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Sample records for class ii peptide

  1. 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*02:0...... both HLA class I and class I restricted responses, a quality which might be of potential interest for peptide-based vaccine development....

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

    OpenAIRE

    Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren; Rasmussen, Michael; Korsholm, Karen Smith; Nielsen, Morten; Claesson, Mogens Helweg

    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*02:01 and HLA-DRB1*01:01 molecules were identified by bioinformatics and biochemical technology. Immunization of transgenic HLA-A*02:01/HLA-DRB1*01:01 mice with four of these double binding peptides gave ...

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

    DEFF Research Database (Denmark)

    Justesen, Sune; Harndahl, Mikkel; Lamberth, Kasper; Nielsen, Lise-Lotte B; Buus, Søren

    2009-01-01

    . coli , extracted into urea, and purified under denaturing and non-reducing conditions using conventional column chromatography. Subsequently, diluting the two chains into a folding reaction with appropriate peptide resulted in efficient peptide-MHC-II complex formation. Several different formats of......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 in the...... generation of MHC-II molecules as reagents to study and manipulate specific T helper cell responses. Methods to generate functional MHC-II molecules recombinantly, and measure their interaction with peptides, would be highly desirable; however, no consensus methodology has yet emerged. RESULTS: We generated...

  4. 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

  5. THERMODYNAMICS OF PEPTIDE-MHC CLASS II INTERACTIONS: NOT ALL COMPLEXES ARE CREATED EQUAL

    Directory of Open Access Journals (Sweden)

    Andrea eFerrante

    2013-10-01

    Full Text Available The adaptive immune response begins when CD4+ T cells recognize antigenic peptides bound to class II molecules of the Major Histocompatibility Complex (MHCII. The interaction between peptides and MHCII has been historically interpreted as a rigid docking event. However, this model has been challenged by the evidence that conformational flexibility plays an important role in peptide-MHCII complex formation. Thermodynamic analysis of the binding reaction suggests a model of complexation in which the physical-chemical nature of the peptide determines the variability in flexibility of the substates in the peptide-MHC conformational ensemble. This review discusses our understanding of the correlation between thermodynamics of peptide binding and structural features of the resulting complex as well as their impact on HLA-DM activity and on our ability to predict MHCII-restricted epitopes.

  6. Effect of gliadin and other food peptides on expression of MHC class II molecules by HT-29 cells.

    OpenAIRE

    Mothes, T; Bendix, U; Pfannschmidt, C; Lehmann, I

    1995-01-01

    Expression of major histocompatibility (MHC) class II molecules by enterocytes is known to be enhanced in coeliac disease and other disorders characterised by intestinal inflammation--an effect thought to be mediated via intestinal lymphocytes. To investigate if food peptides can exert direct effects on class II expression, the influence of gliadins, casein, and beta lactoglobulin on an intestinal epithelial cell line (HT-29) was examined in the absence of immune cells. Class II expression wa...

  7. Antibodies against a class II HLA-peptide complex raised by active immunization of mice with antigen mimicking peptides

    DEFF Research Database (Denmark)

    Dam-Tuxen, R; Riise, Erik Skjold

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune disease linked to the human leucocyte antigen (HLA) class II genes DRB1*1501, DRB5*0101 and DQB1*0602. T cells reactive towards the DRB1*1501 in complex with various peptides derived from myelin basic protein (MBP), which is the major component of myelin......, have been found in the peripheral blood of MS patients. These autoreactive T cells are believed to play a role in the pathogenesis of MS. In this article, antibodies against the HLA complex DR2b (DRA1*0101/DRB1*1501) in complex with the MBP-derived peptide MBP(85-99) have been generated by immunization...

  8. 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.

  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; Stryhn, A

    1996-01-01

    the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing. The NH2-terminal end of the longer peptide could, even while bound to major histocompatibility complex (MHC) class II molecules, be digested by APN with dramatic consequences...

  10. 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 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...

  11. Force-Regulated In Situ TCR-Peptide-Bound MHC Class II Kinetics Determine Functions of CD4+ T Cells.

    Science.gov (United States)

    Hong, Jinsung; Persaud, Stephen P; Horvath, Stephen; Allen, Paul M; Evavold, Brian D; Zhu, Cheng

    2015-10-15

    We have recently shown that two-dimensional (2D) and force-regulated kinetics of TCR-peptide-bound MHC class I (pMHC-I) interactions predict responses of CD8(+) T cells. To test whether these findings are applicable to CD4(+) T cells, we analyzed the in situ 3.L2 TCR-pMHC-II interactions for a well-characterized panel of altered peptide ligands on the T cell surface using the adhesion frequency assay with a micropipette and the thermal fluctuation and force-clamp assays with a biomembrane force probe. We found that the 2D effective TCR-pMHC-II affinity and off-rate correlate with, but better predict the T cell response than, the corresponding measurements with the surface plasmon resonance in three dimensions. The 2D affinity of the CD4 for MHC-II was very low, approaching the detection limit, making it one to two orders of magnitude lower than the affinity of CD8 for MHC-I. In addition, the signal-dependent cooperation between TCR and coreceptor for pMHC binding previously observed for CD8 was not observed for CD4. Interestingly, force elicited TCR-pMHC-II catch-slip bonds for agonists but slip-only bonds for antagonists, thereby amplifying the power of discrimination between altered peptide ligands. These results show that the force-regulated 2D binding kinetics of the 3.L2 TCR for pMHC-II determine functions of CD4(+) T cells. PMID:26336148

  12. Boosting immune response with the invariant chain segments via association with non-peptide binding region of major histocompatibility complex class II molecules

    Directory of Open Access Journals (Sweden)

    Chen Fangfang

    2012-09-01

    Full Text Available Abstract Background Based on binding of invariant chain (Ii to major histocompatibility complex (MHC class II molecules to form complexes, Ii-segment hybrids, Ii-key structure linking an epitope, or Ii class II-associated invariant chain peptide (CLIP replaced with an epitope were used to increase immune response. It is currently unknown whether the Ii-segment cytosolic and transmembrane domains bind to the MHC non-peptide binding region (PBR and consequently influence immune response. To investigate the potential role of Ii-segments in the immune response via MHC II/peptide complexes, a few hybrids containing Ii-segments and a multiepitope (F306 from Newcastle disease virus fusion protein (F were constructed, and their binding effects on MHC II molecules and specific antibody production were compared using confocal microscopy, immunoprecipitation, western blotting and animal experiments. Results One of the Ii-segment/F306 hybrids, containing ND (Asn–Asp outside the F306 in the Ii-key structure (Ii-key/F306/ND, neither co-localized with MHC II molecules on plasma membrane nor bound to MHC II molecules to form complexes. However, stimulation of mice with the structure produced 4-fold higher antibody titers compared with F306 alone. The two other Ii-segment/F306 hybrids, in which the transmembrane and cytosolic domains of Ii were linked to this structure (Cyt/TM/Ii-key/F306/ND, partially co-localized on plasma membrane with MHC class II molecules and weakly bound MHC II molecules to form complexes. They induced mice to produce approximately 9-fold higher antibody titers compared with F306 alone. Furthermore, an Ii/F306 hybrid (F306 substituting CLIP co-localized well with MHC II molecules on the membrane to form complexes, although it increased antibody titer about 3-fold relative to F306 alone. Conclusions These results suggest that Ii-segments improve specific immune response by binding to the non-PBR on MHC class II molecules and enabling

  13. HLA-DMA polymorphisms differentially affect MHC class II peptide loading.

    Science.gov (United States)

    Álvaro-Benito, Miguel; Wieczorek, Marek; Sticht, Jana; Kipar, Claudia; Freund, Christian

    2015-01-15

    During the adaptive immune response, MHCII proteins display antigenic peptides on the cell surface of APCs for CD4(+) T cell surveillance. HLA-DM, a nonclassical MHCII protein, acts as a peptide exchange catalyst for MHCII, editing the peptide repertoire. Although they map to the same gene locus, MHCII proteins exhibit a high degree of polymorphism, whereas only low variability has been observed for HLA-DM. As HLA-DM activity directly favors immunodominant peptide presentation, polymorphisms in HLA-DM (DMA or DMB chain) might well be a contributing risk factor for autoimmunity and immune disorders. Our systematic comparison of DMA*0103/DMB*0101 (DMA-G155A and DMA-R184H) with DMA*0101/DMB*0101 in terms of catalyzed peptide exchange and dissociation, as well as direct interaction with several HLA-DR/peptide complexes, reveals an attenuated catalytic activity of DMA*0103/DMB*0101. The G155A substitution dominates the catalytic behavior of DMA*0103/DMB*0101 by decreasing peptide release velocity. Preloaded peptide-MHCII complexes exhibit ∼2-fold increase in half-life in the presence of DMA*0103/DMB*0101 when compared with DMA*0101/DMB*0101. We show that this effect leads to a greater persistence of autoimmunity-related Ags in the presence of high-affinity competitor peptide. Our study therefore reveals that HLA-DM polymorphic residues have a considerable impact on HLA-DM catalytic activity. PMID:25505276

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

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Appella, E; Adorini, L; Grey, H M

    1990-01-01

    Previous work from our and other laboratories indicates that T cells recognize a complex between the MHC restriction element and peptide antigen fragments. This paper reviews the structural characteristics of the formation of such a complex. By analyzing in detail the interactions between purified...

  15. Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions

    DEFF Research Database (Denmark)

    Jönsson, Peter; Southcombe, Jennifer H; Santos, Ana Mafalda;

    2016-01-01

    value is two to three orders of magnitude higher than previously measured 2D Kd values for interacting leukocyte surface proteins. Calculations indicated, however, that CD4/pMHC II binding would increase rates of T-cell receptor (TCR) complex phosphorylation by threefold via the recruitment of Lck, with...

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

    International Nuclear Information System (INIS)

    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

  17. TCR-like antibodies distinguish conformational and functional differences in two- versus four-domain auto reactive MHC class II-peptide complexes.

    Science.gov (United States)

    Dahan, Rony; Tabul, Moran; Chou, Yuan K; Meza-Romero, Roberto; Andrew, Shayne; Ferro, Adolph J; Burrows, Gregory G; Offner, Halina; Vandenbark, Arthur A; Reiter, Yoram

    2011-05-01

    Antigen-presenting cell-associated four-domain MHC class II (MHC-II) molecules play a central role in activating autoreactive CD4(+) T cells involved in multiple sclerosis (MS) and type 1 diabetes (T1D). In contrast, two-domain MHC-II structures with the same covalently attached self-peptide (recombinant T-cell receptor ligands (RTLs)) can regulate pathogenic CD4(+) T cells and reverse clinical signs of experimental autoimmune diseases. RTL1000, which is composed of the β1α1 domains of human leukocyte antigen (HLA)-DR2 linked to the encephalitogenic human myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide, was recently shown to be safe and well tolerated in a phase I clinical trial in MS. To evaluate the opposing biological effects of four- versus two-domain MHC-II structures, we screened phage Fab antibodies (Abs) for the neutralizing activity of RTL1000. Five different TCR-like Abs were identified that could distinguish between the two- versus four-domain MHC-peptide complexes while the cognate TCR was unable to make such a distinction. Moreover, Fab detection of native two-domain HLA-DR structures in human plasma implies that there are naturally occurring regulatory MHC-peptide complexes. These results demonstrate for the first time distinct conformational determinants characteristic of activating versus tolerogenic MHC-peptide complexes involved in human autoimmunity. PMID:21469129

  18. Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes

    NARCIS (Netherlands)

    M.M. van Luijn; M.E.D. Chamuleau; M.E. Ressing; E.J. Wiertz; S. Ostrand-Rosenberg; Y. Souwer; A. Zevenbergen; G.J. Ossenkoppele; A.A. van de Loosdrecht; S.M. Ham

    2010-01-01

    During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA cl

  19. Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection.

    Science.gov (United States)

    Leroux, Louis-Philippe; Nishi, Manami; El-Hage, Sandy; Fox, Barbara A; Bzik, David J; Dzierszinski, Florence S

    2015-10-01

    Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, namely, the MHC-II-associated invariant chain (Ii or CD74) and the peptide editor H2-DM, in professional antigen-presenting cells (pAPCs). Genetic deletion of CD74 restored the ability of infected dendritic cells to present a parasite antigen in the context of MHC-II in vitro. CD74 mRNA and protein levels were, surprisingly, elevated in infected cells, whereas MHC-II and H2-DM expression was inhibited. CD74 accumulated mainly in the endoplasmic reticulum (ER), and this phenotype required live parasites, but not active replication. Finally, we compared the impacts of genetic deletion of CD74 and H2-DM genes on parasite dissemination toward lymphoid organs in mice, as well as activation of CD4(+) T cells and interferon gamma (IFN-γ) levels during acute infection. Cyst burdens and survival during the chronic phase of infection were also evaluated in wild-type and knockout mice. These results highlight the fact that the infection is influenced by multiple levels of parasite manipulation of the MHC-II antigen presentation pathway. PMID:26195549

  20. High-affinity binding of short peptides to major histocompatibility complex class II molecules by anchor combinations.

    OpenAIRE

    Hammer, J.; Belunis, C; Bolin, D; Papadopoulos, J.; Walsky, R; Higelin, J; Danho, W; Sinigaglia, F; Nagy, Z A

    1994-01-01

    We have previously identified four anchor positions in HLA-DRB1*0101-binding peptides, and three anchors involved in peptide binding to DRB1*0401 and DRB1*1101 molecules, by screening of an M13 peptide display library (approximately 20 million independent nonapeptides) for DR-binding activity. In this study, high stringency screening of the M13 library for DRB1*0401 binding has resulted in identification of three further anchor positions. Taken together, a peptide-binding motif has been obtai...

  1. Human Immunodeficiency Virus Type 1 Envelope Epitope-Specific CD4+ T Lymphocytes in Simian/Human Immunodeficiency Virus-Infected and Vaccinated Rhesus Monkeys Detected Using a Peptide-Major Histocompatibility Complex Class II Tetramer

    OpenAIRE

    Kuroda, Marcelo J.; Schmitz, Jörn E.; Lekutis, Christine; Nickerson, Christine E.; Lifton, Michelle A.; Franchini, Genoveffa; Harouse, Janet M.; Cheng-Mayer, Cecilia; Letvin, Norman L.

    2000-01-01

    A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide complex was used to quantitate human immunodeficiency virus type 1 (HIV-1) envelope (Env)-specific CD4+ T cells in vaccinated and in simian/human immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) were employed to construct this tetrameric complex. A p46-specific proliferative response was seen in sorted, tetramer-binding, ...

  2. A novel method to measure HLA-DM-susceptibility of peptides bound to MHC class II molecules based on peptide binding competition assay and differential IC(50) determination.

    Science.gov (United States)

    Yin, Liusong; Stern, Lawrence J

    2014-04-01

    HLA-DM (DM) functions as a peptide editor that mediates the exchange of peptides loaded onto MHCII molecules by accelerating peptide dissociation and association kinetics. The relative DM-susceptibility of peptides bound to MHCII molecules correlates with antigen presentation and immunodominance hierarchy, and measurement of DM-susceptibility has been a key effort in this field. Current assays of DM-susceptibility, based on differential peptide dissociation rates measured for individually labeled peptides over a long time base, are difficult and cumbersome. Here, we present a novel method to measure DM-susceptibility based on peptide binding competition assays performed in the presence and absence of DM, reported as a delta-IC(50) (change in 50% inhibition concentration) value. We simulated binding competition reactions of peptides with various intrinsic and DM-catalyzed kinetic parameters and found that under a wide range of conditions the delta-IC(50) value is highly correlated with DM-susceptibility as measured in off-rate assay. We confirmed experimentally that DM-susceptibility measured by delta-IC(50) is comparable to that measured by traditional off-rate assay for peptides with known DM-susceptibility hierarchy. The major advantage of this method is that it allows simple, fast and high throughput measurement of DM-susceptibility for a large set of unlabeled peptides in studies of the mechanism of DM action and for identification of CD4+ T cell epitopes. PMID:24583195

  3. 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

    International Nuclear Information System (INIS)

    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-DQ2PQPELPYPQ diffracted to 3.9 Å, while the HLA-DQ8EGSFQPSQE 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+ 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

  4. 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.

  5. Comprehensive Analysis of Contributions from Protein Conformational Stability and Major Histocompatibility Complex Class II-Peptide Binding Affinity to CD4+ Epitope Immunogenicity in HIV-1 Envelope Glycoprotein

    Science.gov (United States)

    Li, Tingfeng; Steede, N. Kalaya; Nguyen, Hong-Nam P.; Freytag, Lucy C.; McLachlan, James B.; Mettu, Ramgopal R.; Robinson, James E.

    2014-01-01

    ABSTRACT Helper T-cell epitope dominance in human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is not adequately explained by peptide binding to major histocompatibility complex (MHC) proteins. Antigen processing potentially influences epitope dominance, but few, if any, studies have attempted to reconcile the influences of antigen processing and MHC protein binding for all helper T-cell epitopes of an antigen. Epitopes of gp120 identified in both humans and mice occur on the C-terminal flanks of flexible segments that are likely to be proteolytic cleavage sites. In this study, the influence of gp120 conformation on the dominance pattern in gp120 from HIV strain 89.6 was examined in CBA mice, whose MHC class II protein has one of the most well defined peptide-binding preferences. Only one of six dominant epitopes contained the most conserved element of the I-Ak binding motif, an aspartic acid. Destabilization of the gp120 conformation by deletion of single disulfide bonds preferentially enhanced responses to the cryptic I-Ak motif-containing sequences, as reported by T-cell proliferation or cytokine secretion. Conversely, inclusion of CpG in the adjuvant with gp120 enhanced responses to the dominant CD4+ T-cell epitopes. The gp120 destabilization affected secretion of some cytokines more than others, suggesting that antigen conformation could modulate T-cell functions through mechanisms of antigen processing. IMPORTANCE CD4+ helper T cells play an essential role in protection against HIV and other pathogens. Thus, the sites of helper T-cell recognition, the dominant epitopes, are targets for vaccine design; and the corresponding T cells may provide markers for monitoring infection and immunity. However, T-cell epitopes are difficult to identify and predict. It is also unclear whether CD4+ T cells specific for one epitope are more protective than T cells specific for other epitopes. This work shows that the three-dimensional (3D) structure of an

  6. Structural Properties of MHC Class II Ligands, Implications for the Prediction of MHC Class II Epitopes

    DEFF Research Database (Denmark)

    Jørgensen, Kasper Winther; Buus, Søren; Nielsen, Morten

    2010-01-01

    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...

  7. Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection

    OpenAIRE

    Leroux, Louis-Philippe; Nishi, Manami; El-Hage, Sandy; Fox, Barbara A.; Bzik, David J.; Dzierszinski, Florence S.

    2015-01-01

    Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4+ T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms...

  8. Class II-associated invariant chain peptide down-modulation enhances the immunogenicity of myeloid leukemic blasts resulting in increased CD4(+) T-cell responses

    NARCIS (Netherlands)

    M.M. van Luijn; M.E.D. Chamuleau; J.A. Thompson; S. Ostrand-Rosenberg; T.M. Westers; Y. Souwer; G.J. Ossenkoppele; S.M. Ham; A.A. van de Loosdrecht

    2010-01-01

    Background Disease recurrence in patients with acute myeloid leukemia may be partially explained by the escape of leukemic blasts from CD4(+) T-cell recognition. The current study investigates the role of aberrant HLA class II antigen presentation on leukemic blasts by determining both the clinical

  9. 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; Buus, S

    1992-01-01

    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...

  10. Comprehensive Analysis of Contributions from Protein Conformational Stability and Major Histocompatibility Complex Class II-Peptide Binding Affinity to CD4+ Epitope Immunogenicity in HIV-1 Envelope Glycoprotein

    OpenAIRE

    Li, Tingfeng; Steede, N. Kalaya; Nguyen, Hong-Nam P.; Freytag, Lucy C.; McLachlan, James B.; Mettu, Ramgopal R.; Robinson, James E.; Landry, Samuel J.

    2014-01-01

    Helper T-cell epitope dominance in human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is not adequately explained by peptide binding to major histocompatibility complex (MHC) proteins. Antigen processing potentially influences epitope dominance, but few, if any, studies have attempted to reconcile the influences of antigen processing and MHC protein binding for all helper T-cell epitopes of an antigen. Epitopes of gp120 identified in both humans and mice occur on the C-te...

  11. 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

    ., 2008] and [Larsen et al., 2010]). HTMS involves HLA typing, immunoaffinity chromatography of HLA molecules, HLA extraction, and chromatography combined with tandem mass spectrometry, followed by the application of computational algorithms for peptide characterization (Bassani-Sternberg et al., 2010......). Hundreds of naturally processed HLA class I associated peptides have been identified in individual studies using HTMS in normal (Escobar et al., 2008), cancer ( [Antwi et al., 2009] and [Bassani-Sternberg et al., 2010]), autoimmunity-related (Ben Dror et al., 2010), and infected samples (Wahl et al, 2010...... 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...

  12. MHC Class II epitope predictive algorithms

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lund, Ole; Buus, S; Lundegaard, Claus

    2010-01-01

    for this is that the MHC-II molecule is open at both ends allowing binding of peptides extending out of the groove. The binding core of MHC-II-bound peptides is therefore not known a priori and the binding motif is hence not readily discernible. Recent progress has been obtained by including the......-specific methods have been able to make reasonably accurate predictions for alleles that were not included in the training data. These methods can be used to define supertypes (clusters) of MHC-II alleles where alleles within each supertype have similar binding specificities. Furthermore, the pan-specific methods...

  13. Prediction of MHC class I binding peptides, using SVMHC

    Directory of Open Access Journals (Sweden)

    Elofsson Arne

    2002-09-01

    Full Text Available Abstract Background T-cells are key players in regulating a specific immune response. Activation of cytotoxic T-cells requires recognition of specific peptides bound to Major Histocompatibility Complex (MHC class I molecules. MHC-peptide complexes are potential tools for diagnosis and treatment of pathogens and cancer, as well as for the development of peptide vaccines. Only one in 100 to 200 potential binders actually binds to a certain MHC molecule, therefore a good prediction method for MHC class I binding peptides can reduce the number of candidate binders that need to be synthesized and tested. Results Here, we present a novel approach, SVMHC, based on support vector machines to predict the binding of peptides to MHC class I molecules. This method seems to perform slightly better than two profile based methods, SYFPEITHI and HLA_BIND. The implementation of SVMHC is quite simple and does not involve any manual steps, therefore as more data become available it is trivial to provide prediction for more MHC types. SVMHC currently contains prediction for 26 MHC class I types from the MHCPEP database or alternatively 6 MHC class I types from the higher quality SYFPEITHI database. The prediction models for these MHC types are implemented in a public web service available at http://www.sbc.su.se/svmhc/. Conclusions Prediction of MHC class I binding peptides using Support Vector Machines, shows high performance and is easy to apply to a large number of MHC class I types. As more peptide data are put into MHC databases, SVMHC can easily be updated to give prediction for additional MHC class I types. We suggest that the number of binding peptides needed for SVM training is at least 20 sequences.

  14. 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. PMID:23288359

  15. 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...

  16. 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.

  17. The Two-Peptide (Class-IIb) Bacteriocins: Genetics, Biosynthesis, Structure, and Mode of Action

    Science.gov (United States)

    Nissen-Meyer, Jon; Oppegård, Camilla; Rogne, Per; Haugen, Helen Sophie; Kristiansen, Per Eugen

    The two-peptide (class-IIb) bacteriocins consist of two different peptides, both of which are required to obtain high antimicrobial activity. These bacteriocins kill target-cells by inducing membrane-leakage and they seem to display some specificity with respect to the molecules they transfer across membranes. The genes encoding the two peptides of two-peptide bacteriocins are next to each other on the same operon. In the same or a nearby operon are genes encoding (i) the immunity protein that protects the bacteriocin-producer from its own bacteriocin, (ii) a dedicated ABC-transporter that exports the bacteriocin from cells and cleaves off the N-terminal bacteriocin leader sequence, and (iii) an accessory protein whose exact function has not been fully clarified. Some two-peptide bacteriocins appear to be produced constitutively, whereas the production of other two-peptide bacteriocins is regulated through a three-component regulatory system that consists of a peptide pheromone, a membrane-associated histidine protein kinase, and response regulators. It has recently been proposed that the two peptides of (some) two-peptide bacteriocins may form a membrane-penetrating helix-helix structure involving helix-helix interacting GxxxG-motifs present in all currently characterized two-peptide bacteriocins. It has also been suggested that the helix-helix structure interacts with an integrated membrane (transport) protein, thus inducing a conformational change in the protein, which in turn causes membrane-leakage. This proposed mode-of-action is similar to that of the pediocin-like (class-IIa) bacteriocins and lactococcin A, which bind to a part of the mannose phosphotransferase permease that is embedded in the cell membrane, thereby altering the conformation of the ­permease in a manner that causes membrane-leakage and cell death.

  18. Characterization of structural features controlling the receptiveness of empty class II MHC molecules

    DEFF Research Database (Denmark)

    Rupp, Bernd; Günther, Sebastian; Makhmoor, Talat;

    2011-01-01

    MHC class II molecules (MHC II) play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC mol...

  19. Molecular basis for the control of motor-based transport of MHC class II compartments

    NARCIS (Netherlands)

    Rocha, Nuno

    2008-01-01

    Antigen presentation by MHC class II is critical for immune responses against pathogens and tumors. Antigen loading occurs primarily in lysosomal-related organelles (LROs) known as MIICs. Ultimately, the MHC II-peptide complexes are transported for cell surface display. Here, we study intracellular

  20. Class II malocclusion occlusal severity description

    Directory of Open Access Journals (Sweden)

    Guilherme Janson

    2010-08-01

    Full Text Available OBJECTIVES: It is well known that the efficacy and the efficiency of a Class II malocclusion treatment are aspects closely related to the severity of the dental anteroposterior discrepancy. Even though, sample selection based on cephalometric variables without considering the severity of the occlusal anteroposterior discrepancy is still common in current papers. In some of them, when occlusal parameters are chosen, the severity is often neglected. The purpose of this study is to verify the importance given to the classification of Class II malocclusion, based on the criteria used for sample selection in a great number of papers published in the orthodontic journal with the highest impact factor. MATERIAL AND METHODS: A search was performed in PubMed database for full-text research papers referencing Class II malocclusion in the history of the American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO. RESULTS: A total of 359 papers were retrieved, among which only 72 (20.06% papers described the occlusal severity of the Class II malocclusion sample. In the other 287 (79.94% papers that did not specify the anteroposterior discrepancy severity, description was considered to be crucial in 159 (55.40% of them. CONCLUSIONS: Omission in describing the occlusal severity demands a cautious interpretation of 44.29% of the papers retrieved in this study.

  1. Exposing the specific roles of the invariant chain isoforms in shaping the MHC class II peptidome

    Directory of Open Access Journals (Sweden)

    Jean-Simon eFortin

    2013-12-01

    Full Text Available The peptide repertoire (peptidome associated with MHC class II molecules (MHCIIs is influenced by the polymorphic nature of the peptide binding groove but also by cell-intrinsic factors. The invariant chain (Ii chaperones MHCIIs, affecting their folding and trafficking. Recent discoveries relating to Ii functions have provided insights as to how it edits the MHCII peptidome. In humans, the Ii gene encodes four different isoforms for which structure-function analyses have highlighted common properties but also some non-redundant roles. Another layer of complexity arises from the fact that Ii heterotrimerizes, a characteristic that has the potential to affect the maturation of associated MHCIIs in many different ways, depending on the isoform combinations. Here, we emphasize the peptide editing properties of Ii and discuss the impact of the various isoforms on the MHCII peptidome.

  2. Lateral cephalometric diagnosis of asymmetry in Angle Class II subdivision compared to Class I and II

    OpenAIRE

    Aparecida Fernanda Meloti; Renata de Cássia Gonçalves; Ertty Silva; Lídia Parsekian Martins; Ary dos Santos-Pinto

    2014-01-01

    INTRODUCTION: Lateral cephalometric radiographs are traditionally required for orthodontic treatment, yet rarely used to assess asymmetries. OBJECTIVE: The objective of the present study was to use lateral cephalometric radiographs to identify existing skeletal and dentoalveolar morphological alterations in Class II subdivision and to compare them with the existing morphology in Class I and II relationship. MATERIAL AND METHODS: Ninety initial lateral cephalometric radiographs of male...

  3. Towards universal structure-based prediction of class II MHC epitopes for diverse allotypes.

    Directory of Open Access Journals (Sweden)

    Andrew J Bordner

    Full Text Available The binding of peptide fragments of antigens to class II MHC proteins is a crucial step in initiating a helper T cell immune response. The discovery of these peptide epitopes is important for understanding the normal immune response and its misregulation in autoimmunity and allergies and also for vaccine design. In spite of their biomedical importance, the high diversity of class II MHC proteins combined with the large number of possible peptide sequences make comprehensive experimental determination of epitopes for all MHC allotypes infeasible. Computational methods can address this need by predicting epitopes for a particular MHC allotype. We present a structure-based method for predicting class II epitopes that combines molecular mechanics docking of a fully flexible peptide into the MHC binding cleft followed by binding affinity prediction using a machine learning classifier trained on interaction energy components calculated from the docking solution. Although the primary advantage of structure-based prediction methods over the commonly employed sequence-based methods is their applicability to essentially any MHC allotype, this has not yet been convincingly demonstrated. In order to test the transferability of the prediction method to different MHC proteins, we trained the scoring method on binding data for DRB1*0101 and used it to make predictions for multiple MHC allotypes with distinct peptide binding specificities including representatives from the other human class II MHC loci, HLA-DP and HLA-DQ, as well as for two murine allotypes. The results showed that the prediction method was able to achieve significant discrimination between epitope and non-epitope peptides for all MHC allotypes examined, based on AUC values in the range 0.632-0.821. We also discuss how accounting for peptide binding in multiple registers to class II MHC largely explains the systematically worse performance of prediction methods for class II MHC compared with

  4. Towards universal structure-based prediction of class II MHC epitopes for diverse allotypes.

    Science.gov (United States)

    Bordner, Andrew J

    2010-01-01

    The binding of peptide fragments of antigens to class II MHC proteins is a crucial step in initiating a helper T cell immune response. The discovery of these peptide epitopes is important for understanding the normal immune response and its misregulation in autoimmunity and allergies and also for vaccine design. In spite of their biomedical importance, the high diversity of class II MHC proteins combined with the large number of possible peptide sequences make comprehensive experimental determination of epitopes for all MHC allotypes infeasible. Computational methods can address this need by predicting epitopes for a particular MHC allotype. We present a structure-based method for predicting class II epitopes that combines molecular mechanics docking of a fully flexible peptide into the MHC binding cleft followed by binding affinity prediction using a machine learning classifier trained on interaction energy components calculated from the docking solution. Although the primary advantage of structure-based prediction methods over the commonly employed sequence-based methods is their applicability to essentially any MHC allotype, this has not yet been convincingly demonstrated. In order to test the transferability of the prediction method to different MHC proteins, we trained the scoring method on binding data for DRB1*0101 and used it to make predictions for multiple MHC allotypes with distinct peptide binding specificities including representatives from the other human class II MHC loci, HLA-DP and HLA-DQ, as well as for two murine allotypes. The results showed that the prediction method was able to achieve significant discrimination between epitope and non-epitope peptides for all MHC allotypes examined, based on AUC values in the range 0.632-0.821. We also discuss how accounting for peptide binding in multiple registers to class II MHC largely explains the systematically worse performance of prediction methods for class II MHC compared with those for class I MHC

  5. Immunization with synthetic peptides containing epitopes of the class 1 outer-membrane protein of Neisseria meningitidis: production of bactericidal antibodies on immunization with a cyclic peptide.

    Science.gov (United States)

    Christodoulides, M; McGuinness, B T; Heckels, J E

    1993-08-01

    The class 1 outer-membrane protein of Neisseria meningitidis is the target for subtype-specific, bactericidal monoclonal antibodies (mAbs). The epitopes recognized by these antibodies have been mapped previously to linear peptides corresponding to the sequences thought to be exposed at the apices of surface-exposed loops of the protein. In this work several synthetic peptides containing the subtype Pl.16b epitope have been synthetized with the aim of inducing a polyclonal immune response resembling the reactivity of the mAbs. Initially, peptides of 9 and 15 amino acid residues were synthesized and used for immunization after coupling to a carrier protein. The reactivity of the resulting antisera, with synthetic linear decapeptides, resembled that seen in previous epitope mapping experiments with the protective mAbs. However, despite the induction of antibodies having the desired specificity, the antisera reacted poorly with the native protein in outer membranes, and were non-bactericidal. A 36mer peptide, consisting of the entire surface-exposed loop 4 of the class 1 protein was then synthesized and used for immunization as (i) free peptide, (ii) peptide coupled to carrier and (iii) peptide subjected to cyclization, in an attempt to restrict it to conformations that might more closely resemble the native loop structure. In contrast to antisera raised against linear peptides, antibodies raised by immunization with the 36mer cyclic peptide, did not react with linear peptides recognized by the mAbs, but instead appeared to recognize conformational determinants. This antiserum promoted complement-mediated bactericidal killing of the homologous meningococcal strain, demonstrating the potential of synthetic peptide immunogens for inducing a protective immune response against group B meningococci. PMID:7691983

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

    DEFF Research Database (Denmark)

    Trolle, Thomas; Metushi, Imir G.; Greenbaum, Jason;

    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 giv......-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...... 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...

  7. Lasso peptides: an intriguing class of bacterial natural products.

    Science.gov (United States)

    Hegemann, Julian D; Zimmermann, Marcel; Xie, Xiulan; Marahiel, Mohamed A

    2015-07-21

    Natural products of peptidic origin often represent a rich source of medically relevant compounds. The synthesis of such polypeptides in nature is either initiated by deciphering the genetic code on the ribosome during the translation process or driven by ribosome-independent processes. In the latter case, highly modified bioactive peptides are assembled by multimodular enzymes designated as nonribosomal peptide synthetases (NRPS) that act as a protein-template to generate chemically diverse peptides. On the other hand, the ribosome-dependent strategy, although relying strictly on the 20-22 proteinogenic amino acids, generates structural diversity by extensive post-translational-modification. This strategy seems to be highly distributed in all kingdoms of life. One example for this is the lasso peptides, which are an emerging class of ribosomally assembled and post-translationally modified peptides (RiPPs) from bacteria that were first described in 1991. A wide range of interesting biological activities are known for these compounds, including antimicrobial, enzyme inhibitory, and receptor antagonistic activities. Since 2008, genome mining approaches allowed the targeted isolation and characterization of such molecules and helped to better understand this compound class and their biosynthesis. Their defining structural feature is a macrolactam ring that is threaded by the C-terminal tail and held in position by sterically demanding residues above and below the ring, resulting in a unique topology that is reminiscent of a lariat knot. The ring closure is achieved by an isopeptide bond formed between the N-terminal α-amino group of a glycine, alanine, serine, or cysteine and the carboxylic acid side chain of an aspartate or glutamate, which can be located at positions 7, 8, or 9 of the amino acid sequence. In this Account, we discuss the newest findings about these compounds, their biosynthesis, and their physicochemical properties. This includes the suggested

  8. 25 CFR 502.3 - Class II gaming.

    Science.gov (United States)

    2010-04-01

    ....3 Class II gaming. Class II gaming means: (a) Bingo or lotto (whether or not electronic, computer... pattern on such cards; (b) If played in the same location as bingo or lotto, pull-tabs, punch boards,...

  9. Identification of peptides fromm foot-and-mouth disease virus structural proteins bound by class I swine leucocyte antigen (SLA) alleles, SLA-1*0401 and SLA-2*0401

    Science.gov (United States)

    The analysis of peptide binding to porcine major histocompatibility complex (MHC) class I molecules has not been extensively performed. Critical to understanding the adaptive immune response of swine to infection is characterization of Swine Leucocyte Antigens (SLA) class I and class II peptide bind...

  10. 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

    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...

