relative precipitating activity of the antibodies was IgG2a greater than IgG1 much greater than IgG2b. Analysis by enzyme-linked immunosorbent assay of the reactivity of the three isotypes with cryptococcal polysaccharide showed identical titers and slopes, suggesting that the variable region of the class-switch antibodies was unaltered. This system allowed us to examine the effect of the Fc portion of the antibody on opsonization of encapsulated cryptococci. Yeast cells were precoated with antibodies of each isotype and incubated with murine macrophages or cultured human monocytes. Antibodies of all three isotypes exhibited a dose-dependent opsonization for phagocytosis by both human and murine phagocytes. The relative opsonic activity of the antibodies was IgG2a greater than IgG1 greater than IgG2b.

  4. Leishmania Infection: Laboratory Diagnosing in the Absence of a “Gold Standard”

    Science.gov (United States)

    Rodríguez-Cortés, Alhelí; Ojeda, Ana; Francino, Olga; López-Fuertes, Laura; Timón, Marcos; Alberola, Jordi

    2010-01-01

    There is no gold standard for diagnosing leishmaniases. Our aim was to assess the operative validity of tests used in detecting Leishmania infection using samples from experimental infections, a reliable equivalent to the classic definition of gold standard. Without statistical differences, the highest sensitivity was achieved by protein A (ProtA), immunoglobulin (Ig)G2, indirect fluorescenece antibody test (IFAT), lymphocyte proliferation assay, quantitative real-time polymerase chain reaction of bone marrow (qPCR-BM), qPCR-Blood, and IgG; and the highest specificity by IgG1, IgM, IgA, qPCR-Blood, IgG, IgG2, and qPCR-BM. Maximum positive predictive value was obtained simultaneously by IgG2, qPCR-Blood, and IgG; and maximum negative predictive value by qPCR-BM. Best positive and negative likelihood ratios were obtained by IgG2. The test having the greatest, statistically significant, area under the receiver operating characteristics curve was IgG2 enzyme-linked immunosorbent assay (ELISA). Thus, according to the gold standard used, IFAT and qPCR are far from fulfilling the requirements to be considered gold standards, and the test showing the highest potential to detect Leishmania infection is Leishmania-specific ELISA IgG2. PMID:20134001

  5. Domus Revaliensis in Reval/Tallinn / Florian Anton

    Index Scriptorium Estoniae

    Anton, Florian

    2005-01-01

    13 aastat tagasi asutati baltisakslaste ja lätlaste poolt Riias "Domus Rigensis", mille aasta kõrghetkeks on juulis toimuvad baltisaksa-läti kultuuripäevad. Seekord toimusid sarnased kultuuripäevad "Domus-Revaliensis-Tage" 26.-28. augustini esimest korda Tallinnas

  6. Mis tuleb

    Index Scriptorium Estoniae

    2008-01-01

    5.-15. V seto pitsi päevad Setu Talumuuseumis. 29.-31. V Aseri savipäevad. 31. V-1. VI käsitöö-, vanavara- ja kunstilaat Atla mõisas ja Liiwimaa antiigi-, kunsti- ja etnograafialaat Põlvamaal Pikajärve Cantervilla lossis

  7. Tähtpäevakalendri kujundamisest Nõukogude Eestis aastatel 1945-1985 / Tiiu Kreegipuu

    Index Scriptorium Estoniae

    Kreegipuu, Tiiu, 1977-

    2011-01-01

    Kalendritähtpäevade ajaloolisest taustast Eestis ja Nõukogude Liidus, sarnasustest ja erinevustest. Pühade ja tähtpäevade funktsioonidest Nõukogude kalendris. Nõukogude Eesti tähtpäevakalendri analüüs

  8. Mis tuleb

    Index Scriptorium Estoniae

    2007-01-01

    2.-8. VII kunstinädal "Kultuurikatapuldid 2007" Haapsalus. 7. VII-3. VIII Haapsalu klaasipäevad. 9.-14. VII Järvamaa kangakudujate päevad Sõrandus. Kuni 22. VII Järvakandi Klaasimuuseumis Mark Anguse meistriklassi klaasimaalide näitus "Maalitud muinaslood"

  9. Uus kunstikool näitab oma nägu ja hambaid / Karen Jagodin

    Index Scriptorium Estoniae

    Jagodin, Karen, 1982-

    2004-01-01

    Positivistliku Kunsttööstuskooli kampaaniapäevad algasid Performance Week'iga Ku galeriis. Avamisel esines Mari Sobolev performance'iga "Lost in the system". Kampaaniapäevad kulmineeruvad Paide tegevuskunstifestivaliga "Aeg. Ruum. Liikumine: unplugged". Festivali kuraator on Mari Sobolev

  10. Derek, Sally ja Tilda Swinton / Kalmer Saar

    Index Scriptorium Estoniae

    Saar, Kalmer

    2004-01-01

    Briti Nõukogu toetusel toimuvad Pärnus, Tartus ja Tallinnas PÖFFi suvekino organiseerimisel inglise filmide päevad "Geeniuste mäss", kus näidatakse seitset inglise väärtfilmi. Lähemalt Derek Jarmani filmist "Edward II" (1991) ja Sally Potteri Virginia Woolfi ekraniseeringust "Orlando" (1992). Lisatud filmipäevade kava

  11. Analysis of intrahepatic HBV-specific cytotoxic T-cells during and after acute HBV infection in humans

    NARCIS (Netherlands)

    Sprengers, Dave; van der Molen, Renate G.; Kusters, Johannes G.; de Man, Robert A.; Niesters, Hubert G. M.; Schalm, Solko W.; Janssen, Harry L. A.

    2006-01-01

    Characteristics of the intrahepatic virus-specific T-cell response in patients with acute hepatitis B virus (HBV) infection have not been studied due to the risk of complications associated with standard liver biopsies. In this study we aimed to characterize the virus-specific CD8 + T-cell response

  12. High levels of Porphyromonas gingivalis-induced immunoglobulin G2 are associated with lower high-density lipoprotein levels in chronic periodontitis.

    Science.gov (United States)

    Ardila, Carlos M; Guzmán, Isabel C

    2016-11-01

    To investigate the association between the presence of Porphyromonas gingivalis-induced immunoglobulin G antibodies and the high-density lipoprotein (HDL) level. A total of 108 individuals were examined. The presence of P. gingivalis was detected using primers designed to target the 16S rRNA gene sequence. Peripheral blood was collected from each subject to determine the levels of P. gingivalis-induced IgG1 and IgG2 serum antibodies. The HDL levels were determined using fully enzymatic methods. A higher proportion of periodontitis patients had high levels of P. gingivalis-induced IgG1 and IgG2, and the proportion of subjects with a HDL level of chronic periodontitis patients. In the unadjusted regression model, the presence of high levels of P. gingivalis-induced IgG2 was associated with a HDL level of periodontitis patients with high levels of P. gingivalis-induced IgG2 showed 3.2 more chances of having pathological HDL levels (odds ratio = 3.2, 95% confidence interval = 1.2-9.8). High levels of P. gingivalis-induced IgG2 were associated with low HDL concentrations in patients with periodontitis, which suggests that the response of the host to periodontal infection may play an important role in the pathogenesis of cardiovascular diseases. © 2015 Wiley Publishing Asia Pty Ltd.

  13. An optimal controller for an electric ventricular-assist device: theory, implementation, and testing.

    Science.gov (United States)

    Klute, G K; Tasch, U; Geselowitz, D B

    1992-04-01

    This paper addresses the development and testing of an optimal position feedback controller for the Penn State electric ventricular-assist device (EVAD). The control law is designed to minimize the expected value of the EVAD's power consumption for a targeted patient population. The closed-loop control law is implemented on an Intel 8096 microprocessor and in vitro test runs show that this controller improves the EVAD's efficiency by 15-21%, when compared with the performance of the currently used feedforward control scheme.

  14. Influence of a cocoa-enriched diet on specific immune response in ovalbumin-sensitized rats.

    Science.gov (United States)

    Pérez-Berezo, Teresa; Ramiro-Puig, Emma; Pérez-Cano, Francisco J; Castellote, Cristina; Permanyer, Joan; Franch, Angels; Castell, Margarida

    2009-03-01

    Previous studies in young rats have reported the impact of 3 weeks of high cocoa intake on healthy immune status. The present article describes the effects of a longer-term cocoa-enriched diet (9 weeks) on the specific immune response to ovalbumin (OVA) in adult Wistar rats. At 4 weeks after immunization, control rats produced anti-OVA antibodies, which, according their amount and isotype, were arranged as follows: IgG1 > IgG2a > IgM > IgG2b > IgG2c. Both cocoa diets studied (4% and 10%) down-modulated OVA-specific antibody levels of IgG1 (main subclass associated with the Th2 immune response in rats), IgG2a, IgG2c and IgM isotypes. Conversely, cocoa-fed rats presented equal or higher levels of anti-OVA IgG2b antibodies (subclass linked to the Th1 response). Spleen and lymph node cells from OVA-immunized control and cocoa-fed animals proliferated similarly under OVA stimulation. However, spleen cells from cocoa-fed animals showed decreased interleukin-4 secretion (main Th2 cytokine), and lymph node cells from the same rats displayed higher interferon-gamma secretion (main Th1 cytokine). These changes were accompanied by a reduction in the number of anti-OVA IgG-secreting cells in spleen. In conclusion, cocoa diets induced attenuation of antibody synthesis that may be attributable to specific down-regulation of the Th2 immune response.

  15. Analysis of ovine colostrum to detect antibody against progressive pneumonia virus.

    OpenAIRE

    Taylor, T B; Banowetz, G M; Schipper, I A; Gabrielson, D A

    1982-01-01

    Immunoglobulins were isolated and purified from the colostrum and serum of progressive pneumonia virus infected sheep and also from non-infected control sheep. Four classes of immunoglobulins were isolated from sheep colostrum (IgG1, IgG2, IgA and Ig10s). Three classes of immunoglobulins were isolated from sheep serum (IgG1, IgG2 and IgM). Low levels of virus neutralizing activity were demonstrated only in the whole serum and purified serum IgG1 preparations. No complement fixing activity was...

  16. Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats

    International Nuclear Information System (INIS)

    Arquilla, E.R.; Stenger, D.; McDougall, B.; Ulich, T.R.

    1987-01-01

    The bioavailability, distribution, and metabolic fate of 125 I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125 I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125 I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125 I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125 I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125 I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125 I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125 I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies

  17. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide.

    OpenAIRE

    Sanford, J E; Lupan, D M; Schlageter, A M; Kozel, T R

    1990-01-01

    The in vivo properties of an immunoglobulin isotype-switch family of monoclonal antibodies specific for the polysaccharide capsule of Cryptococcus neoformans were examined in a murine model of cryptococcosis. Subclass-switch variants were isolated by sequential sublining of an immunoglobulin G subclass 1 (IgG1)-secreting cell line. Antibodies of the IgG1, IgG2a, and IgG2b isotypes with identical reactivities with cryptococcal polysaccharide were prepared. The antibodies had the distinct biolo...

  18. Benjamin Verdery teeb klassikast laheda show / Mari Hiiemäe

    Index Scriptorium Estoniae

    Hiiemäe, Mari

    2008-01-01

    Seitsmendate Eesti kitarrimuusikapäevade Fiesta de la Guitarra 2008 ja peaesinejast, USAst pärit kitarristist Benjamin Verdery'st (esineb 8. nov. Tallinnas Mederi saalis ja 9. nov. Vanemuise kammersaalis), festivalist

  19. Pärnus on nädalavahetus täis ooperit / Ülle Hallik

    Index Scriptorium Estoniae

    Hallik, Ülle, 1963-

    2006-01-01

    V. Bellini ooperist "Norma" Moskva Novaja Opera solistide, sümfooniaorkestri ja ooperikoori esituses ning galaõhtust "Bravissimo" Pärnu IV ooperipäevade raames 14.-15. juulil Pärnu Kontserdimajas

  20. Saksa vastupanu ja prantsuse tundeelu / Endel Link

    Index Scriptorium Estoniae

    Link, Endel

    2005-01-01

    Berliini 55. filmifestivalist ja festivali filmidest : sakslase Marc Rothemundi "Sophie Scholl - viimased päevad", prantslase Régis Wargineri "Man to Man" ja teise prantslase André Téchiné "Muutunud aeg"

  1. Eesti Instituudi, välisministeeriumi, Londoni suursaatkonna, kultuuriministeeriumi...

    Index Scriptorium Estoniae

    2005-01-01

    1. XI algasid Eesti päevad Shotimaal. Shoti parlamendis on avatud Endel Grensmanni aerofotode näitus "Linnu Eesti". Eesti Instituut andis välja eriväljaande "de cultu civili estonico/Estonian Culture"

  2. Pursuit and Evasion Strategies in Football.

    Science.gov (United States)

    O'Connell, James

    1995-01-01

    Explores strategies in the situation of a runner trying to evade a tackler on a football field. Enables the student to test intuitive strategies in a familiar situation using simple graphical and numerical methods or direct experimentation. (JRH)

  3. Näiteid rahvusvaheliste kultuuriprojektide turundamisest

    Index Scriptorium Estoniae

    2005-01-01

    Ilmunud ka: International cultural marketing conference : November 3-4, 2005, Tartu : a collection of speeches. lk. 27-34. Lars Blicher-Hansen tutvustab Hans Christian Anderseni aasta ja Urmas Kõiv XXV rahvusvaheliste hansapäevade turundusstrateegiaid

  4. Muusikamaailm / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2005-01-01

    Milano La Scala alustas hooaega. "Ameerika tragöödia" New Yorgi Metis. Huddersfieldi festivalilt. Ricard Straussi päevad Dresdenis. Viiuldajate konkurss Helsingis. Haruldasi leide. Tunnustusi ja preemiaid

  5. Seminaril jagus õpetust, kosutust, osadust ja mustikaid / Kirsti Malmi

    Index Scriptorium Estoniae

    Malmi, Kirsti

    2009-01-01

    Augustis toimus Nõval selleaastane EELK Misjonikeskuse suveseminar. Seminaripäevade jooksul uuriti lähemalt piiblisalme, mis kirjeldasid kolmainu jumala erinevaid palgeid. Koolitajaks oli süstemaatilise teoloogia professor Robert Kolb St. Louisi Concordia seminarist USAs.

