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Sample records for class ii peptide

  1. MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation

    DEFF Research Database (Denmark)

    Rosloniec, E F; Vitez, L J; Buus, S

    1990-01-01

    the alpha k-3 peptide binds slightly less well. These combined data, suggesting that class II-derived peptides can bind to MHC class II molecules, including the autologous molecule from which they are derived, have important implications for the molecular basis of alloreactivity and autoreactivity. Further...... found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k-3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323......-339) immunodominant peptide to the I-Ad-restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3...

  2. Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides

    DEFF Research Database (Denmark)

    Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren

    2016-01-01

    The aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02...... four of the double binding peptides did result in HLA-A*02:01 restricted responses only. According to their cytokine profile, the CD4 T cell responses were of the Th2 type. In influenza infected mice, we were unable to detect natural processing in vivo of the double restricted peptides and in line...... with this, peptide vaccination did not decrease virus titres in the lungs of intranasally influenza challenged mice. Our data show that HLA class I and class II double binding peptides can be identified by bioinformatics and biochemical technology. By immunization, double binding peptides can give rise...

  3. Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model

    Directory of Open Access Journals (Sweden)

    Mittelmann Hans D

    2010-01-01

    Full Text Available Abstract Background The binding of peptide fragments of extracellular peptides to class II MHC is a crucial event in the adaptive immune response. Each MHC allotype generally binds a distinct subset of peptides and the enormous number of possible peptide epitopes prevents their complete experimental characterization. Computational methods can utilize the limited experimental data to predict the binding affinities of peptides to class II MHC. Results We have developed the Regularized Thermodynamic Average, or RTA, method for predicting the affinities of peptides binding to class II MHC. RTA accounts for all possible peptide binding conformations using a thermodynamic average and includes a parameter constraint for regularization to improve accuracy on novel data. RTA was shown to achieve higher accuracy, as measured by AUC, than SMM-align on the same data for all 17 MHC allotypes examined. RTA also gave the highest accuracy on all but three allotypes when compared with results from 9 different prediction methods applied to the same data. In addition, the method correctly predicted the peptide binding register of 17 out of 18 peptide-MHC complexes. Finally, we found that suboptimal peptide binding registers, which are often ignored in other prediction methods, made significant contributions of at least 50% of the total binding energy for approximately 20% of the peptides. Conclusions The RTA method accurately predicts peptide binding affinities to class II MHC and accounts for multiple peptide binding registers while reducing overfitting through regularization. The method has potential applications in vaccine design and in understanding autoimmune disorders. A web server implementing the RTA prediction method is available at http://bordnerlab.org/RTA/.

  4. Functional recombinant MHC class II molecules and high-throughput peptide-binding assays

    DEFF Research Database (Denmark)

    Justesen, Sune; Harndahl, Mikkel; Lamberth, Kasper

    2009-01-01

    BACKGROUND: Molecules of the class II major histocompability complex (MHC-II) specifically bind and present exogenously derived peptide epitopes to CD4+ T helper cells. The extreme polymorphism of the MHC-II hampers the complete analysis of peptide binding. It is also a significant hurdle......-II molecules and accompanying HTS peptide-binding assay were successfully developed for nine different MHC-II molecules including the DPA1*0103/DPB1*0401 (DP401) and DQA1*0501/DQB1*0201, where both alpha and beta chains are polymorphic, illustrating the advantages of producing the two chains separately....... CONCLUSION: We have successfully developed versatile MHC-II resources, which may assist in the generation of MHC class II -wide reagents, data, and tools....

  5. Predicting peptides binding to MHC class II molecules using multi-objective evolutionary algorithms

    Directory of Open Access Journals (Sweden)

    Feng Lin

    2007-11-01

    Full Text Available Abstract Background Peptides binding to Major Histocompatibility Complex (MHC class II molecules are crucial for initiation and regulation of immune responses. Predicting peptides that bind to a specific MHC molecule plays an important role in determining potential candidates for vaccines. The binding groove in class II MHC is open at both ends, allowing peptides longer than 9-mer to bind. Finding the consensus motif facilitating the binding of peptides to a MHC class II molecule is difficult because of different lengths of binding peptides and varying location of 9-mer binding core. The level of difficulty increases when the molecule is promiscuous and binds to a large number of low affinity peptides. In this paper, we propose two approaches using multi-objective evolutionary algorithms (MOEA for predicting peptides binding to MHC class II molecules. One uses the information from both binders and non-binders for self-discovery of motifs. The other, in addition, uses information from experimentally determined motifs for guided-discovery of motifs. Results The proposed methods are intended for finding peptides binding to MHC class II I-Ag7 molecule – a promiscuous binder to a large number of low affinity peptides. Cross-validation results across experiments on two motifs derived for I-Ag7 datasets demonstrate better generalization abilities and accuracies of the present method over earlier approaches. Further, the proposed method was validated and compared on two publicly available benchmark datasets: (1 an ensemble of qualitative HLA-DRB1*0401 peptide data obtained from five different sources, and (2 quantitative peptide data obtained for sixteen different alleles comprising of three mouse alleles and thirteen HLA alleles. The proposed method outperformed earlier methods on most datasets, indicating that it is well suited for finding peptides binding to MHC class II molecules. Conclusion We present two MOEA-based algorithms for finding motifs

  6. Improved methods for predicting peptide binding affinity to MHC class II molecules

    DEFF Research Database (Denmark)

    Jensen, Kamilla Kjærgaard; Andreatta, Massimo; Marcatili, Paolo

    2018-01-01

    Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented b...... are publicly available at www.cbs.dtu.dk/services/NetMHCII-2.3 and www.cbs.dtu.dk/services/NetMHCIIpan-3.2. This article is protected by copyright. All rights reserved....

  7. MHC class II tetramers made from isolated recombinant α and β chains refolded with affinity-tagged peptides

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Justesen, Sune Frederik Lamdahl; Osterbye, Thomas

    2013-01-01

    Targeting CD4+ T cells through their unique antigen-specific, MHC class II-restricted T cell receptor makes MHC class II tetramers an attractive strategy to identify, validate and manipulate these cells at the single cell level. Currently, generating class II tetramers is a specialized undertaking...... effectively limiting their use and emphasizing the need for improved methods of production. Using class II chains expressed individually in E. coli as versatile recombinant reagents, we have previously generated peptide-MHC class II monomers, but failed to generate functional class II tetramers. Adding...... a monomer purification principle based upon affinity-tagged peptides, we here provide a robust method to produce class II tetramers and demonstrate staining of antigen-specific CD4+ T cells. We also provide evidence that both MHC class II and T cell receptor molecules largely accept affinity-tagged peptides...

  8. Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells

    OpenAIRE

    Walseng, Even; Furuta, Kazuyuki; Bosch, Berta; Weih, Karis A.; Matsuki, Yohei; Bakke, Oddmund; Ishido, Satoshi; Roche, Paul A.

    2010-01-01

    The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface e...

  9. Improved methods for predicting peptide binding affinity to MHC class II molecules.

    Science.gov (United States)

    Jensen, Kamilla Kjaergaard; Andreatta, Massimo; Marcatili, Paolo; Buus, Søren; Greenbaum, Jason A; Yan, Zhen; Sette, Alessandro; Peters, Bjoern; Nielsen, Morten

    2018-01-06

    Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen-presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC-II-peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan. These were constructed using an extended data set of quantitative MHC-peptide binding affinity data obtained from the Immune Epitope Database covering HLA-DR, HLA-DQ, HLA-DP and H-2 mouse molecules. We show that training with this extended data set improved the performance for peptide binding predictions for both methods. Both methods are publicly available at www.cbs.dtu.dk/services/NetMHCII-2.3 and www.cbs.dtu.dk/services/NetMHCIIpan-3.2. © 2018 John Wiley & Sons Ltd.

  10. Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

    Science.gov (United States)

    Chen, B P; Madrigal, A; Parham, P

    1990-09-01

    Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

  11. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction

    Directory of Open Access Journals (Sweden)

    Lund Ole

    2009-09-01

    Full Text Available Abstract Background The major histocompatibility complex (MHC molecule plays a central role in controlling the adaptive immune response to infections. MHC class I molecules present peptides derived from intracellular proteins to cytotoxic T cells, whereas MHC class II molecules stimulate cellular and humoral immunity through presentation of extracellularly derived peptides to helper T cells. Identification of which peptides will bind a given MHC molecule is thus of great importance for the understanding of host-pathogen interactions, and large efforts have been placed in developing algorithms capable of predicting this binding event. Results Here, we present a novel artificial neural network-based method, NN-align that allows for simultaneous identification of the MHC class II binding core and binding affinity. NN-align is trained using a novel training algorithm that allows for correction of bias in the training data due to redundant binding core representation. Incorporation of information about the residues flanking the peptide-binding core is shown to significantly improve the prediction accuracy. The method is evaluated on a large-scale benchmark consisting of six independent data sets covering 14 human MHC class II alleles, and is demonstrated to outperform other state-of-the-art MHC class II prediction methods. Conclusion The NN-align method is competitive with the state-of-the-art MHC class II peptide binding prediction algorithms. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCII-2.0.

  12. Design of Peptide Immunotherapies for MHC Class-II-Associated Autoimmune Disorders

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    Masha Fridkis-Hareli

    2013-01-01

    Full Text Available Autoimmune disorders, that occur when autoreactive immune cells are induced to activate their responses against self-tissues, affect one percent of the world population and represent one of the top 10 leading causes of death. The major histocompatibility complex (MHC is a principal susceptibility locus for many human autoimmune diseases, in which self-tissue antigens providing targets for pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated alleles. In spite of the attempts to design strategies for inhibition of antigen presentation targeting the MHC-peptide/TCR complex via generation of blocking antibodies, altered peptide ligands (APL, or inhibitors of costimulatory molecules, potent therapies with minimal side effects have yet to be developed. Copaxone (glatiramer acetate, GA is a random synthetic amino acid copolymer that reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis (MS patients. Based on the elucidated binding motifs of Copaxone and of the anchor residues of the immunogenic myelin basic protein (MBP peptide to HLA-DR molecules, novel copolymers have been designed and proved to be more effective in suppressing MS-like disease in mice. In this report, we describe the rationale for design of second-generation synthetic random copolymers as candidate drugs for a number of MHC class-II-associated autoimmune disorders.

  13. Identification of MHC class II restricted T‐cell‐mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides

    DEFF Research Database (Denmark)

    Wang, Mingjun; Tang, Sheila Tuyet; Stryhn, Anette

    2011-01-01

    Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide...

  14. Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes

    Czech Academy of Sciences Publication Activity Database

    Kropshofer, H.; Spindeldreher, S.; Rohn, T. A.; Platania, N.; Grygar, C.; Daniel, N.; Wolpl, A.; Langen, H.; Hořejší, Václav; Vogt, A. B.

    2002-01-01

    Roč. 3, č. 1 (2002), s. 61-68 ISSN 1529-2908 Institutional research plan: CEZ:AV0Z5052915 Keywords : MHC II * tetraspan microdomains * peptide presentation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 27.868, year: 2002

  15. Citrullination only infrequently impacts peptide binding to HLA class II MHC

    DEFF Research Database (Denmark)

    Sidney, John; Becart, Stephane; Zhou, Mimi

    2017-01-01

    It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and th...

  16. Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance

    Directory of Open Access Journals (Sweden)

    Lisa K. Denzin

    2013-12-01

    Full Text Available Major histocompatibility class II (MHCII molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs. This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM. DM activity is directly opposed by HLA-DO (DO, another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.

  17. Structural requirements for the interaction between class II MHC molecules and peptide antigens

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Appella, E

    1990-01-01

    of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity (IA(d) or IE(d)); 3) IA(d) and IE(d) molecules recognize different and independent structures on the antigen molecule; 4) only about 10% of the single...... IA(d) and IE(d) molecules and their peptide ligands, we found that some structural characteristics apply to both antigen-MHC interactions. In particular, we found: 1) each MHC molecule is capable of binding many unrelated peptides through the same peptide-binding site; 2) despite this permissiveness...... amino acid substitutions tested on two IA(d)- and IE(d)-binding peptides had significant effect on their MHC-binding capacities, while over 80% of these substitutions significantly impaired T cell recognition of the Ia-peptide complex; 5) based on the segregation between residues that are crucial for T...

  18. Limitations of Ab Initio Predictions of Peptide Binding to MHC Class II Molecules

    DEFF Research Database (Denmark)

    Zhang, Hao; Lund, Ole; Nielsen, Morten

    2010-01-01

    potentials derived from the analysis of known protein structures; energetic evaluation of different peptide snapshots in a molecular dynamics simulation; and direct analysis of contacts made in known 3D structures of peptide:MHC complexes. These methods are ab initio in that they require structural data...

  19. Machine Learning Reveals a Non-Canonical Mode of Peptide Binding to MHC class II Molecules

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Jurtz, Vanessa Isabell; Kaever, Thomas

    2017-01-01

    binding motif with a non-canonical binding core of length different from nine. This previously undescribed mode of peptide binding to MHCII molecules gives a more complete picture of peptide presentation by MHCII and allows us to model more accurately this event. This article is protected by copyright...

  20. Semi-empirical quantum evaluation of peptide - MHC class II binding

    Science.gov (United States)

    González, Ronald; Suárez, Carlos F.; Bohórquez, Hugo J.; Patarroyo, Manuel A.; Patarroyo, Manuel E.

    2017-01-01

    Peptide presentation by the major histocompatibility complex (MHC) is a key process for triggering a specific immune response. Studying peptide-MHC (pMHC) binding from a structural-based approach has potential for reducing the costs of investigation into vaccine development. This study involved using two semi-empirical quantum chemistry methods (PM7 and FMO-DFTB) for computing the binding energies of peptides bonded to HLA-DR1 and HLA-DR2. We found that key stabilising water molecules involved in the peptide binding mechanism were required for finding high correlation with IC50 experimental values. Our proposal is computationally non-intensive, and is a reliable alternative for studying pMHC binding interactions.

  1. Naturally processed measles virus peptide eluted from class II HLA-DRB1*03 recognized by T lymphocytes from human blood

    International Nuclear Information System (INIS)

    Ovsyannikova, Inna G.; Johnson, Kenneth L.; Naylor, Stephen; Muddiman, David C.; Poland, Gregory A.

    2003-01-01

    This is the first report of the direct identification of a HLA-DRB1*03 measles-derived peptide from measles virus infected EBV-transformed B cells. We purified HLA-DR3-peptide complexes from EBV-B cells infected with measles virus (Edmonston strain) and sequenced the HLA-DR3-peptides by mass spectrometry. A class II peptide, derived from a measles phosphoprotein, ASDVETAEGGEIHELLRLQ (P1, residues 179-197), exhibited the capacity to stimulate peripheral blood mononuclear cells to proliferate. Our data provides direct evidence that the antigenic peptide of measles virus was processed by antigen-presenting cells, presented in the context of HLA class II molecules, and was recognized by peripheral blood T cells from healthy individuals previously immunized with measles vaccine. The approach described herein provides a useful methodology for the future identification of HLA-presented pathogen-derived epitopes using mass spectrometry. The study of cell-mediated immune responses to the measles-derived peptide in immune persons should provide significant insight into the design and development of new vaccines

  2. Quantum chemical analysis explains hemagglutinin peptide-MHC Class II molecule HLA-DRβ1*0101 interactions

    International Nuclear Information System (INIS)

    Cardenas, Constanza; Villaveces, Jose Luis; Bohorquez, Hugo; Llanos, Eugenio; Suarez, Carlos; Obregon, Mateo; Patarroyo, Manuel Elkin

    2004-01-01

    We present a new method to explore interactions between peptides and major histocompatibility complex (MHC) molecules using the resultant vector of the three principal multipole terms of the electrostatic field expansion. Being that molecular interactions are driven by electrostatic interactions, we applied quantum chemistry methods to better understand variations in the electrostatic field of the MHC Class II HLA-DRβ1*0101-HA complex. Multipole terms were studied, finding strong alterations of the field in Pocket 1 of this MHC molecule, and weak variations in other pockets, with Pocket 1 >> Pocket 4 > Pocket 9 ∼ Pocket 7 > Pocket 6. Variations produced by 'ideal' amino acids and by other occupying amino acids were compared. Two types of interactions were found in all pockets: a strong unspecific one (global interaction) and a weak specific interaction (differential interaction). Interactions in Pocket 1, the dominant pocket for this allele, are driven mainly by the quadrupole term, confirming the idea that aromatic rings are important in these interactions. Multipolar analysis is in agreement with experimental results, suggesting quantum chemistry methods as an adequate methodology to understand these interactions

  3. Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II peptide-pulsed DCs

    Directory of Open Access Journals (Sweden)

    Satthaporn Sukchai

    2009-03-01

    Full Text Available Abstract Background Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i DC activation/maturation milieu (TNF-α +/- IFN-α and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865, (ii CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672-pulsed DCs, prepared without IFN-α, (iii association between circulating T regulatory cells (Tregs and clinical responses. Methods Autologous DCs were generated from 10 patients (HLA-0201 with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI was pulsed with only one type of hTERT peptide (p540 or p865 and both preparations were injected into separate lymph node draining regions every 2–3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865-loaded DCT with or without class II cognate help (p766 and p672 in 6 patients. T regulatory cells were evaluated in 8 patients. Results (i DCTIs and DCTs, pulsed with hTERT peptides, were comparable (p = 0.45, t-test in inducing peptide-specific CD8+ T cell responses. (ii Class II cognate help, significantly enhanced (p (iii Clinical responders had significantly lower (p Conclusion Addition of IFN-α to ex vivo monocyte-derived DCs, did not significantly enhance peptide-specific T cell responses in vivo, compared with TNF-α alone. Class II cognate help significantly augments peptide-specific T cell responses. Clinically favourable responses were seen in patients

  4. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lund, Ole

    2009-01-01

    this binding event. RESULTS: Here, we present a novel artificial neural network-based method, NN-align that allows for simultaneous identification of the MHC class II binding core and binding affinity. NN-align is trained using a novel training algorithm that allows for correction of bias in the training data...

  5. Quantification of HLA-DM-Dependent Major Histocompatibility Complex of Class II Immunopeptidomes by the Peptide Landscape Antigenic Epitope Alignment Utility

    Directory of Open Access Journals (Sweden)

    Miguel Álvaro-Benito

    2018-05-01

    Full Text Available The major histocompatibility complex of class II (MHCII immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research. A key challenge in the case of MHCII immunopeptidomes, often determined for different samples at distinct conditions, is to derive quantitative information on consensus epitopes from antigenic peptides of variable lengths. Here, we present the design and benchmarking of a new algorithm [peptide landscape antigenic epitope alignment utility (PLAtEAU] allowing the identification and label-free quantification (LFQ of shared consensus epitopes arising from series of nested peptides. The algorithm simplifies the complexity of the dataset while allowing the identification of nested peptides within relatively short segments of protein sequences. Moreover, we apply this algorithm to the comparison of the ligandomes of cell lines with two different expression levels of the peptide-exchange catalyst HLA-DM. Direct comparison of LFQ intensities determined at the peptide level is inconclusive, as most of the peptides are not significantly enriched due to poor sampling. Applying the PLAtEAU algorithm for grouping of the peptides into consensus epitopes shows that more than half of the total number of epitopes is preferentially and significantly enriched for each condition. This simplification and deconvolution of the complex and ambiguous peptide-level dataset highlights the value of the PLAt

  6. Structural properties of MHC class II ligands, implications for the prediction of MHC class II epitopes.

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    Kasper Winther Jørgensen

    2010-12-01

    Full Text Available Major Histocompatibility class II (MHC-II molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100-200 peptides per allele to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined prediction method was shown to significantly outperform the state-of-the-art MHC class II peptide binding prediction method when used to identify MHC class II ligands. We also tried to integrate N- and O-glycosylation in our prediction methods but this additional information was found not to improve prediction performance. In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule.

  7. MHC Class II epitope predictive algorithms

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lund, Ole; Buus, S

    2010-01-01

    Major histocompatibility complex class II (MHC-II) molecules sample peptides from the extracellular space, allowing the immune system to detect the presence of foreign microbes from this compartment. To be able to predict the immune response to given pathogens, a number of methods have been...... developed to predict peptide-MHC binding. However, few methods other than the pioneering TEPITOPE/ProPred method have been developed for MHC-II. Despite recent progress in method development, the predictive performance for MHC-II remains significantly lower than what can be obtained for MHC-I. One reason...

  8. Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes is Limited by their Intrinsic Ability to Process and Present Antigenic Peptides

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    Aftab A. Ansari

    2003-01-01

    Full Text Available In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1 to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR β1*0301 pulsed with the influenza A matrix 1 (58-66 peptide (M1 were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC. Pretreatment of these M1-VAC targets with IFN-γ partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-γ pretreated W-1's could not process tetanus toxin (TT or present the TT(830-843 peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-γ to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-γ pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation.

  9. T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides

    DEFF Research Database (Denmark)

    Larsen, S L; Pedersen, L O; Buus, S

    1996-01-01

    Endocytosed protein antigens are believed to be fragmented in what appears to be a balance between proteolysis and MHC-mediated epitope protection, and the resulting peptide-MHC complexes are transported to the surface of the antigen-presenting cells (APC) and presented to T cells. The events tha...

  10. Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

    DEFF Research Database (Denmark)

    Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

    2017-01-01

    Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is...

  11. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

    2007-12-01

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

  12. The systems biology of MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra

    2012-01-01

    Major histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC). They present peptides derived from endocytosed material to T helper lymphocytes. Consequently, MHC class

  13. Shark class II invariant chain reveals ancient conserved relationships with cathepsins and MHC class II.

    Science.gov (United States)

    Criscitiello, Michael F; Ohta, Yuko; Graham, Matthew D; Eubanks, Jeannine O; Chen, Patricia L; Flajnik, Martin F

    2012-03-01

    The invariant chain (Ii) is the critical third chain required for the MHC class II heterodimer to be properly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells. Here, we report the isolation of the nurse shark Ii gene, and the comparative analysis of Ii splice variants, expression, genomic organization, predicted structure, and function throughout vertebrate evolution. Alternative splicing to yield Ii with and without the putative protease-protective, thyroglobulin-like domain is as ancient as the MHC-based adaptive immune system, as our analyses in shark and lizard further show conservation of this mechanism in all vertebrate classes except bony fish. Remarkable coordinate expression of Ii and class II was found in shark tissues. Conserved Ii residues and cathepsin L orthologs suggest their long co-evolution in the antigen presentation pathway, and genomic analyses suggest 450 million years of conserved Ii exon/intron structure. Other than an extended linker preceding the thyroglobulin-like domain in cartilaginous fish, the Ii gene and protein are predicted to have largely similar physiology from shark to man. Duplicated Ii genes found only in teleosts appear to have become sub-functionalized, as one form is predicted to play the same role as that mediated by Ii mRNA alternative splicing in all other vertebrate classes. No Ii homologs or potential ancestors of any of the functional Ii domains were found in the jawless fish or lower chordates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Machine learning competition in immunology – Prediction of HLA class I binding peptides

    DEFF Research Database (Denmark)

    Zhang, Guang Lan; Ansari, Hifzur Rahman; Bradley, Phil

    2011-01-01

    of peptide binding, therefore, determines the accuracy of the overall method. Computational predictions of peptide binding to HLA, both class I and class II, use a variety of algorithms ranging from binding motifs to advanced machine learning techniques ( [Brusic et al., 2004] and [Lafuente and Reche, 2009...

  15. pH dependence of the interaction between immunogenic peptides and MHC class II molecules. Evidence for an acidic intracellular compartment being the organelle of interaction

    DEFF Research Database (Denmark)

    Mouritsen, S; Buus, Anette Stryhn; Petersen, B L

    1992-01-01

    and most notably in the endosome-lysosome compartment in which Ag processing is thought to occur. Thus, Ag processing and interaction with MHC class II molecules can potentially happen in the very same compartment. This yet undefined acidic compartment would have to contain proteolytic enzymes and MHC...

  16. Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity: in silico bioinformatic step-by-step guide using quantitative structure-activity relationships.

    Science.gov (United States)

    Hattotuwagama, Channa K; Doytchinova, Irini A; Flower, Darren R

    2007-01-01

    Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method

  17. The optimization of peptide cargo bound to MHC class I molecules by the peptide-loading complex.

    Science.gov (United States)

    Elliott, Tim; Williams, Anthony

    2005-10-01

    Major histocompatibility complex (MHC) class I complexes present peptides from both self and foreign intracellular proteins on the surface of most nucleated cells. The assembled heterotrimeric complexes consist of a polymorphic glycosylated heavy chain, non-polymorphic beta(2) microglobulin, and a peptide of typically nine amino acids in length. Assembly of the class I complexes occurs in the endoplasmic reticulum and is assisted by a number of chaperone molecules. A multimolecular unit termed the peptide-loading complex (PLC) is integral to this process. The PLC contains a peptide transporter (transporter associated with antigen processing), a thiooxido-reductase (ERp57), a glycoprotein chaperone (calreticulin), and tapasin, a class I-specific chaperone. We suggest that class I assembly involves a process of optimization where the peptide cargo of the complex is edited by the PLC. Furthermore, this selective peptide loading is biased toward peptides that have a longer off-rate from the assembled complex. We suggest that tapasin is the key chaperone that directs this action of the PLC with secondary contributions from calreticulin and possibly ERp57. We provide a framework model for how this may operate at the molecular level and draw parallels with the proposed mechanism of action of human leukocyte antigen-DM for MHC class II complex optimization.

  18. Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Worning, Peder

    2004-01-01

    Prediction of which peptides will bind a specific major histocompatibility complex (MHC) constitutes an important step in identifying potential T-cell epitopes suitable as vaccine candidates. MHC class II binding peptides have a broad length distribution complicating such predictions. Thus......, identifying the correct alignment is a crucial part of identifying the core of an MHC class II binding motif. In this context, we wish to describe a novel Gibbs motif sampler method ideally suited for recognizing such weak sequence motifs. The method is based on the Gibbs sampling method, and it incorporates...

  19. Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

    Science.gov (United States)

    Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

  20. Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.

    Science.gov (United States)

    Nedrud, John G; Bagheri, Nayer; Schön, Karin; Xin, Wei; Bergroth, Hilda; Eliasson, Dubravka Grdic; Lycke, Nils Y

    2013-01-01

    A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB). The protective efficacy of the selected peptides together with cholera toxin (CT) was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD) that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.

  1. Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.

    Directory of Open Access Journals (Sweden)

    John G Nedrud

    Full Text Available A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB. The protective efficacy of the selected peptides together with cholera toxin (CT was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.

  2. A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra; van den Hoorn, Tineke; Jongsma, Marlieke L. M.; Bakker, Mark J.; Hengeveld, Rutger; Janssen, Lennert; Cresswell, Peter; Egan, David A.; van Ham, Marieke; ten Brinke, Anja; Ovaa, Huib; Beijersbergen, Roderick L.; Kuijl, Coenraad; Neefjes, Jacques

    2011-01-01

    MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and

  3. MHC class II expression in lung cancer.

    Science.gov (United States)

    He, Yayi; Rozeboom, Leslie; Rivard, Christopher J; Ellison, Kim; Dziadziuszko, Rafal; Yu, Hui; Zhou, Caicun; Hirsch, Fred R

    2017-10-01

    Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). Seven (12.7%) NSCLC cell lines were positive for MHC Class II. No SCLC cell lines were found to be MHC Class II positive. We assessed 139 lung cancer samples available in the Hirsch Lab for MHC Class II. There was no positive MHC Class II staining on SCLC tumor cells. MHC Class II expression on TILs in SCLC was significantly lower than that on TILs in NSCLC (P<0.001). MHC Class II was also assessed in an additional 139 NSCLC tumor tissues from Medical University of Gdansk, Poland. Patients with positive staining of MHC Class II on TILs had longer regression-free survival (RFS) and overall survival (OS) than those whose TILs were MHC Class II negative (2.980 years, 95% CI 1.628-4.332 vs. 1.050 years, 95% CI 0.556-1.554, P=0.028) (3.230 years, 95% CI 2.617-3.843 vs. 1.390 years, 95% CI 0.629-2.151, P=0.014). MHC Class II was expressed both in NSCLC cell lines and tissues. However, MHC Class II was not detected in SCLC cell lines or tissue tumor cells. MHC Class II expression was lower on SCLC TILs than on NSCLC TILs. Loss of expression of MHC Class II on SCLC tumor cells and reduced expression on SCLC TILs may be a means of escaping anti-cancer immunity. Higher MHC Class II expression on TILs was correlated with better prognosis in patients with NSCLC. Copyright © 2017. Published by Elsevier B.V.

  4. Finishing occlusion in Class II or Class III molar relation: therapeutic Class II and III.

    Science.gov (United States)

    Nangia, A; Darendeliler, M A

    2001-11-01

    The most frequent extraction regime consists of the removal of upper and lower premolars. Depending on anchorage requirements, camouflage treatment options, surgical intervention, or the absence of teeth in only one arch, it may become necessary to finalize the occlusion with a one-dental-unit discrepancy between the upper and lower dental arches. Guidelines are presented for finishing occlusions in Class II or Class III molar relation.

  5. Sibling rivalry: competition between MHC class II family members inhibits immunity.

    Science.gov (United States)

    Denzin, Lisa K; Cresswell, Peter

    2013-01-01

    Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

  6. Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity

    DEFF Research Database (Denmark)

    Harndahl, Mikkel Nors; Rasmussen, Michael; Nielsen, Morten

    2012-01-01

    Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity Mikkel Harndahla, Michael Rasmussena, Morten Nielsenb, Soren Buusa,∗ a Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Denmark b Center for Biological Seq...... al., 2007. J. Immunol. 178, 7890–7901. doi:10.1016/j.molimm.2012.02.025...

  7. Antimicrobial peptides: a new class of antimalarial drugs?

    Directory of Open Access Journals (Sweden)

    Nuno eVale

    2014-12-01

    Full Text Available A range of antimicrobial peptides (AMP exhibit activity on malaria parasites, Plasmodium spp, in their blood or mosquito stages, or both. These peptides include a diverse array of both natural and synthetic molecules varying greatly in size, charge, hydrophobicity and secondary structure features. Along with an overview of relevant literature reports regarding AMP that display antiplasmodial activity, this review makes a few considerations about those molecules as a potential new class of antimalarial drugs.

  8. Morphological caracteristics of malocclusion class II

    Directory of Open Access Journals (Sweden)

    Pavlović J.

    2015-01-01

    Full Text Available Class II malocclusion are complex anomalies of the skeletal and dental systems. The aim of this study is that the rengenkefalometrics analysis closer determine the morphological characteristics of this malocclusion. For this study were used 30 patients aged 18-30, previously clinically diagnosed class II, before the planned orthodontic treatment. The results analisis lateral cephalometric radiographs were compared with the 30 patients with class I malocclusion. Analyzed three linear and two angular cranial base dimensions and nine angular and four linear measures from the facial skeleton. The Results show: No statistically significant differensis in cranial base angle (SNBa and anterior cranial base length (S-N between class II and control Class I. Angle maxillar prognathism ( SNA is no signifikant different between class I and Class II but SNB angle were signifikant smaller. The length of maxillary base (A'-SnP is longer and the length of mandibule (Pg'-MT1/MT is signifficantly smaller. The gonial angle (ArGo-Me was smaller with open articular angle (GoArSN. Morphological characteristics of class II malocclusion are , retrognathic and smaller mandibular ligth, normognathic and longer maxilla, open articular angle with vertical tendency of the craniofacial growth pattern.

  9. pH dependence of MHC class I-restricted peptide presentation

    DEFF Research Database (Denmark)

    Stryhn, A; Pedersen, L O; Romme, T

    1996-01-01

    The function of MHC class I molecules is to bind and present antigenic peptides to cytotoxic T cells. Here, we report that class I-restricted peptide presentation is strongly pH dependent. The presentation of some peptides was enhanced at acidic pH, whereas the presentation of others was inhibited....... Biochemical peptide-MHC class I binding assays demonstrated that peptide-MHC class I complexes are more stable at neutral pH than at acidic pH. We suggest that acid-dependent peptide dissociation can generate empty class I molecules and that the resulting binding potential can be exploited by a subset...

  10. HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses

    DEFF Research Database (Denmark)

    Wang, M. J.; Larsen, Mette Voldby; Nielsen, Morten

    2010-01-01

    of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC depleted of CD4(+) or CD8(+) T cells prior to the ELISPOT culture revealed...... that effectors are either CD4(+) (the majority of reactivities) or CD8(+) T cells, never a mixture of these subsets. Three of the peptides, recognized by CD4(+) T cells showed binding to recombinant DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 molecules in a recently developed biochemical assay. Conclusions....../Significance: HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4(+) T cell responses restricted by HLA-II molecules....

  11. Circumvention of MHC class II restriction by genetic immunization.

    Science.gov (United States)

    Schuler, K; Lu, C; Chang, H D; Croft, M; Zanetti, M; Gerloni, M

    2001-11-12

    The fate of T cell responses to peptide-based vaccination is subject to constraints by the major histocompatibility complex (MHC), MHC restriction. Using as a model system of T and B cell epitopes from the circumsporozoite protein of Plasmodium falciparum malaria parasite, we show that vaccination by somatic transgene immunization readily primes Balb/c mice (H-2(d)) a strain previously reported to be non-responder to immunization with a synthetic peptide vaccine encompassing these epitopes. Following genetic vaccination Balb/c mice developed a primary T cell response comparable to that of the responder strain C57Bl/6 (H-2(b)). Following booster immunization on day 45 Balb/c mice responded with a typical T cell memory response. Priming induced the formation of specific antibodies, which rose sharply after booster immunization. These findings suggests that genetic immunization can circumvent MHC class II restriction.

  12. Automated benchmarking of peptide-MHC class I binding predictions

    Science.gov (United States)

    Trolle, Thomas; Metushi, Imir G.; Greenbaum, Jason A.; Kim, Yohan; Sidney, John; Lund, Ole; Sette, Alessandro; Peters, Bjoern; Nielsen, Morten

    2015-01-01

    Motivation: Numerous in silico methods predicting peptide binding to major histocompatibility complex (MHC) class I molecules have been developed over the last decades. However, the multitude of available prediction tools makes it non-trivial for the end-user to select which tool to use for a given task. To provide a solid basis on which to compare different prediction tools, we here describe a framework for the automated benchmarking of peptide-MHC class I binding prediction tools. The framework runs weekly benchmarks on data that are newly entered into the Immune Epitope Database (IEDB), giving the public access to frequent, up-to-date performance evaluations of all participating tools. To overcome potential selection bias in the data included in the IEDB, a strategy was implemented that suggests a set of peptides for which different prediction methods give divergent predictions as to their binding capability. Upon experimental binding validation, these peptides entered the benchmark study. Results: The benchmark has run for 15 weeks and includes evaluation of 44 datasets covering 17 MHC alleles and more than 4000 peptide-MHC binding measurements. Inspection of the results allows the end-user to make educated selections between participating tools. Of the four participating servers, NetMHCpan performed the best, followed by ANN, SMM and finally ARB. Availability and implementation: Up-to-date performance evaluations of each server can be found online at http://tools.iedb.org/auto_bench/mhci/weekly. All prediction tool developers are invited to participate in the benchmark. Sign-up instructions are available at http://tools.iedb.org/auto_bench/mhci/join. Contact: mniel@cbs.dtu.dk or bpeters@liai.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25717196

  13. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Engberg, J; Stryhn, A

    2000-01-01

    -peptide pair into the Fab combining site. Interestingly, the most energetically favored binding mode shows numerous analogies to the recently determined recognition of class I MHC-peptide complexes by alpha beta T cell receptors (TCRs). The pSAN13.4.1 also binds diagonally across the MHC binding groove......The recombinant antibody, pSAN13.4.1, has a unique T cell like specificity; it binds an Influenza Hemagglutinin octapeptide (Ha255-262) in an MHC (H-2Kk)-restricted manner, and a detailed comparison of the fine specificity of pSAN13.4.1 with the fine specificity of two Ha255-262-specific, H-2Kk......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

  14. Predicted MHC peptide binding promiscuity explains MHC class I 'hotspots' of antigen presentation defined by mass spectrometry eluted ligand data.

    Science.gov (United States)

    Jappe, Emma Christine; Kringelum, Jens; Trolle, Thomas; Nielsen, Morten

    2018-02-15

    Peptides that bind to and are presented by MHC class I and class II molecules collectively make up the immunopeptidome. In the context of vaccine development, an understanding of the immunopeptidome is essential, and much effort has been dedicated to its accurate and cost-effective identification. Current state-of-the-art methods mainly comprise in silico tools for predicting MHC binding, which is strongly correlated with peptide immunogenicity. However, only a small proportion of the peptides that bind to MHC molecules are, in fact, immunogenic, and substantial work has been dedicated to uncovering additional determinants of peptide immunogenicity. In this context, and in light of recent advancements in mass spectrometry (MS), the existence of immunological hotspots has been given new life, inciting the hypothesis that hotspots are associated with MHC class I peptide immunogenicity. We here introduce a precise terminology for defining these hotspots and carry out a systematic analysis of MS and in silico predicted hotspots. We find that hotspots defined from MS data are largely captured by peptide binding predictions, enabling their replication in silico. This leads us to conclude that hotspots, to a great degree, are simply a result of promiscuous HLA binding, which disproves the hypothesis that the identification of hotspots provides novel information in the context of immunogenic peptide prediction. Furthermore, our analyses demonstrate that the signal of ligand processing, although present in the MS data, has very low predictive power to discriminate between MS and in silico defined hotspots. © 2018 John Wiley & Sons Ltd.

  15. The properties of the single chicken MHC classical class II alpha chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

    DEFF Research Database (Denmark)

    Salomonsen, Jan; Marston, Denise; Avila, David

    2003-01-01

    for the cloning and sequencing of the cDNA. We found only one class II alpha chain transcript, which bears the major features of a classical class II alpha sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most...... the mammalian DR and E isotypes in three properties: the presence of the critical peptide-binding residues, the low level of polymorphism and sequence diversity, and the recombinational separation from the class II beta chain genes. These results indicate that the sequence features of this lineage are both......In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) alpha chain from outbred chickens as the basis...

  16. 25 CFR 502.3 - Class II gaming.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Class II gaming. 502.3 Section 502.3 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.3 Class II gaming. Class II gaming means: (a) Bingo or lotto (whether or not electronic, computer...

  17. Direct binding of autoimmune disease related T cell epitopes to purified Lewis rat MHC class II molecules

    DEFF Research Database (Denmark)

    Joosten, I; Wauben, M H; Holewijn, M C

    1994-01-01

    New strategies applied in the treatment of experimental autoimmune disease models involve blocking or modulation of MHC-peptide-TCR interactions either at the level of peptide-MHC interaction or, alternatively, at the level of T cell recognition. In order to identify useful competitor peptides one...... characteristics of the Lewis rat MHC class II RT1.B1 molecule. We have now developed a biochemical binding assay which enables competition studies in which the relative MHC binding affinity of a set of non-labelled peptides can be assessed while employing detection of biotinylated marker peptides...

  18. MHC class II molecules and tumour immunotherapy

    International Nuclear Information System (INIS)

    Oven, I.

    2005-01-01

    Background. Tumour immunotherapy attempts to use the specificity and capability of the immune system to kill malignant cells with a minimum damage to normal tissue. Increasing knowledge of the identity of tumour antigens should help us design more effective therapeutic vaccines. Increasing evidence has demonstrated that MHC class II molecules and CD4+ T cells play important roles in generating and maintaining antitumour immune responses in animal models. These data suggest that it may be necessary to involve both CD4+ and CD8+ T cells for more effective antitumour therapy. Novel strategies have been developed for enhancing T cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells, by the inclusion of MHC class II-restricted tumour antigens and by genetically modifying tumour cells to present antigen to T lymphocytes directly. Conclusions. Vaccines against cancers aim to induce tumour-specific effector T cells that can reduce tumour mass and induce development of tumour-specific T cell memory, that can control tumour relapse. (author)

  19. MHC class II molecules regulate growth in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K

    1994-01-01

    MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

  20. The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics.

    Science.gov (United States)

    Escano, Jerome; Stauffer, Byron; Brennan, Jacob; Bullock, Monica; Smith, Leif

    2014-12-01

    Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that promotes the core peptide's interaction with the post translational modification (PTM) enzymes. Following PTMs, mutacin 1140 is transported out of the cell and the leader peptide is cleaved to yield the antibacterial peptide. Mutacin 1140 leader peptide is structurally unique compared to other class I lantibiotic leader peptides. Herein, we further our understanding of the structural differences of mutacin 1140 leader peptide with regard to other class I leader peptides. We have determined that the length of the leader peptide is important for the biosynthesis of mutacin 1140. We have also determined that mutacin 1140 leader peptide contains a novel four amino acid motif compared to related lantibiotics. PTM enzyme recognition of the leader peptide appears to be evolutionarily distinct from related class I lantibiotics. Our study on mutacin 1140 leader peptide provides a basis for future studies aimed at understanding its interaction with the PTM enzymes. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  1. Protective influences on experimental autoimmune encephalomyelitis by MHC class I and class II alleles

    DEFF Research Database (Denmark)

    Mustafa, M; Vingsbo, C; Olsson, T

    1994-01-01

    are resistant. Interestingly, rats with the MHC u haplotype develop an immune response to the MBP 63-88, but do not get EAE. In this study we have used intra-MHC recombinant rat strains to compare the influences of the MHC u with the a haplotype. We discovered the following: 1) The class II region of the MHC...... a haplotype permits EAE and a Th1 type of immune response as measured by IFN-gamma production after in vitro challenge of in vivo-primed T cells with MBP 63-88. 2) The class II region of the u haplotype is associated with a disease-protective immune response characterized by production of not only IFN......Experimental autoimmune encephalomyelitis (EAE) is influenced by polymorphism of the MHC. We have previously found that Lewis rats with certain MHC haplotypes are susceptible to disease induced with the myelin basic protein (MBP) peptide 63-88, whereas Lewis rats with other MHC haplotypes...

  2. Selective peptide bond hydrolysis of cysteine peptides in the presence of Ni(II) ions.

    Science.gov (United States)

    Protas, Anna Maria; Bonna, Arkadiusz; Kopera, Edyta; Bal, Wojciech

    2011-01-01

    Recently, we described a sequence-specific R1-(Ser/Thr) peptide bond hydrolysis reaction in peptides of a general sequence R1-(Ser/Thr)-Xaa-His-Zaa-R, which occurs in the presence of Ni(II) ions [A. Krężel, E. Kopera, A. M. Protas, A. Wysłouch-Cieszyńska, J. Poznański, W. Bal, J. Am. Chem. Soc. 132 (2010) 3355-3366]. In this study we explored the possibility of substituting the Ser/Thr and the His residues, necessary for the reaction to occur according to the Ni(II)-assisted acyl shift reaction mechanism, with Cys residues. We tested this concept by synthesizing three homologous peptides: R1-Ser-Arg-Cys-Trp-R2, R1-Cys-Arg-His-Trp-R2, and R1-Cys-Arg-Cys-Trp-R2, and the R1-Ser-Arg-His-Trp-R2 peptide as comparator (R1 and R2 were CH3CO-Gly-Ala and Lys-Phe-Leu-NH2, respectively). We studied their hydrolysis in the presence of Ni(II) ions, under anaerobic conditions and in the presence of TCEP as a thiol group antioxidant. We measured hydrolysis rates using HPLC and identified products of reaction using electrospray mass spectrometry. Potentiometry and UV-vis spectroscopy were used to assess Ni(II) complexation. We demonstrated that Ni(II) is not compatible with the Cys substitution of the Ser/Thr acyl acceptor residue, but the substitution of the Ni(II) binding His residue with a Cys yields a peptide susceptible to Ni(II)-related hydrolysis. The relatively high activity of the R1-Ser-Arg-Cys-Trp-R2 peptide at pH 7.0 suggests that this peptide and its Cys-containing analogs might be useful in practical applications of Ni(II)-dependent peptide bond hydrolysis. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Lund, Ole

    2007-01-01

    the correct alignment of a peptide in the binding groove a crucial part of identifying the core of an MHC class II binding motif. Here, we present a novel stabilization matrix alignment method, SMM-align, that allows for direct prediction of peptide:MHC binding affinities. The predictive performance...... of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC) and three mouse H2-IA alleles. RESULTS: The predictive performance of the SMM-align method was demonstrated to be superior to that of the Gibbs sampler, TEPITOPE, SVRMHC, and MHCpred methods. Cross validation...... between peptide data set obtained from different sources demonstrated that direct incorporation of peptide length potentially results in over-fitting of the binding prediction method. Focusing on amino terminal peptide flanking residues (PFR), we demonstrate a consistent gain in predictive performance...

  4. The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-γ

    International Nuclear Information System (INIS)

    Zhang Benyue; Li Ping; Wang Exing; Brahmi, Zacharie; Dunn, Kenneth W.; Blum, Janice S.; Roman, Ann

    2003-01-01

    Major histocompatibility complex (MHC) class II antigens are expressed on human foreskin keratinocytes (HFKs) following exposure to interferon gamma. The expression of MHC class II proteins on the cell surface may allow keratinocytes to function as antigen-presenting cells and induce a subsequent immune response to virus infection. Invariant chain (Ii) is a chaperone protein which plays an important role in the maturation of MHC class II molecules. The sequential degradation of Ii within acidic endocytic compartments is a key process required for the successful loading of antigenic peptide onto MHC class II molecules. Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late endosomes in HFKs, the E5 protein may be able to affect proper peptide loading onto the MHC class II molecule. To test this hypothesis, HFKs were infected with either control virus or a recombinant virus expressing HPV16 E5 and the infected cells were subsequently treated with interferon-γ. ELISAs revealed a decrease of MHC class II expression on the surface of E5-expressing cells compared with control virus-infected cells after interferon treatment. Western blot analysis showed that, in cells treated with interferon gamma, E5 could prevent the breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC class II dimers, correlating with diminished surface MHC class II expression. These data suggest that HPV16 E5 may be able to decrease immune recognition of infected keratinocytes via disruption of MHC class II protein function

  5. Early Intervention in Skeletal Class II and dental Class II division I malocclusion

    Directory of Open Access Journals (Sweden)

    Zeeshan Iqbal Bhat

    2013-01-01

    Full Text Available A Class II malocclusion may occur as a result of mandibular deficiency, maxillary excess, or a combination of both. However, the most common finding is mandibular skeletal retrusion. The use of functional jaw orthopedics, at the right time during growth, can ultimately result in malocclusion patients achieving an excellent functional occlusion, a broad beautiful smile, a full face with a beautiful jaw line, and profile. Functional jaw orthopedic (FJO appliances are designed to encourage adaptive skeletal growth by maintaining the mandible in a corrected forward position. The activator developed by Andresen is one of the most widely used for this purpose. A 12-year-old boy with skeletal Class II malocclusion and dental Class II div I malocclusion, a low mandibular plane angle was treated with growth modulation using an activator followed by molar distalization using fixed orthodontics for detailing of the occlusion. The major effects of the activator treatment in this case have been due to increase in condylar growth and also an increase in mandibular base length. Further, non-extraction fixed orthodontic treatment for proper interdigitation of the dentition also helped to maintain the stability of the satisfactory results achieved.

  6. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method.

    Science.gov (United States)

    Nielsen, Morten; Lundegaard, Claus; Lund, Ole

    2007-07-04

    Antigen presenting cells (APCs) sample the extra cellular space and present peptides from here to T helper cells, which can be activated if the peptides are of foreign origin. The peptides are presented on the surface of the cells in complex with major histocompatibility class II (MHC II) molecules. Identification of peptides that bind MHC II molecules is thus a key step in rational vaccine design and developing methods for accurate prediction of the peptide:MHC interactions play a central role in epitope discovery. The MHC class II binding groove is open at both ends making the correct alignment of a peptide in the binding groove a crucial part of identifying the core of an MHC class II binding motif. Here, we present a novel stabilization matrix alignment method, SMM-align, that allows for direct prediction of peptide:MHC binding affinities. The predictive performance of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC) and three mouse H2-IA alleles. The predictive performance of the SMM-align method was demonstrated to be superior to that of the Gibbs sampler, TEPITOPE, SVRMHC, and MHCpred methods. Cross validation between peptide data set obtained from different sources demonstrated that direct incorporation of peptide length potentially results in over-fitting of the binding prediction method. Focusing on amino terminal peptide flanking residues (PFR), we demonstrate a consistent gain in predictive performance by favoring binding registers with a minimum PFR length of two amino acids. Visualizing the binding motif as obtained by the SMM-align and TEPITOPE methods highlights a series of fundamental discrepancies between the two predicted motifs. For the DRB1*1302 allele for instance, the TEPITOPE method favors basic amino acids at most anchor positions, whereas the SMM-align method identifies a preference for hydrophobic or neutral amino acids at the anchors. The SMM-align method was shown to outperform other

  7. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method

    Directory of Open Access Journals (Sweden)

    Lund Ole

    2007-07-01

    Full Text Available Abstract Background Antigen presenting cells (APCs sample the extra cellular space and present peptides from here to T helper cells, which can be activated if the peptides are of foreign origin. The peptides are presented on the surface of the cells in complex with major histocompatibility class II (MHC II molecules. Identification of peptides that bind MHC II molecules is thus a key step in rational vaccine design and developing methods for accurate prediction of the peptide:MHC interactions play a central role in epitope discovery. The MHC class II binding groove is open at both ends making the correct alignment of a peptide in the binding groove a crucial part of identifying the core of an MHC class II binding motif. Here, we present a novel stabilization matrix alignment method, SMM-align, that allows for direct prediction of peptide:MHC binding affinities. The predictive performance of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC and three mouse H2-IA alleles. Results The predictive performance of the SMM-align method was demonstrated to be superior to that of the Gibbs sampler, TEPITOPE, SVRMHC, and MHCpred methods. Cross validation between peptide data set obtained from different sources demonstrated that direct incorporation of peptide length potentially results in over-fitting of the binding prediction method. Focusing on amino terminal peptide flanking residues (PFR, we demonstrate a consistent gain in predictive performance by favoring binding registers with a minimum PFR length of two amino acids. Visualizing the binding motif as obtained by the SMM-align and TEPITOPE methods highlights a series of fundamental discrepancies between the two predicted motifs. For the DRB1*1302 allele for instance, the TEPITOPE method favors basic amino acids at most anchor positions, whereas the SMM-align method identifies a preference for hydrophobic or neutral amino acids at the anchors. Conclusion

  8. CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides.

    Science.gov (United States)

    Nishioka, Yusuke; Masuda, Sakiko; Tomaru, Utano; Ishizu, Akihiro

    2018-01-01

    NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II. CD1d-restricted type I NKT cells express invariant T cell receptors (TCRs) and react with lipid antigens, including the marine sponge-derived glycolipid α-galactosylceramide. On the contrary, CD1d-restricted type II NKT cells recognize a wide variety of antigens, including glycolipids, phospholipids, and hydrophobic peptides, by their diverse TCRs. In this review, we focus particularly on CD1d-restricted type II NKT cells that recognize endogenous hydrophobic peptides presented by CD1d. Previous studies have demonstrated that CD1d-restricted type I NKT cells usually act as pro-inflammatory cells but sometimes behave as anti-inflammatory cells. It has been also demonstrated that CD1d-restricted type II NKT cells play opposite roles to CD1d-restricted type I NKT cells; thus, they function as anti-inflammatory or pro-inflammatory cells depending on the situation. In line with this, CD1d-restricted type II NKT cells that recognize type II collagen peptide have been demonstrated to act as anti-inflammatory cells in diverse inflammation-induction models in mice, whereas pro-inflammatory CD1d-restricted type II NKT cells reactive with sterol carrier protein 2 peptide have been demonstrated to be involved in the development of small vessel vasculitis in rats.

  9. New design of MHC class II tetramers to accommodate fundamental principles of antigen presentation.

    Science.gov (United States)

    Landais, Elise; Romagnoli, Pablo A; Corper, Adam L; Shires, John; Altman, John D; Wilson, Ian A; Garcia, K Christopher; Teyton, Luc

    2009-12-15

    Direct identification and isolation of Ag-specific T cells became possible with the development of MHC tetramers, based on fluorescent avidins displaying biotinylated peptide-MHC complexes. This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells. In addition, a very large number of these reagents, although capable of specifically activating T cells after being coated on solid support, is still unable to stain. To try to understand this puzzle and design usable tetramers, we examined each parameter critical for the production of pMHCT-2 using the I-A(d)-OVA system as a model. Through this process, the geometry of peptide-MHC display by avidin tetramers was examined, as well as the stability of rMHC molecules. However, we discovered that the most important factor limiting the reactivity of pMHCT-2 was the display of peptides. Indeed, long peptides, as presented by MHC class II molecules, can be bound to I-A/HLA-DQ molecules in more than one register, as suggested by structural studies. This mode of anchorless peptide binding allows the selection of a broader repertoire on single peptides and should favor anti-infectious immune responses. Thus, beyond the technical improvements that we propose, the redesign of pMHCT-2 will give us the tools to evaluate the real size of the CD4 T cell repertoire and help us in the production and testing of new vaccines.

  10. NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ

    DEFF Research Database (Denmark)

    Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas

    2013-01-01

    Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great importa......MHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0....

  11. The roles of MHC class II genes and post-translational modification in celiac disease.

    Science.gov (United States)

    Sollid, Ludvig M

    2017-08-01

    Our increasing understanding of the etiology of celiac disease, previously considered a simple food hypersensitivity disorder caused by an immune response to cereal gluten proteins, challenges established concepts of autoimmunity. HLA is a chief genetic determinant, and certain HLA-DQ allotypes predispose to the disease by presenting posttranslationally modified (deamidated) gluten peptides to CD4 + T cells. The deamidation of gluten peptides is mediated by transglutaminase 2. Strikingly, celiac disease patients generate highly disease-specific autoantibodies to the transglutaminase 2 enzyme. The dual role of transglutaminase 2 in celiac disease is hardly coincidental. This paper reviews the genetic mapping and involvement of MHC class II genes in disease pathogenesis, and discusses the evidence that MHC class II genes, via the involvement of transglutaminase 2, influence the generation of celiac disease-specific autoantibodies.