  11. High-resolution analysis of the murine MHC class II immunopeptidome.

    Science.gov (United States)

    Sofron, Adriana; Ritz, Danilo; Neri, Dario; Fugmann, Tim

    2016-02-01

    The reliable identification of peptides bound to major histocompatibility complex (MHC) class II is fundamental for the study of the host immune response against pathogens and the pathogenesis of autoimmune conditions. Here, we describe an improved methodology combining immuno-affinity enrichment of MHC class II complexes, optimized elution conditions and quadrupole Orbitrap mass spectrometry-based characterization of the immunopeptidome. The methodology allowed the identification of over 1000 peptides with 1% false discovery rate from 10(8) murine A20 lymphoma cells. The study revealed the I-A(d) -specific motif in high resolution after multisequence alignment. The methodology was generally applied to the purification of MHC class II from cell lines and murine spleens. We identified 2963 peptides from BALB/c and 2712 from C57BL/6 mouse spleens. The identification of peptides bound to MHC class II in vitro and in vivo will facilitate the characterization of T-cell specificities, as well as the development of biotherapeutics and vaccines. PMID:26495903

  12. Lateral cephalometric diagnosis of asymmetry in Angle Class II subdivision compared to Class I and II

    Directory of Open Access Journals (Sweden)

    Aparecida Fernanda Meloti

    2014-08-01

    Full Text Available INTRODUCTION: Lateral cephalometric radiographs are traditionally required for orthodontic treatment, yet rarely used to assess asymmetries. OBJECTIVE: The objective of the present study was to use lateral cephalometric radiographs to identify existing skeletal and dentoalveolar morphological alterations in Class II subdivision and to compare them with the existing morphology in Class I and II relationship. MATERIAL AND METHODS: Ninety initial lateral cephalometric radiographs of male and female Brazilian children aged between 12 to 15 years old were randomly and proportionally divided into three groups: Group 1 (Class I, Group 2 (Class II and Group 3 (Class II subdivision. Analysis of lateral cephalometric radiographs included angular measurements, horizontal linear measurements and two indexes of asymmetry that were prepared for this study. RESULTS: In accordance with an Index of Dental Asymmetry (IDA, greater mandibular dental asymmetry was identified in Group 3. An Index of Mandibular Asymmetry (IMA revealed less skeletal and dental mandibular asymmetry in Group 2, greater skeletal mandibular asymmetry in Group 1, and greater mandibular dental asymmetry in Group 3. CONCLUSION: Both IDA and IMA revealed greater mandibular dental asymmetry for Group 3 in comparison to Groups 1 and 2. These results are in accordance with those found by other diagnostic methods, showing that lateral cephalometric radiography is an acceptable method to identify existing skeletal and dentoalveolar morphological alterations in malocclusions.

  13. Presence of Third Molar Germs in Orthodontic Patients with Class II/2 and Class III Malocclusions

    OpenAIRE

    Maričić, Barbara Mady; Legović, Mario; Šlaj, Martina; Lapter Varga, Marina; Žuvić Butorac, Marta; Kapović, Miljenko

    2009-01-01

    The aim of this study was to determine the presence of third molar germs in patients with Class II/2 and Class III malocclusions. The study comprised 146 examinees from Zagreb and Istria. Examinees with Class II/2 malocclusions amounted to 77 and those with Class III 69. With regard to development of dentition the examinees were divided into two groups: Group I subjects with early mixed dentition (23 subjects with Class II/2 and 21 subjects with Class III), and Group II subjects with late mix...

  14. Human HLA class I- and HLA class II-restricted cloned cytotoxic T lymphocytes identify a cluster of epitopes on the measles virus fusion protein.

    Science.gov (United States)

    van Binnendijk, R S; Versteeg-van Oosten, J P; Poelen, M C; Brugghe, H F; Hoogerhout, P; Osterhaus, A D; Uytdehaag, F G

    1993-01-01

    The transmembrane fusion (F) glycoprotein of measles virus is an important target antigen of human HLA class I- and class II-restricted cytotoxic T lymphocytes (CTL). Genetically engineered F proteins and nested sets of synthetic peptides spanning the F protein were used to determine sequences of F recognized by a number of F-specific CTL clones. Combined N- and C-terminal deletions of the respective peptides revealed that human HLA class I and HLA class II-restricted CTL efficiently recognize nonapeptides or decapeptides representing epitopes of F. Three distinct sequences recognized by three different HLA class II (DQw1, DR2, and DR4/w53)-restricted CTL clones appear to cluster between amino acids 379 and 466 of F, thus defining an important T-cell epitope area of F. Within this same region, a nonamer peptide of F was found to be recognized by an HLA-B27-restricted CTL clone, as expected on the basis of the structural homology between this peptide and other known HLA-B27 binding peptides. PMID:7680390

  15. Poor correspondence between predicted and experimental binding of peptides to class I MHC molecules

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Tan, L.; Søndergaard, Ib;

    2000-01-01

    Naturally processed peptides presented by class I major histocompatibility complex (MHC) molecules display a characteristic allele specific motif of two or more essential amino acid side chains, the so-called peptide anchor residues, in the context of an 8-10 amino acid long peptide. Knowledge of...

  16. Preformed purified peptide/major histocompatibility class I complexes are potent stimulators of class I-restricted T cell hybridomas

    DEFF Research Database (Denmark)

    Stryhn, A; Pedersen, L O; Ortiz-Navarrete, V;

    1994-01-01

    A panel of antigen-specific, major histocompatibility complex class I-restricted T cell hybridomas has been generated to examine the capacity of peptide/class I complexes to stimulate T cells at the molecular level. Peptide/class I complexes were generated in detergent solution, purified and...... quantitated. Latex particles were subsequently coated with known amounts of preformed complexes and used to stimulate the T cell hybridomas. Stimulation was specific, i.e. only the appropriate peptide/class I combination were stimulatory, and quite sensitive, i.e. as little as 300 complexes per bead could be...... detected by the T cells. Preformed complexes were about 500,000 times more potent than free peptide in terms of T cell stimulation, demonstrating the physiological relevancy of the biochemically generated complexes. Surprisingly, the majority (including the most sensitive of the hybridomas) had lost CD8...

  17. Mixed α/β-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability.

    Science.gov (United States)

    Mangelschots, Jeroen; Bibian, Mathieu; Gardiner, James; Waddington, Lynne; Van Wanseele, Yannick; Van Eeckhaut, Ann; Acevedo, Maria M Diaz; Van Mele, Bruno; Madder, Annemieke; Hoogenboom, Richard; Ballet, Steven

    2016-02-01

    Peptide hydrogels are a highly promising class of materials for biomedical application, albeit facing many challenges with regard to stability and tunability. Here, we report a new class of amphipathic peptide hydrogelators, namely mixed α/β-peptide hydrogelators. These mixed α/β-gelators possess good rheological properties (high storage moduli) and form transparent self-supporting gels with shear-thinning behavior. Infrared spectroscopy indicates the presence of β-sheets as the underlying secondary structure. Interestingly, self-assembled nanofibers of the mixed α/β-peptides display unique structural morphologies with alteration of the C-terminus (acid vs amide) playing a key role in the fiber formation and gelation properties of the resulting hydrogels. The incorporation of β3-homoamino acid residues within the mixed α/β-peptide gelators led to an increase in proteolytic stability of the peptides under nongelating conditions (in solution) as well as gelating conditions (as hydrogel). Under diluted conditions, degradation of mixed α/β-peptides in the presence of elastase was slowed down 120-fold compared to that of an α-peptide, thereby demonstrating beneficial enzymatic resistance for hydrogel applications in vivo. In addition, increased half-life values were obtained for the mixed α/β-peptides in human blood plasma, as compared to corresponding α-peptides. It was also found that the mixed α/β-peptides were amenable to injection via needles used for subcutaneous administrations. The preformed peptide gels could be sheared upon injection and were found to quickly reform to a state close to that of the original hydrogel. The shown properties of enhanced proteolytic stability and injectability hold great promise for the use of these novel mixed α/β-peptide hydrogels for applications in the areas of tissue engineering and drug delivery. PMID:26741458

  18. Archform Comparisons between Skeletal Class II and III Malocclusions

    OpenAIRE

    Zou, Wei; Wu, Jiaqi; Jiang, JiuHui; Xu, Tianmin; Li, CuiYing

    2014-01-01

    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 t...

  19. Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides.

    Science.gov (United States)

    Kessler, Jan H; Mommaas, Bregje; Mutis, Tuna; Huijbers, Ivo; Vissers, Debby; Benckhuijsen, Willemien E; Schreuder, Geziena M Th; Offringa, Rienk; Goulmy, Els; Melief, Cornelis J M; van der Burg, Sjoerd H; Drijfhout, Jan W

    2003-02-01

    We report the development, validation, and application of competition-based peptide binding assays for 13 prevalent human leukocyte antigen (HLA) class I alleles. The assays are based on peptide binding to HLA molecules on living cells carrying the particular allele. Competition for binding between the test peptide of interest and a fluorescein-labeled HLA class I binding peptide is used as read out. The use of cell membrane-bound HLA class I molecules circumvents the need for laborious biochemical purification of these molecules in soluble form. Previously, we have applied this principle for HLA-A2 and HLA-A3. We now describe the assays for HLA-A1, HLA-A11, HLA-A24, HLA-A68, HLA-B7, HLA-B8, HLA-B14, HLA-B35, HLA-B60, HLA-B61, and HLA-B62. Together with HLA-A2 and HLA-A3, these alleles cover more than 95% of the Caucasian population. Several allele-specific parameters were determined for each assay. Using these assays, we identified novel HLA class I high-affinity binding peptides from HIVpol, p53, PRAME, and minor histocompatibility antigen HA-1. Thus these convenient and accurate peptide-binding assays will be useful for the identification of putative cytotoxic T lymphocyte epitopes presented on a diverse array of HLA class I molecules. PMID:12559627

  20. 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

  1. PENELOPE. Taking advantage of Class II simulation

    International Nuclear Information System (INIS)

    PENELOPE is a general-purpose Monte Carlo code for the simulation of electron-photon showers in arbitrary materials. It covers the energy range from ∼1 keV up to ∼1 GeV. The simulation of electron and positron transport is based on a mixed (Class II) simulation scheme. The cut-off angular deflection, which separates soft and hard (catastrophic) elastic collisions, is allowed to vary with the energy of the particle in such a way that the multiple soft interactions which occur between two consecutive hard events produce only gentle deflections of the track. Space displacements are generated by a simple and accurate algorithm that works even in the vicinity of interfaces. The physics of PENELOPE, the simulation algorithm for charged particle transport and the structure and operation of the code system are described. The distribution package also includes subroutines for simulation in quadric geometries (i.e. material systems consisting of homogeneous bodies limited by quadric surfaces) and a simple geometry viewer. (author)

  2. 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

    significantly in the peptide-binding alpha(1) domain. The cDNA and genomic DNA sequences from chickens of diverse origins show few alleles, which differ in only four nucleotides and one amino acid. In contrast, significant restriction fragment length polymorphism is detected by Southern blot analysis of genomic...... DNA, suggesting considerable diversity around the gene. Analysis of a large back-cross family indicates that the class II alpha chain locus ( B-LA) is located roughly 5.6 cM from the MHC locus, which encodes the classical class II beta chains. Thus the chicken class II alpha chain gene is like the...

  3. Evaluation of arch width among Class I normal occlusion, Class II Division 1, Class II Division 2, and Class III malocclusion in Indian population

    OpenAIRE

    Dolly Patel; Falguni Mehta; Nimesh Patel; Nishit Mehta; Ipist Trivedi; Apexa Mehta

    2015-01-01

    Objective: To test the hypothesis that there is no difference between Class I (CI) normal occlusion, Class II division 1 (CIId1) and CII division 2 (CIId2), and Class III (CIII) malocclusion with respect to arch widths, width of the maxillary and mandibular arches, gender dimorphism within groups, and gender comparisons. Materials and Methods: Samples of 40 CI subjects, 40 CIId1 subjects, 40 CIId2 subjects, and 34 CIII subjects were studied. All subjects were Indians with no history of or...

  4. 78 FR 37114 - Self-Regulation of Class II Gaming

    Science.gov (United States)

    2013-06-20

    ... the issuance of a certificate for tribal self-regulation of Class II gaming. 78 FR 20236, April 4... National Indian Gaming Commission 25 CFR Part 518 RIN 3141-AA44 Self-Regulation of Class II Gaming AGENCY: National Indian Gaming Commission, Department of the Interior. ACTION: Final rule; technical and...

  5. Dentofacial characteristics of patients with Angle Class I and Class II malocclusions

    Directory of Open Access Journals (Sweden)

    Rogério Lacerda dos Santos

    2012-04-01

    Full Text Available OBJECTIVE: The present study assessed some cephalometric measurements of the soft tissue profile in order to observe the behavior of facial convexity in patients with Class I, Class II division 1, and Class II division 2 malocclusions. METHODS: One hundred and thirty pre-treatment teleradiographs of Caucasian patients aged 10-16 years (mean age of 12.6 years were selected for study and divided into 3 groups. The cephalometric measurements used in the present study were the following: H.SN, Cx, NLA, MLA, UL-SUL-S, LL-S, IMPA, and 1-SN. Analysis of variance and Tukey's test were applied for measurements H.SN, Cx, IMPA, 1-SN, MLA, and NLA, whereas Kruskal-Wallis and Dunn's tests were applied for UL-S and LL-S. RESULTS: The results showed statistically significant differences for the measurements H.SN, Cx, UL-S, and IMPA between Groups I, II-1 and II-2 (p < 0.05. Measurements LL-S and MLA showed statistically significant difference between Groups I and II-1 only (p < 0.05. On the other hand, no statistically significant differences were found for measurement NLA among the 3 groups (p < 0.05. CONCLUSION: Regarding facial characteristics expressed by measurements H.SN, Cx, and UL-S, one could conclude that Class II division 1 and Class II division 2 malocclusions, both differed from Class I malocclusion. In addition, Class II division 1 malocclusion was found to have facial characteristics expressed by MLA, which differentiate it from the Class II division 2 and Class 1 malocclusions. Class I, Class II division 1 and Class II division 2 malocclusions showed no difference in facial characteristics expressed by the measurement NLA, and measurement LL-S was directly related to eversion of the lower lip.

  6. The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice.

    Directory of Open Access Journals (Sweden)

    Marc A J Morgan

    Full Text Available The spontaneous destruction of insulin producing pancreatic beta cells in non-obese diabetic (NOD mice provides a valuable model of type 1 diabetes. As in humans, disease susceptibility is controlled by the classical MHC class II genes that guide CD4(+ T cell responses to self and foreign antigens. It has long been suspected that the dedicated class II chaperone designated HLA-DM in humans or H-2M in mice also makes an important contribution, but due to tight linkage within the MHC, a possible role played by DM peptide editing has not been previously tested by conventional genetic approaches. Here we exploited newly established germ-line competent NOD ES cells to engineer a loss of function allele. DM deficient NOD mice display defective class II peptide occupancy and surface expression, and are completely protected against type 1 diabetes. Interestingly the mutation results in increased proportional representation of CD4(+Foxp3(+ regulatory T cells and the absence of pathogenic CD4(+ T effectors. Overall, this striking phenotype establishes that DM-mediated peptide selection plays an essential role in the development of autoimmune diabetes in NOD mice.

  7. Postura de cabeça nas deformidades dentofaciais classe II e classe III Head posture in the presence of class II and class III dentofacial deformities

    Directory of Open Access Journals (Sweden)

    Marcela Ralin de Carvalho Deda

    2012-04-01

    Full Text Available OBJETIVO: este estudo investiga se existe diferença entre grupos com diferentes deformidades dentofaciais (padrão classe II e classe III e o grupo sem a deformidade em relação à postura de cabeça. MÉTODO: participaram deste estudo, voluntariamente, 25 pacientes (entre 16 e 40 anos. Dez pacientes com diagnóstico de deformidade dentofacial classe II e 15 pacientes com o diagnóstico de classe III esquelética e 15 voluntários sadios, com equivalência em sexo e idade ao grupo de deformidade, formando o grupo controle. Primeiramente foi realizada a inspeção da postura de cabeça. Logo em seguida foi realizada a avaliação postural de cabeça por meio da fotografia postural (fotogrametria. RESULTADOS: não houve diferença significante (p>0,05 entre os grupos em relação à avaliação postural utilizando-se a fotogrametria. Já em relação à avaliação postural pela inspeção clínica, observou-se uma postura anterior de cabeça nos indivíduos com a deformidade dentofacial padrão classe II, comparados ao padrão classe III (p = 0,001 e ao grupo controle (p = 0,001. Foi visto também que o grupo deformidade classe II apresentou um percentual inferior de indivíduos com posição neutra de cabeça comparado ao grupo deformidade classe III (p = 0,008 e ao grupo controle (p = 0,001. CONCLUSÃO: indivíduos com deformidade dentofacial classe II podem apresentar uma anteriorização de cabeça. Não há influência da deformidade no aumento ou na redução do ângulo cabeça-pescoço, analisado por meio da fotogrametria.PURPOSE: this study investigates whether there is a difference in head posture between groups with different dentofacial deformities (class II and class III and a group with no deformity. METHOD: 25 volunteers aged from 16 to 40 year old took part in the study. Ten patients had a diagnosis of class II dentofacial deformity, 15 had a diagnosis of class III skeletal deformity, and 15 healthy volunteers matched for sex and

  8. Utility of characteristic QTOF MS/MS fragmentation for MHC class I peptides.

    Science.gov (United States)

    Escobar, Hernando; Reyes-Vargas, Eduardo; Jensen, Peter E; Delgado, Julio C; Crockett, David K

    2011-05-01

    Systematic investigation of cellular process by mass spectrometric detection of peptides obtained from proteins digestion or directly from immuno-purification can be a powerful tool when used appropriately. The true sequence of these peptides is defined by the interpretation of spectral data using a variety of available algorithms. However peptide match algorithm scoring is typically based on some, but not all, of the mechanisms of peptide fragmentation. Although algorithm rules for soft ionization techniques generally fit very well to tryptic peptides, manual validation of spectra is often required for endogenous peptides such as MHC class I molecules where traditional trypsin digest techniques are not used. This study summarizes data mining and manual validation of hundreds of peptide sequences from MHC class I molecules in publically available data files. We herein describe several important features to improve and quantify manual validation for these endogenous peptides--post automated algorithm searching. Important fragmentation patterns are discussed for the studied MHC Class I peptides. These findings lead to practical rules that are helpful when performing manual validation. Furthermore, these observations may be useful to improve current peptide search algorithms or development of novel software tools. PMID:21413816

  9. Cathelicidin peptides as candidates for a novel class of antimicrobials.

    Science.gov (United States)

    Zanetti, Margherita; Gennaro, Renato; Skerlavaj, Barbara; Tomasinsig, Linda; Circo, Raffaella

    2002-01-01

    Cathelicidin peptides are a numerous group of mammalian cationic antimicrobial peptides. Despite a common evolutionary origin of their genes, peptides display a remarkable variety of sizes, sequences and structures. Their spectra of antimicrobial activity are varied and cover a range of organisms that includes bacteria, fungi and enveloped viruses. In addition, they bind to and neutralize the effects of endotoxin. These features make this family of peptides good candidates in view of a therapeutic use. The most promising ones are currently under evaluation as leads for the development of novel anti-infectives, and synthetic variants are in an advanced stage of development for specific clinical applications. This review focuses on recent studies on the structure and in vitro and in vivo biological activities of these peptides. PMID:11945171

  10. MHC class II proteins contain a potential binding site for the verotoxin receptor glycolipid CD77.

    Science.gov (United States)

    George, T; Boyd, B; Price, M; Lingwood, C; Maloney, M

    2001-11-01

    Globotriaosyl ceramide or CD77 functions as a cell surface receptor for toxins of the Shiga toxin/verotoxin family and as a marker for germinal center stage B-cells. The B-cell protein CD19 and the interferon-alpha receptor possess verotoxin-like amino acid sequences in their extracellular domains, and CD77 has been shown to function in CD19-mediated adhesion and interferon-induced growth inhibition. The Burkitt's lymphoma cell line, Daudi, is similar to germinal center B-cells in their expression of CD77, CD19 and MHC class II molecules. Using the multiple sequence alignment program, ClustalW, we have identified a verotoxin-like amino acid sequence on the beta-chain of human and murine MHC class II molecules. Binding of CD77 at this site could modulate the peptide-binding properties of these MHC class II molecules. Using Western blot analysis of whole cell extracts, we found that CD77-positive Daudi cells have higher levels of HLA-D proteins than VT500 cells, a Daudi-derived CD77-deficient mutant cell line. In contrast, MHC class II-mediated adhesion and surface expression are similar in the two cell lines. Therefore, CD77 could play a functional or regulatory role in MHC class II-mediated functions specifically relating to antigen presentation by B-cells to T helper cells. PMID:11838965

  11. The Specificity of Trimming of MHC Class I-Presented Peptides in the Endoplasmic Reticulum1

    OpenAIRE

    Hearn, Arron; Ian A York; Rock, Kenneth L.

    2009-01-01

    Aminopeptidases in the endoplasmic reticulum (ER) can cleave antigenic peptides and in so doing either create or destroy MHC class I-presented epitopes. However the specificity of this trimming process overall and of the major ER aminopeptidase ERAP1 in particular is not well understood. This issue is important because peptide trimming influences the magnitude and specificity of CD8 T cell responses. By systematically varying the N-terminal flanking sequences of peptides in a cell free bioche...

  12. 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; Buus, S

    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...

  13. 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

    The Human MHC Project aims at large-scale description of peptide-HLA binding to a wide range of HLA molecules covering all populations of the world and the accompanying generation of bioinformatics tools capable of predicting binding of any given peptide to any given HLA molecule. Here, the authors...... present a homogenous, proximity-based assay for detection of peptide binding to HLA class I molecules. It uses a conformation-dependent anti-HLA class I antibody, W6/32, as one tag and a biotinylated recombinant HLA class I molecule as the other tag, and a proximity-based signal is generated through 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...

  14. Intracellular transport of MHC class II and associated invariant chain in antigen presenting cells from AP-3-deficient mocha mice.

    Science.gov (United States)

    Sevilla, L M; Richter, S S; Miller, J

    2001-06-15

    MHC class II-restricted antigen presentation requires trafficking of newly synthesized class II-invariant chain complexes from the trans-Golgi network to endosomal, peptide-loading compartments. This transport is mediated by dileucine-like motifs within the cytosolic tail of the invariant chain. Although these signals have been well characterized, the cytosolic proteins that interact with these dileucine signals and mediate Golgi sorting and endosomal transport have not been identified. Recently, an adaptor complex, AP-3, has been identified that interacts with dileucine motifs and mediates endosomal/lysosomal transport in yeast, Drosophila, and mammals. In this report, we have assessed class II-invariant chain trafficking in a strain of mice (mocha) which lacks expression of AP-3. Our studies demonstrate that the lack of AP-3 does not affect the kinetics of invariant chain degradation, the route of class II-invariant chain transport, or the rate and extent of class II-peptide binding as assessed by the generation of SDS-stable dimers. The possible role of other known or unknown adaptor complexes in class II-invariant chain transport is discussed. PMID:11520080

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

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K;

    1994-01-01

    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......-like) as well as T cells producing both cytokines (THO-like) responded to class II mAb. The costimulatory effect was not restricted to IL-2-driven T cell growth, since TCR/CD3-induced T cell activation was also enhanced by HLA-DR mAb. Moreover, class II costimulation potentiated CD28-mAb-induced T cell...

  16. Class II barodontalgia: review and report of a case.

    Science.gov (United States)

    Woodmansey, Karl

    2008-01-01

    Barodontalgia is a rarely reported condition involving changes in ambient pressure resulting in tooth pain. According to Ferjentsik and Aker, Class II barodontalgia is observed in teeth that have pre-existing pulpal disease and an ultimate diagnosis of irreversible pulpitis.1 This article describes a case of Class II barodontalgia that was experienced on a commercial airline flight and reviews current knowledge regarding this phenomenon, including proposed etiologic mechanisms. PMID:21444271

  17. 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.

  18. Towards the improved discovery and design of functional peptides: common features of diverse classes permit generalized prediction of bioactivity.

    Directory of Open Access Journals (Sweden)

    Catherine Mooney

    Full Text Available The conventional wisdom is that certain classes of bioactive peptides have specific structural features that endow their particular functions. Accordingly, predictions of bioactivity have focused on particular subgroups, such as antimicrobial peptides. We hypothesized that bioactive peptides may share more general features, and assessed this by contrasting the predictive power of existing antimicrobial predictors as well as a novel general predictor, PeptideRanker, across different classes of peptides.We observed that existing antimicrobial predictors had reasonable predictive power to identify peptides of certain other classes i.e. toxin and venom peptides. We trained two general predictors of peptide bioactivity, one focused on short peptides (4-20 amino acids and one focused on long peptides (> 20 amino acids. These general predictors had performance that was typically as good as, or better than, that of specific predictors. We noted some striking differences in the features of short peptide and long peptide predictions, in particular, high scoring short peptides favour phenylalanine. This is consistent with the hypothesis that short and long peptides have different functional constraints, perhaps reflecting the difficulty for typical short peptides in supporting independent tertiary structure.We conclude that there are general shared features of bioactive peptides across different functional classes, indicating that computational prediction may accelerate the discovery of novel bioactive peptides and aid in the improved design of existing peptides, across many functional classes. An implementation of the predictive method, PeptideRanker, may be used to identify among a set of peptides those that may be more likely to be bioactive.

  19. Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

    Science.gov (United States)

    Minias, Piotr; Bateson, Zachary W; Whittingham, Linda A; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O

    2016-01-01

    Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

  20. MHC Class II Derived Recombinant T Cell Receptor Ligands Protect DBA/1LacJ Mice from Collagen-Induced Arthritis1

    OpenAIRE

    Huan, Jianya; Kaler, Laurie J.; Mooney, Jeffery L.; Subramanian, Sandhya; Hopke, Corwyn; Vandenbark, Arthur A.; Rosloniec, Edward F.; Burrows, Gregory G.; Offner, Halina

    2008-01-01

    We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), single-chain two domain complexes of the α1 and β1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257–270) suitable for use in DBA/1LacJ mice that develop ...

  1. Non-extraction treatment of skeletal class II malocclusion

    Directory of Open Access Journals (Sweden)

    Abhay K Jain

    2012-01-01

    Full Text Available Introduction: Every orthodontist at some point in his clinical practice has faced the dilemma of how ′best′ to manage a mild to moderate Class II malocclusion. Aims and Objectives: To demonstrate the efficacy of Forsus™ Fatigue Resistant Device in the management of Class II malocclusion. Materials and Method: A patient having Class II division 1 malocclusion with functional jaw retrusion was treated using MBT 0.022" prescription and Forsus FRD appliance. Pre- and post-treatment photographs and lateral cephalograms were taken. Cephalometric analysis was done, and results were superimposed. Result: 7-8 months of Forsus wear obtained stable and successful results with improvement in facial profile, skeletal jaw relationship, and mild increase in IMPA. Discussion and Conclusion: Greater forward displacement of the mandible was the predominant factor for successful treatment Class II patient. Forsus gives good results for class II management, and it would be wise to consider treating such cases by non-extraction approach rather than contemplating extractions.

  2. Dentofacial characteristics of patients with Angle Class I and Class II malocclusions

    OpenAIRE

    Rogério Lacerda dos Santos; Antônio Carlos de Oliveira Ruellas

    2012-01-01

    OBJECTIVE: The present study assessed some cephalometric measurements of the soft tissue profile in order to observe the behavior of facial convexity in patients with Class I, Class II division 1, and Class II division 2 malocclusions. METHODS: One hundred and thirty pre-treatment teleradiographs of Caucasian patients aged 10-16 years (mean age of 12.6 years) were selected for study and divided into 3 groups. The cephalometric measurements used in the present study were the following: H.SN, C...

  3. Novel structural class of four disulfide-bridged peptides from Tityus serrulatus venom.

    Science.gov (United States)

    Pimenta, Adriano M C; Legros, Christian; Almeida, Flávia de Marco; Mansuelle, Pascal; De Lima, Maria Elena; Bougis, Pierre E; Martin-Eauclaire, Marie France

    2003-02-21

    A new structural class of short peptides folded by four disulfide-bridges was found in the venom of the Brazilian scorpion Tityus serrulatus. Peptides were put on evidence independently by means of two different approaches of structurally guided prospection. First, a cDNA sequence was obtained using a degenerate primer constructed according to the C-terminal sequence of kaliotoxin (KTx2), from the Androctonus australis venom. Second, MALDI-TOF mass spectrometry analyses of toxic fraction FIII from T. serrulatus venom revealed a family of molecules ranging approximately from 2900 to 3000 Da. Three new peptides were isolated and named TsPep1, TsPep2, and TsPep3. Biochemical characterization showed that they are 29 amino acids long, constrained by a new pattern of four disulfide-bridges. These results enable us to classify these new molecules as part of a novel structural class of short peptides from scorpion venoms. PMID:12589824

  4. Prediction of peptides binding to MHC class I alleles by partial periodic pattern mining

    OpenAIRE

    Meydan, Cem; Sezerman, Uğur; Sezerman, Ugur; Otu, Hasan

    2009-01-01

    MHC (Major Histocompatibility Complex) is a key player in the immune response of an organism. It is important to be able to predict which antigenic peptides will bind to a spe-cific MHC allele and which will not, creating possibilities for controlling immune response and for the applications of immunotherapy. However a problem encountered in the computational binding prediction methods for MHC class I is the presence of bulges and loops in the peptides, changing the total length. Most machine...

  5. Partial MHC class II constructs inhibit MIF/CD74 binding and downstream effects

    OpenAIRE

    Benedek, Gil; Meza-Romero, Roberto; Andrew, Shayne; Leng, Lin; Burrows, Gregory G.; Bourdette, Dennis; Offner, Halina; Bucala, Richard; Vandenbark, Arthur A.

    2013-01-01

    Macrophage migration inhibitory factor (MIF) and its receptor, CD74, are pivotal regulators of the immune system. Here we demonstrate for the first time that partial MHC class II constructs comprised of linked β1α1 domains with covalently attached antigenic peptides (also referred to as recombinant T-cell receptor ligands - RTLs) can inhibit MIF activity by not only blocking the binding of rhMIF to immunopurified CD74, but also down-regulating CD74 cell-surface expression. This bi-functional ...

  6. 14 CFR 21.223 - Class II provisional airworthiness certificates.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Class II provisional airworthiness certificates. 21.223 Section 21.223 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... the aircraft has been issued to the manufacturer. (c) The applicant must submit a statement by...

  7. Changes in Cranial Base Morphology in Class I and Class II Division 1 Malocclusions

    OpenAIRE

    Agarwal, Anirudh; Pandey, Harsh; Bajaj, Kamal; Pandey, Lavesh

    2013-01-01

    Introduction: The cranial base plays a key role in craniofacial growth; it helps to integrate spatially and functionally different patterns of growth in various adjoining regions of the skull such as components of the brain, the nasal and oral cavity and the pharynx. The aim of this study was to evaluate the difference in cranial base flexure between skeletal and dental Class I and Class II division 1.

  8. Treatment of Class II Division 1 Malocclusion using Cervical Headgear

    Directory of Open Access Journals (Sweden)

    Priska Lestari Hendrawan

    2013-07-01

    Full Text Available Class II division 1 malocclusions have many variation and treatment options. Choosing the right treatment begins with a correct diagnosis. The aim of this article is to describe treatment of Class II division 1 malocclusion in a growing patient using combined cervical headgear and non-extraction fixed orthodontic therapy. Class I molar and canine relationship was achieved with normal overbite and overjet. There is improvement in jaw relationship and facial profile. This correction was achieved by downward displacement and inhibition of the forward growth of maxilla with favorable growth of mandible, upper molar distalization and retraction of upper incisors from cervical headgear use. There was neither downward rotation of the mandible nor maxillary first molar extrusion. Treatment time, favorable mandibular growth pattern and patient compliance proved to be determining factors in the success of this treatment.DOI: 10.14693/jdi.v16i3.106

  9. 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.

  10. DNA polymorphism of HLA class II genes in alopecia areata

    DEFF Research Database (Denmark)

    Morling, N; Frentz, G; Fugger, L;

    1992-01-01

    We investigated the DNA restriction polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DQA, -DQB, -DPA, and -DPB in 20 Danish patients with alopecia areata (AA) and in healthy Danes. The frequency in AA of the DQB1*0301 and DQw7 associated DQB Bgl/II 4.2 kb...... of the serologically defined HLA-DQw7 specificity. Individuals who carried both DQA1*0501 and DQB1*0301 seemed to have a further increased risk of developing AA compared to individuals carrying only one of these HLA class II genes. Analysis of the combined presence of DQB1*0301 and DPA1*0103 in AA suggests...

  11. A detailed comparison of peptides presented by different HLA class I loci: an in silico approach

    NARCIS (Netherlands)

    Rao, X.

    2012-01-01

    Human Leukocyte Antigen (HLA) class I is a group of genes located on human chromosome 6 which play a crucial role in initiating potentially protective immune responses, by presenting pathogen-derived peptides to CD8+ T cells and thus targeting infected cells for elimination. Compare to other HLA cla

  12. A comparative study on applying functional therapeutic method versus class II elastics edgewise in class II skeletal patients

    Directory of Open Access Journals (Sweden)

    Eslamian L

    2002-06-01

    Full Text Available Various comparative studies have been conducted to investigate the effect of functional and fixed appliances in treatment of class II skeletal disorders. The aim of this study was to compare Bionator and Edgewise appliances associated with class II elastics in the treatment of class II skeletal patients, without extraction. Lateral cephalograms of 30 patients (16 girls, 14 boys, 10-13 years old, with class II div I maolocclusion, treated with Bionater and Edgewise appliances were investigated before and after treatment. SNA, SNB, ANB, " to SN, IMP A, mandibular and maxillary lengths, upper anterior facial height to lower anterior facial height, overjet and overbite were measured in each group before and after treatment. The results were analyzed by paired t- test. The magnification of linear measurements were calculated. The differences between variables in 2 groups were compared by t-test. There was no significant difference, regarding age and sex. In both groups, increase in SNB, mandibular length, and IMPA and decrease in " to SN, overjet and overbite and upper anterior face height to lower anterior face height after treatment were statistically significant. Comparing 2 groups before and after treatment showed that increase in SNB and decrease of ANB, overjet and overbite were more in Bionator group than fixed group, which were significant. Decrease in upper anterior face height to lower anterior face height, and increase in IMPA and mandibular length were more in Bionater group but the differences were not statistically significant.

  13. A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes

    OpenAIRE

    Salvat, Regina; Moise, Leonard; Bailey-Kellogg, Chris; Griswold, Karl E

    2014-01-01

    Biochemical assays with recombinant human MHC II molecules can provide rapid, quantitative insights into immunogenic epitope identification, deletion, or design1,2. Here, a peptide-MHC II binding assay is scaled to 384-well format. The scaled down protocol reduces reagent costs by 75% and is higher throughput than previously described 96-well protocols1,3-5. Specifically, the experimental design permits robust and reproducible analysis of up to 15 peptides against one MHC II allele per 384-we...

  14. HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1

    OpenAIRE

    de la Salle, Henri; Zimmer, Jacques; Fricker, Dominique; Angenieux, Catherine; Cazenave, Jean-Pierre; Okubo, Mitsuo; Maeda, Hiroo; Plebani, Alessandro; Tongio, Marie-Marthe; Dormoy, Anne; Hanau, Daniel

    1999-01-01

    The transporter associated with antigen processing (TAP), which is composed of two subunits (TAP1 and TAP2) that have different biochemical and functional properties, plays a key role in peptide loading and the cell surface expression of HLA class I molecules. Three cases of HLA class I deficiency have previously been shown to result from the absence of a functional TAP2 subunit. In the present study, we analyzed two cases displaying not only the typical lung syndrome of HLA class I deficienc...