  6. Ohrannõje firmõ i ihh klientõ : obstanovka nakaljajetsja / Nikolai Andrejev

    Index Scriptorium Estoniae

    Andrejev, Nikolai

    2004-01-01

    Enamus Narva ettevõtjaid on otsustanud loobuda turvafirmade Falck ja Securitas teenetest, süüdistades neid ebaprofessionaalsuses. Turvafirmad peavad seda ebaausa konkurentsi ilminguks ning näevad võimalust uue firma tekkeks

  7. Transnational Crime and the Criminal-Terrorist Nexus: Synergies and Corporate Trends

    National Research Council Canada - National Science Library

    Hesterman, Jennifer

    2004-01-01

    ... to continually evade law enforcement. Exacerbating the growing problem is the fact that the groups involved in transnational crime operate with a level of sophistication previously only found in multinational corporations...

  8. Transnational Crime and the Criminal-Terrorist Nexus: Synergies and Corporate Trends

    National Research Council Canada - National Science Library

    Hesterman, Jennifer L

    2005-01-01

    ... to evade law enforcement continually. Exacerbating the growing problem is the fact that the groups involved in transnational crime operate with a level of sophistication previously only found in multinational corporations...

  9. MTÜ Eesti Klaasikunstnike Ühendus koostöös OSTA.EEga korraldab 17.-26. V heategevusliku internetioksjoni...

    Index Scriptorium Estoniae

    2004-01-01

    Oksjonil osaleb 14 kunstnikku, tulu läheb rahvusvahelise kuumaklaasiürituse korraldamiseks Haapsalus. II Haapsalu klaasipäevad toimuvad 28. VI-4. VII, klaasikunstinäitus Evald Okase muuseumis 4.-31. VII

  10. Maaleht soovitab : Klassikud Mooste mõisas. Romantiline Karlova päev

    Index Scriptorium Estoniae

    2008-01-01

    String Kvarteti kontserdist kavaga "Klassikud kammerlikult" 23. mail Mooste mõisas. Bonzo, Tõuni ja meeste vokaalansambli Võta See esinemisest 17. mail Karlova päevade raames Tartu ülikooli õpetajate seminari saalis (Salme 1a)

  11. Näitused / Mari Sobolev

    Index Scriptorium Estoniae

    Sobolev, Mari, 1968-

    1998-01-01

    Vaal-galerii: Peeter Laurits "Taeva Atlas" (gigitaaltehnoloogias kollaazhid); Sammas-galerii: "Maailma nägu"; Tartu Kunstimaja: "Viljandi kunstipäevad Tartus"; Estonia Talveaed: Mall Mets&Erika Pedak "Due Canzoni" (vaibakunst).

  12. Nashi na moksieivisko teatro dienos 2002

    Index Scriptorium Estoniae

    2002-01-01

    25. - 30. maini toimus Kaunases V rahvusvaheline teatrifestival "Kooliteatri päevad", millele oli kutsutud Vene Noorsooteater Aplaus. Esitati W. Shakespeare'i "Romeo ja Julia" ja L. Razumovskaja "Langenud inglid"

  13. Tulised mustlasviisid ja hingehaarav kummardus Tšaikovskile / Ruslan Kamatškov ; intervjueerinud Kristi Hinsberg

    Index Scriptorium Estoniae

    Kamatškov, Rustam

    2009-01-01

    Küsimustele vastab tšellist Rustam Kamatškov, kes esineb 4. augustil Kuressaare Kultuurikeskuses XV Kuressaare kammermuusikapäevade avakontserdil trioga Julia Igonina - Rustam Komatškov - Andres Paas

  14. Кто кроме статистиков видит статистические данные, позволяющие установить личность?

    Index Scriptorium Estoniae

    2009-01-01

    Kes peale statistikakogujate näevad isiku tuvastamist võimaldavaid statistilisi andmeid? Uuest riikliku statistika seaduse eelnõust, mis muu hulgas reguleerib praegusest seadusest täpsemalt konfidentsiaalsete statistikaandmete levitamist

  15. Kurioosne filmilavastaja Katariina kiriku seinte vahel

    Index Scriptorium Estoniae

    2008-01-01

    Saksa filmirežissööri Ernst Lubitschi (1892-1947) filmidest, mis linastuvad Katariina kirikus seoses Tallinna Vanalinna Päevade raames toimuva Ernst Lubitschi filmide festivaliga "The Lubitsch Touch"

  16. Sangpomm ei taha lahkuda ehk uuenduslikkust tuleb üritusturundusse visalt / Olavi Andla

    Index Scriptorium Estoniae

    Andla, Olavi, 1970-

    2013-01-01

    Firma suvepäevade korraldamisest, kuhu tehnoloogia kasutamine toob uudseid lahendusi. Lähemalt kahest ürituse formaadist - Action Track ja Amazing Race, mida saab kasutada seiklusmängude korraldamisel

  17. Drug-Driven Phenotypic Convergence Supports Rational Treatment Strategies of Chronic Infections

    DEFF Research Database (Denmark)

    Imamovic, Lejla; Ellabaan, Mostafa Mostafa Hashim; Dantas Machado, Ana Manuel

    2018-01-01

    Chronic Pseudomonas aeruginosa infections evade antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P. aeruginosa toward clinically relevant antibiotics leads to phenotypic convergence toward distinct states. These s...

  18. Muusikamaailm / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    Wolfgang Wagner loobub Bayreuthi festivalist, "Towards the Millennium" Londonis, Kammerkontserdite mammutsari Põhja-Rhein-Westfaali liidumaal, Kreneki päevad Viinis, Leipzigi ooperi järgmine hooaeg

  19. Pärt: kultuurilis-diplomaatiline missioon Vatikanis täidetud / Valner Valme

    Index Scriptorium Estoniae

    Valme, Valner, 1970-

    2011-01-01

    23. augustil Katariina kirikus toimunud uue singli "Vater Unser" esitlusest. Selle pala kinkis A. Pärt paavstile 4. juulil Vatikanis. Esitlusel viibis ka president Toomas Hendrik Ilves. Pärdi päevade raames toimuvatest üritustest

  20. 76 FR 77670 - Retail Commodity Transactions Under Commodity Exchange Act

    Science.gov (United States)

    2011-12-14

    ... following methods: Agency Web site, via its Comments Online process: http://comments.cftc.gov . Follow the... Zelener decision, many [fraudsters] were given a roadmap to evade CFTC jurisdiction and to scam customers...

  1. Muudatustest hooldusravis / Heli Paluste

    Index Scriptorium Estoniae

    Paluste, Heli

    2010-01-01

    Alates 1. jaanuarist 2010. a. moodustab hooldusravi voodipäevade hinnast isiku omaosalus 15 % (VV määrusest nr. 49 (19. veebruarist 2009. a.), mis jõustus 1. jaanuaril 2010. a. ja millega hooldusravi rahastamine muutus)

  2. South African Journal of Higher Education - Vol 16, No 2 (2002)

    African Journals Online (AJOL)

    South African Journal of Higher Education - Vol 16, No 2 (2002) ... Rewarding quality teaching in higher education: the evading dream? ... Employers' perceptions of the profile of MBA graduates · EMAIL FULL TEXT EMAIL FULL TEXT

  3. Thrombin-activatable fibrinolysis inhibitor is degraded by Salmonella enterica and Yersinia pestis

    NARCIS (Netherlands)

    Valls Serón, M.; Haiko, J.; de Groot, P. G.; Korhonen, T. K.; Meijers, J. C. M.

    2010-01-01

    Background: Pathogenic bacteria modulate the host coagulation system to evade immune responses or to facilitate dissemination through extravascular tissues. In particular, the important bacterial pathogens Salmonella enterica and Yersinia pestis intervene with the plasminogen/fibrinolytic system.

  4. Kirev moepillerkaar / Britt Rosen

    Index Scriptorium Estoniae

    Rosen, Britt, 1968-

    2008-01-01

    FIBITi moepäevad ja Kuldnõela gala Viru keskuses. Eesti parima moekunstniku tiitli pälvis Riina Põldroos. Kommentaarid Riina Põldroosilt, Aldo Järvsoolt, Urmas Väljaotsalt, Kirill Safonovilt. 17 ill

  5. Vom Klangrausch des Nordwinds und der leeren Tafel der Seele. Lepo Sumeras vierte Symphonie "Serena Borealis" in Karlsruhe uraufgeführt: Eri Klas dirigierte im Konzert der Badischen Staatskapelle zu den Kulturtagen auch Musik von Arvo Pärt und Edua

    Index Scriptorium Estoniae

    Hartmann, Ulrich

    1992-01-01

    Lepo Sumera neljanda sümfoonia "Serena Borealis" esiettekanne Karlsruhes: Eri Klas dirigeeris kontserdil kultuuripäevade raames ka Arvo Pärdi ja Eduard Tubina muusikat. Eesti muusikute esinemisest Karlsruhe kultuuripäevadel

  6. Kannatuste rada, to be continued / Karlo Funk

    Index Scriptorium Estoniae

    Funk, Karlo, 1971-

    2000-01-01

    Dokumentaalfilm "Viimased päevad" ("The Last Days") Eesti välisministeeriumi pressikeskuses. režissöör James Moll : Ameerika Ühendriigid 1998. Survivors of the Shoah Visual History Foundation algatus

  7. India dokfilmide paremik jõuab taaralinna

    Index Scriptorium Estoniae

    2007-01-01

    Tartus täna algavatest India dokumentaalfilmide päevadest, mida korraldavad Maailmafilmi festival, Eesti Rahva Muuseum ja organisatsioon Films For Freedom India. Lisatud nimekiri "India dokfilmi päevad"

  8. Modernistid modernismi vastu : Loos, Schenker ja ilustuste kriitika / Nicolas Cook

    Index Scriptorium Estoniae

    Cook, Nicolas

    2008-01-01

    Seoseid tänapäeva tuntuima muusikaanalüüsi meetodi leiutaja Heinrich Schenkeri teooria ja Viini modernistliku arhitekti Adolf Loosi ornamendikriitika vahel. Ettekanne Pärnu Nüüdismuusika Päevade konverentsil 2005

  9. Personnel Recovery: Using Game Theory to Model Strategic Decision Making in the Contemporary Operating Environment

    National Research Council Canada - National Science Library

    Ecklund, Marshall V

    2005-01-01

    .... Thus, the central research question is as follows: Given a report of the physical location of an evader, is the military using the most rational decision-making model to offset the predictable nature of traditional recovery activities...

  10. Eksperimenteeriv briti kino / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2004-01-01

    PÖFFi Suvekino inglise filmide päevad "Geeniuste mäss" pakuvad täna ja homme Tallinnas Katariina kirikus Derek Jarmani filme "Edward II" (1991) ja "Viimne pilk Inglismaale" ("The Last of England", 1987)

  11. Romantiline ajareis olevikust tulevikku mineviku kaudu / Gerhard Lock

    Index Scriptorium Estoniae

    Lock, Gerhard, 1978-

    2011-01-01

    26. veebruaril Eesti muusika päevade ja programmi "Tallinn - Euroopa kultuuripealinn 2011" raames Salme kultuurikeskuses toimunud Tatjana Kozlova autorikontserdist, kus kaasa tegid Annamaria Morini (flööt, Itaalia), Enzo Porta (viiul, Itaalia) ja ansambel Resonabilis

  12. Suurbritannia film kliima soojenemisest täna 50 riigi kinodes / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    Franny Armstrongi dokumentaal-, mängu- ja animafilmi seguna vormistatud filmi "Rumaluse ajastu" ("The Age of Stupid") ülemaailmne esilinastus toimub ÜRO peaassamblee kliimakoosoleku eelõhtul. Eestlased näevad seda Von Krahli teatris

  13. Hallmarks of glioblastoma

    DEFF Research Database (Denmark)

    Nørøxe, Dorte Schou; Poulsen, Hans Skovgaard; Lassen, Ulrik

    2017-01-01

    immortality', 'inducing angiogenesis', 'reprogramming cellular energetics' and 'evading immune destruction'. This includes the importance of molecular diagnostics according to the new WHO classification and how next generation sequencing is being implemented in the clinical daily life. Molecular results...