  12. Characterisation of four major histocompatibility complex class II genes of the koala (Phascolarctos cinereus).

    Science.gov (United States)

    Lau, Quintin; Jobbins, Sarah E; Belov, Katherine; Higgins, Damien P

    2013-01-01

    Major histocompatibility complex (MHC) class II molecules have an integral role in the adaptive immune response, as they bind and present antigenic peptides to T helper lymphocytes. In this study of koalas, species-specific primers were designed to amplify exon 2 of the MHC class II DA and DB genes, which contain much of the peptide-binding regions of the α and β chains. A total of two DA α1 domain variants and eight DA β1 (DAB), three DB α1 and five DB β1 variants were amplified from 20 koalas from two free-living populations from South East Queensland and the Port Macquarie region in northern New South Wales. We detected greater variation in the β1 than in the α1 domains as well as evidence of positive selection in DAB. The present study provides a springboard to future investigation of the role of MHC in disease susceptibility in koalas.

  13. Class II correction prior to orthodontics with the carriere distalizer.

    Science.gov (United States)

    McFarlane, Bruce

    2013-01-01

    Class II correction is a challenge in orthodontics with many existing devices being complex, too compliance-driven, or too prone to breakage. The Carriere Distalizer allows for straightforward Class II correction prior to orthodontics (fixed or clear aligners) at a time when no other mechanics interfere, and compliance is at its best.

  14. The Ia.2 Epitope Defines a Subset of Lipid Raft Resident MHC Class II Molecules Crucial to Effective Antigen Presentation1

    Science.gov (United States)

    Busman-Sahay, Kathleen; Sargent, Elizabeth; Harton, Jonathan A.; Drake, James R.

    2016-01-01

    Previous work has established that binding of the 11-5.2 anti-I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-Ak mAb that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2 bearing subset of I-Ak class II molecules is critically necessary for effective B cell–T cell interactions especially at low antigen doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-Ak class II molecules possessing a β chain-tethered HEL peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2 negative tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous antigen to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II confomer vital to the initiation of MHC class II restricted B cell–T cell interactions. PMID:21543648

  15. Exploring the nature of the H-bonds between the human class II MHC protein, HLA-DR1 (DRB*0101) and the influenza virus hemagglutinin peptide, HA306-318, using the quantum theory of atoms in molecules.

    Science.gov (United States)

    Aray, Yosslen; Aguilera-García, Ricardo; Izquierdo, Daniel R

    2018-01-02

    The nature of the H-bonds between the human protein HLA-DR1 (DRB*0101) and the hemagglutinin peptide HA306-318 has been studied using the Quantum Theory of Atoms in Molecules for the first time. We have found four H-bond groups: one conventional CO··HN bond group and three nonconventional CO··HC, π··HC involving aromatic rings and HN··HC aliphatic groups. The calculated electron density at the determined H-bond critical points suggests the follow protein pocket binding trend: P1 (2,311) > P9 (1.109) > P4 (0.950) > P6 (0.553) > P7 (0.213) which agrees and reveal the nature of experimental findings, showing that P1 produces by a long way the strongest binding of the HLA-DR1 human protein molecule with the peptide backbone as consequence of the vast number of H-bonds in the P1 area and at the same time the largest specific binding of the peptide Tyr308 residue with aromatic residues located at the binding groove floor. The present results suggest the topological analysis of the electronic density as a valuable tool that allows a non-arbitrary partition of the pockets binding energy via the calculated electron density at the determined critical points.

  16. Longer peptide can be accommodated in the MHC class I binding site by a protrusion mechanism

    DEFF Research Database (Denmark)

    Stryhn, A; Pedersen, L O; Holm, A

    2000-01-01

    and C termini of a bound peptide interact through hydrogen bonding networks to conserved residues at either end of the class I binding site. Accordingly, it is thought that the termini are fixed and that only minor variations in peptide size are possible through a central bulging mechanism. We find...

  17. Identification of diverse archaeal proteins with class III signal peptides cleaved by distinct archaeal prepilin peptidases

    NARCIS (Netherlands)

    Szabó, Zalán; Oliveira Stahl, Adriana; Albers, Sonja-V.; Kissinger, Jessica C.; Driessen, Arnold J.M.; Pohlschröder, Mechthild; Pohlschroder, M.

    2007-01-01

    Most secreted archaeal proteins are targeted to the membrane via a tripartite signal composed of a charged N terminus and a hydrophobic domain, followed by a signal peptidase-processing site. Signal peptides of archaeal flagellins, similar to class III signal peptides of bacterial type IV pilins,

  18. Archform comparisons between skeletal class II and III malocclusions.

    Directory of Open Access Journals (Sweden)

    Wei Zou

    Full Text Available The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2 and Skeletal Class III (SC3 malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crownand WALA points (the most prominent point on the soft-tissue ridgewere employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2. In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

  19. Mandibular condyle dimensions in Peruvian patients with Class II and Class III skeletal patterns.

    Directory of Open Access Journals (Sweden)

    Hugo Zegarra-Baquerizo

    2017-10-01

    Full Text Available Objective: To compare condylar dimensions of young adults with Class II and Class III skeletal patterns using cone-beam computed tomography (CBCT. Materials and methods: 124 CBCTs from 18-30 year-old patients, divided into 2 groups according to skeletal patterns (Class II and Class III were evaluated. Skeletal patterns were classified by measuring the ANB angle of each patient. The anteroposterior diameter (A and P of the right and left mandibular condyle was assessed from a sagittal view by a line drawn from point A (anterior to P (posterior. The coronal plane allowed the evaluation of the medio-lateral diameter by drawing a line from point M (medium to L (lateral; all distances were measured in mm. Results: In Class II the A-P diameter was 9.06±1.33 and 8.86±1.56 for the right and left condyles respectively, in Class III these values were 8.71±1.2 and 8.84±1.42. In Class II the M-L diameter was 17.94±2.68 and 17.67±2.44 for the right and left condyles respectively, in Class III these values were 19.16±2.75 and 19.16±2.54. Conclusion: Class III M-L dimensions showed higher values than Class II, whereas these differences were minimal in A-P.

  20. Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Maraganore, J.M.; Bourdon, P.; Jablonski, J.; Ramachandran, K.L. (Biogen, Inc., Cambridge, MA (USA)); Fenton, J.W. II (New York State Department of Health, Albany (USA))

    1990-07-31

    A novel class of synthetic peptides has been designed that inhibit the thrombin catalytic site and exhibit specificity for the anion-binding exosite (ABE) of {alpha}-thrombin. These peptides, called hirulogs, consist of (i) an active-site specificity sequence with a restricted Arg-Pro scissile bond, (ii) a polymeric linker of glycyl residues from 6 to 18 {angstrom} in length, and (iii) an ABE recognition sequence such as that in the hirudin C-terminus. Hirulog-1 ((D-Phe)-Pro-Arg-Pro-(Gly){sub 4}-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Tyr-Leu) inhibits the thrombin-catalyzed hydrolysis of a tripeptide p-nitroanilide substrate with K{sub i} = 2.3 nM. In contrast, the synthetic C-terminal hirudin peptide S-Hir{sub 53-64}, which binds to the thrombin ABE, blocked the fibrinogen clotting activity of the enzyme with K{sub i} = 144 nM but failed to inhibit the hydrolysis of p-nitroanilide substrates at concentrations as high as 1 mM. Hirulog-1, but not S-Hir{sub 53-64}, was found to inhibit the incorporation of ({sup 14}C)diisopropyl fluorophosphate in thrombin. Hirulog-1 appears specific for thrombin as it lacks inhibitory activities toward human factor Xa, human plasmin, and bovine trypsin at inhibitor:enzyme concentrations 3 orders of magnitude higher than those required to inhibit thrombin. The optimal inhibitory activity of hirulog-1 depends upon all three components of its structure. Comparison of anticoagulant activities of hirulog-1, hirudin, and S-Hir{sub 53-64} showed that the synthetic hirulog-1 is 2-fold more potent than hirudin and 100-fold more active than S-Hir{sub 53-64} in increasing the activated partial thromboplastin time of normal human plasma.

  1. Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

    Science.gov (United States)

    Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

    2011-04-14

    Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

  2. The CLASS blazar survey - II. Optical properties

    NARCIS (Netherlands)

    Caccianiga, A; Marcha, MJ; Anton, S; Mack, KH; Neeser, MJ

    2002-01-01

    This paper presents the optical properties of the objects selected in the CLASS blazar survey. Because an optical spectrum is now available for 70 per cent of the 325 sources present in the sample, a spectral classification, based on the appearance of the emission/absorption lines, is possible. A

  3. Evolution of major histocompatibility complex class I and class II genes in the brown bear

    Science.gov (United States)

    2012-01-01

    Background Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia. PMID:23031405

  4. Evolution of major histocompatibility complex class I and class II genes in the brown bear

    Directory of Open Access Journals (Sweden)

    Kuduk Katarzyna

    2012-10-01

    Full Text Available Abstract Background Major histocompatibility complex (MHC proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN exceeded the rate of synonymous substitutions (dS at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

  5. Evolution of major histocompatibility complex class I and class II genes in the brown bear.

    Science.gov (United States)

    Kuduk, Katarzyna; Babik, Wiesław; Bojarska, Katarzyna; Sliwińska, Ewa B; Kindberg, Jonas; Taberlet, Pierre; Swenson, Jon E; Radwan, Jacek

    2012-10-02

    Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

  6. Features of target cell lysis by class I and class II MHC restricted cytolytic T lymphocytes

    International Nuclear Information System (INIS)

    Maimone, M.M.; Morrison, L.A.; Braciale, V.L.; Braciale, T.J.

    1986-01-01

    The lytic activity of influenza virus-specific muvine cytolytic T lymphocyte (CTL) clones that are restricted by either H-2K/D (class I) or H-2I (class II) major histocompatibility (MHC) locus products was compared on an influenza virus-infected target cell expressing both K/D and I locus products. With the use of two in vitro measurements of cytotoxicity, conventional 51 Cr release, and detergent-releasable radiolabeled DNA (as a measure of nuclear disintegration in the early post-lethal hit period), the authors found no difference between class I and class II MHC-restricted CTL in the kinetics of target cell destruction. In addition, class II MHC-restricted antiviral CTL failed to show any lysis of radiolabeled bystander cells. Killing of labeled specific targets by these class II MHC-restricted CTL was also efficiently inhibited by unlabeled specific competitor cells in a cold target inhibition assay. In sum, these data suggest that class I and class II MHC-restricted CTL mediate target cell destruction by an essentially similar direct mechanism

  7. Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

    Science.gov (United States)

    Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

    2007-07-01

    To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

  8. NetMHCpan 4.0: Improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data

    OpenAIRE

    Jurtz, Vanessa; Paul, Sinu; Andreatta, Massimo; Marcatili, Paolo; Peters, Bjoern; Nielsen, Morten

    2017-01-01

    Cytotoxic T cells are of central importance in the immune systems response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC (major histocompatibility complex) class I molecules. Peptide binding to MHC molecules is the single most selective step in the antigen presentation pathway. On the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has therefore attracted large attention. In the past, predictors of peptide-...

  9. A retrospective study of Class II mixed-dentition treatment.

    Science.gov (United States)

    Oh, Heesoo; Baumrind, Sheldon; Korn, Edward L; Dugoni, Steven; Boero, Roger; Aubert, Maryse; Boyd, Robert

    2017-01-01

    To consider the effectiveness of early treatment using one mixed-dentition approach to the correction of moderate and severe Class II malocclusions. Three groups of Class II subjects were included in this retrospective study: an early treatment (EarlyTx) group that first presented at age 7 to 9.5 years (n = 54), a late treatment (LateTx) group whose first orthodontic visit occurred between ages 12 and 15 (n = 58), and an untreated Class II (UnTx) group to assess the pretreatment comparability of the two treated groups (n = 51). Thirteen conventional cephalometric measurements were reported for each group and Class II molar severity was measured on the study casts of the EarlyTx and LateTx groups. Successful Class II correction was observed in approximately three quarters of both the EarlyTx group and the LateTx group at the end of treatment. EarlyTx patients had fewer permanent teeth extracted than did the LateTx patients (5.6% vs 37.9%, P < .001) and spent less time in full-bonded appliance therapy in the permanent dentition than did LateTx patients (1.7 ± 0.8 vs 2.6 ± 0.7years, P < .001). When supervision time is included, the EarlyTx group had longer total treatment time and averaged more visits than did the LateTx group (53.1 ± 18. 8 vs 33.7 ± 8.3, P < .0001). Fifty-five percent of the LateTx extraction cases involved removal of the maxillary first premolars only and were finished in a Class II molar relationship. EarlyTx comprehensive mixed-dentition treatment was an effective modality for early correction of Class II malocclusions.

  10. The relationship between Class I and Class II methanol masers at high angular resolution

    Science.gov (United States)

    McCarthy, T. P.; Ellingsen, S. P.; Voronkov, M. A.; Cimò, G.

    2018-06-01

    We have used the Australia Telescope Compact Array (ATCA) to make the first high-resolution observations of a large sample of class I methanol masers in the 95-GHz (80-71A+) transition. The target sources consist of a statistically complete sample of 6.7-GHz class II methanol masers with an associated 95-GHz class I methanol maser, enabling a detailed study of the relationship between the two methanol maser classes at arcsecond angular resolution. These sources have been previously observed at high resolution in the 36- and 44-GHz transitions, allowing comparison between all three class I maser transitions. In total, 172 95-GHz maser components were detected across the 32 target sources. We find that at high resolution, when considering matched maser components, a 3:1 flux density ratio is observed between the 95- and 44-GHz components, consistent with a number of previous lower angular resolution studies. The 95-GHz maser components appear to be preferentially located closer to the driving sources and this may indicate that this transition is more strongly inverted nearby to background continuum sources. We do not observe an elevated association rate between 95-GHz maser emission and more evolved sources, as indicated by the presence of 12.2-GHz class II masers. We find that in the majority of cases where both class I and class II methanol emission is observed, some component of the class I emission is associated with a likely outflow candidate.

  11. A cephalometric analysis of Class II dentate subjects to establish a formula to determine the occlusal plane in Class II edentate subjects: A neo adjunct

    OpenAIRE

    Nikita Sinha; K Mahendranadh Reddy; Nidhi Gupta; Y M Shastry

    2017-01-01

    Purpose: Occlusal plane (OP) differs considerably in participants with skeletal Class I and Class II participants. In this study, cephalometrics has been used to help in the determination of orientation of the OP utilizing the nonresorbable bony anatomic landmarks in skeletal Class II participants and an attempt has been made to predict and examine the OP in individuals with skeletal class II jaw relationship. Materials and Methods: One hundred dentulous participants with skeletal Class II...

  12. Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses.

    Science.gov (United States)

    Bergmann, Tobias; Lindvall, Mikaela; Moore, Erin; Moore, Eugene; Sidney, John; Miller, Donald; Tallmadge, Rebecca L; Myers, Paisley T; Malaker, Stacy A; Shabanowitz, Jeffrey; Osterrieder, Nikolaus; Peters, Bjoern; Hunt, Donald F; Antczak, Douglas F; Sette, Alessandro

    2017-05-01

    Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Utilizing analyses of endogenously bound and eluted ligands and the screening of positional scanning combinatorial libraries, detailed and quantitative peptide-binding motifs were derived for both alleles. Eqca-16*00101 preferentially binds peptides with aliphatic/hydrophobic residues in position 2 and at the C-terminus, and Eqca-1*00201 has a preference for peptides with arginine in position 2 and hydrophobic/aliphatic residues at the C-terminus. Interestingly, the Eqca-16*00101 motif resembles that of the human HLA A02-supertype, while the Eqca-1*00201 motif resembles that of the HLA B27-supertype and two macaque class I alleles. It is expected that the identified motifs will facilitate the selection of candidate epitopes for the study of immune responses in horses.

  13. Deciphering complex patterns of class-I HLA-peptide cross-reactivity via hierarchical grouping.

    Science.gov (United States)

    Mukherjee, Sumanta; Warwicker, Jim; Chandra, Nagasuma

    2015-07-01

    T-cell responses in humans are initiated by the binding of a peptide antigen to a human leukocyte antigen (HLA) molecule. The peptide-HLA complex then recruits an appropriate T cell, leading to cell-mediated immunity. More than 2000 HLA class-I alleles are known in humans, and they vary only in their peptide-binding grooves. The polymorphism they exhibit enables them to bind a wide range of peptide antigens from diverse sources. HLA molecules and peptides present a complex molecular recognition pattern, as many peptides bind to a given allele and a given peptide can be recognized by many alleles. A powerful grouping scheme that not only provides an insightful classification, but is also capable of dissecting the physicochemical basis of recognition specificity is necessary to address this complexity. We present a hierarchical classification of 2010 class-I alleles by using a systematic divisive clustering method. All-pair distances of alleles were obtained by comparing binding pockets in the structural models. By varying the similarity thresholds, a multilevel classification was obtained, with 7 supergroups, each further subclassifying to yield 72 groups. An independent clustering performed based only on similarities in their epitope pools correlated highly with pocket-based clustering. Physicochemical feature combinations that best explain the basis of clustering are identified. Mutual information calculated for the set of peptide ligands enables identification of binding site residues contributing to peptide specificity. The grouping of HLA molecules achieved here will be useful for rational vaccine design, understanding disease susceptibilities and predicting risk of organ transplants.

  14. Pan-specific prediction of peptide-MHC Class I complex stability, a correlate of T cell immunogenicity

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Fenoy, Emilio; Harndahl, Mikkel

    2016-01-01

    Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally b...

  15. ER stress affects processing of MHC class I-associated peptides

    Directory of Open Access Journals (Sweden)

    Meloche Sylvain

    2009-02-01

    Full Text Available Abstract Background Viral infection and neoplastic transformation trigger endoplasmic reticulum (ER stress. Thus, a large proportion of the cells that must be recognized by the immune system are stressed cells. Cells respond to ER stress by launching the unfolded protein response (UPR. The UPR regulates the two key processes that control major histocompatibility complex class I (MHC I-peptide presentation: protein synthesis and degradation. We therefore asked whether and how the UPR impinges on MHC I-peptide presentation. Results We evaluated the impact of the UPR on global MHC I expression and on presentation of the H2Kb-associated SIINFEKL peptide. EL4 cells stably transfected with vectors coding hen egg lysozyme (HEL-SIINFEKL protein variants were stressed with palmitate or exposed to glucose deprivation. UPR decreased surface expression of MHC I but did not affect MHC I mRNA level nor the total amount of intracellular MHC I proteins. Impaired MHC I-peptide presentation was due mainly to reduced supply of peptides owing to an inhibition of overall protein synthesis. Consequently, generation of H2Kb-SIINFEKL complexes was curtailed during ER stress, illustrating how generation of MHC I peptide ligands is tightly coupled to ongoing protein synthesis. Notably, the UPR-induced decline of MHC I-peptide presentation was more severe when the protein source of peptides was localized in the cytosol than in the ER. This difference was not due to changes in the translation rates of the precursor proteins but to increased stability of the cytosolic protein during ER stress. Conclusion Our results demonstrate that ER stress impairs MHC I-peptide presentation, and that it differentially regulates expression of ER- vs. cytosol-derived peptides. Furthermore, this work illustrates how ER stress, a typical feature of infected and malignant cells, can impinge on cues for adaptive immune recognition.

  16. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Harndahl, Mikkel; Rasmussen, Michael

    2011-01-01

    a HLA-I molecule (HLA-A*11:01), thereby generating recombinant human/swine chimeric MHC-I molecules as well as the intact SLA-1*0401 molecule. Biochemical peptide-binding assays and positional scanning combinatorial peptide libraries were used to analyze the peptide-binding motifs of these molecules....... A pan-specific predictor of peptide–MHC-I binding, NetMHCpan, which was originally developed to cover the binding specificities of all known HLA-I molecules, was successfully used to predict the specificities of the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules. These data......In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC...

  17. Binding stability of peptides on major histocompatibility complex class I proteins: role of entropy and dynamics

    Science.gov (United States)

    Gul, Ahmet; Erman, Burak

    2018-03-01

    Prediction of peptide binding on specific human leukocyte antigens (HLA) has long been studied with successful results. We herein describe the effects of entropy and dynamics by investigating the binding stabilities of 10 nanopeptides on various HLA Class I alleles using a theoretical model based on molecular dynamics simulations. The fluctuational entropies of the peptides are estimated over a temperature range of 310-460 K. The estimated entropies correlate well with experimental binding affinities of the peptides: peptides that have higher binding affinities have lower entropies compared to non-binders, which have significantly larger entropies. The computation of the entropies is based on a simple model that requires short molecular dynamics trajectories and allows for approximate but rapid determination. The paper draws attention to the long neglected dynamic aspects of peptide binding, and provides a fast computation scheme that allows for rapid scanning of large numbers of peptides on selected HLA antigens, which may be useful in defining the right peptides for personal immunotherapy.

  18. Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

    Energy Technology Data Exchange (ETDEWEB)

    Osterman, Ilya A.; Khabibullina, Nelli F.; Komarova, Ekaterina S.; Kasatsky, Pavel; Kartsev, Victor G.; Bogdanov, Alexey A.; Dontsova, Olga A.; Konevega, Andrey L.; Sergiev, Petr V.; Polikanov, Yury S. (InterBioScreen); (UIC); (MSU-Russia); (Kurchatov)

    2017-05-13

    The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.

  19. 78 FR 20236 - Self-Regulation of Class II Gaming

    Science.gov (United States)

    2013-04-04

    ... self- regulation. (2) Will coordinate an on-site review and verification of the information submitted... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Part 518 RIN 3141-AA44 Self... petitions seeking the issuance of a certificate for tribal self-regulation of Class II gaming. DATES...

  20. 77 FR 4714 - Self-Regulation of Class II Gaming

    Science.gov (United States)

    2012-01-31

    ...: Notice of proposed rulemaking. SUMMARY: This action proposes to amend the NIGC's self-regulation regulations to tailor the self-regulating qualifying criteria to a tribe's regulation of class II gaming activity and more clearly define and streamline the self-regulation certification process. By tailoring the...

  1. NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data

    DEFF Research Database (Denmark)

    Jurtz, Vanessa Isabell; Paul, Sinu; Andreatta, Massimo

    2017-01-01

    by mass spectrometry have been reported containing information about peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides. In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data leveraging......Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway....... Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data. Recently, an increasing number of MHC-presented peptides identified...

  2. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers

    OpenAIRE

    Day, Cheryl L.; Seth, Nilufer P.; Lucas, Michaela; Appel, Heiner; Gauthier, Laurent; Lauer, Georg M.; Robbins, Gregory K.; Szczepiorkowski, Zbigniew M.; Casson, Deborah R.; Chung, Raymond T.; Bell, Shannon; Harcourt, Gillian; Walker, Bruce D.; Klenerman, Paul; Wucherpfennig, Kai W.

    2003-01-01

    Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells has not been achieved. To further define the phenotype and function of these cells, we developed a novel approach for the generation of tetrameric forms of MHC class II/peptide complexes that is based on the cellular peptide-exchange mechanism. HLA-DR molecules were expressed as precursors with a c...

  3. Establishment of a quantitative ELISA capable of determining peptide - MHC class I interaction

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Kristensen, N; Blicher, T

    2002-01-01

    dependent manner. Here, we exploit the availability of these molecules to generate a quantitative ELISA-based assay capable of measuring the affinity of the interaction between peptide and MHC-I. This assay is simple and sensitive, and one can easily envisage that the necessary reagents, standards......Many different assays for measuring peptide-MHC interactions have been suggested over the years. Yet, there is no generally accepted standard method available. We have recently generated preoxidized recombinant MHC class I molecules (MHC-I) which can be purified to homogeneity under denaturing...

  4. Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Claudia A. Nold-Petry

    2017-12-01

    Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp

  5. Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

    DEFF Research Database (Denmark)

    Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper

    2009-01-01

    , better signal-to-background ratios, and a higher capacity. They also describe an efficient approach to screen peptides for binding to HLA molecules. For the occasional user, this will serve as a robust, simple peptide-HLA binding assay. For the more dedicated user, it can easily be performed in a high-throughput...... the luminescent oxygen channeling immunoassay technology (abbreviated LOCI and commercialized as AlphaScreen (TM)). Compared with an enzyme-linked immunosorbent assay-based peptide-HLA class I binding assay, the LOCI assay yields virtually identical affinity measurements, although having a broader dynamic range...... screening mode using standard liquid handling robotics and 384-well plates. We have successfully applied this assay to more than 60 different HLA molecules, leading to more than 2 million measurements. (Journal of Biomolecular Screening 2009: 173-180)...

  6. Recent Progress in the Chemical Synthesis of Class II and S-Glycosylated Bacteriocins

    Directory of Open Access Journals (Sweden)

    François Bédard

    2018-05-01

    Full Text Available A wide variety of antimicrobial peptides produced by lactic acid bacteria (LAB have been identified and studied in the last decades. Known as bacteriocins, these ribosomally synthesized peptides inhibit the growth of a wide range of bacterial species through numerous mechanisms and show a great variety of spectrum of activity. With their great potential as antimicrobial additives and alternatives to traditional antibiotics in food preservation and handling, animal production and in veterinary and medical medicine, the demand for bacteriocins is rapidly increasing. Bacteriocins are most often produced by fermentation but, in several cases, the low isolated yields and difficulties associated with their purification seriously limit their use on a large scale. Chemical synthesis has been proposed for their production and recent advances in peptide synthesis methodologies have allowed the preparation of several bacteriocins. Moreover, the significant cost reduction for peptide synthesis reagents and building blocks has made chemical synthesis of bacteriocins more attractive and competitive. From a protein engineering point of view, the chemical approach offers many advantages such as the possibility to rapidly perform amino acid substitution, use unnatural or modified residues, and make backbone and side chain modifications to improve potency, modify the activity spectrum or increase the stability of the targeted bacteriocin. This review summarized synthetic approaches that have been developed and used in recent years to allow the preparation of class IIa bacteriocins and S-linked glycopeptides from LAB. Synthetic strategies such as the use of pseudoprolines, backbone protecting groups, microwave irradiations, selective disulfide bridge formation and chemical ligations to prepare class II and S-glycosylsated bacteriocins are discussed.

  7. Angle Class II malocclusion treated with extraction of permanent teeth

    Directory of Open Access Journals (Sweden)

    Gustavo Mattos Barreto

    2013-08-01

    Full Text Available Angle Class II malocclusion associated with anterior open bite in adult patients demands a carefully elaborated orthodontic planning, aiming at restoring not only harmonious dental and facial esthetics, but also a balanced masticatory function. Orthognathic surgery or permanent teeth extraction are often the choice of treatment, therefore, treatment decision is related to all dental, skeletal and functional aspects. The present report discusses orthodontic compensation carried out by means of upper premolar extraction performed to correct the Class II canine relationship and, consequently, the anterior open bite, accepting that the upper incisors be retroclined. This clinical case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as part of the requirements for obtaining the BBO Certification.

  8. Relation between Angle Class II malocclusion and deleterious oral habits

    Directory of Open Access Journals (Sweden)

    José Tarcísio Lima Ferreira

    2012-12-01

    Full Text Available INTRODUCTION: Oral habits may interfere on the growth and development of the stomatognathic system and orofacial myofunctional conditions, producing changes in the position of teeth in their dental arches. OBJECTIVE: The purpose of this study was to verify the presence of deleterious oral habits in individuals with malocclusion and see if there is a predominance of Class II malocclusion in these individuals. METHODS: The records of 140 patients treated at the Clinic of Preventive Orthodontics FORP-USP who had already completed treatment were randomly selected and analyzed. Their ages ranged from 6 to 10 years and 11 months. Associations were made between the presence or absence of deleterious oral habits, type and number of habits found in each individual and the type of malocclusion according to Angle classification. The statistical analysis used was the Chi-square test with a significance level of 5%. History of deleterious oral habits was found in 67.1% of individuals. RESULTS: The Class I malocclusion was most frequent (82.9%, followed by Class II malocclusion (12.1% and Class III (5%. CONCLUSION: There was a predominance of Class II malocclusion in individuals with a history of deleterious oral habits.INTRODUÇÃO: hábitos bucais podem interferir no crescimento e desenvolvimento do sistema estomatognático e nas condições miofuncionais bucofaciais, acarretando alterações no posicionamento dos dentes nas respectivas arcadas dentárias. OBJETIVO: o objetivo dessa pesquisa foi verificar a presença de hábitos bucais deletérios em indivíduos portadores de má oclusão e observar se existe predominância de má oclusão Classe II de Angle nesses indivíduos. MÉTODOS: foram selecionadas, aleatoriamente, e analisadas 140 fichas de pacientes atendidos na Clínica de Ortodontia Preventiva da FORP-USP, que já haviam recebido alta no tratamento. A faixa etária variou dos 6 anos a 10 anos e 11 meses. Foram realizadas associações entre

  9. Dynamics of major histocompatibility complex class I association with the human peptide-loading complex.

    Science.gov (United States)

    Panter, Michaela S; Jain, Ankur; Leonhardt, Ralf M; Ha, Taekjip; Cresswell, Peter

    2012-09-07

    Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC.

  10. MHC Class II haplotypes of Colombian Amerindian tribes

    Science.gov (United States)

    Yunis, Juan J.; Yunis, Edmond J.; Yunis, Emilio

    2013-01-01

    We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family), Embera, Waunana (Choco linguistic family), Puinave and Nukak (Maku-Puinave linguistic families), Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family), Guahibo and Guayabero (Guayabero Linguistic Family), Curripaco and Piapoco (Arawak linguistic family) and Yucpa (Karib linguistic family). for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1). Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America. PMID:23885196

  11. Deep convolutional neural networks for pan-specific peptide-MHC class I binding prediction.

    Science.gov (United States)

    Han, Youngmahn; Kim, Dongsup

    2017-12-28

    Computational scanning of peptide candidates that bind to a specific major histocompatibility complex (MHC) can speed up the peptide-based vaccine development process and therefore various methods are being actively developed. Recently, machine-learning-based methods have generated successful results by training large amounts of experimental data. However, many machine learning-based methods are generally less sensitive in recognizing locally-clustered interactions, which can synergistically stabilize peptide binding. Deep convolutional neural network (DCNN) is a deep learning method inspired by visual recognition process of animal brain and it is known to be able to capture meaningful local patterns from 2D images. Once the peptide-MHC interactions can be encoded into image-like array(ILA) data, DCNN can be employed to build a predictive model for peptide-MHC binding prediction. In this study, we demonstrated that DCNN is able to not only reliably predict peptide-MHC binding, but also sensitively detect locally-clustered interactions. Nonapeptide-HLA-A and -B binding data were encoded into ILA data. A DCNN, as a pan-specific prediction model, was trained on the ILA data. The DCNN showed higher performance than other prediction tools for the latest benchmark datasets, which consist of 43 datasets for 15 HLA-A alleles and 25 datasets for 10 HLA-B alleles. In particular, the DCNN outperformed other tools for alleles belonging to the HLA-A3 supertype. The F1 scores of the DCNN were 0.86, 0.94, and 0.67 for HLA-A*31:01, HLA-A*03:01, and HLA-A*68:01 alleles, respectively, which were significantly higher than those of other tools. We found that the DCNN was able to recognize locally-clustered interactions that could synergistically stabilize peptide binding. We developed ConvMHC, a web server to provide user-friendly web interfaces for peptide-MHC class I binding predictions using the DCNN. ConvMHC web server can be accessible via http://jumong.kaist.ac.kr:8080/convmhc

  12. Spectral energy distribution analysis of class I and class II FU Orionis stars

    Energy Technology Data Exchange (ETDEWEB)

    Gramajo, Luciana V.; Gómez, Mercedes [Observatorio Astronómico, Universidad Nacional de Córdoba, Argentina, Laprida 854, 5000 Córdoba (Argentina); Rodón, Javier A., E-mail: luciana@oac.uncor.edu, E-mail: mercedes@oac.uncor.edu, E-mail: jrodon@eso.org [European Southern Observatory, Alonso de Córdova 3107, Vitacura, Casilla 19001, Santiago 19 (Chile)

    2014-06-01

    FU Orionis stars (FUors) are eruptive pre-main sequence objects thought to represent quasi-periodic or recurring stages of enhanced accretion during the low-mass star-forming process. We characterize the sample of known and candidate FUors in a homogeneous and consistent way, deriving stellar and circumstellar parameters for each object. We emphasize the analysis in those parameters that are supposed to vary during the FUor stage. We modeled the spectral energy distributions of 24 of the 26 currently known FUors, using the radiative transfer code of Whitney et al. We compare our models with those obtained by Robitaille et al. for Taurus class II and I sources in quiescence periods by calculating the cumulative distribution of the different parameters. FUors have more massive disks: we find that ∼80% of the disks in FUors are more massive than any Taurus class II and I sources in the sample. Median values for the disk mass accretion rates are ∼10{sup –7} M {sub ☉} yr{sup –1} versus ∼10{sup –5} M {sub ☉} yr{sup –1} for standard young stellar objects (YSOs) and FUors, respectively. While the distributions of envelope mass accretion rates for class I FUors and standard class I objects are similar, FUors, on average, have higher envelope mass accretion rates than standard class II and class I sources. Most FUors (∼70%) have envelope mass accretion rates above 10{sup –7} M {sub ☉} yr{sup –1}. In contrast, 60% of the classical YSO sample has an accretion rate below this value. Our results support the current scenario in which changes experimented by the circumstellar disk explain the observed properties of these stars. However, the increase in the disk mass accretion rate is smaller than theoretically predicted, although in good agreement with previous determinations.

  13. Transport of Streptococcus pneumoniae capsular polysaccharide in MHC Class II tubules.

    Directory of Open Access Journals (Sweden)

    Tom Li Stephen

    2007-03-01

    Full Text Available Bacterial capsular polysaccharides are virulence factors and are considered T cell-independent antigens. However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+ T cells in a major histocompatibility complex (MHC class II-dependent manner. The mechanism of carbohydrate presentation to CD4(+ T cells is unknown. We show in live murine dendritic cells (DCs that Sp1 translocates from lysosomal compartments to the plasma membrane in MHCII-positive tubules. Sp1 cell surface presentation results in reduction of self-peptide presentation without alteration of the MHCII self peptide repertoire. In DM-deficient mice, retrograde transport of Sp1/MHCII complexes resulting in T cell-dependent immune responses to the polysaccharide in vitro and in vivo is significantly reduced. The results demonstrate the capacity of a bacterial capsular polysaccharide antigen to use DC tubules as a vehicle for its transport as an MHCII/saccharide complex to the cell surface for the induction of T cell activation. Furthermore, retrograde transport requires the functional role of DM in self peptide-carbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens.

  14. Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

    DEFF Research Database (Denmark)

    McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany

    2016-01-01

    HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infect...

  15. Evaluation depth of the curve of Spee in class I, class II, and class III malocclusion: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar

    2015-01-01

    Full Text Available Occlusal plane is an essential consideration when multiple long-span posterior restorations are designed. When restorations are added to an existing tooth arrangement characterized by rotated, tipped, or extruded teeth, excursive interferences may be incorporated, resulting in detrimental squeal. The curve of Spee, which exists in the ideal natural dentition, allows harmony to exist between the anterior tooth and condylar guidance. This curve exists in the sagittal plane and is the best viewed from a lateral aspect. It permits total posterior disclusion on mandibular protrusion, given proper anterior tooth guidance. It is unclear that whether the curve of Spee is a description of the occlusal surface of each arch separately or in maximal intercuspation. The purpose of this study was to examine the differences in the depth of curve of Spee between the class I, class II, class III and to investigate the relationship of depth of curve of Spee with over jet, over-bite.

  16. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

    2016-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

  17. Evaluation of dentoskeletal effects of Farmand functional appliance (Fa II) on class II malocclusion

    OpenAIRE

    Yassaei S.; Aghili H.; Razeghi D.

    2007-01-01

    Background and Aim: Functional appliances refer to a variety of removable or fixed appliances designed to alter the mandibular position both sagitally and vertically, resulting in orthodontic and orthopedic changes. Despite the long history of functional appliances, there is still much controversy related to their effectiveness and mode of action. The aim of this study was to evaluate dental and skeletal effects of Fa II in patients with class II malocclusion due to mandibular deficiency.Mate...

  18. MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

    Directory of Open Access Journals (Sweden)

    Judith A. James

    2012-12-01

    Full Text Available Anthrax Lethal Toxin consists of Protective Antigen (PA and Lethal Factor (LF, and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class II versus non-MHC class II genes in the humoral response to PA and LF immunization using three immunized strains of inbred mice: A/J (H-2k at the MHC class II locus, B6 (H-2b, and B6.H2k (H-2k. IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by the non-MHC class II genetic background. Conversely, the humoral fine specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes, while the specificity of reactivity to PA was more dependent on MHC class II. Common epitopes, reactive in all strains, occurred in both LF and PA responses. These results demonstrate that MHC class II differentially influences humoral immune responses to LF and PA.

  19. [Cephalometric analysis in individuals with Class II/2 malocclusions].

    Science.gov (United States)

    Rak, D

    1990-06-01

    Various orthodontic anomalies class II/2, classified into several experimental groups, and eugnathic occlusion serving as controls, were studied by roentgencephalometry. The objective of the study was to detect possible distinctions in the quantitative values of the chosen variables and to select those which discriminate the group of class II/2 orthodontic anomalies most significantly. Attempts were made to ascertain whether or not there were sex-related differences. The teleroentgenograma of 241 examines, aged 10 to 18 years, of both sexes, were analyzed. The experimental group consisted of 61 examinees class II/2 orthodontic anomalies. The control group consisted of 180 examinees with eugnathic occlusion. Latero-lateral skull roentgenograms were taken according to the rules of roentgencephalometry. Using acetate paper, the drawings of profile teleroentgenograms were elaborated and the reference points and lineas were entered. A total of 38 variables were analyzed, of which 10 were linear, 19 angular, 8 variables were obtained by mathematical calculations, and the age variable was also analyzed. For statistical analyses and electronic computer was used. The results are presented in tables and graphs. The results obtained have shown: that, when compared to the findings in the control group, the subjects in the experimental groups manifested significant changes in the following craniofacial characteristics: retroposition and retroinclination of the upper incisors; increased difference of the position of the apical basis of the jaw; marked convexity of the osseous profile; mandibular retrognathism and increased proportion of the maxillary compared to mandibular base; that, with regard to the sex of the examines, only linear variables of significantly discriminating character were selected. Thus it could be concluded that there were no significant sex differences among the morphological characteristics of the viscerocranium.

  20. Interfacial Chemistry of Moisture-Aged Class II Composite Restorations

    Science.gov (United States)

    Spencer, Paulette; Wang, Yong; Bohaty, Brenda

    2007-01-01

    Under in vivo conditions, the adhesive/dentin bond at the gingival margin of class II composite restorations can be the first defense against substances that may penetrate and ultimately undermine the composite restoration. Deterioration of this bond during aqueous aging is an area of intense investigation, but to date, the majority of our techniques have provided only an indirect assessment of the degrading components. The purpose of this study was to analyze the in situ molecular structure of adhesive/dentin interfaces in class II composite restorations, following aging in aqueous solutions. Class II preparations were cut from 12 unerupted human third molars, with a water-cooled, high-speed, dental handpiece. The prepared teeth were randomly selected for restoration with single bond (SB) and Z100 (3M). Teeth were restored, as per the manufacturer’s directions, under environmental conditions that simulated humidity and temperature characteristics of the oral cavity. Restored teeth were kept in sterile Delbecco’s phosphate saline for 48 h or 90 days. The samples were sectioned occlusogingivally and micro-Raman spectra were acquired at ~1.5 μm spatial resolution across the composite/adhesive/dentin interfaces at the gingival margins. Samples were wet throughout spectral acquisition. The relative intensity of bands associated with the adhesive in the interfacial region decreased dramatically after aqueous storage. This decrease in concert with the similar depth of dentin demineralization provides direct spectroscopic evidence of leaching of adhesive monomer from the interface during the 90 days of storage. SB adhesive infiltrated 4 –5 μm of 12-μm demineralized dentin at the gingival margin. After 90 days of aqueous storage, SB adhesive infiltration was reduced to ~2 μm, leaving ~10 μm of demineralized dentin collagen exposed at the gingival margin. The unprotected collagen at the gingival margin of the aged class II composite restorations was disorganized

  1. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II

    NARCIS (Netherlands)

    Hasper, Hester E.; Kramer, Naomi E.; Smith, James L.; Hillman, J. D.; Zachariah, Cherian; Kuipers, Oscar P.; de Kruijff, Ben; Breukink, Eefjan

    2006-01-01

    Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II - targeted lantibiotics are too short to be

  2. HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition

    Directory of Open Access Journals (Sweden)

    Azim Hossain

    2011-01-01

    Full Text Available While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity.

  3. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato

    2009-09-01

    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  4. Characterization of MHC class I and II genes in a subantarctic seabird, the blue petrel, Halobaena caerulea (Procellariiformes).

    Science.gov (United States)

    Strandh, Maria; Lannefors, Mimi; Bonadonna, Francesco; Westerdahl, Helena

    2011-10-01

    The great polymorphism observed in the major histocompatibility complex (MHC) genes is thought to be maintained by pathogen-mediated selection possibly combined with MHC-disassortative mating, guided by MHC-determined olfactory cues. Here, we partly characterize the MHC class I and II B of the blue petrel, Halobaena caerulea (Procellariiformes), a bird with significant olfactory abilities that lives under presumably low pathogen burdens in Subantarctica. Blue petrels are long-lived, monogamous birds which suggest the necessity of an accurate mate choice process. The species is ancestral to songbirds (Passeriformes; many MHC loci), although not to gamefowls (Galliformes; few MHC loci). Considering the phylogenetic relationships and the low subantarctic pathogen burden, we expected few rather than many MHC loci in the blue petrel. However, when we analysed partial MHC class I and class II B cDNA and gDNA sequences we found evidence for as many as at least eight MHC class I loci and at least two class II B loci. These class I and II B sequences showed classical MHC characteristics, e.g. high nucleotide diversity, especially in putative peptide-binding regions where signatures of positive selection was detected. Trans-species polymorphism was found between MHC class II B sequences of the blue petrel and those of thin-billed prion, Pachyptila belcheri, two species that diverged ∼25 MYA. The observed MHC allele richness in the blue petrel may well serve as a basis for mate choice, especially since olfactory discrimination of MHC types may be possible in this species.

  5. Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies.

    Directory of Open Access Journals (Sweden)

    Dharanesh Gangaiah

    2016-12-01

    Full Text Available Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown.We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree.CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.

  6. Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies.

    Science.gov (United States)

    Gangaiah, Dharanesh; Spinola, Stanley M

    2016-12-01

    Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown. We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree. CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.

  7. Interaction of the chaperone calreticulin with proteins and peptides of different structural classes

    DEFF Research Database (Denmark)

    Duus, K; Sandhu, N; Jørgensen, C S

    2009-01-01

    The interaction of calreticulin with native and denatured forms and polypeptides in proteolytic digests of proteins representing structural classes of all-alpha-helix (hemoglobin, serum albumin), all-beta-sheet (IgG) and alpha-helix + beta-sheets (lysozyme, ovalbumin) was investigated. The binding...... of calreticulin to denatured proteins was found to depend on conformation and structural class of the protein. No interaction was observed with the native proteins, whereas binding was seen for the denatured proteins, the order of interaction being lysozyme = IgG > ovalbumin >> hemoglobin = serum albumin....... Moreover, the interaction between calreticulin and the heat-denatured proteins depended on the temperature and time used for denaturation and the degree of proteolytic fragmentation. Calreticulin bound well to peptides in proteolytic digests from protease K or chymotrypsin treatment of lysozyme, Ig...

  8. A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures

    OpenAIRE

    Wootten, Denise; Reynolds, Christopher A.; Koole, Cassandra; Smith, Kevin J.; Mobarec, Juan C.; Simms, John; Quon, Tezz; Coudrat, Thomas; Furness, Sebastian G. B.; Miller, Laurence J.; Christopoulos, Arthur; Sexton, Patrick M.

    2016-01-01

    The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60190, N3.43240, Q7.49394, and H6.52363 as key residues involved in peptide-mediated biased agonism, with R2.60190, N3.43240, and Q7.49394 predicted to form a polar int...

  9. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P

    1991-01-01

    Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce...... adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human...... class II-positive monocytic (I937) and T leukemic (HUT78) tumor cell lines and Epstein-Barr virus (EBV) transformed B-lymphoid cell lines (EBV-LCL). Class II-negative cell lines (U-937 and the EBV-LCL mutant line 616) were not induced to aggregate. An HLA-G-transfected EBV-LCL, 221-AGN...

  10. Evaluation of dentoskeletal effects of Farmand functional appliance (Fa II on class II malocclusion

    Directory of Open Access Journals (Sweden)

    Yassaei S.

    2007-07-01

    Full Text Available Background and Aim: Functional appliances refer to a variety of removable or fixed appliances designed to alter the mandibular position both sagitally and vertically, resulting in orthodontic and orthopedic changes. Despite the long history of functional appliances, there is still much controversy related to their effectiveness and mode of action. The aim of this study was to evaluate dental and skeletal effects of Fa II in patients with class II malocclusion due to mandibular deficiency.Materials and Methods: In this before-after clinical trial, 35 patients with class II div I malocclusion were selected. These samples were under treatment with Fa II appliance for 11 months. The range of age of females was 10-13 years and males 11-14 years. Combination analysis was used to determine skeletal and dental effects. Paired t-test was used to compare the differences of mean value pre and post treatment. P<0.05 was considered as the level of significance. Results: There was significant difference between pre and post treatment in respect to posterior and anterior facial height, eruption of upper and lower posterior teeth, eruption of upper anterior teeth, mandibular body length, ANB angle, IMPA and 1 to SN. No significant difference was observed between pre and post treatment regarding facial growth.Conclusion: Treatment with Fa II functional appliance leads to significant alterations in dental and skeletal elements of craniofacial complex and improvement of dental and jaws relationship.

  11. NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data.

    Science.gov (United States)

    Jurtz, Vanessa; Paul, Sinu; Andreatta, Massimo; Marcatili, Paolo; Peters, Bjoern; Nielsen, Morten

    2017-11-01

    Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway. Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data. Recently, an increasing number of MHC-presented peptides identified by mass spectrometry have been reported containing information about peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides. In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increase in predictive performance compared with state-of-the-art methods when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules

    DEFF Research Database (Denmark)

    Pandya, Mital; Rasmussen, Michael; Hansen, Andreas

    2015-01-01

    Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8+ T cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presentation......, and different antigen peptide motifs are associated with specific genetic sequences of class I molecules. Understanding bovine leukocyte antigen (BoLA), peptide-MHC class I binding specificities may facilitate development of vaccines or reagents for quantifying the adaptive immune response to intracellular...... pathogens, such as foot-and-mouth disease virus (FMDV). Six synthetic BoLA class I (BoLA-I) molecules were produced, and the peptide binding motif was generated for five of the six molecules using a combined approach of positional scanning combinatorial peptide libraries (PSCPLs) and neural network...

  13. Enterocin 96, a Novel Class II Bacteriocin Produced by Enterococcus faecalis WHE 96, Isolated from Munster Cheese▿

    Science.gov (United States)

    Izquierdo, Esther; Wagner, Camille; Marchioni, Eric; Aoude-Werner, Dalal; Ennahar, Saïd

    2009-01-01

    Enterococcus faecalis WHE 96, a strain isolated from soft cheese based on its anti-Listeria activity, produced a 5,494-Da bacteriocin that was purified to homogeneity by ultrafiltration and cation-exchange and reversed-phase chromatographies. The amino acid sequence of this bacteriocin, named enterocin 96, was determined by Edman degradation, and its structural gene was sequenced, revealing a double-glycine leader peptide. After a comparison with other bacteriocins, it was shown that enterocin 96 was a new class II bacteriocin that showed very little similarity with known structures. Enterocin 96 was indeed a new bacteriocin belonging to class II bacteriocins. The activity spectrum of enterocin 96 covered a wide range of bacteria, with strong activity against most gram-positive strains but very little or no activity against gram-negative strains. PMID:19411428

  14. Enterocin 96, a novel class II bacteriocin produced by Enterococcus faecalis WHE 96, isolated from Munster cheese.

    Science.gov (United States)

    Izquierdo, Esther; Wagner, Camille; Marchioni, Eric; Aoude-Werner, Dalal; Ennahar, Saïd

    2009-07-01

    Enterococcus faecalis WHE 96, a strain isolated from soft cheese based on its anti-Listeria activity, produced a 5,494-Da bacteriocin that was purified to homogeneity by ultrafiltration and cation-exchange and reversed-phase chromatographies. The amino acid sequence of this bacteriocin, named enterocin 96, was determined by Edman degradation, and its structural gene was sequenced, revealing a double-glycine leader peptide. After a comparison with other bacteriocins, it was shown that enterocin 96 was a new class II bacteriocin that showed very little similarity with known structures. Enterocin 96 was indeed a new bacteriocin belonging to class II bacteriocins. The activity spectrum of enterocin 96 covered a wide range of bacteria, with strong activity against most gram-positive strains but very little or no activity against gram-negative strains.

  15. Surgical Orthodontic Treatment of Severe Skeletal Class II

    Science.gov (United States)

    Alsulaimani, Fahad F.; Al-Sebaei, Maisa O.; Afify, Ahmed R.

    2013-01-01

    This paper describes an adult Saudi male patient who presented with a severe skeletal class II deformity. The case was managed with a combination of presurgical orthodontic treatment followed by a double jaw orthognathic surgery and then another phase of orthodontic treatment for final occlusal detailing. Extraction of the four first premolars was done during the presurgical orthodontic phase of treatment to decompensate upper and lower incisors and to give room for surgical setback of the maxillary anterior segment. Double jaw surgery was performed: bilateral sagittal split ramus osteotomy for 8 mm mandibular advancement combined with three-piece Le Fort I maxillary osteotomy, 6 mm setback of the anterior segment, 8 mm impaction of the maxilla, and 5 mm advancement genioplasty. Although the anteroposterior discrepancy and the facial convexity were so severe, highly acceptable results were obtained, both esthetically as well as occlusally. PMID:23573428

  16. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

    Directory of Open Access Journals (Sweden)

    Songhua Zhang

    Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

  17. Autoimmunity and inflammation are independent of class II transactivator type PIV-dependent class II major histocompatibility complex expression in peripheral tissues during collagen-induced arthritis.

    Science.gov (United States)

    Waldburger, Jean-Marc; Palmer, Gaby; Seemayer, Christian; Lamacchia, Celine; Finckh, Axel; Christofilopoulos, Panayiotis; Baeten, Dominique; Reith, Walter; Gabay, Cem

    2011-11-01

    To determine the regulation of class II major histocompatibility complex (MHC) expression in fibroblast-like synoviocytes (FLS) in order to investigate their role as nonprofessional antigen-presenting cells in collagen-induced arthritis (CIA). Expression of class II MHC, class II MHC transactivator (CIITA), and Ciita isoforms PI, PIII, and PIV was examined by real-time quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry in human synovial tissues, arthritic mouse joints, and human and murine FLS. CIA was induced in mice in which isoform PIV of Ciita was knocked out (PIV(-/-) ), in PIV(-/-) mice transgenic for CIITA in the thymus (K14 CIITA), and in their control littermates. HLA-DRA, total CIITA, and CIITA PIII messenger RNA levels were significantly increased in synovial tissue samples from patients with rheumatoid arthritis compared with the levels in tissue from patients with osteoarthritis. Human FLS expressed surface class II MHC via CIITA PIII and PIV, while class II MHC expression in murine FLS was entirely mediated by PIV. Mice with a targeted deletion of CIITA PIV lack CD4+ T cells and were protected against CIA. The expression of CIITA was restored in the thymus of PIV(-/-) K14 CIITA-transgenic mice, which had a normal CD4+ T cell repertoire and normal surface levels of class II MHC on professional antigen-presenting cells, but did not induce class II MHC on FLS. Synovial inflammation and immune responses against type II collagen were similar in PIV(-/-) K14 CIITA-transgenic mice and control mice with CIA, but bone erosion was significantly reduced in the absence of PIV. Overexpression of class II MHC is tightly correlated with CIITA expression in arthritic synovium and in FLS. Selective targeting of Ciita PIV in peripheral tissues abrogates class II MHC expression by murine FLS but does not protect against inflammation and autoimmune responses in CIA. Copyright © 2011 by the American College of Rheumatology.

  18. Urolinin: The First Linear Peptidic Urotensin-II Receptor Agonist.

    Science.gov (United States)

    Bandholtz, Sebastian; Erdmann, Sarah; von Hacht, Jan Lennart; Exner, Samantha; Krause, Gerd; Kleinau, Gunnar; Grötzinger, Carsten

    2016-11-23

    This study investigated the role of individual U-II amino acid positions and side chain characteristics important for U-IIR activation. A complete permutation library of 209 U-II variants was studied in an activity screen that contained single substitution variants of each position with one of the other 19 proteinogenic amino acids. Receptor activation was measured using a cell-based high-throughput fluorescence calcium mobilization assay. We generated the first complete U-II substitution map for U-II receptor activation, resulting in a detailed view into the structural features required for receptor activation, accompanied by complementary information from receptor modeling and ligand docking studies. On the basis of the systematic SAR study of U-II, we created 33 further short and linear U-II variants from eight to three amino acids in length, including d- and other non-natural amino acids. We identified the first high-potency linear U-II analogues. Urolinin, a linear U-II agonist (nWWK-Tyr(3-NO 2 )-Abu), shows low nanomolar potency as well as improved metabolic stability.