  15. The Association of HLA-Class I and Class II with Hodgkin’s Lymphoma in Iranian Patients

    OpenAIRE

    Arezou Sayad; Mohammad Taghi Akbari; Mahshid Mehdizadeh; Abolfazl Movafagh; Abbas Hajifathali

    2014-01-01

    The Hodgkin's lymphoma disease (HD) is a common malignant neoplasm with germinal centre B-cell origin. It has been suggested that the HLA class I and class II regions have susceptibility effects on HD. In different ethnic groups, different HLA class I and class II alleles affect HD. As a result, there is no consensus which of the different HLA alleles confers susceptibility to HD. In this study, we aimed to ascertain the role of HLA class I and class II alleles in association with Hodgkin's l...

  16. 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.

  17. 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

  18. Predominant Occupation of the Class I MHC Molecule H-2Kwm7 with a Single Self-peptide Suggests a Mechanism for its Diabetes-protective Effect

    Energy Technology Data Exchange (ETDEWEB)

    Brims, D.; Qian, J; Jarchum, I; Mikesh, L; Palmieri, E; Ramagopal, U; Malashkevich, V; Chaparro, R; Lund, T; et. al.

    2010-01-01

    Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of insulin-producing pancreatic {beta} cells. In both humans and the non-obese diabetic (NOD) mouse model of T1D, class II MHC alleles are the primary determinant of disease susceptibility. However, class I MHC genes also influence risk. These findings are consistent with the requirement for both CD{sup 4+} and CD{sup 8+} T cells in the pathogenesis of T1D. Although a large body of work has permitted the identification of multiple mechanisms to explain the diabetes-protective effect of particular class II MHC alleles, studies examining the protective influence of class I alleles are lacking. Here, we explored this question by performing biochemical and structural analyses of the murine class I MHC molecule H-2K{sup wm7}, which exerts a diabetes-protective effect in NOD mice. We have found that H-2K{sup wm7} molecules are predominantly occupied by the single self-peptide VNDIFERI, derived from the ubiquitous protein histone H2B. This unexpected finding suggests that the inability of H-2K{sup wm7} to support T1D development could be due, at least in part, to the failure of peptides from critical {beta}-cell antigens to adequately compete for binding and be presented to T cells. Predominant presentation of a single peptide would also be expected to influence T-cell selection, potentially leading to a reduced ability to select a diabetogenic CD{sup 8+} T-cell repertoire. The report that one of the predominant peptides bound by T1D-protective HLA-A*31 is histone derived suggests the potential translation of our findings to human diabetes-protective class I MHC molecules.

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

    OpenAIRE

    José Tarcísio Lima Ferreira; Maria do Rosário Ferreira Lima; Luciana Zappeloni Pizzolato

    2012-01-01

    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...

  20. Applying the Listening to Mothers II Results in Lamaze Classes

    OpenAIRE

    Day, Elizabeth H.

    2007-01-01

    Childbirth educators can use Childbirth Connection's Listening to Mothers II survey as a resource for updating their curriculum and teaching methods. The survey reveals that issues surrounding a woman's choice of care providers, her nutrition and fitness habits, and her possible experiences with depression and abuse may not be addressed sufficiently in a traditional, third-trimester, Lamaze class and may need greater emphasis in early pregnancy. The survey's results also show that women turn ...

  1. MHC Class II haplotypes of Colombian Amerindian tribes

    Directory of Open Access Journals (Sweden)

    Juan J. Yunis

    2013-01-01

    Full Text Available 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.

  2. 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.

  3. Evolução dos preparos das cavidades de classe II Developments in preparation of class II cavities

    Directory of Open Access Journals (Sweden)

    Mary Miyuki ONO

    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 retençãoDevelopments in preparation of class II cavities with the introduction of new materials and awareness of the importance of preservation of a sound dental structure are broached in preparations of the type Almqvist, Roggenkamp and tunnel, where the need for less wear of the dental structure was observed with an increase in fracture strength, better aesthetics, and better retention

  4. Zn(II) and Hg(II) binding to a designed peptide that accommodates different coordination geometries.

    Science.gov (United States)

    Szunyogh, Dániel; Gyurcsik, Béla; Larsen, Flemming H; Stachura, Monika; Thulstrup, Peter W; Hemmingsen, Lars; Jancsó, Attila

    2015-07-28

    Designed metal ion binding peptides offer a variety of applications in both basic science as model systems of more complex metalloproteins, and in biotechnology, e.g. in bioremediation of toxic metal ions, biomining or as artificial enzymes. In this work a peptide (HS: Ac-SCHGDQGSDCSI-NH2) has been specifically designed for binding of both Zn(II) and Hg(II), i.e. metal ions with different preferences in terms of coordination number, coordination geometry, and to some extent ligand composition. It is demonstrated that HS accommodates both metal ions, and the first coordination sphere, metal ion exchange between peptides, and speciation are characterized as a function of pH using UV-absorption-, synchrotron radiation CD-, (1)H-NMR-, and PAC-spectroscopy as well as potentiometry. Hg(II) binds to the peptide with very high affinity in a {HgS2} coordination geometry, bringing together the two cysteinates close to each end of the peptide in a loop structure. Despite the high affinity, Hg(II) is kinetically labile, exchanging between peptides on the subsecond timescale, as indicated by line broadening in (1)H-NMR. The Zn(II)-HS system displays more complex speciation, involving monomeric species with coordinating cysteinates, histidine, and a solvent water molecule, as well as HS-Zn(II)-HS complexes. In summary, the HS peptide displays conformational flexibility, contains many typical metal ion binding groups, and is able to accommodate metal ions with different structural and ligand preferences with high affinity. As such, the HS peptide may be a scaffold offering binding of a variety of metal ions, and potentially serve for metal ion sequestration in biotechnological applications. PMID:26040991

  5. 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.

  6. 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; Hvid, C.S.; Lamberth, K.; Buus, S.; Brunak, Søren; Lund, Ole

    2004-01-01

    , 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...... MHC class II complex HLA-DR4(B1*0401). Prior identification of information-rich (anchor) positions in the binding motif is shown to improve the predictive performance of the Gibbs sampler. Similarly, a consensus solution obtained from an ensemble average over suboptimal solutions is shown to...... conventional alignment algorithm of ClustalW. The calculation demonstrates that the predictive performance of the Gibbs sampler is higher than that of ClustalW and in most cases also higher than that of the TEPITOPE method....

  7. Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition

    OpenAIRE

    1992-01-01

    The routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein (F) of measles virus (MV) to HLA class I and class II presentable peptides have been examined, using cloned cytotoxic T lymphocytes in functional assays. Presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines was achieved using live virus, ultraviolet light-inactivated virus, and purified MV- F delivered either as such or incorporated in immunostimulating complexes (MV-F-ISCO...

  8. 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.

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

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H;

    2015-01-01

    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...

  10. Simultaneous observation of water and class I methanol masers toward class II methanol maser sources

    CERN Document Server

    Kang, Hyunwoo; Byun, Do-Young; Lee, Seokho; Park, Yong-Sun

    2015-01-01

    We present a simultaneous single-dish survey of 22 GHz water maser and 44 GHz and 95 GHz class I methanol masers toward 77 6.7 GHz class II methanol maser sources, which were selected from the Arecibo methanol maser Galactic plane survey (AMGPS) catalog.Water maser emission is detected in 39 (51%) sources, of which 15 are new detections. Methanol maser emission at 44 GHz and 95 GHz is found in 25 (32%) and 19 (25%) sources, of which 21 and 13 sources are newly detected, respectively. We find 4 high-velocity (> 30 km/s) water maser sources, including 3 dominant blue- or redshifted outflows.The 95 GHz masers always appear with the 44 GHz maser emission. They are strongly correlated with 44 GHz masers in velocity, flux density, and luminosity, while they are not correlated with either water or 6.7 GHz class II methanol masers. The average peak flux density ratio of 95 GHz to 44 GHz masers is close to unity, which is two times higher than previous estimates. The flux densities of class I methanol masers are more ...

  11. 78 FR 24061 - Minimum Technical Standards for Class II Gaming Systems and Equipment

    Science.gov (United States)

    2013-04-24

    ... ensuring the integrity of electronic Class II games and aids. 73 FR 60508, Oct. 10, 2008. The technical... Class II gaming system; and to clarify the term ``alternate standard.'' 77 FR 58473, Sept. 21, 2012. In... control standards (MICS) for Class II gaming. 77 FR 58708, Sept. 21, 2012. Similar to the part...

  12. 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.

  13. High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients' sera.

    Science.gov (United States)

    Ritz, Danilo; Gloger, Andreas; Weide, Benjamin; Garbe, Claus; Neri, Dario; Fugmann, Tim

    2016-05-01

    The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high-confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan-reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies. PMID:26992070

  14. Implication des peptides de fusion des glycoprotéines de fusion virales de classe I dans la fusion membranaire

    OpenAIRE

    Brasseur R.; Charloteaux B.; Lins L.; Lorin A.

    2007-01-01

    The implication of fusion peptides of class I viral fusion glycoproteins in the membrane fusion. Viral infection involves fusion between the viral envelope and the target cell plasmic membrane. The fusion is induced by a glycoprotein anchored in the viral envelope. After activation, the glycoprotein undergoes a conformational change inducing the exposure of a region named « fusion peptide » essential for the fusion process. Studies on glycoproteins and on isolated fusion peptides have allowed...

  15. 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.

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

    DEFF Research Database (Denmark)

    McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany; Remesh, Soumya G.; Kaever, Thomas; Bardet, Wilfried; Jackson, Kenneth; McLeod, Rima; Sette, Alessandro; Nielsen, Morten; Zajonc, Dirk M.; Blader, Ira J.; Peters, Bjoern; Hildebrand, William

    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 infected...

  17. TCR-like antibodies distinguish conformational and functional differences in two vs. four-domain auto-reactive MHC II-peptide complexes

    Science.gov (United States)

    Dahan, Rony; Tabul, Moran; Chou, Yuan K.; Meza-Romero, Roberto; Andrew, Shayne; Ferro, Adolph J.; Burrows, Gregory G.; Offner, Halina; Vandenbark, Arthur A.; Reiter, Yoram

    2011-01-01

    SUMMARY Antigen presenting cell-associated four-domain MHC class-II molecules play a central role in activating autoreactive CD4+ T-cells involved in Multiple Sclerosis (MS) and Type 1 Diabetes (T1D). In contrast, two-domain MHC-II structures with the same covalently-attached self peptide (Recombinant T-cell receptor Ligands=RTLs) can regulate pathogenic CD4+ T-cells and reverse clinical signs of experimental autoimmune diseases. RTL1000, comprised of the β1α1 domains of HLA-DR2 linked to the encephalitogenic human MOG-35-55 peptide, was recently shown to be safe and well-tolerated in a Phase I clinical trial in MS. To evaluate the opposing biological effects of four- vs. two-domain class-II structures, we screened phage Fab antibodies (Abs) for neutralizing activity of RTL1000. . Five different TCR-like Abs were identified that could distinguish between the two- vs. four-domain MHC peptide complexes, while the cognate TCR was unable to make such a distinction. Moreover, Fab detection of native two-domain HLA-DR structures in human plasma implies that there are naturally-occurring regulatory MHC-peptide complexes. These results demonstrate for the first time distinct conformational determinants characteristic of activating vs. tolerogenic MHC-peptide complexes involved in human autoimmunity. PMID:21469129

  18. Toward a network model of MHC class II-restricted antigen processing

    Directory of Open Access Journals (Sweden)

    Laurence C Eisenlohr

    2013-12-01

    Full Text Available The standard model of Major Histocompatibility Complex class II (MHCII-restricted antigen processing depicts a straightforward, linear pathway: Internalized antigens are converted into peptides that load in a chaperone dependent manner onto nascent MHCII in the late endosome, the complexes subsequently trafficking to the cell surface for recognition by CD4+ T cells (TCD4+. Several variations on this theme, both moderate and radical, have come to light but these alternatives have remained peripheral, the conventional pathway generally presumed to be the primary driver of TCD4+ responses. Here we continue to press for the conceptual repositioning of these alternatives toward the center while proposing that MHCII processing be thought of less in terms of discrete pathways and more in terms of a network whose major and minor conduits are variable depending upon many factors, including the epitope, the nature of the antigen, the source of the antigen, and the identity of the antigen-presenting cell.

  19. Synthesis and ESI mass spectrometric analysis of the association of mercury(II) with multi-cysteinyl peptides.

    Science.gov (United States)

    Ngu-Schwemlein, Maria; Lin, Xiuli; Rudd, Brent; Bronson, Matthew

    2014-04-01

    In order to gain more insight into the associations of mercury(II) with cysteinyl peptides, we investigated the effect of increasing cysteinyl residues on complex type formations. Three series of di-, tri-, and tetra-cysteinyl peptides, D[CGD]nCG (CP 2A, CP 3A, and CP 4A), E[CEG]nCG (CP 2B, CP 3B, and CP 4B) and E[CDG]nCG (CP 2C, CP 3C, and CP 4C), where n=1, 2, or 3, were prepared by microwave-assisted solid phase peptide synthesis. Complexes formed in different relative ratios of mercury(II) to cysteinyl peptides were characterized by electrospray orbitrap mass spectrometry utilizing complex specific mercury isotopic patterns. In equimolar mercury(II) to peptide ratio, all three series of di-, tri-, and tetra-cysteinyl peptides form predominantly the 1:1Hg(peptide) complex type, indicating that the intervening amino acid residues do not elicit preferential complex type formation. However, in non-equivalent mercury(II) to peptide ratio, the number of cysteinyl residues has a significant effect on the Hg:peptide stoichiometry in the complex formed. For example, in four times excess peptide, the 1:2Hg(peptide)2 and 1:1Hg(peptide) complexes are formed for di-cysteinyl peptides but not for the tri- and tetra-cysteinyl peptides. In contrast, the 2:1Hg2(peptide) and 1:1Hg(peptide) complexes are formed for the tri- and tetra-cysteinyl peptides. In excess mercury(II), CP 4C formed exclusively the 2:1Hg2(peptide) complex. The exact number of deprotonations observed for each complex could be derived from its signature mercury isotope pattern and monoisotopic peak mass. These multi-cysteinyl peptides present an attractive option for mercury chelation or environmental heavy metal remediation. PMID:24413258

  20. 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 ab

  1. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules

    OpenAIRE

    Yan, Jingbo; Parekh, Vrajesh V.; Mendez-Fernandez, Yanice; Olivares-Villagómez, Danyvid; Dragovic, Srdjan; Hill, Timothy; Roopenian, Derry C.; Joyce, Sebastian; Van Kaer, Luc

    2006-01-01

    Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present s...

  2. 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.

  3. Assessment of upper airways measurements in patients with mandibular skeletal Class II malocclusion

    OpenAIRE

    Silva, Nayanna Nadja e; Rosa Helena Wanderley Lacerda; Alexandre Wellos Cunha Silva; Tania Braga Ramos

    2015-01-01

    Objective: Mandibular Class II malocclusions seem to interfere in upper airways measurements. The aim of this study was to assess the upper airways measurements of patients with skeletal Class II malocclusion in order to investigate the association between these measurements and the position and length of the mandible as well as mandibular growth trend, comparing the Class II group with a Class I one.Methods:A total of 80 lateral cephalograms from 80 individuals aged between 10 and 17 years o...

  4. Assessment of upper airways measurements in patients with mandibular skeletal Class II malocclusion

    OpenAIRE

    Silva, Nayanna Nadja e; Lacerda, Rosa Helena Wanderley; Silva, Alexandre Wellos Cunha; Ramos, Tania Braga

    2015-01-01

    Objective: Mandibular Class II malocclusions seem to interfere in upper airways measurements. The aim of this study was to assess the upper airways measurements of patients with skeletal Class II malocclusion in order to investigate the association between these measurements and the position and length of the mandible as well as mandibular growth trend, comparing the Class II group with a Class I one. Methods: A total of 80 lateral cephalograms from 80 individuals aged between 10 and 17 years...

  5. Peptide‐MHC class I stability is a better predictor than peptide affinity of CTL immunogenicity

    DEFF Research Database (Denmark)

    Harndahl, Mikkel Nors; Rasmussen, Michael; Roder, Gustav; Dalgaard Pedersen, Ida; Sørensen, Mikael; Nielsen, Morten; Buus, Søren

    2012-01-01

    Efficient presentation of peptide‐MHC class I (pMHC‐I) complexes to immune T cells should benefit from a stable peptide‐MHC‐I interaction. However, it has been difficult to distinguish stability from other requirements for MHC‐I binding, for example, affinity. We have recently established a high......‐throughput assay for pMHC‐I stability. Here, we have generated a large database containing stability measurements of pMHC‐I complexes, and re‐examined a previously reported unbiased analysis of the relative contributions of antigen processing and presentation in defining cytotoxic T lymphocyte (CTL) immunogenicity...... [Assarsson et al., J. Immunol. 2007. 178: 7890–7901]. Using an affinity‐balanced approach, we demonstrated that immunogenic peptides tend to be more stably bound to MHC‐I molecules compared with nonimmunogenic peptides. We also developed a bioinformatics method to predict pMHC‐I stability, which suggested...

  6. Evaluation of the dental arch asymmetry in natural normal occlusion and Class II malocclusion individuals

    OpenAIRE

    Paulo Estevão Scanavini; Luiz Renato Paranhos; Fernando César Torres; Maria Helena Ferreira Vasconcelos; Renata Pilli Jóias; Marco Antonio Scanavini

    2012-01-01

    OBJECTIVE: To verify the presence and degree of asymmetry of dental arches in Brazilian individuals with natural normal occlusion and Class II, Divisions 1 and 2 malocclusions. METHODS: The study evaluated the symmetry of the maxillary and mandibular dental arches of 180 pairs of dental casts, divided into: Group I = 60 pairs of natural normal occlusion individuals; Group II = 60 pairs of Class II, Division 1 malocclusion individuals; and Group III = 60 pairs of Class II, Division 2 malocclus...

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

    Science.gov (United States)

    Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8positive T-cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presenta...

  8. 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.

  9. Removable functional appliances effective in patients with Class II malocclusions.

    Science.gov (United States)

    Madurantakam, Parthasarathy

    2016-03-01

    Data sourcesMedline (Pubmed), Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, Evidence-based Medicine, Scopus, LILACS database, Ovid database, Bibliografia Brasileira de Odontolgogia, Bandolier, Atypon Link, African Journals Online, ProQuest, Conference Paper Index, German National Library of Medicine, metaRegister of Controlled Trials.Study selectionRandomised Controlled Trials (RCT) or prospective Controlled Clinical Trials (pCCT) in patients with Class II malocclusions that compared at least one removable functional appliance (RFA) with a non-intervention control. Primary outcomes were angular measurements of skeletal, dental and soft tissue changes as measured by lateral cephalographs.Data extraction and synthesisTwo reviewers independently extracted data and assessed risk of bias. A third author assessed bias across studies. Pooling of data was done if similar control groups were used and if the same angular cephalometric measurements were reported. A random-effects model was used to analyse pooled estimates and results were expressed as mean differences (MDs) and 95% confidence intervals (CI). The extent and impact of heterogeneity was assessed.ResultsData were pooled from seventeen studies (seven RCTs and ten pCCT) involving 1031 patients with a mean age of 10.6 years. Most of the RCTs were associated with high risk of bias while most of the pCCTs were without serious methodological limitations. RFA treatment in Class II malocclusions was shown to have a statistically significant short-term effect on skeletal, dental and soft tissue relationships when compared to untreated controls. There is a minimal reduction of SNA (MD=-0.26 degree/year, 95% CI=-0.44 to -0.12 degree/year), minimal increase of SNB (MD=0.62 degree/year, 95% CI=0.36 to 0.88 degree/year) and a small decrease in ANB (MD= -1.14degree/year, 95% CI=-1.52 to 0.77 degree/year). Maxillary incisors were significantly

  10. Structural Basis for the Presentation of Tumor-Associated MHC Class II-Restricted Phosphopeptides to CD4+ T Cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Depontieu, F; Sidney, J; Salay, T; Engelhard, V; Hunt, D; Sette, A; Topalian, S; Mariuzza, R

    2010-01-01

    Dysregulated protein phosphorylation is a hallmark of malignant transformation. Transformation can generate major histocompatibility complex (MHC)-bound phosphopeptides that are differentially displayed on tumor cells for specific recognition by T cells. To understand how phosphorylation alters the antigenic identity of self-peptides and how MHC class II molecules present phosphopeptides for CD4{sup +} T-cell recognition, we determined the crystal structure of a phosphopeptide derived from melanoma antigen recognized by T cells-1 (pMART-1), selectively expressed by human melanomas, in complex with HLA-DR1. The structure revealed that the phosphate moiety attached to the serine residue at position P5 of pMART-1 is available for direct interactions with T-cell receptor (TCR) and that the peptide N-terminus adopts an unusual conformation orienting it toward TCR. This structure, combined with measurements of peptide affinity for HLA-DR1 and of peptide-MHC recognition by pMART-1-specific T cells, suggests that TCR recognition is focused on the N-terminal portion of pMART-1. This recognition mode appears to be distinct from that of foreign antigen complexes but is remarkably reminiscent of the way autoreactive TCRs engage self- or altered self-peptides, consistent with the tolerogenic nature of tumor-host immune interactions.

  11. Management of severe class II division II malocclusion using simplified MPA - A case report

    Directory of Open Access Journals (Sweden)

    Yugandhar Garlapati

    2013-01-01

    Full Text Available A fully established Class II Div. II malocclusion case with severe mandibular deficiency treated with simplified mandibular protraction appliance (MPA along with Begg′s looped archwire is presented. This type of case with antero-posterior and vertical skeletal dysplasia demands correction of the underlying skeletal malocclusions in growing patients. The task becomes very daunting especially in patients with skeletal deep bite with retroclined upper incisors. One such case treated to produce optimal skeletal and dentoalveolar relationship with the help of a fixed functional device is illustrated in this case report.

  12. Comprehensive analysis of cooperative gene mutations between class I and class II in de novo acute myeloid leukemia.

    Science.gov (United States)

    Ishikawa, Yuichi; Kiyoi, Hitoshi; Tsujimura, Akane; Miyawaki, Shuichi; Miyazaki, Yasushi; Kuriyama, Kazutaka; Tomonaga, Masao; Naoe, Tomoki

    2009-08-01

    Acute myeloid leukemia (AML) has been thought to be the consequence of two broad complementation classes of mutations: class I and class II. However, overlap-mutations between them or within the same class and the position of TP53 mutation are not fully analyzed. We comprehensively analyzed the FLT3, cKIT, N-RAS, C/EBPA, AML1, MLL, NPM1, and TP53 mutations in 144 newly diagnosed de novo AML. We found 103 of 165 identified mutations were overlapped with other mutations, and most overlap-mutations consisted of class I and class II mutations. Although overlap-mutations within the same class were found in seven patients, five of them additionally had the other class mutation. These results suggest that most overlap-mutations within the same class might be the consequence of acquiring an additional mutation after the completion both of class I and class II mutations. However, mutated genes overlapped with the same class were limited in N-RAS, TP53, MLL-PTD, and NPM1, suggesting the possibility that these irregular overlap-mutations might cooperatively participate in the development of AML. Notably, TP53 mutation was overlapped with both class I and class II mutations, and associated with morphologic multilineage dysplasia and complex karyotype. The genotype consisting of complex karyotype and TP53 mutation was an unfavorable prognostic factor in entire AML patients, indicating this genotype generates a disease entity in de novo AML. These results collectively suggest that TP53 mutation might be a functionally distinguishable class of mutation. PMID:19309322

  13. Inhibitory Effect of Curcumin-Cu(II) and Curcumin-Zn(II) Complexes on Amyloid-Beta Peptide Fibrillation

    OpenAIRE

    Rona Banerjee

    2014-01-01

    Mononuclear complexes of Curcumin with Cu(II) and Zn(II) have been synthesized and, characterized and their effects on the fibrillization and aggregation of amyloid-beta (Aβ) peptide have been studied. FTIR spectroscopy and atomic force microscopy (AFM) observations demonstrate that the complexes can inhibit the transition from less structured oligomers to β-sheet rich protofibrils which act as seeding factors for further fibrillization. The metal complexes also impart more improved inhibitor...

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

    DEFF Research Database (Denmark)

    Duus, K; Sandhu, N; Jørgensen, C S; Hansen, Paul Robert; Steinø, A; Thaysen-Andersen, M; Højrup, P; Houen, G

    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...

  15. Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice.

    Science.gov (United States)

    Maehr, René; Hang, Howard C; Mintern, Justine D; Kim, You-Me; Cuvillier, Armelle; Nishimura, Mikio; Yamada, Kenji; Shirahama-Noda, Kanae; Hara-Nishimura, Ikuko; Ploegh, Hidde L

    2005-06-01

    Class II MHC molecules survey the endocytic compartments of APCs and present antigenic peptides to CD4 T cells. In this context, lysosomal proteases are essential not only for the generation of antigenic peptides but also for proteolysis of the invariant chain to allow the maturation of class II MHC molecules. Recent studies with protease inhibitors have implicated the asparagine endopeptidase (AEP) in class II MHC-restricted Ag presentation. We now report that AEP-deficient mice show no differences in processing of the invariant chain or maturation of class II MHC products compared with wild-type mice. In the absence of AEP, presentation to primary T cells of OVA and myelin oligodendrocyte glycoprotein, two Ags that contain asparagine residues within or in proximity to the relevant epitopes was unimpaired. Cathepsin (Cat) L, a lysosomal cysteine protease essential for the development to CD4 and NK T cells, fails to be processed into its mature two-chain form in AEP-deficient cells. Despite this, the numbers of CD4 and NK T cells are normal, showing that the single-chain form of Cat L is sufficient for its function in vivo. We conclude that AEP is essential for processing of Cat L but not for class II MHC-restricted Ag presentation. PMID:15905550

  16. 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.

  17. Class II fusion protein of alphaviruses drives membrane fusion through the same pathway as class I proteins

    OpenAIRE

    Zaitseva, Elena; Mittal, Aditya; Griffin, Diane E.; Chernomordik, Leonid V.

    2005-01-01

    Viral fusion proteins of classes I and II differ radically in their initial structures but refold toward similar conformations upon activation. Do fusion pathways mediated by alphavirus E1 and influenza virus hemagglutinin (HA) that exemplify classes II and I differ to reflect the difference in their initial conformations, or concur to reflect the similarity in the final conformations? Here, we dissected the pathway of low pH–triggered E1-mediated cell–cell fusion by reducing the numbers of a...

  18. 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

    OpenAIRE

    Rogério Lacerda dos Santos; Antônio Carlos de Oliveira Ruellas

    2009-01-01

    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...

  19. Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2004-11-01

    Full Text Available Abstract The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes, encoded by members of the Alphaviridae and Flaviviridae, are comprised of three antiparallel beta sheet domains with an internal fusion peptide located at the end of domain II. Proteomics computational analyses indicate that the carboxyl terminal glycoprotein (Gc encoded by Sandfly fever virus (SAN, a phlebovirus, has a significant amino acid sequence similarity with envelope protein 1 (E1, the class II fusion protein of Sindbis virus (SIN, an Alphavirus. Similar sequences and common structural/functional motifs, including domains with a high propensity to interface with bilayer membranes, are located collinearly in SAN Gc and SIN E1. Gc encoded by members of each Bunyavirus genus share several sequence and structural motifs. These results suggest that Gc of Bunyaviridae, and similar proteins of Tenuiviruses and a group of Caenorhabditis elegans retroviruses, are class II viral fusion proteins. Comparisons of divergent viral fusion proteins can reveal features essential for virion:cell fusion, and suggest drug and vaccine strategies.

  20. Polymorphism and Balancing Selection of MHC Class II DAB Gene in 7 Selective Flounder (Paralichthys olivaceus Families

    Directory of Open Access Journals (Sweden)

    Min Du

    2011-01-01

    Full Text Available In order to determine the genetic variation of the MHC class IIB exon2 allele in the offspring, 700 fry from seven families of Japanese flounder challenged with V. anguillarum were studied, and different mortality rates were found in those families. Five to ten surviving and dead fry from each of the seven families were selected to study the MHC class II B exon2 gene with PCR and a direct sequencing method. One hundred and sixteen different exon2 sequences were found and 116 different alleles were identified, while a minimum of four loci were revealed in the MHC class II B exon2 gene. The ratio (dN/dS of nonsynonymous substitution (dN to synonymous substitutions (dS in the peptide-binding region (PBR of the MHC class IIB gene was 6.234, which indicated that balancing selection is acting on the MHC class IIB genes. The MHC IIB alleles were thus being passed on to their progeny. Some alleles were significantly more frequent in surviving than dead individuals. All together our data suggested that the alleles Paol-DAB*4301, Paol-DAB*4601, Paol-DAB*4302, Paol-DAB*3803, and Paol-DAB*4101 were associated with resistance to V. anguillarum in flounder.

  1. 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.

  2. Management of Class I and Class II Amalgam Restorations with Localized Defects: Five-Year Results

    Directory of Open Access Journals (Sweden)

    Javier Martin

    2013-01-01

    Full Text Available Replacement of dental restorations has been the traditional treatment for defective restorations. This five-year prospective clinical trial evaluated amalgam restorations with localized defects that were treated by means of repair or refurbishing. Fifty-two patients (50% female and 50% male, mean age 28.3±18.1 years, range 18–80 with 160 class I and class II defective restorations were included. The study focused on the application of two minimally invasive treatments for localized restoration defects and compared these with no treatment and total replacement as negative and positive controls, respectively. Restorations were assessed by two calibrated examiners according to modified U.S. Public Health Service criteria, including marginal adaptation, anatomic form, secondary caries, and roughness. At five years, recall was examined in 45 patients with 108 restorations (67.5%. The results suggest that repair treatment is as effective as total replacement of restorations with localized defects, reducing biological costs to the patient and providing new tools to the clinician. Refinishing restoration is a useful treatment for localized anatomic form defects.

  3. 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

  4. Structural of the class II enzyme of human liver alcohol dehydrogenase: combined cDNA and protein sequence determination of the π subunit

    International Nuclear Information System (INIS)

    The class II enzyme of human liver alcohol dehydrogenase was isolated, carboxymethylated, and cleaved with CNBr and proteolytic enzymes. Sequence analysis of peptides established structures corresponding to the π subunit. Two segments from the C-terminal region unique to π were selected for synthesis of oligodeoxyribonucleotide probes to screen a human liver cDNA library constructed in plasmid pT4. Sequence analysis of two identical hybridization-positive clones with cDNA inserts of about 2000 nucleotides gave the entire coding region of the π subunit, a 61-nucleotide 5' noncoding region and a 741-nucleotide 3' noncoding region containing four possible polyadenylation sites. Translation of the coding region yields a 391-residue polypeptide, which in all regions except the C-terminal segment corresponds to the protein structure as determined directly by peptide analysis. With the class I numbering system, the exception concerns a residue exchange at position 368, the actual C-terminus which is Phe-374 by peptide data but a 12 residue extension by cDNA data, and possibly two further residue exchanges at positions 303 and 312. The size difference might indicate the existence of posttranslational modifications of the mature protein or, in combination with the residue exchanges, the existence of polymorphism at the locus for class II subunits. The π subunit analyzed directly results in a 379-residue polypeptide and is the only class II size thus far known to occur in the mature protein. Comparison of the π structure with those of the class I subunits (α, β, and γ) reveals a homology with extensive differences. Large variations in segments affecting relationships at the active site and the area of subunit interactions account for the significant alterations of enzymatic specificities and other properties that differentiate class II from class I enzymes

  5. Cu(II) mediates kinetically distinct, non-amyloidogenic aggregation of amyloid-β peptides

    DEFF Research Database (Denmark)

    Pedersen, Jeppe T.; Østergaard, Jesper; Rozlosnik, Noemi; Gammelgaard, Bente; Heegaard, Niels H. H.

    2011-01-01

    aggregates, which shifted from fibrillar to non-fibrillar at increasing Cu(II):Aβ ratios. We observed dynamic morphological changes of the aggregates, and that the formation of spherical aggregates appeared to be a common morphological end point independent on the Cu(II) concentration. Experiments with Aβ1......Cu(II) ions are implicated in the pathogenesis of Alzheimer disease by influencing the aggregation of the amyloid-β (Aβ) peptide. Elucidating the underlying Cu(II)-induced Aβ aggregation is paramount for understanding the role of Cu(II) in the pathology of Alzheimer disease. The aim of this study...... was to characterize the qualitative and quantitative influence of Cu(II) on the extracellular aggregation mechanism and aggregate morphology of Aβ1-40 using spectroscopic, microelectrophoretic, mass spectrometric, and ultrastructural techniques. We found that the Cu(II):Aβ ratio in solution has a...

  6. 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

    become particularly attractive as first-line methods in epitope discovery. However, only a few so-called pan-specific prediction methods capable of predicting binding to any MHC molecule with known protein sequence are currently available, and all of them are limited to HLA-DR. Here, we present the first...... pan-specific method capable of predicting peptide binding to any HLA class II molecule with a defined protein sequence. The method employs a strategy common for HLA-DR, HLA-DP and HLA-DQ molecules to define the peptide-binding MHC environment in terms of a pseudo sequence. This strategy allows the......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....

  7. 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.

  8. 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 spectro...

  9. Bioavailability Enhancement Techniques for BCS Class II Drugs: A Review

    Directory of Open Access Journals (Sweden)

    Honey Kansara

    2015-03-01

    Full Text Available Traditionally, nearly 40% of the new chemical entities (NCEs identified by pharmaceutical industry screening programs have failed to be developed because of poor water-solubility, which makes their formulation difficult or even impossible. The solubility issues complicating the delivery of these new drugs also affect the delivery of many existing drugs. The various traditional and novel techniques that that can be used for solubility enhancement of BCS Class II drugs are briefly discussed in this article. The Traditional techniques that has been discussed in this article includes use of co-solvents, Hydrotropy, Micronization, change in dielectric constant of solvent, amorphousforms, chemical modification of drug, use of surfactants, inclusion complex, alteration of pH ofsolvent, use of hydrates or solvates, use of soluble prodrugs, application of ultrasonic waves, functional polymer technology, controlled precipitation technology, evaporative precipitation in aqueous solution, use of precipitation inhibitors, solvent deposition, precipitation, selective adsorption on insoluble carriers. Novel drug delivery technologies developed in recent years for solubility enhancement of insoluble drugs are size reduction technologies, lipid based delivery system, micellar technologies,porous micro particle technology. Solid Dispersion Technique and various types of solid dispersion systems have also been explained briefly.

  10. 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.

  11. 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.

  12. Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity.

    Science.gov (United States)

    Rasmussen, Michael; Fenoy, Emilio; Harndahl, Mikkel; Kristensen, Anne Bregnballe; Nielsen, Ida Kallehauge; Nielsen, Morten; Buus, Søren

    2016-08-15

    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 been quantified by the strength of the interaction, that is, the binding affinity, yet it has been shown that the stability of the peptide-MHC-I complex is a better correlate of immunogenicity compared with binding affinity. In this study, we have experimentally analyzed peptide-MHC-I complex stability of a large panel of human MHC-I allotypes and generated a body of data sufficient to develop a neural network-based pan-specific predictor of peptide-MHC-I complex stability. Integrating the neural network predictors of peptide-MHC-I complex stability with state-of-the-art predictors of peptide-MHC-I binding is shown to significantly improve the prediction of CTL epitopes. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCstabpan. PMID:27402703

  13. TCR-like antibodies distinguish conformational and functional differences in two vs. four-domain auto-reactive MHC II-peptide complexes

    OpenAIRE

    Dahan, Rony; Tabul, Moran; Yuan K. Chou; Meza-Romero, Roberto; Andrew, Shayne; Ferro, Adolph J.; Burrows, Gregory G.; Offner, Halina; Vandenbark, Arthur A.; Reiter, Yoram

    2011-01-01

    Antigen presenting cell-associated four-domain MHC class-II molecules play a central role in activating autoreactive CD4+ T-cells involved in Multiple Sclerosis (MS) and Type 1 Diabetes (T1D). In contrast, two-domain MHC-II structures with the same covalently-attached self peptide (Recombinant T-cell receptor Ligands=RTLs) can regulate pathogenic CD4+ T-cells and reverse clinical signs of experimental autoimmune diseases. RTL1000, comprised of the β1α1 domains of HLA-DR2 linked to the encepha...