  14. Saateks / Krista Kerge

    Index Scriptorium Estoniae

    Kerge, Krista, 1952-

    2006-01-01

    Eesti-Soome koostööst keele alal. 31. keeleteaduse päevad toimusid 2004. a. Tallinna Ülikoolis, kogumik "Finest linguistics" sisaldab valiku artikliteks vormunud ettekannetest, mis sel konverentsil peeti

  15. Sem betonnõh skulptur dlja Kunda

    Index Scriptorium Estoniae

    2006-01-01

    Kundasse paigaldatakse seitse betoonskulptuur-büsti tsemenditehase rajajast John Girard de Soucantonist (1826-1896). Kujud valmistasid 6 eesti ja 1 läti skulptor (nimed) Kunda betoonipäevade raames

  16. Pärnu linn toetab kultuurikavasid 4,5 miljoni krooniga

    Index Scriptorium Estoniae

    2007-01-01

    Toetuste saajateks ka muusikaüritused: David Oistrahhi festival, laste- ja noorte muusikafestival "Muusikamoos", MTÜ Suupilliklubi Piccolo, Pärnu Ooperipäevad, rahvusvaheline folkloorifestival "Baltica 2007"

  17. Amazoni majandusseis seni arvatust kehvem / Kaja Koovit

    Index Scriptorium Estoniae

    Koovit, Kaja, 1968-

    2002-01-01

    Nädalapäevad tagasi kiitles internetikaubamaja Amazon.com esimest korda kasumisse jõudmisega, kuid majandusseisu lähemal uurimisel selgub, et ettevõttel ei pruugi olla piisavalt varasid oma kohustuste täitmiseks

  18. ISATT konverents: teooria kohtub praktikaga / Tiina Anspal

    Index Scriptorium Estoniae

    Anspal, Tiina

    2015-01-01

    Hariduse koostööpäevade raames toimunud rahvusvahelisest konverentsist, mille eesmärgiks oli tutvustada hariduspraktikale oluliste uuringute tulemusi ja aidata tõstatada koolipraktikast tulenevaid uurimist vajavaid teemasid

  19. Lapse sünd, abiellumine ja juubel toovad töötajale lisaraha / Kristel Kossar

    Index Scriptorium Estoniae

    Kossar, Kristel

    2005-01-01

    Konsultatsioonifirma Fontes 2004. aasta palgauuringu andmetel teeb 75 protsenti ettevõtetest töötajatele tähtpäevade puhul kingitusi, milleks on tavaliselt rahaline preemia, ilu- või tarbeese. Lisa: Ettevõtted kingivad

  20. Raamatulett / Jaanus Tamm

    Index Scriptorium Estoniae

    Tamm, Jaanus

    1996-01-01

    Highsmith, Patricia. Ripley mäng ; Chichester, J. J. Vahialune vaikib ; Kuznetsova, Agnia. Dolly ; Kallas, Aino. Suurlinnade udus ja säras ; Kallas, Aino. Pööripäevad ; Singer, Isaac Bashevis. Saatan Gorais; Patukahetseja

  1. Ekskursioon Kozlova tämbrimaailma / Igor Garšnek

    Index Scriptorium Estoniae

    Garšnek, Igor, 1958-

    2011-01-01

    26. veebruaril Eesti muusika päevade ja programmi "Tallinn - Euroopa kultuuripealinn 2011" raames Salme kultuurikeskuses toimunud Tatjana Kozlova autorikontserdist, kus kaasa tegid Annamaria Morini (flööt, Itaalia), Enzo Porta (viiul, Itaalia) ja ansambel Resonabilis

  2. Empaatiline helilooja Tatjana Kozlova / Mirje Mändla

    Index Scriptorium Estoniae

    Mändla, Mirje

    2011-01-01

    26. veebruaril Eesti muusika päevade ja programmi "Tallinn - Euroopa kultuuripealinn 2011" raames Salme kultuurikeskuses toimunud Tatjana Kozlova autorikontserdist, kus kaasa tegid Annamaria Morini (flööt, Itaalia), Enzo Porta (viiul, Itaalia) ja ansambel Resonabilis

  3. Staaride värbamine läänelik veidrus / Tuuli Koch

    Index Scriptorium Estoniae

    Koch, Tuuli

    2004-01-01

    Modell Carmen Kass astus Res Publica noorteühenduse Juventus liikmeks. Politoloogid ja Res Publica võimupartnerid näevad staaride kaasamises europarlamendi valimiskampaaniasse lääneliku poliitika veidruste ülevõtmist

  4. Loomeliitude pleenum või rahvaühenduste ümarlaud / Märt Kubo

    Index Scriptorium Estoniae

    Kubo, Märt

    2001-01-01

    Ümarlaua kokkukutsujad (ÜRO arenguprogramm, Eesti valitsuse ja Eesti mittetulundusühingute ja sihtasutuste liidu ühisprojekt, Eesti vabatahtlike keskus) näevad selles mittetulundussektori esinduskogu. Erinevus loomeliitude pleenumist. Autor: Keskerakond

  5. "Atypical" Employment and the Failure of Labour Law.

    Science.gov (United States)

    Stewart, Andrew

    1992-01-01

    Increased casual employment and contract labor challenge the protective nature of Australian labor law. Laws and social policies should not cause casual and self-employed workers to be denied benefits nor allow employers to evade standards. (SK)

  6. Rahu, ainult rahu / Karin Bachmann

    Index Scriptorium Estoniae

    Bachmann, Karin, 1976-

    2013-01-01

    Eesti Kunstiakadeemia X Urbanistika ja linnamaastike päevad "Between Architecture of War and Military Urbanism" ("Sõjaarhitektuuri ja militaarurbanistika vahel") 25.-28. aprillil 2013. a. Telliskivi Loomelinnakus Tallinnas. Konverentsi peaesinejad Stephen Graham ja Steven Flusty

  7. Siidii / Kreete Reval

    Index Scriptorium Estoniae

    Reval, Kreete

    2003-01-01

    Heliplaatidest: "Erkki Otsman", Kärt Tomingas "Sinine kivi", Whitney Houston "Just Whitney", Amon Tobin "Out From Out Where", Gregorian "Masters Of Chant Chapter III", "Eesti heliloojad IV: Eesti Muusika Päevad 2002"

  8. Klaasikunstnikud kohtuvad Okase muuseumi õuel / Katrina Sokk

    Index Scriptorium Estoniae

    Sokk, Katrina

    2005-01-01

    Haapsalu klaasifestivalist, mille tänavune nimi on "Valge klaasi päevad". Osalevad kunstnikud Euroopast, Hiinast, Koreast, Kanadast. Kati Kerstna kommentaarid. Avatavatest klaasinäitustest Haapsalu galeriides

  9. Eesti Muinsuskaitse Seltsi rahvusvaheline koostöö / Helle Solnask

    Index Scriptorium Estoniae

    Solnask, Helle

    2009-01-01

    Osalemisest Euroopa Muinsuskaitsepäevade koordinaatorite töögrupis, HEREIN'is, Europa Nostras, Euroopa Ajalooliste Kalmistute Assotsiatsioonis ASCE, Euroopa Muuseumi- ja Turismiraudteede Föderatsioonis

  10. Properties of Cells Carrying the Herpes Simplex Virus Type 2 Thymidine Kinase Gene: Mechanisms of Reversion to a Thymidine Kinase-Negative Phenotype

    Science.gov (United States)

    Bastow, K. F.; Darby, G.; Wildy, P.; Minson, A. C.

    1980-01-01

    We have isolated cells with a thymidine kinase-negative (tk−) phenotype from cells which carry the herpes simplex virus type 2 tk gene by selection in 5-bromodeoxyuridine or 9-(2-hydroxyethoxymethyl)guanine. Both selection routines generated revertants with a frequency of 10−3 to 10−4, and resistance to either compound conferred simultaneous resistance to the other. tk− revertants fell into three classes: (i) cells that arose by deletion of all virus sequences, (ii) cells that had lost the virus tk gene but retained a nonselected virus-specific function and arose by deletion of part of the virus-specific sequence, and (iii) cells that retained the potential to express all of the virus-specific functions of the parental cells and retained all of the virus-specific DNA sequences. Images PMID:16789205

  11. Validation of exposure visualization and audible distance emission for navigated temporal bone drilling in phantoms.

    Directory of Open Access Journals (Sweden)

    Eduard H J Voormolen

    Full Text Available BACKGROUND: A neuronavigation interface with extended function as compared with current systems was developed to aid during temporal bone surgery. The interface, named EVADE, updates the prior anatomical image and visualizes the bone drilling process virtually in real-time without need for intra-operative imaging. Furthermore, EVADE continuously calculates the distance from the drill tip to segmented temporal bone critical structures (e.g. the sigmoid sinus and facial nerve and produces audiovisual warnings if the surgeon drills in too close vicinity. The aim of this study was to evaluate the accuracy and surgical utility of EVADE in physical phantoms. METHODOLOGY/PRINCIPAL FINDINGS: We performed 228 measurements assessing the position accuracy of tracking a navigated drill in the operating theatre. A mean target registration error of 1.33±0.61 mm with a maximum error of 3.04 mm was found. Five neurosurgeons each drilled two temporal bone phantoms, once using EVADE, and once using a standard neuronavigation interface. While using standard neuronavigation the surgeons damaged three modeled temporal bone critical structures. No structure was hit by surgeons utilizing EVADE. Surgeons felt better orientated and thought they had improved tumor exposure with EVADE. Furthermore, we compared the distances between surface meshes of the virtual drill cavities created by EVADE to actual drill cavities: average maximum errors of 2.54±0.49 mm and -2.70±0.48 mm were found. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that EVADE gives accurate feedback which reduces risks of harming modeled critical structures compared to a standard neuronavigation interface during temporal bone phantom drilling.

  12. International Tax Evasion, State Purchases of Confidential Bank Data and Voluntary Disclosures

    OpenAIRE

    Bethmann, Dirk; Kvasnicka, Michael

    2017-01-01

    State purchases of bank data on suspected tax evaders from international tax havens constitute a potential tool to combat international tax evasion. Using self-compiled data for North-Rhine Westphalia on the timing and content of such data acquisitions from whistleblowers and on monthly voluntary disclosures of international tax evasion involving Swiss banks, we show that purchases of data by tax authorities on potential tax evaders have a positive and sizeable effect on voluntary disclosures.

  13. Accumulation of immunoglobulin-containing cells in the gut mucosa and presence of faecal immunoglobulin in severe combined immunodeficient (scid) mice with T cell-induced inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Brimnes, J; Reimann, J

    1998-01-01

    and IgG2b were found to accumulate in colon segments displaying the most severe histopathology, including inflammatory cellular infiltration, epithelial hyperplasia and ulcerative lesions. Compared with colon segments of normal C.B-17 mice, the lesional scid colon shows increased levels of cells positive...

  14. Quantitation of immunoglobulins in ovine sera and secretions by laser nephelometry. Comparison with the radial immunodiffusion (RID) technique

    NARCIS (Netherlands)

    Goudswaard, J.; Verdouw-Chamalaun, C.V.M.; Noordzij, A.

    In twenty-five ovine body fluids (serum, lung fluid and cerebro-spinal fluid), the concentrations of IgG1, IgG2, IgM and IgA were determined by laser nephelometry and radial immunodiffusion (RID). When nephelometric assays are carried out, antisera free from any turbidity are essential. Methods

  15. Untitled

    African Journals Online (AJOL)

    taux élevé des anticorps IgG2 serait did a 'état constant de l'infestation. Les antiges spécificues ..... ELISA and suggest increased antibody production as infestation or ... have considered the molting infective larva as an im- portant target for the ...

  16. Binding of the mannose-specific lectin, griffithsin, to HIV-1 gp120 exposes the CD4-binding site

    CSIR Research Space (South Africa)

    Alexandre, Kabamba B

    2011-09-01

    Full Text Available of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs). We found that GRFT enhanced the binding of HIV-1 onto plates coated with anti-CD4bs antibodies b12, b6 or the CD4 receptor mimetic, CD4-IgG2...

  17. Prevention of lethal graft-versus-host disease in mice by monoclonal antibodies directed against T cells or their subsets.I.Evidence for the induction of a state of tolerance based on suppression

    NARCIS (Netherlands)

    Knulst, A.C.; Tibbe, G.J.M.; Noort, W.A.; Bril-Bazuin, C.; Benner, R.; Savelkoul, H.F.J.

    1994-01-01

    Lethal GVHD in the fully allogeneic BALB/c (donor)-(C57BL x CBA)F1 (recipient) mouse strain combination could be prevented by a single dose of IgG2b monoclonal antibodies (moAb) directed to T cells. The influence of the time of administration of this moAb after GVHD induction and the effect of

  18. Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis.

    Science.gov (United States)

    Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid

    2017-03-01

    There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  19. Monoclonal antibody PAL-E specific for endothelium

    NARCIS (Netherlands)

    Schlingemann, R. O.; Dingjan, G. M.; Emeis, J. J.; Blok, J.; Warnaar, S. O.; Ruiter, D. J.

    1985-01-01

    A monoclonal antibody, PAL-E, is described that is specific for endothelial cells. The monoclonal antibody, an IgG2a, markedly stains endothelium of capillaries, medium-sized and small veins, and venules in frozen sections of human and some animal tissues tested. It reacts not at all or only weakly

  20. Use of IgG avidity ELISA to differentiate acute from persistent infection with Salmonella Dublin in cattle

    DEFF Research Database (Denmark)

    Hansen, K.R.; Nielsen, L.R.; Lind, Peter

    2006-01-01

    Aims: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. Methods...

  1. IgG4 antibodies in Egyptian patients with schistosomiasis

    NARCIS (Netherlands)

    Iskander, R.; Das, P. K.; Aalberse, R. C.