  19. Hyoid bone position and head posture comparison in skeletal Class I and Class II subjects: A retrospective cephalometric study

    Directory of Open Access Journals (Sweden)

    Pawankumar Dnyandeo Tekale

    2014-01-01

    Full Text Available Objective: The aim of the study was to investigate the hyoid bone position and the head posture using lateral cephalograms in subjects with skeletal Class I and skeletal Class II pattern and to investigate the gender differences. Materials and Methods: The study used lateral cephalograms of 40 subjects (20 skeletal Class I pattern; 20 skeletal Class II pattern. Lateral cephalograms were traced and analyzed for evaluation of the hyoid bone position and the head posture using 34 parameters. Independent sample t-test was performed to compare the differences between the two groups and between genders in each group. Statistical tests were performed using NCSS 2007 software (NCSST, Kaysville, Utah, USA. Results: The linear measurements between the hyoid bone (H and cervical spine (CV2ia, the nasion-sella line, palatal line nasion line, the anterior nasal spine (ANS to perpendicular projection of H on the NLP (NLP- Nasal Linear Projection (H-NLP/ANS as well as the posterior cranial points (Bo, Ar and S points were found to be less in skeletal Class II subjects. The measurement H-CV2ia was found to be less in males with skeletal Class I pattern and H-CV4ia was found to be less in males with skeletal Class II pattern. The natural head posture showed no significant gender differences. Conclusion: The position of hyoid bone was closer to the cervical vertebra horizontally in skeletal Class II subjects when compared with skeletal Class I subjects. In males, the hyoid bone position was closer to the cervical vertebra horizontally both in skeletal Class I and skeletal Class II subjects.

  20. Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex

    DEFF Research Database (Denmark)

    Stryhn, A; Andersen, P S; Pedersen, L O

    1996-01-01

    Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide...... each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T...... cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody....

  1. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

    Science.gov (United States)

    Corin, Karolina; Baaske, Philipp; Ravel, Deepali B; Song, Junyao; Brown, Emily; Wang, Xiaoqiang; Wienken, Christoph J; Jerabek-Willemsen, Moran; Duhr, Stefan; Luo, Yuan; Braun, Dieter; Zhang, Shuguang

    2011-01-01

    A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  2. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

    Directory of Open Access Journals (Sweden)

    Karolina Corin

    Full Text Available A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  3. Peptide-selective inrichment of MHC II-peptide complexes in tetraspan microdomains distinct from lipid rafts

    Czech Academy of Sciences Publication Activity Database

    Kropshofer, H.; Spindeldreher, S.; Rohn, T. A.; Platania, N.; Grygar, C.; Wolpl, A.; Langen, H.; Hořejší, Václav; Vogt, A. B.

    2002-01-01

    Roč. 3, č. 1 (2002), s. 61-68 ISSN 1529-2908 R&D Projects: GA MŠk LN00A026 Keywords : Microdomain * tetraspan proteins * MHC class II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 27.868, year: 2002

  4. Development of a class II lanthipeptide production system

    NARCIS (Netherlands)

    Zwart, Hannah Louise

    2016-01-01

    Drug resistance of bacterial pathogens has become a serious problem in healthcare. To overcome resistance, a new generation of antimicrobial compounds based on novel structures is needed. Lanthipeptides are small ribosomally produced peptides that contain so-called lanthionine rings. These peptides

  5. Importance of lipopolysaccharide aggregate disruption for the anti-endotoxic effects of heparin cofactor II peptides.

    Science.gov (United States)

    Singh, Shalini; Papareddy, Praveen; Kalle, Martina; Schmidtchen, Artur; Malmsten, Martin

    2013-11-01

    Lipid membrane and lipopolysaccharide (LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-potential measurements. Antimicrobial effects of these peptides were compared to their ability to disorder bacterial lipid membranes, while their capacity to block endotoxic effects of LPS was correlated to the binding of these peptides to LPS and its lipid A moiety, and to charge, secondary structure, and morphology of peptide/LPS complexes. While the peptide KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) displayed potent antimicrobial and anti-endotoxic effects, its truncated variants KYE21 (KYEITTIHNLFRKLTHRLFRR) and NLF20 (NLFRKLTHRLFRRNFGYTLR) provide some clues on structure-activity relations, since KYE21 retains both the antimicrobial and anti-endotoxic effects of KYE28 (although both attenuated), while NLF20 retains the antimicrobial but only a fraction of the anti-endotoxic effect, hence locating the anti-endotoxic effects of KYE28 to its N-terminus. The antimicrobial effect, on the other hand, is primarily located at the C-terminus of KYE28. While displaying quite different endotoxic effects, these peptides bind to a similar extent to both LPS and lipid A, and also induce comparable LPS scavenging on model eukaryotic membranes. In contrast, fragmentation and densification of LPS aggregates, in turn dependent on the secondary structure in the peptide/LPS aggregates, correlate to the anti-endotoxic effect of these peptides, thus identifying peptide-induced packing transitions in LPS aggregates as key for anti-endotoxic functionality. This aspect therefore needs to be taken into account in the development of novel anti-endotoxic peptide therapeutics. Copyright © 2013. Published by Elsevier B.V.

  6. Comparison of second molar eruption patterns in patients with skeletal Class II and skeletal Class I malocclusions.

    Science.gov (United States)

    Brin, Ilana; Camasuvi, Semin; Dali, Nasser; Aizenbud, Dror

    2006-12-01

    The eruptive positions of the second molars in Class I and Class II malocclusions were studied. Pretreatment records of 221 patients with a mean age of 11.3 years were evaluated. About 19% of them had skeletal Class I, 31% had skeletal maxillary Class II, and 50% had skeletal mandibular Class II malocclusions. The mean values of the dental and chronologic ages of the subjects were similar. The eruptive positions in relation to a reference line, the developmental stages of the patients' second molars and dental ages were recorded from the panoramic roentgenograms. The distribution of the various developmental stages in each malocclusion group was similar, and no association between skeletal malocclusion and dental developmental stage of the second molars was encountered. The eruptive position of the maxillary second molars was more occlusal only in the oldest maxillary Class II group, above 12 years of age (P = .02). These results support, in part, previous reports suggesting that the maxillary second molars may erupt earlier in patients with skeletal maxillary Class II malocclusions.

  7. An Approach for a Synthetic CTL Vaccine Design against Zika Flavivirus Using Class I and Class II Epitopes Identified by Computer Modeling

    Directory of Open Access Journals (Sweden)

    Edecio Cunha-Neto

    2017-06-01

    Full Text Available The threat posed by severe congenital abnormalities related to Zika virus (ZKV infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue class I epitopes and by using a Major Histocompatibility Complex (MHC binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.

  8. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation

    OpenAIRE

    Balamurugan, Appakalai N.; Green, Michael L.; Breite, Andrew G.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G.; Williams, Stuart K.; Hering, Bernhard J.; Dwulet, Francis E.; McCarthy, Robert C.

    2015-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation.

  9. Different Roles Of Class-I And Class-II Clostridium-histolyticum Collagenase In Rat Pancreatic-islet Isolation

    NARCIS (Netherlands)

    Wolters, G. H. J.; Vos-Scheperkeuter, Greetje; Lin, Hun-Chi; van Schilfaarde, R

    Crude Clostridium histolyticum collagenase was purified by gel filtration and fractionated by anion exchange chromatography into class I with high collagen digestion activity (CDA) and low FALGPA (2-furanacryloyl-L-leucylglycyl-L-prolyI-L-alanine )hydrolysis activity (FHA), class II with low CDA and

  10. Glass ionomer-silver cermet Class II tunnel-restorations for primary molars.

    Science.gov (United States)

    Croll, T P

    1988-01-01

    Tunnel preparations preserve the anatomical marginal ridge and minimize the loss of healthy tooth structure adjacent to the carious lesion. When the practitioner has developed proficiency in restoring class II carious lesions with tunnel restorations, less treatment time is required than with traditional class II preparations. The technique for restoring a primary first molar with a class II carious lesion, using a tunnel preparation and Ketac-Silver restorative material is described.

  11. MHC class II diversity of koala (Phascolarctos cinereus) populations across their range.

    Science.gov (United States)

    Lau, Q; Jaratlerdsiri, W; Griffith, J E; Gongora, J; Higgins, D P

    2014-10-01

    Major histocompatibility complex class II (MHCII) genes code for proteins that bind and present antigenic peptides and trigger the adaptive immune response. We present a broad geographical study of MHCII DA β1 (DAB) and DB β1 (DBB) variants of the koala (Phascolarctos cinereus; n=191) from 12 populations across eastern Australia, with a total of 13 DAB and 7 DBB variants found. We identified greater MHCII variation and, possibly, additional gene copies in koala populations in the north (Queensland and New South Wales) relative to the south (Victoria), confirmed by STRUCTURE analyses and genetic differentiation using analysis of molecular variance. The higher MHCII diversity in the north relative to south could potentially be attributed to (i) significant founder effect in Victorian populations linked to historical translocation of bottlenecked koala populations and (ii) increased pathogen-driven balancing selection and/or local genetic drift in the north. Low MHCII genetic diversity in koalas from the south could reduce their potential response to disease, although the three DAB variants found in the south had substantial sequence divergence between variants. This study assessing MHCII diversity in the koala with historical translocations in some populations contributes to understanding the effects of population translocations on functional genetic diversity.

  12. NMR study of the possible interaction in solution of angiotensin II with a peptide encoded by angiotensin II complementary RNA

    International Nuclear Information System (INIS)

    Eaton, H.L.; Fesik, S.W.; Austin, R.E.; Martin, S.F.

    1989-01-01

    The potential binding of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) (AII) to a peptide encoded by its complementary RNA (Lys-Gly-Val-Asp-Val-Try-Ala-Val) (IIA) has been studied by monitoring the 1 H NMR spectrum of IIA in aqueous phosphate or Tris·HCl buffer ( 2 H 2 O) as it is titrated with AII. For molar ratios of AII/IIA ranging from 0.2 to 1.8, the NMR spectra are unchanged as compared to the spectra of the isolated peptides. Based on these findings, the K d for the putative biomolecular complex of the two peptides under these conditions is calculated to be >10 -4 M. This result does not support the suggestion of Elton et al. that AII and IIA engage in high-affinity binding (K d ∼ 5 x 10 -8 M) with each other

  13. OGLE II Eclipsing Binaries In The LMC: Analysis With Class

    Science.gov (United States)

    Devinney, Edward J.; Prsa, A.; Guinan, E. F.; DeGeorge, M.

    2011-01-01

    The Eclipsing Binaries (EBs) via Artificial Intelligence (EBAI) Project is applying machine learning techniques to elucidate the nature of EBs. Previously, Prsa, et al. applied artificial neural networks (ANNs) trained on physically-realistic Wilson-Devinney models to solve the light curves of the 1882 detached EBs in the LMC discovered by the OGLE II Project (Wyrzykowski, et al.) fully automatically, bypassing the need for manually-derived starting solutions. A curious result is the non-monotonic distribution of the temperature ratio parameter T2/T1, featuring a subsidiary peak noted previously by Mazeh, et al. in an independent analysis using the EBOP EB solution code (Tamuz, et al.). To explore this and to gain a fuller understanding of the multivariate EBAI LMC observational plus solutions data, we have employed automatic clustering and advanced visualization (CAV) techniques. Clustering the OGLE II data aggregates objects that are similar with respect to many parameter dimensions. Measures of similarity for example, could include the multidimensional Euclidean Distance between data objects, although other measures may be appropriate. Applying clustering, we find good evidence that the T2/T1 subsidiary peak is due to evolved binaries, in support of Mazeh et al.'s speculation. Further, clustering suggests that the LMC detached EBs occupying the main sequence region belong to two distinct classes. Also identified as a separate cluster in the multivariate data are stars having a Period-I band relation. Derekas et al. had previously found a Period-K band relation for LMC EBs discovered by the MACHO Project (Alcock, et al.). We suggest such CAV techniques will prove increasingly useful for understanding the large, multivariate datasets increasingly being produced in astronomy. We are grateful for the support of this research from NSF/RUI Grant AST-05-75042 f.

  14. Two putative subunits of a peptide pump encoded in the human major histocompatability complex class 2 region

    International Nuclear Information System (INIS)

    Bahram, S.; Arnold, D.; Bresnahan, M.; Strominger, J.L.; Spies, T.

    1991-01-01

    The class 2 region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class 1 molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class 1 molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class 2 DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by γ interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class 1 molecules, although a distinct function of PSF2 cannot be ruled out

  15. Características cefalométricas de pacientes portadores de más oclusões Classe I e Classe II de Angle Cephalometric characteristics of patients with Angle Class I and Class II malocclusions

    Directory of Open Access Journals (Sweden)

    Rogério Lacerda dos Santos

    2009-06-01

    Full Text Available OBJETIVOS: o presente estudo comparou algumas medidas cefalométricas relacionadas às características faciais em pacientes com má oclusão Classe I, Classe II 1ª divisão e Classe II 2ª divisão. METODOLOGIA: foram selecionadas 130 telerradiografias de pacientes leucodermas em fase inicial de tratamento ortodôntico, com idades entre 10 e 16 anos (média de 12,6 anos; e divididos em 3 grupos. As medidas cefalométricas utilizadas neste estudo foram: ANB, ı-SN, IMPA, AML, Ls-ı, Li-ī e EI. A análise de variância e o teste de Tukey foram realizados nas medidas ANB, IMPA, AML, ı-SN e Li-ī. Para as demais variáveis (EI e Ls-ı foi utilizado o teste de Kruskal Wallis e Dunn. RESULTADOS: os resultados mostraram que as medidas Ls-ı e EI tiveram diferença estatisticamente significativa entre os grupos I e II-1 e entre os grupos II-1 e II-2 (p AIM: The present study compared some cephalometric measurements related to facial characteristics in patients having Class I, Class II division 1, and Class II division 2 malocclusions. METHODS: One hundred and thirty teleradiographs of Caucasian patients aged 10-16 years (mean age of 12.6 years under initial orthodontic treatment were selected for study and divided into 3 groups. The cephalometric measurements used in the present study were the following: ANB, ı-SN, IMPA, AML, Ls-ı, Li-ī, and EI. Variance analysis and Tukey's test were carried out for ANB, IMPA, AML, ı-SN, and Li-ī measurements, whereas Kruskal-Wallis and Dunn's tests were used for EI and Ls-ı. RESULTS: Statistically significant differences were found for EI and Ls-ı measurements when Group II-1 was compared to Group I and Group II-2 (p < 0.05. ANB and IMPA measurements also had statistically significant differences when Group I was compared to Group II-1 and Group II-2 (p < 0.05. The measurement ı-SN had statistically significant differences between the 3 groups (p < 0.05. CONCLUSIONS: One can conclude that the measurement

  16. The diabetogenic mouse MHC class II molecule I-A[subscript g7] is endowed with a switch that modulates TCR affinity

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Kenji; Corper, Adam L.; Herro, Rana; Jabri, Bana; Wilson, Ian A.; Teyton, Luc (Scripps); (UC)

    2011-11-16

    Genetic susceptibility to autoimmunity is frequently associated with specific MHC alleles. Diabetogenic MHC class II molecules, such as human HLA-DQ8 and mouse I-A{sub g7}, typically have a small, uncharged amino acid residue at position 57 of their {beta} chain ({beta}57); this results in the absence of a salt bridge between {beta}57 and Arg{alpha}76, which is adjacent to the P9 pocket of the peptide-binding groove. However, the influence of Arg{alpha}76 on the selection of the TCR repertoire remains unknown, particularly when the MHC molecule binds a peptide with a neutral amino acid residue at position P9. Here, we have shown that diabetogenic MHC class II molecules bound to a peptide with a neutral P9 residue primarily selected and expanded cells expressing TCRs bearing a negatively charged residue in the first segment of their complementarity determining region 3{beta}. The crystal structure of one such TCR in complex with I-A{sub g7} bound to a peptide containing a neutral P9 residue revealed that a network of favorable long-range (greater than 4 {angstrom}) electrostatic interactions existed among Arg{alpha}76, the neutral P9 residue, and TCR, which supported the substantially increased TCR/peptide-MHC affinity. This network could be modulated or switched to a lower affinity interaction by the introduction of a negative charge at position P9 of the peptide. Our results support the existence of a switch at residue {beta}57 of the I-Ag7 and HLA-DQ8 class II molecules and potentially link normal thymic TCR selection with abnormal peripheral behavior.

  17. MHC class II polymorphisms, autoreactive T-cells and autoimmunity

    Directory of Open Access Journals (Sweden)

    Sue eTsai

    2013-10-01

    Full Text Available Major histocompatibility complex (MHC genes, also known as human leukocyte antigen genes (HLA in humans, are the prevailing contributors of genetic susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D, Multiple Sclerosis (MS, and Rheumatoid arthritis (RA, among others (Todd and Wicker, 2001;MacKay et al., 2002;Hafler et al., 2007. Although the pathways through which MHC molecules afford autoimmune risk or resistance remain to be fully mapped out, it is generally accepted that they do so by shaping the central and peripheral T cell repertoires of the host towards autoimmune proclivity or resistance, respectively. Disease-predisposing MHC alleles would both spare autoreactive thymocytes from central tolerance and bias their development towards a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote central deletion of autoreactive thymocytes and skew their development towards non-pathogenic phenotypes. This interpretation of the data is at odds with two other observations: that in MHC-heterozygous individuals, resistance is dominant over susceptibility; and that it is difficult to understand how deletion of one or a few clonal autoreactive T cell types would suffice to curb autoimmune responses driven by hundreds if not thousands of autoreactive T cell specificities. This review provides an update on current advances in our understanding of the mechanisms underlying MHC class II-associated autoimmune disease susceptibility and/or resistance and attempts to reconcile these seemingly opposing concepts.

  18. Gravitational Waves in Locally Rotationally Symmetric (LRS Class II Cosmologies

    Directory of Open Access Journals (Sweden)

    Michael Bradley

    2017-10-01

    Full Text Available In this work we consider perturbations of homogeneous and hypersurface orthogonal cosmological backgrounds with local rotational symmetry (LRS, using a method based on the 1 + 1 + 2 covariant split of spacetime. The backgrounds, of LRS class II, are characterised by that the vorticity, the twist of the 2-sheets, and the magnetic part of the Weyl tensor all vanish. They include the flat Friedmann universe as a special case. The matter contents of the perturbed spacetimes are given by vorticity-free perfect fluids, but otherwise the perturbations are arbitrary and describe gravitational, shear, and density waves. All the perturbation variables can be given in terms of the time evolution of a set of six harmonic coefficients. This set decouples into one set of four coefficients with the density perturbations acting as source terms, and another set of two coefficients describing damped source-free gravitational waves with odd parity. We also consider the flat Friedmann universe, which has been considered by several others using the 1 + 3 covariant split, as a check of the isotropic limit. In agreement with earlier results we find a second-order wavelike equation for the magnetic part of the Weyl tensor which decouples from the density gradient for the flat Friedmann universes. Assuming vanishing vector perturbations, including the density gradient, we find a similar equation for the electric part of the Weyl tensor, which was previously unnoticed.

  19. Performance assessment for the class L-II disposal facility

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This draft radiological performance assessment (PA) for the proposed Class L-II Disposal Facility (CIIDF) on the Oak Ridge Reservation (ORR) has been prepared to demonstrate compliance with the requirements of the US Department of Energy Order 5820.2A. This PA considers the disposal of low-level radioactive wastes (LLW) over the operating life of the facility and the long-term performance of the facility in providing protection to public health and the environment. The performance objectives contained in the order require that the facility be managed to accomplish the following: (1) Protect public health and safety in accordance with standards specified in environmental health orders and other DOE orders. (2) Ensure that external exposure to the waste and concentrations of radioactive material that may be released into surface water, groundwater, soil, plants, and animals results in an effective dose equivalent (EDE) that does not exceed 25 mrem/year to a member of the public. Releases to the atmosphere shall meet the requirements of 40 CFR Pt. 61. Reasonable effort should be made to maintain releases of radioactivity in effluents to the general environment as low as reasonably achievable. (1) Ensure that the committed EDEs received by individual who inadvertently may intrude into the facility after the loss of active institutional control (100 years) will not exceed 100 mrem/year for continuous exposure of 500 mrem for a single acute exposure. (4) Protect groundwater resources, consistent with federal, state, and local requirements.

  20. The Spider Venom Peptide Lycosin-II Has Potent Antimicrobial Activity against Clinically Isolated Bacteria

    Directory of Open Access Journals (Sweden)

    Yongjun Wang

    2016-04-01

    Full Text Available Antimicrobial peptides have been accepted as excellent candidates for developing novel antibiotics against drug-resistant bacteria. Recent studies indicate that spider venoms are the source for the identification of novel antimicrobial peptides. In the present study, we isolated and characterized an antibacterial peptide named lycosin-II from the venom of the spider Lycosa singoriensis. It contains 21 amino acid residue lacking cysteine residues and forms a typical linear amphipathic and cationic α-helical conformation. Lycosin-II displays potent bacteriostatic effect on the tested drug-resistant bacterial strains isolated from hospital patients, including multidrug-resistant A. baumannii, which has presented a huge challenge for the infection therapy. The inhibitory ability of lycosin-II might derive from its binding to cell membrane, because Mg2+ could compete with the binding sites to reduce the bacteriostatic potency of lycosin-II. Our data suggest that lycosin-II might be a lead in the development of novel antibiotics for curing drug-resistant bacterial infections.

  1. Maxillary and mandibular contribution to the establishment of class II malocclusion in an adult Lebanese population.

    Science.gov (United States)

    El Hajj, Nadine; Bassil-Nassif, Nayla; Tauk, Alain; Mouhanna-Fattal, Carole; Bouserhal, Joseph P

    2017-12-01

    The main aim of this study was to describe the contribution of the maxilla and the mandible to the establishment of a Class II skeletal malocclusion in an adult Lebanese population. Secondary aims were to detect the presence of sex-based dimorphism and to study the influence of the vertical dimension on the Class II skeletal pattern. A sample of 90 adults in skeletal Class II was recruited and equally distributed according to sex and vertical typology. The study describes the skeletal and dentoalveolar cephalometric characteristics of the Class II sample, essentially according to Coben's cephalometric analysis. The total effective depth of the cranial base and the anterior cranial base angle (SN-BaH) were both greater in the Class II sample. In females, the effective depth of the maxilla (Ptm-A) was larger than normal while SNB was smaller. The parameters describing the size and shape of the body of the mandible were significantly different from those of normal subjects. The upper incisors were in a retrusive position, while the axis of the lower incisors was located normally. The mandibular molars had a more distal sagittal position. Hyperdivergent subjects had more significant posterior alveolar growth, a more retrusive mandibular position and smaller mandibular dimensions than the other two vertical sub-groups. The cranial base contributes to the establishment of a Class II malocclusion, and mandibular retrusion cannot be considered as a characteristic shared by all skeletal Class II subjects. Lessening of the absolute length of the mandibular body is the second most frequent etiological factor noted in the Class II sample studied. Most individuals in skeletal Class II have an associated dental Class II malocclusion, and the vertical dimension has an influence on the Class II skeletal pattern. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

  2. Diagnostic performance of increased overjet in Class II division 1 malocclusion and incisor trauma.

    Science.gov (United States)

    Baccetti, Tiziano; Giuntini, Veronica; Vangelisti, Andrea; Darendeliler, M Ali; Franchi, Lorenzo

    2010-01-01

    The objectives of this study were: 1) to evaluate the associations between an increased overjet (IO) and other dentoskeletal characteristics of Class II division 1 malocclusions in the mixed dentition; 2) to assess whether Class II division 1 malocclusions or rather an increased overjet per se is a risk factor for upper incisor trauma (UIT). A sample of 900 mixed dentition subjects, was observed by clinical inspection, analysis of dental casts, and lateral cephalograms. The diagnostic performance of IO (overjet ≥ 7 mm) was evaluated in relation to other Class II dentoskeletal features (Class II molar and canine relationships, and skeletal Class II relationships). Secondly, the diagnostic performance of IO and of the other Class II dentoskeletal components was tested with regard to the prevalence of UIT. Diagnostic performance was assessed by odds ratio and positive likelihood ratio. The diagnostic performance of IO with regard to the other dentoskeletal components of Class II malocclusions was not significant. The only Class II features associated significantly with an increased risk of UIT was IO. When used as an isolated occlusal feature, IO is not a valid diagnostic indicator for Class II division 1 malocclusions. An increased overjet per se, and not Class II malocclusions, appears to be a significant risk factor for UIT. These findings recommend discrimination between clinical conditions showing an isolated IO from comprehensive Class II malocclusions during diagnosis, analysis of treatment outcomes, and evaluation of the risk of upper incisor trauma. Copyright © 2010 Società Italiana di Ortodonzia SIDO. Published by Elsevier Srl. All rights reserved.

  3. Bioorthogonal Diversification of Peptides through Selective Ruthenium(II)-Catalyzed C-H Activation.

    Science.gov (United States)

    Schischko, Alexandra; Ren, Hongjun; Kaplaneris, Nikolaos; Ackermann, Lutz

    2017-02-01

    Methods for the chemoselective modification of amino acids and peptides are powerful techniques in biomolecular chemistry. Among other applications, they enable the total synthesis of artificial peptides. In recent years, significant momentum has been gained by exploiting palladium-catalyzed cross-coupling for peptide modification. Despite major advances, the prefunctionalization elements on the coupling partners translate into undesired byproduct formation and lengthy synthetic operations. In sharp contrast, we herein illustrate the unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions. The ligand-accelerated C-H activation strategy proved water-tolerant and set the stage for direct fluorescence labelling as well as various modes of peptide ligation with excellent levels of positional selectivity in a bioorthogonal fashion. The synthetic utility of our approach is further demonstrated by twofold C-H arylations for the complexity-increasing assembly of artificial peptides within a multicatalytic C-H activation manifold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Anteroposterior condylar position: a comparative study between subjects with normal occlusion and patients with Class I, Class II Division 1, and Class III malocclusions.

    Science.gov (United States)

    Fraga, Marcelo Reis; Rodrigues, Andréia Fialho; Ribeiro, Luiz Claudio; Campos, Marcio José da Silva; Vitral, Robert Willer Farinazzo

    2013-10-29

    The present study aimed to determine and compare the anteroposterior position of the condyle in the mandibular fossa between groups of asymptomatic subjects with normal occlusion and asymptomatic subjects with Class I, Class II Division 1, and Class III malocclusions. Thirty persons with normal occlusion, 30 with Class I malocclusion, 30 with Class II Division 1, and 30 with Class III had computed tomography scans of their temporomandibular joints. The anterior joint space/posterior joint space (AJS/PJS) ratio was determined for the right and left joints. The paired t test was used to analyze the AJS/PJS ratio between both sides for each group. The ANOVA test was applied to verify the differences between the groups for the measurements of the right and left sides. In case the ANOVA test confirmed significance, the Dunnett's t test was performed to compare the groups of malocclusion with that of normal occlusion. The paired t test between the AJS/PJS relationships in the right and left sides showed the following p values: Class I (0.168), Class II Division 1 (0.662), Class III (0.991), and normal occlusion (0.390). The ANOVA test showed a p value of 0.445 for the comparisons of the right side and 0.040 for the left side. The Dunnett's t test demonstrated a statistically significant difference between the Class II group and the normal occlusion group (p value of 0.026) in the joints of the left side. Bilateral symmetry and lack of condyle centralization were common characteristics among all groups. The greatest condylar decentralization was observed in the Class II group, whereas the least condylar decentralization was found in the normal occlusion group.

  5. Ranked solutions to a class of combinatorial optimizations - with applications in mass spectrometry based peptide sequencing

    Science.gov (United States)

    Doerr, Timothy; Alves, Gelio; Yu, Yi-Kuo

    2006-03-01

    Typical combinatorial optimizations are NP-hard; however, for a particular class of cost functions the corresponding combinatorial optimizations can be solved in polynomial time. This suggests a way to efficiently find approximate solutions - - find a transformation that makes the cost function as similar as possible to that of the solvable class. After keeping many high-ranking solutions using the approximate cost function, one may then re-assess these solutions with the full cost function to find the best approximate solution. Under this approach, it is important to be able to assess the quality of the solutions obtained, e.g., by finding the true ranking of kth best approximate solution when all possible solutions are considered exhaustively. To tackle this statistical issue, we provide a systematic method starting with a scaling function generated from the fininte number of high- ranking solutions followed by a convergent iterative mapping. This method, useful in a variant of the directed paths in random media problem proposed here, can also provide a statistical significance assessment for one of the most important proteomic tasks - - peptide sequencing using tandem mass spectrometry data.

  6. MHC class I–associated peptides derive from selective regions of the human genome

    Science.gov (United States)

    Pearson, Hillary; Granados, Diana Paola; Durette, Chantal; Bonneil, Eric; Courcelles, Mathieu; Rodenbrock, Anja; Laverdure, Jean-Philippe; Côté, Caroline; Thibault, Pierre

    2016-01-01

    MHC class I–associated peptides (MAPs) define the immune self for CD8+ T lymphocytes and are key targets of cancer immunosurveillance. Here, the goals of our work were to determine whether the entire set of protein-coding genes could generate MAPs and whether specific features influence the ability of discrete genes to generate MAPs. Using proteogenomics, we have identified 25,270 MAPs isolated from the B lymphocytes of 18 individuals who collectively expressed 27 high-frequency HLA-A,B allotypes. The entire MAP repertoire presented by these 27 allotypes covered only 10% of the exomic sequences expressed in B lymphocytes. Indeed, 41% of expressed protein-coding genes generated no MAPs, while 59% of genes generated up to 64 MAPs, often derived from adjacent regions and presented by different allotypes. We next identified several features of transcripts and proteins associated with efficient MAP production. From these data, we built a logistic regression model that predicts with good accuracy whether a gene generates MAPs. Our results show preferential selection of MAPs from a limited repertoire of proteins with distinctive features. The notion that the MHC class I immunopeptidome presents only a small fraction of the protein-coding genome for monitoring by the immune system has profound implications in autoimmunity and cancer immunology. PMID:27841757

  7. Glucagon-like peptide-1 and its class B G Protein-coupled receptors: A long march to therapeutic successes.

    NARCIS (Netherlands)

    de Graaf, C.; Donnely, D.; Wootten, D.; Lau, J.; Sexton, P.M.; Miller, L.J.; Ahn, J.M.; Liao, J.; Fletcher, M.M.; Yang, D.; Brown, A.J.; Zhou, C.; Deng, J.; Wang, M.W.

    2016-01-01

    Theglucagon-likepeptide (GLP)-1receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secretedfromthreemajor tissues inhumans,enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which

  8. Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07

    NARCIS (Netherlands)

    Marino, Fabio; Mommen, Geert P M; Jeko, Anita; Meiring, Hugo D; van Gaans-van den Brink, Jacqueline A M; Scheltema, Richard A; van Els, Cécile A C M; Heck, Albert J R

    Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA

  9. A cephalometric analysis of Class II dentate subjects to establish a formula to determine the occlusal plane in Class II edentate subjects: A neo adjunct.

    Science.gov (United States)

    Sinha, Nikita; Reddy, K Mahendranadh; Gupta, Nidhi; Shastry, Y M

    2017-01-01

    Occlusal plane (OP) differs considerably in participants with skeletal Class I and Class II participants. In this study, cephalometrics has been used to help in the determination of orientation of the OP utilizing the nonresorbable bony anatomic landmarks in skeletal Class II participants and an attempt has been made to predict and examine the OP in individuals with skeletal class II jaw relationship. One hundred dentulous participants with skeletal Class II malocclusion who came to the hospital for correcting their jaw relationship participated in the study. Their right lateral cephalogram was taken using standardized procedures, and all the tracings were manually done by a single trained examiner. The cephalograms which were taken for the diagnostic purpose were utilized for the study, and the patient was not exposed to any unnecessary radiation. The numerical values obtained from the cephalograms were subjected to statistical analysis. Pearson's correlation of orientation of the OP in Class II edentulous participants. Pearson's correlation coefficient and linear regression analysis were performed, and a high correlation was found between A2 and (A2 + B2)/(B2 + C2) with " r " value of 0.5. A medium correlation was found between D2 and (D2 + E2)/(E2 + F2) with " r " value of 0.42. The formula obtained for posterior reference frame through linear regression equation was y = 0.018* × +0.459 and the formula obtained for anterior reference frame was y1 = 0.011* × 1 + 0.497. It was hypothesized that by substituting these formulae in the cephalogram obtained from the Class II edentate individual, the OP can be obtained and verified. It was concluded that cephalometrics can be useful in examining the orientation of OP in skeletal Class II participants.

  10. Coordination of two high-affinity hexamer peptides to copper(II) and palladium(II) models of the peptide-metal chelation site on IMAC resins.

    Science.gov (United States)

    Chen, Y; Pasquinelli, R; Ataai, M; Koepsel, R R; Kortes, R A; Shepherd, R E

    2000-03-20

    The coordination of peptides Ser-Pro-His-His-Gly-Gly (SPHHGG) and (His)6 (HHHHHH) to [PdII(mida)(D2O)] (mida2- = N-methyliminodiacetate) was studied by 1H NMR as model reactions for CuII(iminodiacetate)-immobilized metal affinity chromatography (IMAC) sites. This is the first direct physical description of peptide coordination for IMAC. A three-site coordination is observed which involves the first, third, and fourth residues along the peptide chain. The presence of proline in position 2 of SPHHGG achieves the best molecular mechanics and bonding angles in the coordinated peptide and enhances the interaction of the serine amino nitrogen. Histidine coordination of H1, H3, and H4 of (His)6 and H3 and H4 of SPHHGG was detected by 1H NMR contact shifts and H/D exchange of histidyl protons. The EPR spectra of SPHHGG and HHHHHH attached to the [CuII(mida)] unit were obtained for additional modeling of IMAC sites. EPR parameters of the parent [Cu(mida)(H2O)2] complex are representative: gzz = 2.31; gyy = 2.086; gxx = 2.053; A parallel = 161G; AN = 19G (three line, one N coupling). Increased rhombic distortion is detected relative to the starting aqua complex in the order of [Cu(mida)L] for distortion of HHHHHH > SPHHGG > (H2O)2. The lowering of symmetry is also seen in the decrease in the N-shf coupling, presumably to the imino nitrogen of mida2- in the order 19 G (H2O), 16 G (SPHHGG) and 11 G (HHHHHH). Visible spectra of the [Cu(mida)(SPHHGG)] and [Cu(mida)(HHHHHH)] as a function of pH indicate coordination of one histidyl donor at ca. 4.5, two in the range of pH 5-7, and two chelate ring attachments involving the terminal amino donor for SPHHGG or another histidyl donor of HHHHHH in the pH domain of 7-8 in agreement with the [PdII(mida)L] derivatives which form the two-chelate-ring attachment even at lower pH as shown by the 1H NMR methods.

  11. Cleavage specificity analysis of six type II transmembrane serine proteases (TTSPs using PICS with proteome-derived peptide libraries.

    Directory of Open Access Journals (Sweden)

    Olivier Barré

    Full Text Available Type II transmembrane serine proteases (TTSPs are a family of cell membrane tethered serine proteases with unclear roles as their cleavage site specificities and substrate degradomes have not been fully elucidated. Indeed just 52 cleavage sites are annotated in MEROPS, the database of proteases, their substrates and inhibitors.To profile the active site specificities of the TTSPs, we applied Proteomic Identification of protease Cleavage Sites (PICS. Human proteome-derived database searchable peptide libraries were assayed with six human TTSPs (matriptase, matriptase-2, matriptase-3, HAT, DESC and hepsin to simultaneously determine sequence preferences on the N-terminal non-prime (P and C-terminal prime (P' sides of the scissile bond. Prime-side cleavage products were isolated following biotinylation and identified by tandem mass spectrometry. The corresponding non-prime side sequences were derived from human proteome databases using bioinformatics. Sequencing of 2,405 individual cleaved peptides allowed for the development of the family consensus protease cleavage site specificity revealing a strong specificity for arginine in the P1 position and surprisingly a lysine in P1' position. TTSP cleavage between R↓K was confirmed using synthetic peptides. By parsing through known substrates and known structures of TTSP catalytic domains, and by modeling the remainder, structural explanations for this strong specificity were derived.Degradomics analysis of 2,405 cleavage sites revealed a similar and characteristic TTSP family specificity at the P1 and P1' positions for arginine and lysine in unfolded peptides. The prime side is important for cleavage specificity, thus making these proteases unusual within the tryptic-enzyme class that generally has overriding non-prime side specificity.

  12. Tubulation of Class II MHC Compartments Is Microtubule Dependent and Involves Multiple Endolysosomal Membrane Proteins in Primary Dendritic Cells1

    Science.gov (United States)

    Vyas, Jatin M.; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J. Christopher; Van der Veen, Annemarthe G.; Ploegh, Hidde L.

    2009-01-01

    Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. PMID:17513769

  13. Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells.

    Science.gov (United States)

    Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J Christopher; Van der Veen, Annemarthe G; Ploegh, Hidde L

    2007-06-01

    Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.

  14. Optimization of reagent concentration for radioiodination of rat C-peptide II in development of radioimmunoassay procedure for rats

    Directory of Open Access Journals (Sweden)

    B R Manupriya

    2018-01-01

    Full Text Available Rat C-peptide is a polypeptide molecule made up of 31 amino acids and secreted from pancreas into circulation in two isoforms I and II. Quantification of rat C-peptide II in rat serum is important as it is directly related to the diagnosis of carbohydrate metabolism abnormalities, pancreatic performance analysis, monitoring of hypoglycemia, and diabetes-related illness in rat model. The aim of the present work is to develop a tracer by chloramine-T method for radioimmunoassay (RIA procedure and to determine the optimum amount of chloramine-T required for the preparation of stable radioiodinated product with a specific activity of around 24.97 MBq/μg, corresponding to 1 125I atom per molecule of the peptide. Tyrosylated rat C-peptide II was selected for the radioiodination procedure as rat C-peptide II does not contain either tyrosine or histidine which is mandatory for the incorporation of 125I atom to the rat C-peptide II. Tyrosylated rat C-peptide II was subjected to radioiodination by chloramine-T method with different concentrations of chloramine-T and sodium metabisulfite (MBS to obtain a stable radiolabeled compound. Optimized reaction conditions relating to the concentration of chloramine-T (10 μg and MBS (20 μg yielded a stable 125I-rat C-peptide II with specific activity of 21.01 MBq/μg corresponding to 0.84 125I atoms per molecule of the peptide. Preparation of high integrity tracer of rat C-peptide II was achieved by combining one molecule of oxidant (chloramine-T and two molecule of reductant (MBS.

  15. Detection of autoreactive CD4 T cells using major histocompatibility complex class II dextramers

    Directory of Open Access Journals (Sweden)

    Kuszynski Charles

    2011-07-01

    Full Text Available Abstract Background Tetramers are useful tools to enumerate the frequencies of antigen-specific T cells. However, unlike CD8 T cells, CD4 T cells - especially self-reactive cells - are challenging to detect with major histocompatibility complex (MHC class II tetramers because of low frequencies and low affinities of their T cell receptors to MHC-peptide complexes. Here, we report the use of fluorescent multimers, designated MHC dextramers that contain a large number of peptide-MHC complexes per reagent. Results The utility of MHC dextramers was evaluated in three autoimmune disease models: 1 proteolipid protein (PLP 139-151-induced experimental autoimmune encephalomyelitis in SJL/J (H-2s mice; 2 myelin oligodendrocyte glycoprotein (MOG 35-55-induced experimental autoimmune encephalomyelitis in C57Bl/6 (H-2b mice; and 3 cardiac myosin heavy chain (Myhc-α 334-352-induced experimental autoimmune myocarditis in A/J (H-2a mice. Flow cytometrically, we demonstrate that IAs/PLP 139-151, IAb/MOG 35-55 and IAk/Myhc-α 334-352 dextramers detect the antigen-sensitized cells with specificity, and with a detection sensitivity significantly higher than that achieved with conventional tetramers. Furthermore, we show that binding of dextramers, but not tetramers, is less dependent on the activation status of cells, permitting enumeration of antigen-specific cells ex vivo. Conclusions The data suggest that MHC dextramers are useful tools to track the generation and functionalities of self-reactive CD4 cells in various experimental systems.

  16. 40 CFR 82.19 - Apportionment of baseline consumption allowances for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... allowances for class II controlled substances. 82.19 Section 82.19 Protection of Environment ENVIRONMENTAL... Consumption Controls § 82.19 Apportionment of baseline consumption allowances for class II controlled... Ineos Fluor Americas HCFC-22 2,546,305 Kivlan & Company HCFC-22 2,081,018 MDA Manufacturing HCFC-22 2...

  17. 40 CFR 82.17 - Apportionment of baseline production allowances for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... allowances for class II controlled substances. 82.17 Section 82.17 Protection of Environment ENVIRONMENTAL... Consumption Controls § 82.17 Apportionment of baseline production allowances for class II controlled... 1,759,681 MDA Manufacturing HCFC-22 2,383,835 Solvay Solexis HCFC-142b 6,541,764 [ 74 FR 66446, Dec...

  18. 40 CFR 147.2201 - State-administered program-Class II wells

    Science.gov (United States)

    2010-07-01

    ... Application to Oil, Gas, and Geothermal Resource Operations, sections .051.02.02.000 to .051.02.02.080... wells 147.2201 Section 147.2201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Texas § 147.2201 State-administered program—Class II wells The UIC program for Class II wells in the...

  19. 77 FR 58473 - Minimum Technical Standards for Class II Gaming Systems and Equipment

    Science.gov (United States)

    2012-09-21

    ... to all equipment, including computer, electronic, or other technologic aids used with Class II games..., computer, or other technologic aids in connection with the play of Class II games. This part establishes... gaming system, causes a discontinuance of game play or other component functions. Financial instrument...

  20. Long-term evaluation of Class II subdivision treatment with unilateral maxillary first molar extraction

    NARCIS (Netherlands)

    Livas, Christos; Pandis, Nikolaos; Booij, Johan Willem; Katsaros, Christos; Ren, Yijin

    Objective: To evaluate the long-term effects of asymmetrical maxillary first molar (M1) extraction in Class II subdivision treatment. Materials and Methods: Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0 years; SD, 1.7 years) consecutively treated with the Begg technique

  1. 40 CFR 147.2551 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ..., “Re: Application for Primacy in the Regulation of Class II Injection Wells,” March 8, 1982; (5) Letter... Class II Injection Wells under Section 1425 of the Safe Drinking Water Act,” November 1981; (2) Letter...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  2. 40 CFR 147.3400 - Navajo Indian lands-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... to Operate an Underground Injection Control Program under the Safe Drinking Water Act”, October 11... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Navajo Indian Lands § 147.3400 Navajo Indian lands—Class II wells. The UIC program for Class II injection wells...

  3. Maxillary first molar extraction in Class II malocclusion : Follow-up studies on treatment effects

    NARCIS (Netherlands)

    Livas, Christos

    2015-01-01

    This PhD research investigated treatment effects of extraction of one and two maxillary first molars in Class II subdivision and Class II/1 malocclusion cases respectively from a longer time perspective. Private practice records were scrutinized to evaluate aspects of a treatment technique combining

  4. The effectiveness of different polymerization protocols for class II composite resin restorations.

    NARCIS (Netherlands)

    Jong, L.C.G. de; Opdam, N.J.M.; Bronkhorst, E.M.; Roeters, F.J.M.; Wolke, J.G.C.; Geitenbeek, B.

    2007-01-01

    OBJECTIVES: To investigate the effect of reduced light exposure times on Vickers hardness (VH) of class II composite resin restorations. METHODS: Class II restorations were made in vitro in three 2mm thick increments in a human molar. Two composite resins (Clearfil AP-X; Esthet-X) were polymerized

  5. The Effect of MHC Class II Transactivator on the Growth and Metastasis of Breast Tumors

    Science.gov (United States)

    1999-06-01

    F. Manca, and R. S. Accolla. 1998. HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA...Cestari, A. D’Agostino, ’ A M Megiovanni, F. Manca, and R. S. Accolla. 1998. HLA class II expression in uninducible hepatocarcinoma cells after

  6. H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

    Science.gov (United States)

    Bland, David A; Suarez, Giovanni; Beswick, Ellen J; Sierra, Johanna C; Reyes, Victor E

    2006-01-01

    AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells. PMID:16981259

  7. DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

    Science.gov (United States)

    Murphy, Shawn P; Holtz, Renae; Lewandowski, Nicole; Tomasi, Thomas B; Fuji, Hiroshi

    2002-09-15

    MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA). Analysis of stable hybrids suggests that CIITA expression is repressed by a dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA and class II expression in class II negative L1210 cells, and this effect appears to be restricted to transformed cell lines derived from the early stages of B cell ontogeny. Transient transfection assays demonstrated that the CIITA type III promoter is active in class II(-) L1210 cells, despite the fact that the endogenous gene is not expressed, which suggests that these cells have all of the transacting factors necessary for CIITA transcription. An inverse correlation between methylation of the CIITA transcriptional regulatory region and CIITA expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment activated CIITA expression in class II-negative L1210 cells. Collectively, our results suggest that 1) CIITA gene expression is repressed in class II(-) L1210 cells by methylation of the CIITA upstream regulatory region, and 2) treatment with DNA-alkylating agents overcomes methylation-based silencing of the CIITA gene in L1210 cells.

  8. Glucagon-Like Peptide-1 and Its Class B G Protein–Coupled Receptors: A Long March to Therapeutic Successes

    Science.gov (United States)

    de Graaf, Chris; Donnelly, Dan; Wootten, Denise; Lau, Jesper; Sexton, Patrick M.; Miller, Laurence J.; Ahn, Jung-Mo; Liao, Jiayu; Fletcher, Madeleine M.; Brown, Alastair J. H.; Zhou, Caihong; Deng, Jiejie; Wang, Ming-Wei

    2016-01-01

    The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein–coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a two-domain–binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidic GLP-1R agonists have been hampered, small-molecule modulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders. PMID:27630114

  9. Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa.

    Science.gov (United States)

    Goeury, T; Creary, L E; Brunet, L; Galan, M; Pasquier, M; Kervaire, B; Langaney, A; Tiercy, J-M; Fernández-Viña, M A; Nunes, J M; Sanchez-Mazas, A

    2018-01-01

    With the aim to understand how next-generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well-documented population from sub-Saharan Africa (Mandenka). The results of full-gene NGS-MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity. A comprehensive analysis of exons 2, 3, 4 and 5 nucleotide diversity at the 8 HLA loci revealed remarkable differences among these gene regions, notably a greater variation concentrated in the antigen recognition sites of class I exons 3 and some class II exons 2, likely associated with their peptide-presentation function, a lower diversity of HLA-C exon 3, possibly related to its role as a KIR ligand, and a peculiar molecular diversity of HLA-A exon 2, revealing demographic signals. Based on full-length HLA sequences, we also propose that the most frequent DRB1 allele in the studied population, DRB1*13:04, emerged from an allelic conversion involving 3 potential alleles as donors and DRB1*11:02:01 as recipient. Finally, our analysis revealed a high occurrence of the DRB1*13:04-DQA1*05:05:01-DQB1*03:19 haplotype, possibly resulting from a selective sweep due to protection to Onchorcerca volvulus, a prevalent pathogen in West Africa. This study unveils highly relevant information on the molecular evolution of HLA genes in relation to their immune function, calling for similar analyses in other populations living in contrasting environments. © 2017 The Authors HLA: Immune Response Genetics Published by John Wiley & Sons Ltd.

  10. MHC class II B diversity in blue tits: a preliminary study.

    Science.gov (United States)

    Aguilar, Juan Rivero-de; Schut, Elske; Merino, Santiago; Martínez, Javier; Komdeur, Jan; Westerdahl, Helena

    2013-07-01

    In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were investigated using both PCR-based methods and unamplified genomic DNA with restriction fragment length polymorphism (RFLP) and southern blots. A total of 13 different exon 2 sequences were obtained independently from DNA and/or RNA, thus confirming gene transcription and likely functionality of the genes. Nine out of 13 alleles were found in more than one country, and two alleles appeared in all countries. Positive selection was detected in the region coding for the peptide binding region (PBR). A maximum of three alleles per individual was detected by sequencing and the RFLP pattern consisted of 4-7 fragments, indicating a minimum number of 2-4 loci per individual. A phylogenetic analysis, demonstrated that the blue tit sequences are divergent compared to sequences from other passerines resembling a different MHC lineage than those possessed by most passerines studied to date.

  11. Selection on MHC class II supertypes in the New Zealand endemic Hochstetter's frog.

    Science.gov (United States)

    Lillie, Mette; Grueber, Catherine E; Sutton, Jolene T; Howitt, Robyn; Bishop, Phillip J; Gleeson, Dianne; Belov, Katherine

    2015-04-13

    The New Zealand native frogs, family Leiopelmatidae, are among the most archaic in the world. Leiopelma hochstetteri (Hochstetter's frog) is a small, semi-aquatic frog with numerous, fragmented populations scattered across New Zealand's North Island. We characterized a major histocompatibility complex (MHC) class II B gene (DAB) in L. hochstetteri from a spleen transcriptome, and then compared its diversity to neutral microsatellite markers to assess the adaptive genetic diversity of five populations ("evolutionarily significant units", ESUs). L. hochstetteri possessed very high MHC diversity, with 74 DAB alleles characterized. Extremely high differentiation was observed at the DAB locus, with only two alleles shared between populations, a pattern that was not reflected in the microsatellites. Clustering analysis on putative peptide binding residues of the DAB alleles indicated four functional supertypes, all of which were represented in 4 of 5 populations, albeit at different frequencies. Otawa was an exception to these observations, with only two DAB alleles present. This study of MHC diversity highlights extreme population differentiation at this functional locus. Supertype differentiation was high among populations, suggesting spatial and/or temporal variation in selection pressures. Low DAB diversity in Otawa may limit this population's adaptive potential to future pathogenic challenges.

  12. pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-β peptide

    International Nuclear Information System (INIS)

    Ghalebani, Leila; Wahlström, Anna; Danielsson, Jens; Wärmländer, Sebastian K.T.S.; Gräslund, Astrid

    2012-01-01

    Highlights: ► Cu(II) and Zn(II) display pH-dependent binding to the Aβ(1–40) peptide. ► At pH 7.4 both metal ions display residue-specific binding to the Aβ peptide. ► At pH 5.5 the binding specificity is lost for Zn(II). ► Differential Cu(II) and Zn(II) binding may help explain metal-induced AD toxicity. -- Abstract: Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer’s disease amyloid plaques. The amyloid-β (Aβ) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with 15 N- and 13 C, 15 N-labeled Aβ(1–40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to Aβ may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the Aβ peptide under these conditions.

  13. Application of Ni(II-assisted peptide bond hydrolysis to non-enzymatic affinity tag removal.

    Directory of Open Access Journals (Sweden)

    Edyta Kopera

    Full Text Available In this study, we demonstrate a non-enzymatic method for hydrolytic peptide bond cleavage, applied to the removal of an affinity tag from a recombinant fusion protein, SPI2-SRHWAP-His(6. This method is based on a highly specific Ni(II reaction with (S/TXHZ peptide sequences. It can be applied for the protein attached to an affinity column or to the unbound protein in solution. We studied the effect of pH, temperature and Ni(II concentration on the efficacy of cleavage and developed an analytical protocol, which provides active protein with a 90% yield and ∼100% purity. The method works well in the presence of non-ionic detergents, DTT and GuHCl, therefore providing a viable alternative for currently used techniques.

  14. Uncovering the Peptide-Binding Specificities of HLA-C: A General Strategy To Determine the Specificity of Any MHC Class I Molecule

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette

    2014-01-01

    MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide...... library approach with a peptide-HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices...... representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C-specific peptide...

  15. Limnonectins: a new class of antimicrobial peptides from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis).

    Science.gov (United States)

    Wu, Youjia; Wang, Lei; Zhou, Mei; Ma, Chengbang; Chen, Xiaole; Bai, Bing; Chen, Tianbao; Shaw, Chris

    2011-06-01

    Amphibian skin secretions are rich sources of biologically-active peptides with antimicrobial peptides predominating in many species. Several studies involving molecular cloning of biosynthetic precursor-encoding cDNAs from skin or skin secretions have revealed that these exhibit highly-conserved domain architectures with an unusually high degree of conserved nucleotide and resultant amino acid sequences within the signal peptides. This high degree of nucleotide sequence conservation has permitted the design of primers complementary to such sites facilitating "shotgun" cloning of skin or skin secretion-derived cDNA libraries from hitherto unstudied species. Here we have used such an approach using a skin secretion-derived cDNA library from an unstudied species of Chinese frog - the Fujian large-headed frog, Limnonectes fujianensis - and have discovered two 16-mer peptides of novel primary structures, named limnonectin-1Fa (SFPFFPPGICKRLKRC) and limnonectin-1Fb (SFHVFPPWMCKSLKKC), that represent the prototypes of a new class of amphibian skin antimicrobial peptide. Unusually these limnonectins display activity only against a Gram-negative bacterium (MICs of 35 and 70 μM) and are devoid of haemolytic activity at concentrations up to 160 μM. Thus the "shotgun" cloning approach described can exploit the unusually high degree of nucleotide conservation in signal peptide-encoding domains of amphibian defensive skin secretion peptide precursor-encoding cDNAs to rapidly expedite the discovery of novel and functional defensive peptides in a manner that circumvents specimen sacrifice without compromising robustness of data. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus).

    Science.gov (United States)

    Scherman, Kristin; Råberg, Lars; Westerdahl, Helena

    2014-05-01

    The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.

  17. Applications of neural network prediction of conformational states for small peptides from spectra and of fold classes

    DEFF Research Database (Denmark)

    Bohr, Henrik; Røgen, Peter; Jalkanen, Karl J.

    2001-01-01

    but already at this stage they could be compared with reasonable agreements to experiments. The neural networks are shown to be good in distinguishing the different conformers of the small alanine peptides. especially when in the gas phase. Also the task of predicting protein fold-classes, defined from line...... to construct vibrational spectra for each of the conformational states with low energy. From the spectra, neural networks could be trained to distinguish between the various states and thus be able to generate a larger set of relevant structures and their relation to secondary structures of the peptides....... The calculations were done both with solvent atoms (up to ten water molecules) and without, and hence the neural networks could be used to monitor the influence of the solvent on hydrogen bond formation. The calculations at this stage only involved very short peptide fragments of a few alanine amino acids...

  18. New horizons in mouse immunoinformatics: reliable in silico prediction of mouse class I histocompatibility major complex peptide binding affinity.