  14. 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...

  15. 40 CFR 144.22 - Existing Class II enhanced recovery and hydrocarbon storage wells.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells. 144.22 Section 144.22 Protection of Environment ENVIRONMENTAL... of Underground Injection by Rule § 144.22 Existing Class II enhanced recovery and hydrocarbon storage wells. (a) An existing Class II enhanced recovery or hydrocarbon storage injection well is authorized...

  16. 40 CFR 82.15 - Prohibitions for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Prohibitions for class II controlled substances. 82.15 Section 82.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls § 82.15 Prohibitions for class II...

  17. 40 CFR 82.16 - Phaseout schedule of class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Phaseout schedule of class II controlled substances. 82.16 Section 82.16 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls § 82.16 Phaseout schedule of class II...

  18. HLA class I and class II haplotypes in admixed families from several regions of Mexico.

    Science.gov (United States)

    Barquera, Rodrigo; Zúñiga, Joaquín; Hernández-Díaz, Raquel; Acuña-Alonzo, Victor; Montoya-Gama, Karla; Moscoso, Juan; Torres-García, Diana; García-Salas, Claudia; Silva, Beatriz; Cruz-Robles, David; Arnaiz-Villena, Antonio; Vargas-Alarcón, Gilberto; Granados, Julio

    2008-02-01

    We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA-A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies. PMID:17904223

  19. Thermodynamics of the complexation of Hg(II) by cysteinyl peptide ligands using isothermal titration calorimetry

    International Nuclear Information System (INIS)

    The present study was undertaken to better understand the complexation of mercury (II) by cysteine, histidine, tryptophan, and their di- and tri-peptides. Their mercury (II) binding affinities and associated thermodynamic parameters are evaluated by isothermal titration calorimetry. Cysteine S-donor atoms form the strongest complexes, which can be attributed to a more exothermic Hg-S soft acid and soft base interaction. These thiol S-donor peptide ligands show two sequential binding for mercury (II). Their stability constants for the first binding (108 M-1 to >1010 M-1) are largely due to favorable contribution of the enthalpy term to the free energy of complexation. As more mercury (II) ions are added, this enthalpy contribution decreases and the free energy of the second binding (105 M-1 to 106 M-1) is partially compensated by the entropy term. The dependency of the fluorescence intensity for these peptides on mercury (II) concentration shows two different Stern-Volmer plots, which corroborates the calorimetric data and supports the formation of two types of stable complexes.

  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. Long-term pharyngeal airway changes after bionator treatment in adolescents with skeletal Class II malocclusions

    OpenAIRE

    Han, Seimin; Choi, Yoon Jeong; Chung, Chooryung J.; Kim, Ji Young; Kim, Kyung-Ho

    2014-01-01

    Objective The aim of this study was to evaluate long-term changes in the pharyngeal airway dimensions after functional appliance treatment in adolescents with skeletal Class II malocclusions. Methods Pharyngeal airway dimensions were compared between subjects with skeletal Class II malocclusions (n = 24; mean age: 11.6 ± 1.29 years) treated with a Class II bionator and age-matched control subjects with skeletal Class I occlusions (n = 24; mean age: 11.0 ± 1.21 years) using a series of lateral...

  2. Anti-Plasmodium Activity of Angiotensin II and Related Synthetic Peptides

    OpenAIRE

    Ceres Maciel; Vani Xavier de Oliveira Junior; Marcos Antonio Fázio; Rafael Nacif-Pimenta; Antonio Miranda; Pimenta, Paulo F. P.; Margareth Lara Capurro

    2008-01-01

    Plasmodium species are the causative agents of malaria, the most devastating insect-borne parasite of human populations. Finding and developing new drugs for malaria treatment and prevention is the goal of much research. Angiotensins I and II (ang I and ang II) and six synthetic related peptides designated Vaniceres 1-6 (VC1-VC6) were assayed in vivo and in vitro for their effects on the development of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the thoraces of th...

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

    Science.gov (United States)

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

    2006-09-15

    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 able to span the lipid bilayer and cannot form pores, but somehow they maintain their antibacterial efficacy. We describe an alternative mechanism by which members of the lantibiotic family kill Gram-positive bacteria by removing lipid II from the cell division site (or septum) and thus block cell wall synthesis. PMID:16973881

  4. Inhibition of Class II Major Histocompatibility Complex Antigen Processing by Escherichia coli Heat-Labile Enterotoxin Requires an Enzymatically Active A Subunit

    Science.gov (United States)

    Matousek, Milita P.; Nedrud, John G.; Cieplak, Witold; Harding, Clifford V.

    1998-01-01

    Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT) were found to inhibit intracellular antigen processing. Processing was not inhibited by mutant LT with attenuated ADP-ribosyltransferase activity, CT B or LT B subunit, which enhanced presentation of preexisting cell surface peptide-class II major histocompatibility complex complexes. Inhibition of antigen processing correlated with A subunit ADP-ribosyltransferase activity. PMID:9632629

  5. Characterization of major histocompatibility complex class I and class II genes from the Tasmanian devil (Sarcophilus harrisii).

    Science.gov (United States)

    Siddle, Hannah V; Sanderson, Claire; Belov, Katherine

    2007-09-01

    The Tasmanian devil (Sarcophilus harrisii) is currently threatened by an emerging wildlife disease, devil facial tumour disease. The disease is decreasing devil numbers dramatically and may lead to the extinction of the species. At present, nothing is known about the immune genes or basic immunology of the devil. In this study, we report the construction of the first genetic library for the Tasmanian devil, a spleen cDNA library, and the isolation of full-length MHC Class I and Class II genes. We describe six unique Class II beta chain sequences from at least three loci, which belong to the marsupial Class II DA gene family. We have isolated 13 unique devil Class I sequences, representing at least seven Class I loci, two of which are most likely non-classical genes. The MHC Class I sequences from the devil have little heterogeneity, indicating recent divergence. The MHC genes described here are most likely involved in antigen presentation and are an important first step for studying MHC diversity and immune response in the devil. PMID:17673996

  6. Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles

    OpenAIRE

    De la Hera, Belén; Urcelay, Elena; Brassat, David; Chan, Andrew; Vidal-Jordana, Angela; Salmen, Anke; Villar, Luisa Maria; Álvarez-Cermeño, José Carlos; Izquierdo, Guillermo; Fernández, Oscar; Oliver, Begoña; Saiz, Albert; Ara, Jose Ramón; Vigo, Ana G.; Arroyo, Rafael

    2014-01-01

    Objectives: We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. Methods: HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. Results:...

  7. Reduction of Cu(II) complexes of histidine and histidyl peptides. A pulse radiolysis study

    International Nuclear Information System (INIS)

    The reduction mechanism of Cu(II) complexes of histidine and histidyl peptides was investigated using the pulse radiolysis method. The hydrated electron, used as a reducing agent, was found to react with the complexes by a bimolecular process. In the Cu(II)-histidine and Cu(II)-glycyl-histidine complexes at pH 11, the reaction with the e/sub aq//sup -/ is direct with the Cu(II) ion and no secondary reactions were found to occur up to 5 msec after the pulse. In the Cu(II)-glycyl-histidine complex at pH 6.5 and Cu(II)-β-alanyl-histidine at pH 7.5, the decay of the electron was followed by the appearance of a transient absorption band centered at 360 nm. This band is assigned to the adduct of an electron in the imidazole ring of the histidyl peptides. The radical ion is formed by the direct reaction of the e/sub aq//sup -/ with the liganded histidyl residue. The Im decays via a first order process at the same rate at which the Cu(II) ion is reduced. CO2- reduces all the complexes studied via a bimolecular reaction. It is suggested that this is a direct reaction of the CO2-with the metal ion. An attempt to correlate these reaction steps to the reactivity of the reductants and to the structure of the complexes is made

  8. HLA Class II Haplotypic Association and DQCAR Microsatellite Polymorphisms in Croatian Patients with Psoriasis

    OpenAIRE

    Grubić, Z.; Žunec, R.; Kaštelan, M.; Čečuk-Jeličić, E.; Gruber, F; Kaštelan, A.

    2002-01-01

    The purpose of the present study was to investigate polymorphism of HLA class II haplotypic associations (HLA-DRB1, -DQA1, -DQB1) and DQCAR alleles in 78 Croatian patients with psoriasis. Patients were divided into two groups according to a family history of disease and age of onset: type I (positive family history and early onset) and type II (negative family history and late onset). The difference in frequency of HLA class II haplotypic associations between type I patients an...

  9. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDING: 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. CONCLUSIONS: 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.

  10. Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide.

    Science.gov (United States)

    Datta, G; Chaddha, M; Hama, S; Navab, M; Fogelman, A M; Garber, D W; Mishra, V K; Epand, R M; Epand, R F; Lund-Katz, S; Phillips, M C; Segrest, J P; Anantharamaiah, G M

    2001-07-01

    We have recently shown that a class A amphipathic peptide 5F with increased amphipathicity protected mice from diet-induced atherosclerosis (Garber et al. J. Lipid Res. 2001. 42: 545-552). We have now examined the effects of increasing the hydrophobicity of a series of homologous class A amphipathic peptides, including 5F, on physical and functional properties related to atherosclerosis inhibition by systematically replacing existing nonpolar amino acids with phenylalanine. The peptides, based on the sequence Ac-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-NH(2) (Ac-18A-NH(2) or 2F) were: 3F(3)(Ac-F(3)18A-NH(2)), 3F(14)(Ac-F(14)18A-NH(2)), 4F(Ac-F(3,14)18A-NH(2)), 5F(Ac-F(11,14,17) 18A-NH(2)), 6F(Ac-F(10,11,14,17)18A-NH(2)), and 7F(Ac-F(3,10,11,14,17) 18A-NH(2)). Measurements of aqueous solubility, HPLC retention time, exclusion pressure for penetration into an egg phosphatidylcholine (EPC) monolayer, and rates of EPC solubilization revealed an abrupt increase in the hydrophobicity between peptides 4F and 5F; this was accompanied by increased ability to associate with phospholipids. The peptides 6F and 7F were less effective, indicating a limit to increased hydrophobicity for promoting lipid interaction in these peptides. Despite this marked increase in lipid affinity, these peptides were less effective than apoA-I in activating the plasma enzyme, lecithin:cholesterol acyltransferase, with 5F activating LCAT the best (80% of apoA-I). Peptides 4F, 5F, and 6F were equally potent in inhibiting LDL-induced monocyte chemotactic activity. These studies suggest that an appropriate balance between peptide-peptide and peptide-lipid interactions is required for optimal biological activity of amphipathic peptides. These studies provide a rationale for the design of small apoA-I-mimetics with increased potency for atherosclerosis inhibition. PMID:11441137

  11. MHC class II antigen expression was different from MHC class I antigen expression in irradiated and recovering rat thymus

    International Nuclear Information System (INIS)

    We exposed rats to a heavy, but sublethal, dose of X-radiation that was calculated as the maximum that left them alive. Immediately after irradiation the rats lost body and thymus weight. The number of thymocytes decreased and the structure of the thymus was destroyed. The thymus weights then increased rapidly for a few days from day 7 followed by a slower increase. Immunohistochemically, the recovery of major histocompatibility complex (MHC) class II-positive cells in the thymus was slower than that of MHC class I-positive cells. Recovery of MHC class II-positive and ED1-positive cells in the thymus was slow, especially in the medulla. Thymus structure appeared similar to normal control animals on day 14, although the number of MHC class II- and ED1-positive cells in the medulla was lower than that of controls even 21 days after radiation exposure. The delay in recovery of MHC class II-positive stromal cells might affect the regeneration of thymocyte subpopulations after irradiation. (author)

  12. Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance

    OpenAIRE

    Ian A York; Brehm, Michael A.; Zendzian, Sophia; Towne, Charles F.; Rock, Kenneth L.

    2006-01-01

    CD8+ T cells respond to short peptides bound to MHC class I molecules. Although most antigenic proteins contain many sequences that could bind to MHC class I, few of these peptides actually stimulate CD8+ T cell responses. Moreover, the T cell responses that are generated often follow a very reproducible hierarchy to different peptides for reasons that are poorly understood. We find that the loss of a single enzyme, endoplasmic reticulum aminopeptidase 1 (ERAP1), in the antigen-processing pat...

  13. Diversity at the major histocompatibility complex Class II in the platypus, Ornithorhynchus anatinus.

    Science.gov (United States)

    Lillie, Mette; Woodward, Rachael E; Sanderson, Claire E; Eldridge, Mark D B; Belov, Katherine

    2012-07-01

    The platypus (Ornithorhynchus anatinus) is the sole survivor of a previously widely distributed and diverse lineage of ornithorhynchid monotremes. Its dependence on healthy water systems imposes an inherent sensitivity to habitat degradation and climate change. Here, we compare genetic diversity at the major histocompatibility complex (MHC) Class II-DZB gene and 3 MHC-associated microsatellite markers with diversity at 6 neutral microsatellite markers in 70 platypuses from across their range, including the mainland of Australia and the isolated populations of Tasmania, King Island, and Kangaroo Island. Overall, high DZB diversity was observed in the platypus, with 57 DZB β1 alleles characterized. Significant positive selection was detected within the DZB peptide-binding region, promoting variation in this domain. Low levels of genetic diversity were detected at all markers in the 2 island populations, King Island (endemic) and Kangaroo Island (introduced), with the King Island platypuses monomorphic at the DZB locus. Loss of MHC diversity on King Island is of concern, as the population may have compromised immunological fitness and reduced ability to resist changing environmental conditions. PMID:22563128

  14. Partial MHC class II constructs inhibit MIF/CD74 binding and downstream effects.

    Science.gov (United States)

    Benedek, Gil; Meza-Romero, Roberto; Andrew, Shayne; Leng, Lin; Burrows, Gregory G; Bourdette, Dennis; Offner, Halina; Bucala, Richard; Vandenbark, Arthur A

    2013-05-01

    MIF and its receptor, CD74, are pivotal regulators of the immune system. Here, we demonstrate for the first time that partial MHC class II constructs comprised of linked β1α1 domains with covalently attached antigenic peptides (also referred to as recombinant T-cell receptor ligands - RTLs) can inhibit MIF activity by not only blocking the binding of rhMIF to immunopurified CD74, but also downregulating CD74 cell-surface expression. This bifunctional inhibition of MIF/CD74 interactions blocked downstream MIF effects, including enhanced secretion of proinflammatory cytokines, anti-apoptotic activity, and inhibition of random migration that all contribute to the reversal of clinical and histological signs of EAE. Moreover, we demonstrate that enhanced CD74 cell-surface expression on monocytes in mice with EAE and subjects with multiple sclerosis can be downregulated by humanized RTLs, resulting in reduced MIF binding to the cells. Thus, binding of partial MHC complexes to CD74 blocks both the accessibility and availability of CD74 for MIF binding and downstream inflammatory activity. PMID:23576302

  15. Special classes of iron(II) azole spin crossover compounds

    OpenAIRE

    Koningsbruggen, Petra J. van; Gutlich, P.; Goodwin, HA

    2004-01-01

    In this chapter, selected results obtained so far on Fe(II) spin crossover compounds of 1,2,4-triazole, isoxazole and tetrazole derivatives are summarized and analysed. These materials include the only compounds known to have Fe(II)N(6) spin crossover chromophores consisting of six chemically identical heterocyclic ligands. Particular attention is paid to the coordination modes for substituted 1,2,4-triazole derivatives towards Fe(II) resulting in polynuclear and mononuclear compounds exhibit...

  16. Diversified Anchoring Features the Peptide Presentation of DLA-88*50801: First Structural Insight into Domestic Dog MHC Class I.

    Science.gov (United States)

    Xiao, Jin; Xiang, Wangzhen; Chai, Yan; Haywood, Joel; Qi, Jianxun; Ba, Limin; Qi, Peng; Wang, Ming; Liu, Jun; Gao, George F

    2016-09-15

    Canines represent a crucial animal model for studying human diseases and organ transplantation, as well as the evolution of domestic animals. MHCs, with a central role in cellular immunity, are commonly used in the study of dog population genetics and genome evolution. However, the molecular basis for the peptide presentation of dog MHC remains largely unknown. In this study, peptide presentation by canine MHC class I DLA-88*50801 was structurally determined, revealing diversified anchoring modes of the binding peptides. Flexible and large pockets composed of both hydrophobic and hydrophilic residues can accommodate pathogen-derived peptides with diverse anchor residues, as confirmed by thermostability measurements. Furthermore, DLA-88*50801 contains an unusual α2 helix with a large coil in the TCR contact region. These results further our understanding of canine T cell immunity through peptide presentation of MHC class I and shed light on the molecular basis for vaccine development for canine infectious diseases, for example, canine distemper virus. PMID:27511732

  17. 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.

  18. Kinetics of expression of interleukin 2 receptors on class I and class II restricted murine T cell clones

    International Nuclear Information System (INIS)

    The kinetics of interleukin 2 receptor (IL-2R) expression has been examined on various class I and class II restricted, influenza specific murine T cell clones. Expression and relative levels of IL-2R were examined by Fluorescence Activated Cell Sorter analysis utilizing 3 anti-murine IL-2R monoclonal antibodies. Receptor expression was analyzed by scatchard analysis using radiolabeled recombinant human interleukin 2 to access the number of high and low affinity IL-2R per cell as well as the affinity of binding. The clones tested bound all 3 monoclonal antibodies and were inhibited in an IL-2 dependent proliferation assay by the addition of the antibodies to the culture. There was, however, differing degrees of inhibition ranging up to 99%, depending on the clone and the antibody used. IL-2R expression was detectable as early as 4-6 hours after antigenic stimulation of quiescent cells. After maximal levels of receptors were expressed, which was about 24 hours after stimulation, expression of IL-2R decreased with time on all clones examined (both class I and class II restricted). Differing rates of receptor loss is seen however, with some class II restricted clones retaining relatively high levels of receptors

  19. Osmotically induced membrane tension modulates membrane permeabilization by class L amphipathic helical peptides: nucleation model of defect formation.

    OpenAIRE

    Polozov, I V; Anantharamaiah, G.M.; Segrest, J P; Epand, R M

    2001-01-01

    The mechanism of action of lytic peptides on membranes is widely studied and is important in view of potential medical applications. Previously (I. V. Polozov, A. I. Polozova, E. M. Tytler, G. M. Anantharamaiah, J. P. Segrest, G. A. Woolley, and R. M., Biochemistry, 36:9237--9245) we analyzed the mechanism of membrane permeabilization by 18L, the archetype lytic peptide featuring the class L amphipathic alpha-helix, according to the classification of Segrest et al. (J. P. Segrest, G. de Loof,...

  20. Predicted class-I aminoacyl tRNA synthetase-like proteins in non-ribosomal peptide synthesis

    Directory of Open Access Journals (Sweden)

    Iyer Lakshminarayan M

    2010-08-01

    Full Text Available Abstract Background Recent studies point to a great diversity of non-ribosomal peptide synthesis systems with major roles in amino acid and co-factor biosynthesis, secondary metabolism, and post-translational modifications of proteins by peptide tags. The least studied of these systems are those utilizing tRNAs or aminoacyl-tRNA synthetases (AAtRS in non-ribosomal peptide ligation. Results Here we describe novel examples of AAtRS related proteins that are likely to be involved in the synthesis of widely distributed peptide-derived metabolites. Using sensitive sequence profile methods we show that the cyclodipeptide synthases (CDPSs are members of the HUP class of Rossmannoid domains and are likely to be highly derived versions of the class-I AAtRS catalytic domains. We also identify the first eukaryotic CDPSs in fungi and in animals; they might be involved in immune response in the latter organisms. We also identify a paralogous version of the methionyl-tRNA synthetase, which is widespread in bacteria, and present evidence using contextual information that it might function independently of protein synthesis as a peptide ligase in the formation of a peptide- derived secondary metabolite. This metabolite is likely to be heavily modified through multiple reactions catalyzed by a metal-binding cupin domain and a lysine N6 monooxygenase that are strictly associated with this paralogous methionyl-tRNA synthetase (MtRS. We further identify an analogous system wherein the MtRS has been replaced by more typical peptide ligases with the ATP-grasp or modular condensation-domains. Conclusions The prevalence of these predicted biosynthetic pathways in phylogenetically distant, pathogenic or symbiotic bacteria suggests that metabolites synthesized by them might participate in interactions with the host. More generally, these findings point to a complete spectrum of recruitment of AAtRS to various non-ribosomal biosynthetic pathways, ranging from the

  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. Expression of MHC class II antigens in human B-cell leukaemia and non-Hodgkin's lymphoma.

    OpenAIRE

    Guy, K.; Krajewski, A S; Dewar, A E

    1986-01-01

    In this review we have summarized our experiences of serological analysis of MHC class II antigen expression in human B cell malignant disease. Cells from a large number of cases of B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) have been examined for expression of class II antigens. Using a number of monoclonal antibodies which in some cases are specific for class II subregion products (DP, DQ and DR), MHC class II antigens were detected by indirect immunofluores...

  3. A New Humanized HLA Transgenic Mouse Model of Multiple Sclerosis Expressing Class II on Mouse CD4 T Cells

    OpenAIRE

    Mangalam, Ashutosh; Rodriguez, Moses; David, Chella

    2007-01-01

    Among all the genetic factors associated with MS susceptibility, strongest association has been seen with expression of certain MHC class II molecules, although analysis of their exact function remains complicated. In general expression of class II is restricted to professional antigen presenting cells, however human but not mice CD4+ T cells express class II on their surface. Functional studies of classII+CD4+ T cells have been hampered due to lack of proper animal model. Here we describe de...

  4. Dual MHC class I and class II restriction of a single T cell receptor: distinct modes of tolerance induction by two classes of autoantigens.

    Science.gov (United States)

    Arsov, I; Vukmanović, S

    1999-02-15

    In the final stages of thymic development, immature T cells undergo three distinct processes (positive selection, negative selection, and lineage commitment) that all depend on interactions of thymocyte TCRs with MHC molecules. It is currently thought that TCRs are preferentially restricted by either MHC class I or class II molecules. In this report, we present direct evidence that the TCR previously described as H-Y/H-2Db specific cross-reacts with H-2IAb if expressed in CD4+ cells. We also demonstrate an increase in thymocyte numbers in H-Y TCR-trangenic mice deficient in MHC class II, suggesting a relatively discrete form of negative selection by MHC class II compared with that induced by H-Y/H-2Db. We propose that inability to generate CD4+ T cells expressing H-Y TCR in different experimental settings may be due to tolerance to self-MHC class II. These results, therefore, support an intriguing possibility that tolerance to self may influence and/or interfere with the outcome of the lineage commitment. PMID:9973472

  5. Structural features of class I H-2 antigens revealed by anti-peptide antibodies specific for intracytoplasmic determinants

    International Nuclear Information System (INIS)

    Rabbit antisera specific for synthetic peptides corresponding to each of the three intracytoplasmic exons (i.e. exons 6, 7 and 8) of the H-2K/sup b/ gene have been prepared and characterized in terms of their reactivity with class I H-2 molecules. Using lentil lectin-purified glycoproteins isolated from 125I-surface-labelled EL-4 (H-2/sup b/) cells, it has been possible to demonstrate that after clearance of the glycoprotein preparation with either anti-mouse β2-microglobulin, or alloantisera directed against H-2K/sup b/ and D/sup b/, there remains a non-β2-microglobulin-associated (i.e. free) class I heavy chain which can be immunoprecipitated by anti-peptide 8 antisera. This free class I heavy chain has the same 2D gel spot pattern as heavy chains from dimeric H-2K/sup b/, suggesting that conformational alterations resulting from the dissociation of β2-microglobulin, rather than chemical changes, are responsible for the loss of the alloantigenic determinants. Evidence has also been obtained indicating that the reaction of dimeric class I molecules with anti-peptide 6 induces the dissociation of β2-microglobulin, suggesting the potential for significant transmembrane conformational perturbations of the external domains as a result of interactions with the intracytoplasmic region

  6. 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...

  7. 76 FR 40377 - Agency Information Collection Activities; Proposed Collection; Comment Request; Class II Special...

    Science.gov (United States)

    2011-07-08

    ... without spermicidal lubricant containing nonoxynol-9 are classified in class II. They were originally... final rule (64 FR 13254, March 17, 1999). Because the packaging requirements for condoms are similar...

  8. Correction of an adult Class II division 2 individual using fixed functional appliance: A noncompliance approach

    Directory of Open Access Journals (Sweden)

    Shrinivas Basavaraddi

    2016-01-01

    Full Text Available This case report describes the application of fixed functional appliance in the treatment of an adult female having Class II division 2 malocclusion with retroclination of upper incisors. Fixed functional appliance was used to correct the overjet after the uprighting of upper incisors. Fixed functional appliance was fitted on a rigid rectangular arch wire. Application of fixed functional appliance achieved a good Class I molar relationship along with Class I canine relationship with normal overjet and overbite. Fixed functional appliance is effective in the treatment of Class II malocclusions, even in adult patients, and can serve as an alternate choice of treatment instead of orthognathic surgery. This is a case; wherein, fixed functional appliance was successfully used to relieve deep bite and overjet that was ensued after leveling and aligning. We demonstrate that fixed functional appliance can act as a “noncompliant corrector” and use of Class II elastics can be avoided.

  9. SKELETODENTAL CHANGES DURING THE PUBERTAL GROWTH SPURT IN CLASS II DIV I FEMALES: A LONGITUDINAL STUDY

    Directory of Open Access Journals (Sweden)

    M. Shirazi Sh. Etemad Moghadam

    1996-07-01

    Full Text Available This study aimed to determine the quantity and character of growth changes in the skeletodental complex of class II div I malocclusion during the pubertal growth spurt in females. Longitudinal hand-wrist radiographs were obtained from each subject and the onset anil end of the pubertal growth spurt was determined. Accordingly two lateral cephaliograms were taken, superimposed and analyzed. This sample consisted of 36 girls (18 class I ami 18 class II div I malocclusions, with no history of orthodontic treatment. Tl"e results indicate that true changes exist during the short period of pubertal growth spurt, which differ in amount ami direction, in various parts of the face am! cranium; also the pubertal growth spurt may have different effects on identical parameters, when compared between class I and class II div I subjects.

  10. Data on HLA class I/II profile in Brazilian pemphigus patients.

    Science.gov (United States)

    Franco Brochado, Maria José; Nascimento, Daniela Francisca; Saloum Deghaide, Neifi Hassan; Donadi, Eduardo Antonio; Roselino, Ana Maria

    2016-09-01

    Pemphigus are blistering autoimmune diseases related with genetic and environmental factors. Here we describe HLA genotyping in pemphigus patients. First, we review the HLA class I/II data on pemphigus reported in Brazilian samples and then present the HLA class I (-A, -B, -C) and class II (-DRB1, -DQA1, -DQB1) alleles related to susceptibility/resistance to pemphigus by comparing 86 patients with pemphigus foliaceus, 83 patients with pemphigus vulgaris, and 1592 controls from the northeastern region of the state of São Paulo, Southeastern Brazil. The data presented here are related to the manuscript "Differential HLA class I and class II associations in Pemphigus Foliaceus and Pemphigus Vulgaris patients from a prevalent Southeastern Brazilian region" Brochado et al. (2016) [1]. PMID:27331116

  11. 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

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

    OpenAIRE

    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 (...

  13. The Class II/1 anomaly of hereditary etiology vs. Thumb-sucking etiology

    OpenAIRE

    Pădure, H; Negru, AR; Stanciu, D

    2012-01-01

    Rationale: The etiology of class II division 1 Angle anomaly comprises many entities, including heredity and the vicious habit of sucking the finger. A close connection between the etiology and the clinical features needs to be outlined, in order to have a more appropriate treatment approach. Aim: This study aims to find common clinical features for two groups of Class II division 1 etiological factors (heredity and the vicious habit of sucking the finger), outlining a characteristic dento-fa...

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

    OpenAIRE

    Carmen L Mueller Storrer; Gabriela dos Santos Kummer; Shaban Mirco; Joao Cesar Zielak

    2014-01-01

    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 a...

  15. Camouflage of Severe Skeletal Class II Gummy Smile Patient Treated Nonsurgically with Mini Implants

    OpenAIRE

    Irfan Qamruddin; Fazal Shahid; Mohammad Khursheed Alam; Wafa Zehra Jamal

    2014-01-01

    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 de...

  16. Neurotrophins inhibit major histocompatibility class II inducibility of microglia: Involvement of the p75 neurotrophin receptor

    OpenAIRE

    Neumann, Harald; Misgeld, Thomas; Matsumuro, Kenji; Wekerle, Hartmut

    1998-01-01

    Major histocompatibility complex (MHC) molecules are rare in the healthy brain tissue, but are heavily expressed on microglial cells after inflammatory or neurodegenerative processes. We studied the conditions leading to the induction of MHC class II molecules in microglia by using explant cultures of neonatal rat hippocampus, a model of interacting neuronal networks. Interferon-γ (IFN-γ)-dependent MHC class II inducibility in microglia cells was very low, but strongly increased in the hippoc...

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

    OpenAIRE

    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 maxillary first molar extraction(s) and Begg brackets; outcome stability, influence on the position of maxillary third molars, interference of adjacent anatomical structures in closing extraction ...

  18. Wide tissue distribution of axolotl class II molecules occurs independently of thyroxin.

    Science.gov (United States)

    Völk, H; Charlemagne, J; Tournefier, A; Ferrone, S; Jost, R; Parisot, R; Kaufman, J

    1998-04-01

    Unlike most salamanders, the Mexican axolotl (Ambystoma mexicanum) fails to produce enough thyroxin to undergo anatomical metamorphosis, although a "cryptic metamorphosis" involving a change from fetal to adult hemoglobins has been described. To understand to what extent the development of the axolotl hemopoietic system is linked to anatomical metamorphosis, we examined the appearance and thyroxin dependence of class II molecules on thymus, blood, and spleen cells, using both flow cytometry and biosynthetic labeling followed by immunoprecipitation. Class II molecules are present on B cells as early as 7 weeks after hatching, the first time analyzed. At this time, most thymocytes, all T cells, and all erythrocytes lack class II molecules, but first thymocytes at 17 weeks, then T cells at 22 weeks, and finally erythrocytes at 26-27 weeks virtually all bear class II molecules. Class II molecules and adult hemoglobin appear at roughly the same time in erythrocytes. These data are most easily explained by populations of class II-negative cells being replaced by populations of class II-positive cells, and they show that the hemopoietic system matures at a variety of times unrelated to the increase of thyroxin that drives anatomical metamorphosis. We found that administration of thyroxin during axolotl ontogeny does not accelerate or otherwise affect the acquisition of class II molecules, nor does administration of drugs that inhibit thyroxin (sodium perchlorate, thiourea, methimazole, and 1-methyl imidazole) retard or abolish this acquisition, suggesting that the programs for anatomical metamorphosis and some aspects of hemopoietic development are entirely separate. PMID:9510551

  19. 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.

  20. 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 a

  1. 40 CFR 82.23 - Transfers of allowances of class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Transfers of allowances of class II controlled substances. 82.23 Section 82.23 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls § 82.23 Transfers of allowances of class...

  2. Molecular characterization of MHC class II in the Australian invasive cane toad reveals multiple splice variants.

    Science.gov (United States)

    Lillie, Mette; Cui, Jian; Shine, Richard; Belov, Katherine

    2016-07-01

    The cane toad has gained notoriety for its invasion across the Australian landscape, with significant impacts on the native Australian fauna. The invasion has accelerated over time, with invading cane toads adapted for highly dispersive traits. This, however, has come at the cost of the immune system, with lower investment in some immune functions. To investigate the cane toad's immunogenetics, we characterized four major histocompatibility complex (MHC) class IIA and three MHC class IIB loci. Preliminary observations suggest very low allelic diversity at all loci. We also observed various splice isoforms. One isoform seen at one class IIA and two class IIB loci was missing exon 2, which is essential to peptide binding and presentation. The other isoform, observed at a class IIA locus, is likely to be a soluble MHC product. These results may suggest a significant role of alternative splicing of MHC loci in the Australian cane toad. PMID:27233954

  3. Implication des peptides de fusion des glycoprotéines de fusion virales de classe I dans la fusion membranaire

    Directory of Open Access Journals (Sweden)

    Brasseur R.

    2007-01-01

    Full Text Available The implication of fusion peptides of class I viral fusion glycoproteins in the membrane fusion. Viral infection involves fusion between the viral envelope and the target cell plasmic membrane. The fusion is induced by a glycoprotein anchored in the viral envelope. After activation, the glycoprotein undergoes a conformational change inducing the exposure of a region named « fusion peptide » essential for the fusion process. Studies on glycoproteins and on isolated fusion peptides have allowed to better understand the mechanisms involved in membrane fusion. It was notably shown that fusion peptides induce fusion and leakage of membranes. These peptides are able to insert obliquely in a membrane when helical. This orientation induces lipid destabilisation, favouring membrane fusion. However, to date, none of these in vitro, in vivo or in silico studies has determined the minimal sequence required for membrane fusion. Using the obliquity-fusogenicity relationship, the latter was determined by molecular modelling for two viruses, the Human Immunodeficiency Virus and the Bovine Leukaemia Virus. These new results are of particular interest in the development of vaccines and antiviral drugs.

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

    International Nuclear Information System (INIS)

    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 127I. 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 125I 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 125I in iodopeptide D also increased with time

  5. Zinc Induces Dimerization of the Class II Major Histocompatibility Complex Molecule That Leads to Cooperative Binding to a Superantigen

    Energy Technology Data Exchange (ETDEWEB)

    Li,H.; Zhao, Y.; Guo, Y.; Li, Z.; Eislele, L.; Mourad, W.

    2007-01-01

    Dimerization of class II major histocompatibility complex (MHC) plays an important role in the MHC biological function. Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing specific T cell receptor V{beta} elements. Here we have used structural, sedimentation, and surface plasmon resonance detection approaches to investigate the molecular interactions between MAM and the class II MHC molecule HLA-DR1 in the context of a hemagglutinin peptide-(306-318) (HA). Our results revealed that zinc ion can efficiently induce the dimerization of the HLA-DR1/HA complex. Because the crystal structure of the MAM/HLA-DR1/hemagglutinin complex in the presence of EDTA is nearly identical to the structure of the complex crystallized in the presence of zinc ion, Zn{sup 2+} is evidently not directly involved in the binding between MAM and HLA-DR1. Sedimentation and surface plasmon resonance studies further revealed that MAM binds the HLA-DR1/HA complex with high affinity in a 1:1 stoichiometry, in the absence of Zn{sup 2+}. However, in the presence of Zn{sup 2+}, a dimerized MAM/HLA-DR1/HA complex can arise through the Zn{sup 2+}-induced DR1 dimer. In the presence of Zn{sup 2+}, cooperative binding of MAM to the DR1 dimer was also observed.

  6. Management of severe Class II malocclusion with sequential modified twin block and fixed orthodontic appliances

    Directory of Open Access Journals (Sweden)

    Sonal Chowdhary

    2016-01-01

    Full Text Available Functional appliance is an effective way of treating skeletal Class II malocclusion in children and adolescents. A 12 months stepwise mandibular advancement protocol with Herbst appliance has been proved to enhance condylar growth and improve mandibular prognathism. The present case report documents a 12-year-old boy presenting with Angle's Class II, division 1 malocclusion associated with excessive overjet (11 mm, 100% deep bite, and retrognathic mandible. He was treated by a phase I growth modification therapy using twin block appliance with lip pads in a stepwise mandibular advancement protocol followed by a phase II preadjusted Edgewise appliance therapy.

  7. 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.