    1981-01-01

    Serum immunoglobulins were determined in 40 Egyptian patients with schistosomiasis. In addition to the well-established elevation in total IgE, a striking imbalance in the IgG subclass levels was found: IgG3 and IgG4 levels were markedly elevated, whereas IgG2 levels were normal. The IgG4 level did

  2. Human IgG subclass antibodies to the 19 kilodalton carboxy ...

    African Journals Online (AJOL)

    IgG2 or IgG4 antibodies were virtually nonexistent. The cross-reactivity between the 4 sequence variants (E-KNG, E-TSR, Q-KNG and. Q-TSR) of MSP119 was confirmed; however, a minority of sera preferentially recognised the KNG but not the TSR variants. All 33 P. falciparum isolates from different parts ofm Uganda

  3. Radiolabeled Humanized Anti-CD3 Monoclonal Antibody Visilizumab for Imaging Human T-Lymphocytes

    NARCIS (Netherlands)

    Malviya, Gaurav; D'Alessandria, Calogero; Bonanno, Elena; Vexler, Vladimir; Massari, Roberto; Trotta, Carlo; Scopinaro, Francesco; Dierckx, Rudi; Signore, Alberto

    2009-01-01

    Visilizumab is an IgG(2) humanized monoclonal antibody (mAb) characterized by non-Fc gamma R binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a

  4. Identification of a novel 27-kDa protein from Mycobacterium tuberculosis culture fluid by a monoclonal antibody specific for the Mycobacterium tuberculosis complex

    NARCIS (Netherlands)

    Rambukkana, A.; Das, P. K.; Kolk, A. H.; Burggraaf, J. D.; Kuijper, S.; Harboe, M.

    1993-01-01

    Mycobacterium tuberculosis antigens inducing species-specific immune responses are likely to be particularly important for serodiagnosis or for skin testing of tuberculosis. In the present study, we describe the characterization of two novel monoclonal antibodies (MoAbs) A3h4 (IgG2a) and B5g1 (IgM)

  5. MONOCLONAL ANTIBODIES TO IDENTIFY TOMATO MOSAIC TOBAMOVIRUS (TOMV

    Directory of Open Access Journals (Sweden)

    Duarte Keila M.R.

    2001-01-01

    Full Text Available Monoclonal antibodies were obtained against Tomato mosaic tobamovirus (ToMV isolated in Brazil. One antibody (8G7G2 isotyped as IgG2b (kappa light chain showed strong specificity and very low cross reaction with the Tobacco mosaic virus (TMV. It can be used in identification of tomato mosaic virus (ToMV.

  6. Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

    Science.gov (United States)

    Estes, D M; Tuo, W; Brown, W C; Goin, J

    1998-12-01

    In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.

  7. Application of monoclonal antibodies in functional and comparative investigations of heavy-chain immunoglobulins in new world camelids.

    Science.gov (United States)

    Daley, L P; Gagliardo, L F; Duffy, M S; Smith, M C; Appleton, J A

    2005-03-01

    Of the three immunoglobulin G (IgG) isotypes described to occur in camelids, IgG2 and IgG3 are distinct in that they do not incorporate light chains. These heavy-chain antibodies (HCAbs) constitute approximately 50% of the IgG in llama serum and as much as 75% of the IgG in camel serum. We have produced isotype-specific mouse monoclonal antibodies (MAbs) in order to investigate the roles of HCAbs in camelid immunity. Seventeen stable hybridomas were cloned, and three MAbs that were specific for epitopes on the gamma chains of llama IgG1, IgG2, or IgG3 were characterized in detail. Affinity chromatography revealed that each MAb bound its isotype in solution in llama serum. The antibodies bound to the corresponding alpaca IgGs, to guanaco IgG1 and IgG2, and to camel IgG1. Interestingly, anti-IgG2 MAbs bound three heavy-chain species in llama serum, confirming the presence of three IgG2 subisotypes. Two IgG2 subisotypes were detected in alpaca and guanaco sera. The MAbs detected llama serum IgGs when they were bound to antigen in enzyme-linked immunosorbent assays and were used to discern among isotypes induced during infection with a parasitic nematode. Diseased animals, infected with Parelaphostrongylus tenuis, did not produce antigen-specific HCAbs; rather, they produced the conventional isotype, IgG1, exclusively. Our data document the utility of these MAbs in functional and physiologic investigations of the immune systems of New World camelids.

  8. Cocoa-enriched diets modulate intestinal and systemic humoral immune response in young adult rats.

    Science.gov (United States)

    Pérez-Berezo, Teresa; Franch, Angels; Ramos-Romero, Sara; Castellote, Cristina; Pérez-Cano, Francisco J; Castell, Margarida

    2011-05-01

    Previous studies have shown that a highly enriched cocoa diet affects both intestinal and systemic immune function in young rats. The aim of this study was to elucidate whether diets containing lower amounts of cocoa could also influence the systemic and intestinal humoral immune response. Fecal and serum samples were collected during the study and, at the end, intestinal washes were obtained and mesenteric lymph nodes and small-intestine walls were excised for gene expression assessment. IgA, IgM, IgG1, IgG2a, IgG2b and IgG2c concentrations were quantified in serum whereas S-IgA and S-IgM were determined in feces and intestinal washes. Animals receiving 5 and 10% cocoa for 3 wk showed no age-related increase in serum IgG1 and IgG2a concentrations, and IgG2a values were significantly lower than those in reference animals. Serum IgM was also decreased by the 10% cocoa diet. The 5 and 10% cocoa diets dramatically reduced intestinal S-IgA concentration and modified the expression of several genes involved in IgA synthesis. A diet containing 2% cocoa had no effect on most of the studied variables. The results demonstrate the downregulatory effect of a 5% or higher cocoa diet on the systemic and intestinal humoral immune response in adult rats. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Contributions to Pursuit-Evasion Game Theory

    Science.gov (United States)

    Oyler, Dave Wilson

    This dissertation studies adversarial conflicts among a group of agents moving in the plane, possibly among obstacles, where some agents are pursuers and others are evaders. The goal of the pursuers is to capture the evaders, where capture requires a pursuer to be either co-located with an evader, or in close proximity. The goal of the evaders is to avoid capture. These scenarios, where different groups compete to accomplish conflicting goals, are referred to as pursuit-evasion games, and the agents are called players. Games featuring one pursuer and one evader are analyzed using dominance, where a point in the plane is said to be dominated by a player if that player is able to reach the point before the opposing players, regardless of the opposing players' actions. Two generalizations of the Apollonius circle are provided. One solves games with environments containing obstacles, and the other provides an alternative solution method for the Homicidal Chauffeur game. Optimal pursuit and evasion strategies based on dominance are provided. One benefit of dominance analysis is that it extends to games with many players. Two foundational games are studied; one features multiple pursuers against a single evader, and the other features a single pursuer against multiple evaders. Both are solved using dominance through a reduction to single pursuer, single evader games. Another game featuring competing teams of pursuers is introduced, where an evader cooperates with friendly pursuers to rendezvous before being captured by adversaries. Next, the assumption of complete and perfect information is relaxed, and uncertainties in player speeds, player positions, obstacle locations, and cost functions are studied. The sensitivity of the dominance boundary to perturbations in parameters is provided, and probabilistic dominance is introduced. The effect of information is studied by comparing solutions of games with perfect information to games with uncertainty. Finally, a pursuit law

  10. Quantification of anti-Leishmania antibodies in saliva of dogs.

    Science.gov (United States)

    Cantos-Barreda, Ana; Escribano, Damián; Bernal, Luis J; Cerón, José J; Martínez-Subiela, Silvia

    2017-08-15

    Detection of serum anti-Leishmania antibodies by quantitative or qualitative techniques has been the most used method to diagnose Canine Leishmaniosis (CanL). Nevertheless, saliva may represent an alternative to blood because it is easy to collect, painless and non-invasive in comparison with serum. In this study, two time-resolved immunofluorometric assays (TR-IFMAs) for quantification of anti-Leishmania IgG2 and IgA antibodies in saliva were developed and validated and their ability to distinguish Leishmania-seronegative from seropositive dogs was evaluated. The analytical study was performed by evaluation of assay precision, sensitivity and accuracy. In addition, serum from 48 dogs (21 Leishmania-seropositive and 27 Leishmania-seronegative) were analyzed by TR-IFMAs. The assays were precise, with an intra- and inter-assay coefficients of variation lower than 11%, and showed high level of accuracy, as determined by linearity under dilution (R 2 =0.99) and recovery tests (>88.60%). Anti-Leishmania IgG2 antibodies in saliva were significantly higher in the seropositive group compared with the seronegative (pLeishmania IgA antibodies between both groups were observed. Furthermore, TR-IFMA for quantification of anti-Leishmania IgG2 antibodies in saliva showed higher differences between seropositive and seronegative dogs than the commercial assay used in serum. In conclusion, TR-IFMAs developed may be used to quantify anti-Leishmania IgG2 and IgA antibodies in canine saliva with an adequate precision, analytical sensitivity and accuracy. Quantification of anti-Leishmania IgG2 antibodies in saliva could be potentially used to evaluate the humoral response in CanL. However, IgA in saliva seemed not to have diagnostic value for this disease. For future studies, it would be desirable to evaluate the ability of the IgG2 assay to detect dogs with subclinical disease or with low antibody titers in serum and also to study the antibodies behaviour in saliva during the treatment of CanL. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Dynamics of tax evasion through an epidemic-like model

    Science.gov (United States)

    Brum, Rafael M.; Crokidakis, Nuno

    In this work, we study a model of tax evasion. We considered a fixed population divided in three compartments, namely honest tax payers, tax evaders and a third class between the mentioned two, which we call susceptibles to become evaders. The transitions among those compartments are ruled by probabilities, similarly to a model of epidemic spreading. These probabilities model social interactions among the individuals, as well as the government’s fiscalization. We simulate the model on fully-connected graphs, as well as on scale-free and random complex networks. For the fully-connected and random graph cases, we observe that the emergence of tax evaders in the population is associated with an active-absorbing nonequilibrium phase transition, that is absent in scale-free networks.

  12. Indirect reciprocity can overcome free-rider problems on costly moral assessment.

    Science.gov (United States)

    Sasaki, Tatsuya; Okada, Isamu; Nakai, Yutaka

    2016-07-01

    Indirect reciprocity is one of the major mechanisms of the evolution of cooperation. Because constant monitoring and accurate evaluation in moral assessments tend to be costly, indirect reciprocity can be exploited by cost evaders. A recent study crucially showed that a cooperative state achieved by indirect reciprocators is easily destabilized by cost evaders in the case with no supportive mechanism. Here, we present a simple and widely applicable solution that considers pre-assessment of cost evaders. In the pre-assessment, those who fail to pay for costly assessment systems are assigned a nasty image that leads to them being rejected by discriminators. We demonstrate that considering the pre-assessment can crucially stabilize reciprocal cooperation for a broad range of indirect reciprocity models. In particular for the most leading social norms, we analyse the conditions under which a prosocial state becomes locally stable. © 2016 The Authors.

  13. Deficient CD4+ T cell priming and regression of CD8+ T cell functionality in virus-infected mice lacking a normal B cell compartment

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Kauffmann, Susanne Ørding; Thomsen, Allan Randrup

    2003-01-01

    of virus-specific CD4(+) T cells was markedly impaired in B(-/-) mice infected with either virus strain. Thus, our results indicate that B cells play an important role in antiviral immunity not only as Ab producers, but also in promoting an optimal and sustained T cell response. The T cell defects......In this study, we investigate the state of T cell-mediated immunity in B cell-deficient (B(-/-)) mice infected with two strains of lymphocytic choriomeningitis virus known to differ markedly in their capacity to persist. In B(-/-) C57BL mice infected with the more persisting virus, virus......-specific CD8(+) T cells are initially generated that are qualitatively similar to those in wild-type mice. However, although cell numbers are well sustained over time, the capacity to produce cytokines is rapidly impaired. In similarly infected B(-/-) BALB/c mice, virus-specific CD8(+) T cells are completely...

  14. Memory vs memory-like: The different facets of CD8+ T-cell memory in HCV infection.

    Science.gov (United States)

    Hofmann, Maike; Wieland, Dominik; Pircher, Hanspeter; Thimme, Robert

    2018-05-01

    Memory CD8 + T cells are essential in orchestrating protection from re-infection. Hallmarks of virus-specific memory CD8 + T cells are the capacity to mount recall responses with rapid induction of effector cell function and antigen-independent survival. Growing evidence reveals that even chronic infection does not preclude virus-specific CD8 + T-cell memory formation. However, whether this kind of CD8 + T-cell memory that is established during chronic infection is indeed functional and provides protection from re-infection is still unclear. Human chronic hepatitis C virus infection represents a unique model system to study virus-specific CD8 + T-cell memory formation during and after cessation of persisting antigen stimulation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Modeling spatial navigation in the presence of dynamic obstacles: a differential games approach.