    Science.gov (United States)

    Hattotuwagama, Channa K; Guan, Pingping; Doytchinova, Irini A; Flower, Darren R

    2004-11-21

    Quantitative structure-activity relationship (QSAR) analysis is a main cornerstone of modern informatic disciplines. Predictive computational models, based on QSAR technology, of peptide-major histocompatibility complex (MHC) binding affinity have now become a vital component of modern day computational immunovaccinology. Historically, such approaches have been built around semi-qualitative, classification methods, but these are now giving way to quantitative regression methods. The additive method, an established immunoinformatics technique for the quantitative prediction of peptide-protein affinity, was used here to identify the sequence dependence of peptide binding specificity for three mouse class I MHC alleles: H2-D(b), H2-K(b) and H2-K(k). As we show, in terms of reliability the resulting models represent a significant advance on existing methods. They can be used for the accurate prediction of T-cell epitopes and are freely available online ( http://www.jenner.ac.uk/MHCPred).

  19. MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

    OpenAIRE

    Garman, Lori; Dumas, Eric K.; Kurella, Sridevi; Hunt, Jonathan J.; Crowe, Sherry R.; Nguyen, Melissa L.; Cox, Philip M.; James, Judith A.; Farris, A. Darise

    2012-01-01

    Anthrax Lethal Toxin consists of Protective Antigen (PA) and Lethal Factor (LF), and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class I...

  20. Use of cyanoacrylate as barrier in guided tissue regeneration in class II furcation defects

    Directory of Open Access Journals (Sweden)

    Carmen L Mueller Storrer

    2014-01-01

    Full Text Available The guided bone regeneration (GBR is a technique that uses resorbable and non-resorbable membranes in association with other filling biomaterials. GBR is one of the optional treatments for therapy of class II furcation defects. The current case report evaluates clinically and radiographically the use of the cyanoacrylate membrane (Glubran ®2 associated with organic bovine bone (GenOx for the treatment of vestibular class II furcation defect on the lower left molar. Conclusion: The GBR is an option in the treatment of vestibular class II furcation defects and cyanoacrylate surgical glue, acting as a mechanic barrier and providing an efficient stability for the graft.

  1. The P9 pocket of HLA-DQ2 (non-Aspbeta57) has no particular preference for negatively charged anchor residues found in other type 1 diabetes-predisposing non-Aspbeta57 MHC class II molecules

    DEFF Research Database (Denmark)

    Quarsten, H; Paulsen, G; Johansen, B H

    1998-01-01

    Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno......-pathogenic peptides. Recent studies in man and mouse have revealed that some type 1 diabetes-predisposing non-Aspbeta57 class II molecules (i.e. DQ8, DR4Dw15 and I-Ag7) preferentially bind peptides with a negatively charged anchor residue at P9. It has been suggested that this is a common feature of type 1 diabetes......-predisposing class II molecules. The molecular explanation for such a phenomenon could be that class II beta chains with Aspbeta57 form a salt bridge between Aspbeta57 and a conserved Arg of the a chain, whereas in non-Aspbeta57 molecules the Arg is unopposed and free to interact with negatively charged P9 peptide...

  2. Pharyngeal airway dimensions in skeletal class II: A cephalometric growth study

    International Nuclear Information System (INIS)

    Uslu-Akcam, Ozge

    2017-01-01

    This retrospective study aimed to evaluate the nasopharyngeal and oropharyngeal dimensions of individuals with skeletal class II, division 1 and division 2 patterns during the pre-peak, peak, and post-peak growth periods for comparison with a skeletal class I control group. Totally 124 lateral cephalograms (47 for skeletal class I; 45 for skeletal class II, division 1; and 32 for skeletal class II, division 2) in pre-peak, peak, and post-peak growth periods were selected from the department archives. Thirteen landmarks, 4 angular and 4 linear measurements, and 4 proportional calculations were obtained. The ANOVA and Duncan test were applied to compare the differences among the study groups during the growth periods. Statistically significant differences were found between the skeletal class II, division 2 group and other groups for the gonion-gnathion/sella-nasion angle. The sella-nasion-B-point angle was different among the groups, while the A-point-nasion-B-point angle was significantly different for all 3 groups. The nasopharyngeal airway space showed a statistically significant difference among the groups throughout the growth periods. The interaction among the growth periods and study groups was statistically significant regarding the upper oropharyngeal airway space measurement. The lower oropharyngeal airway space measurement showed a statistically significant difference among the groups, with the smallest dimension observed in the skeletal class II, division 2 group. The naso-oropharyngeal airway dimensions showed a statistically significant difference among the class II, division 1; class II, division 2; and class I groups during different growth periods

  3. Pharyngeal airway dimensions in skeletal class II: A cephalometric growth study

    Energy Technology Data Exchange (ETDEWEB)

    Uslu-Akcam, Ozge [Clinic of Orthodontics, Ministry of Health, Tepebasi Oral and Dental Health Hospital, Ankara (Turkmenistan)

    2017-03-15

    This retrospective study aimed to evaluate the nasopharyngeal and oropharyngeal dimensions of individuals with skeletal class II, division 1 and division 2 patterns during the pre-peak, peak, and post-peak growth periods for comparison with a skeletal class I control group. Totally 124 lateral cephalograms (47 for skeletal class I; 45 for skeletal class II, division 1; and 32 for skeletal class II, division 2) in pre-peak, peak, and post-peak growth periods were selected from the department archives. Thirteen landmarks, 4 angular and 4 linear measurements, and 4 proportional calculations were obtained. The ANOVA and Duncan test were applied to compare the differences among the study groups during the growth periods. Statistically significant differences were found between the skeletal class II, division 2 group and other groups for the gonion-gnathion/sella-nasion angle. The sella-nasion-B-point angle was different among the groups, while the A-point-nasion-B-point angle was significantly different for all 3 groups. The nasopharyngeal airway space showed a statistically significant difference among the groups throughout the growth periods. The interaction among the growth periods and study groups was statistically significant regarding the upper oropharyngeal airway space measurement. The lower oropharyngeal airway space measurement showed a statistically significant difference among the groups, with the smallest dimension observed in the skeletal class II, division 2 group. The naso-oropharyngeal airway dimensions showed a statistically significant difference among the class II, division 1; class II, division 2; and class I groups during different growth periods.

  4. Availability of endogenous peptides limits expression of an M3a-Ld major histocompatibility complex class I chimera

    Science.gov (United States)

    1994-01-01

    Taking advantage of our understanding of the peptide specificity of the major histocompatibility complex class I-b molecule M3a, we sought to determine why these molecules are poorly represented on the cell surface. To this end we constructed a chimeric molecule with the alpha 1 and alpha 2 domains of M3a and alpha 3 of Ld thereby allowing use of available monoclonal antibodies to quantify surface expression. Transfected, but not control, B10.CAS2 (H-2M3b) cells were lysed readily by M3a-restricted monoclonal cytotoxic T lymphocytes. Thus, the chimera bound, trafficked, and presented endogenous mitochondrial peptides. However, despite high levels of M3a-Ld mRNA, transfectants were negative by surface staining. This finding was consistent with inefficient trafficking to the cell surface. Incubation at 26 degrees C, thought to permit trafficking of unoccupied heavy (H) chains, resulted in detectable cell surface expression of chimeric molecules. Incubation with exogenous peptide at 26 degrees C (but not at 37 degrees C) greatly enhanced expression of M3a-Ld molecules in a dose- dependent manner, suggesting stabilization of unoccupied molecules. Stable association of beta 2-microglobulin with the chimeric H chain was observed in labeled cell lysates only in the presence of exogenous specific peptide, indicating that peptide is required for the formation of a ternary complex. These results indicate that surface expression of M3a-Ld is limited largely by the steady-state availability of endogenous peptides. Since most known M3a-binding peptides are N- formylated, native M3a may normally be expressed at high levels only during infection by intracellular bacteria. PMID:8270862

  5. Design of a peptidic turn with high affinity for HgII

    DEFF Research Database (Denmark)

    Pires, Sara; Habjanic, Jelena; Sezer, Murat

    2012-01-01

    A four amino acid peptide containing the ß-turn template dPro-Pro in the middle and two cysteines (Cys) in the terminal positions (CdPPC) has been synthesized and its mercury(II) coordination properties studied using different spectroscopic methods. The UV-vis, CD, (199m)Hg PAC, and Raman...... spectroscopic studies indicate the binding of Hg(II) to the two Cys, forming the dithiolatemercury(II) complex Hg(CdPPC). Electrospray ionization mass spectrometry corroborates the 1:1 complex formation. A log K = 40.0 was determined for the formation constant of the Hg(CdPPC) complex using competition...... potentiometric studies. Replacement of the dPro-Pro motif by a Pro-Pro unit generated a peptide (CPPC) capable of forming a similar species [Hg(CPPC)] but showing a lower affinity for Hg(II) (at least 3-3.5 orders of magnitude lower). The introduction of the dPro-Pro motif is crucial to induce the folding...

  6. An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Singh, Shalini; Mörgelin, Matthias; Schmidtchen, Artur; Malmsten, Martin

    2014-05-01

    Host defense peptides are key components of the innate immune system, providing multi-facetted responses to invading pathogens. Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock. The peptide displays antimicrobial effects through direct membrane disruption, also at physiological salt concentration and in the presence of plasma and serum. Biophysical investigations of model lipid membranes showed the antimicrobial action of GKS26 to be mirrored by peptide incorporation into, and disordering of, bacterial lipid membranes. GKS26 furthermore binds extensively to bacterial lipopolysaccharide (LPS), as well as its endotoxic lipid A moiety, and displays potent anti-inflammatory effects, both in vitro and in vivo. Thus, for mice challenged with ip injection of LPS, GKS26 suppresses pro-inflammatory cytokines, reduces vascular leakage and infiltration in lung tissue, and normalizes coagulation. Together, these findings suggest that GKS26 may be of interest for further investigations as therapeutic against severe infections and septic shock. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Trans-species polymorphism and selection in the MHC class II DRA genes of domestic sheep.

    Directory of Open Access Journals (Sweden)

    Keith T Ballingall

    Full Text Available Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries. We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201 differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901, which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T

  8. Similar hormone-rich peptides from thyroglobulins of five vertebrate classes

    International Nuclear Information System (INIS)

    Kim, P.S.; Dunn, J.T.; Kaiser, D.L.

    1984-01-01

    Thyroglobulins (Tgs) were purified from five species (rat, chicken, turtle, frog, and goldfish), each representing a different vertebrate class. On reduction with mercaptoethanol, each Tg produced five major iodopeptides, designated A-E, with ranges of estimated molecular mass, in kilodaltons (K), as follows: A, more than 300K; B, 210-280K; C, 30-42K; D, 19-28K; and E, 10-23K. Of these, the two smallest, D and E, had 40-80% of their iodine as iodothyronine, compared with 15-20% for the parent Tgs. They contained 25-63% of Tg's total iodothyronines but only a few percent of its peptide material. Calculations from amino acid analyses and iodine contents showed approximately 1 mol each of D and E/mol 660,000 dalton Tg. In comparisons of amino acid compositions by cluster analysis, iodopeptides D and E resembled each other and their counterparts in other species more than they resembled their parent Tgs. Also, the Tgs from different species were more similar to each other and to iodopeptides D and E than to nonthyroidal proteins randomly selected from the literature. 125 was injected into rats and turtles, and compared its distribution among the iodopeptides to that of 127 I. These dual isotope experiments showed that as Tg was iodinated in vivo, iodopeptide B decreased both in molecular size and in its share of Tg's iodine, while the sum of iodopeptides D and E increased, indicating that B may be the precursor of D and E. In vivo iodination of rat Tg with 125 I for different periods of time suggested that iodopeptide E and its iodothyronines are derived from a larger portion of the Tg molecule, perhaps iodopeptide B. The amount of 125 I in iodopeptide D also increased with time

  9. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...... by herbimycin A. MHC class II ligation on B-lymphocytes resulted in cell death, which was both qualitatively distinct from Fas-induced apoptosis and partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family...

  10. Hall effects on hydromagnetic Couette flow of Class-II in a rotating ...

    African Journals Online (AJOL)

    International Journal of Engineering, Science and Technology ... Couette flow of class-II of a viscous, incompressible and electrically conducting fluid with ... Numerical solution of energy equation and numerical values of rate of heat transfer at ...

  11. Modified geometry three-layered tablet as a platform for class II ...

    African Journals Online (AJOL)

    Modified geometry three-layered tablet as a platform for class II drugs zero-order release system. Abdullah Monahi Albogami, Mustafa E. Omer, Abdulkareem M. Al Bekairy, Abdulmalik Alkatheri, Alaa Eldeen B. Yassin ...

  12. 25 CFR 547.6 - What are the minimum technical standards for enrolling and enabling Class II gaming system...

    Science.gov (United States)

    2010-04-01

    ... and enabling Class II gaming system components? 547.6 Section 547.6 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED... enabling Class II gaming system components? (a) General requirements. Class II gaming systems shall provide...

  13. Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

    Directory of Open Access Journals (Sweden)

    Caixia Gao

    2017-12-01

    Full Text Available Swine leukocyte antigen (SLA class I molecules play a crucial role in generating specific cellular immune responses against viruses and other intracellular pathogens. They mainly bind and present antigens of intracellular origin to circulating MHC I-restricted cytotoxic T lymphocytes (CTLs. Binding of an appropriate epitope to an SLA class I molecule is the single most selective event in antigen presentation and the first step in the killing of infected cells by CD8+ CTLs. Moreover, the antigen epitopes are strictly restricted to specific SLA molecules. In this study, we constructed SLA class I complexes in vitro comprising viral epitope peptides, the extracellular region of the SLA-1 molecules, and β2-microglobulin (β2m using splicing overlap extension polymerase chain reaction (SOE-PCR. The protein complexes were induced and expressed in an Escherichia coli prokaryotic expression system and subsequently purified and refolded. Specific binding of seven SLA-1 proteins to one classical swine fever virus (CSFV and four porcine reproductive and respiratory syndrome virus (PRRSV epitope peptides was detected by enzyme-linked immunosorbent assay (ELISA-based method. The SLA-1∗13:01, SLA-1∗11:10, and SLA-1∗11:01:02 proteins were able to bind specifically to different CTL epitopes of CSFV and PRRSV and the MHC restrictions of the five epitopes were identified. The fixed combination of Asn151Val152 residues was identified as the potentially key amino acid residues influencing the binding of viral several CTL epitope peptides to SLA-1∗13:01 and SLA-1∗04:01:01 proteins. The more flexible pocket E in the SLA-1∗13:01 protein might have fewer steric limitations and therefore be able to accommodate more residues of viral CTL epitope peptides, and may thus play a critical biochemical role in determining the peptide-binding motif of SLA-1∗13:01. Characterization of the binding specificity of peptides to SLA class I molecules provides an

  14. Major histocompatibility complex class II compatibility, but not class I, predicts mate choice in a bird with highly developed olfaction.

    Science.gov (United States)

    Strandh, Maria; Westerdahl, Helena; Pontarp, Mikael; Canbäck, Björn; Dubois, Marie-Pierre; Miquel, Christian; Taberlet, Pierre; Bonadonna, Francesco

    2012-11-07

    Mate choice for major histocompatibility complex (MHC) compatibility has been found in several taxa, although rarely in birds. MHC is a crucial component in adaptive immunity and by choosing an MHC-dissimilar partner, heterozygosity and potentially broad pathogen resistance is maximized in the offspring. The MHC genotype influences odour cues and preferences in mammals and fish and hence olfactory-based mate choice can occur. We tested whether blue petrels, Halobaena caerulea, choose partners based on MHC compatibility. This bird is long-lived, monogamous and can discriminate between individual odours using olfaction, which makes it exceptionally well suited for this analysis. We screened MHC class I and II B alleles in blue petrels using 454-pyrosequencing and quantified the phylogenetic, functional and allele-sharing similarity between individuals. Partners were functionally more dissimilar at the MHC class II B loci than expected from random mating (p = 0.033), whereas there was no such difference at the MHC class I loci. Phylogenetic and non-sequence-based MHC allele-sharing measures detected no MHC dissimilarity between partners for either MHC class I or II B. Our study provides evidence of mate choice for MHC compatibility in a bird with a high dependency on odour cues, suggesting that MHC odour-mediated mate choice occurs in birds.

  15. Post-Retention Changes in Class II Correction With the Forsus (trademark) Appliance

    Science.gov (United States)

    2015-06-01

    level of significance was defined when p≤0.02. Error of Measurement Study In dentistry , when interpreting the results of a study, the investigator...Class II malocclusion in children 8-10 years of age. Angle Orthod. 1981;51:177-202. 4) Jones G, Buschang PH, Kim KB, Oliver DR. Class II non...2: Dahlberg’s error, Bland-Altman method, and Kappa coefficient. Restorative Dentistry and Endodontics 2013;38;3;182-185. 39) Springate, SD. The

  16. Stability of class II subdivision malocclusion treatment with 3 and 4 premolar extractions

    OpenAIRE

    Janson, Guilherme; Araki, Janine; Estelita, S?rgio; Camardella, Leonardo T

    2014-01-01

    Background The purpose of this study was to compare the occlusal stability of class II subdivision malocclusion treatment with 3 and 4 first premolar extractions. A sample of 156 dental casts from 52 patients with class II subdivision malocclusion was divided into two groups according to the extraction protocol. Group 1 comprised 24 patients treated with 3 premolar extractions and group 2 included 28 patients treated with 4 premolar extractions. Methods Peer assessment rating (PAR) indexes we...

  17. MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency

    NARCIS (Netherlands)

    Buch, Thorsten; Polic, Bojan; Clausen, Björn E.; Weiss, Susanne; Akilli-Ozturk, Ozlem; Chang, Cheong-Hee; Flavell, Richard; Schulz, Ansgar; Jonjic, Stipan; Waisman, Ari; Förster, Irmgard

    2006-01-01

    MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine

  18. 49 CFR 238.317 - Class II brake test.

    Science.gov (United States)

    2010-10-01

    ....315(a)(1); (3) When previously tested units (i.e., cars that received a Class I brake test within the... hours) are added to the train; (4) When cars or equipment are removed from the train; and (5) When an... locomotives that utilize an electric signal to communicate a service brake application and only a pneumatic...

  19. 78 FR 37114 - Self-Regulation of Class II Gaming

    Science.gov (United States)

    2013-06-20

    ... Commission) is revising its rules concerning the issuance of certificates for tribal self-regulation of Class... Office of Self Regulation's recommendation and report; and to correct referencing errors in two of its... certificate of self- regulation. 25 U.S.C. 2710(c). The Act authorizes the Commission to ``promulgate such...

  20. Effect of timing on the outcomes of 1-phase nonextraction therapy of Class II malocclusion.

    Science.gov (United States)

    Baccetti, Tiziano; Franchi, Lorenzo; Kim, Ludia H

    2009-10-01

    The aim of this cephalometric study was to evaluate the role of timing in relation to skeletal maturity on the outcomes of nonextraction comprehensive Class II therapy. Three samples of patients with Class II Division 1 malocclusion were treated with headgear combined with fixed appliances and Class II elastics. Lateral cephalograms were taken of all subjects before therapy (T1) and at an average interval of 6 months after therapy (T2). The first sample (23 subjects) was treated before the pubertal growth spurt, the second sample (24 subjects) received therapy during the pubertal growth spurt, and the third sample (13 subjects) was treated at a postpubertal stage of development. The average T1 to T2 interval was approximately 30 months for all patients, with an average treatment duration of 24 months. Longitudinal observations of a group of 17 subjects with untreated Class II malocclusions were compared with the treated groups at the 3 skeletal maturation intervals with nonparametric statistics. Class II treatment before or during the pubertal growth spurt induced significant favorable skeletal changes (restricted maxillary advancement in prepubertal patients and enhanced mandibular growth in pubertal patients). Patients treated after the pubertal growth spurt had only significant dentoalveolar changes. The greatest amount of dentoskeletal correction of Class II malocclusion with 1-phase nonextraction treatment occurred in patients treated during the pubertal growth spurt.

  1. Factors affecting buccal corridor space in Angle′s Class II Division 1 malocclusion

    Directory of Open Access Journals (Sweden)

    Rashmi Bhat

    2014-01-01

    Full Text Available Background and Objectives: Buccal corridor space has been thought of primarily in terms of maxillary width, but there is also evidence that they are heavily influenced by the antero-posterior position of maxilla. The present study was undertaken with an aim of evaluating and comparing the dental and skeletal factors related to buccal corridor space in individuals having Class I and Class II Division 1 malocclusions. Materials and Methods: A total of 80 subjects of which 40 were males and 40 were females in the age group of 20-30 years were selected as per inclusion criteria and were grouped as Group I having Class I malocclusion and as Group II having Class II malocclusions based on angle ANB. 12 linear and 2 angular cephalometric measurements and 4 study cast measurements were used to correlate with the buccal corridor linear ratio (BCLR, calculated on smile photograph using the Adobe Photoshop 7.0 software (Adobe Systems Inc., San Jose, California, USA. The data obtained was statistically evaluated using independent t-test and multiple linear regression analysis. Result: Buccal corridor space is larger in individuals with Class II Division 1 malocclusion when compared with individuals with Class I malocclusions. There exists a significant difference in buccal corridor space between males and females. Conclusion: The present study helps in establishing the correlation between certain factors and the amount of buccal corridor space in individuals having skeletal Class II pattern.

  2. Facial attractiveness of skeletal class I and class II malocclusion as perceived by laypeople, patients and clinicians.

    Science.gov (United States)

    Pace, Michela; Cioffi, Iacopo; D'antò, Vincenzo; Valletta, Alessandra; Valletta, Rosa; Amato, Massimo

    2018-06-01

    Physical attractiveness is dependent on facial appearance. The facial profile plays a crucial role in facial attractiveness and can be improved with orthodontic treatment. The aesthetic assessment of facial appearance may be influenced by the cultural background and education of the assessor and dependent upon the experience level of dental professionals. This study aimed to evaluate how the sagittal jaw relationship in Class I and Class II individuals affects facial attractiveness, and whether the assessor's professional education and background affect the perception of facial attractiveness. Facial silhouettes simulating mandibular retrusion, maxillary protrusion, mandibular retrusion combined with maxillary protrusion, bimaxillary protrusion and severe bimaxillary protrusion in class I and class II patients were assessed by five groups of people with different backgrounds and education levels (i.e., 23 expert orthodontists, 21 orthodontists, 15 maxillofacial surgeons, 19 orthodontic patients and 28 laypeople). Straight facial profiles were judged to be more attractive than convex profiles due to severe mandibular retrusion and to mandibular retrusion combined with maxillary protrusion (all Pattractive by clinicians than by patients and laypeople (all Pattractive than Class I profiles. The assessment of facial attractiveness is dependent on the assessor's education and background. Laypeople and patients are considerably less sensitive to abnormal sagittal jaw relationships than orthodontists.

  3. Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases

    Science.gov (United States)

    Haupt, V. Joachim; Schroeder, Michael; Labudde, Dirk

    2018-01-01

    The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The one unifying aspect of both classes is their function of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most compact ATP binding motifs characteristic for each Class. Geometric analysis shows a structural rearrangement of the Backbone Brackets upon ATP binding, indicating a general mechanism of all Class I structures. Regarding the origin of aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS classes is the result of their primordial forms, called Protozymes, being encoded on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers were traced back to the proposed Protozymes and their more efficient successors, the Urzymes. Both structural motifs can be observed as pairs of residues in contemporary structures and it seems that the time of their addition, indicated by their placement in the ancient aaRS, coincides with the evolutionary trace of Proto- and Urzymes. PMID:29659563

  4. Modes of salmonid MHC class I and II evolution differ from the primate paradigm

    NARCIS (Netherlands)

    Shum, B.P.; Guethlein, L.; Flodin, L.R.; Adkison, M.A.; Hedrick, R.P.; Nehring, R.B.; Stet, R.J.M.; Secombes, C.; Parham, P.

    2001-01-01

    Rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) represent two salmonid genera separated for 15-20 million years. cDNA sequences were determined for the classical MHC class I heavy chain gene UBA and the MHC class II β-chain gene DAB from 15 rainbow and 10 brown trout. Both genes

  5. Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lund, Ole; Nielsen, Morten

    2008-01-01

    Several accurate prediction systems have been developed for prediction of class I major histocompatibility complex (MHC):peptide binding. Most of these are trained on binding affinity data of primarily 9mer peptides. Here, we show how prediction methods trained on 9mer data can be used for accurate...

  6. Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography.

    Science.gov (United States)

    Baysal, Asli; Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

    2013-06-01

    To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients.

  7. Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation.

    Science.gov (United States)

    Akiyama, Y; Zicht, R; Ferrone, S; Bonnard, G D; Herberman, R B

    1985-04-01

    We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti-beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells

  8. 40 CFR 82.70 - Nonessential Class II products and exceptions.

    Science.gov (United States)

    2010-07-01

    ... provide for motor vehicle safety in accordance with Federal Motor Vehicle Safety Standards until January 1... 21 CFR 2.125(e); (ii) Lubricants, coatings or cleaning fluids for electrical or electronic equipment...; (iii) Lubricants, coatings or cleaning fluids used for aircraft maintenance, which contain class II...

  9. Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

    Science.gov (United States)

    Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

    2006-09-15

    Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

  10. A new class of synthetic anti-lipopolysaccharide peptides inhibits influenza A virus replication by blocking cellular attachment.

    Science.gov (United States)

    Hoffmann, Julia; Schneider, Carola; Heinbockel, Lena; Brandenburg, Klaus; Reimer, Rudolph; Gabriel, Gülsah

    2014-04-01

    Influenza A viruses are a continuous threat to human health as illustrated by the 2009 H1N1 pandemic. Since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. Here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; SALPs) for their potential to inhibit influenza virus replication in vitro and in vivo. We found that particularly SALP PEP 19-2.5 shows high binding affinities for the influenza virus receptor molecule, N-Acetylneuraminic acid, leading to impaired viral attachment and cellular entry. As a result, replication of several influenza virus subtypes (H7N7, H3N2 and 2009 pandemic H1N1) was strongly reduced. Furthermore, mice co-treated with PEP 19-2.5 were protected against an otherwise 100% lethal H7N7 influenza virus infection. These findings show that SALPs exhibit antiviral activity against influenza viruses by blocking virus attachment and entry into host cells. Thus, SALPs present a new class of broad-spectrum antiviral peptides for further development for influenza virus therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Glenoid fossa position in Class II malocclusion associated with mandibular retrusion.

    Science.gov (United States)

    Giuntini, Veronica; De Toffol, Laura; Franchi, Lorenzo; Baccetti, Tiziano

    2008-09-01

    To assess the position of the glenoid fossa in subjects with Class II malocclusion associated with mandibular retrusion and normal mandibular size in the mixed dentition. A sample of 30 subjects (16 male, 14 female), age 9 years +/- 6 months, with skeletal and dental Class II malocclusion associated with mandibular retrusion, normal skeletal vertical relationships, and normal mandibular dimensions, was compared with a matched group of 37 subjects (18 male, 19 female) with skeletal and dental Class I relationships. The comparisons between the Class II group and the control group on the cephalometric measures for the assessment of glenoid fossa position were performed by means of a nonparametric test for independent samples (Mann-Whitney U-test, P < .05). Subjects with Class II malocclusion presented with a significantly more distal position of the glenoid fossa, when compared with the control group as measured by means of three parameters (GF-S on FH, GF-Ptm on FH, and GF-FMN). A posteriorly displaced glenoid fossa is a possible diagnostic feature of Class II malocclusion associated with mandibular retrusion. An effective cephalometric measurement to evaluate glenoid fossa position is the distance from the glenoid fossa to the frontomaxillonasal suture (GF-FMN).

  12. Successful treatment of Class II malocclusion with bidental protrusion using standard edgewise prescription

    Directory of Open Access Journals (Sweden)

    Mohd Ayaz

    2016-01-01

    Full Text Available This case report deals with the successful orthodontic treatment of a 14-year-old female patient having Class II malocclusion with bidental protrusion using standard edgewise prescription. She reported with forwardly placed upper front teeth and difficulty in closing lips. She had prognathic maxilla, retrognathic mandible, and full cusp Class II molar and canine relation bilaterally with overjet of 7 mm. She was in cervical vertebrae maturation indicator Stage IV. The case was treated by fixed extraction mechanotherapy. Interarch Class II mechanics was used to retract the upper incisor and to mesialize the lower molars. Simultaneously, Class I mechanics was used to upright lower incisors. Tip back bend, curve of Spee, and extra palatal root torque were incorporated in upper archwire to maintain molars in upright position and prevent extrusion and deepening of bite, respectively. There was satisfactory improvement in facial profile at the end of 24 months. After a follow-up of 6 months, occlusion was stable.

  13. Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

    Science.gov (United States)

    Villarroel-Dorrego, Mariana; Speight, Paul M; Barrett, A William

    2005-01-01

    Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

  14. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Martina Kalle

    Full Text Available Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  15. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; van der Plas, Mariena J A; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2014-01-01

    Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  16. Benchmarking of copper(II) LFMM parameters for studying amyloid-β peptides.

    Science.gov (United States)

    Mutter, Shaun T; Deeth, Robert J; Turner, Matthew; Platts, James A

    2018-04-01

    Ligand field molecular mechanics (LFMM) parameters have been benchmarked for copper (II) bound to the amyloid-β 1-16 peptide fragment. Several density functional theory (DFT) optimised small test models, representative of different possible copper coordination modes, have been used to test the accuracy of the LFMM copper bond lengths and angles, resulting in errors typically less than 0.1 Å and 5°. Ligand field molecular dynamics (LFMD) simulations have been carried out on the copper bound amyloid-β 1-16 peptide and snapshots extracted from the subsequent trajectory. Snapshots have been optimised using DFT and the semi-empirical PM7 method resulting in good agreement against the LFMM calculated geometry. Analysis of substructures within snapshots shows that the larger contribution of geometrical difference, as measured by RMSD, lies within the peptide backbone, arising from differences in DFT and AMBER, and the copper coordination sphere is reproduced well by LFMM. PM7 performs excellently against LFMM with an average RMSD of 0.2 Å over 21 tested snapshots. Further analysis of the LFMD trajectory shows that copper bond lengths and angles have only small deviations from average values, with the exception of a carbonyl moiety from the N-terminus, which can act as a weakly bound fifth ligand.

  17. Testes de toxicidade aguda através de bioensaios no extrato solubilizado dos resíduos classe II A - não inertes e classe II B - inertes Acute toxicity tests by bioassays applied to the solubilized extracts of solid wastes class II A - non inerts and class II B - inerts

    Directory of Open Access Journals (Sweden)

    Nébora Liz Vendramin Brasil Rodrigues

    2007-03-01

    Full Text Available A grande diversidade de substâncias potencialmente tóxicas contribuem para a deterioração do meio ambiente. O objetivo deste trabalho foi propor a utilização de bioensaios, através de testes de toxicidade aguda com Daphnia magna e Vibrio fischeri, como mais um parâmetro a ser analisado no extrato solubilizado dos resíduos que, segundo a NBR 10004/04 fossem classificados como classe II A - não inertes ou classe II B - inertes. Realizaram-se, também, testes de toxicidade no drenado dos aterros classe II A e II B. Verificou-se que a toxicidade foi constatada nos extratos solubilizados dos 18 resíduos analisados e que, apenas três das amostras estariam próprias para lançamento, ou seja os resíduos 04, 14 e 15. Já, a toxicidade encontrada no drenado dos aterros, ficou muito superior do que a toxicidade de cada extrato solubilizado analisado separadamente.A great diversity of substances potencially toxic contributes to the deterioration of the environment. The aim of this research was to propose the use of bioassays using Daphnia magna and Vibrio fischeri, as another parameter to be analyzed in the solubilized extraction of waste according to NBR 10004/04 and classified as class II A - non inerts or class II B - inerts. Besides, another test was performed to measure the level of toxicity in the drainage of the landfill class II A and II B. It was verified that the toxicity found in the solubilized extracts of the 18 wastes analysed.Only 3 wastes (04, 14 and 15 were within the emission limits. On the other hand the toxicity found in the drainage of the landfill, from which all the samples came from, was much higher than the individual one.

  18. Treatment of periodontal abcess with Class II furcation involvement

    Directory of Open Access Journals (Sweden)

    Nur Rahmah

    2016-06-01

    Full Text Available Treatment of periodontal abscess with furcation involvement has its own challenges in achieving the success of periodontal treatment. Teeth with periodontal abscesses often indicate the presence of furcation involvement. Most periodontal abscess occurs in approximately 92.5% molar. Furcation involvement on tooth abscesses had a greater challenge to the success of periodontal therapy. A male patient aged 36 years came to the clinic with active periodontal disease. On examination, the teeth are sensitive to percussion and 2o mobility. There is 13 mm deep pockets around the roots of teeth. On radiographic examination, appears severe bone destruction in the root area and furcation. Oral hygiene status was fair. Patients had a history of systemic disease type II diabetes mellitus. The periodontal abscess with furcation involvement with systemic disease type II diabetes mellitus can be treated with open flap and debridement so it can achieve a better prognosis. Systemic disease do not become a hindrance in periodontal treatment as long as the disease is controlled. Prognosis of teeth with abscess depend on the nature and extent of bone loss. Chronic periodontal abscess has a slow progressive bone destruction.

  19. Type II collagen in cartilage evokes peptide-specific tolerance and skews the immune response.

    Science.gov (United States)

    Malmström, V; Kjellén, P; Holmdahl, R

    1998-06-01

    T cell recognition of type II collagen (CII) is a crucial event in the induction of collagen-induced arthritis in the mouse. Several CII peptides have been shown to be of importance, dependent on which MHC haplotype the mouse carries. By sequencing the rat CII and comparing the sequence with mouse, human, bovine and chicken CII, we have found that the immunodominant peptides all differ at critical positions compared with the autologous mouse sequence. Transgenic expression of the immunodominant Aq-restricted heterologous CII 256-270 epitope inserted into type I collagen (TSC mice) or type II collagen (MMC-1 mice) led to epitope-specific tolerance. Immunization of TSC mice with chick CII led to arthritis and immune responses, dependent on the subdominant, Aq-restricted and chick-specific CII 190-200 epitope. Immunization of F1 mice, expressing both H-2q and H-2r as well as transgenic expression of the Aq-restricted CII 256-270 epitope in cartilage, with bovine CII, led to arthritis, dependent on the Ar-restricted, bovine-specific epitope CII 607-621. These data show that the immunodominance of CII recognition is directed towards heterologous determinants, and that T cells directed towards the corresponding autologous epitopes are tolerated without evidence of active suppression.

  20. Occlusal stability of adult Class II Division 1 treatment with the Herbst appliance.

    Science.gov (United States)

    Bock, Niko Christian; von Bremen, Julia; Ruf, Sabine

    2010-08-01

    During recent years, some articles have been published on Herbst appliance treatment in adult patients, an approach that has been shown to be most effective in Class II treatment in both early and late adulthood. However, no results on stability have yet been published. Our objective was to analyze the short-term occlusal stability of Herbst therapy in adults with Class II Division 1 malocclusions. The subjects comprised 26 adults with Class II Division 1 malocclusions exhibiting a Class II molar relationship > or =0.5 cusp bilaterally or > or =1.0 cusp unilaterally and an overjet of > or =4.0 mm. The average treatment time was 8.8 months (Herbst phase) plus 14.7 months (subsequent multi-bracket phase). Study casts from before and after treatment and after an average retention period of 32 months were analyzed. After retention, molar relationships were stable in 77.6% and canine relationships in 71.2% of the teeth. True relapses were found in 8.2% (molar relationships) and 1.9% (canine relationships) of the teeth. Overjet was stable in 92.3% and overbite in 96.0% of the patients; true relapse did not occur. Herbst treatment showed good occlusal stability 2.5 years after treatment in adults with Class II Division 1 malocclusions. Copyright (c) 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  1. Dentofacial growth changes in subjects with untreated Class II malocclusion from late puberty through young adulthood.

    Science.gov (United States)

    Baccetti, Tiziano; Stahl, Franka; McNamara, James A

    2009-02-01

    The purpose of this longitudinal study was to compare dentofacial growth changes in untreated subjects with Class II Division 1 malocclusion with those in subjects with normal (Class I) occlusion from late puberty through young adulthood. The Class II Division 1 sample consisted of 23 subjects (10 male, 13 female). The Class I sample included 30 subjects (13 male, 17 female). The lateral cephalograms of the subjects in both groups were analyzed at 2 consecutive stages of development: T1, postpubertal observation (cervical vertebral maturation stage 6), and T2, young adulthood stage. The average time between T1 and T2 was 3.5 years. The statistical comparisons of the growth changes in the 2 groups were performed with Mann-Whitney U tests. From late puberty through young adulthood, dentofacial growth in subjects with untreated Class II malocclusion does not show significant differences when compared with that observed in untreated subjects with normal occlusion. These findings show that Class II dentoskeletal disharmony does not exhibit significant growth change from late puberty through young adulthood.

  2. Treatment outcome of bimaxillary surgery for asymmetric skeletal class II deformity.

    Science.gov (United States)

    Chen, Yun-Fang; Liao, Yu-Fang; Chen, Yin-An; Chen, Yu-Ray

    2018-05-04

    Facial asymmetry is one of the main concerns in patients with a dentofacial deformity. The aims of the study were to (1) evaluate the changes in facial asymmetry after bimaxillary surgery for asymmetric skeletal class II deformity and (2) compare preoperative and postoperative facial asymmetry of class II patients with normal controls. The facial asymmetry was assessed for 30 adults (21 women and 9 men, mean age: 29.3 years) who consecutively underwent bimaxillary surgery for asymmetric skeletal class II deformity using cone-beam computed tomography before and at least 6 months after surgery. Thirty soft tissue and two dental landmarks were identified on each three-dimensional facial image, and the asymmetry index of each landmark was calculated. Results were compared with those of 30 normal control subjects (21 women and 9 men, mean age: 26.2 years) with skeletal class I structure. Six months after surgery, the asymmetric index of the lower face and total face decreased significantly (17.8 ± 29.4 and 16.6 ± 29.5 mm, respectively, both p class II patients had residual chin asymmetry. The postoperative total face asymmetric index was positively correlated with the preoperative asymmetric index (r = 0.37, p class II deformity resulted in a significant improvement in lower face asymmetry. However, approximately 50% of the patients still had residual chin asymmetry. The total face postoperative asymmetry was moderately related to the initial severity of asymmetry. These findings could help clinicians better understand orthognathic outcomes on different facial regions for patients with asymmetric class II deformity.

  3. Association of maternal anti-HLA class II antibodies with protection from allergy in offspring.

    Science.gov (United States)

    Jones, M; Jeal, H; Harris, J M; Smith, J D; Rose, M L; Taylor, A N; Cullinan, P

    2013-09-01

    Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years. Anti-HLA class I and II antibodies were measured in maternal serum (n = 284) and levels correlated to numbers of pregnancies and birth order, and allergic outcomes in offspring at 8 years of age. Maternal anti-HLA class I and II antibodies were significantly higher when birth order, and the number of pregnancies were larger. Anti-HLA class II, but not class I antibodies were associated with significantly less atopy and seasonal rhinitis in the offspring at age 8 years. Mothers with nonatopic (but not atopic) offspring had a significant increase in anti-HLA class I and II antibodies with birth order. This study suggests that the 'birth order' effect in children may be due to parity-related changes in the maternal immune response to foetal antigens. We have observed for the first time an association between maternal anti-HLA class II antibodies and protection from allergy in the offspring. Further work is required to determine immunologically how HLA disparity between mother and father can protect against allergy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

    Science.gov (United States)

    Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

    2017-04-01

    Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV

  5. Coronal microleakage of four temporary restorative materials in Class II-type endodontic access preparations

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    Sang-Mi Yun

    2012-02-01

    Full Text Available Objectives The purpose of this study was to evaluate the microleakage of 4 temporary materials in teeth with Class II-type endodontic access preparations by using a glucose penetration model. Materials and Methods Glucose reaction test was performed to rule out the presence of any reaction between glucose and temporary material. Class II-type endodontic access preparations were made in extracted human premolars with a single root (n = 10. Each experimental group was restored with Caviton (GC, Spacer (Vericom, IRM (Dentsply-Caulk, or Fuji II(GC. Microleakage of four materials used as temporary restorative materials was evaluated by using a glucose penetration model. Data were analyzed by the one-way analysis of variance followed by a multiple-comparison Tukey test. The interface between materials and tooth were examined under a scanning electron microscope (SEM. Results There was no significant reaction between glucose and temporary materials used in this study. Microleakage was significantly lower for Caviton and Spacer than for Fuji II and IRM. SEM observation showed more intimate adaptation of tooth-restoration interfaces in Caviton and Spacer than in IRM and Fuji II. Conclusions Compared to IRM and Fuji II, Caviton and Spacer can be considered better temporary sealing materials in Class II-type endodontic access cavities.

  6. Vaccination against lymphocytic choriomeningitis virus infection in MHC class II-deficient mice

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2011-01-01

    response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8(+) T cell-mediated protection...... against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4(+) T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute...... mortality was not observed in any vaccinated mice following infection with the less-invasive Traub strain. However, LCMV Traub infection caused accelerated late mortality in unvaccinated MHC class II-deficient mice; in this case, we observed a strong trend toward delayed mortality in vaccinated mice...

  7. DNA sequence of the Peromyscus leucopus MHC class II gene Aa (MhcPeleAa)

    Energy Technology Data Exchange (ETDEWEB)

    Crew, M.D.; Bates, L.M. [Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States)

    1996-09-01

    The genus Peromyscus has been extensively studied by populations biologists and ecologists for over eighty years, with P. leucopus (the white-footed mouse) being one of the most intensively investigated species. Polymorphic major histocompatibility complex (MHC) genes have proven useful in population genetic studies and might be helpful in understanding the population dynamics of Peromyscus species which are ubiquitously distributed over North and Central America. Polymorphism of P. leucopus MHC (MhcPele) class II genes was evident by restriction fragment length polymorphism (RFLP) analyses using human and mouse probes and Pele class II loci exhibited degrees of polymorphism similar to H2 class II genes (A-like>E-like). 8 refs., 2 figs.

  8. The dominantly expressed class I molecule of the chicken MHC is explained by coevolution with the polymorphic peptide transporter (TAP) genes

    DEFF Research Database (Denmark)

    Walker, Brian A; Hunt, Lawrence G; Sowa, Anna K

    2011-01-01

    In most mammals, the MHC class I molecules are polymorphic and determine the specificity of peptide presentation, whereas the transporter associated with antigen presentation (TAP) heterodimers are functionally monomorphic. In chickens, there are two classical class I genes but only one is expres...

  9. Establishment of a quantitative ELISA capable of determining peptide - MHC class I interaction

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Kristensen, N; Blicher, T

    2002-01-01

    dependent manner. Here, we exploit the availability of these molecules to generate a quantitative ELISA-based assay capable of measuring the affinity of the interaction between peptide and MHC-I. This assay is simple and sensitive, and one can easily envisage that the necessary reagents, standards...

  10. The Influence of Class II Division 2 Malocclusions on the Harmony of the Human Face Profile.

    Science.gov (United States)

    Perović, Tatjana

    2017-11-24

    BACKGROUND Persons with class II division 2 malocclusion are characterized by a very specific dento-skeletal and soft-tissue profile (a profile in which a protruding nose and chin, retruding lips, concave and shortened lower third of the face, and gummy smile are dominant), which is the opposite of the currently modern profiles (convex profile of protruding lips and small chin). The aim of this research was to determine the differences in parameters of harmonies of facial profiles between persons with class II division 2 malocclusions and class I, and to establish the significance of those differences. MATERIAL AND METHODS For this study, 50 patients with class II division 2 malocclusions and 50 patients with class I were selected; profile photos were recorded and a photometric analysis was done: a type of profile according to Schwarz, the shape of a nose, the prominence of chin, biometrical field, the position of lips in relation to the tangent Sn-Pg, S-line (Steiner), E-line (Riketts) and a facial angle according to Arnett. RESULTS The significant differences in profiles of persons with class II division 2 compared to class I were: position and prominence of the chin, the position of the lower and upper lip in relation to the S-line, and smaller value of a facial angle in relation to persons with class I. CONCLUSIONS The differences seen in skeletal profiles were not associated with significant differences in the profiled facial contours of the examined groups. The compensatory role of the fullness of soft tissues of the lips is probably the reason why there were not significant deviations in all the examined parameters.

  11. Class II malocclusion with accentuated occlusal plane inclination corrected with miniplate: a case report

    Science.gov (United States)

    Farret, Marcel Marchiori; Farret, Milton M. Benitez

    2016-01-01

    ABSTRACT Introduction: A canted occlusal plane presents an unesthetic element of the smile. The correction of this asymmetry has been typically considered difficult by orthodontists, as it requires complex mechanics and may sometimes even require orthognathic surgery. Objective: This paper outlines the case of a 29-year-old woman with Class II malocclusion, pronounced midline deviation and accentuated occlusal plane inclination caused by mandibular deciduous molar ankylosis. Methods: The patient was treated with a miniplate used to provide anchorage in order to intrude maxillary teeth and extrude mandibular teeth on one side, thus eliminating asymmetry. Class II was corrected on the left side by means of distalization, anchored in the miniplate as well. On the right side, maxillary first premolar was extracted and molar relationship was kept in Class II, while canines were moved to Class I relationship. The patient received implant-prosthetic rehabilitation for maxillary left lateral incisor and mandibular left second premolar. Results: At the end of treatment, Class II was corrected, midlines were matched and the canted occlusal plane was totally corrected, thereby improving smile function and esthetics. PMID:27409658

  12. Class II malocclusion with accentuated occlusal plane inclination corrected with miniplate: a case report

    Directory of Open Access Journals (Sweden)

    Marcel Marchiori Farret

    Full Text Available ABSTRACT Introduction: A canted occlusal plane presents an unesthetic element of the smile. The correction of this asymmetry has been typically considered difficult by orthodontists, as it requires complex mechanics and may sometimes even require orthognathic surgery. Objective: This paper outlines the case of a 29-year-old woman with Class II malocclusion, pronounced midline deviation and accentuated occlusal plane inclination caused by mandibular deciduous molar ankylosis. Methods: The patient was treated with a miniplate used to provide anchorage in order to intrude maxillary teeth and extrude mandibular teeth on one side, thus eliminating asymmetry. Class II was corrected on the left side by means of distalization, anchored in the miniplate as well. On the right side, maxillary first premolar was extracted and molar relationship was kept in Class II, while canines were moved to Class I relationship. The patient received implant-prosthetic rehabilitation for maxillary left lateral incisor and mandibular left second premolar. Results: At the end of treatment, Class II was corrected, midlines were matched and the canted occlusal plane was totally corrected, thereby improving smile function and esthetics.

  13. Treatment of Class II Malocclusion by Nonextraction Therapy using Microimplants and Pendex Appliance

    Directory of Open Access Journals (Sweden)

    Rajkumar S Alle

    2012-01-01

    Full Text Available The treatment of Class II cases is always challenging. Treatment modalities involve growth modulation, expansion of the maxillary arch or extraction of premolars and retraction. The patient compliance is key factor in success of the treatment. In the present article a male patient with Class II malocclusion was treated using a Pendex appliance to simultaneously expand the upper arch and distalize the molars. The maxillary anteriors were retracted using microimplants. The results were satisfactory. This approach can be used in patients with mild skeletal discrepancy and with slight increase in the gingival display.

  14. Combined orthodontic and surgical correction of adult skeletal class II with hyperdivergent jaws.

    Science.gov (United States)

    Abraham, Jiku; Bagchi, Paulami; Gupta, Swati; Gupta, Hemant; Autar, Ram

    2012-01-01

    A case of severe Class II skeletal malocclusion with anterior open bite having vertical growth pattern and matching soft tissue profile is presented. Considering age of the patient and the severity of the malocclusion, it was decided to combine orthodontic treatment with surgery. A 0.022 Roth Pre-adjusted Edgewise Appliance was chosen for the orthodontic correction and Le-Fort 1 differential vertical impaction of maxilla with mandibular autorotation and augmentation genioplasty was considered as the treatment plan. The main aim was to reduce the gummy smile and correct the class II profile.

  15. HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the Present Day Tunisian Population.

    Directory of Open Access Journals (Sweden)

    Abdelhafidh Hajjej

    Full Text Available In view of its distinct geographical location and relatively small area, Tunisia witnessed the presence of many civilizations and ethnic groups throughout history, thereby questioning the origin of present-day Tunisian population. We investigated HLA class I and class II gene profiles in Tunisians, and compared this profile with those of Mediterranean and Sub-Sahara African populations. A total of 376 unrelated Tunisian individuals of both genders were genotyped for HLA class I (A, B and class II (DRB1, DQB1, using reverse dot-blot hybridization (PCR-SSO method. Statistical analysis was performed using Arlequin software. Phylogenetic trees were constructed by DISPAN software, and correspondence analysis was carried out by VISTA software. One hundred fifty-three HLA alleles were identified in the studied sample, which comprised 41, 50, 40 and 22 alleles at HLA-A,-B,-DRB1 and -DQB1 loci, respectively. The most frequent alleles were HLA-A*02:01 (16.76%, HLA-B*44:02/03 (17.82%, HLA-DRB1*07:01 (19.02%, and HLA-DQB1*03:01 (17.95%. Four-locus haplotype analysis identified HLA-A*02:01-B*50:01-DRB1*07:01-DQB1*02:02 (2.2% as the common haplotype in Tunisians. Compared to other nearby populations, Tunisians appear to be genetically related to Western Mediterranean population, in particular North Africans and Berbers. In conclusion, HLA genotype results indicate that Tunisians are related to present-day North Africans, Berbers and to Iberians, but not to Eastern Arabs (Palestinians, Jordanians and Lebanese. This suggests that the genetic contribution of Arab invasion of 7th-11th century A.D. had little impact of the North African gene pool.

  16. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

    DEFF Research Database (Denmark)

    Odum, Niels; Kanner, S B; Ledbetter, J A

    1993-01-01

    MHC class II-positive T cells are found in tissues involved in autoimmune and infectious disorders. Because stimulation of class II molecules by mAb or bacterial superantigens induces protein tyrosine phosphorylation through activation of PTK3 in T cells, we hypothesized that class II signals play...... tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...... a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4-induced proliferation. The costimulatory effect was most pronounced...

  17. Distribution of class ii major histocompatibility complex antigenexpressing cells in human dental pulp with carious lesions

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2012-09-01

    Full Text Available Background: Dental caries is a bacterial infection which causes destruction of the hard tissues of the tooth. Exposure of the dentin to the oral environment as a result of caries inevitably results in a cellular response in the pulp. The major histocompatibility complex (MHC is a group of genes that code for cell-surface histocompatibility antigens. Cells expressing class II MHC molecules participate in the initial recognition and the processing of antigenic substances to serve as antigen-presenting cells. Purpose: The aim of the study was to elucidate the alteration in the distribution of class II MHC antigen-expressing cells in human dental pulp as carious lesions progressed toward the pulp. Methods: Fifteen third molars with caries at the occlusal site at various stages of decay and 5 intact third molars were extracted and used in this study. Before decalcifying with 10% EDTA solution (pH 7.4, all the samples were observed by micro-computed tomography to confirm the lesion condition three-dimensionally. The specimens were then processed for cryosection and immunohistochemistry using an anti-MHC class II monoclonal antibody. Results: Class II MHC antigen-expressing cells were found both in normal and carious specimens. In normal tooth, the class II MHC-immunopositive cells were observed mainly at the periphery of the pulp tissue. In teeth with caries, class II MHC-immunopositive cells were located predominantly subjacent to the carious lesions. As the caries progressed, the number of class II MHC antigen-expressing cells was increased. Conclusion: The depth of carious lesions affects the distribution of class II MHC antigen-expressing cells in the dental pulp.Latar belakang: Karies merupakan penyakit infeksi bakteri yang mengakibatkan destruksi jaringan keras gigi. Dentin yang terbuka akibat karies akan menginduksi respon imun seluler pada pulpa. Kompleks histokompatibilitas utama (MHC merupakan sekumpulan gen yang mengkode histokompatibilitas

  18. Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Montero, Ana; Leman, Luke J.

    2012-01-01

    We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC...