  8. Assessment of upper airways measurements in patients with mandibular skeletal Class II malocclusion

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    Nayanna Nadja e Silva

    2015-10-01

    Full Text Available Objective: Mandibular Class II malocclusions seem to interfere in upper airways measurements. The aim of this study was to assess the upper airways measurements of patients with skeletal Class II malocclusion in order to investigate the association between these measurements and the position and length of the mandible as well as mandibular growth trend, comparing the Class II group with a Class I one.Methods:A total of 80 lateral cephalograms from 80 individuals aged between 10 and 17 years old were assessed. Forty radiographs of Class I malocclusion individuals were matched by age with forty radiographs of individuals with mandibular Class II malocclusion. McNamara Jr., Ricketts, Downs and Jarabak's measurements were used for cephalometric evaluation. Data were submitted to descriptive and inferential statistical analysis by means of SPSS 20.0 statistical package. Student's t-test, Pearson correlation and intraclass correlation coefficient were used. A 95% confidence interval and 5% significance level were adopted to interpret the results.Results:There were differences between groups. Oropharynx and nasopharynx sizes as well as mandibular position and length were found to be reduced in Class II individuals. There was a statistically significant positive correlation between the size of the oropharynx and Xi-Pm, Co-Gn and SNB measurements. In addition, the size of the nasopharynx was found to be correlated with Xi-Pm, Co-Gn, facial depth, SNB, facial axis and FMA.Conclusion: Individuals with mandibular Class II malocclusion were shown to have upper airways measurements diminished. There was a correlation between mandibular length and position and the size of oropharynx and nasopharynx.

  9. Evaluation of the dental arch asymmetry in natural normal occlusion and Class II malocclusion individuals

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    Paulo Estevão Scanavini

    2012-02-01

    Full Text Available OBJECTIVE: To verify the presence and degree of asymmetry of dental arches in Brazilian individuals with natural normal occlusion and Class II, Divisions 1 and 2 malocclusions. METHODS: The study evaluated the symmetry of the maxillary and mandibular dental arches of 180 pairs of dental casts, divided into: Group I = 60 pairs of natural normal occlusion individuals; Group II = 60 pairs of Class II, Division 1 malocclusion individuals; and Group III = 60 pairs of Class II, Division 2 malocclusion individuals. A device was used to measure dental midline deviation and the canine tip in the dental arches (in degrees. It was also verified the distance of the upper canines from the palatal suture, intercanine distance, and anteroposterior upper and lower first molar position. RESULTS: Dental arches of individuals from all groups presented asymmetry, regardless of the presence of malocclusion. Group I showed a lower asymmetry degree in relation to Groups II and III. The asymmetry in Groups II and III was similar. CONCLUSION: The dental arches of individuals with natural normal occlusion and with Class II, Division 1 and Division 2 malocclusions showed asymmetry. The asymmetry degree was higher in the mandibular dental arches than in the maxillary dental arches in all 3 evaluated groups.

  10. Anti-plasmodium activity of angiotensin II and related synthetic peptides.

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    Ceres Maciel

    Full Text Available Plasmodium species are the causative agents of malaria, the most devastating insect-borne parasite of human populations. Finding and developing new drugs for malaria treatment and prevention is the goal of much research. Angiotensins I and II (ang I and ang II and six synthetic related peptides designated Vaniceres 1-6 (VC1-VC6 were assayed in vivo and in vitro for their effects on the development of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the thoraces of the insects reduced mean intensities of infection in the mosquito salivary glands by 88% and 76%, respectively. Although the mechanism(s of action is not completely understood, we have demonstrated that these peptides disrupt selectively the P.gallinaceum cell membrane. Additionally, incubation in vitro of sporozoites with VC5 reduced the infectivity of the parasites to their vertebrate host. VC5 has no observable agonist effects on vertebrates, and this makes it a promising drug for malaria prevention and chemotherapy.

  11. 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.

  12. Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule.

    Science.gov (United States)

    Wynne, James W; Woon, Amanda P; Dudek, Nadine L; Croft, Nathan P; Ng, Justin H J; Baker, Michelle L; Wang, Lin-Fa; Purcell, Anthony W

    2016-06-01

    Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome-like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes. In this study, we used an affinity purification/mass spectrometry approach to demonstrate that a bat MHC class I molecule, Ptal-N*01:01, binds antigenic peptides and associates with peptide-loading complex components. We identified several bat MHC class I-binding partners, including calnexin, calreticulin, protein disulfide isomerase A3, tapasin, TAP1, and TAP2. Additionally, endogenous peptide ligands isolated from Ptal-N*01:01 displayed a relatively broad length distribution and an unusual preference for a C-terminal proline residue. Finally, we demonstrate that this preference for C-terminal proline residues was observed in Hendra virus-derived peptides presented by Ptal-N*01:01 on the surface of infected cells. To our knowledge, this is the first study to identify endogenous and viral MHC class I ligands for any bat species and, as such, provides an important avenue for monitoring and development of vaccines against major bat-borne viruses both in the reservoir and spillover hosts. Additionally, it will provide a foundation to understand the role of adaptive immunity in bat antiviral responses. PMID:27183594

  13. Sodium Dodecyl Sulfate Monomers Induce XAO Peptide Polyproline II to α-Helix Transition

    OpenAIRE

    Hong, Zhenmin; Damodaran, Krishnan; Asher, Sanford A.

    2014-01-01

    XAO peptide (Ac–X2A7O2–NH2; X: diaminobutyric acid side chain, −CH2CH2NH3 +; O: ornithine side chain, −CH2CH2CH2NH3 +) in aqueous solution shows a predominantly polyproline II (PPII) conformation without any detectable α-helix-like conformations. Here we demonstrate by using circular dichroism (CD), ultraviolet resonance Raman (UVRR) and nuclear magnetic resonance (NMR) spectroscopy that sodium dodecyl sulfate (SDS) monomers bind to XAO and induce formation of α-helix-like conformations. The ...

  14. Diversity in functional organization of class I and class II biotin protein ligase.

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    Sudha Purushothaman

    Full Text Available The cell envelope of Mycobacterium tuberculosis (M. tuberculosis is composed of a variety of lipids including mycolic acids, sulpholipids, lipoarabinomannans, etc., which impart rigidity crucial for its survival and pathogenesis. Acyl CoA carboxylase (ACC provides malonyl-CoA and methylmalonyl-CoA, committed precursors for fatty acid and essential for mycolic acid synthesis respectively. Biotin Protein Ligase (BPL/BirA activates apo-biotin carboxyl carrier protein (BCCP by biotinylating it to an active holo-BCCP. A minimal peptide (Schatz, an efficient substrate for Escherichia coli BirA, failed to serve as substrate for M. tuberculosis Biotin Protein Ligase (MtBPL. MtBPL specifically biotinylates homologous BCCP domain, MtBCCP(87, but not EcBCCP(87. This is a unique feature of MtBPL as EcBirA lacks such a stringent substrate specificity. This feature is also reflected in the lack of self/promiscuous biotinylation by MtBPL. The N-terminus/HTH domain of EcBirA has the self-biotinable lysine residue that is inhibited in the presence of Schatz peptide, a peptide designed to act as a universal acceptor for EcBirA. This suggests that when biotin is limiting, EcBirA preferentially catalyzes, biotinylation of BCCP over self-biotinylation. R118G mutant of EcBirA showed enhanced self and promiscuous biotinylation but its homologue, R69A MtBPL did not exhibit these properties. The catalytic domain of MtBPL was characterized further by limited proteolysis. Holo-MtBPL is protected from proteolysis by biotinyl-5' AMP, an intermediate of MtBPL catalyzed reaction. In contrast, apo-MtBPL is completely digested by trypsin within 20 min of co-incubation. Substrate selectivity and inability to promote self biotinylation are exquisite features of MtBPL and are a consequence of the unique molecular mechanism of an enzyme adapted for the high turnover of fatty acid biosynthesis.

  15. Reduced classes and curve counting on surfaces II: calculations

    CERN Document Server

    Kool, M

    2011-01-01

    We calculate the "surface part" of the reduced residue stable pair theory on the canonical bundle $K_S$ of a projective surface $S$. For fixed curve class $\\beta\\in H^2(S)$ the results are entirely topological, depending on $\\beta^2, \\beta.c_1(S), c_1(S)^2, c_2(S), b_1(S)$ and invariants of the ring structure on $H^*(S)$ such as the Pfaffian of $\\beta$ considered as an element of $\\Lambda^2 H^1(S)^*$. We also give conditions under which this calculates the full 3-fold reduced residue theory of $K_S$. This is related to the reduced residue Gromov-Witten theory of $S$ via the MNOP conjecture. When the surface has no holomorphic 2-forms this can be expressed as saying that certain Gromov-Witten invariants of $S$ are topological. Our method uses the results of \\cite{KT1} to express the reduced virtual cycle in terms of Euler classes of bundles over a natural smooth ambient space.

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

    OpenAIRE

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

    2013-01-01

    Objective 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. Methods 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...

  17. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a “molecular ruler” mechanism

    OpenAIRE

    Chang, Shih-Chung; Momburg, Frank; Bhutani, Nidhi; Goldberg, Alfred L.

    2005-01-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an IFN-γ-induced aminopeptidase in the endoplasmic reticulum that trims longer precursors to the antigenic peptides presented on MHC class I molecules. We recently reported that purified ERAP1 trimmed N-extended precursors but spared peptides of 8-9 residues, the length required for binding to MHC class I molecules. Here, we show another remarkable property of ERAP1: that it strongly prefers substrates 9-16 residues long, the lengths of peptid...

  18. Fixed Lingual Mandibular Growth Modificator: a new appliance for Class II correction

    Directory of Open Access Journals (Sweden)

    Osama Hasan Alali

    2013-08-01

    Full Text Available INTRODUCTION: This article demonstrates the description and use of a new appliance for Class II correction. MATERIAL AND METHODS: A case report of a 10-year 5 month-old girl who presented with a skeletally-based Class II division 1 malocclusion (ANB = 6.5º on a slightly low-angle pattern, with ML-NSL angle of 30º and ML-NL angle of 22.5º. Overjet was increased (7 mm and associated with a deep bite. RESULTS: Overjet and overbite reduction was undertaken with the new appliance, Fixed Lingual Mandibular Growth Modificator (FLMGM. CONCLUSION: FLMGM may be effective in stimulating the growth of the mandible and correcting skeletal Class II malocclusions. Clinicians can benefit from the unique clinical advantages that FLMGM provides, such as easy handling and full integration with bracketed appliance at any phase.

  19. Non-neutral evolution and reciprocal monophyly of two expressed Mhc class II B genes in Leach's storm-petrel.

    Science.gov (United States)

    Dearborn, Donald C; Gager, Andrea B; Gilmour, Morgan E; McArthur, Andrew G; Hinerfeld, Douglas A; Mauck, Robert A

    2015-02-01

    The major histocompatibility complex (Mhc) is subject to pathogen-mediated balancing selection and can link natural selection with mate choice. We characterized two Mhc class II B loci in Leach's storm-petrel, Oceanodroma leucorhoa, focusing on exon 2 which encodes the portion of the protein that binds pathogen peptides. We amplified and sequenced exon 2 with locus-specific nested PCR and Illumina MiSeq using individually barcoded primers. Repeat genotyping of 78 single-locus genotypes produced identical results in 77 cases (98.7%). Sequencing of messenger RNA (mRNA) from three birds confirmed expression of both loci, consistent with the observed absence of stop codons or frameshifts in all alleles. In 48 birds, we found 9 and 12 alleles at the two loci, respectively, and all 21 alleles translated to unique amino acid sequences. Unlike many studies of duplicated Mhc genes, alleles of the two loci clustered into monophyletic groups. Consistent with this phylogenetic result, interlocus gene conversion appears to have affected only two short fragments of the exon. As predicted under a paradigm of pathogen-mediated selection, comparison of synonymous and non-synonymous substitution rates found evidence of a history of positive selection at putative peptide binding sites. Overall, the results suggest that the gene duplication event leading to these two loci is not recent and that point mutations and positive selection on the peptide binding sites may be the predominant forces acting on these genes. Characterization of these loci sets the stage for population-level work on the evolutionary ecology of Mhc in this species. PMID:25416539

  20. Kinetics of the inhibition of calcium/calmodulin-dependent protein kinase II by pea protein-derived peptides.

    Science.gov (United States)

    Li, Huan; Aluko, Rotimi E

    2005-11-01

    Calcium/calmodulin-dependent protein kinase II (CaMKII) catalyzes the phosphorylation of various cellular proteins and excessive activities have been implicated in the pathogenesis of various chronic diseases. We hypothesized that positively charged peptides can be produced through enzymatic hydrolysis of pea proteins; such peptides could then bind to negatively charged calmodulin (CaM) at a physiological pH level and inhibit CaMKII activity. Pea protein isolate was hydrolyzed with an alkaline protease (alcalase) and filtered through a 1000-mol wt cutoff membrane. The permeate, which contained low-molecular weight peptides, was used to isolate cationic peptides on an SP-Sepharose column by ion exchange chromatography. Separation of the permeate on the SP-Sepharose column yielded two fractions with net positive charges that were subsequently used for enzyme inhibition studies. Fraction I eluted earlier from the column and contained lower contents of lysine and arginine than Fraction II, which eluted later. Results show that both peptide fractions inhibited CaMKII activity mostly in a competitive manner, although kinetic data suggested that inhibition by Fraction II may be of the mixed type. Kinetic analysis (K(m) and K(i)) showed that affinity of peptides in Fraction II for CaM was more than that in Fraction I, which was directly correlated with the higher inhibitory properties of Fraction II against CaMKII. The results suggest that it may be possible to use pea protein-derived cationic peptides to modulate CaMKII activities. PMID:16111873

  1. Linkage of bacterial protein synthesis and presentation of MHC class I-restricted Listeria monocytogenes-derived antigenic peptides.

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    Silke Grauling-Halama

    Full Text Available The processing and MHC class I-restricted presentation of antigenic peptides derived from the p60 protein of the facultative intracellular bacterium Listeria monocytogenes is tightly linked to bacterial protein synthesis. We used non-linear regression analysis to fit a mathematical model of bacterial antigen processing to a published experimental data set showing the accumulation and decay of p60-derived antigenic peptides in L. monocytogenes-infected cells. Two alternative models equally describe the experimental data. The simulation accounting for a stable and a hypothetical rapidly degraded form of antigen predicts that the antigenic peptides p60 217-225 and p60 449-457 are derived from a putative instable form of p60 with an average intracellular half-life of approximately 3 minutes accounting for approximately 31% of all p60 molecules synthesized. The alternative model predicts that both antigenic peptides are processed from p60 degraded intracellularly with a half-life of 109 min and that antigen processing only occurs as long as bacterial protein synthesis is not inhibited. In order to decide between both models the intracellular accumulation of p60 in infected cells was studied experimentally and compared with model predictions. Inhibition of p60 degradation by the proteasome inhibitor epoxomicin revealed that during the first 3 h post infection approximately 30% of synthesized p60 molecules were degraded. This value is significantly lower than the approximately 50% degradation of p60 that would be expected in the presence of the predicted putative short-lived state of p60 and also fits precisely with the predictions of the alternative model, indicating that the tight connection of bacterial protein biosynthesis and antigen processing and presentation of L. monocyctogenes-derived antigenic peptides is not caused by the presence of a highly instable antigenic substrate.

  2. Association of class II human histocompatibility leukocyte antigens with rheumatic fever.

    OpenAIRE

    Ayoub, E M; Barrett, D J; Maclaren, N K; Krischer, J P

    1986-01-01

    The association of class I and II HLA antigens with rheumatic fever and its manifestations was examined in 72 patients, including 48 blacks and 24 Caucasians. No significant association was found between class I antigens and rheumatic fever. In contrast, HLA-DR2 and HLA-DR4 phenotypes were encountered in a significantly higher frequency in black and Caucasian patients with rheumatic fever, respectively, compared with the control populations (P less than 0.005). The most significant associatio...

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

    OpenAIRE

    Rashmi Bhat; Ravi M. Subrahmanya

    2014-01-01

    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 w...

  4. Relationship between vertical facial patterns and dental arch form in class II malocclusion

    OpenAIRE

    Grippaudo, Cristina; Oliva, Bruno; Greco, Anna Lucia; Sferra, Simone; Deli, Roberto

    2013-01-01

    Background The purpose of this study is to evaluate the relationship between dental arch form and the vertical facial pattern determined by the angle between the mandibular plane and the anterior cranial base (Sella-nasion/mandibular plane angle (SN-MP)) in skeletal class II untreated patients. Methods A sample of 73 Caucasians patients with untreated skeletal class II in permanent dentition was divided into three groups according to the values of the angle SN-MP. An evaluation of the arch fo...

  5. Is traditional treatment a good option for an adult with a Class II deepbite malocclusion?

    Science.gov (United States)

    Abdo Quintão, Catia Cardoso; Miguel, Jose Augusto Mendes; Brunharo, Ione Portela; Zanardi, Gustavo; Feu, Daniela

    2012-01-01

    The Tweed-Merrifield directional force technique is a useful treatment approach for a patient with a Class II malocclusion with dentoalveolar protrusion. The purpose of this case report was to present the diagnosis and treatment descriptions of a patient with an Angle Class II malocclusion complicated by tooth losses, severe dentoalveolar protrusion, and skeletal discrepancy. Treatment involved extraction of the maxillary first premolars, high-pull headgear to enhance anchorage, and high-pull J-hook headgear to retract and intrude the maxillary anterior segments. A successful outcome was achieved with traditional orthodontic treatment in this borderline surgical case. PMID:22196191

  6. Stability of molar relationship after non-extraction Class II malocclusion treatment

    OpenAIRE

    Darwin Vaz de Lima; Karina Maria Salvatore de Freitas; Marcos Roberto de Freitas; Guilherme Janson; José Fernando Castanha Henriques; Arnaldo Pinzan

    2013-01-01

    OBJECTIVE: This study aimed to evaluate the stability of molar relationship after non-extraction treatment of Class II malocclusion. METHODS: The sample comprised 39 subjects (16 females, 23 males) with initial Class II malocclusion treated with no extractions, using fixed appliances. Mean age at the beginning of treatment was 12.94 years, at the end of treatment was 15.14 years and at post-retention stage was 21.18 years. Mean treatment time was 2.19 years and mean time of post-treatment eva...

  7. Improved results in proteomics by use of local and peptide-class specific false discovery rates

    Directory of Open Access Journals (Sweden)

    Bukowski-Wills Jimi-Carlo

    2009-06-01

    Full Text Available Abstract Background Proteomic protein identification results need to be compared across laboratories and platforms, and thus a reliable method is needed to estimate false discovery rates. The target-decoy strategy is a platform-independent and thus a prime candidate for standardized reporting of data. In its current usage based on global population parameters, the method does not utilize individual peptide scores optimally. Results Here we show that proteomic analyses largely benefit from using separate treatment of peptides matching to proteins alone or in groups based on locally estimated false discovery rates. Our implementation reduces the number of false positives and simultaneously increases the number of proteins identified. Importantly, single peptide identifications achieve defined confidence and the sequence coverage of proteins is optimized. As a result, we improve the number of proteins identified in a human serum analysis by 58% without compromising identification confidence. Conclusion We show that proteins can reliably be identified with a single peptide and the sequence coverage for multi-peptide proteins can be increased when using an improved estimation of false discovery rates.

  8. A Review of Class I and Class II Pet Food Recalls Involving Chemical Contaminants from 1996 to 2008

    OpenAIRE

    Rumbeiha, Wilson; Morrison, Jamie

    2010-01-01

    Commercial pet food in USA is generally safe, but adulteration does occur. Adulterated food has to be recalled to protect pets and public health. All stakeholders, including food firms, distributors, and government agencies such as the Food and Drug Administration (FDA) participate in food recall. The objective of this review is to describe the pet food recall procedure from start to finish, and to review class I and II pet food recalls from 1996 to 2008, with a specific focus on those due to...

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

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    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

  10. Linear short histidine and cysteine modified arginine peptides constitute a potential class of DNA delivery agents.

    Science.gov (United States)

    Mann, Anita; Shukla, Vasundhara; Khanduri, Richa; Dabral, Spoorti; Singh, Harpal; Ganguli, Munia

    2014-03-01

    The success of gene therapy relies on the development of safe and efficient multifunctional carriers of nucleic acids that can overcome extra- and intracellular barriers, protect the nucleic acid and mediate its release at the desired site allowing gene expression. Peptides bear unique properties that are indispensable for any carrier, e.g., they can mediate DNA condensation, cellular targeting, membrane translocation, endosomal escape and nuclear localization. In an effort to design a multifunctional peptide, we have modified an arginine homopeptide R16 by replacement of seven arginines with histidines and addition of one cysteine at each end respectively to impart endosomal escape property while maintaining the DNA condensation and release balance. Addition of histidines imparts endosomal escape property to arginine homopeptide, but their arrangement with respect to arginines is more critical in controlling DNA condensation, release and transfection efficiency. Intriguingly, R5H7R4 peptide where charge/arginine is distributed in blocks is preferred for strong condensation while more efficient transfection is seen in the variants R9H7 and H4R9H3, which exhibit weak condensation and strong release. Addition of cysteine to each of these peptides further fine-tuned the condensation-release balance without application of any oxidative procedure unlike other similar systems reported in the literature. This resulted in a large increase in the transfection efficiency in all of the histidine modified peptides irrespective of the arginine and histidine positions. This series of multifunctional peptides shows comparable transfection efficiency to commercially available transfection reagent Lipofectamine 2000 at low charge ratios, with simple preparative procedure and exhibits much less toxicity. PMID:24476132

  11. 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.

  12. Biochemical Characterization of the Split Class II Ribonucleotide Reductase from Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Mikael Crona

    Full Text Available The opportunistic pathogen Pseudomonas aeruginosa can grow under both aerobic and anaerobic conditions. Its flexibility with respect to oxygen load is reflected by the fact that its genome encodes all three existing classes of ribonucleotides reductase (RNR: the oxygen-dependent class I RNR, the oxygen-indifferent class II RNR, and the oxygen-sensitive class III RNR. The P. aeruginosa class II RNR is expressed as two separate polypeptides (NrdJa and NrdJb, a unique example of a split RNR enzyme in a free-living organism. A split class II RNR is also found in a few closely related γ-Proteobacteria. We have characterized the P. aeruginosa class II RNR and show that both subunits are required for formation of a biologically functional enzyme that can sustain vitamin B12-dependent growth. Binding of the B12 coenzyme as well as substrate and allosteric effectors resides in the NrdJa subunit, whereas the NrdJb subunit mediates efficient reductive dithiol exchange during catalysis. A combination of activity assays and activity-independent methods like surface plasmon resonance and gas phase electrophoretic macromolecule analysis suggests that the enzymatically active form of the enzyme is a (NrdJa-NrdJb2 homodimer of heterodimers, and a combination of hydrogen-deuterium exchange experiments and molecular modeling suggests a plausible region in NrdJa that interacts with NrdJb. Our detailed characterization of the split NrdJ from P. aeruginosa provides insight into the biochemical function of a unique enzyme known to have central roles in biofilm formation and anaerobic growth.

  13. Major histocompatibility complex class II-associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L

    OpenAIRE

    1996-01-01

    The invariant chain (Ii) is associated with major histocompatibility complex class II molecules during early stages of their intracellular transport. In an acidic endosomal/lysosomal compartment, it is proteolytically cleaved and removed from class II heterodimers. Participation of aspartic and cysteine proteases has been observed in in vitro degradation of Ii, but the specific enzymes responsible for its in vivo processing are as yet undefined. We have previously isolated a noncovalent compl...

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

    Science.gov (United States)

    Khumsarn, Nattida; Patanaporn, Virush; Jotikasthira, Dhirawat

    2016-01-01

    Purpose 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). Materials and Methods 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. Results 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. Conclusion 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. PMID:27358819

  15. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene

    DEFF Research Database (Denmark)

    Blume, N; Petersen, J S; Andersen, L C;

    1992-01-01

    Synthetic peptides representing unique sequences in rat proinsulin C-peptide I and II were used to generate highly specific antisera, which, when applied on sections of normal rat pancreas, confirm a homogeneous coexpression of the two C-peptides in all islet beta-cells. Insulin gene expression is...... insulin-producing cells showed highly differential expression at the cellular level of the three proinsulin C-peptide immunoreactivities, as follows: C-peptide I greater than human C-peptide greater than C-peptide II. The fractions of cells expressing human C-peptide and C-peptide II decreased in time and...... species of proinsulin-C-peptide immunoreactivity but still at high levels. However, rat C-peptide II and human C-peptide were often colocalized, even in later passages. In situ hybridization studies combined with the immunocytochemical data suggest that the differential expression occurs at the level of...

  16. 37 GHz Methanol Masers : Horsemen of the Apocalypse for the Class II Methanol Maser Phase?

    Science.gov (United States)

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

    2011-12-01

    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.

  17. 37 GHz METHANOL MASERS : HORSEMEN OF THE APOCALYPSE FOR THE CLASS II METHANOL MASER PHASE?

    Energy Technology Data Exchange (ETDEWEB)

    Ellingsen, S. P.; Breen, S. L. [School of Mathematics and Physics, University of Tasmania, Private Bag 37, Hobart, TAS 7001 (Australia); Sobolev, A. M. [Astronomical Observatory, Ural Federal University, Lenin avenue 51, 620000 Ekaterinburg (Russian Federation); Voronkov, M. A.; Caswell, J. L. [CSIRO Astronomy and Space Science, Australia Telescope National Facility, P.O. Box 76, Epping, NSW 1710 (Australia); Lo, N., E-mail: Simon.Ellingsen@utas.edu.au [Departamento de Astronomia, Universidad de Chile, Camino El Observatorio 1515, Las Condes, Santiago, Casilla 36-D (Chile)

    2011-12-01

    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.

  18. 37 GHz METHANOL MASERS : HORSEMEN OF THE APOCALYPSE FOR THE CLASS II METHANOL MASER PHASE?

    International Nuclear Information System (INIS)

    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.

  19. 37 GHz methanol masers : Horsemen of the Apocalypse for the class II methanol maser phase?

    CERN Document Server

    Ellingsen, S P; 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 towards a sample of 70 high-mass star formation regions. We primarily searched towards 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 hypothesised 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.

  20. 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.

  1. 78 FR 14015 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Powered Patient Transport

    Science.gov (United States)

    2013-03-04

    ..., 1998 (63 FR 3142). Section 510(m)(2) of the FD&C Act provides that FDA may exempt a device from..., p. 3.) In the Federal Register of June 1, 2012 (77 FR 32642), FDA published a notice announcing that... against the criteria laid out in the Class II 510(k) Exemption Guidance and in 63 FR 3142, and agrees...

  2. The effect of anterior inclined plane treatment on the dentoskeletal of Class II division 1 patients

    Directory of Open Access Journals (Sweden)

    Emami Meibodi

    2007-09-01

    Full Text Available Most of Class II malocclusions are due to underdeveloped mandible with increased overjet and overbite. Lack of incisal contact results in the extrusion of the upper and lower anterior dentoalveolar complex, which helps to lock the mandible and prevent its normal growth and development, and this abnormality is exaggerated by soft tissue imbalance. The purpose of this study was to evaluate the skeletal and dental changes in patients treated with anterior inclined plane appliance in growing patients with moderate Class II Division 1 having deep overbite. In this study, 25 patients, including 15 girls and 10 boys, with a mean age of 9 ±1.2 years were selected; all of them presented with moderate Class II deep bite with increased overjet and normal or horizontal growth pattern. Pre- and post-treatment X-rays and photos for an average of 8 months were taken. The statistical assessment of the data suggested that there were no significant changes in the vertical skeletal parameters. The mandibular incisors were protruded, whereas the maxillary incisors were retruded. Overbite and overjet were also reduced. There was significant increase in the mandibular length. The results revealed that in mixed dentition patients, the inclined plane corrected Class II discrepancies mostly through dentoskeletal changes.

  3. 75 FR 17093 - Neurological and Physical Medicine Devices; Designation of Special Controls for Certain Class II...

    Science.gov (United States)

    2010-04-05

    ... Physical Medicine Devices; Designation of Special Controls for Certain Class II Devices and Exemption From... and Drug Administration (FDA) is proposing to amend certain neurological device and physical medicine.... Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of...

  4. Very few indications justify early treatment for severe Class II malocclusions

    NARCIS (Netherlands)

    Ren, Yijin

    2004-01-01

    DESIGN: This was a single-centre two-phased, parallel, randomised clinical trial (RCT) conducted over a period of more than 10 years. INTERVENTION: Children were enrolled who had severe (=7 mm overjet) Class II malocclusions and who were developmentally at least a year before their peak pubertal gro

  5. 77 FR 58473 - Minimum Technical Standards for Class II Gaming Systems and Equipment

    Science.gov (United States)

    2012-09-21

    ... Class II Games. 73 FR 60508. The rule added a new part to the Commission's regulations establishing a.... 75 FR 70680. On April 4, 2011, after consulting with tribes and reviewing all comments, the NIGC... review. 76 FR 18457. Part 547 was included in the third regulatory group reviewed pursuant to the NRR....

  6. Current Teaching of Proximal Retention Grooves for Class II Amalgam Preparations.

    Science.gov (United States)

    Moore, David L.

    1992-01-01

    A survey gathered information on methods of class II amalgam preparation taught in 59 dental schools. Focus was on the teaching and testing of proximal retention groove use, stated rationale for placing retention grooves, and the relationship of the instruction to board criteria for cavity preparation. (MSE)

  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

    2013-01-01

    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 investigate

  8. Guided tissue regeneration in the treatment of class II furcation defects

    Directory of Open Access Journals (Sweden)

    Tatiana Miranda DELIBERADOR

    2008-12-01

    Full Text Available Introduction: Numerous surgical techniques have been evaluated toattempt the regeneration of furcation defects. Objective and literature review: Among the regenerative techniques, guided tissue regeneration(GTR has been largely used in the treatment of class II furcation defects, the main indication for GTR. Several clinical studies have compared the GTR technique with surgical debridement alone for the treatment of class II furcation defects in mandibular molars. A number of membrane materials have been tested in those studies.Varying results have been observed using non-absorbable expanded polytetrafluoroethylene (e-PTFE membranes. In some studies, the difference between the treatments was not clinically significant. When second generation absorbable membranes were used, the clinicalresults were also variable. However, some clinical studies foundfavorable results using the GTR technique, especially when a polylactic acid membrane was used. Similar modest results were observed when absorbable and non-absorbable membranes were compared clinically in the treatment of class II furcation defects in mandibular molars.Significant differences were not found between the membranes for most of the clinical parameters evaluated.Conclusion: Considering the literature, it can be concluded that the use of GTR for the treatment of mandibular molars with class II furcation defects yielded highly variable and unpredictable results.

  9. 40 CFR 82.19 - Apportionment of baseline consumption allowances for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Apportionment of baseline consumption allowances for class II controlled substances. 82.19 Section 82.19 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls §...

  10. 40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Class II Controlled Substances a B Appendix B to Subpart A of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls Pt. 82, Subpt. A, App. B Appendix B to Subpart A...

  11. 40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Recordkeeping and reporting requirements for class II controlled substances. 82.24 Section 82.24 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls § 82.24 Recordkeeping...

  12. 40 CFR 82.17 - Apportionment of baseline production allowances for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Apportionment of baseline production allowances for class II controlled substances. 82.17 Section 82.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and Consumption Controls §...

  13. 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

    -activated human T-cells. In both tonsillar B-lymphocytes and B-cell leukemia lines, p72syk was rapidly phosphorylated on tyrosine residues following HLA-DR cross-linking. Tyrosine phosphorylation of p72syk induced through ligation of either the B-cell antigen receptor or class II molecules was potently inhibited...... 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-DR in...... antibody induced receptor ligation, bacterial superantigen (SEA and SEB) treatment of HLA-DR+ T-cells stimulated ZAP-70 tyrosine phosphorylation, consistent with class II transmembrane signaling by ligation of HLA-DR and V beta in cis. Modulation of the TCR/CD3 led to abrogation of class II induced ZAP-70...

  14. 78 FR 42942 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-07-18

    ... corporate audit agreement pursuant to EPA's policy on Incentives for Self- Policing: Discovery, Disclosure, Correction and Prevention of Violations (Audit Policy), 65 FR 19618 (Apr. 11, 2000), regarding 88 office... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and...

  15. 75 FR 4552 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment, and Opportunity...

    Science.gov (United States)

    2010-01-28

    ... Violations Final Policy Statement (Audit Policy), 65 FR 19618 (Apr. 11, 2000). Hydro also provided supplemental audit reports in 2006 and 2007. EPA and Hydro have signed an administrative Consent Agreement... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment, and...

  16. 78 FR 5800 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-01-28

    ..., Correction and Prevention of Violations (Audit Policy), 65 FR 19,618 (April 11, 2000). EPA determined that AboveNet's disclosures satisfied all the conditions set forth in the Audit Policy, and therefore qualify... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and...

  17. 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...... association of HLA alleles and KIR ligands according to OCB status in MS patients (n=3876). Specific KIR ligands were associated with patients when compared to controls (n=3148), supporting a role for NK cells in MS pathogenesis. HLA class I alleles and KIR ligands did not differ between OCB phenotypes, but...... HLA class II associations were convincingly replicated....

  18. Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis.

    Science.gov (United States)

    van Luijn, Marvin M; Kreft, Karim L; Jongsma, Marlieke L; Mes, Steven W; Wierenga-Wolf, Annet F; van Meurs, Marjan; Melief, Marie-José; der Kant, Rik van; Janssen, Lennert; Janssen, Hans; Tan, Rusung; Priatel, John J; Neefjes, Jacques; Laman, Jon D; Hintzen, Rogier Q

    2015-06-01

    C-type lectins are key players in immune regulation by driving distinct functions of antigen-presenting cells. The C-type lectin CLEC16A gene is located at 16p13, a susceptibility locus for several autoimmune diseases, including multiple sclerosis. However, the function of this gene and its potential contribution to these diseases in humans are poorly understood. In this study, we found a strong upregulation of CLEC16A expression in the white matter of multiple sclerosis patients (n = 14) compared to non-demented controls (n = 11), mainly in perivascular leukocyte infiltrates. Moreover, CLEC16A levels were significantly enhanced in peripheral blood mononuclear cells of multiple sclerosis patients (n = 69) versus healthy controls (n = 46). In peripheral blood mononuclear cells, CLEC16A was most abundant in monocyte-derived dendritic cells, in which it strongly co-localized with human leukocyte antigen class II. Treatment of these professional antigen-presenting cells with vitamin D, a key protective environmental factor in multiple sclerosis, downmodulated CLEC16A in parallel with human leukocyte antigen class II. Knockdown of CLEC16A in distinct types of model and primary antigen-presenting cells resulted in severely impaired cytoplasmic distribution and formation of human leucocyte antigen class II-positive late endosomes, as determined by immunofluorescence and electron microscopy. Mechanistically, CLEC16A participated in the molecular machinery of human leukocyte antigen class II-positive late endosome formation and trafficking to perinuclear regions, involving the dynein motor complex. By performing co-immunoprecipitations, we found that CLEC16A directly binds to two critical members of this complex, RILP and the HOPS complex. CLEC16A silencing in antigen-presenting cells disturbed RILP-mediated recruitment of human leukocyte antigen class II-positive late endosomes to perinuclear regions. Together, we identify CLEC16A as a pivotal gene in multiple sclerosis

  19. Sodium dodecyl sulfate monomers induce XAO peptide polyproline II to α-helix transition.

    Science.gov (United States)

    Hong, Zhenmin; Damodaran, Krishnan; Asher, Sanford A

    2014-09-11

    XAO peptide (Ac-X2A7O2-NH2; X: diaminobutyric acid side chain, -CH2CH2NH3(+); O: ornithine side chain, -CH2CH2CH2NH3(+)) in aqueous solution shows a predominantly polyproline II (PPII) conformation without any detectable α-helix-like conformations. Here we demonstrate by using circular dichroism (CD), ultraviolet resonance Raman (UVRR) and nuclear magnetic resonance (NMR) spectroscopy that sodium dodecyl sulfate (SDS) monomers bind to XAO and induce formation of α-helix-like conformations. The stoichiometry and the association constants of SDS and XAO were determined from the XAO-SDS diffusion coefficients measured by pulsed field gradient NMR. We developed a model for the formation of XAO-SDS aggregate α-helix-like conformations. Using UVRR spectroscopy, we calculated the Ramachandran ψ angle distributions of aggregated XAO peptides. We resolved α-, π- and 3(10)-helical conformations and a turn conformation. XAO nucleates SDS aggregation at SDS concentrations below the SDS critical micelle concentration. The XAO4-SDS16 aggregates have four SDS molecules bound to each XAO to neutralize the four side chain cationic charges. We propose that the SDS alkyl chains partition into a hydrophobic core to minimize the hydrophobic area exposed to water. Neutralization of the flanking XAO charges enables α-helix formation. Four XAO-SDS4 aggregates form a complex with an SDS alkyl chain-dominated hydrophobic core and a more hydrophilic shell where one face of the α-helix peptide contacts the water environment. PMID:25121643

  20. Structural Basis for the Recognition of Mutant Self by a Tumor-Specific, MHC Class II-Restricted T Cell Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Deng,L.; Langley, R.; Brown, P.; Xu, G.; Teng, L.; Wang, Q.; Gonzales, M.; Callender, G.; Nishimura, M.; et al.