    Science.gov (United States)

    Darekar, Anuja; Goussev, Valery; McFadyen, Bradford J; Lamontagne, Anouk; Fung, Joyce

    2018-03-01

    Obstacle circumvention strategies can be shaped by the dynamic interaction of an individual (evader) and an obstacle (pursuer). We have developed a mathematical model with predictive and emergent components, using experimental data from seven healthy young adults walking toward a target while avoiding collision with a stationary or moving obstacle (approaching head-on, or diagonally 30° left or right) in a virtual environment. Two linear properties from the predictive component enable the evader to predict the minimum distance between itself and the obstacle at all times, including the future intersection of trajectories. The emergent component uses the classical differential games model to solve for an optimal circumvention while reaching the target, wherein the locomotor strategy is influenced by the obstacle, target, and the evader velocity. Both model components were fitted to a different set of experimental data obtained from five poststroke and healthy participants to derive the minimum predicted distance (predictive component) and obstacle influence dimensions (emergent component) during circumvention. Minimum predicted distance between evader and pursuer was kept constant when the evader was closest to the obstacle in all participants. Obstacle influence dimensions varied depending on obstacle approach condition and preferred side of circumvention, reflecting differences in locomotor strategies between poststroke and healthy individuals. Additionally, important associations between model outputs and observed experimental outcomes were found. The model, supported by experimental data, suggests that both predictive and emergent processes can shape obstacle circumvention strategies in healthy and poststroke individuals. NEW & NOTEWORTHY Obstacle circumvention during goal-directed locomotion is modeled with a new mathematical approach comprising both predictive and emergent elements. The major novelty is using differential games solutions to illustrate the

  16. Construction contract risk and reasonable evasions

    International Nuclear Information System (INIS)

    Wu Yunpeng

    2012-01-01

    Construction project has the characteristics such as large-scale investment, long-period implementation, excessive uncertainties,a single piece of production, etc. These characteristics determine the complexity of a construction project contract. To guarantee the time limit and quality of a project, finding ways to reduce and evade the contract risks as well as avoid unnecessary disputes are urgent requirements for each project manager. According to the practical situation, project contract risks are analyzed and illustrated in detail, and the concrete solutions for evading those risks are put forward. (authors)

  17. Lähme, naised / Tiina Kuuler

    Index Scriptorium Estoniae

    Kuuler, Tiina, 1969-

    2008-01-01

    Muusikasündmustest: "Peipsimaa kultuuripäevad" 1.-2. aug. Mustvee kultuurikeskuses, Mõisaküla kodukandipäevad" 1.-2. aug. Mõisakülas, "Kapa festival" 2. ja 3. aug. Kohilas Tohisoo pargis, "Heamuusika 2008" 1.- ja 2. aug. Võrtsjärve kaldal Ulgel, "Pillipiknik" 2. aug. Põlvamaal Süvahavval Kalmatemäel, "Marko Matvere merelaulud" 2. aug. Tartus Lodjakojas, Leigo Järvemuusika festival 2. augustil, Katalaani rahvusfestival 2. ja 3. aug. Tallinnas Raekoja platsil, "Viru Folk"8.-10. aug. Käsmus

  18. Tax Rates, Tax Evasion, and Growth in a Multi-period Economy

    OpenAIRE

    Jordi Caballé; Judith Panadés

    2007-01-01

    We extend the basic tax evasion model to a multi-period economy exhibiting sustained growth. When individuals conceal part of their true income from the tax authority, they face the risk of being audited and hence of paying the corresponding fine. Both taxes and fines determine individual saving and the rate of capital accumulation. We show that, if the penalty imposed on tax evaders is proportional to the amount of evaded taxes, then the growth rate is decreasing in the tax rate. However, th...

  19. Taovad elutud kivid elavaiks / Sirje Eelma

    Index Scriptorium Estoniae

    Eelma, Sirje, 1950-

    1998-01-01

    "Kunstisuve" raames toimuva Selgase dolomiidipäevade üks korraldajatest S. Eelma probleemidest, mis on üles kerkinud seoses paaril viimasel suvel tekkinud skulptuuri workshopide, päevade ja sümpoosionide rohkusega. Kujudest on saanud linnamiljöö kujundajad. 19.-25. juulini toimunud Selgase dolomiidipäevadest. Osalesid Ari Koch Soomest (töö "Lapi maastik"), Tõnu Smidt ("Päikeseloojang"), Ekke Väli ("Karjääri lõpp"). Loobusid Jüri Ojaver, Paul Rodgers.

  20. Immunoglobulin subclass in experimental murine Toxocara cati infection

    Directory of Open Access Journals (Sweden)

    Kusnoto

    2017-11-01

    Full Text Available Aim: The aim of this study was to detect specific immunoglobulin (Ig that could be used to determine monoclonal antibody in conjugate-making an effort for the indirect enzyme-linked immunosorbent assay (ELISA diagnostic kit of toxocariasis in human. Materials and Methods: The study was conducted to assess the Ig profile, based on ELISA-isotyping, in mice infected with second stage larvae eggs of Toxocara cati. The optical density values of anti-T. cati mice serum IgG subclasses were analyzed by applying ANOVA factorial. Results: The specific IgG subclass in mice infected with T. cati mice was found to be IgG2β. Conclusion: Subclass of IgG, especially IgG2β, can provide leads about the use of the monoclonal antibody in conjugate making an effort for the indirect ELISA diagnostic kit.

  1. Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

    Science.gov (United States)

    Reyes, L; Hartikka, J; Bozoukova, V; Sukhu, L; Nishioka, W; Singh, G; Ferrari, M; Enas, J; Wheeler, C J; Manthorpe, M; Wloch, M K

    2001-06-14

    Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

  2. Dynamics of the carbohydrate chains attached to the Fc portion of immunoglobulin G as studied by NMR spectroscopy assisted by selective 13C labeling of the glycans

    International Nuclear Information System (INIS)

    Yamaguchi, Yoshiki; Kato, Koichi; Shindo, Mitsuru; Aoki, Shin; Furusho, Kumiko; Koga, Kenji; Takahashi, Noriko; Arata, Yoji; Shimada, Ichio

    1998-01-01

    A systematic method for 13 C labeling of the glycan of immunoglobulin G for NMR study has been developed. A mouse immunoglobulin of subclass IgG2b has been used for the experiment. On the basis of chemical shift and linewidth data, it has been concluded that (1) the mobility of the carbohydrate chain in IgG2b is comparable to that of the backbone polypeptide chain with the exception of the galactose residue at the nonreducing end of the Man α 1-3 branch, which is extremely mobile and (2) agalactosylation does not induce any significant change in the mobility. The results obtained indicate that even in the agalactosyl form the glycans are buried in the protein. Biological significance of the NMR results obtained is also briefly discussed

  3. Evaluation of the immune response to CRA and FRA recombinant antigens of Trypanosoma cruzi in C57BL/6 mice.

    Science.gov (United States)

    Pereira, Valéria Rêgo Alves; de Lorena, Virginia Maria Barros; Nakazawa, Mineo; da Silva, Ana Paula Galvão; Montarroyos, Ulisses; Correa-Oliveira, Rodrigo; Gomes, Yara de Miranda

    2003-01-01

    Humoral and cellular immune responses were evaluated in 44 C57BL/6 mice immunized with the Trypanosoma cruzi recombinant antigens CRA and FRA. Both antigens induced cutaneous immediate-type hypersensitivity response. The levels of IgG1, IgG2a, IgG2b and IgG3 were high in CRA immunized mice. IgG3 was the predominant isotype. Although no difference in antibody levels was observed in FRA-immunized mice when compared to control mice, both antigens were able to induce lymphoproliferation in immunized mice. Significant differences were observed between incorporation of [ H]- thymidine by spleen cell stimulated in vitro with CRA or FRA and the control group. These results suggest that CRA and FRA could be involved in mechanisms of resistance to Trypanosoma cruzi infection.

  4. Assessment of a DNA vaccine encoding an anchored-glycosylphosphatidylinositol tegumental antigen complexed to protamine sulphate on immunoprotection against murine schistosomiasis

    Directory of Open Access Journals (Sweden)

    Eduardo JM Nascimento

    2007-02-01

    Full Text Available Protamine sulphate/DNA complexes have been shown to protect DNA from DNase digestion in a lipid system for gene transfer. A DNA-based vaccine complexed to protamine sulphate was used to induce an immune response against Schistosoma mansoni anchored-glycosylphosphatidylinositol tegumental antigen in BALB/c mice. The protection elicited ranged from 33 to 44%. The spectrum of the elicited immune response induced by the vaccine formulation without protamine was characterized by a high level of IgG (IgG1> IgG2a. Protamine sulphate added to the DNA vaccine formulation retained the green fluorescent protein encoding-plasmid longer in muscle and spleen. The experiments in vivo showed that under protamine sulphate effect, the scope of protection remained unchanged, but a modulation in antibody production (IgG1= IgG2a was observed.

  5. Differences in the pharmacokinetic and biodistribution in rates of the monoclonal antibody 125I-ior t1 due to I use of different methods of iodogen direct

    International Nuclear Information System (INIS)

    Montenegro, A.

    1997-01-01

    The monoclonal antibody ior t1, an IgG2a, was labeled with 125I , using the chloramine T, iodogen and iodine monochloride methods produce an important deiodination, demonstrated by ascending paper chromatography and the similarities between his serum profile respect to the radioactivity serum profile of the free 125I in Wistar rats. The plasma radioactivity declined in apparently bioexponential manner with the use of chloramine T and iodine monochloride, and show a monoexponential declined with the iodogen reagent. The pharmacokinetic of 125I ior t1, in the chloramine T methods, was very erractic. We consider the possible of an unspecific binding in blood in the experiment with iodogen reagents. The biodistribution show a similar pattern with other IgG2a in rats

  6. Enrichment of measles virus-like RNA in the nucleocapsid fraction isolated from subacute sclerosing panencephalitis brains

    Energy Technology Data Exchange (ETDEWEB)

    Bedows, E; Payne, F E [Michigan Univ., Ann Arbor (USA). School of Public Health; Kohne, D E [Center for Neurologic Study, San Diego, CA, USA; Tourtellotte, W W [Neurology Service, V.A. Wadsworth Hospital Center, Los Angeles, CA, USA

    1982-02-01

    A procedure has been developed which facilitates the detection of measles virus RNA sequences in human brains. The procedure involves isolating subviral components (nucleocapsids) from brain tissues prior to RNA purification, followed by hybridization of these RNAs to cDNA synthesized from measles virus 50 S RNA template. Using these techniques we were able to obtain an RNA fraction which was manyfold enriched in measles virus-specific RNA, relative to unfractionated subacute sclerosing panencephalitis (SSPE) brain RNAs. 70-100% of the measles virus-specific RNA present in these SSPE brain samples were recovered in this enriched fraction.

  7. Enrichment of measles virus-like RNA in the nucleocapsid fraction isolated from subacute sclerosing panencephalitis brains

    International Nuclear Information System (INIS)

    Bedows, E.; Payne, F.E.; Kohne, D.E.; Tourtellotte, W.W.

    1982-01-01

    A procedure has been developed which facilitates the detection of measles virus RNA sequences in human brains. The procedure involves isolating subviral components (nucleocapsids) from brain tissues prior to RNA purification, followed by hybridization of these RNAs to cDNA synthesized from measles virus 50 S RNA template. Using these techniques we were able to obtain an RNA fraction which was manyfold enriched in measles virus-specific RNA, relative to unfractionated subacute sclerosing panencephalitis (SSPE) brain RNAs. 70-100% of the measles virus-specific RNA present in these SSPE brain samples were recovered in this enriched fraction. (Auth.)

  8. Dynamics of Inter-heavy Chain Interactions in Human Immunoglobulin G (IgG) Subclasses Studied by Kinetic Fab Arm Exchange

    NARCIS (Netherlands)

    Rispens, Theo; Davies, Anna M.; Ooijevaar-de Heer, Pleuni; Absalah, Samira; Bende, Onno; Sutton, Brian J.; Vidarsson, Gestur; Aalberse, Rob C.

    2014-01-01

    Background: Fab arm exchange requires weak interactions between CH3 domains, such as in human IgG4. Results: CH3-CH3 interactions differ >1,000,000-fold between human subclasses and allotypes due to variations Lys/Asn-392, Val/Met-397, and Lys/Arg-409. Conclusion: For IgG2 and IgG3, but not IgG1,

  9. Evaluation of the adjuvant effect of Escherichia coli heat-labile ...

    African Journals Online (AJOL)

    Data on IgG antibody isotype profiles showed that IgG 1 and IgG 2a were predominant in mice immunized with rMVNP + LT or LTK63 whereas IgG 1 predominated when rMVNP was given on its own implying that LT and LTK63 induce both Th1 and Th2-type immune responses. These results highlight the great potential of ...

  10. Canine antibody response to Phlebotomus perniciosus bites negatively correlates with the risk of Leishmania infantum transmission.

    Directory of Open Access Journals (Sweden)

    Michaela Vlkova

    2011-10-01

    Full Text Available BACKGROUND: Phlebotomine sand flies are blood-sucking insects that can transmit Leishmania parasites. Hosts bitten by sand flies develop an immune response against sand fly salivary antigens. Specific anti-saliva IgG indicate the exposure to the vector and may also help to estimate the risk of Leishmania spp. transmission. In this study, we examined the canine antibody response against the saliva of Phlebotomus perniciosus, the main vector of Leishmania infantum in the Mediterranean Basin, and characterized salivary antigens of this sand fly species. METHODOLOGY/PRINCIPAL FINDINGS: Sera of dogs bitten by P. perniciosus under experimental conditions and dogs naturally exposed to sand flies in a L. infantum focus were tested by ELISA for the presence of anti-P. perniciosus antibodies. Antibody levels positively correlated with the number of blood-fed P. perniciosus females. In naturally exposed dogs the increase of specific IgG, IgG1 and IgG2 was observed during sand fly season. Importantly, Leishmania-positive dogs revealed significantly lower anti-P. perniciosus IgG2 compared to Leishmania-negative ones. Major P. perniciosus antigens were identified by western blot and mass spectrometry as yellow proteins, apyrases and antigen 5-related proteins. CONCLUSIONS: Results suggest that monitoring canine antibody response to sand fly saliva in endemic foci could estimate the risk of L. infantum transmission. It may also help to control canine leishmaniasis by evaluating the effectiveness of anti-vector campaigns. Data from the field study where dogs from the Italian focus of L. infantum were naturally exposed to P. perniciosus bites indicates that the levels of anti-P. perniciosus saliva IgG2 negatively correlate with the risk of Leishmania transmission. Thus, specific IgG2 response is suggested as a risk marker of L. infantum transmission for dogs.