  19. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

    Science.gov (United States)

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J; Telenti, Amalio; de Bakker, Paul I W; Walker, Bruce D; Ripke, Stephan; Brumme, Chanson J; Pulit, Sara L; Carrington, Mary; Kadie, Carl M; Carlson, Jonathan M; Heckerman, David; Graham, Robert R; Plenge, Robert M; Deeks, Steven G; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P; Guiducci, Candace; Gupta, Namrata; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L; Lemay, Paul; O'Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L; Vine, Seanna; Addo, Marylyn M; Allen, Todd M; Altfeld, Marcus; Henn, Matthew R; Le Gall, Sylvie; Streeck, Hendrik; Haas, David W; Kuritzkes, Daniel R; Robbins, Gregory K; Shafer, Robert W; Gulick, Roy M; Shikuma, Cecilia M; Haubrich, Richard; Riddler, Sharon; Sax, Paul E; Daar, Eric S; Ribaudo, Heather J; Agan, Brian; Agarwal, Shanu; Ahern, Richard L; Allen, Brady L; Altidor, Sherly; Altschuler, Eric L; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C; Benson, Anne M; Berger, Judith; Bernard, Nicole F; Bernard, Annette M; Birch, Christopher; Bodner, Stanley J; Bolan, Robert K; Boudreaux, Emilie T; Bradley, Meg; Braun, James F; Brndjar, Jon E; Brown, Stephen J; Brown, Katherine; Brown, Sheldon T; Burack, Jedidiah; Bush, Larry M; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H; Carmichael, J Kevin; Casey, Kathleen K; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T; Chez, Nancy; Chirch, Lisa M; Cimoch, Paul J; Cohen, Daniel; Cohn, Lillian E; Conway, Brian; Cooper, David A; Cornelson, Brian; Cox, David T; Cristofano, Michael V; Cuchural, George; Czartoski, Julie L; Dahman, Joseph M; Daly, Jennifer S; Davis, Benjamin T; Davis, Kristine; Davod, Sheila M; DeJesus, Edwin; Dietz, Craig A; Dunham, Eleanor; Dunn, Michael E; Ellerin, Todd B; Eron, Joseph J; Fangman, John J W; Farel, Claire E; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A; French, Neel K; Fuchs, Jonathan D; Fuller, Jon D; Gaberman, Jonna; Gallant, Joel E; Gandhi, Rajesh T; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C; Gaultier, Cyril R; Gebre, Wondwoosen; Gilman, Frank D; Gilson, Ian; Goepfert, Paul A; Gottlieb, Michael S; Goulston, Claudia; Groger, Richard K; Gurley, T Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W David; Harrigan, P Richard; Hawkins, Trevor N; Heath, Sonya; Hecht, Frederick M; Henry, W Keith; Hladek, Melissa; Hoffman, Robert P; Horton, James M; Hsu, Ricky K; Huhn, Gregory D; Hunt, Peter; Hupert, Mark J; Illeman, Mark L; Jaeger, Hans; Jellinger, Robert M; John, Mina; Johnson, Jennifer A; Johnson, Kristin L; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C; Kauffman, Carol A; Khanlou, Homayoon; Killian, Robert K; Kim, Arthur Y; Kim, David D; Kinder, Clifford A; Kirchner, Jeffrey T; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P Todd; Kurisu, Wayne; Kwon, Douglas S; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M; Lee, David M; Lee, Jean M L; Lee, Marah J; Lee, Edward T Y; Lemoine, Janice; Levy, Jay A; Llibre, Josep M; Liguori, Michael A; Little, Susan J; Liu, Anne Y; Lopez, Alvaro J; Loutfy, Mono R; Loy, Dawn; Mohammed, Debbie Y; Man, Alan; Mansour, Michael K; Marconi, Vincent C; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N; Martin, Harold L; Mayer, Kenneth Hugh; McElrath, M Juliana; McGhee, Theresa A; McGovern, Barbara H; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X; Menezes, Prema; Mesa, Greg; Metroka, Craig E; Meyer-Olson, Dirk; Miller, Andy O; Montgomery, Kate; Mounzer, Karam C; Nagami, Ellen H; Nagin, Iris; Nahass, Ronald G; Nelson, Margret O; Nielsen, Craig; Norene, David L; O'Connor, David H; Ojikutu, Bisola O; Okulicz, Jason; Oladehin, Olakunle O; Oldfield, Edward C; Olender, Susan A; Ostrowski, Mario; Owen, William F; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M; Perlmutter, Aaron M; Pierce, Michael N; Pincus, Jonathan M; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J; Rhame, Frank S; Richards, Constance Shamuyarira; Richman, Douglas D; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C; Rosenberg, Eric S; Rosenthal, Daniel; Ross, Polly E; Rubin, David S; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R; Sanchez, William C; Sanjana, Veeraf M; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M; Shalit, Peter; Shay, William; Shirvani, Vivian N; Silebi, Vanessa I; Sizemore, James M; Skolnik, Paul R; Sokol-Anderson, Marcia; Sosman, James M; Stabile, Paul; Stapleton, Jack T; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F Lisa; Stone, Valerie E; Stone, David R; Tambussi, Giuseppe; Taplitz, Randy A; Tedaldi, Ellen M; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A; Trinh, Phuong D; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J; Vecino, Isabel; Vega, Vilma M; Veikley, Wenoah; Wade, Barbara H; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J; Warner, Daniel A; Weber, Robert D; Webster, Duncan; Weis, Steve; Wheeler, David A; White, David J; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G; van't Wout, Angelique; Wright, David P; Yang, Otto O; Yurdin, David L; Zabukovic, Brandon W; Zachary, Kimon C; Zeeman, Beth; Zhao, Meng

    2010-12-10

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

  20. The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

    Science.gov (United States)

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David; de Bakker, Paul I.W.; Pereyra, Florencia; de Bakker, Paul I.W.; Graham, Robert R.; Plenge, Robert M.; Deeks, Steven G.; Walker, Bruce D.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P.; Guiducci, Candace; Gupta, Namrata; Carrington, Mary; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Pereyra, Florencia; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O’Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Henn, Matthew R.; Le Gall, Sylvie; Streeck, Hendrik; Walker, Bruce D.; Haas, David W.; Kuritzkes, Daniel R.; Robbins, Gregory K.; Shafer, Robert W.; Gulick, Roy M.; Shikuma, Cecilia M.; Haubrich, Richard; Riddler, Sharon; Sax, Paul E.; Daar, Eric S.; Ribaudo, Heather J.; Agan, Brian; Agarwal, Shanu; Ahern, Richard L.; Allen, Brady L.; Altidor, Sherly; Altschuler, Eric L.; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J.; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C.; Benson, Anne M.; Berger, Judith; Bernard, Nicole F.; Bernard, Annette M.; Birch, Christopher; Bodner, Stanley J.; Bolan, Robert K.; Boudreaux, Emilie T.; Bradley, Meg; Braun, James F.; Brndjar, Jon E.; Brown, Stephen J.; Brown, Katherine; Brown, Sheldon T.; Burack, Jedidiah; Bush, Larry M.; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H.; Carmichael, J. Kevin; Casey, Kathleen K.; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T.; Chez, Nancy; Chirch, Lisa M.; Cimoch, Paul J.; Cohen, Daniel; Cohn, Lillian E.; Conway, Brian; Cooper, David A.; Cornelson, Brian; Cox, David T.; Cristofano, Michael V.; Cuchural, George; Czartoski, Julie L.; Dahman, Joseph M.; Daly, Jennifer S.; Davis, Benjamin T.; Davis, Kristine; Davod, Sheila M.; Deeks, Steven G.; DeJesus, Edwin; Dietz, Craig A.; Dunham, Eleanor; Dunn, Michael E.; Ellerin, Todd B.; Eron, Joseph J.; Fangman, John J.W.; Farel, Claire E.; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A.; French, Neel K.; Fuchs, Jonathan D.; Fuller, Jon D.; Gaberman, Jonna; Gallant, Joel E.; Gandhi, Rajesh T.; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C.; Gaultier, Cyril R.; Gebre, Wondwoosen; Gilman, Frank D.; Gilson, Ian; Goepfert, Paul A.; Gottlieb, Michael S.; Goulston, Claudia; Groger, Richard K.; Gurley, T. Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W. David; Harrigan, P. Richard; Hawkins, Trevor N.; Heath, Sonya; Hecht, Frederick M.; Henry, W. Keith; Hladek, Melissa; Hoffman, Robert P.; Horton, James M.; Hsu, Ricky K.; Huhn, Gregory D.; Hunt, Peter; Hupert, Mark J.; Illeman, Mark L.; Jaeger, Hans; Jellinger, Robert M.; John, Mina; Johnson, Jennifer A.; Johnson, Kristin L.; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C.; Kauffman, Carol A.; Khanlou, Homayoon; Killian, Robert K.; Kim, Arthur Y.; Kim, David D.; Kinder, Clifford A.; Kirchner, Jeffrey T.; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P. Todd; Kurisu, Wayne; Kwon, Douglas S.; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M.; Lee, David M.; Lee, Jean M.L.; Lee, Marah J.; Lee, Edward T.Y.; Lemoine, Janice; Levy, Jay A.; Llibre, Josep M.; Liguori, Michael A.; Little, Susan J.; Liu, Anne Y.; Lopez, Alvaro J.; Loutfy, Mono R.; Loy, Dawn; Mohammed, Debbie Y.; Man, Alan; Mansour, Michael K.; Marconi, Vincent C.; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N.; Martin, Harold L.; Mayer, Kenneth Hugh; McElrath, M. Juliana; McGhee, Theresa A.; McGovern, Barbara H.; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X.; Menezes, Prema; Mesa, Greg; Metroka, Craig E.; Meyer-Olson, Dirk; Miller, Andy O.; Montgomery, Kate; Mounzer, Karam C.; Nagami, Ellen H.; Nagin, Iris; Nahass, Ronald G.; Nelson, Margret O.; Nielsen, Craig; Norene, David L.; O’Connor, David H.; Ojikutu, Bisola O.; Okulicz, Jason; Oladehin, Olakunle O.; Oldfield, Edward C.; Olender, Susan A.; Ostrowski, Mario; Owen, William F.; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M.; Perlmutter, Aaron M.; Pierce, Michael N.; Pincus, Jonathan M.; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C.; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J.; Rhame, Frank S.; Richards, Constance Shamuyarira; Richman, Douglas D.; Robbins, Gregory K.; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C.; Rosenberg, Eric S.; Rosenthal, Daniel; Ross, Polly E.; Rubin, David S.; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R.; Sanchez, William C.; Sanjana, Veeraf M.; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M.; Shalit, Peter; Shay, William; Shirvani, Vivian N.; Silebi, Vanessa I.; Sizemore, James M.; Skolnik, Paul R.; Sokol-Anderson, Marcia; Sosman, James M.; Stabile, Paul; Stapleton, Jack T.; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F. Lisa; Stone, Valerie E.; Stone, David R.; Tambussi, Giuseppe; Taplitz, Randy A.; Tedaldi, Ellen M.; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A.; Trinh, Phuong D.; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J.; Vecino, Isabel; Vega, Vilma M.; Veikley, Wenoah; Wade, Barbara H.; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J.; Warner, Daniel A.; Weber, Robert D.; Webster, Duncan; Weis, Steve; Wheeler, David A.; White, David J.; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G.; Wout, Angelique van’t; Wright, David P.; Yang, Otto O.; Yurdin, David L.; Zabukovic, Brandon W.; Zachary, Kimon C.; Zeeman, Beth; Zhao, Meng

    2011-01-01

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection. PMID:21051598

  1. Association of SNP variants of MHC Class II DRB gene with thermo-physiological traits in tropical goats.

    Science.gov (United States)

    Yakubu, Abdulmojeed; Salako, Adebowale E; De Donato, Marcos; Peters, Sunday O; Takeet, Michael I; Wheto, Mathew; Okpeku, Moses; Imumorin, Ikhide G

    2017-02-01

    Host defense in vertebrates depend on many secreted regulatory proteins such as major histocompatibility complex (MHC) class II which provide important regulatory and effector functions of T cells. Gene polymorphism in the second exon of Capra-DRB gene in three major Nigerian goat breeds [West African Dwarf (WAD), Red Sokoto (RS), and Sahel (SH)] was analyzed by restriction fragment length polymorphisms (RFLP). Four restriction enzymes, BsaHI, AluI, HaeIII, and SacII, were utilized. The association between the polymorphic sites and some heat tolerance traits were also investigated in a total of 70 WAD, 90 RS, and 50 SH goats. Fourteen different types of alleles identified in the Nigerian goats, four of which were found in the peptide coding region (A57G, Q89R, G104D, and T112I), indicate a high degree of polymorphism at the DRB locus in this species. An obvious excess (P  0.05), except AluI in RS goats and HaeIII in WAD goats (P goat populations, ranged from 0.16 to 0.50. Genotypes AA (BsaHI), GG, GC and CC (AluI) and GG, GA, AA (HaeIII) appeared better in terms of heat tolerance. The heat-tolerant ability of SH and RS goats to the hot and humid tropical environment of Nigeria seemed better than that of the WAD goats. Sex effect (P tropics.

  2. Long-term effects of Class II orthodontic treatment on oral health.

    Science.gov (United States)

    Bock, N C; Saffar, M; Hudel, H; Evälahti, M; Heikinheimo, K; Rice, D P C; Ruf, S

    2018-03-01

    To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH). All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence. Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19-44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm). Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

  3. Juvenile idiopathic arthritis (JIA): a screening study to measure class II skeletal pattern, TMJ PDS and use of systemic corticosteroids.

    LENUS (Irish Health Repository)

    Mandall, Nicky A

    2010-03-01

    To screen patients with oligoarticular and polyarticular forms of Juvenile Idiopathic Arthritis (JIA) to determine (i) the severity of their class II skeletal pattern; (ii) temporomandibular joint signs and symptoms and (iii) use of systemic corticosteroids.

  4. Comparison of interradicular distances and cortical bone thickness in Thai patients with class I and class II skeletal patterns using cone-beam computed tomography

    International Nuclear Information System (INIS)

    Khumsarn, Nattida; Patanaporn, Virush; Janhom, Apirum; Jotikasthira, Dhirawat

    2016-01-01

    This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns

  5. Comparison of interradicular distances and cortical bone thickness in Thai patients with class I and class II skeletal patterns using cone-beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Khumsarn, Nattida [Dental Division of Lamphun Hospital, Lamphun (Thailand); Patanaporn, Virush; Janhom, Apirum; Jotikasthira, Dhirawat [Faculty of Dentistry, Chiang Mai University, Chiang Mai (Thailand)

    2016-06-15

    This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns.

  6. Predictors of favorable soft tissue profile outcomes following Class II Twin-block treatment.

    Science.gov (United States)

    Kim, Ji-Eun; Mah, Su-Jung; Kim, Tae-Woo; Kim, Su-Jung; Park, Ki-Ho; Kang, Yoon-Goo

    2018-01-01

    The aim of this study was to determine cephalometric factors that help predict favorable soft-tissue profile outcomes following treatment with the Class II Twin-block appliance. Pre- and post-treatment lateral cephalograms of 45 patients treated with the Class II Twin-block appliance were retrospectively analyzed. Profile silhouettes were drawn from the cephalograms and evaluated by three orthodontists in order to determine the extent of improvement. Samples were divided into a favorable group (upper 30% of visual analogue scale [VAS] scores, n = 14) and an unfavorable group (lower 30% of VAS scores, n = 14). Skeletal and soft-tissue measurements were performed on the cephalograms and an intergroup comparison was conducted. An independent t -test revealed that the following pre-treatment values were lower in the favorable group compared to the unfavorable group: lower incisor to mandibular plane angle, lower incisor to pogonion distance, point A-nasion-point B angle, sella-nasion line (SN) to maxillary plane angle, SN to mandibular plane angle, gonial angle, and symphysis inclination. The favorable group had a larger incisor inclination to occlusal plane. Moreover, the favorable group showed larger post-treatment changes in gonial angle, B point projection, and pogonion projection than did the unfavorable group. Class II malocclusion patients with a low divergent skeletal pattern and reduced lower incisor protrusions are likely to show more improvement in soft-tissue profile outcomes following Class II Twin-block treatment.

  7. MHC class II B diversity in blue tits : A preliminary study

    NARCIS (Netherlands)

    Rivero-de Aguilar, Juan; Schut, Elske; Merino, Santiago; Martinez, Javier; Komdeur, Jan; Westerdahl, Helena

    In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were

  8. 78 FR 14013 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Wheelchair Elevator

    Science.gov (United States)

    2013-03-04

    ... Elevator AGENCY: Food and Drug Administration, HHS. ACTION: Final order. SUMMARY: The Food and Drug... requirements for wheelchair elevator devices commonly known as inclined platform lifts and vertical platform... wheelchair elevators, class II devices, from premarket notification and establishes conditions for exemption...

  9. Variation in MHC class II B genes in marbled murrelets: implications for delineating conservation units

    Science.gov (United States)

    C. Vásquez-Carrillo; V. Friesen; L. Hall; M.Z. Peery

    2013-01-01

    Conserving genetic variation is critical for maintaining the evolutionary potential and viability of a species. Genetic studies seeking to delineate conservation units, however, typically focus on characterizing neutral genetic variation and may not identify populations harboring local adaptations. Here, variation at two major histocompatibility complex (MHC) class II...

  10. 37 GHz METHANOL MASERS : HORSEMEN OF THE APOCALYPSE FOR THE CLASS II METHANOL MASER PHASE?

    International Nuclear Information System (INIS)

    Ellingsen, S. P.; Breen, S. L.; Sobolev, A. M.; Voronkov, M. A.; Caswell, J. L.; Lo, N.

    2011-01-01

    We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  11. Building Students' Reasoning Skills by Promoting Student-Led Discussions in an Algebra II Class

    Science.gov (United States)

    DeJarnette, Anna F.; González, Gloriana

    2013-01-01

    Current research and professional organizations call for greater emphasis on reasoning and sense making in algebra (Chazan, 2000; Cuoco, Goldenberg, & Mark, 1996; Harel & Sowder, 2005; National Council of Teachers of Mathematics [NCTM], 2009, 2010). This paper illustrates how students in an Algebra II class had opportunities to develop…

  12. Oral HPV infection and MHC class II deficiency (A study of two cases with atypical outcome

    Directory of Open Access Journals (Sweden)

    Guirat-Dhouib Naouel

    2012-04-01

    Full Text Available Abstract Background Major histocompatibility complex class II deficiency, also referred to as bare lymphocyte syndrome is a rare primary Immunodeficiency disorder characterized by a profondly deficient human leukocyte antigen class II expression and a lack of cellular and humoral immune responses to foreign antigens. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections. The infections begin in the first year of life and involve usually the respiratory system and the gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood. Bone marrow transplantation is the curative treatment. Case reports Here we report two cases with a late outcome MHC class II deficiency. They had a long term history of recurrent bronchopulmonary and gastrointestinal infections. Bone marrow transplantation could not be performed because no compatible donor had been identified. At the age of 12 years, they developed oral papillomatous lesions related to HPV (human papillomavirus. The diagnosis of HPV infection was done by histological examination. HPV typing performed on the tissue obtained at biopsy showed HPV type 6. The lesions were partially removed after two months of laser treatment. Conclusions Viral infections are common in patients with MHC class II and remain the main cause of death. Besides warts caused by HPV infection do not exhibit a propensity for malignant transformation; they can cause great psychosocial morbidity.

  13. 75 FR 55269 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2010-09-10

    ... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Parts 542 and 543 RIN 3141-AA-37 Minimum Internal Control Standards for Class II Gaming AGENCY: National Indian Gaming Commission. ACTION: Delay of effective date of final rule; request for comments. SUMMARY: The National Indian Gaming...

  14. 76 FR 53817 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2011-08-30

    ... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Parts 542 and 543 Minimum Internal Control Standards for Class II Gaming AGENCY: National Indian Gaming Commission, Interior. ACTION: Final rule; delay of effective date and request for comments. SUMMARY: The National Indian Gaming...

  15. 77 FR 60625 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2012-10-04

    ... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Parts 542 and 543 RIN 3141-AA-37 Minimum Internal Control Standards for Class II Gaming AGENCY: National Indian Gaming Commission. ACTION: Final rule; delay of effective date; suspension. SUMMARY: The National Indian Gaming Commission...

  16. HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan.

    Science.gov (United States)

    Kuranov, A B; Kozhamkulov, U A; Vavilov, M N; Belova, E S; Bismilda, V L; Alenova, A H; Ismailov, S S; Momynaliev, K T

    2014-02-01

    The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P = 0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Evidence for multiple major histocompatibility class II X-box binding proteins.

    OpenAIRE

    Celada, A; Maki, R

    1989-01-01

    The X box is a loosely conserved DNA sequence that is located upstream of all major histocompatibility class II genes and is one of the cis-acting regulatory elements. Despite the similarity between all X-box sequences, each promoter-proximal X box in the mouse appears to bind a separate nuclear factor.

  18. Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

    Science.gov (United States)

    Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

    2012-01-01

    Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction. PMID:22833118

  19. The impact of functional jaw orthopedics in subjects with unfavorable Class II skeletal patterns.

    Science.gov (United States)

    Baccetti, Tiziano; McNamara, James A

    2010-01-01

    To evaluate the outcomes of functional jaw orthopedics (FJO) followed by fixed appliances in Class II patients showing cephalometric signs predictive of unfavorable responsiveness to orthopedic treatment. A total of 48 treated subjects (20 males, 28 females) with unfavorable Class II malocclusions were treated with FJO at the adolescent growth spurt, followed by fixed appliances. Treatment outcomes were compared with the growth changes in a matched control group of untreated subjects with "unfavorable" Class II malocclusions. A significant prevalence rate of successful outcome was recorded within the treated group (64.5%). When compared with the untreated controls, both the overall treated group and the successful treated subgroup revealed a significant reduction in maxillary growth and sagittal position, along with a significant enhancement in mandibular length, sagittal advancement of the mandible, and significant improvements in the maxillo-mandibular relationships. Both overjet and molar relation showed significant favorable changes in the treated group. FJO at the pubertal spurt followed by fixed appliances is a viable therapeutical option in patients with "unfavorable" Class II malocclusions, although skeletal changes are of minor entity. Copyright © 2010 Società Italiana di Ortodonzia SIDO. Published by Elsevier Srl. All rights reserved.

  20. HLA class II linkage disequilibrium and haplotype evolution in the Cayapa Indians of Ecuador

    Energy Technology Data Exchange (ETDEWEB)

    Trachtenberg, E.A.; Erlich, H.A. [Roche Molecular Systems, Alameda, CA (United States); Klitz, W. [Univ. of California, Berkeley, CA (United States)] [and others

    1995-08-01

    DNA-based typing of the HLA class II loci in a sample of the Cayapa Indians of Ecuador reveals several lines of evidence that selection has operated to maintain and to diversify the existing level of polymorphism in the class II region. As has been noticed for other Native American groups, the overall level of polymorphism at the DRB1, DQA1, DQB1, and DPB1 loci is reduced relative to that found in other human populations. Nonetheless, the relative eveness in the distribution of allele frequencies at each of the four loci points to the role of balancing selection in the maintenance of the polymorphism. The DQA1 and DQB1 loci, in particular, have near-maximum departures from the neutrality model, which suggests that balancing selection has been especially strong in these cases. Several novel DQA1-DQB1 haplotypes and the discovery of a new DRB1 allele demonstrate an evolutionary tendency favoring the diversification of class II alleles and haplotypes. The recombination interval between the centromeric DPB1 locus and the other class II loci will, in the absence of other forces such as selection, reduce disequilibrium across this region. However, nearly all common alleles were found to be part of DR-DP haplotypes in strong disequilibrium, consistent with the recent action of selection acting on these haplotypes in the Cayapa. 50 refs., 3 figs., 3 tabs.

  1. DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis

    DEFF Research Database (Denmark)

    Morling, N; Friis, J; Fugger, L

    1991-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments a...

  2. Evaluation of proximal contact tightness of Class II resin composite restorations.

    NARCIS (Netherlands)

    Saber, M.H.; Loomans, B.A.C.; Zohairy, A. El; Dorfer, C.E.; El-Badrawy, W.

    2010-01-01

    OBJECTIVE: The objective of the current study was to compare in-vitro the proximal contact tightness (PCT) of Class II resin composite restorations (RCR) placed with different established and new placement techniques. METHODS: 105 ivorine lower left first molars with standardized MO cavities were

  3. 40 CFR 147.50 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... Carry Out Underground Injection Control Program Relating to Class II Wells as Described in Federal Safe... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alabama... application: (a) Incorporation by reference. The requirements set forth in the State statutes and regulations...

  4. The effect of proximal contour on marginal ridge fracture of Class II composite resin restorations.

    NARCIS (Netherlands)

    Loomans, B.A.C.; Roeters, F.J.M.; Opdam, N.J.M.; Kuijs, R.H.

    2008-01-01

    OBJECTIVES: To compare the marginal ridge fracture strength of Class II composite resin restorations placed with a straight or contoured matrix band using composite resins with different modulus of elasticity. METHODS: In 60 artificial first molars standardized MO-preparations were ground. Two

  5. A treatment method for Class II Division 1 patients with extraction of permanent maxillary first molars.

    NARCIS (Netherlands)

    Booij, J.W.; Kuijpers-Jagtman, A.M.; Katsaros, C.

    2009-01-01

    Throughout the years, various treatment modalities have been presented for the treatment of Class II Division 1 malocclusions. The goal of this paper is to present a treatment approach that involves the extraction of the maxillary first molars followed by use of fixed appliances with low-friction

  6. Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins

    DEFF Research Database (Denmark)

    Rognan, D; Lauemoller, S L; Holm, A

    1999-01-01

    A simple and fast free energy scoring function (Fresno) has been developed to predict the binding free energy of peptides to class I major histocompatibility (MHC) proteins. It differs from existing scoring functions mainly by the explicit treatment of ligand desolvation and of unfavorable protein...... coordinates of the MHC-bound peptide have first been determined with an accuracy of about 1-1.5 A. Furthermore, it may be easily recalibrated for any protein-ligand complex.......) and of a series of 16 peptides to H-2K(k). Predictions were more accurate for HLA-A2-binding peptides as the training set had been built from experimentally determined structures. The average error in predicting the binding free energy of the test peptides was 3.1 kJ/mol. For the homology model-derived equation...

  7. Oligoclonal band phenotypes in MS differ in their HLA class II association, while specific KIR ligands at HLA class I show association to MS in general

    DEFF Research Database (Denmark)

    Gustavsen, Marte W; Viken, Marte K; Celius, Elisabeth G

    2014-01-01

    Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated the associ......Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated...

  8. Peptide-binding motif prediction by using phage display library for SasaUBA*0301, a resistance haplotype of MHC class I molecule from Atlantic Salmon (Salmo salar)

    DEFF Research Database (Denmark)

    Zhao, Heng; Hermsen, Trudi; Stet, Rene J M

    2008-01-01

    The structure of the peptide-binding specificity of major histocompatibility complex (MHC) class I has been analyzed extensively in human and mouse. For fish, there are no crystallographic models of MHC molecules, neither are there data on the peptide-binding specificity. In this study, we descri...... and there is a significant association between MHC polymorphism and the disease resistance. Therefore, our study might contribute to designing a peptide vaccine against this viral disease....... class I molecule might have a very similar binding motif at the C-terminus compared with a known mouse class I molecule H2-Kb which has L, or I, V, M at p8. Previous work showed that Atlantic Salmon carrying the allele SasaUBA*0301 are resistant to infectious Salmon aneamia virus...

  9. Self-esteem in adolescents with Angle Class I, II and III malocclusion in a Peruvian sample.

    Science.gov (United States)

    Florián-Vargas, Karla; Honores, Marcos J Carruitero; Bernabé, Eduardo; Flores-Mir, Carlos

    2016-01-01

    To compare self-esteem scores in 12 to 16-year-old adolescents with different Angle malocclusion types in a Peruvian sample. A cross-sectional study was conducted in a sample of 276 adolescents (159, 52 and 65 with Angle Class I, II and III malocclusions, respectively) from Trujillo, Peru. Participants were asked to complete the Rosenberg Self-Esteem Scale (RSES) and were also clinically examined, so as to have Angle malocclusion classification determined. Analysis of covariance (ANCOVA) was used to compare RSES scores among adolescents with Class I, II and III malocclusions, with participants' demographic factors being controlled. Mean RSES scores for adolescents with Class I, II and III malocclusions were 20.47 ± 3.96, 21.96 ± 3.27 and 21.26 ± 4.81, respectively. The ANCOVA test showed that adolescents with Class II malocclusion had a significantly higher RSES score than those with Class I malocclusion, but there were no differences between other malocclusion groups. Supplemental analysis suggested that only those with Class II, Division 2 malocclusion might have greater self-esteem when compared to adolescents with Class I malocclusion. This study shows that, in general, self-esteem did not vary according to adolescents' malocclusion in the sample studied. Surprisingly, only adolescents with Class II malocclusion, particularly Class II, Division 2, reported better self-esteem than those with Class I malocclusion. A more detailed analysis assessing the impact of anterior occlusal features should be conducted.

  10. Subclassification of Recursive Partitioning Analysis Class II Patients With Brain Metastases Treated Radiosurgically

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Masaaki, E-mail: BCD06275@nifty.com [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Tokyo Women' s Medical University Medical Center East, Tokyo (Japan); Sato, Yasunori [Clinical Research Center, Chiba University Graduate School of Medicine, Chiba (Japan); Serizawa, Toru [Tokyo Gamma Unit Center, Tsukiji Neurologic Clinic, Tokyo (Japan); Kawabe, Takuya [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto (Japan); Higuchi, Yoshinori [Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba (Japan); Nagano, Osamu [Gamma Knife House, Chiba Cardiovascular Center, Ichihara (Japan); Barfod, Bierta E. [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Ono, Junichi [Gamma Knife House, Chiba Cardiovascular Center, Ichihara (Japan); Kasuya, Hidetoshi [Department of Neurosurgery, Tokyo Women' s Medical University Medical Center East, Tokyo (Japan); Urakawa, Yoichi [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan)

    2012-08-01

    Purpose: Although the recursive partitioning analysis (RPA) class is generally used for predicting survival periods of patients with brain metastases (METs), the majority of such patients are Class II and clinical factors vary quite widely within this category. This prompted us to divide RPA Class II patients into three subclasses. Methods and Materials: This was a two-institution, institutional review board-approved, retrospective cohort study using two databases: the Mito series (2,000 consecutive patients, comprising 787 women and 1,213 men; mean age, 65 years [range, 19-96 years]) and the Chiba series (1,753 patients, comprising 673 female and 1,080 male patients; mean age, 65 years [range, 7-94 years]). Both patient series underwent Gamma Knife radiosurgery alone, without whole-brain radiotherapy, for brain METs during the same 10-year period, July 1998 through June 2008. The Cox proportional hazard model with a step-wise selection procedure was used for multivariate analysis. Results: In the Mito series, four factors were identified as favoring longer survival: Karnofsky Performance Status (90% to 100% vs. 70% to 80%), tumor numbers (solitary vs. multiple), primary tumor status (controlled vs. not controlled), and non-brain METs (no vs. yes). This new index is the sum of scores (0 and 1) of these four factors: RPA Class II-a, score of 0 or 1; RPA Class II-b, score of 2; and RPA Class II-c, score of 3 or 4. Next, using the Chiba series, we tested whether our index is valid for a different patient group. This new system showed highly statistically significant differences among subclasses in both the Mito series and the Chiba series (p < 0.001 for all subclasses). In addition, this new index was confirmed to be applicable to Class II patients with four major primary tumor sites, that is, lung, breast, alimentary tract, and urogenital organs. Conclusions: Our new grading system should be considered when designing future clinical trials involving brain MET

  11. A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

    Science.gov (United States)

    Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

    2015-01-01

    Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

  12. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

    Science.gov (United States)

    Balamurugan, Appakalai N; Green, Michael L; Breite, Andrew G; Loganathan, Gopalakrishnan; Wilhelm, Joshua J; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G; Williams, Stuart K; Hering, Bernhard J; Dwulet, Francis E; McCarthy, Robert C

    2016-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

  13. Computational screening of Six Antigens for potential MHC class II restricted epitopes and evaluating its CD4+ T-Cell Responsiveness against Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Manas Ranjan

    2017-12-01

    Full Text Available Visceral leishmaniasis is one of the most neglected tropical diseases for which no vaccine exists. In spite of extensive efforts, no successful vaccine is available against this dreadful infectious disease. To support the vaccine development, immunoinformatics approach was applied to search for potential MHC-classII restricted epitopes that can activate the immune cells. Initially, a total of 37 epitopes derived from six, stage dependent over expressed antigens were predicted, which were presented by at least 26 diverse MHC class II alleles including: DRB10101, DRB10301, DRB10401, DRB10404, DRB10405, DRB10701, DRB10802, DRB10901, DRB11101, DRB11302, DRB11501, DRB30101, DRB40101, DRB50101, DPA10103-DPB10401, DPA10103-DPB10201, DPA10201-DPB10101, DPA10103-DPB10301_DPB10401, DPA10301-DPB10402, DPA10201-DPB105021, DQA10102-DQB10602, DQA10401-DQB10402, DQA10501-QB10201, DQA10501-DQB10301, DQA10301-DQB10302 and DQA10101-DQB10501. Based on the population coverage analysis and HLA cross presentation ability, six epitopes namely, FDLFLFSNGAVVWWG (P1, YPVYPFLASNAALLN (P2, VYPFLASNAALLNLI (P3, LALLIMLYALIATQF (P4, LIMLYALIATQFSDD (P5, IMLYALIATQFSDDA (P6 were selected for further analysis. Stimulation with synthetic peptide alone or as a cocktail triggered the intracellular IFN-γ production. Moreover, specific IgG class of antibodies was detected in the serum of active VL cases against P1, P4, P and P6 in order to evaluate peptide effect on humoral immune response. Additionally, most of the peptides, except P2, were found to be non-inducer of CD4+ IL-10 against both active VL as well as treated VL subjects. Peptide immunogenicity was validated in BALB/c mice immunized with cocktail of synthetic peptide emulsified in complete Freund’s adjuvant/incomplete Freund’s adjuvant. The immunized splenocytes induced strong spleen cell proliferation upon parasite re-stimulation. Furthermore, an increased IFN-γ, IL-12, IL-17 and IL-22 production augmented with

  14. MHC class II+ (HLA-DP-like) cells in the cow reproductive tract: II. Immunolocalization of MHC class II+ cells in oviduct and vagina.

    Science.gov (United States)

    Eren, U; Kum, S; Sandikçi, M; Eren, V; Ilhan, F

    2009-08-01

    The aim of this study was to determine and examine the distribution of major frequency MHC II+ cells in the oviduct and vagina of cows during the oestrous and dioestrus phases. Right oviduct (ampulla, isthmus) and vaginal samples taken from a total of twenty seven multiparous cows were used. Tissue samples were processed to obtain both cryostat and paraffin sections. Sections were stained immunocytochemically using StreptABC method using a specific monoclonal antibody to MHC II+ cell population. Intra-epithelial and subepithelial areas along with lamina propria, muscularis mucosae and serosa of both ampulla and isthmus and intra-epithelial/subepithelial areas and mucosae of vagina were examined for the presence of MHC II+ cells. The density of immune positive cells was determined using a subjective scoring system. MHC II+ cells were demonstrated in all areas examined in both oestrus and dioestrus. In oestrus, the density of MHC II+ cells decreased in subepithelial areas (in between the epithelial cells and the basal membrane) of isthmus, whereas the density of immune positive cells was increased in muscularis mucosae of isthmus (P < 0.05), lamina propria and muscularis mucosae of ampulla (P < 0.05) as well as in the mucosae of vagina (P II+ cells observed in the oviduct and vagina increases in the majority of areas examined due to the effect of oestrogen.

  15. Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II.

    Science.gov (United States)

    Hartlehnert, Maike; Derksen, Angelika; Hagenacker, Tim; Kindermann, David; Schäfers, Maria; Pawlak, Mathias; Kieseier, Bernd C; Meyer Zu Horste, Gerd

    2017-10-02

    The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo. Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cells in mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic pain using the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia and, to a lesser extent, also diminishes mechanical allodynia in CCI in female mice. This was accompanied by a reduction of intraneural CD4+ T cells and greater preservation of preferentially large-caliber axons. Activation of T helper cells by MHC-II on Schwann cells thus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cells gain antigen-presenting function in vivo and modulate local immune responses and diseases in the peripheral nerves.

  16. Class II young adult treatment with Twin Force Bite corrector: 10-year follow-up

    Directory of Open Access Journals (Sweden)

    Ozge Uslu-Akcam

    2017-01-01

    Full Text Available One of the most preferred compliance free fixed functional appliances in nongrowing patients is Twin Force Bite corrector (TFBC. The aim of this case report is to evaluate the effectiveness of TFBC in the treatment of an adult Class II case. A 16-year 1-month-old boy having skeletal and dental Class II relationship was selected. Roth 0.018 × 0.025 inch slots brackets were attached; a fixed lingual arch in the mandibular dental arch and a Nance appliance in the maxillary dental arch were used to increase anchorage. The TFBC therapy used for sagittal activation and stimulation of forward mandibular growth lasted for 3 months. The post-TFBC treatment lasted 6 months and the total treatment time was 9 months. Treatment of a young adult Class II malocclusion with TFBC resulted in a Class I molar occlusion, an ideal overjet, overbite, and incisor angulation in a short time and maintained in the 10-year follow-up.

  17. Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Stanley K.L. [Singapore Immunology Network A-STAR (Singapore); Neo, Soek-Ying, E-mail: neo_soek_ying@sics.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Yap, Yann-Wan [Singapore Immunology Network A-STAR (Singapore); Karuturi, R. Krishna Murthy; Loh, Evelyn S.L. [Genome Institute of Singapore A-STAR (Singapore); Liau, Kui-Hin [Department of General Surgery, Tan Tock Seng Hospital (Singapore); Ren, Ee-Chee, E-mail: ren_ee_chee@immunol.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)

    2009-09-18

    Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2{alpha}) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2{alpha} mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2{alpha} was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2{alpha} can modulate HCC cell growth.

  18. Signal peptide-dependent inhibition of MHC class I heavy chain translation by rhesus cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Colin J Powers

    2008-10-01

    Full Text Available The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I, we examined whether this is also observed for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV lacking US2-11 was still able to inhibit MHC-I expression in infected fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism. Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC-I expression is fully restored upon additional deletion of rh178. The protein encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain (HC expression, but did not inhibit mRNA transcription or association of HC mRNA with translating ribosomes. Proteasome inhibitors stabilized a HC degradation intermediate in the absence of rh178, but not in its presence, suggesting that rh178 prevents completion of HC translation. This interference was signal sequence-dependent since replacing the signal peptide with that of CD4 or murine HC rendered human HCs resistant to rh178. We have identified an inhibitor of antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of homology to any other known protein and in its mechanism of action. By preventing signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11 which attack MHC-I proteins after protein synthesis is completed. Rh178 is the first viral protein known to interfere at this step of the MHC-I pathway, thus taking advantage of the conserved nature of HC leader peptides, and represents a new mechanism of translational interference.

  19. Orthodontic treatment of nongrowing patient with class II division 2 malocclusion by Herbst appliance

    Directory of Open Access Journals (Sweden)

    Nedeljković Nenad

    2009-01-01

    Full Text Available Background. Inheritance is most casual etiological factor of Class II division 2 malocclusion. This kind of malocclusion is very difficult for treatment specially in older patients. Case report. In the female patient, 20 years old, at the beginning of the treatment at the School of Dentistry in Belgrade, lateral cephalogram showed skeletal and dentoalveolar Class II division 2 malocclusion. She was in the Herbst treatment for 8 months and 12 months more with a fixed multibracket appliance. The measurements were performed on lateral cephalograms before and after the treatment: ii, is, mi, ms, Pg and ss. The distance from these points to occlusal perpendicular line (Olp were measured and compared from cephalogram before to cephalogram after the treatment. Temporomandibular joint (TMJ tomograms were compared from before and after the treatment by superimposition. Correction was found in molar and incisor relation, overjet and overbite. There were found sagital skeletal changes and soft tissue profile improvement. Conclusion. Herbst appliance is effective in the treatment of Class II malocclusions, even in adult patients. Dental and skeletal changes as a result of Herbst treatment could be good choice instead of camouflage orthodontics or surgical decision.

  20. Skeletal and dental changes induced by bionator in early treatment of class II

    Directory of Open Access Journals (Sweden)

    Dirceu Barnabé Raveli

    2016-09-01

    Full Text Available The purpose was to investigate the amount of skeletal and dentoalveolar changes after early treatment of Class II, Division 1 malocclusion with bionator appliance in prepubertal growing patients. Forty Class II patients were divided in two groups. Treated group consisted of 20 subjects treated consecutively with bionator. Mean age at the start of treatment (T0 was 9.1 years, while it was 10.6 years at the end of treatment (T1. Mean treatment time was 17.7 months. Pretreatment and post-treatment cephalometric records of treated group were evaluated and compared with a control group consisted of 20 patients with untreated Class II malocclusion. Intergroup comparisons were performed using Student’s t-tests and chi-square test with Yates’ correction at a significance level of 5 per cent. Bionator appliance was effective in generating differential growth between the jaws. Cephalometric skeletal measurements ANB, WITS, Lafh, Co-A and dental L6-Mp, U1.Pp, IsIi, OB, OJ showed statistically significantly different from the control. Bionator induced more dentoalveolar changes than skeletal during treatment in prepubertal stage.

  1. Cephalometric assessment of lips in skeletal class ii patients by steiner's line

    International Nuclear Information System (INIS)

    Bokhari, F.; Amin, F.; Asad, S.

    2013-01-01

    Introduction: Steiner's (S) Line has been used as reference line to assess anteroposterior position of lips cephalometrically and has been an effective diagnostic aid in this era of soft tissue paradigm. Norms for Sline has been established for different populations and it has been used widely to assess treatment outcomes in Skeletal Class II malocclusion, however anteroposterior position of lips and determinants of lip position in Skeletal Class II has not been explored. Study Design: This Prospective study was aimed to find out the anteroposterior position of lips on cephalograph using S-line in patients with retrognathic pro-file and to establish correlation between determinants of lip prominence. Data was collected using nonprobability convenience sampling technique following the selection criteria. Materials and Methods: The study was conducted on 65 subjects, with retrognathic profile as judged by orthodontists in consensus and confirmed by lateral cephalogram (ANB > 4 degree). S-Line was drawn on lateral cephalograph to assess the prominence of upper Lip and lower lip. SPSS 17.0 was used for statistical evaluation. Results: Antero-posterior position of upper and lower lip in patients with retrognathic profile with reference to S-line was 1.96 +- 2.6 mm and 3.09 +- 3.16 mm respectively. Moreover it was found that statistically significant correlation existed between lower lip prominence as assessed by S-line and upper lip prominence using the same reference line (r = 0.411), Lower incisor inclination (r = 0.535) and Skeletal Class II as assessed by ANB angle (r = 0.27). Upper lip prominence as assessed S-line was found to be statistically significantly correlated with lower incisor inclination and lower lip prominence. Discussion: Results were compliant with the previous studies.Conclusion: In the present study both upper and lower lips were more prominent in Skeletal Class II patients as compared to Steiner's norms for skeletal class I. (author)

  2. Influence of unilateral maxillary first molar extraction treatment on second and third molar inclination in Class II subdivision patients

    NARCIS (Netherlands)

    Livas, Christos; Pandis, Nikolaos; Booij, Johan Willem; Halazonetis, Demetrios J.; Katsaros, Christos; Ren, Yijin

    Objective: To assess the maxillary second molar (M2) and third molar (M3) inclination following orthodontic treatment of Class II subdivision malocclusion with unilateral maxillary first molar (M1) extraction. Materials and Methods: Panoramic radiographs of 21 Class II subdivision adolescents (eight

  3. 75 FR 69089 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0514] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance...

  4. 77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-03-19

    ... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...

  5. 76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

    Science.gov (United States)

    2011-05-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance Document... of the guidance entitled ``Guidance for Industry and Food and Drug Administration Staff; Class II...

  6. Survival of self-etch adhesive Class II composite restorations using ART and conventional cavity preparations in primary molars.

    NARCIS (Netherlands)

    Eden, E.; Topaloglu-Ak, A.; Frencken, J.E.F.M.; Hof, M.A. van 't

    2006-01-01

    PURPOSE: To test the null-hypothesis that there was no difference in the survival percentages of Class II composite restorations in primary teeth produced through either ART or conventional approaches after 2 years. METHODS: 157 children with 325 Class II cavitated dentin lesions were included in a

  7. 25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

    Science.gov (United States)

    2010-04-01

    ... on a Class II gaming system? 547.12 Section 547.12 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY... gaming system? This section provides standards for downloading on a Class II gaming system. (a) Downloads...

  8. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Science.gov (United States)

    2010-04-01

    ... applicable to Class II gaming systems? 547.7 Section 547.7 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY... gaming systems? (a) General requirements. (1) The Class II gaming system shall operate in compliance with...

  9. Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments

    NARCIS (Netherlands)

    Wubbolts, R.; Fernandez-Borja, M.; Jordens, I.; Reits, E.; Dusseljee, S.; Echeverri, C.; Vallee, R. B.; Neefjes, J.

    1999-01-01

    MHC class II molecules exert their function at the cell surface by presenting to T cells antigenic fragments that are generated in the endosomal pathway. The class II molecules are targetted to early lysosomal structures, termed MIIC, where they interact with antigenic fragments and are subsequently

  10. A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere.

    Science.gov (United States)

    Rutenber, E E; McPhee, F; Kaplan, A P; Gallion, S L; Hogan, J C; Craik, C S; Stroud, R M

    1996-09-01

    The essential role of HIV-1 protease (HIV-1 PR) in the viral life cycle makes it an attractive target for the development of substrate-based inhibitors that may find efficacy as anti-AIDS drugs. However, resistance has arisen to potent peptidomimetic drugs necessitating the further development of novel chemical backbones for diversity based chemistry focused on probing the active site for inhibitor interactions and binding modes that evade protease resistance. AQ148 is a potent inhibitor of HIV-1 PR and represents a new class of transition state analogues incorporating an aminimide peptide isostere. A 3-D crystallographic structure of AQ148, a tetrapeptide isostere, has been determined in complex with its target HIV-1 PR to a resolution of 2.5 A and used to evaluate the specific structural determinants of AQ148 potency and to correlate structure-activity relationships within the class of related compounds. AQ148 is a competitive inhibitor of HIV-1 PR with a Ki value of 137 nM. Twenty-nine derivatives have been synthesized and chemical modifications have been made at the P1, P2, P1', and P2' sites. The atomic resolution structure of AQ148 bound to HIV-1 PR reveals both an inhibitor binding mode that closely resembles that of other peptidomimetic inhibitors and specific protein/inhibitor interactions that correlate with structure-activity relationships. The structure provides the basis for the design, synthesis and evaluation of the next generation of hydroxyethyl aminimide inhibitors. The aminimide peptide isostere is a scaffold with favorable biological properties well suited to both the combinatorial methods of peptidomimesis and the rational design of potent and specific substrate-based analogues.

  11. 454 sequencing reveals extreme complexity of the class II Major Histocompatibility Complex in the collared flycatcher

    Directory of Open Access Journals (Sweden)

    Gustafsson Lars

    2010-12-01

    Full Text Available Abstract Background Because of their functional significance, the Major Histocompatibility Complex (MHC class I and II genes have been the subject of continuous interest in the fields of ecology, evolution and conservation. In some vertebrate groups MHC consists of multiple loci with similar alleles; therefore, the multiple loci must be genotyped simultaneously. In such complex systems, understanding of the evolutionary patterns and their causes has been limited due to challenges posed by genotyping. Results Here we used 454 amplicon sequencing to characterize MHC class IIB exon 2 variation in the collared flycatcher, an important organism in evolutionary and immuno-ecological studies. On the basis of over 152,000 sequencing reads we identified 194 putative alleles in 237 individuals. We found an extreme complexity of the MHC class IIB in the collared flycatchers, with our estimates pointing to the presence of at least nine expressed loci and a large, though difficult to estimate precisely, number of pseudogene loci. Many similar alleles occurred in the pseudogenes indicating either a series of recent duplications or extensive concerted evolution. The expressed alleles showed unambiguous signals of historical selection and the occurrence of apparent interlocus exchange of alleles. Placing the collared flycatcher's MHC sequences in the context of passerine diversity revealed transspecific MHC class II evolution within the Muscicapidae family. Conclusions 454 amplicon sequencing is an effective tool for advancing our understanding of the MHC class II structure and evolutionary patterns in Passeriformes. We found a highly dynamic pattern of evolution of MHC class IIB genes with strong signals of selection and pronounced sequence divergence in expressed genes, in contrast to the apparent sequence homogenization in pseudogenes. We show that next generation sequencing offers a universal, affordable method for the characterization and, in perspective

  12. MHC polymorphism and disease resistance in Atlantic salmon (Salmo salar); facing pathogens with single expressed major histocompatibility class I and class II loci

    NARCIS (Netherlands)

    Grimholt, U.; Larsen, S.; Nordmo, R.; Midtlyng, P.; Kjoeglum, S.; Storset, A.; Saebo, S.; Stet, R.J.M.

    2003-01-01

    Few studies have yet addressed the functional aspects of MHC molecules in fish. To lay the foundation for this, we evaluated the association between disease resistance and MHC class I and class II polymorphism in Atlantic salmon. Standardized disease challenge trials were performed on a semi-wild

  13. Characterization of EBV gB indicates properties of both class I and class II viral fusion proteins

    International Nuclear Information System (INIS)

    Backovic, Marija; Leser, George P.; Lamb, Robert A.; Longnecker, Richard; Jardetzky, Theodore S.

    2007-01-01

    To gain insight into Epstein-Barr virus (EBV) glycoprotein B (gB), recombinant, secreted variants were generated. The role of putative transmembrane regions, the proteolytic processing and the oligomerization state of the gB variants were investigated. Constructs containing 2 of 3 C-terminal hydrophobic regions were secreted, indicating that these do not act as transmembrane anchors. The efficiency of cleavage of the gB furin site was found to depend on the nature of C-terminus. All of the gB constructs formed rosette structures reminiscent of the postfusion aggregates formed by other viral fusion proteins. However, substitution of putative fusion loop residues, WY 112-113 and WLIY 193-196 , with less hydrophobic amino acids from HSV-1 gB, produced trimeric protein and abrogated the ability of the EBV gB ectodomains to form rosettes. These data demonstrate biochemical features of EBV gB that are characteristic of other class I and class II viral fusion proteins, but not of HSV-1 gB

  14. Identification of MHC class I H-2 Kb/Db-restricted immunogenic peptides derived from retinal proteins

    DEFF Research Database (Denmark)

    Wang, Mingjun; Bai, Fang; Pries, Mette

    2006-01-01

    PURPOSE: To identify H-2 Kb/Db-binding immunogenic peptides derived from retinal proteins. METHODS: Computer-based prediction was used to identify potentially H-2 Kb/Db-binding peptides derived from the interphotoreceptor retinol-binding protein (IRBP), soluble retinal antigen (S...... on day 21 after immunization with IRBP or IRBP and the immunogenic peptides. RESULTS: All the 21 predicted peptides were found to upregulate expression of H-2 Kb/Db on RMA-S cells. Five peptides, the two IRBP-derived peptides IRBP89-96 and IRBP(101-108), and the three PEDF-derived peptides, PEDF389....... The immunogenic peptides alone did not induce inflammation in the eyes, but they could enhance severity of uveitis induced by IRBP. CONCLUSIONS: Five of 21 H-2 Kb/Db-binding retinal protein-derived peptides were found to be immunogenic, suggesting that these peptides could function as autoantigenic epitopes...

  15. Isolation and characterization of major histocompatibility complex class II B genes in cranes.

    Science.gov (United States)

    Kohyama, Tetsuo I; Akiyama, Takuya; Nishida, Chizuko; Takami, Kazutoshi; Onuma, Manabu; Momose, Kunikazu; Masuda, Ryuichi

    2015-11-01

    In this study, we isolated and characterized the major histocompatibility complex (MHC) class II B genes in cranes. Genomic sequences spanning exons 1 to 4 were amplified and determined in 13 crane species and three other species closely related to cranes. In all, 55 unique sequences were identified, and at least two polymorphic MHC class II B loci were found in most species. An analysis of sequence polymorphisms showed the signature of positive selection and recombination. A phylogenetic reconstruction based on exon 2 sequences indicated that trans-species polymorphism has persisted for at least 10 million years, whereas phylogenetic analyses of the sequences flanking exon 2 revealed a pattern of concerted evolution. These results suggest that both balancing selection and recombination play important roles in the crane MHC evolution.

  16. Incisor root resorption in class II division 2 patients in relation to orthodontic treatment

    DEFF Research Database (Denmark)

    Faxén Sepanian, Varro; Sonnesen, Liselotte

    2018-01-01

    Background/Objectives: The aims were 1. to analyse differences in the occurrence of orthodontic induced inflammatory root resorption (OIIRR) of the upper and lower incisors in Angle Class II division 2 patients, between patients treated with fixed appliance only (one-phase treatment group......-four subjects treated for Class II division 2 malocclusion were divided into two groups: 46 patients in the one-phase treatment group (28 girls, 18 boys, mean age 14.4) and 28 patients in the two-phase treatment group (18 girls, 10 boys, mean age 12.4) where 336 and 201 incisors were analysed respectively...... group showed significantly more OIIRR for lower central incisors (P = 0.002) compared to the two-phase treatment group. For the both groups combined, boys showed more OIIRR than girls (P = 0.002) and patients with agenesis showed more OIIRR than patients without agenesis (P = 0.019) for the lower...

  17. Efficacy of MTA and CEM Cement with Collagen Membranes for Treatment of Class II Furcation Defects.

    Directory of Open Access Journals (Sweden)

    Habib Ollah Ghanbari

    2014-06-01

    Full Text Available This study aimed to compare the efficacy of MTA and CEM cement in Class II furcation defects in human mandibular molars.Forty furcation defects were treated in 16 patients with chronic periodontitis. The clinical parameters of probing depth (PD, vertical and horizontal clinical attachment levels (VCAL and HCAL, open vertical and horizontal furcation depths (OVFD and OHFD, and gingival margin level (GML were measured at baseline and at 3- and 6-month (re-entry surgery postoperatively. Data were analyzed at a significance level of P<0.05.Use of MTA and CEM caused significant decreases in PD, VCAL, HCAL, OVFD and OHFD at re-entry, with no statistically significant differences between the two treatment options in soft and hard tissue parameters.Both treatment modalities caused significant gains in attachment levels and bone fills, proving efficacy for treatment of Class II furcation involvements.

  18. Durability of a low shrinkage TEGDMA/HEMA-free resin composite system in Class II restorations

    DEFF Research Database (Denmark)

    van Dijken, Jan WV; Pallesen, Ulla

    2017-01-01

    with a mean age of 53 years (range 29-82). Each participant received at random two, as similar as possible, Class II restorations. In the first cavity of each pair the TEGDMA/HEMA-free resin composite system was placed with its 3-step etch-and-rinse adhesive (cmf-els). In the second cavity a 1-step HEMA......Objective: The objective of this randomized controlled prospective trial was to evaluate the durability of a low shrinkage and TEGDMA/HEMA-free resin composite system in posterior restorations in a 6-year follow up. Material and methods: 139 Class II restorations were placed in 67 patients......-free self-etch adhesive was used (AdheSe One F). The restorations were evaluated using slightly modified USPHS criteria at baseline and then yearly during 6 years. Caries risk and parafunctional habits of the participants were estimated. Results: Three molar teeth showed mild post-operative sensitivity...