    2007-01-01

    Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.

  1. Combinatorial assembly of simple and complex D-lysergic acid alkaloid peptide classes in the ergot fungus Claviceps purpurea.

    Science.gov (United States)

    Ortel, Ingo; Keller, Ullrich

    2009-03-13

    The ergot fungus Claviceps purpurea produces both ergopeptines and simple d-lysergic acid alkylamides. In the ergopeptines, such as ergotamine, d-lysergic acid is linked to a bicyclic tripeptide in amide-like fashion, whereas in the d-lysergylalkanolamides it is linked to an amino alcohol derived from alanine. We show here that these compound classes are synthesized by a set of three non-ribosomal lysergyl peptide synthetases (LPSs), which interact in a combinatorial fashion for synthesis of the relevant product. The trimodular LPS1 assembles with LPS2, the d-lysergic acid recruiting module, to synthesize the d-lysergyltripeptide precursors of ergopeptines from d-lysergic acid and the three amino acids of the peptide chain. Alternatively, LPS2 can assemble with a distinct monomodular non-ribosomal peptide synthetase (NRPS) subunit (ergometrine synthetase) to synthesize the d-lysergic acid alkanolamide ergometrine from d-lysergic acid and alanine. The synthesis proceeds via covalently bound d-lysergyl alanine and release of dipeptide as alcohol with consumption of NADPH. Enzymatic and immunochemical analyses showed that ergometrine synthetase is most probably the enzyme LPS3 whose gene had been identified previously as part of the ergot alkaloid biosynthesis gene cluster in C. purpurea. Inspections of all LPS sequences showed no recognizable peptide linkers for their protein-protein interactions as in NRPS subunits of bacteria. Instead, they all carry conserved N-terminal domains (C0-domains) with similarity to the C-terminal halves of NRPS condensation domains pointing to an alternative mechanism of subunit-subunit interactions in fungal NRPS systems. Phylogenetic analysis of LPS modules and the C0-domains suggests that these enzyme systems most probably evolved by module duplications and rearrangements from a bimodular ancestor. PMID:19139103

  2. A randomized controlled 27 years follow up of three resin composites in Class II restorations

    DEFF Research Database (Denmark)

    Pallesen, Ulla; van Dijken, Jan WV

    2015-01-01

    Objective: To evaluate the durability of three conventional resin composites in Class II restorations during 27 years. Methods: Thirty participants, 25 female and 5 male (mean age 38.2 years, range 25–63), received at least three (one set) as similar as possible Class II restorations of moderate...... size. The three cavities were chosen at random to be restored with a chemical-cured (Clearfil Posterior) and two visible light-cured resin composites (Adaptic II, Occlusin). A chemical-cured enamel bonding agent (Clearfil New Bond) was applied after Ca(OH)2 covering of dentin and enamel etch. Marginal.......1%), followed by occlusal wear (21.6%) and material fracture (18.9%). Non-acceptable color match was seen in 24 (28.3%) of the restorations (AII 2, CP 16, O 6). Cox regression-analysis showed significant influence of the covariates tooth type, caries risk, and bruxing activity of the participants. Conclusions...

  3. Positive allosteric modulators to peptide GPCRs:a promising class of drugs

    Institute of Scientific and Technical Information of China (English)

    Tamas BARTFAI; Ming-wei WANG

    2013-01-01

    The task of finding selective and stable peptide receptor agonists with low molecular weight,desirable pharmacokinetic properties and penetrable to the blood-brain barrier has proven too difficult for many highly coveted drug targets,including receptors for endothelin,vasoactive intestinal peptide and galanin.These receptors and ligand-gated ion channels activated by structurally simple agonists such as glutamate,glycine and GABA present such a narrow chemical space that the design of subtype-selective molecules capable of distinguishing a dozen of glutamate and GABA receptor subtypes and possessing desirable pharmacokinetic properties has also been problematic.In contrast,the pharmaceutical industry demonstrates a remarkable success in developing 1,4-benzodiazepines,positive allosteric modulators (PMAs) of the GABAA receptor.They were synthesized over 50 years ago and discovered to have anxiolytic potential through an in vivo assay.As exemplified by Librium,Valium and Dormicum,these allosteric ligands of the receptor became the world's first blockbuster drugs.Through molecular manipulation over the past 2 decades,including mutations and knockouts of the endogenous ligands or their receptors,and by in-depth physiological and pharmacological studies,more peptide and glutamate receptors have become well-validated drug targets for which an agonist is sought.In such cases,the pursuit for PAMs has also intensified,and a working paradigm to identify drug candidates that are designed as PAMs has emerged.This review,which focuses on the general principles of finding PAMs of peptide receptors in the 21st century,describes the workflow and some of its resulting compounds such as PAMs of galanin receptor 2 that act as potent anticonvulsant agents.

  4. 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

    CTL staining and manipulation. This has enabled a complete mapping of all HLA-I specificities (“the Human MHC Project”). Here, we demonstrate that these approaches can be applied to other species. We systematically transferred domains of the frequently expressed swine MHC-I molecule, SLA-1*0401, onto...... 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...

  5. 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

  6. 76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-02-07

    ... cooling systems for aesthetic use may comply with the requirement of special controls for class II devices..., FDA is publishing a final rule classifying contact cooling systems for aesthetic use into class II... current thinking on contact cooling systems for aesthetic use. It does not create or confer any rights...

  7. HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma

    NARCIS (Netherlands)

    Diepstra, Arjan; van Imhoff, Gustaaf W.; Karim-Kos, Henrike E.; van den Berg, Anke; te Meerman, Gerard J.; Niens, Marijke; Nolte, Ilja M.; Bastiaannet, Esther; Schaapveld, Michael; Vellenga, Edo; Poppema, Sibrand

    2007-01-01

    Purpose The neoplastic Hodgkin Reed-Sternberg ( HRS) cells in classical Hodgkin's lymphoma ( cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown. Patients and Methods Immunohistochemistry results for HLA class II were evaluated in 292 p

  8. 40 CFR 144.21 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells.

    Science.gov (United States)

    2010-07-01

    ... recovery and hydrocarbon storage) and III wells. 144.21 Section 144.21 Protection of Environment... hydrocarbon storage) and III wells. (a) An existing Class I, II (except enhanced recovery and hydrocarbon... decision; or (9) For Class II wells (except enhanced recovery and hydrocarbon storage), five years...

  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

    ... Pressure Wound Therapy (NPWT).'' This guidance document describes a means by which non-powered suction apparatus devices intended for NPWT may comply with the requirement of special controls for class II devices... suction apparatus devices intended for NPWT into class II (special controls). This guidance document...

  10. Active suppression of major histocompatibility complex class II gene expression during differentiation from B cells to plasma cells

    International Nuclear Information System (INIS)

    Constitutive expression of major histocompatibility complex class II genes is acquired very early in B-cell ontogeny and is maintained up to the B-cell blast stage. Terminal differentiation in plasma cells is, however, accompanied by a loss of class II gene expression. In B cells this gene system is under the control of several loci encoding transacting factors with activator function, one of which, the aIr-1 gene product, operates across species barriers. In this report human class II gene expression is shown to be extinguished in somatic cell hybrids between the human class II-positive B-cell line Raji and the mouse class-II negative plasmacytoma cell line P3-U1. Since all murine chromosomes are retained in these hybrids and no preferential segregation of a specific human chromosome is observed, the results are compatible with the presence of suppressor factors of mouse origin, operating across species barriers and inhibiting class II gene expression. Suppression seems to act at the level of transcription or accumulation of class II-specific mRNA, since no human, and very few murine, class II transcripts are detectable in the hybrids

  11. 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)...

  12. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Science.gov (United States)

    2010-04-01

    ... authority. (k) Door access detection. All components of the Class II gaming system that are locked in order... Class II gaming system component that reads account access media shall be located within a secure... direct control of a gaming operation employee or agent shall be located within a secure, locked...

  13. 25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY... instrument accepted by the Class II gaming system shall be tracked independently per financial instrument... attendant pay. Each type of financial instrument paid by the Class II Gaming System shall be...

  14. The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation

    International Nuclear Information System (INIS)

    KSHV LANA1, a latent protein expressed during chronic infection to maintain a viral genome, inhibits major histocompatibility complex class I (MHC I) peptide presentation in cis as a means of immune evasion. Through deletional cloning, we localized this function to the LANA1 central repeat 1 (CR1) subregion. Other CR subregions retard LANA1 translation and proteasomal processing but do not markedly inhibit LANA1 peptide processing by MHC I. Inhibition of proteasomal processing ablates LANA1 peptide presentation. Direct expression of LANA1 within the endoplasmic reticulum (ER) overcomes CR1 inhibition suggesting that CR1 acts prior to translocation of cytoplasmic peptides into the ER. By physically separating CR1 from other subdomains, we show that LANA1 evades MHC I peptide processing by a mechanism distinct from other herpesviruses including Epstein-Barr virus (EBV). Although LANA1 and EBV EBNA1 are functionally similar, they appear to use different mechanisms to evade host cytotoxic T lymphocyte surveillance.

  15. The Microfloral Analysis of Secondary Caries Biofilm around Class I and Class II Composite and Amalgam Fillings

    Directory of Open Access Journals (Sweden)

    Mo Si-su

    2010-08-01

    Full Text Available Abstract Background Secondary caries is responsible for 60 percent of all replacement restorations in the typical dental practice. The diversity of the bacterial sources and the different types of filling materials could play a role in secondary caries. The aim of this study was to determine and compare the microbial spectrum of secondary caries biofilms around amalgam and composite resin restorations. Methods Clinical samples were collected from freshly extracted teeth diagnosed with clinical secondary caries. Samples were categorized into four groups according to the types of restoration materials and the classification of the cavity. Biofilms were harvested from the tooth-restoration interface using a dental explorer and after dilution were incubated on special agars. The bacteria were identified using the biochemical appraisal system. Statistical calculations were carried out using SPSS11.5 software to analyze the prevalence of the bacteria involved in secondary caries. Results Samples from a total of four groups were collected: two groups were collected from amalgam restorations, each had 21 samples from both Class I and Class II caries; and the other two groups were from composite resin restorations, each had 13 samples from both class I and class II caries. Our results showed: (1 Anaerobic species were dominant in both restoration materials. (2 In terms of the types of individual bacteria, no significant differences were found among the four groups according to the geometric mean of the detected bacteria (P > 0.05. However, there were significant differences among the detected bacteria within each group (P 0.05, but showed significant differences among the detected bacteria in each group (P 0.05, however, the detection rate of each bacterium within each group was statistically different among the detected bacteria (P Conclusions The proportion of obligatory anaerobic species was much greater than the facultative anaerobic species in the

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

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Montero, Ana; Leman, Luke J.; Ghadiri, M. Reza

    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 HD......6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines....

  17. 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......6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines....

  18. Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii).

    Science.gov (United States)

    Cheng, Yuanyuan; Sanderson, Claire; Jones, Menna; Belov, Katherine

    2012-07-01

    The largest remaining carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii), is currently under threat of extinction due to a fatal contagious cancer-devil facial tumour disease. Low major histocompatibility complex (MHC) class I diversity is believed to have contributed to the transmission of the tumour allograft through devil populations. Here, we report low MHC class II variability in this species, with DA β chain genes (Saha-DAB1, 2 and 3) exhibiting very limited diversity and the sole α chain gene (Saha-DAA) monomorphic. Three, six and three alleles were found at Saha-DAB1, 2 and 3, respectively, with a predominant allele found at each locus. Heterozygosity at these three loci is low in the eastern population and modestly higher in northwestern individuals. The results are indicative of a selective sweep likely due to an infectious disease resulting in the fixation of selectively favoured alleles and depletion of genetic diversity at devil class II loci. Several attempts were made to isolate the other marsupial classical class II gene family, namely, DB, resulting in only one DBB pseudogene being found. These findings further support the view that this species has a compromised capacity to respond to pathogen evolution, emerging infectious diseases and environmental changes. PMID:22460528

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

    International Nuclear Information System (INIS)

    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 (PIK3C2α) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2α mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2α 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 PIK3C2α can modulate HCC cell growth.

  20. Protein kinase C betaII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury.

    Science.gov (United States)

    Omiyi, Didi; Brue, Richard J; Taormina, Philip; Harvey, Margaret; Atkinson, Norrell; Young, Lindon H

    2005-08-01

    Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) betaII peptide inhibitor was used to test the hypothesis that PKC betaII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC betaII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC betaII inhibitor (10 microM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt(max)) cardiac function indices (p < 0.01). The PKC betaII inhibitor at 10 microM significantly increased endothelial NO release from a basal value of 1.85 +/- 0.18 pmol NO/mg tissue to 3.49 +/- 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 +/- 0.01 to 0.02 +/- 0.004 (p < 0.01) at 10 microM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC betaII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC betaII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs. PMID:15878997

  1. 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.

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

    International Nuclear Information System (INIS)

    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)

  3. A step-by-step overview of the dynamic process of epitope selection by major histocompatibility complex class II for presentation to helper T cells.

    Science.gov (United States)

    Sadegh-Nasseri, Scheherazade

    2016-01-01

    T cell antigen receptors (TCRs) expressed on cytotoxic or helper T cells can only see their specific target antigen as short sequences of peptides bound to the groove of proteins of major histocompatibility complex (MHC) class I, and class II respectively. In addition to the many steps, several participating proteins, and multiple cellular compartments involved in the processing of antigens, the MHC structure, with its dynamic and flexible groove, has perfectly evolved as the underlying instrument for epitope selection. In this review, I have taken a step-by-step, and rather historical, view to describe antigen processing and determinant selection, as we understand it today, all based on decades of intense research by hundreds of laboratories. PMID:27347387

  4. 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; Buus, S; Tschinke, V

    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...... interactions were found to contribute the most to HLA-A0201-peptide interactions, whereas H-bonding predominates in H-2K(k) recognition. Both cross-validated models were afterward used to predict the binding affinity of a test set of 26 peptides to HLA-A0204 (an HLA allele closely related to HLA-A0201) and of...

  5. Development of an MHC class I Ld-restricted PSA peptide-loaded tetramer for detection of PSA-specific CD8+ T cells in the mouse

    OpenAIRE

    Lemke, Caitlin D.; Graham, Jessica B.; Lubaroff, David M.; Salem, Aliasger K.

    2011-01-01

    Objectives We set out to develop a prostate specific antigen (PSA) peptide-loaded tetramer for enumeration of PSA-specific CD8+ T cells in the Balb/c mouse model. Methods A candidate MHC class I PSA peptide (HPQKVTKFML188–197) was selected based on its ability to restimulate PSA-specific CD8+ T cells to secrete IFN-γ in our assays. Next, H-2Ld-restricted peptide-loaded and fluorescently labeled tetramers were produced in conjunction with the NIH Tetramer Core Facility. This tetramer was then ...

  6. 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...

  7. 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

  8. Characterization of antigen processing and presentation by peptide-linked MHC class I molecules

    OpenAIRE

    Tiwari, Neeraj

    2005-01-01

    MHC-Klasse-I-Moleküle präsentieren gewöhnlich Peptide, die aus zytosolischen Antigenproteinen durch proteasomalen Verdau generiert und anschließend vom TAP-Peptidtransporter ins endoplasmatische Retikulum transportiert werden. Es können jedoch auch endozytierte Antigene für die MHC-Klasse-I-vermittelten Antigenpräsentation prozessiert werden, wobei dieser alternative Weg entweder in einer Proteasom/TAP-abhängigen oder unabhängigen Weise abläuft. Während diese so genannte „Kreuzpräsentation“ f...

  9. Characterization and expression pattern ofpouII1,a novel class Ⅱ POU gene in zebrafish

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    POU domain transcription factors that share a conserved DNA-binding domain, POU domain, are important regulators for the development of embryos in various animal species. A novel zebrafish POU domain gene, pouII1has been cloned. The pouII1 cDNA is 2080 kb in length and encodes a putative polypeptide of 596 amino acids. It is placed into class Ⅱ POU family since it shares a high degree of homology with the known members of this family.Northern hybridization identifies a major transcript of approximately 2.1 kb that was present in embryos at the single-cell stage throughout 24 h postfertilizafion. The whole mountin situ hybridization shows thatpouII1 transcripts are present in the single-cell embryos, strongly suggesting that these transcripts are of maternal origin. During early development of the embryos, pouII1 mRNA was ubiquitously distributed in all cells and tissues. The transcripts are gradually limited to brains and become completely undetectable by day 3. To our knowledge, pouII1 is the first class Ⅱ POU gene identified in zebrafish.``

  10. Expression of major histocompatibility complex class I and class II antigens in human Schwann cell cultures and effects of infection with Mycobacterium leprae.

    Science.gov (United States)

    Samuel, N M; Mirsky, R; Grange, J M; Jessen, K R

    1987-06-01

    Recent experiments on rats have raised the possibility that Schwann cells can present antigens to T lymphocytes. We have investigated whether this mechanism might be relevant in leprosy by determining under what conditions human Schwann cells express class I and class II antigens, and whether infection with Mycobacterium leprae affects this expression. The distribution of these antigens was examined on human Schwann cells in dissociated cell cultures derived from human fetal peripheral nerves. We find that both Schwann cells and fibroblastic cells in these cultures normally express class I antigens but not class II antigens. When Schwann cells are infected with live Mycobacterium leprae for 48 h, 73% of Schwann cells phagocytose the bacteria. Mycobacterium leprae prevents 3H-thymidine incorporation into cultured human Schwann cells, but does not affect class I expression in these cells. Treatment of normal and Mycobacterium leprae infected cultures with gamma-interferon for 72 h induces class II expression on most Schwann cells but not on the majority of fibroblastic cells. The fact that human Schwann cells infected with Mycobacterium leprae can be induced by gamma-interferon to express class II antigens suggests that they may be able to present Mycobacterium leprae antigens to T lymphocytes and thus initiate immune responses against the bacteria. We suggest that a failure of this response, such as that seen within nerve trunks in lepromatous leprosy, is caused by deficient class II expression on Schwann cells. This deficiency in class II expression, in turn, may be caused by the reduced gamma-interferon production characteristic of lepromatous leprosy. PMID:3115648

  11. Heparan Sulfate Proteoglycans Promote Telomerase Internalization and MHC Class II Presentation on Dendritic Cells.

    Science.gov (United States)

    Galaine, Jeanne; Kellermann, Guillaume; Guillaume, Yves; Boidot, Romain; Picard, Emilie; Loyon, Romain; Queiroz, Lise; Boullerot, Laura; Beziaud, Laurent; Jary, Marine; Mansi, Laura; André, Claire; Lethier, Lydie; Ségal-Bendirdjian, Evelyne; Borg, Christophe; Godet, Yann; Adotévi, Olivier

    2016-09-01

    Telomerase is a prototype-shared tumor Ag and represents an attractive target for anticancer immunotherapy. We have previously described promiscuous and immunogenic HLA-DR-restricted peptides derived from human telomerase reverse transcriptase (hTERT) and referred as universal cancer peptide (UCP). In nonsmall cell lung cancer, the presence of spontaneous UCP-specific CD4 T cell responses increases the survival of chemotherapy-responding patients. However, the precise mechanisms of hTERT's uptake, processing, and presentation on MHC-II molecules to stimulate CD4 T cells are poorly understood. In this work, by using well-characterized UCP-specific CD4 T cell clones, we showed that hTERT processing and presentation on MHC-II involve both classical endolysosomal and nonclassical cytosolic pathways. Furthermore, to our knowledge, we demonstrated for the first time that hTERT's internalization by dendritic cells requires its interaction with surface heparan sulfate proteoglycans. Altogether, our findings provide a novel mechanism of tumor-specific CD4 T cell activation and will be useful for the development of novel cancer immunotherapies that harness CD4 T cells. PMID:27481844

  12. Typing of HLA class II and class I antigens using PHA-activated, IL-2-propagated T lymphocytes.

    Science.gov (United States)

    Leshem, B; Cohen, I; Sherman, L; Brautbar, C; Kedar, E

    1988-06-28

    We describe here a simple procedure, by which HLA class II antigens can be accurately and reliably identified in those patients where there is minimal or absent expression of HLA-DR,DQw antigens on B cells, or when the total number of leukocytes recovered from the patients do not permit reliable typing. Ficoll-Hypaque-separated peripheral blood mononuclear leukocytes, fresh or cryopreserved, were activated by PHA and then propagated in IL-2-containing medium until enough cells for typing were obtained (usually 7-14 days). At this stage, the cultured cells were shown to be primarily T cells (greater than 90% CD3+). Since the activated T cells propagate in the presence of IL-2, even a small number (10(4] of fresh or cryopreserved patients' cells suffice for this protocol. To date we have been able to successfully HLA-DR,DQw type 34/34 bone marrow transplantation candidates and 12/12 long-term dialysis patients, who were untypable using fresh cells. HLA-DR,DQw antigens on activated T cells from normal individuals were identical to those found on their uncultured B cells. In addition, class I antigens that were undetectable on the uncultured cells of one patient could be identified on activated T cells. The HLA antigens identified on the patients' activated T cells were confirmed by phenotypic analysis of cells from family members. PMID:3260612

  13. Long-term surgical versus functional Class II correction: a comparison of identical twins.

    Science.gov (United States)

    Chhibber, Aditya; Upadhyay, Madhur; Uribe, Flavio; Nanda, Ravindra

    2015-01-01

    The purpose of this twin case comparison was to assess the short- and long-term effects of nonsurgical treatment vs orthognathic surgical treatment for Class II correction. Two identical twins (age 13 years 3 months) were treated for Class II correction where one patient was treated nonsurgically using a fixed functional appliance, while the other was treated using orthognathic mandibular advancement surgery. The patients were recalled and evaluated 5 years in retention. Comparing changes in the short and long term, surgical treatment led to superior skeletal results compared to the nonsurgical twin. However, the soft tissue profile was remarkably similar for both patients suggesting that soft tissue profile changes may not necessarily follow similar changes in the bony skeletal structures. PMID:25075777

  14. 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.

  15. In vitro evaluation of the marginal microleakage of class II amalgam restoration associated with dentin adhesive

    Directory of Open Access Journals (Sweden)

    OLIVEIRA Fabiana Sodré de

    1999-01-01

    Full Text Available The marginal microleakage of class II amalgam restorations (Dispersalloy associated with copal varnish (Copalite and with two dentin bonding agents (Scotchbond Multi-uso Plus and Multi Bond Alpha was evaluated in vitro and compared by two methods: scores and linear measurements. Forty-five sound premolars were used, on which two separated class II cavities were prepared on the M and D surfaces. After the restoration, the specimens were thermocycled and stored in a solution of 0.5% basic fuchsin during 24 hours. The analysis allowed to conclude that none of the three restorative systems were able to eliminate the marginal microleakage. Nevertheless, the leakage was significantly smaller on the restorations associated with dentin bonding agents when compared to copal varnish. The linear measurement method was more sensitive than the score criteria.

  16. Expansion design for a radioactive sources handling laboratory type II class B

    International Nuclear Information System (INIS)

    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)

  17. Restricted dog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles

    OpenAIRE

    Soutter, Francesca; Kennedy, Lorna J; Ollier, William E R; Solano-Gallego, Laia; Catchpole, Brian

    2015-01-01

    Beagles are commonly used in vaccine trials as part of the regulatory approval process. Genetic restriction within this breed and the impact this might have on vaccine responses are rarely considered. This study was designed to characterise diversity of dog leucocyte antigen (DLA) class II genes in a breeding colony of laboratory Beagles, whose offspring are used in vaccine studies. DLA haplotypes were determined by PCR and sequence-based typing from genomic DNA extracted from blood. Breeding...

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

    OpenAIRE

    Tetiana Haniastuti

    2012-01-01

    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-pr...

  19. The HLA Class II Associations with Rheumatic Heart Disease in South Indian Patients: A Preliminary Study

    OpenAIRE

    Bajoria, Divya; Menon, Thangam

    2013-01-01

    Introduction: Rheumatic heart disease (RHD) occurs in 30-45% of the patients with rheumatic fever (RF) and it leads to chronic valvular lesions. The human leukocyte antigen (HLA) might confer a susceptibility to RHD. The aim of the present study was to determine the prevalent HLA class II DR/DQ allelic types which were associated with rheumatic heart disease (RHD) in a small group of south Indian patients and to compare them with those in the control subjects.

  20. The application of NISA II FEM package in seismic qualification of small class IE electric motors

    International Nuclear Information System (INIS)

    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)

  1. Unilateral Maxillary First Molar Extraction in Class II Subdivision: An Unconventional Treatment Alternative

    Science.gov (United States)

    Booij, J. W.; Livas, Christos

    2016-01-01

    The asymmetrical intra-arch relationship in Class II subdivision malocclusion poses challenges in the treatment planning and mechanotherapy of such cases. This case report demonstrates a treatment technique engaging unilateral extraction of a maxillary first molar and Begg fixed appliances. The outcome stability and the enhancing effect on the eruption of the third molar in the extraction segment were confirmed by a 4-year follow-up examination. PMID:27200194

  2. Compensatory orthodontic treatment of Angle Class II malocclusion with posterior open bite

    Directory of Open Access Journals (Sweden)

    José Newton Torres

    2013-10-01

    Full Text Available The present case report addresses the treatment of an Angle Class II malocclusion in an adult female patient, long face pattern, with posterior open bite and dental arches extremely expanded, due to previous treatment. The patient and parents rejection to a treatment with orthognathic surgery led to orthodontic camouflage of the skeletal discrepancies. This clinical case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as one of the requirements to become a BBO Diplomate.

  3. FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression

    OpenAIRE

    Li, Bin; Samanta, Arabinda; Song, Xiaomin; Iacono, Kathryn T.; Bembas, Kathryn; Tao, Ran; Basu, Samik; Riley, James L.; Hancock, Wayne W.; Shen, Yuan; Saouaf, Sandra J.; Mark I. Greene

    2007-01-01

    The forkhead family protein FOXP3 acts as a repressor of transcription and is both an essential and sufficient regulator of the development and function of regulatory T cells. The molecular mechanism by which FOXP3-mediated transcriptional repression occurs remains unclear. Here, we report that transcriptional repression by FOXP3 involves a histone acetyltransferase–deacetylase complex that includes histone acetyltransferase TIP60 (Tat-interactive protein, 60 kDa) and class II histone deacety...

  4. 454 sequencing reveals extreme complexity of the class II Major Histocompatibility Complex in the collared flycatcher

    OpenAIRE

    Gustafsson Lars; Stuglik Michał; Babik Wiesław; Zagalska-Neubauer Magdalena; Cichoń Mariusz; Radwan Jacek

    2010-01-01

    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 ge...

  5. Evaluation of the position of lower incisors in the mandibular symphysis of individuals with Class II malocclusion and Pattern II profiles

    Directory of Open Access Journals (Sweden)

    Djalma Roque Woitchunas

    2012-06-01

    Full Text Available OBJECTIVES: This study evaluated the position of mandibular incisors in the mandibular symphysis of individuals with Class II malocclusion and Pattern II profiles. METHODS: The sample consisted of 40 Caucasian patients (20 male and 20 female with Class II malocclusion and Pattern II profile from 10 to 18 years of age (mean age of 12.84 years who were selected from the records of the School of Dentistry of Universidade de Passo Fundo, Brazil. The linear cephalometric measurements used in this study were Ricketts' 1- AP, Interlandi's line I and Vigorito's 1-VT; and the angular measurement studied was the mandibular plane angle (IMPA. RESULTS: Mandibular incisors of individuals with Class II malocclusion and Pattern II profile tended to be buccally inclined and protruded.

  6. 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. PMID:8894111

  7. Class II malocclusion treatment using Jasper Jumper appliance associated to intermaxillary elastics: a case report

    Directory of Open Access Journals (Sweden)

    Francyle Simões Herrera-Sanches

    2013-04-01

    Full Text Available INTRODUCTION: Skeletal, dental and profile discrepancies can be amended by using functional orthodontic appliances. OBJECTIVE: This study is a report of the treatment of a patient, 11 years and 4 months old, with Class II, division 1, malocclusion, convex profile, protrusion of upper incisors, pronounced overjet and overbite, and mild crowding. METHODS: The patient was treated with a Jasper Jumper associated to fixed appliances for 6 months and Class II intermaxillary elastics (3/16in during the last 4 months. After debonding, a Hawley retainer was used during daytime and a modified Bionator for night use during one year. In the lower dental arch a bonded lingual retainer was used. This treatment combination improved the profile, as well as the overjet, overbite and molar relation. RESULTS: There was clockwise mandibular rotation and increase of lower anterior facial height. The lower incisors were protruded and extruded and the lower molars were extruded. The centric occlusal relation was checked and it was coincident to the maximum usual intercuspation. CONCLUSION: It was demonstrated that the Jasper Jumper is an efficient alternative to Class II malocclusion treatment, providing improvement in the facial profile, although the changes are more dentoalveolar than skeletal.

  8. Dental, skeletal asymmetries and functional characteristics in Class II subdivision malocclusions.

    Science.gov (United States)

    Li, J; He, Y; Wang, Y; Chen, T; Xu, Y; Xu, X; Zeng, H; Feng, J; Xiang, Z; Xue, C; Han, X; Bai, D

    2015-08-01

    Treatment outcomes of Angle Class II subdivision malocclusions may be compromised because of the uncertainty of the aetiology. Previous studies have reported controversial ideas about the origins, but the existence of a primary contributor still remains unknown. Functional factors have been mentioned as a probable cause, but until now, there have been no supporting data. This study was a cross-sectional investigation of the characteristics of Angle Class II subdivision malocclusion, including dental, skeletal and functional factors, by comparison of the subdivision group and the normal occlusion group. The evaluations of dental and skeletal asymmetries of both groups were carried out by cone-beam computed tomography (CBCT) and analysis of dental casts. The functional deviations were evaluated by cast mounting and measuring. In the subdivision group, the asymmetric position of the glenoid fossa was found to be the most significant skeletal asymmetry. No dentoalveolar asymmetry was found in this group. The most important finding was that, in subdivision malocclusions, functional deviation resulting in pseudoasymmetry occurred in 32.86% of the study participants. This deviation is probably related to the disharmonious arch width between maxillary and mandibular dental arches in the premolar section. The origin of Angle Class II subdivision malocclusion is multifactorial, with dental, skeletal and functional factors included. Functional deviation occurs, probably due to dental arch width disharmony. Asymmetric position of the glenoid fossa may account for most of the skeletal asymmetry. PMID:25944587

  9. Expansion design for a Laboratory of Radioactive Sources Handling type II, class B

    International Nuclear Information System (INIS)

    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)

  10. Class I HDACs regulate angiotensin II-dependent cardiac fibrosis via fibroblasts and circulating fibrocytes.

    Science.gov (United States)

    Williams, Sarah M; Golden-Mason, Lucy; Ferguson, Bradley S; Schuetze, Katherine B; Cavasin, Maria A; Demos-Davies, Kim; Yeager, Michael E; Stenmark, Kurt R; McKinsey, Timothy A

    2014-02-01

    Fibrosis, which is defined as excessive accumulation of fibrous connective tissue, contributes to the pathogenesis of numerous diseases involving diverse organ systems. Cardiac fibrosis predisposes individuals to myocardial ischemia, arrhythmias and sudden death, and is commonly associated with diastolic dysfunction. Histone deacetylase (HDAC) inhibitors block cardiac fibrosis in pre-clinical models of heart failure. However, which HDAC isoforms govern cardiac fibrosis, and the mechanisms by which they do so, remains unclear. Here, we show that selective inhibition of class I HDACs potently suppresses angiotensin II (Ang II)-mediated cardiac fibrosis by targeting two key effector cell populations, cardiac fibroblasts and bone marrow-derived fibrocytes. Class I HDAC inhibition blocks cardiac fibroblast cell cycle progression through derepression of the genes encoding the cyclin-dependent kinase (CDK) inhibitors, p15 and p57. In contrast, class I HDAC inhibitors block agonist-dependent differentiation of fibrocytes through a mechanism involving repression of ERK1/2 signaling. These findings define novel roles for class I HDACs in the control of pathological cardiac fibrosis. Furthermore, since fibrocytes have been implicated in the pathogenesis of a variety of human diseases, including heart, lung and kidney failure, our results suggest broad utility for isoform-selective HDAC inhibitors as anti-fibrotic agents that function, in part, by targeting these circulating mesenchymal cells. PMID:24374140

  11. 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.

  12. Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.

    Science.gov (United States)

    Bataille, Arnaud; Cashins, Scott D; Grogan, Laura; Skerratt, Lee F; Hunter, David; McFadden, Michael; Scheele, Benjamin; Brannelly, Laura A; Macris, Amy; Harlow, Peter S; Bell, Sara; Berger, Lee; Waldman, Bruce

    2015-04-22

    The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) can cause precipitous population declines in its amphibian hosts. Responses of individuals to infection vary greatly with the capacity of their immune system to respond to the pathogen. We used a combination of comparative and experimental approaches to identify major histocompatibility complex class II (MHC-II) alleles encoding molecules that foster the survival of Bd-infected amphibians. We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove. Moreover, strong signals of selection acting on these specific sites were evident among all species co-existing with the pathogen. In the laboratory, we experimentally inoculated Australian tree frogs with Bd to test how each binding pocket conformation influences disease resistance. Only the conformation of MHC-II pocket 9 of surviving subjects matched those of Bd-resistant species. This MHC-II conformation thus may determine amphibian resistance to Bd, although other MHC-II binding pockets also may contribute to resistance. Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd. The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal. PMID:25808889

  13. Orthodontic Camouflage Treatment in an Adult Patient with a Class II, Division 1 Malocclusion – A Case Report

    OpenAIRE

    Naragond, Appasaheb; Kenganal, Smitha; Sagarkar, Roshan; Sugaradday,

    2012-01-01

    Since so many decades, various treatment modalities have been presented for the treatment for the class II, div 1 malocclusions. In recent times, we have seen enormously increasing numbers of young adults who desire the shortest, cost effective and a non surgical correction of Class II malocclusions and they accept dental camouflage as a treatment option to mask the skeletal discrepancy. This case report presents one such case of a 22 year old non-growing female who had a skeletal Class II, d...

  14. 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

    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......Ab induced 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...

  15. Complete genome sequence of Lactobacillus paraplantarum L-ZS9, a probiotic starter producing class II bacteriocins.

    Science.gov (United States)

    Liu, Lei; Li, Pinglan

    2016-03-20

    Lactobacillus paraplantarum L-ZS9 is a probiotic starter isolated from fermented sausage and it is a great producer of class II bacteriocins. To the best of our knowledge, this is the first complete sequenced genome of L. paraplantarum deposited in GenBank database. The size of the complete genome of L. paraplantarum L-ZS9 is 3,139,729bp. The genomic sequence revealed that this strain includes 19 genes involved in class II bacteriocins production and regulation. The information fill the gaps of the L. paraplantarum genome information and contribute to the improvement of class II bacteriocins research. PMID:26853479

  16. Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames.