  11. Cytokine profiles and antibody responses to Plasmodium falciparum ...

    African Journals Online (AJOL)

    Estimated higher ratios of IFN-γ/IL-10 and IFN-γ/IL-12 were also observed in the symptomatic children while the asymptomatic controls had higher IL-12/IL-10 ratio. The mean concentration levels of anti-P. falciparum IgG1, IgG2, IgG3 antibodies were statistically significantly higher in the individuals >5 years of age than <5 ...

  12. Protective effect of the LevRad on treat of paracoccidioidomycosis

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Fernandes, Viviane Cristina; Morais, Elis Araujo; Goes, Alfredo M.; Resende, Maria Aparecida de

    2011-01-01

    Paracoccidioides brasiliensis is the agent of Paracoccidioidomycosis (PCM), the most prevalent deep mycosis of Latin America. The period of treat depend on the chemotherapeutic and the severity of disease and its administration not ensure the complete destruction of the fungus. The search for new alternatives is necessary. The aim of this study was to evaluate the protective effect of yeast cells of P. brasiliensis attenuated by gamma irradiation (LevRad) on therapeutic vaccination of BALB/c. The therapeutic potential of LevRad with or without fluconazole was assessed for the first time, intraperitoneally, in BALB/c, 60 days after intratracheal infection with a highly virulent non-irradiated P.brasiliensis isolate. The animals were divided in five experimental groups: uninfected (C-), infected (C+), infected treated with fluconazole (Inmed), infected treated with LevRad (InRad) and infected treated with fluconazole + LevRad (InRadMed). The organs (lungs, spleen and liver) were collected to analyze CFU (colony forming units) and histology. The sera were used to evaluate the immunization efficacy, and to assess IgG subtypes (IgG1, IgG2a, IgG2b, IgG3) and total IgG levels. There was significant decrease in the CFU counts of the lungs of InMed, InRadMed and InRad. No were visualized histopathological alterations in the organs of these groups, except in InRad there was granulomatous lesions unifocal, little and discrete. The levels of IgG and its subtypes IgG2a, IgG2b increased, probably due to the increase of cytokines that promote switching to these isotypes. These preliminary results can provide new prospect for immunotherapy of PCM, but it will be necessary new studies to evaluate administration dose and period treatment. (author)

  13. Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

    Science.gov (United States)

    Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

    2018-05-01

    Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

  14. Schistosoma mansoni infection and the associated antibody ...

    African Journals Online (AJOL)

    Decrease in titres of anti (SWAP IgG1, SEA IgG1, and SEA IgG4) was not significant but decrease of anti (SWAP IgG2, SWAP IgG3 and SWAP IgG4) was significant. Positive correlation existed between age and anti SWAP IgE in before and after treatment sera. On the contrary, age was positively correlated with anti SWAP ...

  15. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide.

    Science.gov (United States)

    Sanford, J E; Lupan, D M; Schlageter, A M; Kozel, T R

    1990-01-01

    The in vivo properties of an immunoglobulin isotype-switch family of monoclonal antibodies specific for the polysaccharide capsule of Cryptococcus neoformans were examined in a murine model of cryptococcosis. Subclass-switch variants were isolated by sequential sublining of an immunoglobulin G subclass 1 (IgG1)-secreting cell line. Antibodies of the IgG1, IgG2a, and IgG2b isotypes with identical reactivities with cryptococcal polysaccharide were prepared. The antibodies had the distinct biological properties associated with the heavy chains of each respective isotype. The antibodies were used prophylactically or therapeutically in an attempt to alter the course of cryptococcal infection in mice. Survival of mice and a tissue census of the numbers of viable cryptococci in the lung, spleen, and brain were used as indicators of efficacy. Passive immunization with the IgG2a and IgG2b antibodies effected a reduction in the numbers of cryptococci in lung and spleen. Passive immunization with the IgG1 antibody was markedly less effective. Passive immunization had little or no effect on the numbers of cryptococci in brain tissue, regardless of the immunoglobulin isotype. Despite apparent efficacy with regard to reduction in the numbers of yeast cells in the lung and spleen, the results showed no improvement in survival from murine cryptococcosis. Our results indicate that passive immunization produces a modest effect on the course of murine cryptococcosis in tissues other than brain. However, under the experimental conditions used, such treatment does not have a measurable impact on the ultimate outcome of the infection. PMID:2341184

  16. APPLICATION OF IMMUNOGLOBULIN-BINDING PROTEINS A, G, L IN THE AFFINITY CHROMATOGRAPHY

    Directory of Open Access Journals (Sweden)

    О. V. Sviatenko

    2014-04-01

    Full Text Available Proteins A, G and L are native or recombinant proteins of microbial origin that bind to mammalian immunoglobulins. Preferably recombinant variants of proteins A, G, L are used in biotechnology for affinity sorbents production. Сomparative characteristics of proteins A, G, L and affinity sorbents on the basis of them, advantages and disadvantages of these proteins application as ligands in the affinity chromatography are done. Analysis of proteins A, G, L properties is presented. Binding specificities and affinities of these proteins differ between species and antibody subclass. Protein А has high affinity to human IgG1, IgG2, IgG4, mouse IgG2a, IgG2b, IgG3, goat and sheep IgG2, dog, cat, guinea pig, rabbit IgG. Protein G binds strongly to human, mouse, cow, goat, sheep and rabbit IgG. Protein L has ability of strong binding to immunoglobulin kappa-chains of human, mouse, rat and pig. Expediency of application of affinity chromatography with usage of sorbents on the basis of immobilized proteins A, G, L are shown for isolation and purification of antibodies different classes. Previously mentioned method is used as an alternative to conventional methods of protein purification, such as ion-exchange, hydrophobic interactions, metal affinity chromatography, ethanol precipitation due to simplicity in usage, possibility of one-step purification process, obtaining of proteins high level purity, multiuse at maintenance of proper storage and usage conditions. Affinity sorbents on the basis of immobilized proteins A, G, L are used not only for antibodies purification, but also for extraction of different antibodies fractions from blood serum.

  17. eCD4-Ig promotes ADCC activity of sera from HIV-1-infected patients.

    Directory of Open Access Journals (Sweden)

    Meredith E Davis-Gardner

    2017-12-01

    Full Text Available Antibody-dependent cell-mediated cytotoxity (ADCC can eliminate HIV-1 infected cells, and may help reduce the reservoir of latent virus in infected patients. Sera of HIV-1 positive individuals include a number of antibodies that recognize epitopes usually occluded on HIV-1 envelope glycoprotein (Env trimers. We have recently described eCD4-Ig, a potent and exceptionally broad inhibitor of HIV-1 entry that can be used to protect rhesus macaques from multiple high-dose challenges with simian-human immunodeficiency virus AD8 (SHIV-AD8. Here we show that eCD4-Ig bearing an IgG1 Fc domain (eCD4-IgG1 can mediate efficient ADCC activity against HIV-1 isolates with differing tropisms, and that it does so at least 10-fold more efficiently than CD4-Ig, even when more CD4-Ig molecules bound cell surface-expressed Env. An ADCC-inactive IgG2 form of eCD4-Ig (eCD4-IgG2 exposes V3-loop and CD4-induced epitopes on cell-expressed trimers, and renders HIV-1-infected cells susceptible to ADCC mediated by antibodies of these classes. Moreover, eCD4-IgG2, but not IgG2 forms of the broadly neutralizing antibodies VRC01 and 10-1074, enhances the ADCC activities of serum antibodies from patients by 100-fold, and significantly enhanced killing of two latently infected T-cell lines reactivated by vorinostat or TNFα. Thus eCD4-Ig is qualitatively different from CD4-Ig or neutralizing antibodies in its ability to mediate ADCC, and it may be uniquely useful in treating HIV-1 infection or reducing the reservoir of latently infected cells.

  18. Evaluation of Immunogenicity of Yersinia enterocolitica O:8 Oligopolysaccaride-DiphtheriaeToxoide Conjugate in Mice

    Directory of Open Access Journals (Sweden)

    SM Rezavian

    2015-06-01

    Full Text Available Background & objectives: Yersiniosis is created by Yersinia enterocolitica O:8 and causes problems in the world especialy in cold and mild countries. The purpose of this study is to evaluate the immunogenicity of Yersinia enterocolitica O:8 oligopolysaccaride (OPS conjugate to diphtheria toxoid (DT as a vaccine candidate.   Methods : After cultivation of bacteria, the LPS were isolated by modified hot phenol method. Then dialysis and concentration were done and the OPS were extracted by acetic acid 2%. To conjugate with diphtheria toxoid, ADH was used as a spacer molecule and EDAC as a linker. Conjugate was purified by gel filtration. Then 4 groups of female BALB/c mice were selected (15 mice in each group. Injection was performed intraperitoneally in three doses with two weeks interval. Then serum samples were collected and antibody response against OPS was measured by indirect ELISA method for detection of total IgG, IgA, IgM, IgG1, IgG2a, IgG2b and IgG3.   Results: After second and third doses, OPS-DT recieved group showed significant increase in all types of antibodies titer in anti-OPS in comparison to group that recived nonconjugated OPS. The increase in titer of antibodies was as: OPS-DT>OPS>DT. A remarkable increase was shown in total IgG and IgM titers (with total amount of 3204 and 670, respectively. In IgG1 subclass the amount was 920 and in other subclasses of IgG (IgG3, IgG2a and IgG2b the amounts were 910, 110, and 99, respectively.   Conclusion: The results shows that OPS of Yersinia enterocolitica O:8 increases the anti-OPS antibodies in the form of conjugate with diphtheria toxoid and could be considered as an appropriate vaccine candidate.

  19. Effects of dietary CLA supplementation, parity and different concentrate levels before calving on immunoglobulin G1, G2 and M concentrations in dairy cows.

    Science.gov (United States)

    Eger, Melanie; Horn, Jana; Hussen, Jamal; Schuberth, Hans-Joachim; Scharf, Maria; Meyer, Ulrich; Dänicke, Sven; Bostedt, Hartwig; Breves, Gerhard

    2017-10-01

    Peripartal dairy cows exhibit a higher susceptibility for infectious diseases, which might be linked to the negative energy balance occurring at the onset of lactation. A dietary supplementation of conjugated linoleic acids (CLA) may reduce milk fat yield and subsequently lower the energy deficit. The utilization of immunoglobulins (Ig) for colostrogenesis might impair humoral immunity in peripartal dairy cows; therefore this study investigated the effects of a CLA supplement, parity and different dietary energy levels on plasma and colostrum IgG1, IgG2 and IgM levels in dairy cows and their calves. Blood samples were collected from 64 cows from 21days before until 56days after parturition and colostrum samples for the first 3days of lactation. Plasma immunoglobulin concentrations of 19 calves were determined before colostrum uptake. Neither plasma IgG1, nor IgG2 levels were affected by CLA or dietary energy level. However, immunoglobulin levels were affected by parity. Heifers possessed the lowest IgG1 concentrations. IgG2 concentrations were highest in cows with 2 lactations prior to parturition and in heifers after parturition. Plasma IgM levels were characterized by a sharp decrease 3days prior to parturition and were scarcely affected by the feeding regimen or parity. Generally, immunoglobulin levels appear to be mostly independent from the peripartal energy balance of the cows and are not influenced by dietary CLA. However, pronounced differences among parities for IgG1 and IgG2 were revealed which should be further evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Immunogenic evaluation of Paracoccidioides brasiliensis radioattenuated yeast cells in murine model

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Fernandes, Viviane Cristina; Morais, Elis Araujo; Goes, Alfredo M.; Resende, Maria Aparecida de

    2011-01-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM), a chronic systemic disease prevalent in Latin American, which is characterized by the formation of granulomatous lesions. To date, there is no effective vaccine to PCM or to any systemic mycosis. In an attempt to induce an efficient response to such agent in an animal model, gamma radiation attenuated P. brasiliensis yeast cells (LevRad) were developed at the Radiobiology Laboratory from CDTN/CNEN. A gamma radiation dose was defined in which the pathogen loses its ability to multiply, while retaining its viability, metabolic activity and antigenic profile. The prophylactic potential of LevRad was assessed after its intravenous administration in male Balb/C mice, challenged 45 days after immunization with intratracheal administration of 3x105 cells of a highly virulent non-radiated P.brasiliensis isolate. At 30 and 90 days post challenge (dpc), lungs, spleen and liver were collected to analyse CFU (colony forming units) recovery, histology, cell proliferation, cytokine (IFN-gamma, IL-4, IL-10, TNF-alpha and TGF-beta) and iNOS production. The sera were used to evaluate the immunization efficacy, and to assess IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) and total IgG levels. The present data show that there was no significant decrease in the CFU counts of the lungs of immunized animals 30 dpc. Nevertheless, no CFU or histopathological alterations were visualized at the organs of immunized animals at 90 dpc. During the same period, IgG2a, IgG2b, IFN-alpha and iNOS levels raised while IL-10, TNF-alpha, TGF-beta and IL-4 maintained low levels, suggesting the prevalence of Th1 response profile. Our results confirmed the protective (author)

  1. Characterisation of up-regulated immunoglobulins in patients with chronic rhinosinusitis

    International Nuclear Information System (INIS)

    Madani, S.A.; Hashemi, S.A

    2014-01-01

    To evaluate the role of immunoglobulins in patients of chronic rhinosinusitis. Methods: Patients were recruited from the Ear, Nose, Throat, Head And Neck Surgery section of Mazandaran University of Medical Sciences, Sari, Iran, from December 2011 to August 2012. Immunoglobulin G, IgG1, IgG2, IgG3, IgG4 were evaluated. Salivary IgA was assessed by direct immunoenzymatic determination. The quantifications of serum IgG, IgG1, IgG2, IgG3, IgG4 and salivary IgA was performed through nephelometric procedure. Serum IgE was measured by enzyme-linked immunoabsorbent assay. SPSS 15 was used for statistical analysis. Results: Of the 50 patients, 22 (44%) were males and 28(56%) were females. The overall age ranged from 1 to 67 years with a mean of 28.06+-15.49. There was significant changes in levels of IgG, IgG1, salivary IgA and IgE (p=0.001). Significant difference was noted for IgG2 (p=0.03) and in IgG4 (p=0.01). There was no significant alteration in IgG3 level (p=0.3). Conclusion: There was high prevalence of humoral immune alterations both in local and systemic response to chronic inflammation in the patients, which suggests that assessment of immunoglobulin before clinical evaluation and management could be important. (author)

  2. Antilymphocytic antibodies and marrow transplantation. VIII. Recipient conditioning with Clq-affine monoclonal anti-pan T antibodies prevents GVHD in homozygous fully mismatched mice

    International Nuclear Information System (INIS)

    Thierfelder, S.; Kummer, U.; Schuh, R.; Mysliwietz, J.