  19. Camouflage of Severe Skeletal Class II Gummy Smile Patient Treated Nonsurgically with Mini Implants

    Directory of Open Access Journals (Sweden)

    Irfan Qamruddin

    2014-01-01

    Full Text Available Skeletal class II has always been a challenge in orthodontics and often needs assistance of surgical orthodontics in nongrowing patients when it presents with severe discrepancy. Difficulty increases more when vertical dysplasia is also associated with sagittal discrepancy. The advent of mini implants in orthodontics has broadened the spectrum of camouflage treatment. This case report presents a 16-year-old nongrowing girl with severe class II because of retrognathic mandible, and anterior dentoalveolar protrusion sagittally and vertically resulted in severe overjet of 13 mm and excessive display of incisors and gums. Both maxillary central incisors were trimmed by general practitioner few years back to reduce visibility. Treatment involved use of micro implant for retraction and intrusion of anterior maxillary dentoalveolar segment while lower incisors were proclined to obtain normal overjet, and overbite and pleasing soft tissue profile. Smile esthetics was further improved with composite restoration of incisal edges of both central incisors.

  20. Expansion design for a radioactive sources handling laboratory type II class B

    International Nuclear Information System (INIS)

    Sanchez S, P. S.; Monroy G, F.; Alanis, J.

    2013-10-01

    The Radioactive Wastes Research Laboratory (RWRL) of the Instituto Nacional de Investigaciones Nucleares (Mexico), at the moment has three sections: instrumental analysis, radioactive material processes, counting and a license type II class C, to manipulate radioactive material. This license limits the open sources handling to 300 kBq for radionuclides of very high radio-toxicity as the Ra-226, for what is being projected the license extension to type II class B, to be able to manage until 370 MBq of this radionuclides type, and the Laboratory, since the location where is the RWRL have unused area. This work presents a proposal of the RWRL expansion, taking into account the current laboratory sections, as well as the established specifications by the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS). The current planes of the RWRL and the expansion proposal of the laboratory are presented. (Author)

  1. Characterization of MHC class II B polymorphism in bottlenecked New Zealand saddlebacks reveals low levels of genetic diversity.

    Science.gov (United States)

    Sutton, Jolene T; Robertson, Bruce C; Grueber, Catherine E; Stanton, Jo-Ann L; Jamieson, Ian G

    2013-08-01

    The major histocompatibility complex (MHC) is integral to the vertebrate adaptive immune system. Characterizing diversity at functional MHC genes is invaluable for elucidating patterns of adaptive variation in wild populations, and is particularly interesting in species of conservation concern, which may suffer from reduced genetic diversity and compromised disease resilience. Here, we use next generation sequencing to investigate MHC class II B (MHCIIB) diversity in two sister taxa of New Zealand birds: South Island saddleback (SIS), Philesturnus carunculatus, and North Island saddleback (NIS), Philesturnus rufusater. These two species represent a passerine family outside the more extensively studied Passerida infraorder, and both have experienced historic bottlenecks. We examined exon 2 sequence data from populations that represent the majority of genetic diversity remaining in each species. A high level of locus co-amplification was detected, with from 1 to 4 and 3 to 12 putative alleles per individual for South and North Island birds, respectively. We found strong evidence for historic balancing selection in peptide-binding regions of putative alleles, and we identified a cluster combining non-classical loci and pseudogene sequences from both species, although no sequences were shared between the species. Fewer total alleles and fewer alleles per bird in SIS may be a consequence of their more severe bottleneck history; however, overall nucleotide diversity was similar between the species. Our characterization of MHCIIB diversity in two closely related species of New Zealand saddlebacks provides an important step in understanding the mechanisms shaping MHC diversity in wild, bottlenecked populations.

  2. The application of NISA II FEM package in seismic qualification of small class IE electric motors

    International Nuclear Information System (INIS)

    Fancev, T.; Saban, I.; Grgic, D.

    1995-01-01

    According to the IEEE standards 323/1974 and 344/1975, seismic qualification of class IE equipment is appropriate combination of test and analysis methods. Complex equipment and assemblies are usually tested through seismic testing. The analysis is recommended for simple equipment that can be easily modeled to correctly predict its response. This article deals with the application of NISA II FEM package in 3D FE modeling and mode shape calculations of small power low voltage electric motors. (author)

  3. Orthodontic Class II:1 treatment-efficiency and outcome quality of Herbst-multibracket appliance therapy.

    Science.gov (United States)

    Bock, N; Ruehl, J; Ruf, S

    2017-12-08

    The aim of this retrospective investigation was to assess the efficiency and outcome quality of Class II:1 treatment (Tx). The investigation is based on the evaluation of all Class II:1 patients that ever (1986-2014) started Tx with a Herbst appliance and subsequently a multibracket appliance (MBA) at the study center. Study casts from before Tx, after Herbst-MBA Tx, and (if available) after ≥ 24 months of retention were evaluated using the Peer Assessment Rating (PAR) index, the Ahlgren scale, and standard occlusal variables. In total, 526 Class II:1 patients with a mean pre-Tx age of 14.4 years (range 9.8-44.4) had received Herbst-MBA Tx; 18 patients discontinued Tx before completion. For 240 patients, data from ≥ 24 months of retention were available. The pre-Tx PAR score of 32.4 ± 8.83 was reduced to 8.0 ± 4.51 during Tx. A slight increase to 8.8 ± 5.11 occurred during retention. The percentage of patients which could be assigned to the category "greatly improved" was 62% after Tx and 57% after retention; only 2-3% had to be assigned to the category "worse/no different." The outcome ratings according to the Ahlgren scale revealed 17% excellent, 35% good, 45% satisfactory, and 3% unsuccessful results. Class II:1 Tx using Herbst-MBA is an efficient approach in orthodontic care. During a mean active Tx period of 2 years, high-quality results can be obtained in the majority of patients. The present investigation is the first to investigate a large unselected cohort of consecutive Herbst-MBA patients to determine representative data on the efficiency and the outcome quality of this Tx approach.

  4. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens

    2014-01-01

    sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast...

  5. A caspase-2-RFXANK interaction and its implication for MHC class II expression.

    Science.gov (United States)

    Forsberg, Jeremy; Li, Xinge; Akpinar, Birce; Salvatori, Roger; Ott, Martin; Zhivotovsky, Boris; Olsson, Magnus

    2018-01-23

    Despite recent achievements implicating caspase-2 in tumor suppression, the enzyme stands out from the apoptotic caspase family as a factor whose function requires further clarification. To specify enzyme characteristics through the definition of interacting proteins in apoptotic or non-apoptotic settings, a yeast 2-hybrid (Y2H) screen was performed using the full-length protein as bait. The current report describes the analysis of a captured prey and putative novel caspase-2 interacting factor, the regulatory factor X-associated ankyrin-containing protein (RFXANK), previously associated with CIITA, the transactivator regulating cell-type specificity and inducibility of MHC class II gene expression. The interaction between caspase-2 and RFXANK was verified by co-immunoprecipitations using both exogenous and endogenous proteins, where the latter approach suggested that binding of the components occurs in the cytoplasm. Cellular co-localization was confirmed by transfection of fluorescently conjugated proteins. Enhanced caspase-2 processing in RFXANK-overexpressing HEK293T cells treated with chemotherapeutic agents further supported Y2H data. Yet, no distinct differences with respect to MHC class II expression were observed in plasma membranes of antigen-presenting cells derived from wild type and caspase-2 -/- mice. In contrast, increased levels of the total MHC class II protein was evident in protein lysates from caspase-2 RNAi-silenced leukemia cell lines and B-cells isolated from gene-targeted mice. Together, these data identify a novel caspase-2-interacting factor, RFXANK, and indicate a potential non-apoptotic role for the enzyme in the control of MHC class II gene regulation.

  6. Treatment of Class II subdivision malocclusion with congenitally missing upper lateral incisors: A case report

    OpenAIRE

    Siddharth Mehta; Ashima Valiathan; Arun Urala

    2014-01-01

    Orthodontic treatment for patients with unilateral or bilateral congenitally missing lateral incisor poses a challenge mainly with regard to treatment planning. The use of a diagnostic setup is one of the most important aids in the decision-making process. Two alternatives, orthodontic space closure or space opening for prosthetic replacement exist. The present case report shows use of the microimplant for unilateral upper molar distalization and space closure in a Class-II division 1 subdivi...

  7. Influence of the HLA class II polymorphism in chronic Chagas' disease.

    Science.gov (United States)

    Fernandez-Mestre, M T; Layrisse, Z; Montagnani, S; Acquatella, H; Catalioti, F; Matos, M; Balbas, O; Makhatadze, N; Dominguez, E; Herrera, F; Madrigal, A

    1998-04-01

    Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol. Comparison of DRB1 and DQB1 allele frequencies among the patients and control subjects showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting independent protective effects to the chronic infection in this population. Allele frequencies comparison between patients with and without cardiomyopathy showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased frequency of DRB1*1501 in the patients with arrhythmia and congestive heart failure. The results suggest that HLA Class II genes may be associated with the development of a chronic infection and with heart damage in Chagas' disease.

  8. Expansion design for a Laboratory of Radioactive Sources Handling type II, class B

    International Nuclear Information System (INIS)

    Sanchez S, P. S.

    2014-01-01

    This work presents the expansion design of the Radioactive Wastes Research Laboratory (RWRL) installation authorized by the Comision Nacional de Seguridad Nuclear y Salvaguardias (Mexico) as type II class C, to manage 40 different radionuclides, approximately. The RWRL has 4 areas at the present time: a laboratory of instrumental analysis, one of radioactive material processes, other of counting and a chemical reagents stock, which is not integrated to the operation license of the RWRL. With the purpose of expanding the operation license of the RWRL to an installation type II class B, to manage until 370 MBq of high radio toxicity radionuclides, is presented in this work an expansion proposal of the RWRL. The expansion proposal is based in: (1) the Mexican Nuclear Standard NOM-027-Nucl-1996 for installations type II class B, (2) the current distribution of water, light, electricity, extraction, gas, air and vacuum services of RWRL, and (3) the available areas inside the building that the RWRL occupies. The proposal contemplates the creation of additional new areas for RWRL: 3 laboratories, 2 dressing rooms, 2 bathrooms and 2 warehouses, one for radioactive materials and another for reagents chemical radiologically inactive. Architectural, electric, hydraulic, extraction and gas planes corresponding to the expansion of RWRL were realized. Inside the proposal the budget required to carry out the mentioned expansion is also presented. (Author)

  9. Class II malocclusion treatment using high-pull headgear with a splint: a systematic review

    Directory of Open Access Journals (Sweden)

    Helder B. Jacob

    2013-04-01

    Full Text Available OBJECTIVE: To systematically review the scientific evidence pertaining to the effectiveness of high-pull headgear in growing Class II subjects. METHODS: A literature survey was performed by electronic database search. The survey covered the period from January 1966 to December 2008 and used Medical Subject Headings (MeSH. Articles were initially selected based on their titles and abstracts; the full articles were then retrieved. The inclusion criteria included growing subjects between 8 to 15 years of age, Class II malocclusion treatment with high-pull headgear, and a control group with Class II malocclusion. References from selected articles were hand-searched for additional publications. Selected studies were evaluated methodologically. RESULTS: Four articles were selected; none were randomized controlled trials. All of the articles clearly formulated their objectives and used appropriate measures. The studies showed that high-pull headgear treatment improves skeletal and dental relationship, distal displacement of the maxilla, vertical eruption control and upper molars distalization. One of the studies showed a slight clockwise rotation of the palatal plane; the others showed no significant treatment effect. The mandible was not affected by the treatment. CONCLUSION: While there is still a lack of strong evidence demonstrating the effects of high-pull headgear with a splint, other studies indicate that the AP relations improve due to distalization of the maxilla and upper molars, with little or no treatment effects in the mandible. Greater attention to the design should be given to improve the quality of such trials.

  10. Treatment timing of MARA and fixed appliance therapy of Class II malocclusion.

    Science.gov (United States)

    Ghislanzoni, Luis Tomas Huanca; Baccetti, Tiziano; Toll, Douglas; Defraia, Efisio; McNamara, James A; Franchi, Lorenzo

    2013-06-01

    The objective of this study is to evaluate the effect of timing on Mandibular Anterior Repositioning Appliance (MARA) and fixed appliance treatment of Class II malocclusion in a prospective clinical trial. The treated sample consisted of 51 consecutively treated patients at prepubertal (n = 21), pubertal (n = 15), and postpubertal (n = 15) stages of development. Control groups for the three treated groups were generated from growth data of untreated Class II subjects. Lateral cephalograms were digitized and superimposed via cephalometric software at T1 (pre-treatment) and T2 (after comprehensive treatment). The T1-T2 changes in the treated groups were compared to those in their corresponding control groups with Mann-Whitney tests with Bonferroni correction. Mandibular elongation was greater at the pubertal stage (Co-Gn +2.6 mm, with respect to controls). Headgear effect on the maxilla was greater in the pre-peak sample (Co-A -1.9 mm, with respect to controls). Dentoalveolar compensations (proclination of lower incisors, extrusion and mesialization of lower molars, and reduction in the overbite) were significant in the pre-peak and post-peak groups. Optimal timing for Class II treatment with MARA appliance is at the pubertal growth spurt, with enhanced mandibular skeletal changes and minimal dentoalveolar compensations.

  11. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2013-01-01

    Full Text Available Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR, root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  12. Methylation of class II transactivator gene promoter IV is not associated with susceptibility to Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lincoln Matthew R

    2008-07-01

    Full Text Available Abstract Background Multiple sclerosis (MS is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology. Methods In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR. Results No methylation or sequence variation of the MHC2TA promoter pIV was found. Conclusion The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.

  13. Stability of class II subdivision malocclusion treatment with 3 and 4 premolar extractions.

    Science.gov (United States)

    Janson, Guilherme; Araki, Janine; Estelita, Sérgio; Camardella, Leonardo T

    2014-12-30

    The purpose of this study was to compare the occlusal stability of class II subdivision malocclusion treatment with 3 and 4 first premolar extractions. A sample of 156 dental casts from 52 patients with class II subdivision malocclusion was divided into two groups according to the extraction protocol. Group 1 comprised 24 patients treated with 3 premolar extractions and group 2 included 28 patients treated with 4 premolar extractions. Peer assessment rating (PAR) indexes were measured on the dental casts obtained before (T1) and after treatment (T2) and at a mean of 6.9 years after the end of treatment (T3). The groups were matching regarding sex distribution, pretreatment, posttreatment and long-term posttreatment ages, and treatment and long-term posttreatment times. They were also comparable concerning the initial malocclusion severity and the occlusal results at the end of treatment. Stability evaluation was calculated by subtracting the posttreatment from the long-term posttreatment index values (T3 - T2). T tests were used to compare the amount and percentage of long-term posttreatment changes. There were no intergroup differences regarding the amount and percentage of long-term posttreatment changes. Treatment of class II subdivision malocclusion with 3 and 4 premolar extractions have a similar long-term posttreatment occlusal stability.

  14. The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.

    Science.gov (United States)

    Andersson, Lisa S; Swinburne, June E; Meadows, Jennifer R S; Broström, Hans; Eriksson, Susanne; Fikse, W Freddy; Frey, Rebecka; Sundquist, Marie; Tseng, Chia T; Mikko, Sofia; Lindgren, Gabriella

    2012-03-01

    Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p (raw) = 2.34 × 10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.

  15. Use of "one-pot, mix-and-read" peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

    DEFF Research Database (Denmark)

    Svitek, Nicholas; Hansen, Andreas Martin; Steinaa, Lucilla

    2014-01-01

    Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8(+) cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and re...

  16. V-src oncogene-specific carboxy-terminal peptide is immunoprotective against Rous sarcoma growth in chickens with MHC class I allele B-F12

    Czech Academy of Sciences Publication Activity Database

    Hofmann, A.; Plachý, Jiří; Hunt, L.; Kaufman, J.; Hála, K.

    2003-01-01

    Roč. 2003, č. 21 (2003), s. 4694-4699 ISSN 0264-410X Institutional research plan: CEZ:AV0Z5052915 Keywords : Rous sarcoma * v-src peptide * chicken MHC class I allele Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.007, year: 2003

  17. The Position of Hyoici Bone in Skeletal Class I, II and III Patients

    Directory of Open Access Journals (Sweden)

    Ravanmehr H

    2000-06-01

    Full Text Available In this investigation, the position of hyoid bone was compared in three skeletal groups of class I, II and III. The study was based on evaluating 77 lateral cephalometric radiographs, 40 girls and 37 boys, which were divided into 3 groups. Group 1, 2, and 3 consist of 26, 25, and 26 radiographs. 19 cephalometric landmarks and 10 planes were used in order to tracing the radiographs. In all patients, 9 skeletal and 4 cervical vertebrae parameters were measured to determine the hyoid bone. These parameters were compared between three skeletal groups regardless of sex and then, in another statistical analysis, parameters were compared based on patients sex. Statistical analysis showed that in class III patients, the hyoid bone was positioned more anteriorly than two other groups. Also in this group, the hyoid bone had less inclination and it was more horizontal in relation to mandibular plane. In skeletal class II patients this bone was positioned more superiorly than two other groups. Due to these findings it can be concluded that perimandibular muscles and bones could affect the growth of mandible. In addition, comparison of the parameters between two sexes revealed that the hyoid bone was positioned more anteriorly and inferiorly in boys. Also it was shown that in the girls, the position of hyoid bone was closer to the position of this bone in skeletal class I patients.

  18. [Morphological analysis of alveolar bone of anterior mandible in high-angle skeletal class II and class III malocclusions assessed with cone-beam computed tomography].

    Science.gov (United States)

    Ma, J; Jiang, J H

    2018-02-18

    To evaluate the difference of features of alveolar bone support under lower anterior teeth between high-angle adults with skeletal class II malocclusions and high-angle adults presenting skeletal class III malocclusions by using cone-beam computed tomography (CBCT). Patients who had taken the images of CBCT were selected from the Peking University School and Hospital of Stomatology between October 2015 and August 2017. The CBCT archives from 62 high-angle adult cases without orthodontic treatment were divided into two groups based on their sagittal jaw relationships: skeletal class II and skeletal class III. vertical bone level (VBL), alveolar bone area (ABA), and the width of alveolar bone were measured respectively at the 2 mm, 4 mm, 6 mm below the cemento-enamel junction (CEJ) level and at the apical level. After that, independent samples t-tests were conducted for statistical comparisons. The ABA of the mandibular alveolar bone in the area of lower anterior teeth was significantly thinner in the patients of skeletal class III than those of skeletal class II, especially in terms of the apical ABA, total ABA on the labial and lingual sides and the ABA at 6 mm below CEJ level on the lingual side (Pclass III than those of skeletal class II, especially regarding the apical level on the labial and lingual side and at the level of 4 mm, 6 mm below CEJ level on the lingual side (Pclass III adult patients with high-angle when compared with the sample of high-angle skeletal class II adult cases. We recommend orthodontists to be more cautious in treatment of high-angle skeletal class III patients, especially pay attention to control the torque of lower anterior teeth during forward and backward movement, in case that the apical root might be absorbed or fenestration happen in the area of lower anterior teeth.

  19. VCD Robustness of the Amide-I and Amide-II Vibrational Modes of Small Peptide Models.

    Science.gov (United States)

    Góbi, Sándor; Magyarfalvi, Gábor; Tarczay, György

    2015-09-01

    The rotational strengths and the robustness values of amide-I and amide-II vibrational modes of For(AA)n NHMe (where AA is Val, Asn, Asp, or Cys, n = 1-5 for Val and Asn; n = 1 for Asp and Cys) model peptides with α-helix and β-sheet backbone conformations were computed by density functional methods. The robustness results verify empirical rules drawn from experiments and from computed rotational strengths linking amide-I and amide-II patterns in the vibrational circular dichroism (VCD) spectra of peptides with their backbone structures. For peptides with at least three residues (n ≥ 3) these characteristic patterns from coupled amide vibrational modes have robust signatures. For shorter peptide models many vibrational modes are nonrobust, and the robust modes can be dependent on the residues or on their side chain conformations in addition to backbone conformations. These robust VCD bands, however, provide information for the detailed structural analysis of these smaller systems. © 2015 Wiley Periodicals, Inc.

  20. Synthesis and Pharmacology of Halogenated δ-Opioid-Selective [D-Ala2]Deltorphin II Peptide Analogues

    Science.gov (United States)

    Pescatore, Robyn; Marrone, Gina F.; Sedberry, Seth; Vinton, Daniel; Finkelstein, Netanel; Katlowitz, Yitzchak E.; Pasternak, Gavril W.; Wilson, Krista R.; Majumdar, Susruta

    2015-01-01

    Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-D-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [D-Ala2]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the μ- and κ-opioid receptors. It is a full agonist in [35S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which 125I isincorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe3. The peptides were characterized for binding affinity at the μ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology. PMID:25844930

  1. Synthesis and pharmacology of halogenated δ-opioid-selective [d-Ala(2)]deltorphin II peptide analogues.

    Science.gov (United States)

    Pescatore, Robyn; Marrone, Gina F; Sedberry, Seth; Vinton, Daniel; Finkelstein, Netanel; Katlowitz, Yitzchak E; Pasternak, Gavril W; Wilson, Krista R; Majumdar, Susruta

    2015-06-17

    Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the μ- and κ-opioid receptors. It is a full agonist in [(35)S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which (125)I is incorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe(3). The peptides were characterized for binding affinity at the μ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology.

  2. Mycobacterium tuberculosis class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III exhibits DNA regulated modes of interaction with the sliding DNA β-clamp.

    Science.gov (United States)

    Khanam, Taran; Rai, Niyati; Ramachandran, Ravishankar

    2015-10-01

    The class-II AP-endonuclease (XthA) acts on abasic sites of damaged DNA in bacterial base excision repair. We identified that the sliding DNA β-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. A novel 239 QLRFPKK245 motif in the DNA-binding domain of XthA was found to be important for the interactions. Likewise, the peptide binding-groove (PBG) and the C-terminal of β-clamp located on different domains interact with XthA. The β-clamp-XthA complex can be disrupted by clamp binding peptides and also by a specific bacterial clamp inhibitor that binds at the PBG. We also identified that β-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the β-clamp onto DNA is required for activity stimulation. A reduction in XthA activity stimulation was observed in the presence of β-clamp binding peptides supporting that direct interactions between the proteins are necessary to cause stimulation. Finally, we found that in the absence of DNA, the PBG located on the second domain of the β-clamp is important for interactions with XthA, while the C-terminal domain predominantly mediates functional interactions in the substrate's presence. © 2015 John Wiley & Sons Ltd.

  3. Stability of Class II fixed functional appliance therapy—a systematic review and meta-analysis

    Science.gov (United States)

    von Bremen, Julia; Ruf, Sabine

    2016-01-01

    Summary Objectives: To systematically search for scientific evidence concerning the stability of treatment (Tx) results achieved by means of Class II fixed functional appliance therapy and to assess possible differences between appliances. Search Methods: An electronic search of databases and orthodontic journals was carried out (until December 2013), with supplemental hand searching. In addition to the names of all identified appliances, the term fixed functional was used in combination with each of the following search terms: long-term, post-Tx, relapse, retention, stability. Selection Criteria: To be included in the review, the articles had to contain clear data on: Class II Tx with a fixed functional appliance (>5 patients), post-Tx period ≥ 1 year, assessment of ANB angle, Wits appraisal, molar relationship, soft-tissue profile convexity excluding the nose, overjet and/or overbite. Data Collection and Analysis: The literature search revealed 20 scientific investigations which corresponded to only two of the 76 identified appliances (Herbst and Twin Force Bite Corrector). As only one publication was found for the Twin Force Bite Corrector, a meta-analysis could only be performed for Herbst Tx. The data were extracted, pooled and weighted according to the number of patients in each study. Results: The mean values for post-Tx relapse (percentages relative to the Tx changes) were: ANB angle 0.2 degrees (12.4 per cent), Wits appraisal 0.5mm (19.5 per cent), sagittal molar relationship 1.2mm/0.1 cusp widths (21.8 per cent /6.5 per cent); soft-tissue profile convexity excluding nose less than 0.1 degrees (1.0 per cent), overjet 1.8mm (26.2 per cent), overbite Class II:1 1.4mm (44.7 per cent), overbite Class II:2 1.0mm (22.2 per cent). Conclusions: The scientific evidence concerning the stability of Tx results is inexistent for most fixed functional appliances for Class II correction except for Herbst appliance Tx. Even if the evidence level of most included studies

  4. Comparison of temporomandibular joint and ramus morphology between class II and class III cases before and after bi-maxillary osteotomy.

    Science.gov (United States)

    Iguchi, Ran; Yoshizawa, Kunio; Moroi, Akinori; Tsutsui, Takamitsu; Hotta, Asami; Hiraide, Ryota; Takayama, Akihiro; Tsunoda, Tatsuya; Saito, Yuki; Sato, Momoko; Baba, Nana; Ueki, Koichiro

    2017-12-01

    The purpose of this study was to compare changes in temporomandibular joint (TMJ) and ramus morphology between class II and III cases before and after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. The subjects were 39 patients (78 sides) who underwent bi-maxillary surgery. They consisted of 2 groups (18 class II cases and 21 class III cases), and were selected randomly from among patients who underwent surgery between 2012 and 2016. The TMJ disc tissue and joint effusion were assessed by magnetic resonance imaging (MRI) and the TMJ space, condylar height, ramus height, ramus inclination and condylar square were assessed by computed tomography (CT), pre- and post-operatively. The number of joints with anterior disc displacement in class II was significantly higher than that in class III (p bi-maxillary surgery. The findings of the numerical analysis also demonstrated that reduction of condylar volume occurred frequently in class II, although TMJ disc position classification did not change significantly, as previously reported. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  5. Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings

    Directory of Open Access Journals (Sweden)

    Cory M. Ayres

    2017-08-01

    Full Text Available Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic “energy landscapes” of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology.

  6. The Dimanganese(II) Site of Bacillus subtilis Class Ib Ribonucleotide Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Boal, Amie K.; Cotruvo, Jr., Joseph A.; Stubbe, JoAnne; Rosenzweig, Amy C. (MIT); (NWU)

    2014-10-02

    Class Ib ribonucleotide reductases (RNRs) use a dimanganese-tyrosyl radical cofactor, Mn{sub 2}{sup III}-Y{sm_bullet}, in their homodimeric NrdF ({beta}2) subunit to initiate reduction of ribonucleotides to deoxyribonucleotides. The structure of the Mn{sub 2}{sup II} form of NrdF is an important component in understanding O{sub 2}-mediated formation of the active metallocofactor, a subject of much interest because a unique flavodoxin, NrdI, is required for cofactor assembly. Biochemical studies and sequence alignments suggest that NrdF and NrdI proteins diverge into three phylogenetically distinct groups. The only crystal structure to date of a NrdF with a fully ordered and occupied dimanganese site is that of Escherichia coli Mn{sub 2}{sup II}-NrdF, prototypical of the enzymes from actinobacteria and proteobacteria. Here we report the 1.9 {angstrom} resolution crystal structure of Bacillus subtilis Mn{sub 2}{sup II}-NrdF, representative of the enzymes from a second group, from Bacillus and Staphylococcus. The structures of the metal clusters in the {beta}2 dimer are distinct from those observed in E. coli Mn{sub 2}{sup II}-NrdF. These differences illustrate the key role that solvent molecules and protein residues in the second coordination sphere of the Mn{sub 2}{sup II} cluster play in determining conformations of carboxylate residues at the metal sites and demonstrate that diverse coordination geometries are capable of serving as starting points for Mn{sub 2}{sup III}-Y{sm_bullet} cofactor assembly in class Ib RNRs.

  7. Self-esteem in adolescents with Angle Class I, II and III malocclusion in a Peruvian sample

    Directory of Open Access Journals (Sweden)

    Karla Florián-Vargas

    2016-04-01

    Full Text Available ABSTRACT Objective: To compare self-esteem scores in 12 to 16-year-old adolescents with different Angle malocclusion types in a Peruvian sample. Material and Methods: A cross-sectional study was conducted in a sample of 276 adolescents (159, 52 and 65 with Angle Class I, II and III malocclusions, respectively from Trujillo, Peru. Participants were asked to complete the Rosenberg Self-Esteem Scale (RSES and were also clinically examined, so as to have Angle malocclusion classification determined. Analysis of covariance (ANCOVA was used to compare RSES scores among adolescents with Class I, II and III malocclusions, with participants' demographic factors being controlled. Results: Mean RSES scores for adolescents with Class I, II and III malocclusions were 20.47 ± 3.96, 21.96 ± 3.27 and 21.26 ± 4.81, respectively. The ANCOVA test showed that adolescents with Class II malocclusion had a significantly higher RSES score than those with Class I malocclusion, but there were no differences between other malocclusion groups. Supplemental analysis suggested that only those with Class II, Division 2 malocclusion might have greater self-esteem when compared to adolescents with Class I malocclusion. Conclusion: This study shows that, in general, self-esteem did not vary according to adolescents' malocclusion in the sample studied. Surprisingly, only adolescents with Class II malocclusion, particularly Class II, Division 2, reported better self-esteem than those with Class I malocclusion. A more detailed analysis assessing the impact of anterior occlusal features should be conducted.

  8. Specific Affinity Enrichment of Electrochemically Cleaved Peptides Based on Cu(II)-Mediated Spirolactone Tagging

    NARCIS (Netherlands)

    Zhang, Tao; de Vries, Marcel P.; Permentier, Hjalmar P.; Bischoff, Rainer

    2017-01-01

    Specific digestion of proteins is an essential step for mass spectrometry-based proteomics, and the chemical labeling of the resulting peptides is often used for peptide enrichment or the introduction of desirable tags. Electrochemical oxidation yielding specific cleavage C-terminal to tyrosine

  9. NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets

    DEFF Research Database (Denmark)

    Nielsen, Morten; Andreatta, Massimo

    2016-01-01

    Background: Binding of peptides to MHC class I molecules (MHC-I) is essential for antigen presentation to cytotoxic T-cells.Results: Here, we demonstrate how a simple alignment step allowing insertions and deletions in a pan-specific MHC-I binding machine-learning model enables combining informat...... specificities and ligand length scales, and demonstrated how this approach significantly improves the accuracy for prediction of peptide binding and identification of MHC ligands. The method is available at www.cbs.dtu.dk/services/NetMHCpan-3.0....

  10. In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function.

    Science.gov (United States)

    Follin, Elna; Karlsson, Maria; Lundegaard, Claus; Nielsen, Morten; Wallin, Stefan; Paulsson, Kajsa; Westerdahl, Helena

    2013-04-01

    The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1-α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their functional and genetic relationships. We found more pronounced clustering of the MHC class I allomorphs (allele specific proteins) in regards to their function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrow and great reed warbler, although these species diverged 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be ruled out.

  11. Additional file 4: of MHC class II expression and potential antigen-presenting cells in the retina during experimental autoimmune uveitis

    OpenAIRE

    Lipski, Deborah; Dewispelaere, RÊmi; Foucart, Vincent; Caspers, Laure; Defrance, Matthieu; Bruyns, Catherine; Willermain, François

    2017-01-01

    Figure S4. MHC class II expression in the retina during classical EAU. Three weeks after immunization, eye cryosections were prepared and stained for MHC class II (green) and IBA1 (red) or endoglin (magenta) detection. Cell nuclei were stained with Hoechst (blue). Each picture was chosen as representative of an experiment conducted on six or more animals. A. MHC class II and IBA1 expression. B. MHC class II and endoglin expression. (PPTX 7276 kb)

  12. Amyloid-β peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.

    Science.gov (United States)

    Hanenberg, Michael; McAfoose, Jordan; Kulic, Luka; Welt, Tobias; Wirth, Fabian; Parizek, Petra; Strobel, Lisa; Cattepoel, Susann; Späni, Claudia; Derungs, Rebecca; Maier, Marcel; Plückthun, Andreas; Nitsch, Roger M

    2014-09-26

    Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. 40 CFR Figure C-2 to Subpart C of... - Illustration of the Slope and Intercept Limits for Class II and Class III PM2.5 Candidate...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Illustration of the Slope and Intercept Limits for Class II and Class III PM2.5 Candidate Equivalent Methods C Figure C-2 to Subpart C of Part 53... Methods and Reference Methods Pt. 53, Subpt. C, Fig. C-2 Figure C-2 to Subpart C of Part 53—Illustration...

  14. Cephalometric effects of the use of 10-hour Force Theory for Class II treatment

    Directory of Open Access Journals (Sweden)

    Marise de Castro Cabrera

    2012-12-01

    Full Text Available OBJECTIVE: This study aimed to evaluate the cephalometric effects promoted by the orthodontic treatment of Class II malocclusion patients with the use of the 10-Hour Force Theory, that consists in the use of fixed appliances with 8 hours a day using a cervical headgear appliance and 16 hours a day using Class II elastics, 8 hours on the first mandibular molar and 8 hours in the second mandibular molar. METHODS: Sample comprised 31 patients with mean initial age of 14.90 years, final mean age of 17.25 years and mean treatment time of 2.35 years. The lateral cephalograms in pre-treatment and post-treatment stages were evaluated. Evaluation of cephalometric changes between initial and final treatment phases was performed by paired t test. RESULTS: The cases treated with the 10-Hour Force Theory presented a slight restriction of anterior displacement of the maxilla, increase in the effective length of the mandible, significant improvement of the maxillomandibular relationship, significant increase in anterior lower face height, distal tipping of the maxillary premolar crowns, extrusion and distal tipping of the roots of maxillary molars, significant proclination and protrusion of mandibular incisors, significant extrusion and mesialization of mandibular molars, besides a significant correction of the molar relationship, overjet and overbite. CONCLUSION: The use of the 10-Hour Force Theory in treatment of Class II malocclusion provided satisfactory results.OBJETIVO: esse estudo objetivou avaliar os efeitos cefalométricos promovidos pelo tratamento ortodôntico de pacientes com má oclusão de Classe II com o uso da Teoria de Força das 10 Horas, que consiste no uso de aparelho ortodôntico fixo, 8 horas diárias de uso de aparelho extrabucal cervical e 16 horas de uso de elásticos de Classe II, sendo 8 horas com apoio no primeiro molar inferior e 8 horas com apoio no segundo molar inferior. MÉTODOS: a amostra consistiu de 31 pacientes, com idade m

  15. Surgical treatment of class II malocclusion in the orthodontic boundaries: a case report.

    Science.gov (United States)

    Bandeca, Matheus Coelho; Porto, Alessandra Nogueira; Valieri, Sidnei; Valieri, Matheus; Borges, Alvaro H; Mattos, Fernanda Zanol

    2014-01-01

    The aim of this study was to report a clinical case of treatment of Class II division I malocclusion with facial aesthetic impairment, whose therapeutic approach comprised the association of orthodontic treatment with orthognathic surgery. The treatment for the present case consisted of decompensation oflower incisors and extraction oftwo lower premolars, in order to obtain horizontal discrepancy allowing the surgery for mandibular advancement. At the end of treatment, we could clinically observe a Class I molar/canine relationship, normal overbite and overjet, presence of lip seal, type I facial profile with considerable aesthetic improvement. We can conclude that the ortho-surgical treatment is a therapeutic alternative providing the best prognosis in terms of aesthetic correction in patients with unpleasant facial profile.

  16. Bilateral sagittal split osteotomy: Surgery first approach for correction of skeletal Class II

    Directory of Open Access Journals (Sweden)

    Revathi Peddu

    2018-01-01

    Full Text Available Most of the skeletal malocclusions which require orthognathic surgeries are treated by traditional approach which requires time-consuming and unesthetic presurgical orthodontic phase. Surgery first approach (SFA avoids these disadvantages of the traditional approach. A 24-year-old female patient with skeletal and dental class II malocclusion due to retrognathic mandible was treated with SFA. Bilateral sagittal split osteotomy with mandibular advancement was done immediately after initial alignment and closure of the existing spaces in the maxillary arch. Angle's class I molar and canine relation was achieved after surgery. Bonding of the mandibular arch was done after 1 month of orthognathic surgery and treatment was completed within 13 months. A wrap-around retainer was placed in upper arch, and bonded lingual retainer was given in the lower arch.

  17. β class II tubulin predominates in normal and tumor breast tissues

    International Nuclear Information System (INIS)

    Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

    2003-01-01

    Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

  18. The effectiveness of the Herbst appliance for patients with Class II malocclusion: a meta-analysis

    Science.gov (United States)

    Yang, Xin; Zhu, Yafen; Long, Hu; Zhou, Yang; Jian, Fan; Ye, Niansong; Gao, Meiya

    2016-01-01

    Summary Objective: To systematically investigate review in literature the effects of the Herbst appliance for patients with Class II malocclusion patients. Method: We performed a comprehensive literature survey on PubMed, Web of Science, Embase, CENTRAL, SIGLE, and ClinicalTrial.gov up to December 2014. The selection criteria: randomized controlled trials or clinical controlled trials; using any kind of Herbst appliances to correct Class II division 1 malocclusions; skeletal and/or dental changes evaluated through lateral cephalograms. And the exclusion criteria: syndromic patients; individual case reports and series of cases; surgical interventions. Article screening, data extraction, assessment of risk of bias, and evaluation of evidence quality through GRADE were conducted independently by two well-trained orthodontic doctors. Consensus was made via group discussion of all authors when there is inconsistent information from the two. After that, sensitivity analysis and subgroup analysis were performed to evaluate the robustness of the meta-analysis. Results: Twelve clinical controlled trials meet the above-mentioned criteria, and were included in this analysis. All included studies have eleven measures taken during both active treatment effect and long term effect periods, including four angular ones (i.e., SNA, SNB, ANB, mandibular plane angle) and seven linear ones (i.e. Co-Go, Co-Gn, overjet, overbite, molar relationship, A point-OLp, Pg-OLp) during active treatment effect period were statistically pooled. Meta-analysis and sensitivity analysis demonstrated that all these measures showed consistent results except for SNA, ANB, and overbite. Subgroup analysis showed significant changes in SNA, overbite, and Pg-OLp. Publication bias was detected in SNB, mandibular plane angle, and A point-OLp. Conclusion: The Herbst appliance is effective for patients with Class II malocclusion in active treatment period. Especially, there are obvious changes on dental

  19. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

    Science.gov (United States)

    Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

    2011-02-01

    Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

    2012-01-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

  1. MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

    2012-02-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

  2. NMR structures of anti-HIV D-peptides derived from the N-terminus of viral chemokine vMIP-II

    International Nuclear Information System (INIS)

    Mori, Mayuko; Liu Dongxiang; Kumar, Santosh; Huang Ziwei

    2005-01-01

    The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi's sarcoma-associated herpesvirus has unique biological activities in that it blocks the cell entry by several different human immunodeficiency virus type 1 (HIV-1) strains via chemokine receptors including CXCR4 and CCR5. In this paper, we report the solution structure of all-D-amino acid peptides derived from the N-terminus of vMIP-II, which have been shown to have strong CXCR4 binding activity and potently inhibit HIV-1 entry via CXCR4, by using long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments. Both of all-D-peptides vMIP-II (1-10) and vMIP-II (1-21), which are designated as DV3 and DV1, respectively, have higher CXCR4 binding ability than their L-peptide counterparts. They are partially structured in aqueous solution, displaying a turn-like structure over residues 5-8. The small temperature coefficients of His-6 amide proton for both peptides also suggest the formation of a small hydrophobic pocket centered on His-6. The structural features of DV3 are very similar to the reported solution structure of all-L-peptide vMIP-II (1-10) [M.P. Crump, E. Elisseeva, J. Gong, I. Clark-Lewis, B.D. Sykes, Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10), FEBS Lett. 489 (2001) 171], which is consistent with the notion that D- and L-enantiomeric peptides can adopt mirror image conformations. The NMR structures of the D-peptides provide a structural basis to understand their mechanism of action and design new peptidomimetic analogs to further explore the structure-activity relationship of D-peptide ligand binding to CXCR4

  3. Class II malocclusion treatment using combined Twin Block and fixed orthodontic appliances – A case report

    Science.gov (United States)

    Al-Anezi, Saud A.

    2010-01-01

    The effect of the Twin Block functional orthodontic appliances is mostly dento-alveolar with small skeletal effect. There are certain clinical indications where functional appliances can be used successfully in class II malocclusion e.g. in a growing patient. The use of these appliances is greatly dependent on the patient’s compliance and they simplify the fixed appliance phase. In this case, a 13-year old adolescent was treated with Twin Block appliance followed by fixed appliance to detail the occlusion. The design and treatment effects were demonstrated in this case report. PMID:24151413

  4. DNA polymorphism of HLA class II genes in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Morling, Niels; Dalhoff, K; Fugger, L

    1992-01-01

    We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary...... than 0.05, 'corrected' P greater than 0.05). No DNA fragments specific for DRB1*0301 (DR3) could be identified. The frequencies in PBC of other genetic markers including DRw8, DRB1*08, HLA-DP antigens, DPA, and DPB genes did not differ significantly from those in controls. The associations between PBC...

  5. Treatment of Class II subdivision malocclusion with congenitally missing upper lateral incisors: A case report

    Directory of Open Access Journals (Sweden)

    Siddharth Mehta

    2014-01-01

    Full Text Available Orthodontic treatment for patients with unilateral or bilateral congenitally missing lateral incisor poses a challenge mainly with regard to treatment planning. The use of a diagnostic setup is one of the most important aids in the decision-making process. Two alternatives, orthodontic space closure or space opening for prosthetic replacement exist. The present case report shows use of the microimplant for unilateral upper molar distalization and space closure in a Class-II division 1 subdivision malocclusion case with bilateral congenitally missing upper lateral incisors.

  6. [Improving the effectiveness of functional jaw orthopedics in Class II malocclusion by appropriate treatment timing].

    Science.gov (United States)

    Baccetti, Tiziano

    2010-12-01

    Time can be considered the fourth dimension in dento-facial orthopedics. Treatment timing can play a significant role in the outcomes of treatment aimed to produce an orthopedic effect in the craniofacial structures. The results of methodologically-sound cephalometric studies of both the past and the recent history of orthodontics clearly indicate that optimal treatment timing for Class II skeletal disharmony with a functional appliance (e.g. twin block) is during or slightly after the peak in mandibular growth as revealed by a reliable biologic indicator of individual skeletal maturity such as the cervical vertebral maturation method. © EDP Sciences, SFODF, 2010.

  7. DNA typing of HLA class II genes in native inhabitants of Chukotka

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, M.Yu.; Erdesz, S.; Alexeeva, L.I. [Institute of Rheumatology, Moscow (Russian Federation)

    1995-06-01

    Polymorphism of HLA class II genes was studied in native Chukotka inhabitants with the use of DNA oligotyping. The characteristics of the distribution of allelic variants of the loci HLA-DRB1, -DQA1, -DQB1, and -DPB1 were revealed; they were similar to those of other Subarctic Mongoloid populations and different from those for comparable populations of other climatic and geographic zones. Our data suggest that the specific features found for the distributions of some alleles of the loci examined are related to the geographic variation in the HLA gene system studied. 20 refs., 4 tabs.

  8. Evolução dos preparos das cavidades de classe II

    Directory of Open Access Journals (Sweden)

    ONO Mary Miyuki

    1997-01-01

    Full Text Available A evolução dos preparos de classe II com a introdução de novos materiais e a conscientização da importância da preservação de estrutura dental sadia são abordadas nos preparos do tipo Almqvist, Roggenkamp e túnel, em que se observa a necessidade de menor desgaste da estrutura dentária, com aumento da resistência à fratura, melhor estética e melhor retenção

  9. Surgical correction of class II skeletal malocclusion in an adult patient

    Directory of Open Access Journals (Sweden)

    Ramakrishnan Balachander

    2014-01-01

    Full Text Available Correction of skeletal deformities in adult patients with orthodontics is limited. Orthognathic surgery is the best option for cases when camouflage treatment is questionable and growth modulation is not possible. This case report illustrates the benefit of the team approach in correcting vertical maxillary excess along with class II skeletal deformity. A cosmetic correction was achieved by superior repositioning of maxilla with LeFort I osteotomy and augmentation genioplasty, along with orthodontic treatment. The patient′s facial appearance was markedly improved along with functional and stable occlusion

  10. Post-treatment occlusal changes in Class II division 2 subjects treated with the Herbst appliance.

    Science.gov (United States)

    Bock, Niko; Ruf, Sabine

    2008-12-01

    The aim of this retrospective study was to analyse and compare the post-treatment occlusal changes of Class II division 2 treatment with the Herbst appliance in early adolescent, late adolescent, and adult subjects. The subjects were 37 Class II division 2 patients (19 females and 18 males) treated at the Orthodontic Department, University of Giessen, Germany. All were in the late mixed or permanent dentition and exhibited a Class II molar relationship > or =0.5 cusp width (CW) bilaterally or > or =1.0 CW unilaterally, an overbite (OB) >3.0 mm, and two upper central incisors retroclined. The subjects were divided into three skeletal maturity groups based on evaluation of hand wrist radiographs: early adolescent (n = 10, stages MP3-E to MP3-FG at start of treatment, age range: 11.3-13.2 years), late adolescent (n = 14, stages MP3-G to MP3-I at start of treatment, age range: 14.1-16.4 years), and adult (n = 13, stages R-I to R-J at the start of treatment, age range: 16.3-25.6 years). Study casts from before treatment (T1), after Herbst-Tip-Edge-Multibracket appliance treatment (T2), and after an average retention time of 27 months (T3) were analysed. Statistical analysis was undertaken using t-tests for paired and unpaired samples. For the whole sample, the molar relationship at T3 was stable in 82.4 per cent, the canine relationship in 82.9 per cent, and OB in 75.7 per cent of the cases. In the different skeletal maturity groups, the stability of the molars, canines, and overbite was as follows: early adolescents: 95.0, 100.0, and 70.0 per cent, respectively; late adolescents: 92.9, 74.1, and 85.7 per cent, respectively; and adults 61.5, 80.8, 69.2 per cent, respectively. Occlusal correction of Class II division 2 malocclusions with Herbst treatment was relatively stable 2 years post-treatment. The outcome of treatment of adolescents was more stable than that of adults.

  11. Interdisciplinary Evaluation of Broadly-Reactive HLA Class II Restricted Epitopes Eliciting HIV-Specific CD4+T Cell Responses

    DEFF Research Database (Denmark)

    Buggert, M.; Norström, M.; Lundegaard, Claus

    2011-01-01

    , the functional and immunodominant discrepancies of CD4+ T cell responses targeting promiscuous MHC II restricted HIV epitopes remains poorly defined. Thus, utilization of interdisciplinary approaches might aid revealing broadly- reactive peptides eliciting CD4 + T cell responses. Methods: We utilized the novel...... bioinformatic prediction program NetMHCIIpan to select 64 optimized MHC II restricted epitopes located in the HIV Gag, Pol, Env, Nef and Tat regions. The epitopes were selected to cover the global diversity of the virus (multiple subtypes) and the human immune system(diverse MHC II types). Optimized...

  12. Microsatellite and HLA class II oligonucleotide typing in a population of Yanomami Indians.

    Science.gov (United States)

    Roewer, L; Nagy, M; Schmidt, P; Epplen, J T; Herzog-Schröder, G

    1993-01-01

    We have used three different microsatellites (on chromosome 12 and Y) together with HLA class II oligonucleotide typing (DQA and DQB) to analyze families of Yanomami indians settling in villages in Southern Venezuela. There exist complex networks of biological relationship between villages as a result of wife exchange, village fissioning and changing patterns of alliances associated with inter-village warfare. Social status in this society is largely determined by the kinship system. Polygyny is common, especially among headmen, with additional wives, frequently being chosen among the sisters of the first wife. Our preliminary results mainly obtained from inhabitants of the village HAP show the expected allele distribution in populations with a high degree of consanguinity: (i) deficiency of observed heterozygotes at the autosomal loci and (ii) almost all men carry the same Y chromosomal allele. Nevertheless in the Yanomami village two thirds of the described autosomal microsatellite alleles were identified. Several paternities were clarified.

  13. Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity

    DEFF Research Database (Denmark)

    Merelo, Paz; Ram, Hathi; Caggiano, Monica Pia

    2016-01-01

    A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD-...... show that class III and class II HD-ZIP proteins act together to repress MIR165/166 via a conserved cis-element in their promoters. Organ morphology and tissue patterning in plants, therefore, depend on a bidirectional repressive circuit involving a set of miRNAs and its targets....

  14. Prediction of individual mandibular changes induced by functional jaw orthopedics followed by fixed appliances in Class II patients.

    Science.gov (United States)

    Franchi, Lorenzo; Baccetti, Tiziano

    2006-11-01

    To identify pretreatment cephalometric variables for the prediction of individual mandibular outcomes of functional jaw orthopedics (FJO) followed by fixed appliances in Class II patients treated at the peak in mandibular growth. The study was performed on 51 subjects (24 females, 27 males) with Class II malocclusion. First-phase therapy was accomplished with a twin block in 16 subjects, a stainless steel crown Herbst in 15 subjects, and an acrylic splint Herbst in 20 subjects. Lateral cephalograms were available at the start of treatment with FJO and at the completion of fixed appliance therapy. All subjects received FJO at the peak in mandibular growth (CS 3 at T1). Individual responsiveness to Class II treatment including FJO was defined on the basis of the T2-T1 increment in total mandibular length (Co-Gn) when compared with untreated Class II subjects. Discriminant analysis identified a single predictive parameter (Co-Go-Me degrees) with a classification power of 80%. Pretreatment vertical and sagittal parameters were not able to improve the prediction based upon the mandibular angle. A Class II patient at the peak in skeletal maturation (CS 3) with a pretreatment Co-Go-Me degrees smaller than 125.5 degrees is expected to respond favorably to treatment including FJO. A Class II patient at CS 3 with a pretreatment value for Co-Go-Me degrees greater than 125.5 degrees is expected to respond poorly to treatment including FJO.

  15. MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency.

    Science.gov (United States)

    Buch, Thorsten; Polic, Bojan; Clausen, Björn E; Weiss, Susanne; Akilli-Ozturk, Ozlem; Chang, Cheong-Hee; Flavell, Richard; Schulz, Ansgar; Jonjic, Stipan; Waisman, Ari; Förster, Irmgard

    2006-02-15

    MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional antigen-presenting cells (APCs) is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium, we observed development of endogenous Th cells with restoration of Th-cell-dependent antibody responses and immunity to cytomegalovirus infection, thus opening the possibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double-deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.

  16. Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins II reactions at side-chain loci in model systems

    International Nuclear Information System (INIS)

    Garrison, W.M.

    1983-11-01

    The major emphasis in radiation biology at the molecular level has been on the nucleic acid component of the nucleic acid-protein complex because of its primary genetic importance. But there is increasing evidence that radiation damage to the protein component also has important biological implications. Damage to capsid protein now appears to be a major factor in the radiation inactivation of phage and other viruses. And, there is increasing evidence that radiation-chemical change in the protein component of chromation leads to changes in the stability of the repressor-operator complexes involved in gene expression. Knowledge of the radiation chemistry of protein is also of importance in other fields such as the application of radiation sterilization to foods and drugs. Recent findings that a class of compounds, the α,α'-diaminodicarboxylic acids, not normally present in food proteins, are formed in protein radiolysis is of particular significance since certain of their peptide derivatives have been showing to exhibit immunological activity. The purpose of this review is to bring together and to correlate our present knowledge of products and mechanisms in the radiolysis of peptides, polypeptides and proteins both aqueous and solid-state. In part 1 we presented a discussion of the radiation-induced reactions of the peptide main-chain in model peptide and polypeptide systems. Here in part 2 the emphasis is on the competing radiation chemistry at side-chain loci of peptide derivatives of aliphatic, aromatic-unsaturated and sulfur-containing amino acids in similar systems. Information obtained with the various experimental techniques of product analysis, competition kinetics, spin-trapping, pulse radiolysis, and ESR spectroscopy are included

  17. Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as a Prerequisite for Canine T Cell Immunotherapy.

    Directory of Open Access Journals (Sweden)

    Sharon M Barth

    Full Text Available There are limitations in pre-clinical settings using mice as a basis for clinical development in humans. In cancer, similarities exist between humans and dogs; thus, the dog patient can be a link in the transition from laboratory research on mouse models to clinical trials in humans. Knowledge of the peptides presented on MHC molecules is fundamental for the development of highly specific T cell-based immunotherapies. This information is available for human MHC molecules but is absent for the canine MHC. In the present study, we characterized the binding motif of dog leukocyte antigen (DLA class I allele DLA-88*50101, using human C1R and K562 transfected cells expressing the DLA-88*50101 heavy chain. MHC class I immunoaffinity-purification revealed 3720 DLA-88*50101 derived peptides, which enabled the determination of major anchor positions. The characterized binding motif of DLA-88*50101 was similar to HLA-A*02:01. Peptide binding analyses on HLA-A*02:01 and DLA-88*50101 via flow cytometry showed weak binding of DLA-88*50101 derived peptides to HLA-A*02:01, and vice versa. Our results present for the first time a detailed peptide binding motif of the canine MHC class I allelic product DLA-88*50101. These data support the goal of establishing dogs as a suitable animal model for the evaluation and development of T cell-based cancer immunotherapies, benefiting both dog and human patients.

  18. Structural characterization of peptides derived from prosomatostatins I and II isolated from the pancreatic islets of two species of teleostean fish: the daddy sculpin and the flounder.

    Science.gov (United States)

    Conlon, J M; Davis, M S; Falkmer, S; Thim, L

    1987-11-02

    The primary structures of three peptides from extracts from the pancreatic islets of the daddy sculpin (Cottus scorpius) and three analogous peptides from the islets of the flounder (Platichthys flesus), two species of teleostean fish, have been determined by automated Edman degradation. The structures of the flounder peptides were confirmed by fast-atom bombardment mass spectrometry. The peptides show strong homology to residues (49-60), (63-96) and (98-125) of the predicted sequence of preprosomatostatin II from the anglerfish (Lophius americanus). The amino acid sequences of the peptides suggest that, in the sculpin, prosomatostatin II is cleaved at a dibasic amino acid residue processing site (corresponding to Lys61-Arg62 in anglerfish preprosomatostatin II). The resulting fragments are further cleaved at monobasic residue processing sites (corresponding to Arg48 and Arg97 in anglerfish preprosomatostatin II). In the flounder the same dibasic residue processing site is utilised but cleavage at different monobasic sites takes place (corresponding to Arg50 and Arg97 in anglerfish preprosomatostatin II). A peptide identical to mammalian somatostatin-14 was also isolated from the islets of both species and is presumed to represent a cleavage product of prosomatostatin I.