    Science.gov (United States)

    Laumont, Céline M; Daouda, Tariq; Laverdure, Jean-Philippe; Bonneil, Éric; Caron-Lizotte, Olivier; Hardy, Marie-Pierre; Granados, Diana P; Durette, Chantal; Lemieux, Sébastien; Thibault, Pierre; Perreault, Claude

    2016-01-01

    In view of recent reports documenting pervasive translation outside of canonical protein-coding sequences, we wished to determine the proportion of major histocompatibility complex (MHC) class I-associated peptides (MAPs) derived from non-canonical reading frames. Here we perform proteogenomic analyses of MAPs eluted from human B cells using high-throughput mass spectrometry to probe the six-frame translation of the B-cell transcriptome. We report that ∼ 10% of MAPs originate from allegedly noncoding genomic sequences or exonic out-of-frame translation. The biogenesis and properties of these 'cryptic MAPs' differ from those of conventional MAPs. Cryptic MAPs come from very short proteins with atypical C termini, and are coded by transcripts bearing long 3'UTRs enriched in destabilizing elements. Relative to conventional MAPs, cryptic MAPs display different MHC class I-binding preferences and harbour more genomic polymorphisms, some of which are immunogenic. Cryptic MAPs increase the complexity of the MAP repertoire and enhance the scope of CD8 T-cell immunosurveillance. PMID:26728094

  17. 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...

  18. 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

  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. PMID:26087405

  20. MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis.

    Science.gov (United States)

    Huan, Jianya; Kaler, Laurie J; Mooney, Jeffery L; Subramanian, Sandhya; Hopke, Corwyn; Vandenbark, Arthur A; Rosloniec, Edward F; Burrows, Gregory G; Offner, Halina

    2008-01-15

    We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), single-chain two domain complexes of the alpha1 and beta1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-Aq-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-Aq/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-gamma production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-Aq/bCII257-270 molecule could also selectively inhibit IL-1beta, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans. PMID:18178865

  1. 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

    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. PMID:27275616

  2. 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.

  3. 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.

  4. Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules

    International Nuclear Information System (INIS)

    Toxic shock syndrome toxin 1 (TSST-1) is a 22-kDa exotoxin produced by strains of Staphylococcus aureus and implicated in the pathogenesis of toxic shock syndrome. In common with other staphylococcal exotoxins, TSST-1 has diverse immunological effects. These include the induction of interleukin 2 receptor expression, interleukin 2 synthesis, proliferation of human T lymphocytes, and stimulation of interleukin 1 synthesis by human monocytes. In the present study, the authors demonstrate that TSST-1 binds with saturation kinetics and with a dissociation constant of 17-43 nM to a single class of binding sites on human mononuclear cells. There was a strong correlation between the number of TSST-1 binding sites and the expression of major histocompatibility complex class II molecules. Affinity chromatography of 125I-labeled cell membranes over TSST-1-agarose resulted in the recovery of two bands of 35 kDa and 31 kDa that comigrated, respectively, with the α and β chains of HLA-DR and that could be immunoprecipitated with anti-HLA-DR monoclonal antibodies. Binding of TSST-1 was demonstrated to HLA-DR and HLA-DQ L-cell transfectants. These results indicate that major histocompatibility complex class II molecules represent the major binding site for TSST-1 on human cells

  5. In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function

    DEFF Research Database (Denmark)

    Follin, Elna; Karlsson, Maria; Lundegaard, Claus; Nielsen, Morten; Wallin, Stefan; Paulsson, Kajsa Maria; Westerdahl, Helena

    2013-01-01

    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 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...

  6. 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

  7. DPA1*02012: A DPA1*0201-related Mhc class II allele in West Africa

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, C.G.; May, J.; Spauke, D.; Schnittger, L. [Bernhard Nocht Institute for Tropical Medicine, Hamburg (Germany)

    1994-12-31

    DNA techniques such as sequence-specific oligonucleotide probe (SSOP) hybridizations, restriction-fragment length polymorphism (RFLP) analyses, and DNA sequencing have greatly supported the characterization of Mhc class II allelic polymorphism. Here the authors describe a DPA 1 allele which has been identified in two male individuals from Liberia and Benin, West Africa, during a survey study on Mhc class II associations with the different manifestations after infection with Onchocerca volvulus. 4 refs., 1 fig.

  8. "HUMAN LEUKOCYTE CLASS I AND II ANTIGENS IN IRANIAN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY"

    Directory of Open Access Journals (Sweden)

    "A. Aghamohammadi

    2004-09-01

    Full Text Available Common variable immunodeficiency (CVID is a heterogeneous heritable disease characterized by arrest in B cell differentiation. An association between CVID and two HLA haplotypes, haplotype I (HLA-A1, HLA-B8, HLA-DR3 and haplotype II (HLA-A29, HLA-B44, HLADR7has been previously documented. In the present study, we have attempted to find an association between susceptibility to CVID and HLA class I and II antigens in Iranian population. Seventeen Iranian patients with CVID (mean age 17, range 3-28 years; 12 male and 5 female, including two couples of brothers and 100 healthy controls were studied. All subjects were typed for HLA class 1, and 12 patients and all controls were typed for HLA class II, using microdroplet lymphocytotoxicity technique. Out of 12 CVID patients typed for HLA-DR and DQ specificities, five patients presented DR-1, which showed an increased frequency in patient (41.6% vs. 12% in controls, and 3 presented DQ-2, which also showed an increased frequency (25% vs. 4% in controls, both of which reached statistical significance (P = 0.018 and P = 0.026, respectively. HLA-DR10 was present in 2 patients (16.6%, which was markedly more frequent compared to controls, but this difference was not significant statistically. Our results suggest that HLA-DR1 and DQ-2 may contribute to susceptibility to CVID. We did not find any significant association between HLA-A1, B8 and DR3 that has been previously reported to be associated with CVID.

  9. Early prevention and intervention of Class II division 1 in growing patients

    Science.gov (United States)

    Keerthi, V. Naga; Kanya, S. Dhivya; Babu, K. Pradeep; Mathew, Anoop; Kumar, A. Nanda

    2016-01-01

    Early screening and diagnosis help in preventing and intercepting the severity of the malocclusion which helps in addressing the esthetic and functional concerns. Growth modulation such as mandibular advancement has been an effective procedure in orthodontics. Mandibular growth advancer (MGA) and PowerScope are gaining popularity recently as these are effective in achieving the mandibular advancement and ease of fabrication, placement, and wear. MGA was fabricated by making the upper and lower splints separately and are placed in the oral cavity by joining the two splints in the new construction bite using cold cure, MGA when worn during growth phase helps in condylar remodeling in the temporomandibular joint thus helps in advancement of the mandible. The proclination of the upper anteriors in Class II division 1 can be moved lingually by activating the labial bow in the splint. Dr. Andy Hayes worked in conjunction with American orthodontics developed PowerScope. PowerScope delivers Class II correction with a combination of patient comfort and ease of use that was unmatched among other appliances. This ready to use chairside solution required no laboratory setup, making for a much quicker, and easier installation process and appointment. PowerScopes high quality, fixed one-piece design requires no patient compliance. These superior qualities of PowerScope help in correction of Class II skeletal growing patient in conjunction with fixed orthodontic therapy. MGA and PowerScope were chosen as a functional appliance for this study, which shows decreased ANB angle and effective mandible length was increased. PMID:27195234

  10. β class II tubulin predominates in normal and tumor breast tissues

    International Nuclear Information System (INIS)

    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

  11. Early prevention and intervention of Class II division 1 in growing patients.

    Science.gov (United States)

    Keerthi, V Naga; Kanya, S Dhivya; Babu, K Pradeep; Mathew, Anoop; Kumar, A Nanda

    2016-04-01

    Early screening and diagnosis help in preventing and intercepting the severity of the malocclusion which helps in addressing the esthetic and functional concerns. Growth modulation such as mandibular advancement has been an effective procedure in orthodontics. Mandibular growth advancer (MGA) and PowerScope are gaining popularity recently as these are effective in achieving the mandibular advancement and ease of fabrication, placement, and wear. MGA was fabricated by making the upper and lower splints separately and are placed in the oral cavity by joining the two splints in the new construction bite using cold cure, MGA when worn during growth phase helps in condylar remodeling in the temporomandibular joint thus helps in advancement of the mandible. The proclination of the upper anteriors in Class II division 1 can be moved lingually by activating the labial bow in the splint. Dr. Andy Hayes worked in conjunction with American orthodontics developed PowerScope. PowerScope delivers Class II correction with a combination of patient comfort and ease of use that was unmatched among other appliances. This ready to use chairside solution required no laboratory setup, making for a much quicker, and easier installation process and appointment. PowerScopes high quality, fixed one-piece design requires no patient compliance. These superior qualities of PowerScope help in correction of Class II skeletal growing patient in conjunction with fixed orthodontic therapy. MGA and PowerScope were chosen as a functional appliance for this study, which shows decreased ANB angle and effective mandible length was increased. PMID:27195234

  12. Characterization of monoclonal antibodies against MHC class II-associated p41 invariant chain fragment

    International Nuclear Information System (INIS)

    Mouse monoclonal antibodies directed against human MHC class II-associated p41 invariant chain fragment have been generated. Mice were immunized with human recombinant Ii-isoform p26. For hybridoma production mouse splenocytes and myeloma cells were fused. Hybridoma cells were screened using ELISA and immunoblotting. Three cell lines (42B10, 42G11 and 43C8) were used for production of specific antibodies, which reacted with p41 fragment and did not bind to cathepsins L or S or their proenyzmes. As primary antibody for immunofluorescence staining of lymph node tissue sections clone 2C12 MAb was selected. Specific localization of p41 fragment in certain cells in lymph nodes was observed. (author)

  13. Development and morphology of class II Kenyon cells in the mushroom bodies of the honey bee, Apis mellifera.

    Science.gov (United States)

    Farris, Sarah M; Abrams, Andrew I; Strausfeld, Nicholas J

    2004-06-28

    Class II Kenyon cells, defined by their early birthdate and unique dendritic arborizations, have been observed in the mushroom bodies of evolutionarily divergent insects. In the fruit fly Drosophila melanogaster, Class II (also called clawed) Kenyon cells are well known for their extensive reorganization that occurs during metamorphosis. The present account reports for the first time the occurrence of mushroom body reorganization during metamorphosis in holometabolous insect species outside of the Diptera. In the honey bee, Apis mellifera, Class II Kenyon cells show signs of degeneration and undergo a subtle reshaping of their axons during metamorphosis. Unlike in Drosophila, reorganization of Class II Kenyon cells in the honey bee does not involve the loss of axon branches. In contrast, the mushroom bodies of closely related hymenopteran species, the polistine wasps, undergo a much more dramatic restructuring near the end of metamorphosis. Immunohistochemistry, dextran fills, and Golgi impregnations illuminate the heterogeneous nature of Class II Kenyon cells in the developing and adult honey bee brain, with subpopulations differing in the location of dendritic arbors within the calyx, and branching pattern in the lobes. Furthermore, polyclonal antibodies against the catalytic subunit of Drosophila protein kinase A (anti-DC0) label an unusual and previously undescribed trajectory for these neurons. The observed variations in morphology indicate that subpopulations of Class II Kenyon cells in the honey bee can likely be further defined by significant differences in their specific connections and functions within the mushroom bodies. PMID:15174077

  14. 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

  15. Microleakage of Class II Combined Amalgam-Composite Restorations Using Different Composites and Bonding Agents

    OpenAIRE

    F. Sharafeddin; H. Moradian

    2008-01-01

    Objective: The purpose of the present study was to assess the microleakage of composite restorations with and without a cervical amalgam base and to compare the results of dif-ferent composites and bonding agents.Materials and Methods: One hundred and twenty mesio-occlusal (MO) and disto-occlusal (DO) Class II cavities were prepared on sixty extracted permanent premolar teeth. The teeth were randomly divided into four groups of 30 and restored as follows:In group A, the mesio-occlusal cavity ...

  16. The great diversity of major histocompatibility complex class II genes in Philippine native cattle

    OpenAIRE

    S.N. Takeshima; Miyasaka, T; M. Polat; Kikuya, M.; Matsumoto, Y; C.N. Mingala; Villanueva, M.A.; Salces, A.J.; ONUMA, M.; Aida, Y.

    2014-01-01

    Bovine leukocyte antigens (BoLA) are extensively used as markers for bovine disease and immunological traits. However, none of the BoLA genes in Southeast Asian breeds have been characterized by polymerase chain reaction (PCR)-sequence-based typing (SBT). Therefore, we sequenced exon 2 of the BoLA class II DRB3 gene from 1120 individual cows belonging to the Holstein, Sahiwal, Simbrah, Jersey, Brahman, and Philippine native breeds using PCR-SBT. Several cross-breeds were also examined. BoLA-D...

  17. Role of PU.1 in MHC Class II Expression via CIITA Transcription in Plasmacytoid Dendritic Cells

    Science.gov (United States)

    Miura, Ryosuke; Kasakura, Kazumi; Nakano, Nobuhiro; Hara, Mutsuko; Maeda, Keiko; Okumura, Ko; Ogawa, Hideoki; Yashiro, Takuya; Nishiyama, Chiharu

    2016-01-01

    The cofactor CIITA is a master regulator of MHC class II expression and several transcription factors regulating the cell type-specific expression of CIITA have been identified. Although the MHC class II expression in plasmacytoid dendritic cells (pDCs) is also mediated by CIITA, the transcription factors involved in the CIITA expression in pDCs are largely unknown. In the present study, we analyzed the role of a hematopoietic lineage-specific transcription factor, PU.1, in CIITA transcription in pDCs. The introduction of PU.1 siRNA into mouse pDCs and a human pDC cell line, CAL-1, reduced the mRNA levels of MHC class II and CIITA. When the binding of PU.1 to the 3rd promoter of CIITA (pIII) in CAL-1 and mouse pDCs was analyzed by a chromatin immunoprecipitation assay, a significant amount of PU.1 binding to the pIII was detected, which was definitely decreased in PU.1 siRNA-transfected cells. Reporter assays showed that PU.1 knockdown reduced the pIII promoter activity and that three Ets-motifs in the human pIII promoter were candidates of cis-enhancing elements. By electrophoretic mobility shift assays, it was confirmed that two Ets-motifs, GGAA (-181/-178) and AGAA (-114/-111), among three candidates, were directly bound with PU.1. When mouse pDCs and CAL-1 cells were stimulated by GM-CSF, mRNA levels of PU.1, pIII-driven CIITA, total CIITA, MHC class II, and the amount of PU.1 binding to pIII were significantly increased. The GM-CSF-mediated up-regulation of these mRNAs was canceled in PU.1 siRNA-introduced cells. Taking these results together, we conclude that PU.1 transactivates the pIII through direct binding to Ets-motifs in the promoter in pDCs. PMID:27105023

  18. Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris.

    OpenAIRE

    Ahmed, A. R.; Wagner, R; Khatri, K; Notani, G.; Awdeh, Z; Alper, C A; Yunis, E J

    1991-01-01

    Previous studies demonstrated that HLA-DR4 was markedly increased among Ashkenazi Jewish patients with pemphigus vulgaris (PV), almost entirely as the common Jewish extended haplotype [HLA-B38, SC21, DR4, DQw8] or as the haplotype HLA-B35, SC31, DR4, DQw8, and that HLA-DR4, DQw8 was distributed among patients in a manner consistent with dominant expression of a class II (D-region or D-region-linked) susceptibility gene. In the present study of major histocompatibility complex (MHC) haplotypes...

  19. Internal and Marginal Fit of Modern Indirect Class II Composite Inlays

    OpenAIRE

    Philipp C. Pott; Agnieszka Rzasa; Meike Stiesch; Michael Eisenburger

    2014-01-01

    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 res...

  20. 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

    reactivity. 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 in the development of inflammatory eye diseases, such as uveitis....

  1. 40 CFR Table F-1 to Subpart F of... - Performance Specifications for PM2.5 Class II Equivalent Samplers

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Performance Specifications for PM2.5 Class II Equivalent Samplers F Table F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL..., Subpt. F, Table F-1 Table F-1 to Subpart F of Part 53—Performance Specifications for PM2.5 Class...

  2. Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences

    International Nuclear Information System (INIS)

    Information was sought on the phenotype of lymphoid cells causing lethal graft-vs-host disease (GVHD) in irradiated mice expressing whole or partial H-2 differences. In all strain combinations tested, pretreating donor lymph node (LN) cells with anti-Thy-1 monoclonal antibodies (MAb) plus complement (C) abolished mortality. With GVHD directed to class I H-2 differences, pretreating LN cells with anti-Lyt-2 MAb prevented mortality, whereas MAb specific for Ly-1 or L3T4 cell surface determinants caused severe mortality. These data imply that lethal GVHD directed to class I H-2 differences is mediated by L3T4-, Lyt-2+ cells; this subset of T cells was shown previously to control GVHD directed to multiple minor histocompatibility antigens, i.e., antigens seen in the context of self-class I molecules. With whole H-2 differences, GVHD appeared to be controlled largely but not exclusively by L3T4+, Lyt-2- T cells. This T cell subset was also the predominant cause of GVHD directed to class II differences. With class II incompatibilities, depleting donor cells of L3T4+ T cells, either by pretreatment with anti-L3T4 MAb + C or by fluorescence activated cell sorter selection, greatly reduced but did not completely abolish GVHD. These data might imply that L3T4-, Lyt-2+ cells have some capacity to elicit anti-class II GVHD. A more likely possibility, however, is that the residual GVHD to class II differences observed with Lyt-2+-enriched cells reflected minor contamination with L3T4+ cells

  3. 25 CFR 547.10 - What are the minimum standards for Class II gaming system critical events?

    Science.gov (United States)

    2010-04-01

    ... the fault is. (ii) Financial storage component full Reported when a financial instrument acceptor or... component is full. (iii) Financial output component empty Reported when a financial instrument dispenser is...) Disable all financial instrument disbursement, unless a test mode is entered. (2) The Class II...

  4. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

    NARCIS (Netherlands)

    Buschow, S.I.; Balkom, B.W.M. van; Aalberts, M.; Heck, A.J.R. van; Wauben, M.; Stoorvogel, W.

    2010-01-01

    Professional antigen-presenting cells secrete major histocompatibility complex class II (MHC II) carrying exosomes with unclear physiological function(s). Exosomes are first generated as the intraluminal vesicles (ILVs) of a specific type of multivesicular body, and are then secreted by fusion of th

  5. NMR structures of anti-HIV D-peptides derived from the N-terminus of viral chemokine vMIP-II

    International Nuclear Information System (INIS)

    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

  6. Unbound position II in MXCXXC metallochaperone model peptides impacts metal binding mode and reactivity: Distinct similarities to whole proteins.

    Science.gov (United States)

    Shoshan, Michal S; Dekel, Noa; Goch, Wojciech; Shalev, Deborah E; Danieli, Tsafi; Lebendiker, Mario; Bal, Wojciech; Tshuva, Edit Y

    2016-06-01

    The effect of position II in the binding sequence of copper metallochaperones, which varies between Thr and His, was investigated through structural analysis and affinity and oxidation kinetic studies of model peptides. A first Cys-Cu(I)-Cys model obtained for the His peptide at acidic and neutral pH, correlated with higher affinity and more rapid oxidation of its complex; in contrast, the Thr peptide with the Cys-Cu(I)-Met coordination under neutral conditions demonstrated weaker and pH dependent binding. Studies with human antioxidant protein 1 (Atox1) and three of its mutants where S residues were replaced with Ala suggested that (a) the binding affinity is influenced more by the binding sequence than by the protein fold (b) pH may play a role in binding reactivity, and (c) mutating the Met impacted the affinity and oxidation rate more drastically than did mutating one of the Cys, supporting its important role in protein function. Position II thus plays a dominant role in metal binding and transport. PMID:26901629

  7. Thermodynamic and Structural Characterization of the Copper(II Complexes of Peptides Containing Both Histidyl and Aspartyl Residues

    Directory of Open Access Journals (Sweden)

    Csilla Kállay

    2007-01-01

    Full Text Available Terminally protected pentapeptides with 2 histidines (Ac-HHVGD-NH2 and Ac-HVGDH-NH2 and the terminally free peptides containing both internal aspartyl and C-terminal histidyl residues (FDAH and VIDAH have been synthesized, and copper(II complexes studied by potentiometric, UV-Vis, CD, and EPR spectroscopic techniques in solution. Both thermodynamic and spectroscopic data reveal that side chain donor atoms of aspartyl and histidyl residues have a significant contribution to the metal binding affinity of peptide molecules. In the case of terminally protected peptides, the role of the imidazole-N donor functions is reflected in the enhanced stability of the 3N and 4N coordinated copper(II complexes. The amino and β-carboxylate groups of FDAH and VIDAH create a very effective metal binding site with the (NH2, N−, β-COO− and (NH2, N−, N−, β-COO− coordination modes including the N-termini, while the histidine sites are available for the formation of the (Nim, N−, N− binding mode resulting in the preference of dinuclear complex formation.

  8. Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei.

    Science.gov (United States)

    Khalesi, Mohammadreza; Jahanbani, Raheleh; Riveros-Galan, David; Sheikh-Hassani, Vahid; Sheikh-Zeinoddin, Mahmoud; Sahihi, Mehdi; Winterburn, James; Derdelinckx, Guy; Moosavi-Movahedi, Ali Akbar

    2016-10-01

    There are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01-0.40mg/mL) were determined. The results show that for HFBII concentrations of 0.04mg/mL and upwards the protein significantly reduced the presence of ABTS(+) radicals in the medium, the IC50 value found to be 0.13mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry. PMID:27211298

  9. 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.

  10. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    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)

  11. Prediction of positive food effect: Bioavailability enhancement of BCS class II drugs.

    Science.gov (United States)

    Raman, Siddarth; Polli, James E

    2016-06-15

    High-throughput screening methods have increased the number of poorly water-soluble, highly permeable drug candidates. Many of these candidates have increased bioavailability when administered with food (i.e., exhibit a positive food effect). Food is known to impact drug bioavailability through a variety of mechanisms, including drug solubilization and prolonged gastric residence time. In vitro dissolution media that aim to mimic in vivo gastrointestinal (GI) conditions have been developed to lessen the need for fed human bioequivalence studies. The objective of this work was to develop an in vitro lipolysis model to predict positive food effect of three BCS Class II drugs (i.e., danazol, amiodarone and ivermectin) in previously developed lipolysis media. This in vitro lipolysis model was comparatively benchmarked against FeSSIF and FaSSIF media that were modified for an in vitro lipolysis approach, as FeSSIF and FaSSIF are widely used in in vitro dissolution studies. The in vitro lipolysis model accurately predicted the in vivo positive food effect for three model BCS class II drugs. The in vitro lipolysis model has potential use as a screening test of drug candidates in early development to assess positive food effect. PMID:27067239

  12. 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.

  13. Major histocompatibility complex class II alleles and haplotypes associated with non-suppurative meningoencephalitis in greyhounds.

    Science.gov (United States)

    Shiel, R E; Kennedy, L J; Nolan, C M; Mooney, C T; Callanan, J J

    2014-09-01

    Non-suppurative meningoencephalitis is a breed-restricted canine neuroinflammatory disorder affecting young greyhounds in Ireland. A genetic risk factor is suspected because of the development of disease in multiple siblings and an inability to identify a causative infectious agent. The aim of this study was to examine potential associations between dog leucocyte antigen (DLA) class II haplotype and the presence of the disease. DLA three locus haplotypes were determined in 31 dogs with non-suppurative meningoencephalitis and in 115 healthy control dogs using sequence-based typing (SBT) methods. All dogs were unrelated at the parental level. Two haplotypes (DRB1*01802/DQA1*00101/DQB1*00802 and DRB1*01501/DQA1*00601/DQB1*02201) were significantly (P = 0.0099 and 0.037) associated with the presence of meningoencephalitis, with odds ratios (95% confidence interval) of 5.531 (1.168-26.19) and 3.736 (1.446-9.652), respectively. These results confirm that there is an association between DLA class II haplotype and greyhound meningoencephalitis, suggesting an immunogenetic risk factor for the development of the disease. Greyhound meningoencephalitis may be a suitable model for human neuroinflammatory diseases with an immunogenetic component. PMID:24851745

  14. Immunotoxin Against a Donor MHC Class II Molecule Induces Indefinite Survival of Murine Kidney Allografts.

    Science.gov (United States)

    Brown, K; Nowocin, A K; Meader, L; Edwards, L A; Smith, R A; Wong, W

    2016-04-01

    Rejection of donor organs depends on the trafficking of donor passenger leukocytes to the secondary lymphoid organs of the recipient to elicit an immune response via the direct antigen presentation pathway. Therefore, the depletion of passenger leukocytes may be clinically applicable as a strategy to improve graft survival. Because major histocompatibility complex (MHC) class II(+) cells are most efficient at inducing immune responses, selective depletion of this population from donor grafts may dampen the alloimmune response and prolong graft survival. In a fully MHC mismatched mouse kidney allograft model, we describe the synthesis of an immunotoxin, consisting of the F(ab')2 fragment of a monoclonal antibody against the donor MHC class II molecule I-A(k) conjugated with the plant-derived ribosomal inactivating protein gelonin. This anti-I-A(k) gelonin immunotoxin depletes I-A(k) expressing cells specifically in vitro and in vivo. When given to recipients of kidney allografts, it resulted in indefinite graft survival with normal graft function, presence of Foxp3(+) cells within donor grafts, diminished donor-specific antibody formation, and delayed rejection of subsequent donor-type skin grafts. Strategies aimed at the donor arm of the immune system using agents such as immunotoxins may be a useful adjuvant to existing recipient-orientated immunosuppression. PMID:26799449

  15. MULTIPRED2: A computational system for large-scale identification of peptides predicted to bind to HLA supertypes and alleles

    DEFF Research Database (Denmark)

    Zhang, Guang Lan; DeLuca, David S.; Keskin, Derin B.;

    2011-01-01

    MULTIPRED2 is a computational system for facile prediction of peptide binding to multiple alleles belonging to human leukocyte antigen (HLA) class I and class II DR molecules. It enables prediction of peptide binding to products of individual HLA alleles, combination of alleles, or HLA supertypes...

  16. Rational Design Synthesis and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases

    Energy Technology Data Exchange (ETDEWEB)

    R Daher; M Coincon; M Fonvielle; P Gest; M Guerin; M Jackson; J Sygusch; M Therisod

    2011-12-31

    We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows Ki against class II Fbas from various pathogens in the nM range, with very high selectivity (up to 105). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.

  17. 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

    Major histocompatibility complex (MHC) molecules play a key role in cell-mediated immune responses presenting bounded peptides for recognition by the immune system cells. Several in silico methods have been developed to predict the binding affinity of a given peptide to a specific MHC molecule. One...... made available, and also new structures of MHC class I molecules with a bound peptide have been published. In order to test if the NetMHCpan method can be improved by integrating this novel information, we created new pseudo-sequence definitions for the MHC-binding cleft environment from sequence and...... but also by a refined definition of the MHC-binding environment including information from non-human species....

  18. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lamberth, K; Harndahl, M;

    2008-01-01

    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 IC50 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...

  19. 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. PMID:10134156

  20. Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins II reactions at side-chain loci in model systems

    International Nuclear Information System (INIS)

    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

  1. Selection of a high-affinity and in vivo bioactive ssDNA aptamer against angiotensin II peptide.

    Science.gov (United States)

    Heiat, Mohammad; Ranjbar, Reza; Latifi, Ali Mohammad; Rasaee, Mohammad Javad

    2016-08-01

    Unique features of aptamers have attracted interests for a broad range of applications. Aptamers are able to specifically bind to targets and inhibit their functions. This study, aimed to isolate the high affinity ssDNA aptamers against bio-regulator peptide angiotensin II (Ang II) and investigate their bioactivity in cellular and animal models. To isolate ssDNA aptamers, 12 rounds of affinity chromatography SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure were carried out. The SPR (surface plasmon resonance) and ELONA (enzyme linked oligonucleotide assay) analysis were used to determine the affinity and specificity of aptamers. The ability of selected aptamers to inhibit the proliferative effect of Ang II on human aortic vascular smooth muscle cells (HA-VSMCs) and their performance on Wistar rat urinary system and serum electrolyte levels were investigated. Two full-length aptamers (FLC112 and FLC125) with high affinity of respectively 7.52±2.44E-10 and 5.87±1.3E-9M were isolated against Ang II. The core regions of these aptamers (CRC112 and CRC125) also showed affinity of 5.33±1.15E-9 and 4.11±1.09E-9M. In vitro analysis revealed that FLC112 and FLC125 can inhibit the proliferative effect of Ang II on HA-VSMCs (Psodium level and increased the urine volume (Pbioactive aptamers may lead to excellent results in blocking Ang II activity. PMID:27298205

  2. Articulación de fones en individuos clase esqueletal I,II y III Speech patterns in skeletal class I, II and III subjects

    Directory of Open Access Journals (Sweden)

    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

  3. Combinatorial Assembly of Simple and Complex d-Lysergic Acid Alkaloid Peptide Classes in the Ergot Fungus Claviceps purpurea*S⃞

    OpenAIRE

    Ortel, Ingo; Keller, Ullrich

    2009-01-01

    The ergot fungus Claviceps purpurea produces both ergopeptines and simple d-lysergic acid alkylamides. In the ergopeptines, such as ergotamine, d-lysergic acid is linked to a bicyclic tripeptide in amide-like fashion, whereas in the d-lysergylalkanolamides it is linked to an amino alcohol derived from alanine. We show here that these compound classes are synthesized by a set of three non-ribosomal lysergyl peptide synthetases (LPSs), which interact in a combinatorial f...

  4. Structural and computational analysis of peptide recognition mechanism of class-C type penicillin binding protein, alkaline D-peptidase from Bacillus cereus DF4-B.

    Science.gov (United States)

    Nakano, Shogo; Okazaki, Seiji; Ishitsubo, Erika; Kawahara, Nobuhiro; Komeda, Hidenobu; Tokiwa, Hiroaki; Asano, Yasuhisa

    2015-01-01

    Alkaline D-peptidase from Bacillus cereus DF4-B, called ADP, is a D-stereospecific endopeptidase reacting with oligopeptides containing D-phenylalanine (D-Phe) at N-terminal penultimate residue. ADP has attracted increasing attention because it is useful as a catalyst for synthesis of D-Phe oligopeptides or, with the help of substrate mimetics, L-amino acid peptides and proteins. Structure and functional analysis of ADP is expected to elucidate molecular mechanism of ADP. In this study, the crystal structure of ADP (apo) form was determined at 2.1 Å resolution. The fold of ADP is similar to that of the class C penicillin-binding proteins of type-AmpH. Docking simulations and fragment molecular orbital analyses of two peptides, (D-Phe)4 and (D-Phe)2-(L-Phe)2, with the putative substrate binding sites of ADP indicated that the P1 residue of the peptide interacts with hydrophobic residues at the S1 site of ADP. Furthermore, molecular dynamics simulation of ADP for 50 nsec suggested that the ADP forms large cavity at the active site. Formation of the cavity suggested that the ADP has open state in the solution. For the ADP, having the open state is convenient to bind the peptides having bulky side chain, such as (D-Phe)4. Taken together, we predicted peptide recognition mechanism of ADP. PMID:26370172

  5. Organization and characteristics of the major histocompatibility complex class II region in the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis).

    Science.gov (United States)

    Ruan, Rui; Ruan, Jue; Wan, Xiao-Ling; Zheng, Yang; Chen, Min-Min; Zheng, Jin-Song; Wang, Ding

    2016-01-01

    Little is known about the major histocompatibility complex (MHC) in the genome of Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) (YFP) or other cetaceans. In this study, a high-quality YFP bacterial artificial chromosome (BAC) library was constructed. We then determined the organization and characterization of YFP MHC class II region by screening the BAC library, followed by sequencing and assembly of positive BAC clones. The YFP MHC class II region consists of two segregated contigs (218,725 bp and 328,435 bp respectively) that include only eight expressed MHC class II genes, three pseudo MHC genes and twelve non-MHC genes. The YFP has fewer MHC class II genes than ruminants, showing locus reduction in DRB, DQA, DQB, and loss of DY. In addition, phylogenic and evolutionary analyses indicated that the DRB, DQA and DQB genes might have undergone birth-and-death evolution, whereas the DQB gene might have evolved under positive selection in cetaceans. These findings provide an essential foundation for future work, such as estimating MHC genetic variation in the YFP or other cetaceans. This work is the first report on the MHC class II region in cetaceans and offers valuable information for understanding the evolution of MHC genome in cetaceans. PMID:26932528

  6. Expression of GFP-mTalin reveals an actin-related role for the Arabidopsis Class II formin AtFH12

    OpenAIRE

    Cvrčková, F.; Grunt, M.; Žárský, V.

    2012-01-01

    Formins (FH2 proteins) are implicated in F-actin nucleation and other aspects of cytoskeletal organization. Plants possess two formin clades, relatively well-described Class I formins and so far poorly characterized Class II formins. Comparison of Class II formin genes of two Arabidopsis species, A. thaliana and A. lyrata, indicates dynamic evolution within the Class II formin clade. Disruption of an outlier A. thaliana Class II formin gene, AtFH12 (At1g42980), whose expression is induced by ...

  7. 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)

    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)

  8. Type I interferon drives a distinctive dendritic cell maturation phenotype that allows continued class II MHC synthesis and antigen processing

    OpenAIRE

    Simmons, Daimon P.; Wearsch, Pamela A.; Canaday, David H; Meyerson, Howard J.; Liu, Yi C.; Wang, Ying; Boom, W Henry; Harding, Clifford V.

    2012-01-01

    Microbial molecules or cytokines can stimulate dendritic cell (DC) maturation, which involves DC migration to lymph nodes and enhanced presentation of Ag to launch T cell responses. Microbial Toll-like receptor (TLR) agonists are the most studied inducers of DC maturation, but type I interferon (IFN-I) also promotes DC maturation. In response to TLR stimulation, DC maturation involves a burst of Ag processing with enhanced expression of peptide-MHC-II complexes and co-stimulator molecules. Su...

  9. 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

    Directory of Open Access Journals (Sweden)

    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.

  10. Study of the number of occlusal contacts in maximum intercuspation before orthodontic treatment in subjects with Angle Class I and Class II Division 1 malocclusion

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Watanabe-Kanno

    2012-02-01

    Full Text Available OBJECTIVE: Define and compare numbers and types of occlusal contacts in maximum intercuspation. METHODS: The study consisted of clinical and photographic analysis of occlusal contacts in maximum intercuspation. Twenty-six Caucasian Brazilian subjects were selected before orthodontic treatment, 20 males and 6 females, with ages ranging between 12 and 18 years. The subjects were diagnosed and grouped as follows: 13 with Angle Class I malocclusion and 13 with Angle Class II Division 1 malocclusion. After analysis, the occlusal contacts were classified according to the established criteria as: tripodism, bipodism, monopodism (respectively, three, two or one contact point with the slope of the fossa; cuspid to a marginal ridge; cuspid to two marginal ridges; cuspid tip to opposite inclined plane; surface to surface; and edge to edge. RESULTS: The mean number of occlusal contacts per subject in Class I malocclusion was 43.38 and for Class II Division 1 malocclusion it was 44.38, this difference was not statistically significant (p>0.05. CONCLUSIONS: There is a variety of factors that influence the number of occlusal contacts between a Class I and a Class II, Division 1 malocclusion. There is no standardization of occlusal contact type according to the studied malocclusions. A proper selection of occlusal contact types such as cuspid to fossa or cuspid to marginal ridge and its location in the teeth should be individually defined according to the demands of each case. The existence of an adequate occlusal contact leads to a correct distribution of forces, promoting periodontal health.

  11. The Atlantic Salmon MHC class II alpha and beta promoters are active in mammalian cell lines.

    Science.gov (United States)

    Vestrheim, O; Lundin, M; Syed, M

    2007-01-01

    The major histocompatibility complex class II (MHCII) genes are only constitutively expressed in certain immune response cells such as B cells, macrophages, dendritic cells and other antigen presenting cells. This cell specific expression pattern and the presence of conserved regions such as the X-, X2-, Y-, and W-boxes make the MHCII promoters especially interesting as vector constructs. We tested whether the Atlantic salmon (Salmo salar L.) MHCII promoters can function in cell lines from other organisms. We found that the salmon MHCII alpha and MHCII beta promoters could drive expression of a LacZ reporter gene in adherent lymphoblast cell lines from dog (DH82) and rabbit (HybL-L). This paper shows that the promoters of Atlantic salmon MHCII alpha and beta genes can function in mammalian cell lines. PMID:17934904

  12. Alkali/Surfactant/Polymer Flooding in the Daqing Oilfield Class II Reservoirs Using Associating Polymer

    Directory of Open Access Journals (Sweden)

    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%.