    1986-01-01

    An approach to suppressing secondary disease with antibodies was studied that differed from conventional antibody treatment of donor marrow in vitro. It consisted of the selection of anti-Thy-1 antibodies with high affinity for Clq, the first subunit of the complement cascade, and a single injection of such antibodies into prospective irradiated marrow recipients. Monoclonal mouse IgM and rat IgG 2c antibodies of high titers in complement-dependent test systems but with low affinity for Clq caused little immunosuppression. Monoclonal rat IgG2b or mouse IgG2a anti-Thy-1 antibodies with high affinity for Clq prevented acute and chronic mortality of graft-v-host disease (GVHD), however, when injected in irradiated CBA or AKR mice prior to C57BL/6 spleen and/or bone marrow cell transfusion. This treatment simultaneously suppressed residual host-v-graft reactivity of the irradiated mice, so that permanent hematopoietic engraftment ensued even at 5 or 6 Gy. Full chimerism and specific tolerance were obtained. Primary immune response to SRBC was clearly depressed in the chimeras; secondary immune response was not. Clearance of T cell antibody activity (greater than 6 days), timing, and dose of injected antibody, as well as other modalities of the conditioning treatment that may have contributed to the remarkable immunosuppression, are discussed

  3. On the efficacy of malaria DNA vaccination with magnetic gene vectors.

    Science.gov (United States)

    Nawwab Al-Deen, Fatin; Ma, Charles; Xiang, Sue D; Selomulya, Cordelia; Plebanski, Magdalena; Coppel, Ross L

    2013-05-28

    We investigated the efficacy and types of immune responses from plasmid malaria DNA vaccine encoding VR1020-PyMSP119 condensed on the surface of polyethyleneimine (PEI)-coated SPIONs. In vivo mouse studies were done firstly to determine the optimum magnetic vector composition, and then to observe immune responses elicited when magnetic vectors were introduced via different administration routes. Higher serum antibody titers against PyMSP119 were observed with intraperitoneal and intramuscular injections than subcutaneous and intradermal injections. Robust IgG2a and IgG1 responses were observed for intraperitoneal administration, which could be due to the physiology of peritoneum as a major reservoir of macrophages and dendritic cells. Heterologous DNA prime followed by single protein boost vaccination regime also enhanced IgG2a, IgG1, and IgG2b responses, indicating the induction of appropriate memory immunity that can be elicited by protein on recall. These outcomes support the possibility to design superparamagnetic nanoparticle-based DNA vaccines to optimally evoke desired antibody responses, useful for a variety of diseases including malaria. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

    Directory of Open Access Journals (Sweden)

    Mohd eKhubaib

    2016-05-01

    Full Text Available PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.

  5. Protection against Fasciola gigantica using paramyosin antigen as a candidate for vaccine production.

    Science.gov (United States)

    Abou-Elhakam, H; Rabee, I; El Deeb, S; El Amir, A

    2013-11-15

    Yet no vaccine to protect ruminants against liver fluke infection has been commercialized. In an attempt to develop a suitable vaccine against Fasciola gigantica (F. gigantica) infection in rabbits, using 97 kDa Pmy antigen. It was found that, the mean worm burdens and bile egg count after challenge were reduced significantly by 58.40 and 61.40%, respectively. On the other hand, immunization of rabbits with Pmy induced a significant expression of humoral antibodies (IgM, total IgG, IgG1, IgG2 and IgG4) and different cytokines (IL-6, IL-10, L-12 and TNF-alpha). Among Ig isotypes, IgG2 and IgG4 were most dominant Post-infection (PI) while, recording a low IgG1 level. The dominance of IgG2 and IgG4 suggested late T helper1 (Th1) involvement in rabbit's cellular response. While, the low IgG1 level suggested Th2 response to adult F. gigantica worm Pmy. Among all cytokines, IL-10 was the highest in rabbits immunized with Pmy PI suggesting also the enhancement of Th2 response. It was clear that the native F. gigantica Pmy is considered as a relevant candidate for vaccination against fascioliasis. Also, these data suggested the immunoprophylactic effect of the native F. gigantica Pmy which is mediated by a mixed Th1/Th2 response.

  6. Mangifera indica L. extract (Vimang) and mangiferin modulate mouse humoral immune responses.

    Science.gov (United States)

    García, D; Leiro, J; Delgado, R; Sanmartín, M L; Ubeira, F M

    2003-12-01

    The present study investigated the effects of orally administered Vimang (an aqueous extract of Mangifera indica) and mangiferin (the major polyphenol present in Vimang) on mouse antibody responses induced by inoculation with spores of microsporidian parasites. Inoculation induced specific antibody production with an exponential timecourse, peaking after about one month. Vimang significantly inhibited this antibody production from about three weeks post-inoculation, and most markedly by four weeks post-inoculation; by contrast, mangiferin had no significant effect. Determination of Ig isotypes showed that the IgM to IgG switch began about four weeks post-inoculation, with IgG2a predominating. Vimang significantly inhibited IgG production, but had no effect on IgM. Mangiferin did no affect either IgM or IgG2a, but significantly enhanced production of IgG1 and IgG2b. Neither Vimang nor mangiferin enhanced specific antibody secretion by splenic plasma cells from mice inoculated with microsporidian spores, whether administered in vivo before serum extraction or in vitro to the culture medium. Inoculation with spores induced splenomegaly, which was significantly reduced by Vimang and significantly enhanced by mangiferin. These results suggest that components of Mangifera indica extracts may be of potential value for modulating the humoral response in different immunopathological disorders. Copyright 2003 John Wiley & Sons, Ltd.

  7. The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium

    Directory of Open Access Journals (Sweden)

    Mutapi Francisca

    2002-01-01

    Full Text Available The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection.

  8. Labeling and stability of radiolabeled antibody fragments by a direct 99mTc-labeling method

    International Nuclear Information System (INIS)

    Pak, K.Y.; Nedelman, M.A.; Tam, S.H.; Wilson, E.; Daddona, P.E.

    1992-01-01

    The in vitro labeling and stability of 99m Tc-labeled antibody Fab' fragments prepared by a direct labeling technique were evaluated. Eight antibody fragments derived from murine IgG1 (N = 5), IgG2a (N = 2) and IgG3 (N = 1) isotypes were labeled with a preformed 99m Tc-D-glucarate complex. No loss of radioactivity incorporation was observed for all the 99m Tc-labeled antibody fragments after 24 h incubation at 37 o C. 99m Tc-labeled antibody fragments (IgG1, N = 2; IgG2a, n = 2; IgG3, N = 1) were stable upon challenge with DTPA, EDTA or acidic pH. Using the affinity chromatography technique, two of the 99m Tc-labeled antibody fragments displayed no loss of immunoreactivity after prolonged incubation in phosphate buffer up to 24 h at 37 o C. Bonding between 99m Tc and antibody fragments was elucidated by challenging with a diamide ditholate (N 2 S 2 ) compound. The Fab' with IgG2a isotype displayed tighter binding to 99m Tc in comparison to Fab' from IgG1 and IgG3 isotype in N 2 S 2 challenge and incubation with human plasma. The in vivo biodistribution of five 99m Tc-labeled fragments were evaluated in normal mice. (Author)

  9. Detection of Bovine IgG Isotypes in a PPA-ELISA for Johne's Disease Diagnosis in Infected Herds.

    Science.gov (United States)

    Fernández, Bárbara; Gilardoni, Liliana Rosa; Jolly, Ana; Colavecchia, Silvia Beatriz; Paolicchi, Fernando Alberto; Mundo, Silvia Leonor

    2012-01-01

    Johne's Disease or Paratuberculosis is a chronic granulomatous enteritis disease affecting ruminants. Detection of subclinically infected animals is difficult, hampering the control of this disease. The aim of this work was to evaluate the performance of detection of IgG isotypes in a PPA-ELISA to improve the recognition of cattle naturally infected with Map in different stages. A total of 108 animals from Tuberculosis-free herds were grouped as follows: exposed (n = 30), subclinically infected (n = 26), clinically infected (n = 14), and healthy controls (n = 38). Receiver-operating characteristic (ROC) curves of isotypes/PPA-ELISAs were constructed and areas under the curves were compared to evaluate the performance of each test. Our study demonstrated that the conventional PPA-ELISA (detecting IgG) is the best to identify clinically infected animals with high sensitivity (92.9%) and specificity (100%). Meanwhile, IgG2/PPA-ELISA improved the number of subclinically infected cattle detected as compared with conventional IgG/PPA-ELISA (53.8 versus 23.1%). In addition, it had the maximum sensitivity (65.0%, taking into account all Map-infected cattle). In conclusion, the combination of IgG and IgG2/PPA-ELISAs may improve the identification of Map-infected cattle in different stages of disease. The usefulness of IgG2 detection in serological tests for Johne's Disease diagnosis should be further evaluated.

  10. Immune recognition of salivary proteins from the cattle tick Rhipicephalus microplus differs according to the genotype of the bovine host.

    Science.gov (United States)

    Garcia, Gustavo Rocha; Maruyama, Sandra Regina; Nelson, Kristina T; Ribeiro, José Marcos Chaves; Gardinassi, Luiz Gustavo; Maia, Antonio Augusto Mendes; Ferreira, Beatriz Rossetti; Kooyman, Frans N J; de Miranda Santos, Isabel K F

    2017-03-14

    Males of the cattle tick Rhipicephalus microplus produce salivary immunoglobulin-binding proteins and allotypic variations in IgG are associated with tick loads in bovines. These findings indicate that antibody responses may be essential to control tick infestations. Infestation loads with cattle ticks are heritable: some breeds carry high loads of reproductively successful ticks, in others, few ticks feed and they reproduce inefficiently. Different patterns of humoral immunity against tick salivary proteins may explain these phenotypes. We describe the profiles of humoral responses against tick salivary proteins elicited during repeated artificial infestations of bovines of a tick-resistant (Nelore) and a tick-susceptible (Holstein) breed. We measured serum levels of total IgG1, IgG2 and IgE immunoglobulins and of IgG1 and IgG2 antibodies specific for tick salivary proteins. With liquid chromatography followed by mass spectrometry we identified tick salivary proteins that were differentially recognized by serum antibodies from tick-resistant and tick-susceptible bovines in immunoblots of tick salivary proteins separated by two-dimensional electrophoresis. Baseline levels of total IgG1 and IgG2 were significantly higher in tick-susceptible Holsteins compared with resistant Nelores. Significant increases in levels of total IgG1, but not of IgG2 accompanied successive infestations in both breeds. Resistant Nelores presented with significantly higher levels of salivary-specific antibodies before and at the first challenge with tick larvae; however, by the third challenge, tick-susceptible Holsteins presented with significantly higher levels of IgG1 and IgG2 tick salivary protein-specific antibodies. Importantly, sera from tick-resistant Nelores reacted with 39 tick salivary proteins in immunoblots of salivary proteins separated in two dimensions by electrophoresis versus only 21 spots reacting with sera from tick-susceptible Holsteins. Levels of tick saliva-specific antibodies were not directly correlated with infestation phenotypes. However, in spite of receiving apparently lower amounts of tick saliva, tick-resistant bovines recognized more tick salivary proteins. These reactive salivary proteins are putatively involved in several functions of parasitism and blood-feeding. Our results indicate that neutralization by host antibodies of tick salivary proteins involved in parasitism is essential to control tick infestations.

  11. fs - kes ta on ja kust ta tuleb : [luuletused] / [Mesikepp, Indrek] fs

    Index Scriptorium Estoniae

    fs, pseud., 1971-

    2004-01-01

    Sisu: fs - kes ta on ja kust ta tuleb ; "töötasin arhiivis..." ; mustad puud mustas vees ; "on päev. on kylm. on öö..." ; "tead ju kyll..." ; "päiksest paistes päevad..." ; "mida sa teed kui on öö..."