  19. 25 CFR 547.10 - What are the minimum standards for Class II gaming system critical events?

    Science.gov (United States)

    2010-04-01

    ...: Event Definition and action to be taken (i) Player interface power off during play This condition is reported by the affected component(s) to indicate power has been lost during game play. (ii) Player... INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II...

  20. Identification of neurotensin-related peptides in human thymic epithelial cell membranes and relationship with major histocompatibility complex class I molecules.

    Science.gov (United States)

    Vanneste, Y; Thome, A N; Vandersmissen, E; Charlet, C; Franchimont, D; Martens, H; Lhiaubet, A M; Schimpff, R M; Rostène, W; Geenen, V

    1997-06-01

    This study shows the expression at the cell surface of human thymic epithelial cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay (RIA) revealed that cultured human TEC contain +/-5 ng immunoreactive (ir) NT/10(6) cells, of which 5% is associated with plasma cell membranes. HPLC analysis of NT-ir present in human TEC showed a major peak of NT-ir corresponding to NT1-13. NT-ir was not detected in the supernatant of human TEC cultures. Using an affinity column prepared with a anti-MHC class I monoclonal antibody, NT-ir-related peptides were retained on the column and eluted together with MHC class I-related proteins. According to the elution time on HPLC of these peptides, they correspond to intact NT1-13, as well as to smaller fragments of NT1-13.

  1. Morphological changes of the facial skeleton in Class II/1 patients treated with orthodontic functional appliances

    Directory of Open Access Journals (Sweden)

    Dana Festila

    2014-01-01

    Full Text Available Aim: The aim of this study was to investigate, using lateral cephalometry, the skeletal changes in maxillary bones induced through functional jaw orthopedic therapy. 30 patients with class II division 1 malocclusion and average age of 10.4 years were included in the study. Material and Methods: Cephalometric data were analyzed with the following methods: Burstone, McNamara, Rickets, Tweed and Wits and treatment changes were evaluated overlapping the lateral cephalograms on cranial base with sella registered. Results: The results showed reduced over-jet in average with 2.46 mm, mandibular advancement with a mean value of 2.72 mm and increasing of the total mandibular length with a mean value of 4.17 mm. Although we found an inhibiting in the anterior development of the maxilla with an average of 1.57 degree, the decrease of the anterior-posterior discrepancy was due especially to the mandible. Conclusions: It can be concluded that functional appliances were effective in correcting class II malocclusion. Changes of the position and mandible′s length determined improved facial profile but did not correct it completely because of the chin that moved not only anterior but also downward, as a result of vertical ramus growth.

  2. DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis

    DEFF Research Database (Denmark)

    Morling, N; Friis, J; Fugger, L

    1991-01-01

    associated with the following HLA class II genes were increased in PJRA when compared to normal controls: DRB1*08 (DRw8) (35.2% vs 10.3%, RR = 4.6, p less than 10(-3), DRB3*01/02/03 (DRw52) (76.3% vs 48.1%, RR 3.5, p less than 10(-3)), DQA1*0401 (41.0% vs 7.4%, RR = 7.9, p less than 10(-3)), DQA1*0501 (55...... of DNA fragments associated with the following HLA class II genes were decreased in PJRA although not statistically significantly so after 'correction' of p values: DRB1*04 (14.8% vs 40.2%, RR = 0.27; p less than 10(-3)), DRB1*07 (0% vs 25.9%, RR = 0.04, p less than 10(-3)), DRB4*0101 (DRw53) (25.9% vs...... 53.6%, RR = 0.31, p less than 10(-3)), DQA1*0102 (11.6% vs 36.0%, RR = 0.25, p less than 10(-4)), and DQA1*0201 (2.6% vs 34.2%, RR = 0.05, p less than 10(-2)).(ABSTRACT TRUNCATED AT 250 WORDS)...

  3. Cephalomteric changes in airway dimensions with twin block therapy in growing Class II patients

    Science.gov (United States)

    Vinoth, Santhana Krishnan; Thomas, Ashwin Varghese; Nethravathy, Ramya

    2013-01-01

    Introduction: Myofunctional appliances are commonly used for correction of skeletal Class II malrelationship. These appliances influence craniofacial and nasopharyngeal dimensions. Objectives: The present study was done to evaluate changes in airway with twin block therapy. Materials and Methods: Cephalometric assessment of airway was done in 25 growing children in the age group of 11-13 years with Class II skeletal pattern. All the patients were treated with twin block appliance. Pre and post treatment lateral cephalograms were taken to evaluate the changes in different airway and craniofacial dimensions during the treatment period. The average treatment duration was 14.5 months. Results: Airway: A significant increase was observed in upper and lower pharyngeal width and area of bony nasopharynx. Craniofacial dimension: There was a significant increase in effective mandibular length, ramal length and mandibular plane angle. There was an increase in SNB angle, which resulted in decreased ANB angle. Conclusion: There was a definite improvement in airway dimension following twin block therapy PMID:23946570

  4. Cephalometric effects of the Jones Jig appliance followed by fixed appliances in Class II malocclusion treatment.

    Science.gov (United States)

    Patel, Mayara Paim; Henriques, José Fernando Castanha; Freitas, Karina Maria Salvatore; Grec, Roberto Henrique da Costa

    2014-01-01

    The aim of this study was to cephalometrically assess the skeletal and dentoalveolar effects of Class II malocclusion treatment performed with the Jones Jig appliance followed by fixed appliances. The sample comprised 25 patients with Class II malocclusion treated with the Jones Jig appliance followed by fixed appliances, at a mean initial age of 12.90 years old. The mean time of the entire orthodontic treatment was 3.89 years. The distalization phase lasted for 0.85 years, after which the fixed appliance was used for 3.04 years. Cephalograms were used at initial (T1), post-distalization (T2) and final phases of treatment (T3). For intragroup comparison of the three phases evaluated, dependent ANOVA and Tukey tests were used. Jones Jig appliance did not interfere in the maxillary and mandibular component and did not change maxillomandibular relationship. Jones Jig appliance promoted distalization of first molars with anchorage loss, mesialization and significant extrusion of first and second premolars, as well as a significant increase in anterior face height at the end of treatment. The majority of adverse effects that occur during intraoral distalization are subsequently corrected during corrective mechanics. Buccal inclination and protrusion of mandibular incisors were identified. By the end of treatment, correction of overjet and overbite was observed. Jones Jig appliance promoted distalization of first molars with anchorage loss represented by significant mesial movement and extrusion of first and second premolars, in addition to a significant increase in anterior face height.

  5. Islamic Educational Transformation through Inmate Social Interaction at Palu Correctional Facility Class II A, Central Sulawesi

    Directory of Open Access Journals (Sweden)

    Yusra

    2017-06-01

    Full Text Available Rehabilitation system adopted by correctional facility is based on Pancasila. All incarcerated men are rehabilitated there with the goal to make them repent, be law-abiding citizens, and uphold moral values. Correctional facility comes as a rehabilitation place to improve social interaction so that inmates can be received by their social environment once they are released from prison. At this point, the researcher focuses on Islamic educational transformation through inmate social interaction training program at Palu correctional facility class II A. This research uses descriptive quantitative design with social legal approach to observe patterns of inmate social interaction. The result of research points out that Islamic educational transformation which is packed into rehabilitation programs and correctional educational activities is remarkably emphasized in inmate social interaction. In this case, Islamic educational transformation applied in Palu correctional facility class II A is defined as ultimum remidium, correctional activities emphasizing on process-based approach. Rehabilitation process given to inmates is able to improve insight and awareness of ethical and moral values in their social interaction. Therefore, when returning to society they can be accepted by social environtment as good responsible people.

  6. Effect of gingival fluid on marginal adaptation of Class II resin-based composite restorations.

    Science.gov (United States)

    Spahr, A; Schön, F; Haller, B

    2000-10-01

    To evaluate in vitro the marginal quality of Class II composite restorations at the gingival enamel margins as affected by contamination of the cavities with gingival fluid (GF) during different steps of resin bonding procedures. 70 Class II cavities were prepared in extracted human molars and restored with composite using a multi-component bonding system (OptiBond FL/Herculite XRV; OPTI) or a single-bottle adhesive (Syntac Sprint/Tetric Ceram; SYN). The cavities were contaminated with human GF: C1 after acid etching, C2 after application of the primer (OPTI) or light-curing of the primer-adhesive (SYN), and C3 after light-curing of the resin adhesive (OPTI). Uncontaminated cavities were used as the control (C0). The restored teeth were subjected to thermocycling (TC) and replicated for SEM analysis of marginal gap formation. Microleakage at the gingival margins was determined by dye penetration with basic fuchsin. non-parametric tests (Kruskal-Wallis test, Mann-Whitney test with Bonferroni correction). In both bonding systems, contamination with GF after acid etching (C1) did not impair the marginal quality; the mean percentages of continuous margin/mean depths of dye penetration were: OPTI: C0: 88.5%/0.10 mm, C1: 95.6%/0.04 mm; SYN: C0: 90.9%/0.08 mm, C1: 97.0%/0.05 mm. Marginal adaptation was adversely affected when GF contamination was performed after

  7. Correlations between dentoskeletal variables and deep bite in Class II Division 1 individuals

    Directory of Open Access Journals (Sweden)

    Leandro Silva Marques

    2011-02-01

    Full Text Available This study aimed to evaluate the cephalometric pattern of Class II Division 1 individuals with deep bite, and to determine possible correlations between dentoskeletal variables and deep bite. Comparisons were also made between genders and cases that were to be treated both with and without premolar extraction. A total of 70 lateral cephalograms were used, from both male (n = 35 and female (n = 35 individuals with an average age of 11.6 years, who simultaneously presented with ANB > 5º and overbite > 4 mm. Statistical analysis involved parametric (t-test and non-parametric (Mann-Whitney tests for independent samples, as well as the Spearman correlation test (p < 0.05. The values of Go-Me, Ar-Pog, PM-1 and PM-CMI were higher in males (p < 0.05. However, no significant differences were found among the averages of the cephalometric measurements when the sample was divided by treatment with and without extraction. Deep bite was positively correlated to the PM-1 and SNA measurements, and negatively correlated to the Go-Me, Ar-Pog, SNB and SNGoMe measurements. The main factors associated with the determination of deep bite in Angle's Class II Division 1 cases were: greater lower anterior dentoalveolar growth and/or lower incisor extrusion, horizontal growth pattern, maxillary protrusion and mandibular retrusion.

  8. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  9. Ultrahigh-energy Cosmic Rays from Fanaroff Riley class II radio galaxies

    Science.gov (United States)

    Rachen, Joerg; Biermann, Peter L.

    1992-08-01

    The hot spots of very powerful radio galaxies (Fanaroff Riley class II) are argued to be the sources of the ultrahigh energy component in Cosmic Rays. We present calculations of Cosmic Ray transport in an evolving universe, taking the losses against the microwave background properly into account. As input we use the models for the cosmological radio source evolution derived by radioastronomers (mainly Peacock 1985). The model we adopt for the acceleration in the radio hot spots has been introduced by Biermann and Strittmatter (1987), and Meisenheimer et al. (1989) and is based on first order Fermi theory of particle acceleration at shocks (see, e.g., Drury 1983). As an unknown the actual proportion of energy density in protons enters, which together with structural uncertainties in the hot spots should introduce no more than one order of magnitude in uncertainty: We easily reproduce the observed spectra of high energy cosmic rays. It follows that scattering of charged energetic particles in intergalactic space must be sufficiently small in order to obtain contributions from sources as far away as even the nearest Fanaroff Riley class II radio galaxies. This implies a strong constraint on the turbulent magnetic field in intergalactic space.

  10. Stability of Class II treatment with the Bionator followed by fixed appliances.

    Science.gov (United States)

    Francisconi, Manoela Fávaro; Henriques, José Fernando Castanha; Janson, Guilherme; Freitas, Karina Maria Salvatore de; Santos, Patrícia Bittencourt Dutra dos

    2013-01-01

    This prospective study assessed the stability of Class II treatment with the Bionator, followed by fixed appliances, 10 years after treatment. The experimental group comprised 23 patients of both sexes (10 boys, 13 girls) at a mean initial age of 11.74 years (late mixed or early permanent dentitions), treated for a mean period of 3.55 years who were evaluated at three stages: initial (T1), final (T2) and long-term posttreatment (T3). A total of 69 lateral cephalograms were evaluated and 69 dental casts were measured using the PAR index. The difference between initial and final PAR indexes, the percentage of occlusal improvement obtained with therapy and the percentage of relapse were calculated, using the PAR index. The variables were compared by repeated measures analysis of variance (ANOVA) followed by Tukey tests. The significant improvement in apical base relationship, the palatal inclination of the maxillary incisors and the labial inclination of the mandibular incisors, and the significant improvement in molar relationship and reduction of overjet and overbite, obtained with treatment, remained stable in the long-term posttreatment period. There was also significant improvement in the occlusal relationships which remained stable in the long-term posttreatment period. The percentage of occlusal improvement obtained was of 81.78% and the percentage of relapse was of 4.90%. Treatment of Class II division 1 malocclusions with the Bionator associated with fixed appliances showed to be stable in the long-term posttreatment period.

  11. Clinical effects of fixed functional Herbst appliance in the treatment of class II/1 malocclusion

    Directory of Open Access Journals (Sweden)

    Nedeljković Nenad

    2009-01-01

    Full Text Available Introduction. Sagittal mandible deficiency is the most common cause of skeletal Class II malocclusion. Treatment objective is to stimulate sagittal mandible growth. Fixed functional Herbst appliance use is beneficial for shortening the time required for treatment and does not depend on patient compliance. Case outline. A 13-year-old girl was referred to the Clinic of Orthodontics, School of Dentistry in Belgrade following previous unsuccessful treatment of her skeletal Class II malocclusion using an activator. The patient's poor cooperation had led to failure of the treatment. Patient was subjected to the Herbst treatment for 6 months followed by fixed appliance for another 8 months. Lateral cephalograms before and after the treatment was performed. The remodelation of condylar and fossal articulation was assessed by superimposition of pre- and post-treatment temporomandibular joint tomograms. The promotion of oral hygiene and fluoride use was performed because orthodontic treatment carries a high caries risk and risk for periodontal disease. Skeletal and dental changes were observed after treatment (correction [Max+Mand]: molar relation 7 mm, overjet 8 mm, skeletal relation 5 mm, molars 2 mm, incisors 3 mm. Combination of Herbst and fixed appliances was effective in the treatment of dental and skeletal irregularities for a short period of time. Conclusion . In the retention period, 14 months after treatment, occlusal stability exists. Follow-up care in oral prevention is based on regular recalls at the dental office and supervision at home by the parents.

  12. Immobilized palladium(II) ion affinity chromatography for recovery of recombinant proteins with peptide tags containing histidine and cysteine.

    Science.gov (United States)

    Kikot, Pamela; Polat, Aise; Achilli, Estefania; Fernandez Lahore, Marcelo; Grasselli, Mariano

    2014-11-01

    Fusion of peptide-based tags to recombinant proteins is currently one of the most used tools for protein production. Also, immobilized metal ion affinity chromatography (IMAC) has a huge application in protein purification, especially in research labs. The combination of expression systems of recombinant tagged proteins with this robust chromatographic system has become an efficient and rapid tool to produce milligram-range amounts of proteins. IMAC-Ni(II) columns have become the natural partners of 6xHis-tagged proteins. The Ni(II) ion is considered as the best compromise of selectivity and affinity for purification of a recombinant His-tagged protein. The palladium(II) ion is also able to bind to side chains of amino acids and form ternary complexes with iminodiacetic acid and free amino acids and other sulfur-containing molecules. In this work, we evaluated two different cysteine- and histidine-containing six amino acid tags linked to the N-terminal group of green fluorescent protein (GFP) and studied the adsorption and elution conditions using novel eluents. Both cysteine-containing tagged GFPs were able to bind to IMAC-Pd(II) matrices and eluted successfully using a low concentration of thiourea solution. The IMAC-Ni(II) system reaches less than 20% recovery of the cysteine-containing tagged GFP from a crude homogenate of recombinant Escherichia coli, meanwhile the IMAC-Pd(II) yields a recovery of 45% with a purification factor of 13. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Improved pan-specific MHC class I peptide-binding predictions using a novel representation of the MHC-binding cleft environment

    DEFF Research Database (Denmark)

    Carrasco Pro, S.; Zimic, M.; Nielsen, Morten

    2014-01-01

    of the current state-of-the-art methods for MHC class I is NetMHCpan, which has a core ingredient for the representation of the MHC class I molecule using a pseudo-sequence representation of the binding cleft amino acid environment. New and large MHC-peptide-binding data sets are constantly being made available...... of different MHC data sets including human leukocyte antigen (HLA), non-human primates (chimpanzee, macaque and gorilla) and other animal alleles (cattle, mouse and swine). From these constructs, we showed that by focusing on MHC sequence positions found to be polymorphic across the MHC molecules used to train...

  14. Integrating MRP (materiel requirements planning) II and JIT to achieve world-class status.

    Science.gov (United States)

    Titone, R C

    1994-05-01

    The concepts and principles of using manufacturing resource planning (MRP II) for planning are not new. Their success has been proven in numerous manufacturing companies in America. The concepts and principles of using just-in-time (JIT) inventory for execution, while more recent, have also been available for some time, and their success in Japan well documented. However, it is the effective integration of these two powerful tools that open the way to achieving world-class manufacturing status. This article will utilize a newly developed world-class manufacturing model, which will review the aspects of planning, beginning with a business plan through the production planning process and culminating with a master schedule that drives a materiel/capacity plan. The importance and interrelationship of these functions are reviewed. The model then illustrates the important aspects of executing these plans beginning with people issues, through total quality control (TQC) and pull systems. We will then utilize this new functional model to demonstrate the relationship between these various functions and the importance of integrating them with a total comprehensive manufacturing strategy that will lead to world-class manufacturing and profits.

  15. An Evaluation of Mandibular Dental and Basal Arch Dimensions in Class I and Class II Division 1 Adult Syrian Patients using Cone-beam Computed Tomography.

    Science.gov (United States)

    Al-Hilal, Layal H; Sultan, Kinda; Hajeer, Mohammad Y; Mahmoud, Ghiath; Wanli, Abdulrahman A

    2018-04-01

    Aim: The aim of this study is (1) to inspect any difference in mandibular arch widths between males and females in class I and class II division 1 (class malocclusions using cone-beam computed tomography (CBCT), (2) to compare the mandibular dental and basal widths between the two groups, and (3) to investigate any possible correlation between dental and basal arch widths in both groups. Materials and methods: The CBCT images of 68 patients aged between 18 and 25 years consisted of 34 class I (17 males and 17 females) and 34 class (17 males and 17 females) who were recruited at the Department of Orthodontics, University of Damascus Dental School (Syria). Using on-demand three-dimensional (3D) on axial views, facial axis points for dental measurements and basal bone center (BBC) points for basal measurements were identified on lower canines and first molars. Dental and basal intercanine width (ICW) and intermolar width (IMW) were measured. Results: Independent t-test showed a statistically significant difference between males and females in several variables in both groups and a statistically significant difference between class I and class groups in the basal ICW for both genders and in the dental ICW for females only (p class I group, Pearson's correlation coefficients between dental and basal measurements showed a strong correlation in the IMW for both genders (r > 0.73; p class group, a moderate correlation in females' IMW (r = 0.67; p Class I patients had larger ICW than class II-1 patients in all measurements and had narrower IMW than class in most measurements for both genders. There were moderate-to-strong correlations between dental and basal dimensions. BBC points might be landmarks that accurately represent the basal bone arch. Clinical significance: CBCT-based assessments of dental and basal arch dimensions provide a great opportunity to accurately evaluate these aspects, to enhance clinicians' decisions regarding proper tooth movements, and to achieve

  16. Treatment stability in patients with Class II malocclusion treated with 2 maxillary premolar extractions or without extractions.

    Science.gov (United States)

    Janson, Guilherme; Camardella, Leonardo Tavares; Araki, Janine Della Valle; de Freitas, Marcos Roberto; Pinzan, Arnaldo

    2010-07-01

    The purpose of this study was to compare the occlusal stability of Class II malocclusion treatment with and without extraction of 2 maxillary premolars. A sample of 59 records from patients with complete Class II malocclusion was used. This sample was divided into 2 groups with the following characteristics: group 1, comprising 29 patients treated without extractions, and group 2, comprising 30 patients treated with extraction of 2 maxillary premolars. Dental cast measurements were obtained before and after treatment and at a minimum of 2.4 years after treatment. The pretreatment, posttreatment, and postretention occlusal statuses were evaluated with the peer assesment rating index. The occlusal indexes at the postretention stage and the posttreatment changes and percentages of posttreatment changes were compared with t tests. The nonextraction and the 2 maxillary premolar extraction treatment protocols of complete Class II malocclusions had no statistically significant differences in occlusal stability. Finishing Class II malocclusion treatment with the molars in a Class II relationship has similar occlusal stability as finishing with the molars in a Class I relationship. Copyright (c) 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  17. A cell-based MHC stabilization assay for the detection of peptide binding to the canine classical class I molecule, DLA-88.

    Science.gov (United States)

    Ross, Peter; Holmes, Jennifer C; Gojanovich, Gregory S; Hess, Paul R

    2012-12-15

    Identifying immunodominant CTL epitopes is essential for studying CD8+ T-cell responses in populations, but remains difficult, as peptides within antigens typically are too numerous for all to be synthesized and screened. Instead, to facilitate discovery, in silico scanning of proteins for sequences that match the motif, or binding preferences, of the restricting MHC class I allele - the largest determinant of immunodominance - can be used to predict likely candidates. The high false positive rate with this analysis ideally requires binding confirmation, which is obtained routinely by an assay using cell lines such as RMA-S that have defective transporter associated with antigen processing (TAP) machinery, and consequently, few surface class I molecules. The stabilization and resultant increased life-span of peptide-MHC complexes on the cell surface by the addition of true binders validates their identity. To determine whether a similar assay could be developed for dogs, we transfected a prevalent class I allele, DLA-88*50801, into RMA-S. In the BARC3 clone, the recombinant heavy chain was associated with murine β2-microglobulin, and importantly, could differentiate motif-matched and -mismatched peptides by surface MHC stabilization. This work demonstrates the potential to use RMA-S cells transfected with canine alleles as a tool for CTL epitope discovery in this species. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. The Relationship Between Class I and II Integrons and Antibiotic Resistance Among Escherichia coli Isolates From Urinary Tract Infections

    Directory of Open Access Journals (Sweden)

    Farshad Nojoomi

    2018-05-01

    Full Text Available Objective: the aim of this study was determination of antibiotic resistance profile, investigation of class I and II integrons among Escherichia coli (E. coli isolates from urinary tract infections. This study was conducted for the investigation of the prevalence of class I and II Integrons among E. coli Isolates from urinary tract infections. Materials and Methods: A total of 100 E. coli clinical isolates were collected from urinary tract infections in Borujerd city, Iran, from… to …. All the isolates were identified with standard laboratory procedures as described everywhere. The antibiotic susceptibility profile was conducted against adopted antibiotic disks following CLSI 2016 guidelines. All the isolates were enrolled in the PCR technique for the presence of class I and II integrons. Results: the highest resistance was against amoxicillin (72%, ciprofloxacin (69%, nalidixic acid (55% and tetracycline (51%. The prevalence of class I and II integrons was 31% and 21%, respectively. A significant relation was observed between resistance to trimethoprim-sulfamethoxazole (p<0.001, nalidixic acid (p<0.01 and tetracycline (p<0.005 with the presence of class I integron. The rate of class I integron in the E. coli isolates was high, possibly playing a role in the spread of multidrug resistant isolates. Conclusion: considering the significant relation observed between the presence of class I integron among multidrug-resistant isolates, establishment implementation of proper procedures to control and suitable treatment strategies in hospitals seems essential for the prevention of more spread of these isolates.

  19. Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

    Science.gov (United States)

    Simske, Steven J.; Bateman, Ted A.; Smith, Erin E.; Ferguson, Virginia L.; Chapes, Stephen K.

    2002-01-01

    We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

  20. Characterization of class II alpha genes and DLA-D region allelic associations in the dog.

    Science.gov (United States)

    Sarmiento, U M; Storb, R F

    1988-10-01

    Human major histocompatibility complex (HLA) cDNA probes were used to analyze the restriction fragment length polymorphism (RFLP) of the alpha genes of the DLA-D region in dogs. Genomic DNA from peripheral blood leucocytes of 23 unrelated DLA-D homozygous dogs representing nine DLA-D types (defined by mixed leucocyte reaction) was digested with restriction enzymes (BamHI, EcoRI, Hind III, Pvu II, Taq I, Rsa I, Msp I, Pst I and Bgl II), separated by agarose gel electrophoresis and transferred onto Biotrace membrane. The Southern blots were successively hybridized with radiolabelled HLA cDNA probes corresponding to DQ, DP, DZ and DR alpha genes. Clear evidence was obtained for the canine homologues of DQ and DR alpha genes with simple bi- or tri-allelic polymorphism respectively. Evidence for a single, nonpolymorphic DP alpha gene was also obtained. However, the presence of a DZ alpha gene could not be clearly demonstrated in canine genomic DNA. This report extends our previous RFLP analysis documenting polymorphism of DLA class II beta genes in the same panel of homozygous typing cell dogs, and provides the basis for DLA-D genotyping at a population level. This study also characterizes the RFLP-defined preferential allelic associations across the DLA-D region in nine different homozygous typing cell specificities.

  1. A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures.

    Science.gov (United States)

    Wootten, Denise; Reynolds, Christopher A; Koole, Cassandra; Smith, Kevin J; Mobarec, Juan C; Simms, John; Quon, Tezz; Coudrat, Thomas; Furness, Sebastian G B; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-03-01

    The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60(190), N3.43(240), Q7.49(394), and H6.52(363) as key residues involved in peptide-mediated biased agonism, with R2.60(190), N3.43(240), and Q7.49(394) predicted to form a polar interaction network. In this study, we used novel insight gained from recent crystal structures of the transmembrane domains of the glucagon and corticotropin releasing factor 1 (CRF1) receptors to develop improved models of the GLP-1 receptor that predict additional key molecular interactions with these amino acids. We have introduced E6.53(364)A, N3.43(240)Q, Q7.49(394)N, and N3.43(240)Q/Q7.49(394)N mutations to probe the role of predicted H-bonding and charge-charge interactions in driving cAMP, calcium, or extracellular signal-regulated kinase (ERK) signaling. A polar interaction between E6.53(364) and R2.60(190) was predicted to be important for GLP-1- and exendin-4-, but not oxyntomodulin-mediated cAMP formation and also ERK1/2 phosphorylation. In contrast, Q7.49(394), but not R2.60(190)/E6.53(364) was critical for calcium mobilization for all three peptides. Mutation of N3.43(240) and Q7.49(394) had differential effects on individual peptides, providing evidence for molecular differences in activation transition. Collectively, this work expands our understanding of peptide-mediated signaling from the GLP-1 receptor and the key role that the central polar network plays in these events. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  2. A peptide-binding assay for the disease-associated HLA-DQ8 molecule

    DEFF Research Database (Denmark)

    Straumfors, A; Johansen, B H; Vartdal, F

    1998-01-01

    The study of peptide binding to HLA class II molecules has mostly concentrated on DR molecules. Since many autoimmune diseases show a primary association to particular DQ molecules rather than DR molecules, it is also important to study the peptide-binding properties of DQ molecules. Here we repo......-affinity binders, whereas peptides derived from myelin basic protein were among the low-affinity binders. The sequence of the high-affinity peptides conformed with a previously published peptide-binding motif of DQ8.......The study of peptide binding to HLA class II molecules has mostly concentrated on DR molecules. Since many autoimmune diseases show a primary association to particular DQ molecules rather than DR molecules, it is also important to study the peptide-binding properties of DQ molecules. Here we report...

  3. The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    Parameters of the virus-specific T-cell response were analysed in order to dissect the contribution of CD4+ and CD8+ T cells to cell-mediated immunity to lymphocytic choriomeningitis virus. In MHC class II deficient mice, initial T-cell responsiveness was not impaired, but virus clearance...... was delayed, and virus-specific Td activity declined more rapidly. Furthermore, class I restricted Tc memory appeared to be impaired in these mice. To directly evaluate the role of CD4+ cells in virus clearance and T-cell mediated inflammation, MHC class I deficient mice were also studied. No virus...... exudate. This low-grade response was associated with some degree of virus control as organ titres were lower in these animals than in matched T-cell deficient nu/nu mice or class I deficient mice treated with anti-CD4 monoclonal antibody. This confirms that CD4+ cells are not needed to induce a virus...

  4. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

    Directory of Open Access Journals (Sweden)

    Emilie Sundqvist

    2014-04-01

    Full Text Available JC polyomavirus (JCV carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA, instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15 and controls (OR = 0.53, p = 2×10(-5. In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006, and controls (OR = 2.69, p = 1×10(-5. The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4 and OR = 1.58, p = 0.03 respectively for these haplotypes. HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and

  5. The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires.

    Science.gov (United States)

    Bergmann, Tobias; Moore, Carrie; Sidney, John; Miller, Donald; Tallmadge, Rebecca; Harman, Rebecca M; Oseroff, Carla; Wriston, Amanda; Shabanowitz, Jeffrey; Hunt, Donald F; Osterrieder, Nikolaus; Peters, Bjoern; Antczak, Douglas F; Sette, Alessandro

    2015-11-01

    Here we describe a detailed quantitative peptide-binding motif for the common equine leukocyte antigen (ELA) class I allele Eqca-1*00101, present in roughly 25 % of Thoroughbred horses. We determined a preliminary binding motif by sequencing endogenously bound ligands. Subsequently, a positional scanning combinatorial library (PSCL) was used to further characterize binding specificity and derive a quantitative motif involving aspartic acid in position 2 and hydrophobic residues at the C-terminus. Using this motif, we selected and tested 9- and 10-mer peptides derived from the equine herpesvirus type 1 (EHV-1) proteome for their capacity to bind Eqca-1*00101. PSCL predictions were very efficient, with an receiver operating characteristic (ROC) curve performance of 0.877, and 87 peptides derived from 40 different EHV-1 proteins were identified with affinities of 500 nM or higher. Quantitative analysis revealed that Eqca-1*00101 has a narrow peptide-binding repertoire, in comparison to those of most human, non-human primate, and mouse class I alleles. Peripheral blood mononuclear cells from six EHV-1-infected, or vaccinated but uninfected, Eqca-1*00101-positive horses were used in IFN-γ enzyme-linked immunospot (ELISPOT) assays. When we screened the 87 Eqca-1*00101-binding peptides for T cell reactivity, only one Eqca-1*00101 epitope, derived from the intermediate-early protein ICP4, was identified. Thus, despite its common occurrence in several horse breeds, Eqca-1*00101 is associated with a narrow binding repertoire and a similarly narrow T cell response to an important equine viral pathogen. Intriguingly, these features are shared with other human and macaque major histocompatibility complex (MHC) molecules with a similar specificity for D in position 2 or 3 in their main anchor motif.

  6. The interaction of beta 2-microglobulin (beta 2m) with mouse class I major histocompatibility antigens and its ability to support peptide binding. A comparison of human and mouse beta 2m

    DEFF Research Database (Denmark)

    Pedersen, L O; Stryhn, A; Holter, T L

    1995-01-01

    of class I molecules are involved in peptide binding, whereas most of class I molecules are involved in beta 2m binding. We propose that mouse beta 2m interacts with the minor peptide binding (i.e. the "empty") fraction with a lower affinity than human beta 2m does, whereas mouse and human beta 2m interact......The function of major histocompatibility complex (MHC) class I molecules is to sample peptides derived from intracellular proteins and to present these peptides to CD8+ cytotoxic T lymphocytes. In this paper, biochemical assays addressing MHC class I binding of both peptide and beta 2-microglobulin...... (beta 2m) have been used to examine the assembly of the trimolecular MHC class I/beta 2m/peptide complex. Recombinant human beta 2m and mouse beta 2ma have been generated to compare the binding of the two beta 2m to mouse class I. It is frequently assumed that human beta 2m binds to mouse class I heavy...

  7. Articulación de fones en individuos clase esqueletal I,II y III Speech patterns in skeletal class I, II and III subjects

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    Pía Villanueva

    2009-09-01

    Full Text Available OBJETIVO: determinar los patrones de articulación de fones consonánticos en sujetos de habla española chilena clases I, II y III esqueletal; comparar las diferencias fonéticas que existan entre clases esqueletales. MÉTODOS: se seleccionaron 54 individuos que cumplían con los criterios de inclusión determinados mediante un examen clínico intraoral y a través del análisis de Ricketts, y se conformaron los grupos de estudio de pacientes clases esqueletales I, II y III. Se les realizó un examen fonoarticulatorio estandarizado para determinar los fones modificados y el patrón articulatorio compensatorio realizado. RESULTADOS: se observaron cambios en el punto de articulación de fones consonánticos en las tres clases esqueletales, con diferencias significativas en los grupos de fones anteriores y medios entre pacientes clases I y II, sólo en el grupo de los fones anteriores entre pacientes I y III. Entre pacientes clases II y III no se observaron diferencias significativas. Se reportan modificaciones y compensaciones cualitativamente distintas entre las clases esqueletales. CONCLUSIONES: en relación a pacientes clase I, los pacientes clase II o III, presentan distinto grado de modificación en el punto de articulación de fones consonánticos. Las diferencias observadas se relacionan con los patrones esqueletales propios de cada clase.PURPOSE: to determine the consonant phonemes articulation patterns in Chilean skeletal class I, II and III Spanish speakers and compare their phonetic differences. METHODS: fifty-four skeletal class I, II and III subjects were selected, based on intraoral clinical examination and Ricketts cephalometric analysis, constituting the study groups. A standardized phonoarticulatory test was applied to each patient to determine the modified phonemes and their compensatory patterns. RESULTS: the findings indicate changes in articulation in all three groups. Significant differences were found in anterior and medium

  8. Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

    Science.gov (United States)

    Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

    2012-01-01

    Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

  9. Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs

    Science.gov (United States)

    Weinstein, Edward A.; Yano, Takahiro; Li, Lin-Sheng; Avarbock, David; Avarbock, Andrew; Helm, Douglas; McColm, Andrew A.; Duncan, Ken; Lonsdale, John T.; Rubin, Harvey

    2005-01-01

    Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. Analysis of the Mtb genome predicts the existence of a branched aerobic respiratory chain terminating in a cytochrome bd system and a cytochrome aa3 system. Both chains can be initiated with type II NADH:menaquinone oxidoreductase. We present a detailed biochemical characterization of the aerobic respiratory chains from Mtb and show that phenothiazine analogs specifically inhibit NADH:menaquinone oxidoreductase activity. The emergence of drug-resistant strains of Mtb has prompted a search for antimycobacterial agents. Several phenothiazines analogs are highly tuberculocidal in vitro, suppress Mtb growth in a mouse model of acute infection, and represent lead compounds that may give rise to a class of selective antibiotics. PMID:15767566

  10. Alkali/Surfactant/Polymer Flooding in the Daqing Oilfield Class II Reservoirs Using Associating Polymer

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    Ru-Sen Feng

    2013-01-01

    Full Text Available Hydrophobically modified associating polyacrylamide (HAPAM has good compatibility with the Daqing heavy alkylbenzene sulfonate surfactant. The HAPAM alkali/surfactant/polymer (ASP system can generate ultralow interfacial tension in a wide range of alkali/surfactant concentrations and maintain stable viscosity and interfacial tension for 120 days. The HAPAM ASP system has good injectivity for the Daqing class II reservoirs (100–300 × 10−3 μm2 and can improve oil recovery by more than 25% on top of water flooding. In the presence of both the alkali and the surfactant, the surfactant interacts with the associating groups of the polymer to form more micelles, which can significantly enhance the viscosity of the ASP system. Compared with using HPAM (Mw = 2.5 MDa, using HAPAM can reduce the polymer use by more than 40%.

  11. Orthodontic camouflage via total arch movement in a Class II with idiopathic condylar resorption

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    Ji-Sung Jang

    2014-01-01

    Full Text Available Idiopathic condylar resorption (ICR, also known as idiopathic condylysis or condylar atrophy, is multifactorial pathology leading to severe mandibular retrognathism. The etiology has been shown to be multifactorial, such as avascular necrosis, traumatic injuries, hormone and autoimmune disease and it is largely difficult to distinguish the exact cause in each individual. In spite of the remarkable morphological alteration, surgical intervention is not readily recruited due to the possibility of recurrence of resorption. In order to restore balanced facial profile and occlusion. In this report, we present a camouflage treatment for skeletal Class II with ICR and facial asymmetry involving total arch movement, for the improvement facial profile and reconstruction of occlusion.

  12. Orthodontic Protocol Using Mini-Implant for Class II Treatment in Patient with Special Needs

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    Fernando Pedrin Carvalho Ferreira

    2016-01-01

    Full Text Available Improving facial and dental appearance and social interaction are the main factors for special needs (SN patients to seek orthodontic treatment. The cooperation of SN patients and their parents is crucial for treatment success. Objective. To show through a case report the satisfactory results, both functional and esthetic, in patients with intellectual disability, congenital nystagmus, and severe scoliosis. Materials Used. Pendulum device with mini-implants as anchorage unit. Results. Improvement of facial and dental esthetics, correction of Class II malocclusion, and no root resorption shown in the radiographic follow-up. Conclusion. Knowing the limitations of SN patients, having a trained team, motivating and counting on the cooperation of parents and patients, and employing quick and low-cost orthodontic therapy have been shown to be the essential factors for treatment success.

  13. Cephalometric-radiographic study, in lateral norm, considering the established standards of white Brazilian teenagers who presented normal occlusions and mal-occlusions of Class I and Class II, 1st Division and the ones from Ricketts' analysis

    International Nuclear Information System (INIS)

    Bismarck, V.E.

    1986-01-01

    In the present work, our purpose was make a cephalometric-radiographic study, comparing white Brazilian teenagers who presented normal occlusion and the ones who presented malocclusions of Class I and Class II, according to RICKETT'S analysis (1960). (author) [pt

  14. Má oclusão Classe II de Angle tratada sem extrações e com controle de crescimento Angle Class II malocclusion treated without extractions and with growth control

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    Flávia Artese

    2009-06-01

    Full Text Available A má oclusão Classe II de Angle é caracterizada por uma discrepância dentária anteroposterior, que geralmente está acompanhada por alterações esqueléticas. O tratamento ortodôntico precoce permite a correção da discrepância esquelética por controle de crescimento (primeira fase, o que favorece a correção do posicionamento dentário, mais tardiamente (segunda fase. Este relato descreve o tratamento de um caso de má oclusão Classe II, divisão 2, de Angle, em duas fases, e foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO. O caso foi avaliado como representante da Categoria 1, ou seja, má oclusão Classe II de Angle tratada sem extrações dentárias e com controle de crescimento.Angle Class II malocclusion is characterized by an anteroposterior dental discrepancy which is generally accompanied by skeletal disharmonies. Early orthodontic treatment allows the correction of skeletal discrepancies using growth control (first phase which favors later correction of tooth positioning (second phase. This case report describes an Angle Class II, division 2, malocclusion treated in two phases and was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as part of the requirements for BBO certification. It was evaluated as a Category 1 case, i.e., Class II malocclusion treated without extractions, with growth control.

  15. Integrated Data Collection Analysis (IDCA) Program - RDX Type II Class 5 Standard, Data Set 1

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorenson, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Moran, Jesse S. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates, Inc., Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Whipple, Richard E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-04-11

    This document describes the results of the first reference sample material—RDX Type II Class 5—examined in the proficiency study for small-scale safety and thermal (SSST) testing of explosive materials for the Integrated Data Collection Analysis (IDCA) Program. The IDCA program is conducting proficiency testing on homemade explosives (HMEs). The reference sample materials are being studied to establish the accuracy of traditional explosives safety testing for each performing laboratory. These results will be used for comparison to results from testing HMEs. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of these materials in perspective with standard military explosives. The results of the study will add SSST testing results for a broad suite of different HMEs to the literature, potentially suggest new guidelines and methods for HME testing, and possibly establish what are the needed accuracies in SSST testing to develop safe handling practices. Described here are the results for impact, friction, electrostatic discharge, and scanning calorimetry analysis of a reference sample of RDX Type II Class 5. The results from each participating testing laboratory are compared using identical test material and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. These results are then compared to historical data from various sources. The performers involved are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Air Force Research Laboratory/ RXQL (AFRL), Indian Head Division, Naval Surface Warfare Center, (IHD-NSWC), and Sandia National Laboratories (SNL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to understand how to compare results when test protocols are not identical.

  16. As implicações da classe II de angle e da desproporção esquelética tipo classe II no aspecto miofuncional The implications of class II angle and class II type skeletal disproportion on the myofunctional aspect

    Directory of Open Access Journals (Sweden)

    Carolina Lisbôa Mezzomo

    2011-08-01

    Full Text Available TEMA: esse trabalho foi baseado na temática de que existe uma associação entre as más oclusões devido a alterações do crescimento craniofacial, e, por conseguinte, a existência de alterações miofuncionais. OBJETIVOS: estudar a associação entre as más oclusões tipo classe II desencadeadas por alterações do crescimento craniofacial e as disfunções do sistema estomatognático (alterações miofuncionais: fala, mastigação, deglutição e fonação. CONCLUSÃO: pode-se concluir que alterações estruturais da face podem ter influência na funcionalidade das mesmas, portanto, enfatiza-se a importância do trabalho multidisciplinar entre os profissionais envolvidos em cada uma dessas aéreas para que o prognóstico desses casos seja pertinente de relevantes melhoras.BACKGROUND: this work has been based on the theme that there is an association between malocclusion due to change in craniofacial growth, and therefore, the existence of malfunctioning abnormalities. PURPOSE: to study the strong association among the malocclusion class II triggered by changes in craniofacial growth and dysfunctions of the stomatognathic system (myofunctional disorders - speech, chewing, swallowing and phonation. CONCLUSION: it may be concluded that structural changes of the face may affect its, and therefore, the importance of multidisciplinary work among professionals involved in each of those areas, is emphasized, so that the prognosis of these cases may have relevant and important improvements.

  17. Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

    Science.gov (United States)

    Ouadghiri, S; El Alaoui Toussi, K; Brick, C; Ait Benhaddou, E H; Benseffaj, N; Benomar, A; El Yahyaoui, M; Essakalli, M

    2013-12-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Cervical microleakage in Class II cavities restored with the Sonicsys approx system.

    Science.gov (United States)

    Rominu, Mihai; Florita, Zeno; Lakatos, Sorin; Rominu, Roxana Otilia

    2009-04-01

    To investigate the cervical microleakage in Class II cavities restored with Sonicsys approx ceramic inserts and four resin-based materials. Forty noncarious and crack-free mandibular third molars were used. These teeth were randomly assigned to four groups each containing 10 teeth. No control group was created. On each tooth, one mesial boxlike cavity was prepared using the active head Sonicsys approx no. 3. The cervical margin of each cavity was in enamel about 1 mm coronal to the cementoenamel junction. According to manufacturer's instructions, the prepared cavities were restored using a Sonicsys approx ceramic inserts no.3 and four resin-based materials as follows: group 1, Tetric Flow; group 2, Admira Flow; group 3, Nexus 2; group 4, X-Flow. After finishing and polishing, all specimens were stored in distilled water for 7 days at 37 degrees C, thermocycled 1,000 cycles between 5 degrees and 55 degrees C, and stored for 24 hours in basic fuchsine 2%. All specimens were then embedded in clear acrylic resin and sectioned along a mesial-distal plane through the middle of the cervical margin. The cervical areas of the resulting sections were examined using an optical microscope to assess the dye penetration. The registered scores were analyzed using Kruskal-Wallis and Mann-Whitney U tests. Microleakage was detected in each experimental group. Kruskal-Wallis test revealed statistically significant differences among groups (P = .009, alpha = .01). The Mann-Whitney U test showed significant differences between Admira Flow group and Tetric Flow (P = .011, alpha = .05), Nexus 2 (P = .001, alpha = .01), and X-Flow (P = .004, alpha = .01), respectively. Within the limitations of this study, the extent of microleakage in the cervical area (enamel) of Class II cavities restored with Sonicsys approx ceramic inserts depends on the material used for luting. The highest leakage occurred when Admira flow was used.

  19. Stability of Class II treatment with the Bionator followed by fixed appliances

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    Manoela Favaro FRANCISCONI

    2013-12-01

    Full Text Available Objective: This prospective study assessed the stability of Class II treatment with the Bionator, followed by fixed appliances, 10 years after treatment. Material and Methods: The experimental group comprised 23 patients of both sexes (10 boys, 13 girls at a mean initial age of 11.74 years (late mixed or early permanent dentitions, treated for a mean period of 3.55 years who were evaluated at three stages: initial (T1, final (T2 and long-term posttreatment (T3. A total of 69 lateral cephalograms were evaluated and 69 dental casts were measured using the PAR index. The difference between initial and final PAR indexes, the percentage of occlusal improvement obtained with therapy and the percentage of relapse were calculated, using the PAR index. The variables were compared by repeated measures analysis of variance (ANOVA followed by Tukey tests. Results: The significant improvement in apical base relationship, the palatal inclination of the maxillary incisors and the labial inclination of the mandibular incisors, and the significant improvement in molar relationship and reduction of overjet and overbite, obtained with treatment, remained stable in the long-term posttreatment period. There was also significant improvement in the occlusal relationships which remained stable in the long-term posttreatment period. The percentage of occlusal improvement obtained was of 81.78% and the percentage of relapse was of 4.90%. Conclusions: Treatment of Class II division 1 malocclusions with the Bionator associated with fixed appliances showed to be stable in the long-term posttreatment period.

  20. Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is IL-4 dependent.

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    Daxu Li

    Full Text Available BACKGROUND: Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic graft rejection mediated by Th2 cytokines remains ill-defined. METHODOLOGY/PRINCIPAL FINDINGS: Wild type and adiponectin-null mice were used as graft recipients in mouse MHC class II disparate cardiac transplantation (bm12 toB6 and the graft rejection was monitored. In adiponectin-null mice we observed that the cellular infiltrate of eosinophils, CD4(+ and CD8(+ T cells was reduced in grafts compared to the controls as was collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil infiltration was increased. Low levels of IL-4 were detected in the grafts and serum. The effect of adiponectin signaling on IL-4 expression was further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked adiponectin enhanced T cell proliferation in mixed lymphocyte reactions. Inhibition of AMPK reduced eosinophil infiltration in skin grafts in wild type recipients and in contrast AMPK activation increased eosinophils in adiponectin-null recipients. The addition of adiponectin increased IL-4 production by the T cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which were suppressed by knockdown of adiponectin receptor 1 and 2. CONCLUSIONS: Our results demonstrate a direct effect of adiponectin on IL-4 expression which contributes to Th2 cytokine mediated rejection in mouse MHC class II histoincompatible transplants. These results add to our understanding of the interrelationship of metabolism and immune regulation and raise the possibility that AMPK inhibitors may be beneficial in selected types of rejection.

  1. Outcome quality and long-term (≥15 years) stability after Class II:2 Herbst-multibracket appliance treatment in comparison to untreated Class I controls.

    Science.gov (United States)

    Bock, Niko C; Saffar, Mitra; Hudel, Helge; Evälahti, Marjut; Heikinheimo, Kaisa; Rice, David P; Ruf, Sabine

    2017-12-09

    To investigate the outcome quality and the long-term (≥15 years) post-treatment (Tx) changes after Class II:2 Herbst-multibracket appliance (MBA) Tx. In this longitudinal observational study, a recall of Class II:2 patients who had been treated by a Herbst-MBA during adolescence was conducted. Study models from before and after active Tx, after retention and after recall were assessed using standard occlusal variables and the peer assessment rating index (PAR). These data were compared to historical untreated Class I controls. Twenty out of 33 patients (61%) could be located and participated at age 33.9 ± 2.7 years. When comparing their data to the 13 patients who did not participate, the pre- and post-Tx occlusal findings did not differ systematically; however, the PAR scores of the non-participants were by 3.3-8.2 points higher at all times and the non-participants were 2.1-2.5 years older. Pre-Tx at age 14.4 ± 2.7 years, the participants showed the following mean values: PAR = 15.0 ± 7.0, Class II molar relationship (MR) = 0.8 ± 0.3 cusp widths (cw), overbite = 5.3 ± 1.3 mm. After Tx, a PAR score of 2.9 ± 1.3 and a super Class I MR (-0.1 ± 0.1 cw) with normal overbite (1.2 ± 0.8 mm) existed. At recall, a PAR score increase to 5.9 ± 3.6 points had occurred, mainly caused by an increase of overbite to 2.5 ± 1.5 mm. The average MR remained Class I (0.0 ± 0.2 cw). For all variables, the untreated controls exhibited similar findings. The occlusal outcome of Class II:2 Herbst-MBA Tx exhibited very good long-term stability. While mild post-Tx changes occurred, the long-term findings are similar to untreated Class I controls. © The Author(s) 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

  2. Key Role of Toll-Like Receptor 2 in the Inflammatory Response and Major Histocompatibility Complex Class II Downregulation in Brucella abortus-Infected Alveolar Macrophages

    Science.gov (United States)

    Ferrero, Mariana C.; Hielpos, M. Soledad; Carvalho, Natalia B.; Barrionuevo, Paula; Corsetti, Patricia P.; Giambartolomei, Guillermo H.; Oliveira, Sergio C.

    2014-01-01

    Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here, we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of tumor necrosis factor alpha (TNF-α), CXCL1 or keratinocyte chemoattractant (KC), interleukin-1β (IL-1β), IL-6, and IL-12 in AM from C57BL/6 mice and BALB/c mice, but these responses were generally weaker and/or delayed compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4, and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a multiplicity of infection-dependent manner the expression of major histocompatibility complex class II (MHC-II) molecules induced by gamma interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19-kDa outer membrane protein of Brucella (L-Omp19), and it was shown to be mediated by TLR2 recognition. In contrast, no significant downregulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intratracheal infection, viable B. abortus was detected in AM from both wild-type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus survives in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival. PMID:24478078

  3. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11.

    Science.gov (United States)

    Lundegaard, Claus; Lamberth, Kasper; Harndahl, Mikkel; Buus, Søren; Lund, Ole; Nielsen, Morten

    2008-07-01

    NetMHC-3.0 is trained on a large number of quantitative peptide data using both affinity data from the Immune Epitope Database and Analysis Resource (IEDB) and elution data from SYFPEITHI. The method generates high-accuracy predictions of major histocompatibility complex (MHC): peptide binding. The predictions are based on artificial neural networks trained on data from 55 MHC alleles (43 Human and 12 non-human), and position-specific scoring matrices (PSSMs) for additional 67 HLA alleles. As only the MHC class I prediction server is available, predictions are possible for peptides of length 8-11 for all 122 alleles. artificial neural network predictions are given as actual IC(50) values whereas PSSM predictions are given as a log-odds likelihood scores. The output is optionally available as download for easy post-processing. The training method underlying the server is the best available, and has been used to predict possible MHC-binding peptides in a series of pathogen viral proteomes including SARS, Influenza and HIV, resulting in an average of 75-80% confirmed MHC binders. Here, the performance is further validated and benchmarked using a large set of newly published affinity data, non-redundant to the training set. The server is free of use and available at: http://www.cbs.dtu.dk/services/NetMHC.

  4. Immunomodulation of glioma cells after gene therapy: induction of major histocompatibility complex class I but not class II antigen in vitro.

    Science.gov (United States)

    Parsa, A T; Chi, J H; Hurley, P T; Jeyapalan, S A; Bruce, J N

    2001-09-01

    Acquired immunity has been demonstrated in Fischer rats bearing syngeneic 9L tumors after herpes simplex virus (HSV) thymidine kinase (TK) gene transfection and ganciclovir treatment. The nature of this immunity in rats and its relevance to the HSV TK/ganciclovir protocol for human subjects remain to be determined. In this study, levels of major histocompatibility complex (MHC) Class I and II antigen expression were measured before and after HSV TK transfection, in an effort to document immunomodulatory changes caused by gene therapy. Tumor cells from the 9L gliosarcoma cell line, three primary human glioma cultures, and the human glioma cell line U87 MG were transduced with HSV TK vector-containing supernatant from fibroblast-producing cells (titer of 5 x 10(6) colony-forming units/ml) and selected in G418 medium for neomycin resistance. Clones were pooled or individually selected for cell-killing assays with ganciclovir, to confirm TK expression (10(3) cells/well in a 96-well dish). Northern analyses using MHC Class I and Class II complementary deoxyribonucleic acid probes were performed on blots containing total ribonucleic acid from wild-type tumor cells and HSV TK transfectants. A beta-actin complementary deoxyribonucleic acid probe served as an internal control. Cell surface expression was confirmed with flow cytometry. The induction of MHC Class I was tested for cycloheximide and genistein sensitivity. All cell cultures exhibited increases in MHC Class I but not MHC Class II expression, as determined by Northern analysis densitometry and flow cytometry. Cycloheximide treatment did not diminish the up-regulation of MHC Class I after retroviral transfection, implicating a signal transduction pathway that does not require ongoing protein synthesis. Genistein pretreatment of cell cultures did diminish the up-regulation of MHC Class I, implicating a tyrosine kinase in the signaling cascade. Induction of MHC Class I in rat and human glioma cells after HSV TK

  5. Spectropolarimetric Inversions of the Ca II 8542 Å Line in an M-class Solar Flare

    Science.gov (United States)

    Kuridze, D.; Henriques, V. M. J.; Mathioudakis, M.; Rouppe van der Voort, L.; de la Cruz Rodríguez, J.; Carlsson, M.