  12. Erakordne aeg või valed mudelid? / Erik Aru

    Index Scriptorium Estoniae

    Aru, Erik

    2008-01-01

    Paul De Grauwe, Leonardo Iania ja Pablo Rovira Kaltwasser arvutasid välja börsidel erakordsemate päevade esinemise tõenäosuse. Nende järelduse kohaselt ei ole mitte praegune aeg erakordne, vaid finantsmudelid on valed. Lisa: Indeks Dow Jones Industrial Average oktoobrikuus

  13. 'Videokunst on tõsine asi,' räägib kunstnik Al Paldrock / Al Paldrok ; interv. Tiiu Leis

    Index Scriptorium Estoniae

    Paldrok, Al, 1969-

    1998-01-01

    Intervjuu Pärnu filmipäevade (2.-4. apr.) ühe peakorraldaja, Helsingis Kuvataide akadeemias video- ja keskkonnakunsti õppinud Al Paldrokiga filmipäevadest (kus esitatakse nii video-, reklaam- kui dokumentaalfilme), eesti filmist ja videokunstist, rühmitusest 'Vedelik'

  14. 29 CFR 1625.8 - Bona fide seniority systems.

    Science.gov (United States)

    2010-07-01

    ... equitable allocation of available employment opportunities and prerogatives among younger and older workers. (b) Adoption of a purported seniority system which gives those with longer service lesser rights, and... upon the circumstances, be a “subterfuge to evade the purposes” of the Act. (c) Unless the essential...

  15. Piip ja Tuut ootavad Amarillosse ja Coca-Cola Plazasse perepäevale

    Index Scriptorium Estoniae

    2004-01-01

    Kord kuus, septembrist 2004 kuni 2005.a. maini korraldatavatest perepäevadest. C-C Plazas on perepäevade ajal kavas eriprogramm ja enne või pärast filmi on pered oodatud Viru hotelli restorani Amarillo, kus kavas spetsiaalne lasteprogramm klounidelt Piip ja Tuut

  16. Pärnus avati monument süütusele

    Index Scriptorium Estoniae

    1999-01-01

    Andrus Joonase Pootsi paepäevade raames valminud monument süütusele avati Academia Non Grata teise aastapäeva puhul Lepa kaubamaja ja karja tänava vahelisel alal; autori arvates on hingeline süütus kunstnikule väga tähtis ja Academia Non Grata ainus õppeasutus, kus õpilased seda hoida saavad.

  17. Deceptive Imprinting and Immune Refocusing in Vaccine Design

    Science.gov (United States)

    A large number of the world’s most widespread and problematic pathogens evade host immune responses by inducing strain specific immunity to immunodominant epitopes with high mutation rates capable of altering antigenic profiles. The immune system appears to be decoyed into reacting to these immunod...

  18. Mis on elus olulisim / Aita Kivi

    Index Scriptorium Estoniae

    Kivi, Aita, 1954-

    2002-01-01

    Sisu : Mitch Albom. Teisipäevad Morrie'ga; Santa Montefiore. Oota mind ombupuu all; Ridley Pearson. Tont teab kus; Sebastian Faulks. Linnulaul; Kerttu Rakke. Iluasjake; Merike Hanni. Kooliraha; Viivi Luik. Ajaloo ilu; Hermann Hesse. Stepihunt; Eesti luulet läbi aegade / [koostanud Marika Vingissar; Philip K. Dick. Ubik; Marion Zimmer Bradley. Avaloni udud; Kuus eesti luuletajat / koostanud Anne Lange

  19. The informal sector in transition: Tax evasion in an institutional vacuum

    NARCIS (Netherlands)

    Gërxhani, K.

    2002-01-01

    This thesis discusses the informal sector mainly focusing on the study of tax evasion. Individuals' decision whether or not to evade taxes is the core of the studies presented here. The role of institutions in this individual decision is considered to be of crucial importance. As a natural

  20. Isast, Pojast ja Pühast Arhitektuurist / Toivo Tammik

    Index Scriptorium Estoniae

    Tammik, Toivo

    2006-01-01

    Dokumentaalfilmist Saaremaalt pärit ameerika arhitektist Louis Kahnist "My Architect : A Son's Journey" (režissöör Nathaniel Kahn, produtsent Susan Behr, USA, 2003, 116 min.) ja viibimisest Philadelphias seoses Louis Kahni päevade ettevalmistamisega

  1. The Image of the Negro in Deep South Public School State History Texts.

    Science.gov (United States)

    McLaurin, Melton

    This report reviews the image portrayed of the Negro, in textbooks used in the deep South. Slavery is painted as a cordial, humane system under kindly masters and the Negro as docile and childlike. Although the treatment of the modern era is relatively more objective, the texts, on the whole, evade treatment of the Civil Rights struggle, violence,…

  2. To tell or not to tell: Negotiating disclosure for people living with HIV ...

    African Journals Online (AJOL)

    From weighing up other people's reactions, to being concerned about the effect of their disclosure on their disclosure targets, to concealing one's status to evade untoward negative reactions towards themselves. Further, negotiating one's disclosure is not only about to whom or how to disclose, it also means finding good ...

  3. Multiple antibiotic resistance iIndex of EscherichiaColi isolates in a ...

    African Journals Online (AJOL)

    Background: The effectiveness of available antibiotics is reducing as microorganisms device means of evading its effects, resulting in the development of superbugs. Pathogens previously susceptible are becoming resistant, and spreading beyond the hospital environment. This change is a major concern for infection ...

  4. Tax evasion and the source of income: An experimental study in Albania and the Netherlands

    NARCIS (Netherlands)

    Gërxhani, K.; Schram, A.

    2003-01-01

    A series of experiments among different social groups in both Albania and the Netherlands give the opportunity to compare behavioral patterns related to tax evasion. Aside from the decision whether or not to evade taxes, subjects have to choose a source of income, where one type enables subsequent

  5. The hypervariable region of Streptococcus pyogenes M protein escapes antibody attack by antigenic variation and weak immunogenicity

    DEFF Research Database (Denmark)

    Lannergård, Jonas; Gustafsson, Caj Ulrik Mattias; Waldemarsson, Johan

    2011-01-01

    Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion...

  6. Diagnostic Evasion of Highly-Resistant Microorganisms: A Critical Factor in Nosocomial Outbreaks.

    Science.gov (United States)

    Zhou, Xuewei; Friedrich, Alexander W; Bathoorn, Erik

    2017-01-01

    Highly resistant microorganisms (HRMOs) may evade screening strategies used in routine diagnostics. Bacteria that have evolved to evade diagnostic tests may have a selective advantage in the nosocomial environment. Evasion of resistance detection can result from the following mechanisms: low-level expression of resistance genes not resulting in detectable resistance, slow growing variants, mimicry of wild-type-resistance, and resistance mechanisms that are only detected if induced by antibiotic pressure. We reviewed reports on hospital outbreaks in the Netherlands over the past 5 years. Remarkably, many outbreaks including major nation-wide outbreaks were caused by microorganisms able to evade resistance detection by diagnostic screening tests. We describe various examples of diagnostic evasion by several HRMOs and discuss this in a broad and international perspective. The epidemiology of hospital-associated bacteria may strongly be affected by diagnostic screening strategies. This may result in an increasing reservoir of resistance genes in hospital populations that is unnoticed. The resistance elements may horizontally transfer to hosts with systems for high-level expression, resulting in a clinically significant resistance problem. We advise to communicate the identification of HRMOs that evade diagnostics within national and regional networks. Such signaling networks may prevent inter-hospital outbreaks, and allow collaborative development of adapted diagnostic tests.

  7. Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Kharazmi, A

    1991-01-01

    Pseudomonas aeruginosa, an extracellular opportunistic pathogen, utilizes two major mechanisms to evade the host defence system. One of these mechanisms is the production of a large number of extracellular products, such as proteases, toxins, and lipases. The two proteases, alkaline protease and ...

  8. Tax Evasion and Swiss Bank Deposits

    DEFF Research Database (Denmark)

    Johannesen, Niels

    Bank deposits in jurisdictions with banking secrecy constitute an effective tool to evade taxes on interest income. A recent EU reform reduces the scope for this type of tax evasion by introducing a source tax on interest income earned by EU residents in Switzerland and several other jurisdictions...

  9. Access and control of agro-biotechnology : Bt cotton, ecological change and risk in China

    NARCIS (Netherlands)

    Ho, Peter; Zhao, Jennifer H.; Xue, Dayuan

    2009-01-01

    This article argues that if the introduction of genetically modified crops (GM crops) in developing countries is to be successful, we can and should not evade questions of access and control of technology. It implies probing into the experiences, perceptions and understanding of GM crops by the

  10. The Ascomycota tree of life: a phylum-wide phylogeny clarifies the origin and evolution of fundamental reproductive and ecological traits

    Science.gov (United States)

    C.L. Schoch; G.-H. Sung; F. Lopez-Giraldez

    2009-01-01

    We present a six-gene, 420-species maximum-likelihood phylogeny of Ascomycota, the largest phylum of fungi. This analysis is the most taxonomically complete to date with species sampled from all 15 currently circumscribed classes. A number of superclass-level nodes that have previously evaded resolution and were unnamed in classifications of the fungi are resolved for...

  11. Occurrence of Photobacterium leiognathi, as the bait organ symbiont in frogfish Antennarius hispidus

    Digital Repository Service at National Institute of Oceanography (India)

    Ramaiah, N.; Chandramohan, D.

    ability for the purpose of: (a) luring smaller prey and (b) evading the attention of aggressive or larger predators. The scanty distribution of P. leiognathi in the water column of both coastal and offshore environs of the Arabian Sea is also highlighted...

  12. The structure of weak interaction

    International Nuclear Information System (INIS)

    Zee, A.

    1977-01-01

    The effect of introducing righthanded currents on the structure of weak interaction is discussed. The ΔI=1/2 rule is in the spotlight. The discussion provides an interesting example in which the so-called Iizuka-Okubo-Zweing rule is not only evaded, but completely negated

  13. Planning the horticultural sector : Managing greenhouse sprawl in the Netherlands

    NARCIS (Netherlands)

    Korthals Altes, W.K.; Van Rij, H.E.

    2013-01-01

    Greenhouses are a typical example of peri-urban land-use, a phenomenon that many planning systems find difficult to address as it mixes agricultural identity with urban appearance. Despite its urban appearance, greenhouse development often manages to evade urban containment policies. But a ban on

  14. Kas holokaust võib korduda? / Elhonen Saks

    Index Scriptorium Estoniae

    Saks, Elhonen, 1927-

    2000-01-01

    Eestit külastas USA Kongressi Esindajatekoja välissuhete komisjoni liige Tom Lantos. Dokumentaalfilm "Viimased päevad" ("The Last Days") Eesti välisministeeriumi pressikeskuses. režissöör James Moll : Ameerika Ühendriigid 1998. Survivors of the Shoah Visual History Foundation algatus. Filmi esitusel osalesid ka L. Meri ja T. H. Ilves.

  15. Commentary

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    gene silencing, DNA microarray data and completion of whole genome sequences of ... Evading this mid-gut barrier is one of the big hurdles for the parasite and is a ... studied in such screens, a small set of genes having a drastic effect on the ...

  16. Kes lavastas Suure Paugu? / Maris Johannes

    Index Scriptorium Estoniae

    Johannes, Maris, 1959-

    2007-01-01

    Eest Muusika päevade raames Tallinna tollilaos etendunud Stephen Hawkingi raamatu "A Brief History of Time" ("Aja lühilugu") ainelisest multimeedialavastusest "Õnne valem", Von Krahli teatrile ja NYYD Ensemble'ile originaalmuusika autor Gavin Bryars, autor ja lavastaja Peeter Jalakas

  17. Tõde jälitab meid kui vari / Vaapo Vaher

    Index Scriptorium Estoniae

    Vaher, Vaapo, 1945-

    2006-01-01

    Erich Maria Remarque'ist seoses romaani "Lissaboni öö" kordustrüki ilmumisega (kirj. Tänapäev). Raamatututvustused: Vaarandi, Debora. Aastad ja päevad : nooruselugu. Tallinn : Tänapäev, 2006 ; Loosaar, Evald. Eesti mehe lugu. Tallinn : Varrak, 2006 ; Kangro, Bernard, Ristikivi, Karl. Kirjad romaanist : 31 kirja aastaist 1966-1977. Tallinn : Varrak, 2006

  18. Personal Data Protection as a Nonfunctional Requirement in the Smart City’s Development

    NARCIS (Netherlands)

    Dalla Corte, L.; van Loenen, B.; Cuijpers, Colette; Anglès Juanpere, Benjamí; Balcells Padullés, Joan

    2017-01-01

    “Smart city” is a buzzword, highly hyped up and evading a unitary characterisation. Its blurriness is highlighted by the broad array of definitions with which academic and corporate literature have attempted at delineating the notion. This paper derives from the elaboration of several definitions

  19. Untitled

    African Journals Online (AJOL)

    Storage root quality varied among varieties and deteriorated with time for all varieties. The magnitude of ... in order to harvest at a time of high market demand as well as evade .... Varietal response to weevil infestation in relation to rainfall ...

  20. 32 CFR 516.10 - Service of civil process within the United States.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Service of civil process within the United States... CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Service of Process § 516.10 Service of civil process within the United States. (a) Policy. DA officials will not prevent or evade the service or process in...