    2018-06-01

    We study the M1.9-class solar flare SOL2015-09-27T10:40 UT using high-resolution full Stokes imaging spectropolarimetry of the Ca II 8542 Å line obtained with the CRISP imaging spectropolarimeter at the Swedish 1-m Solar Telescope. Spectropolarimetric inversions using the non-LTE code NICOLE are used to construct semiempirical models of the flaring atmosphere to investigate the structure and evolution of the flare temperature and magnetic field. A comparison of the temperature stratification in flaring and nonflaring areas reveals strong heating of the flare ribbon during the flare peak. The polarization signals of the ribbon in the chromosphere during the flare maximum become stronger when compared to its surroundings and to pre- and post-flare profiles. Furthermore, a comparison of the response functions to perturbations in the line-of-sight magnetic field and temperature in flaring and nonflaring atmospheres shows that during the flare, the Ca II 8542 Å line is more sensitive to the lower atmosphere where the magnetic field is expected to be stronger. The chromospheric magnetic field was also determined with the weak-field approximation, which led to results similar to those obtained with the NICOLE inversions.

  6. Superantigen and HLA-DR ligation induce phospholipase-C gamma 1 activation in class II+ T cells

    DEFF Research Database (Denmark)

    Kanner, S B; Odum, Niels; Grosmaire, L

    1992-01-01

    Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA-DR) expressed on both APC and activated human T cells, and simultaneously bind to certain V beta chains of the TCR. In this report, we compared early T cell signaling events in human alloantigen-stimulated T cells when...... activated by HLA-DR ligation through antibody cross-linking or by direct enterotoxin superantigen binding. Both types of stimuli induced tyrosine phosphorylation of phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an increase in intracellular calcium concentration; however......, superantigen-induced signaling was stronger than class II ligation alone. Antibody-mediated ligation of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased calcium mobilization, consistent with a mechanism of superantigen activity through a combination of class II and CD3/Ti signals...

  7. Lateral-access Class II restoration using resin-modified glass-ionomer or silver-cermet cement.

    Science.gov (United States)

    Croll, T P

    1995-02-01

    Direct-access preparation of a carious proximal surface is perhaps the most conservative approach to restoration. Physical properties and handling characteristics of silver amalgam and of resin composite and lack of fluoride ion release make these materials unsuitable for direct buccal- or lingual-access proximal restoration. Insufficient strengths and radiolucency of self-hardening glass-ionomer cements preclude their use for Class II restorations. However, glass-ionomer silver-cermet cement and some resin-modified glass-ionomer materials are proving useful for non-stress-bearing Class II restorations and may have applications in preventive dentistry. This article describes lateral-access Class II restoration with modified glass-ionomer cements. Emphasis is placed on careful handling of materials, maintenance of an ideal operative field, and conservation of tooth structure.

  8. A Randomized 10-year Prospective Follow-up of Class II Nanohybrid and Conventional Hybrid Resin Composite Restorations

    DEFF Research Database (Denmark)

    van Dijken, Jan Wv; Pallesen, Ulla

    2014-01-01

    Purpose: To evaluate the 10-year durability of a nanohybrid resin composite in Class II restorations in a randomized controlled intraindividual comparison with its conventional hybrid resin composite predecessor. Materials and Methods: Each of 52 participants received at least two Class II...... restorations that were as similar as possible. The cavities were chosen at random to be restored with a nanohybrid resin composite (Excite/Tetric EvoCeram (TEC); n = 61) and a conventional hybrid (Excite/Tetric Ceram (TC); n = 61). The restorations were evaluated with slightly modified USPHS criteria...... investigated resin composites. Conclusion: The nanohybrid and the conventional hybrid resin composite showed good clinical effectiveness in extensive Class II restorations during the 10-year study....

  9. Characterization and evolution of MHC class II B genes in Galápagos marine iguanas (Amblyrhynchus cristatus).

    Science.gov (United States)

    Glaberman, Scott; Moreno, Maria A; Caccone, Adalgisa

    2009-08-01

    Major histocompatibility complex (MHC) class II molecules play a key role in the adaptive immune system of vertebrates. Class II B genes appear to evolve in a very different manner in mammals and birds. Orthology is commonly observed among mammal loci, while genes tend to cluster phylogenetically within bird species. Here we present class II B data from a representative of another major group of amniotes, the squamates (i.e. lizards, snakes, amphisbaenians), with the ultimate goal of placing mammalian and avian MHC evolution into a broader context. In this study, eight class II B cDNA sequences were obtained from the Galápagos marine iguana (Amblyrhynchus cristatus) which were divided into five locus groups, Amcr-DAB1 through -DAB5, based on similarities along most of the coding and noncoding portions of the transcribed gene. All marine iguana sequences were monophyletic with respect to class II genes from other vertebrates indicating that they originated from a common ancestral locus after squamates split from other reptiles. The beta-1 domain, which is involved in antigen binding, exhibited signatures of positive selection as well as interlocus gene conversion in both long and short tracts-a pattern also observed in birds and fish, but not in mammals. On the other hand, the beta-2 domain was divergent between gene groups, which is characteristic of mammals. Based on these results, we preliminarily show that squamate class II B genes have been shaped by a unique blend of evolutionary forces that have been observed in differing degrees in other vertebrates.

  10. Assessing high affinity binding to HLA-DQ2.5 by a novel peptide library based approach

    DEFF Research Database (Denmark)

    Jüse, Ulrike; Arntzen, Magnus; Højrup, Peter

    2011-01-01

    Here we report on a novel peptide library based method for HLA class II binding motif identification. The approach is based on water soluble HLA class II molecules and soluble dedicated peptide libraries. A high number of different synthetic peptides are competing to interact with a limited amount...... library. The eluted sequences fit very well with the previously described HLA-DQ2.5 peptide binding motif. This novel method, limited by library complexity and sensitivity of mass spectrometry, allows the analysis of several thousand synthetic sequences concomitantly in a simple water soluble format....

  11. Subcellular localization of class II HDAs in Arabidopsis thaliana: nucleocytoplasmic shuttling of HDA15 is driven by light.

    Directory of Open Access Journals (Sweden)

    Malona V Alinsug

    Full Text Available Class II histone deacetylases in humans and other model organisms undergo nucleocytoplasmic shuttling. This unique functional regulatory mechanism has been well elucidated in eukaryotic organisms except in plant systems. In this study, we have paved the baseline evidence for the cytoplasmic and nuclear localization of Class II HDAs as well as their mRNA expression patterns. RT-PCR analysis on the different vegetative parts and developmental stages reveal that Class II HDAs are ubiquitously expressed in all tissues with minimal developmental specificity. Moreover, stable and transient expression assays using HDA-YFP/GFP fusion constructs indicate cytoplasmic localization of HDA5, HDA8, and HDA14 further suggesting their potential for nuclear transport and deacetylating organellar and cytoplasmic proteins. Organelle markers and stains confirm HDA14 to abound in the mitochondria and chloroplasts while HDA5 localizes in the ER. HDA15, on the other hand, shuttles in and out of the nucleus upon light exposure. In the absence of light, it is exported out of the nucleus where further re-exposition to light treatments signals its nuclear import. Unlike HDA5 which binds with 14-3-3 proteins, HDA15 fails to interact with these chaperones. Instead, HDA15 relies on its own nuclear localization and export signals to navigate its subcellular compartmentalization classifying it as a Class IIb HDA. Our study indicates that nucleocytoplasmic shuttling is indeed a hallmark for all eukaryotic Class II histone deacetylases.

  12. [Pre-surgical orthodontic treatment of skeletal class II patients with gingival smile corrected by anterior maxillary segmental osteotomy].

    Science.gov (United States)

    Li, Xiaobing; Xiao, Liwei; Chen, Song; Chen, Yangxi

    2002-11-01

    To discuss the pre-surgical orthodontic treatment of skeletal class II patients with gingiva smile corrected by AMSO. We analyzed the clinical features of 20 skeletal class II patients treated by AMSO combined with Orthodontic treatment and evaluated the effects of AMSO by means of cephalometric analysis. After the AMSO treatment, ANB angle, the height of anterior maxilla, the protrusion of the upper anterior teeth, and the of A point had reduced significantly (P orthodontically to make arch relationship. Extract the upper bicuspid half a year before the surgery was recommended. When necessary, genioplasty could be performed.

  13. Binding of Cu(II) ions to peptides studied by fluorescence spectroscopy and isothermal titration calorimetry

    Science.gov (United States)

    Makowska, Joanna; Żamojć, Krzysztof; Wyrzykowski, Dariusz; Uber, Dorota; Wierzbicka, Małgorzata; Wiczk, Wiesław; Chmurzyński, Lech

    2016-01-01

    Steady-state and time-resolved fluorescence quenching measurements supported by Isothermal Titration Calorimetry (ITC) were used to study the interactions of Cu2 + with four peptides. Two of them were taken from the N-terminal part of the FBP28 protein (formin binding protein) WW domain: Tyr-Lys-Thr-Ala-Asp-Gly-Lys-Thr-Tyr-NH2 (D9) and its mutant Tyr-Lys-Thr-Ala-Asn-Gly-Lys-Thr-Tyr-NH2 (D9_M) as well as two mutated peptides from the B3 domain of the immunoglobulin binding protein G derived from Streptococcus: Asp-Val-Ala-Thr-Tyr-Thr-NH2 (J1) and Glu-Val-Ala-Thr-Tyr-Thr-NH2 (J2). The measurements were carried out at 298.15 K in 20 mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer solution with a pH of 6. The fluorescence of all peptides was quenched by Cu2 + ions. The stoichiometry, conditional stability constants and thermodynamic parameters for the interactions of the Cu2 + ions with D9 and D9_M were determined from the calorimetric data. The values of the conditional stability constants were additionally determined from fluorescence quenching measurements and compared with those obtained from calorimetric studies. There was a good correlation between data obtained from the two techniques. On the other hand, the studies revealed that J1 and J2 do not exhibit an affinity towards metal ions. The obtained results prove that fluorescence quenching experiments may be successfully used in order to determine stability constants of complexes with fluorescent ligands. Finally, based on the obtained results, the coordinating properties of the peptides towards the Cu2 + ions are discussed.

  14. Binding of Cu(II) ions to peptides studied by fluorescence spectroscopy and isothermal titration calorimetry.

    Science.gov (United States)

    Makowska, Joanna; Żamojć, Krzysztof; Wyrzykowski, Dariusz; Uber, Dorota; Wierzbicka, Małgorzata; Wiczk, Wiesław; Chmurzyński, Lech

    2016-01-15

    Steady-state and time-resolved fluorescence quenching measurements supported by Isothermal Titration Calorimetry (ITC) were used to study the interactions of Cu(2+) with four peptides. Two of them were taken from the N-terminal part of the FBP28 protein (formin binding protein) WW domain: Tyr-Lys-Thr-Ala-Asp-Gly-Lys-Thr-Tyr-NH2 (D9) and its mutant Tyr-Lys-Thr-Ala-Asn-Gly-Lys-Thr-Tyr-NH2 (D9_M) as well as two mutated peptides from the B3 domain of the immunoglobulin binding protein G derived from Streptococcus: Asp-Val-Ala-Thr-Tyr-Thr-NH2 (J1) and Glu-Val-Ala-Thr-Tyr-Thr-NH2 (J2). The measurements were carried out at 298.15K in 20mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer solution with a pH of 6. The fluorescence of all peptides was quenched by Cu(2+) ions. The stoichiometry, conditional stability constants and thermodynamic parameters for the interactions of the Cu(2+) ions with D9 and D9_M were determined from the calorimetric data. The values of the conditional stability constants were additionally determined from fluorescence quenching measurements and compared with those obtained from calorimetric studies. There was a good correlation between data obtained from the two techniques. On the other hand, the studies revealed that J1 and J2 do not exhibit an affinity towards metal ions. The obtained results prove that fluorescence quenching experiments may be successfully used in order to determine stability constants of complexes with fluorescent ligands. Finally, based on the obtained results, the coordinating properties of the peptides towards the Cu(2+) ions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Effect of amino acid sequence and pH on nanofiber formation of self-assembling peptides EAK16-II and EAK16-IV.

    Science.gov (United States)

    Hong, Yooseong; Legge, Raymond L; Zhang, S; Chen, P

    2003-01-01

    Atomic force microscopy (AFM) and axisymmetric drop shape analysis-profile (ASDA-P) were used to investigate the mechanism of self-assembly of peptides. The peptides chosen consisted of 16 alternating hydrophobic and hydrophilic amino acids, where the hydrophilic residues possess alternating negative and positive charges. Two types of peptides, AEAEAKAKAEAEAKAK (EAK16-II) and AEAEAEAEAKAKAKAK (EAK16-IV), were investigated in terms of nanostructure formation through self-assembly. The experimental results, which focused on the effects of the amino acid sequence and pH, show that the nanostructures formed by the peptides are dependent on the amino acid sequence and the pH of the solution. For pH conditions around neutrality, one of the peptides used in this study, EAK16-IV, forms globular assemblies and has lower surface tension at air-water interfaces than another peptide, EAK16-II, which forms fibrillar assemblies at the same pH. When the pH is lowered below 6.5 or raised above 7.5, there is a transition from globular to fibrillar structures for EAK16-IV, but EAK16-II does not show any structural transition. Surface tension measurements using ADSA-P showed different surface activities of peptides at air-water interfaces. EAK16-II does not show a significant difference in surface tension for the pH range between 4 and 9. However, EAK16-IV shows a noticeable decrease in surface tension at pH around neutrality, indicating that the formation of globular assemblies is related to the molecular hydrophobicity.

  16. Cu(II) Binding to the Peptide Ala-His-His, a Chimera of the Canonical Cu(II)-Binding Motifs Xxx-His and Xxx-Zzz-His.

    Science.gov (United States)

    Gonzalez, Paulina; Vileno, Bertrand; Bossak, Karolina; El Khoury, Youssef; Hellwig, Petra; Bal, Wojciech; Hureau, Christelle; Faller, Peter

    2017-12-18

    Peptides and proteins with the N-terminal motifs NH 2 -Xxx-His and NH 2 -Xxx-Zzz-His form well-established Cu(II) complexes. The canonical peptides are Gly-His-Lys and Asp-Ala-His-Lys (from the wound healing factor and human serum albumin, respectively). Cu(II) is bound to NH 2 -Xxx-His via three nitrogens from the peptide and an external ligand in the equatorial plane (called 3N form here). In contrast, Cu(II) is bound to NH 2 -Xxx-Zzz-His via four nitrogens from the peptide in the equatorial plane (called 4N form here). These two motifs are not mutually exclusive, as the peptides with the sequence NH 2 -Xxx-His-His contain both of them. However, this chimera has never been fully explored. In this work, we use a multispectroscopic approach to analyze the Cu(II) binding to the chimeric peptide Ala-His-His (AHH). AHH is capable of forming the 3N- and 4N-type complexes in a pH dependent manner. The 3N form predominates at pH ∼ 4-6.5 and the 4N form at ∼ pH 6.5-10. NMR experiments showed that at pH 8.5, where Cu(II) is almost exclusively bound in the 4N form, the Cu(II)-exchange between AHH or the amidated AHH-NH 2 is fast, in comparison to the nonchimeric 4N form (AAH). Together, the results show that the chimeric AHH can access both Cu(II) coordination types, that minor changes in the second (or further) coordination sphere can impact considerably the equilibrium between the forms, and that Cu kinetic exchange is fast even when Cu-AHH is mainly in the 4N form.

  17. Development of a rapid in vitro protein refolding assay which discriminates between peptide-bound and peptide-free forms of recombinant porcine major histocompatibility class I complex (SLA-I)

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Kristensen, B.; Ladekjaer-Mikkelsen, A.S.

    2002-01-01

    The extracellular domains of swine leukocyte antigen class I (SLA-I, major histocompatibility complex protein class 1) were cloned and sequenced for two haplotypes (114 and H7) which do not share any alleles based on serological typing, and which are the most important in Danish farmed pigs....... The extracellular domain of SLA-I was connected to porcine beta2 microglobulin by glycine-rich linkers. The engineered sin.-le-chain proteins, consisting of fused SLA-I and beta2 microglobulin, were overexpressed as inclusion bodies in Escherichia coli. Also, variants were made of the single-chain proteins......, by linking them through glycine-rich linkers to peptides representing T-cell epitopes from classical swine fever virus (CSFV) and foot-and-mouth disease virus (FMDV). An in vitro refold assay was developed, using a monoclonal anti-SLA antibody (PT85A) to gauge refolding. The single best-defined, SLA...

  18. Characterization of major histocompatibility complex class I, and class II DRB loci of captive and wild Indian leopards (Panthera pardus fusca).

    Science.gov (United States)

    Parmar, Drashti R; Mitra, Siuli; Bhadouriya, Snehalata; Rao, Tirupathi; Kunteepuram, Vaishnavi; Gaur, Ajay

    2017-12-01

    The major histocompatibility complex (MHC), in vertebrate animals, is a multi-genic protein complex that encodes various receptors. During a disease, MHC interacts with the antigen and triggers a cascade of adaptive immune responses to overcome a disease outbreak. The MHC is very important region from immunological point of view, but it is poorly characterized among Indian leopards. During this investigation, we examined genetic diversity for MHC class I (MHC-I) and MHC class II-DRB (MHC-II) among wild and captive Indian leopards. This study estimated a pool of 9 and 17 alleles for MHC-I and MHC-II, respectively. The wild group of individuals showed higher nucleotide diversity and amino acid polymorphism compared to the captive group. A phylogenetic comparison with other felids revealed a clustering in MHC-I and interspersed presence in MHC-II sequences. A test for selection also revealed a deviation from neutrality at MHC-II DRB loci and higher non-synonymous substitution rate (dN) among the individuals from wild group. Further, the wild individuals showed higher dN for both MHC I and II genes compared to the group that was bred under captive conditions. These findings suggest the role of micro-evolutionary forces, such as pathogen-mediated selection, to cause MHC variations among the two groups of Indian leopards, because the two groups have been bred in two different environments for a substantial period of time. Since, MHC diversity is often linked with the quality of immunological health; the results obtained from this study fill the gap of knowledge on disease predisposition among wild and captive Indian leopards.

  19. The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif.

    Science.gov (United States)

    Ross, Peter; Nemec, Paige S; Kapatos, Alexander; Miller, Keith R; Holmes, Jennifer C; Suter, Steven E; Buntzman, Adam S; Soderblom, Erik J; Collins, Edward J; Hess, Paul R

    2018-03-01

    Ideally, CD8+ T-cell responses against virally infected or malignant cells are defined at the level of the specific peptide and restricting MHC class I element, a determination not yet made in the dog. To advance the discovery of canine CTL epitopes, we sought to determine whether a putative classical MHC class Ia gene, Dog Leukocyte Antigen (DLA)-88, presents peptides from a viral pathogen, canine distemper virus (CDV). To investigate this possibility, DLA-88*508:01, an allele prevalent in Golden Retrievers, was expressed as a FLAG-tagged construct in canine histiocytic cells to allow affinity purification of peptide-DLA-88 complexes and subsequent elution of bound peptides. Pattern analysis of self peptide sequences, which were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), permitted binding preferences to be inferred. DLA-88*508:01 binds peptides that are 9-to-12 amino acids in length, with a modest preference for 9- and 11-mers. Hydrophobic residues are favored at positions 2 and 3, as are K, R or F residues at the C-terminus. Testing motif-matched and -unmatched synthetic peptides via peptide-MHC surface stabilization assay using a DLA-88*508:01-transfected, TAP-deficient RMA-S line supported these conclusions. With CDV infection, 22 viral peptides ranging from 9-to-12 residues in length were identified in DLA-88*508:01 eluates by LC-MS/MS. Combined motif analysis and surface stabilization assay data suggested that 11 of these 22 peptides, derived from CDV hemagglutinin, large polymerase, matrix, nucleocapsid, and V proteins, were processed and presented, and thus, potential targets of anti-viral CTL in DLA-88*508:01-bearing dogs. The presentation of diverse self and viral peptides indicates that DLA-88 is a classical MHC class Ia gene. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

    Science.gov (United States)

    Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

    2015-07-31

    HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)

    Science.gov (United States)

    Wilbe, Maria; Ziener, Martine Lund; Aronsson, Anita; Harlos, Charlotte; Sundberg, Katarina; Norberg, Elin; Andersson, Lisa; Lindblad-Toh, Kerstin; Hedhammar, Åke; Andersson, Göran; Lingaas, Frode

    2010-01-01

    Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis. PMID:20808798

  2. DLA class II alleles are associated with risk for canine symmetrical lupoid onychodystrophy [corrected](SLO.

    Directory of Open Access Journals (Sweden)

    Maria Wilbe

    Full Text Available Symmetrical lupoid onychodystrophy (SLO is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802 was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33 was present in 16.8% of controls, but only in a single case (0.5%. The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.

  3. Changes in soft tissue profile using functional appliances in the treatment of skeletal class II malocclusion

    Directory of Open Access Journals (Sweden)

    Stamenković Zorana

    2015-01-01

    Full Text Available Introduction. The effects of orthodontic treatment are considered to be successful if the facial harmony is achieved, while the structures of soft tissue profile are in harmony with skeletal structures of neurocranium and viscerocranium. In patients with skeletal distal bite caused by mandibular retrognathism, facial esthetics is disturbed often, in terms of pronounced convexity of the profile and change in the position and relationship of the lips. Objective. The aim of this study was to determine the extent of soft tissue profile changes in patients with skeletal Class II malocclusion treated with three different orthodontic appliances: Fränkel functional regulator type I (FR-I, Balters’ Bionator type I and Hotz appliance. Methods. The study included 60 patients diagnosed with skeletal Class II malocclusion caused by mandibular retrognathism, in the period of early mixed dentition. Each subgroup of 20 patients was treated with a variety of orthodontic appliances. On the lateral cephalogram, before and after treatment, the following parameters were analyzed: T angle, H angle, the height of the upper lip, the position of the upper and lower lip in relation to the esthetic line. Within the statistical analysis the mean, maximum, minimum, standard deviation, coefficient of variation, two-factor analysis of variance with repeated measures and the factor analysis of variance were calculated using ANOVA, Bonferroni test and Student’s t-test. Results. A significant decrease of angles T and H was noticed in the application of FR-I, from 21.60° to 17.15°, and from 16.45° to 13.40° (p<0.001. FR-I decreased the height of the upper lip from 26.15 mm to 25.85 mm, while Hotz appliance and Balters’ Bionator type I increased the height of the upper lip, thereby deteriorating esthetics of the patient. Conclusion. All used orthodontic appliances lead to changes in soft tissue profile in terms of improving facial esthetics, with the most distinctive

  4. Relative Atrial Natriuretic Peptide Deficiency and Inadequate Renin and Angiotensin II Suppression in Obese Hypertensive Men

    DEFF Research Database (Denmark)

    Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B

    2013-01-01

    Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese...... hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure,...

  5. Template Based Design of Anti-Metastatic Drugs from the Active Conformation of Laminin Peptide II

    Science.gov (United States)

    2001-01-01

    affords lactam 10 as a 7 X=OH, Y=H Ph2BuSiO HH separable mixture of diastereomers rather 8 x = CI, Y NO2 9 10 than tricycle 11. Treatment of 10 with base...of mimotopes. explain the fact that pre- treatment of laminin with Amongst the phage that mimic the LBP൜ 9 peptide G in solution increases its...of ca6 - Colnagi, M. I. (1994). The simultaneous expression of integrin receptors and of mRNA encoding the puta- c-erbB-2 oncoprotein and laminin

  6. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency

    Directory of Open Access Journals (Sweden)

    Djidjik Réda

    2012-08-01

    Full Text Available Abstract Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26. Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

  7. 77 FR 37058 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-06-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA 2012-D-0304] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

  8. 76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-04-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0189] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS...

  9. 75 FR 70271 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0515] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

  10. 75 FR 68364 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-D-0275] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Full-Field Digital Mammography System; Availability AGENCY: Food and Drug Administration, HHS. [[Page...

  11. 76 FR 16425 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-03-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0028] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Score Test System; Availability AGENCY: Food and Drug Administration, HHS...

  12. 76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-02-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0645] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

  13. 76 FR 22906 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-04-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

  14. 76 FR 28688 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No. FDA-2011-D-0102] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Bacillus Species Detection AGENCY: Food and...

  15. 76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-07-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0500] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration...

  16. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-07-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...

  17. 77 FR 14403 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2012-03-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

  18. 76 FR 48870 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-08-09

    ... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

  19. 75 FR 59726 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2010-09-28

    ... method comparison section and the sample selection inclusion and exclusion criteria section. The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

  20. 25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

    Science.gov (United States)

    2010-04-01

    ... gaming system accounting functions? 547.9 Section 547.9 Indians NATIONAL INDIAN GAMING COMMISSION... accounting functions? This section provides standards for accounting functions used in Class II gaming systems. (a) Required accounting data.The following minimum accounting data, however named, shall be...

  1. A research for Class II defect Bored Pile’s Accept Criteria: A case of Penang Second Marine bridge

    Science.gov (United States)

    Huang, Kang

    2018-03-01

    The aim of this preliminary research is to study the accept criteria of class II bored pile with subtle defect. According to a detailed comparison of the existed different standards, Chinese ones are more applicable especially for the large diameter bored piles. Through the concrete coring at pile No P25-03 of this case and the comparison to the actual calculation, the Class II pile’s defects were very minor. Comparison was also made for the effects on pile structural capacities before and after repair of the defects. the feasible repair proposal may bring forward to more defects to the piles. The Class II piles don’t need any further repairation when piles have typical of similar character and sonic logging test result with P25-03‘s one. For other Class II piles with some differences in characters, verification is needed through further concrete coring on the pile. The recommendation of this research could be adopted for the similar huge marine structures which installed large diameter bored piles.

  2. 40 CFR Table 4 to Subpart Jjj of... - Class II Emission Limits for Existing Small Municipal Waste Combustion Unitsa

    Science.gov (United States)

    2010-07-01

    ... Small Municipal Waste Combustion Unitsa 4 Table 4 to Subpart JJJ of Part 62 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Pt. 62, Subpt. JJJ, Table 4 Table 4 to Subpart JJJ of Part 62—Class II Emission Limits for Existing Small Municipal Waste Combustion Unitsa ER31JA03.009...

  3. Negative relationships between cellular immune response, Mhc class II heterozygosity and secondary sexual trait in the montane water vole

    Czech Academy of Sciences Publication Activity Database

    Charbonnel, N.; Bryja, Josef; Galan, M.; Deter, J.; Tollenaere, C.; Chaval, Y.; Morand, S.; Cosson, J.-F.

    2010-01-01

    Roč. 3, č. 3 (2010), s. 279-290 ISSN 1752-4571 EU Projects: European Commission(XE) 10284 - EDEN Institutional research plan: CEZ:AV0Z60930519 Keywords : abundance cycles * Dqa and Drb * immunocompetence handicap * Mhc class II genes * parasite-mediated balancing selection * sexual selection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.145, year: 2010

  4. Effectiveness of comprehensive fixed appliance treatment used with the Forsus Fatigue Resistant Device in Class II patients.

    Science.gov (United States)

    Franchi, Lorenzo; Alvetro, Lisa; Giuntini, Veronica; Masucci, Caterina; Defraia, Efisio; Baccetti, Tiziano

    2011-07-01

    To assess the dental, skeletal, and soft tissue effects of comprehensive fixed appliance treatment combined with the Forsus Fatigue Resistant Device (FRD) in Class II patients. Thirty-two Class II patients (mean age 12.7 ± 1.2 years) were treated consecutively with the FRD protocol and compared with a matched sample of 27 untreated Class II subjects (mean age 12.8 ± 1.3 years). Lateral cephalograms were taken before therapy and at the completion of comprehensive therapy. The mean duration of comprehensive treatment was 2.4 ± 0.4 years. Statistical comparisons were carried out with the Student's t-test (P < .05). The success rate was 87.5%. The FRD group showed a significant restraint in the sagittal skeletal position of the maxilla (also at the soft tissue level), a significant increase in mandibular length, and a significant improvement in maxillo-mandibular sagittal skeletal relationships. The treated group exhibited a significant reduction in overjet and a significant increase in molar relationship. The lower incisors were significantly proclined and intruded, while the lower first molars moved significantly in a mesial and vertical direction. The FRD protocol is effective in correcting Class II malocclusion with a combination of skeletal (mainly maxillary) and dentoalveolar (mainly mandibular) modifications.

  5. 75 FR 54637 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-09-08

    ... conferencing and electronic submissions, Mammography Matters, and other device-oriented information. The CDRH... approval) into class II (special controls). DATES: Submit written or electronic comments on this guidance... electronic access to the guidance. Submit electronic comments on the guidance to http://www.regulations.gov...

  6. Stability of skeletal changes induced by growth modulation procedures in the treatment of skeletal Class II malocclusion

    Directory of Open Access Journals (Sweden)

    Prashantha Govinakovi Shivamurthy

    2016-01-01

    Full Text Available Objective: Objective of this study, based on an evaluation of lateral cephalograms, was to evaluate the degree of skeletal changes produced by the various growth modulative procedures in the treatment of skeletal Class II malocclusion and to characterize the stability of these changes in the years after treatment. Materials and Methods: Total of 40 patients with Class II malocclusion was divided into three groups according to appliance used, i.e. removable or fixed functional appliances (n = 10, combination of functional appliance with headgear (n = 10, and only headgear (n = 10. In addition, almost a matched control group (n = 10 also characterized by skeletal Class II pattern and were under observation, for more than 2 years was also selected. Lateral cephalograms of each patient were taken at the start of treatment (T1, at its completion (T2, and long-term posttreatment (T3. Results: This study showed significant improvement in maxillomandibular relationship in treated group compared to control group, and the changes remained stable in posttreatment phase. Restriction of maxillary growth was evident in headgear and combination groups whereas significant forward movement of the mandible was seen in functional group. Conclusion: Analysis of lateral cephalograms indicates that growth modulation therapy in angle Class II malocclusion brings about desired skeletal changes which remain relatively stable over a long-term period.

  7. MHC class II genes in the European badger (Meles meles) : Characterization, patterns of variation, and transcription analysis

    NARCIS (Netherlands)

    Sin, Yung Wa; Dugdale, Hannah L.; Newman, Chris; Macdonald, David W.; Burke, Terry

    The major histocompatibility complex (MHC) comprises many genes, some of which are polymorphic with numerous alleles. Sequence variation among alleles is most pronounced in exon 2 of the class II genes, which encodes the alpha 1 and beta 1 domains that form the antigen-binding site (ABS) for the

  8. Long-term outcomes of mandibular kinematics following class II malocclusion therapy with removable functional appliance therapy.

    Science.gov (United States)

    Linsen, Sabine S; Wolf, Michael; Müßig, Dieter

    2016-11-01

    To evaluate mandibular kinematics in class I adults following class II therapy with removable functional appliances (RFAs) during the growth period in comparison with orthodontically untreated class I and II individuals. Condylar (CRoM) and incisal range of motion (InRoM), velocity during opening and closing, and the mandibular rotation angle were recorded using an ultrasound-based jaw-tracking system in 36 test patients (mean age = 28.03 ± 6.58 years). Significant group effects were found for CRoM towards the posterior in the right joint (p = 0.002) and InRoM towards the anterior (p = 0.043). The post hoc Tukey test indicates a significantly longer CRoM (posterior) for the right condyle in class II (p = 0.003) and RFA individuals (p = 0.023). The kinematic data imply greater dentoalveolar effects due to RFA therapy than adaptive remodeling of the temporomandibular joint. The class I relationship in the RFA group following treatment indicates stable long-term outcomes.

  9. FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides.

    Science.gov (United States)

    Lingueglia, Eric; Deval, Emmanuel; Lazdunski, Michel

    2006-05-01

    FMRFamide and related peptides typically exert their action through G-protein coupled receptors. However, two ionotropic receptors for these peptides have recently been identified. They are both members of the epithelial amiloride-sensitive Na+ channel and degenerin (ENaC/DEG) family of ion channels. The invertebrate FMRFamide-gated Na+ channel (FaNaC) is a neuronal Na+-selective channel which is directly gated by micromolar concentrations of FMRFamide and related tetrapeptides. Its response is fast and partially desensitizing, and FaNaC has been proposed to participate in peptidergic neurotransmission. On the other hand, mammalian acid-sensing ion channels (ASICs) are not gated but are directly modulated by FMRFamide and related mammalian peptides like NPFF and NPSF. ASICs are activated by external protons and are therefore extracellular pH sensors. They are expressed both in the central and peripheral nervous system and appear to be involved in many physiological and pathophysiological processes such as hippocampal long-term potentiation and defects in learning and memory, acquired fear-related behavior, retinal function, brain ischemia, pain sensation in ischemia and inflammation, taste perception, hearing functions, and mechanoperception. The potentiation of ASIC activity by endogenous RFamide neuropeptides probably participates in the response to noxious acidosis in sensory and central neurons. Available data also raises the possibility of the existence of still unknown FMRFamide related endogenous peptides acting as direct agonists for ASICs.

  10. A clinical evaluation of a bioresorbable membrane and porous hydroxyapatite in the treatment of human molar class II furcations

    Directory of Open Access Journals (Sweden)

    K Gita Malathi

    2013-01-01

    Full Text Available Background: The ultimate goal of periodontal therapy is predictable regeneration of a functional attachment apparatus destroyed as a result of periodontitis. Reconstructive procedures have been used with varying success during the past decades to accomplish this goal. Aim: To evaluate whether the use of porous hydroxyapatite alone or a bioresorbable membrane alone would enhance the clinical results in the treatment of class II furcation defects in human lower molars. Materials and Methods: Fifteen patients with chronic periodontitis, aged between 39 and 49 years, with a pair of similar bilateral class II furcation defects (classification of Hamp et al. in mandibular first molars were selected. A split-mouth design was incorporated and the selected 30 furcation defects were assigned to one of the two treatment groups, i.e., Group I treated with a bioresorbable membrane from bovine-derived collagen guided tissue regeneration membrane and Group II treated using porous hydroxyapatite bone graft material on the contralateral sides. Evaluation of clinical parameters, probing depths and attachment levels, and radiographs was done preoperatively and 6 months postoperatively. Results: Both the groups showed statistically significant mean reduction in probing depths and gain in clinical attachment levels and linear bone fill. Comparison between Group I and Group II showed insignificant difference. Conclusion: Within the limits of this study, both the treatment modalities are beneficial for the treatment of human mandibular class II furcation defects.

  11. Two class II D-tagatose-bisphosphate aldolases from enteric bacteria.

    Science.gov (United States)

    Brinkkötter, Andreas; Shakeri-Garakani, Ansiah; Lengeler, Joseph W

    2002-05-01

    Escherichia coli, Salmonella enterica, Klebsiella pneumoniaeand Klebsiella oxytocawere found to contain two D-tagatose 1,6-bisphosphate (TagBP)-specific aldolases involved in catabolism of galactitol (genes gatY gatZ) and of N-acetyl-galactosamine and D-galactosamine (genes kbaY kbaZ,also called agaY agaZ). The two aldolases were closely related (> or = 53.8% identical amino acids) and could substitute for each other in vivo. The catalytic subunits GatY or KbaY alone were sufficient to show aldolase activity. Although substantially shorter than other aldolases (285 amino acids, instead of 358 and 349 amino acids), these subunits contained most or all of the residues that have been identified as essential in substrate/product recognition and catalysis for class II aldolases. In contrast to these, both aldolases required subunits GatZ or KbaZ (420 amino acids) for full activity and for good in vivo and in vitro stability. The Z subunits alone did not show any aldolase activity. Close relatives of these new TagBP aldolases were found in several gram-negative and gram-positive bacteria, e.g., Streptomyces coelicolor.

  12. Internal and Marginal Fit of Modern Indirect Class II Composite Inlays

    Directory of Open Access Journals (Sweden)

    Philipp C. Pott

    2014-06-01

    Full Text Available Introduction: This in vitro study investigates the marginal and internal fit of indirect class II composite restorations. Two different processes for chair-side restorations were compared. In group A, the restorations were fabricated using CAD/CAM technology (Cerec, Sirona, Germany, Bernsheim and in group B they were made by hand (GrandioSO Inlay System, VOCO GmbH, Germany, Cuxhaven. Methods: For a metal tooth with a MOD cavity each 10 restorations were made for groups A and B. For each restoration, a replica of the cement-gap made from light body silicone was produced by placing the restoration into the cavity of the metal tooth. For this purpose, a special restoration-positioning machine was developed. Each replica was sectioned off in the longitudinal axis (L and in the cross axis (C. The thickness of the replicas was measured in both directions, using picture analysis software under a light reflection microscope. To evaluate the fit of the restorations, a special fitting parameter was calculated. Statistical analysis was performed with the t test. Results: The fitting-parameter in group B (L: 97.6µm±73.0µm; C: 71.8µm±46.4µm was significantly lower than that of group A (L: 155.1µm±102.3.0µm; C: 168.2µm±91.9µm (P

  13. Medical devices; exemption from premarket notification; class II devices; wheelchair elevator. Final order.

    Science.gov (United States)

    2013-03-04

    The Food and Drug Administration (FDA) is publishing an order granting a petition requesting exemption from premarket notification requirements for wheelchair elevator devices commonly known as inclined platform lifts and vertical platform lifts. These devices are used to provide a means for a person with a mobility impairment caused by injury or other disease to move from one level to another, usually in a wheelchair. This order exempts wheelchair elevators, class II devices, from premarket notification and establishes conditions for exemption for this device that will provide a reasonable assurance of the safety and effectiveness of the device without submission of a premarket notification (510(k)). This exemption from 510(k), subject to these conditions, is immediately in effect for wheelchair elevators. All other devices classified under FDA's wheelchair elevator regulations, including attendant-operated stair climbing devices for wheelchairs and portable platform lifts, continue to require submission of 510(k)s. FDA is publishing this order in accordance with the section of the Food, Drug, and Cosmetic Act (the FD&C Act) permitting the exemption of a device from the requirement to submit a 510(k).

  14. Outcomes of different Class II treatments : Comparisons using the American Board of Orthodontics Model Grading System.

    Science.gov (United States)

    Akinci Cansunar, Hatice; Uysal, Tancan

    2016-07-01

    The aim of this study was to evaluate the clinical outcomes of three different Class II treatment modalities followed by fixed orthodontic therapy, using the American Board of Orthodontics Model Grading System (ABO-MGS). As a retrospective study, files of patients treated at postgraduate orthodontic  clinics in different cities in Turkey was randomly selected. From 1684 posttreatment records, 669 patients were divided into three groups: 269 patients treated with extraction of two upper premolars, 198 patients treated with cervical headgear, and 202 patients treated with functional appliances. All the cases were evaluated by one researcher using ABO-MGS. The χ (2), Z test, and multivariate analysis of variance were used for statistical evaluation (p < 0.05). No significant differences were found among the groups in buccolingual inclination, overjet, occlusal relationship, and root angulation. However, there were significant differences in alignment, marginal ridge height, occlusal contact, interproximal contact measurements, and overall MGS average scores. The mean treatment time between the extraction and functional appliance groups was significantly different (p = 0.017). According to total ABO-MGS scores, headgear treatment had better results than functional appliances. The headgear group had better tooth alignment than the extraction group. Headgear treatment resulted in better occlusal contacts than the functional appliances and had lower average scores for interproximal contact measurements. Functional appliances had the worst average scores for marginal ridge height. Finally, the functional appliance group had the longest treatment times.

  15. Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

    Directory of Open Access Journals (Sweden)

    Šoltýsová I.

    2016-12-01

    Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

  16. Evaluation of criticality criteria for fissile class II packages in transportation

    International Nuclear Information System (INIS)

    Thomas, J.T.

    1976-01-01

    The nuclear criticality safety of packages in transportation is explored systematically by a surface density representation of reflected array criticality of air-spaced units. Typical perturbations to arrays are shown to be related analytically to the corresponding reactivity changes they produce. The reactivity change associated with the removal of three reflecting surfaces from a totally water reflected array is shown to depend upon the fissile material loading of the packages. For U(93.2) metal, the expected reactivity loss can range from 2 to 21%. Replacement of a three-sided reflector of water on a critical array by one of concrete results in a reactivity increase ranging from 0 to 6%. Mass limits established by criticality data for reflected arrays of air-spaced units can provide a minimum, uniform margin of safety, expressible in terms of reactivity, to more reliably specify subcriticality in transport. Mass limits less than those defined by air-spaced units in water-reflected arrays are unnecessary for Fissile Class II packages. (author)

  17. Association analysis of class II cytokine and receptor genes in vitiligo patients.

    Science.gov (United States)

    Traks, Tanel; Karelson, Maire; Reimann, Ene; Rätsep, Ranno; Silm, Helgi; Vasar, Eero; Kõks, Sulev; Kingo, Külli

    2016-05-01

    The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune mechanisms and lately autoinflammatory mediators have become more emphasized. Among these, a number of class II cytokines and their receptors have displayed altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the regions of respective genes to be genotyped in Estonian case-control sample (109 and 328 individuals, respectively). For more precise analyses, patients were divided into subgroups based on vitiligo progression activity, age of onset, sex, occurrence of vitiligo among relatives, extent of depigmented areas, appearance of Köbner's phenomenon, existence of halo nevi, occurrence of spontaneous repigmentation, and amount of thyroid peroxidase antibodies. No associations appeared in whole vitiligo group. In subgroups, several allelic and haplotype associations were found. The strongest involved SNPs rs12301088 (near IL26 gene), that was associated with familial vitiligo and existence of halo nevi, and rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally, haplotypes consisting of rs12301088 and rs12321603 alleles (IL26-IL22 genes), that were associated with familial vitiligo and existence of halo nevi. In conclusion, several genetic associations with vitiligo subphenotypes were revealed and functional explanations to these remain to be determined in respective studies. Copyright © 2016. Published by Elsevier Inc.

  18. HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis.

    Science.gov (United States)

    Djilali-Saiah, Idriss; Fakhfakh, Amin; Louafi, Hamida; Caillat-Zucman, Sophie; Debray, Dominique; Alvarez, Fernando

    2006-12-01

    Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.

  19. Class I and II histone deacetylase expression in human chronic periodontitis gingival tissue.

    Science.gov (United States)

    Cantley, M D; Dharmapatni, A A S S K; Algate, K; Crotti, T N; Bartold, P M; Haynes, D R

    2016-04-01

    Histone deacetylase inhibitors (HDACi) are being considered to treat chronic inflammatory diseases at low doses. Currently HDACi that are more specific are being developed to target particular HDACs; therefore, this study aimed to determine levels and distribution of class I and II HDAC in human gingival samples obtained from patients with chronic periodontitis. Gingival biopsies were obtained from patients with and without (mild inflammation, no bone loss) periodontitis. Total RNA was isolated for real-time quantitative polymerase chain reaction to determine expression of HDACs 1-10. Immunohistochemistry was used to determine protein distribution of HDACs 1, 5, 8 and 9. Factor VIII, CD3 and tartrate resistant acid phosphatase (TRAP) were detected in serial sections to identify blood vessels, lymphocytes, pre-osteoclasts and osteoclasts cells respectively. Tumour necrosis factor α (TNF-α) expression was also assessed. mRNA for HDAC 1, 5, 8 and 9 were significantly upregulated in chronic periodontitis gingival tissues compared to non-periodontitis samples (p chronic periodontitis samples (p chronic periodontitis gingival tissues. HDAC 1, 5, 8 and 9 expression was higher in gingival tissues from patients with chronic periodontitis compared to non-periodontitis samples. Results suggest that these HDACs could therefore be targeted with specific acting HDACi. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Identification of the peptide derived from S1 domain that inhibits type I and type II feline infectious peritonitis virus infection.

    Science.gov (United States)

    Doki, Tomoyoshi; Takano, Tomomi; Koyama, Yusuke; Hohdatsu, Tsutomu

    2015-06-02

    Feline infectious peritonitis virus (FIPV) can cause a lethal disease in cats, feline infectious peritonitis (FIP). A therapeutic drug that is effective against FIP has not yet been developed. Peptides based on viral protein amino acid sequences have recently been attracting attention as new antiviral drugs. In the present study, we synthesized 30 overlapping peptides based on the amino acid sequence of the S1 domain of the type I FIPV strain KU-2 S protein, and investigated their inhibitory effects on FIPV infection. To evaluate the inhibitory effects on type I FIPV infection of these peptides, we investigated a method to increase the infection efficiency of poorly replicative type I FIPV. The efficiency of type I FIPV infection was increased by diluting the virus with medium containing a polycation. Of the 30 peptides, I-S1-8 (S461-S480), I-S1-9 (S471-S490), I-S1-10 (S481-S500), I-S1-16 (S541-S560), and I-S1-22 (S601-S620) significantly decreased the infectivity of FIPV strain KU-2 while I-S1-9 and I-S1-16 exhibited marked inhibitory effects on FIPV infection. The inhibitory effects on FIPV infection of these 2 peptides on other type I and type II FIPV strains, feline herpesvirus (FHV), and feline calicivirus (FCV) were also examined. These 2 peptides specifically inhibited type I and type II FIPV, but did FHV or FCV infection. In conclusion, the possibility of peptides derived from the S protein of type I FIPV strain KU-2 as anti-FIPV agents effective not only for type I, but also type II FIPV was demonstrated in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Treatment and post-treatment effects of functional therapy on the sagittal pharyngeal dimensions in Class II subjects.

    Science.gov (United States)

    Pavoni, Chiara; Cretella Lombardo, Elisabetta; Franchi, Lorenzo; Lione, Roberta; Cozza, Paola

    2017-10-01

    To evaluate the craniofacial changes induced by functional appliances with special regard to the oro and nasopharyngeal sagittal airway dimensions in subjects with dentoskeletal Class II malocclusions when compared with an untreated Class II control group immediately after therapy and at long-term observation. A group of 40 patients (21 females and 19 males) with Class II malocclusion treated consecutively either with a Bionator or an Activator followed by fixed appliances was compared with a matched control group of 31 subjects (16 females and 15 males) with untreated Class II malocclusion. The treated sample was evaluated at T1, start of treatment (mean age: 9.9 ± 1.4 years); T2, end of functional treatment and prior to fixed appliances (mean age: 11.9 ± 1.3 years); and T3, long-term observation at the end of growth (mean age: 18.2 ± 2.1 years). Statistical comparisons were performed with independent sample t tests at T1 (baseline characteristics) and for the T1-T2, T2-T3, and T1-T3 changes. During active treatment the treated group showed a significant increment in lower airway dimension (PNS-AD1), as well as a significant improvement in the upper airway dimension (PNS-AD2). A significant decrease in the upper adenoid size (AD2-H) was also found. In the longterm evaluation, a significant increase in both lower and upper airway thickness (PNS-AD1; PNS-AD2) and a significant decrease in the upper adenoid thickness were still present in the treated group. The treatment with functional appliances produced significant favorable changes during active treatment in the oro- and nasopharyngeal sagittal airway dimensions in dentoskeletal Class II subjects when compared with untreated controls, and these changes were stable in the long-term. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Simultaneous alignment and clustering of peptide data using a Gibbs sampling approach

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Lund, Ole; Nielsen, Morten

    2013-01-01

    Motivation: Proteins recognizing short peptide fragments play a central role in cellular signaling. As a result of high-throughput technologies, peptide-binding protein specificities can be studied using large peptide libraries at dramatically lower cost and time. Interpretation of such large...... peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides.Results: The algorithm presented in this article, based on Gibbs sampling, identifies multiple specificities...... of unaligned peptide datasets of variable length. Example applications described in this article include mixtures of binders to different MHC class I and class II alleles, distinct classes of ligands for SH3 domains and sub-specificities of the HLA-A*02:01 molecule.Availability: The Gibbs clustering method...

  3. Characterization of the peptide binding specificity of the HLA class I alleles B*38:01 and B*39:06.

    Science.gov (United States)

    Sidney, John; Schloss, Jennifer; Moore, Carrie; Lindvall, Mikaela; Wriston, Amanda; Hunt, Donald F; Shabanowitz, Jeffrey; DiLorenzo, Teresa P; Sette, Alessandro

    2016-03-01

    B*38:01 and B*39:06 are present with phenotypic frequencies 39:06 is the B allele most associated with type 1 diabetes susceptibility and 38:01 is most protective. A previous study derived putative main anchor motifs for both alleles based on peptide elution data. The present study has utilized panels of single amino acid substitution peptide libraries to derive detailed quantitative motifs accounting for both primary and secondary influences on peptide binding. From these analyses, both alleles were confirmed to utilize the canonical position 2/C-terminus main anchor spacing. B*38:01 preferentially bound peptides with the positively charged or polar residues H, R, and Q in position 2 and the large hydrophobic residues I, F, L, W, and M at the C-terminus. B*39:06 had a similar preference for R in position 2, but also well-tolerated M, Q, and K. A more dramatic contrast between the two alleles was noted at the C-terminus, where the specificity of B*39:06 was clearly for small residues, with A as most preferred, followed by G, V, S, T, and I. Detailed position-by-position and residue-by-residue coefficient values were generated from the panels to provide detailed quantitative B*38:01 and B*39:06 motifs. It is hoped that these detailed motifs will facilitate the identification of T cell epitopes recognized in the context of two class I alleles associated with dramatically different dispositions towards type 1 diabetes, offering potential avenues for the investigation of the role of CD8 T cells in this disease.

  4. Polycyclic Polyprenylated Acylphloroglucinols: An Emerging Class of Non-Peptide-Based MRSA- and VRE-Active Antibiotics.

    Science.gov (United States)

    Guttroff, Claudia; Baykal, Aslihan; Wang, Huanhuan; Popella, Peter; Kraus, Frank; Biber, Nicole; Krauss, Sophia; Götz, Friedrich; Plietker, Bernd

    2017-12-11

    In the past 20 years, peptide-based antibiotics, such as vancomycin, teicoplanin, and daptomycin, have often been considered as second-line antibiotics. However, in recent years, an increasing number of reports on vancomycin resistance in pathogens appeared, which forces researchers to find novel lead structures for potent new antibiotics. Herein, we report the total synthesis of a defined endo-type B PPAP library and their antibiotic activity against multiresistant S. aureus and various vancomycin-resistant Enterococci. Four new compounds that combine high activities and low cytotoxicity were identified, indicating that the PPAP core might become a new non-peptide-based lead structure in antibiotic research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Wild-type phosphoribosylpyrophosphate synthase (PRS from Mycobacterium tuberculosis: a bacterial class II PRS?

    Directory of Open Access Journals (Sweden)

    Ardala Breda

    Full Text Available The 5-phospho-α-D-ribose 1-diphosphate (PRPP metabolite plays essential roles in several biosynthetic pathways, including histidine, tryptophan, nucleotides, and, in mycobacteria, cell wall precursors. PRPP is synthesized from α-D-ribose 5-phosphate (R5P and ATP by the Mycobacterium tuberculosis prsA gene product, phosphoribosylpyrophosphate synthase (MtPRS. Here, we report amplification, cloning, expression and purification of wild-type MtPRS. Glutaraldehyde cross-linking results suggest that MtPRS predominates as a hexamer, presenting varied oligomeric states due to distinct ligand binding. MtPRS activity measurements were carried out by a novel coupled continuous spectrophotometric assay. MtPRS enzyme activity could be detected in the absence of P(i. ADP, GDP and UMP inhibit MtPRS activity. Steady-state kinetics results indicate that MtPRS has broad substrate specificity, being able to accept ATP, GTP, CTP, and UTP as diphosphoryl group donors. Fluorescence spectroscopy data suggest that the enzyme mechanism for purine diphosphoryl donors follows a random order of substrate addition, and for pyrimidine diphosphoryl donors follows an ordered mechanism of substrate addition in which R5P binds first to free enzyme. An ordered mechanism for product dissociation is followed by MtPRS, in which PRPP is the first product to be released followed by the nucleoside monophosphate products to yield free enzyme for the next round of catalysis. The broad specificity for diphosphoryl group donors and detection of enzyme activity in the absence of P(i would suggest that MtPRS belongs to Class II PRS proteins. On the other hand, the hexameric quaternary structure and allosteric ADP inhibition would place MtPRS in Class I PRSs. Further data are needed to classify MtPRS as belonging to a particular family of PRS proteins. The data here presented should help augment our understanding of MtPRS mode of action. Current efforts are toward experimental structure

  6. Wild-Type Phosphoribosylpyrophosphate Synthase (PRS) from Mycobacterium tuberculosis: A Bacterial Class II PRS?

    Science.gov (United States)

    Breda, Ardala; Martinelli, Leonardo K. B.; Bizarro, Cristiano V.; Rosado, Leonardo A.; Borges, Caroline B.; Santos, Diógenes S.; Basso, Luiz A.

    2012-01-01

    The 5-phospho-α-D-ribose 1-diphosphate (PRPP) metabolite plays essential roles in several biosynthetic pathways, including histidine, tryptophan, nucleotides, and, in mycobacteria, cell wall precursors. PRPP is synthesized from α-D-ribose 5-phosphate (R5P) and ATP by the Mycobacterium tuberculosis prsA gene product, phosphoribosylpyrophosphate synthase (MtPRS). Here, we report amplification, cloning, expression and purification of wild-type MtPRS. Glutaraldehyde cross-linking results suggest that MtPRS predominates as a hexamer, presenting varied oligomeric states due to distinct ligand binding. MtPRS activity measurements were carried out by a novel coupled continuous spectrophotometric assay. MtPRS enzyme activity could be detected in the absence of Pi. ADP, GDP and UMP inhibit MtPRS activity. Steady-state kinetics results indicate that MtPRS has broad substrate specificity, being able to accept ATP, GTP, CTP, and UTP as diphosphoryl group donors. Fluorescence spectroscopy data suggest that the enzyme mechanism for purine diphosphoryl donors follows a random order of substrate addition, and for pyrimidine diphosphoryl donors follows an ordered mechanism of substrate addition in which R5P binds first to free enzyme. An ordered mechanism for product dissociation is followed by MtPRS, in which PRPP is the first product to be released followed by the nucleoside monophosphate products to yield free enzyme for the next round of catalysis. The broad specificity for diphosphoryl group donors and detection of enzyme activity in the absence of Pi would suggest that MtPRS belongs to Class II PRS proteins. On the other hand, the hexameric quaternary structure and allosteric ADP inhibition would place MtPRS in Class I PRSs. Further data are needed to classify MtPRS as belonging to a particular family of PRS proteins. The data here presented should help augment our understanding of MtPRS mode of action. Current efforts are toward experimental structure determination of Mt

  7. Identification and cloning of class II and III chitinases from alkaline floral nectar of Rhododendron irroratum, Ericaceae.

    Science.gov (United