  13. A randomized controlled 30 years follow up of three conventional resin composites in Class II restorations

    DEFF Research Database (Denmark)

    Pallesen, Ulla; van Dijken, Jan WV

    2015-01-01

    three (one set) as similar as possible Class II restorations of moderate size.After cavity preparation, the three cavities were chosen at random to be restored with twochemical-cured (P10, Miradapt) and one light-cured resin composite (P30). A chemical-curedenamel bonding agent was applied after etching...... of the enamel. The chemical-cured resincomposites were placed in bulk and the light-cured in increments. One operator placed 99restorations (33 sets). The restorations were evaluated with slightly modified USPHS crite-ria at baseline, 2, 3, 5, 10, 15, 20 and 30 years. Statistical analyses were...... performed by theKaplan–Meier, log-rank test and Cox regression analyses. Results. After 30 years, 5 participants with 15 restorations (15%) could not be evaluated duringthe whole evaluation. Seven participants were considered as caries risk and eight partici-pants as having active parafunctional habits...

  14. 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

    OpenAIRE

    Carolina Lisbôa Mezzomo; Patrícia Girarde Machado; Andrielle de Bitencourt Pacheco; Bruna Franciele da Trindade Gonçalves; Carla Franco Hoffmann

    2011-01-01

    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...

  15. Discovery of periodic class II methanol masers associated with G339.986-0.425 region

    Science.gov (United States)

    Maswanganye, J. P.; van der Walt, D. J.; Goedhart, S.; Gaylard, M. J.

    2016-03-01

    10 new class II methanol masers from the 6.7-GHz Methanol Multibeam survey catalogues III and IV were selected for a monitoring programme at both 6.7 and 12.2 GHz with the 26-m Hartebeesthoek Radio Astronomy Observatory radio telescope for 2 yr and 9 months, from 2012 August to 2015 May. In the sample, only masers associated with G339.986-0.425 were found to show periodic variability at both 6.7 and 12.2 GHz. The existence of periodic variation was tested with four independent methods. The analytical method gave the best estimation of the period, which was 246 ± 1 d. The time series of G339.986-0.425 show strong correlations across velocity channels and between the 6.7- and 12.2-GHz masers. The time delay was also measured across channels and shows structure across the spectrum which is continuous between different maser components.

  16. Orthodontic camouflage via total arch movement in a Class II with idiopathic condylar resorption

    Directory of Open Access Journals (Sweden)

    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.

  17. Treatment effects of myofunctional appliances in different jaw rotations in Class II division 1 malocclusion

    Directory of Open Access Journals (Sweden)

    Kyumi V Shethiya

    2015-01-01

    Full Text Available Aim: This retrospective study was conducted to determine skeletal, dentoalveolar changes in children treated with Twin Block or activator for the treatment of Class II Division 1 malocclusion with different jaw rotations. Materials and Methods: Standardized lateral cephalograms of 32 patients (18 boys, 14 girls between the ages of 11 and 14 years were chosen and divided into two groups, high angle (FMA >27 and low angle (FMA <20. Cephalograms were taken at T1 (pre-treatment and T2 (after one year of myofunctional therapy.These were manually traced and analysed. Results: The results showed statistically significant increase in SNB angle, VRP-Pog due to forward movement of the mandible. The overjet reduced significantly due to retroclination of upper incisors and proclination of lower incisors in both groups. Conclusion: It was concluded that both high angle and low angle groups responded equally well to myofunctional therapy showing significant skeletal and dentoalveolar changes.

  18. Partial N-terminal sequence analysis of human class II molecules expressing the DQw3 determinant.

    Science.gov (United States)

    Obata, F; Endo, T; Yoshii, M; Otani, F; Igarashi, M; Takenouchi, T; Ikeda, H; Ogasawara, K; Kasahara, M; Wakisaka, A

    1985-09-01

    HLA-DQ molecules were isolated from DRw9-homozygous and DR4-homozygous cell lines by using a monoclonal antibody HU-18, which recognizes class II molecules carrying the conventional DQw3 determinant. The partial N-terminal sequence analysis of the DQw3 molecules revealed that they have sequences homologous to those of murine I-A molecules. Within the limits of our sequence analysis, the DQw3 molecules from the two cell lines are identical to each other in both the alpha and beta chains. The DQ alpha as well as DQ beta chains were found to have amino acid substitutions when compared to other I-A-like molecules whose sequences have been reported. These differences may contribute to the DQw supertypic specificity. The polymorphic nature of DQ molecules is in marked contrast to that of DR molecules where DR alpha chains are highly conserved while DR beta chains have easily detectable amino acid substitutions. PMID:2411700

  19. Influence of kinship and MHC class II genotype on visual traits in zebrafish larvae (Danio rerio).

    Science.gov (United States)

    Hinz, Cornelia; Gebhardt, Katharina; Hartmann, Alexander K; Sigman, Lauren; Gerlach, Gabriele

    2012-01-01

    Kin recognition can drive kin selection and the evolution of social behaviour. In zebrafish (Danio rerio, Hamilton 1822), kin recognition is based on olfactory and visual imprinting processes. If larvae are exposed to visual and chemical cues of kin at day 5 and 6 post fertilization they will recognize kin throughout life, while exposure to non-kin fails to trigger any recognition. Chemical imprinting signals are transcribed by polymorphic genes of the major histocompatibility complex (MHC) code; however, the underlying mechanism for visual imprinting remains unclear. Here we provide evidence for the existence of family-specific differences in morphometry and pigmentation pattern of six day old zebrafish larvae. While rump, tail and body pigmentation were dependent on relatedness, iris pigmentation and morphometry were also influenced by MHC class II genotype. Our study revealed that the MHC not only influences the chemical signature of individuals, but also their visual appearance. PMID:23251449

  20. Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp. Strain A3.

    Science.gov (United States)

    Baindara, Piyush; Chaudhry, Vasvi; Mittal, Garima; Liao, Luciano M; Matos, Carolina O; Khatri, Neeraj; Franco, Octavio L; Patil, Prabhu B; Korpole, Suresh

    2016-01-01

    Attempts to isolate novel antimicrobial peptides from microbial sources have been on the rise recently, despite their low efficacy in therapeutic applications. Here, we report identification and characterization of a new efficient antimicrobial peptide from a bacterial strain designated A3 that exhibited highest identity with Paenibacillus ehimensis. Upon purification and subsequent molecular characterization of the antimicrobial peptide, referred to as penisin, we found the peptide to be a bacteriocin-like peptide. Consistent with these results, RAST analysis of the entire genome sequence revealed the presence of a lantibiotic gene cluster containing genes necessary for synthesis and maturation of a lantibiotic. While circular dichroism and one-dimension nuclear magnetic resonance experiments confirmed a random coil structure of the peptide, similar to other known lantibiotics, additional biochemical evidence suggests posttranslational modifications of the core peptide yield six thioether cross-links. The deduced amino acid sequence of the putative biosynthetic gene penA showed approximately 74% similarity with elgicin A and 50% similarity with the lantibiotic paenicidin A. Penisin effectively killed methicillin-resistant Staphylococcus aureus (MRSA) and did not exhibit hemolysis activity. Unlike other lantibiotics, it effectively inhibited the growth of Gram-negative bacteria. Furthermore, 80 mg/kg of body weight of penisin significantly reduced bacterial burden in a mouse thigh infection model and protected BALB/c mice in a bacteremia model entailing infection with Staphylococcus aureus MTCC 96, suggesting that it could be a promising new antimicrobial peptide. PMID:26574006

  1. Class I and Class II restorations of resin composite: an FE analysis of the influence of modulus of elasticity on stresses generated by occlusal loading

    DEFF Research Database (Denmark)

    Asmussen, Erik; Peutzfeldt, Anne

    2008-01-01

    was that the marginal stresses would decrease with increasing modulus of elasticity of the restoration. METHODS: A cylindrical tooth was modelled in enamel and dentin and fitted with a Class I or a Class II restoration of resin composite. In one scenario the restoration was bonded to the tooth, in...... another the restoration was left nonbonded. The resin composite was modelled with a modulus of elasticity of 5, 10, 15 or 20 GPa and loaded occlusally with 100 N. By means of the soft-ware program ABAQUS the von Mises stresses in enamel and dentin were calculated. RESULTS: In the bonded scenario, the...

  2. 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.

  3. A class II KNOX gene, KNOX4, controls seed physical dormancy.

    Science.gov (United States)

    Chai, Maofeng; Zhou, Chuanen; Molina, Isabel; Fu, Chunxiang; Nakashima, Jin; Li, Guifen; Zhang, Wenzheng; Park, Jongjin; Tang, Yuhong; Jiang, Qingzhen; Wang, Zeng-Yu

    2016-06-21

    Physical dormancy of seed is an adaptive trait that widely exists in higher plants. This kind of dormancy is caused by a water-impermeable layer that blocks water and oxygen from the surrounding environment and keeps embryos in a viable status for a long time. Most of the work on hardseededness has focused on morphological structure and phenolic content of seed coat. The molecular mechanism underlying physical dormancy remains largely elusive. By screening a large number of Tnt1 retrotransposon-tagged Medicago truncatula lines, we identified nondormant seed mutants from this model legume species. Unlike wild-type hard seeds exhibiting physical dormancy, the mature mutant seeds imbibed water quickly and germinated easily, without the need for scarification. Microscopic observations of cross sections showed that the mutant phenotype was caused by a dysfunctional palisade cuticle layer in the seed coat. Chemical analysis found differences in lipid monomer composition between the wild-type and mutant seed coats. Genetic and molecular analyses revealed that a class II KNOTTED-like homeobox (KNOXII) gene, KNOX4, was responsible for the loss of physical dormancy in the seeds of the mutants. Microarray and chromatin immunoprecipitation analyses identified CYP86A, a gene associated with cutin biosynthesis, as one of the downstream target genes of KNOX4 This study elucidated a novel molecular mechanism of physical dormancy and revealed a new role of class II KNOX genes. Furthermore, KNOX4-like genes exist widely in seed plants but are lacking in nonseed species, indicating that KNOX4 may have diverged from the other KNOXII genes during the evolution of seed plants. PMID:27274062

  4. Microleakage of Class II Combined Amalgam-Composite Restorations Using Different Composites and Bonding Agents

    Directory of Open Access Journals (Sweden)

    F. Sharafeddin

    2008-09-01

    Full Text Available Objective: The purpose of the present study was to assess the microleakage of composite restorations with and without a cervical amalgam base and to compare the results of dif-ferent composites and bonding agents.Materials and Methods: One hundred and twenty mesio-occlusal (MO and disto-occlusal (DO Class II cavities were prepared on sixty extracted permanent premolar teeth. The teeth were randomly divided into four groups of 30 and restored as follows:In group A, the mesio-occlusal cavity (MO, Scotchbond multi purpose plus + Z250 and in the disto-occlusal (DO cavity, Prompt-L-Pop + Z250 were applied. As for group B, in the MO and DO cavities, Clearfil SE Bond + Clearfil APX, and varnish + amalgam (In box + Clearfil SE Bond + Clearfil APX were used respectivelywhile in group C; the teeth were restored with amalgam and varnish mesio-occlusally and with amalgam only disto-occlusally. As for group D, varnish + amalgam (in box + Scotchbond multi purpose plus + Z250 were applied mesio-occlusally and Varnish + Amalgam (in box + Prompt–L–Pop + Z250 disto-occlusally.Marginal leakage was assessed by the degree of dye penetration into various sections of the restored teeth. Chi-square and Fisher's exact tests were used for data analysis.Results: Microleakage in gingival margin was more than that in occlusal margin (P<0.05 and microleakage of combined amalgam-composite restorations was significantly lower than that of conventional composite and amalgam restorations.Conclusion: Marginal microleakage decreased by using amalgam at the base of the box in Class II composite restorations.

  5. 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.

  6. Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor-specific antigens.

    Science.gov (United States)

    Barnea, Eilon; Beer, Ilan; Patoka, Renana; Ziv, Tamar; Kessler, Ofra; Tzehoval, Esther; Eisenbach, Lea; Zavazava, Nicholas; Admon, Arie

    2002-01-01

    The Human MHC Project aims at comprehensive cataloging of peptides presented within the context of different human leukocyte antigens (HLA) expressed by cells of various tissue origins, both in health and in disease. Of major interest are peptides presented on cancer cells, which include peptides derived from tumor antigens that are of interest for immunotherapy. Here, HLA-restricted tumor-specific antigens were identified by transfecting human breast, ovarian and prostate tumor cell lines with truncated genes of HLA-A2 and HLA-B7. Soluble HLA secreted by these cell lines were purified by affinity chromatography and analyzed by nano-capillary electrospray ionization-tandem mass spectrometry. Typically, a large peptide pool was recovered and sequenced including peptides derived from MAGE-B2 and mucin and other new tumor-derived antigens that may serve as potential candidates for immunotherapy. PMID:11782012

  7. Deciding factors in the treatment of Class II division 1 cases with and without single-jaw extractions.

    Science.gov (United States)

    Afaf, Houb-Dine; Bahije, Loubna; Zaoui, Fatima; Abouqal, Redouane; Rerhrhaye, Wiam

    2014-06-01

    Extraction of two upper premolars in Class II division 1 occlusions often constitutes a therapeutic compromise for the orthodontic practitioner. The aim of our study was to compare the initial occlusal and cephalometric severity of Class II division 1 malocclusions in two groups of patients treated with and without extraction of two upper premolars and thus determine the factor or factors determining this therapeutic option. Examination of the casts and cephalometric analysis of 31 patients presenting a Class II division 1 malocclusion were made. The non-extraction group comprised 16 patients and the group undergoing extraction of two upper premolars comprised 15 patients. Discriminant analysis was applied using binary decision trees in order to identify the variable which best distinguished the two groups. Maxillary incisor-canine crowding was selected to discriminate between the patients at pretreatment stage; 93.5% of the patients were correctly classified using this factor. PMID:24820698

  8. 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. In...

  9. Co(II) complexes of amino acids and peptides in aqueous solution studied by 170 NMR

    International Nuclear Information System (INIS)

    Structural, dynamic and kinetic 170 NMR investigations of the complexation of metal ions with amino acids and peptides were performed in Glicine, proling cyclo(Ala '1'70-Ala), cyclo-(Gly170-Pro) and cyclo(Pro170-Gly). The 170 carboxyl and carbonylsignals of paramagnetic complexes with amino acids were observed and allowed for the determinatio, in several cases, of the stoichiometry of the ocmplexes formed and the kinetic and thermodynamic parameters characterizing ligand exchange. It was found that the paramagnetic ions bind to the oxygen of the peptide carboxyl group. (H.W.). 25 refs.; 10 figs.; 3 tabs

  10. Class IIa Bacteriocins: Current Knowledge and Perspectives

    Science.gov (United States)

    Belguesmia, Yanath; Naghmouchi, Karim; Chihib, Nour-Eddine; Drider, Djamel

    Lactic acid bacteria (LAB) are known to produce antibacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. Bacteriocins fall structurally and chemically into three different classes, I, II, and III. Bacteriocins are ribosomally synthesized peptides with antagonism against closely related bacteria. This late observation has evolved because bacteriocins active against Gram-negative bacteria have recently been reported. Members of class IIa bacteriocins, referred to as pediocin-like bacteriocins, are among the most studied bacteriocins. This chapter is aimed at providing an updated review on the biology of class IIa bacteriocins.

  11. Long maximal incremental tests accurately assess aerobic fitness in class II and III obese men.

    Directory of Open Access Journals (Sweden)

    Stefano Lanzi

    Full Text Available This study aimed to compare two different maximal incremental tests with different time durations [a maximal incremental ramp test with a short time duration (8-12 min (STest and a maximal incremental test with a longer time duration (20-25 min (LTest] to investigate whether an LTest accurately assesses aerobic fitness in class II and III obese men. Twenty obese men (BMI≥35 kg.m-2 without secondary pathologies (mean±SE; 36.7±1.9 yr; 41.8±0.7 kg*m-2 completed an STest (warm-up: 40 W; increment: 20 W*min-1 and an LTest [warm-up: 20% of the peak power output (PPO reached during the STest; increment: 10% PPO every 5 min until 70% PPO was reached or until the respiratory exchange ratio reached 1.0, followed by 15 W.min-1 until exhaustion] on a cycle-ergometer to assess the peak oxygen uptake [Formula: see text] and peak heart rate (HRpeak of each test. There were no significant differences in [Formula: see text] (STest: 3.1±0.1 L*min-1; LTest: 3.0±0.1 L*min-1 and HRpeak (STest: 174±4 bpm; LTest: 173±4 bpm between the two tests. Bland-Altman plot analyses showed good agreement and Pearson product-moment and intra-class correlation coefficients showed a strong correlation between [Formula: see text] (r=0.81 for both; p≤0.001 and HRpeak (r=0.95 for both; p≤0.001 during both tests. [Formula: see text] and HRpeak assessments were not compromised by test duration in class II and III obese men. Therefore, we suggest that the LTest is a feasible test that accurately assesses aerobic fitness and may allow for the exercise intensity prescription and individualization that will lead to improved therapeutic approaches in treating obesity and severe obesity.

  12. A mutant L-asparaginase II signal peptide improves the secretion of recombinant cyclodextrin glucanotransferase and the viability of Escherichia coli.

    Science.gov (United States)

    Ismail, Noor Faizah; Hamdan, Salehhuddin; Mahadi, Nor Muhammad; Murad, Abdul Munir Abdul; Rabu, Amir; Bakar, Farah Diba Abu; Klappa, Peter; Illias, Rosli Md

    2011-05-01

    L-Asparaginase II signal peptide was used for the secretion of recombinant cyclodextrin glucanotransferase (CGTase) into the periplasmic space of E. coli. Despite its predominant localisation in the periplasm, CGTase activity was also detected in the extracellular medium, followed by cell lysis. Five mutant signal peptides were constructed to improve the periplasmic levels of CGTase. N1R3 is a mutated signal peptide with the number of positively charged amino acid residues in the n-region increased to a net charge of +5. This mutant peptide produced a 1.7-fold enhancement of CGTase activity in the periplasm and significantly decreased cell lysis to 7.8% of the wild-type level. The formation of intracellular inclusion bodies was also reduced when this mutated signal peptide was used as judged by SDS-PAGE. Therefore, these results provide evidence of a cost-effective means of expression of recombinant proteins in E. coli. PMID:21234789

  13. Dental and orthopedic effects of Bass and Herbst therapy for correction of severe class II division 1 malocclusions

    OpenAIRE

    Ömblus, Jane

    1996-01-01

    Ömblus J (1996). Dental and orthopedic effects of Bass and Herbst therapy for correction of severe Class 1I division l malocclusions. Thesis, Karolinska Institutet. Functional appliance therapy to correct Class II division I malocclusions has been a subject of debate throughout this century. The aims of this thesis, based on six publications, were to evaluate the dental and orthopedic effects of Bass appliance therapy in relation to treatment intensity, age, an...

  14. Direct Activation of Human Dendritic Cells by Particle-Bound but Not Soluble MHC Class II Ligand

    OpenAIRE

    Baleeiro, Renato; Wiesmüller, Karl Heinz; Dähne, Lars; Lademann, Jürgen; Barbuto, José; Walden, Peter

    2013-01-01

    textabstractDendritic cells (DCs) are key activators of cellular immune responses through their capacity to induce naïve T cells and sustained effector T cell responses. This capacity is a function of their superior efficiency of antigen presentation via MHC class I and class II molecules, and the expression of co-stimulatory cell surface molecules and cytokines. Maturation of DCs is induced by microbial factors via pattern recognition receptors such as Toll-like receptors, pro-inflammatory c...

  15. Structural basis of diverse peptide accommodation by the rhesus macaque MHC class I molecule Mamu-B*17: insights into immune protection from simian immunodeficiency virus.

    Science.gov (United States)

    Wu, Yan; Gao, Feng; Liu, Jun; Qi, Jianxun; Gostick, Emma; Price, David A; Gao, George F

    2011-12-15

    The MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA-B*57 in HIV-infected individuals. In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and IW11 (IRYPKTFGWLW). The structures reveal that not only P2, but also P1 and P3, can be used as N-terminal anchor residues by Mamu-B*17-restricted peptides. Moreover, the N-terminal anchor residues exhibit a broad chemical specificity, encompassing basic (H and R), bulky polar aliphatic (Q), and small (T) residues. In contrast, Mamu-B*17 exhibits a very narrow preference for aromatic residues (W and F) at the C terminus, similar to that displayed by HLA-B*57. Flexibility within the whole peptide-binding groove contributes to the accommodation of these diverse peptides, which adopt distinct conformations. Furthermore, the unusually large pocket D enables compensation from other peptide residues if P3 is occupied by an amino acid with a small side chain. In addition, residues located at likely TCR contact regions present highly flexible conformations, which may impact TCR repertoire profiles. These findings provide novel insights into the structural basis of diverse peptide accommodation by Mamu-B*17 and highlight unique atomic features that might contribute to the protective effect of this MHC I molecule in SIV-infected rhesus macaques. PMID:22084443

  16. A kinked antimicrobial peptide from Bombina maxima. II. Behavior in phospholipid bilayers.

    Science.gov (United States)

    Heinzmann, Ralf; Grage, Stephan L; Schalck, Constantin; Bürck, Jochen; Bánóczi, Zoltán; Toke, Orsolya; Ulrich, Anne S

    2011-04-01

    The preceding contribution by Toke et al. has studied the structure of the cationic antimicrobial peptide maximin-4 in detergent micelles and in organic solvent, revealing a different kink angle and side-chain interactions in the two different environments. Here, we have examined the same peptide in lipid bilayers using oriented circular dichroism (OCD) and solid-state (15)N nuclear magnetic resonance (NMR) in aligned samples. OCD showed that maximin-4 is helical and adopts an oblique alignment in the membrane, and lacks the characteristic realignment response that is often observed for amphipathic α-helical peptides at a peptide:lipid ratio between 1:100 and 1:20. Solid-state (15)N-NMR experiments suggest that maximin-4 also remains unaffected by lipid charge and temperature. Analyzing (15)N labels in positions Ala12, Ala13, and Leu14, an oblique tilt angle of the N-terminal helix of ~130° relative to the membrane normal was found, in good agreement with the amphiphilic profile of this segment. An additional constraint at Ala22 in the C-terminal segment is found to be compatible with a continuous α-helix, but unfavorable side-chain interactions make this solution unlikely. Instead, a kink at Gly16 seems fully compatible with all known constraints and with the biophysical expectations in the membrane-bound state, given the liquid-state NMR structures. It thus seems that the flexible kink in maximin-4 allows the two helical segments to adjust to the local environment. The irregular amphiphilic profile and the resulting versatility in shape might explain why maximin-4 lacks the realignment response that has been characteristically observed for many related frog peptides forming straight amphipathic α-helices. PMID:21312034

  17. 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

    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......-based predictions (NetMHCpan). The updated NetMHCpan server was used to predict BoLA-I binding peptides within the P1 structural polyprotein sequence of FMDV (strain A24 Cruzeiro) for BoLA-1*01901, BoLA-2*00801, BoLA-2*01201, and BoLA-4*02401. Peptide binding affinity and stability were determined for these Bo....... The results of these analyses showed that BoLA alleles cluster into three distinct groups with the potential to define “BoLA supertypes.” This streamlined approach identifies potential T cell epitopes from pathogens, such as FMDV, and provides insight into T cell immunity following infection or vaccination....

  18. Enhanced T cell responses to antigenic peptides targeted to B cell surface Ig, Ia, or class I molecules

    OpenAIRE

    1988-01-01

    The helper T cell recognition of soluble globular protein antigens requires that the proteins be processed by an APC, releasing a peptide that is transported to and held on the APC surface where it is recognized by the specific T cell in conjunction with Ia. When cellular processing functions are blocked, APC lose their ability to present native antigens while retaining the capacity to activate T cells when provided with a cognate peptide fragment that contains the T cell antigenic determinan...

  19. Designer Lipid-Like Peptides: A Class of Detergents for Studying Functional Olfactory Receptors Using Commercial Cell-Free Systems

    OpenAIRE

    Corin, Karolina; Baaske, Philipp; Ravel, Deepali B.; Song, Junyao; Brown, Emily; Wang, Xiaoqiang; Wienken, Christoph J.; Jerabek-Willemsen, Moran; Duhr, Stefan; Yuan LUO; 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-helica...

  20. 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; Lund, Ole; Nielsen, Morten; Karlsson, A. C.

    2011-01-01

    Background: CD4+ T cells orchestrate immune protection by ‘‘helping’’ other cells of our immune system to clear viral infections. It is well known that the preferential infection and depletion of CD4+ T cells contributes to hampered systemic T cell help following HIV infection. However, 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...

  1. Recidiva do apinhamento anterossuperior nas más oclusões de Classe I e Classe II tratadas ortodonticamente sem extrações Relapse of maxillary anterior crowding in Class I and Class II malocclusions orthodontically treated without extractions

    Directory of Open Access Journals (Sweden)

    Willian J. G. Guirro

    2011-10-01

    Full Text Available OBJETIVO: o presente estudo objetivou comparar retrospectivamente a estabilidade pós-contenção do alinhamento dos incisivos anterossuperiores em pacientes com Classe I e Classe II. MÉTODOS: a amostra consistiu de 38 pacientes de ambos os sexos, tratados sem extrações e com mecânica Edgewise, divididos em dois grupos - Grupo 1, constituído por 19 pacientes, com idade inicial média de 13,06 anos, portadores da má oclusão de Classe I com apinhamento anterossuperior inicial maior que 3mm; Grupo 2, constituído por 19 pacientes, com idade inicial de 12,54 anos, portadores da má oclusão de Classe II e, também, com apinhamento anterossuperior inicial maior que 3mm. Foram medidos nos modelos de estudo, das fases pré- e pós-tratamento e pós-contenção, o índice de irregularidade de Little, as distâncias intercaninos e entre os primeiros e segundos pré-molares, a distância intermolares e o comprimento da arcada superior. Para a comparação intragrupo nos 3 tempos de avaliação, utilizou-se os testes ANOVA e Tukey. A comparação intergrupos foi realizada pelo teste t independente. Para verificação da presença de correlação, utilizou-se o teste de correlação de Pearson. RESULTADOS: os resultados evidenciaram maior estabilidade do tratamento no Grupo 2 (Classe II, pois, durante o período pós-contenção, foi observada recidiva do apinhamento dos dentes anterossuperiores menor no Grupo 2 (0,80mm do que no Grupo 1 (1,67mm. CONCLUSÃO: concluiu-se que o tratamento do apinhamento dos dentes anterossuperiores é mais estável na má oclusão de Classe II do que na má oclusão de Classe I.OBJECTIVE: The present study aimed to retrospectively compare the postretention stability of maxillary anterior incisors alignment in Class I and Class II patients. METHODS: The sample comprised 38 patients of both genders, treated with nonextraction and Edgewise mechanics, divided into two groups: Group 1, comprised of 19 patients, at a mean

  2. 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

  3. Twenty -year post-treatment assessment of class II division 1 malocclusion treated with non-extraction approach

    Directory of Open Access Journals (Sweden)

    Ashok Karad

    2013-01-01

    This article describes twenty-year post-treatment assessment of a class II division 1 malocclusion case, treated in the late mixed dentition stage, with the non-extraction treatment approach - molar-inserted headgear along with a fixed appliance therapy.

  4. Mutational analysis of divalent metal ion binding in the active site of class II α-mannosidase from sulfolobus solfataricus

    DEFF Research Database (Denmark)

    Hansen, Dennis K.; Webb, Helen; Nielsen, Jonas Willum; Winther, Jakob R.; Willemoes, Martin; Harris, Pernille

    2015-01-01

    Mutational analysis of Sulfolobus solfataricus class II α-mannosidase was focused on side chains that interact with the hydroxyls of the-1 mannosyl of the substrate (Asp-534) or form ligands to the active site divalent metal ion (His-228 and His-533) judged from crystal structures of homologous...

  5. 40 CFR 147.2400 - State-administered program-Class I, II, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2400 Section 147.2400 Protection of Environment ENVIRONMENTAL PROTECTION... between the Washington Department of Ecology and Department of Social and Health Services, Related to...

  6. 40 CFR 147.904 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.904 Section 147.904 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.904 Existing Class II enhanced recovery and hydrocarbon... the owner or operator of an existing enhanced recovery or hydrocarbon storage well may not be...

  7. 40 CFR 147.503 - Existing Class II (except enhanced recovery and hydrocarbon storage) wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class II (except enhanced recovery and hydrocarbon storage) wells authorized by rule. 147.503 Section 147.503 Protection of... recovery and hydrocarbon storage) wells authorized by rule. Maximum injection pressure. To meet...

  8. 40 CFR 147.1653 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.1653 Section 147.1653 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  9. 40 CFR 147.903 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.903 Section 147.903 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  10. 40 CFR 147.1454 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.1454 Section 147.1454 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Nevada § 147.1454 Existing Class II enhanced recovery and hydrocarbon... determines that the owner or operator of an existing enhanced recovery or hydrocarbon storage well may not...

  11. 40 CFR 147.504 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.504 Section 147.504 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Florida § 147.504 Existing Class II enhanced recovery and hydrocarbon... the owner or operator of an existing enhanced recovery or hydrocarbon storage well may not be...

  12. 40 CFR 147.1154 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.1154 Section 147.1154 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1154 Existing Class II enhanced recovery and hydrocarbon... determines that the owner or operator of an existing enhanced recovery or hydrocarbon storage will may not...

  13. 40 CFR 147.1153 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.1153 Section 147.1153 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  14. 40 CFR 147.304 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.304 Section 147.304 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Colorado § 147.304 Existing Class II enhanced recovery and hydrocarbon... the owner or operator of an existing enhanced recovery or hydrocarbon storage well may not be...

  15. 40 CFR 147.1354 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.1354 Section 147.1354 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1354 Existing Class II enhanced recovery and hydrocarbon... existing enhanced recovery or hydrocarbon storage well may not be in compliance with the requirements...

  16. 40 CFR 147.1353 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.1353 Section 147.1353 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  17. 40 CFR 147.303 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.303 Section 147.303 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  18. 40 CFR 147.104 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.104 Section 147.104 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.104 Existing Class II enhanced recovery and hydrocarbon... the owner or operator of an existing enhanced recovery or hydrocarbon storage well may not be...

  19. 40 CFR 147.103 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.103 Section 147.103 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  20. 40 CFR 147.2153 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.2153 Section 147.2153 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  1. 40 CFR 147.1953 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.1953 Section 147.1953 Protection of... enhanced recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection...

  2. 40 CFR 147.1453 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.1453 Section 147.1453 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  3. 40 CFR 147.1654 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.1654 Section 147.1654 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1654 Existing Class II enhanced recovery and hydrocarbon... the owner or operator of an existing enhanced recovery or hydrocarbon storage well may not be...

  4. 40 CFR 147.253 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.253 Section 147.253 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  5. 76 FR 50436 - Class II Gaming Regulation Proposals Submitted by Poarch Band of Creek Indians on Behalf of...

    Science.gov (United States)

    2011-08-15

    ...; ] DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Chapter III Class II Gaming Regulation Proposals Submitted by Poarch Band of Creek Indians on Behalf of Tribal Gaming Working Group AGENCY: National Indian Gaming Commission, Interior. ACTION: Request for comments. SUMMARY: The National...

  6. HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6

    DEFF Research Database (Denmark)

    Ødum, Niels; Milman, N; Jakobsen, B K;

    1991-01-01

    The distribution of HLA class II (DR, DQ, and DP) antigens was studied in 41 patients with symptomatic sarcoidosis (SA) and ethnically matched healthy controls. HLA-DR, -DQw1 and -DQw3 typings were performed with alloantisera in the conventional microcytotoxic test, whereas -DP typings were done...

  7. 40 CFR 82.18 - Availability of production in addition to baseline production allowances for class II controlled...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Availability of production in addition to baseline production allowances for class II controlled substances. 82.18 Section 82.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Production and...

  8. PI3KC2{alpha}, a class II PI3K, is required for dynamin-independent internalization pathways

    DEFF Research Database (Denmark)

    Krag, Claudia; Malmberg, Emily Kim; Salcini, Anna Elisabetta

    2010-01-01

    screen using a cell line expressing a diphtheria toxin receptor (DTR, officially known as HBEGF) anchored to GPI (DTR-GPI), which internalizes diphtheria toxin (DT, officially known as DTX) in a dynamin-independent manner, identified PI3KC2a, a class II phosphoinositide 3-kinase (PI3K), as a specific...

  9. 77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-03-19

    ... class II. These devices are intended to be used as an aid in the diagnosis of pulmonary tuberculosis... work on the final version of the guidance, submit either electronic or written comments on the draft... in the diagnosis of pulmonary tuberculosis when used in conjunction with clinical and...

  10. 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.

  11. Efficient purification of unique antibodies using peptide affinity-matrix columns

    DEFF Research Database (Denmark)

    Jensen, Liselotte Brix; Riise, Erik; Nielsen, Leif Kofoed;

    2004-01-01

    Phage display technology was used to identify peptide ligands with unique specificity for a monoclonal model antibody, MK16, that recognises the human multiple sclerosis associated MHC class II molecule DR2 in complex with a myelin basic protein (MBP)-derived peptide corresponding to residue 85-9...

  12. 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. PMID:26363471

  13. Relationship between conformational dynamics and electron transfer in a desolvated peptide. Part II. Temperature dependence.

    Science.gov (United States)

    Parks, Joel H; Semrouni, David; Clavaguéra, Carine; Ohanessian, Gilles

    2013-02-14

    Recent time-resolved lifetime measurements studied the quenching of the fluorescence emitted by a dye covalently bound to the desolvated peptide Dye-Pro(4)-Arg(+)-Trp. This peptide sequence was chosen for study since intramolecular interactions constrain all large-scale fluctuations except for those of the interacting dye and Trp side chain. It was shown that quenching occurred as a result of interaction between the excited dye and tryptophan side chain. These measurements exhibited a temperature dependence that suggested the quenching mechanism was related to electron transfer. This paper presents a comparison of the experimental quenching rate with the Marcus electron transfer model performed with molecular dynamics (MD) calculations. Taking advantage of the AMOEBA force field that explicitly includes polarizability ensures that the intramolecular electrostatic and polarization interactions in this desolvated peptide ion are treated realistically. MD calculations identify both large-scale fluctuations between conformations as well as small-scale fluctuations within a conformation that are shown to be correlated with torsional dynamics of the Trp side chain. Trajectories of the Dye-Trp distance identify the occurrence of close separations required for efficient electron transfer. The temperature dependence of the quenching rate closely follows the rate predicted by the Marcus electron transfer model within uncertainties resulting from statistical averages. Estimates of the energy parameters characterizing the Marcus model indicate the electronic coupling matrix element and the reaction free energy derived from the fits are consistent with published values for transfer in polyproline bridged peptides. These calculations help to provide a molecular basis for investigating conformational changes in desolvated biomolecular ions by fluorescence quenching measurements. PMID:23297809

  14. Hypothesis: Targeted Ikkβ deletion upregulates MIF signaling responsiveness and MHC class II expression in mouse hepatocytes

    Directory of Open Access Journals (Sweden)

    Katherine S Koch

    2010-03-01

    Full Text Available Katherine S Koch, Hyam L LeffertHepatocyte Growth Control and Stem Cell Laboratory, Department of Pharmacology, School of Medicine, University of California, San Diego, CA, USAAbstract: Macrophage migration inhibitory factor (MIF is causally related to the pathogenesis of chronic liver disease but its hepatocellular mechanisms of action are largely unknown. Scattered reports in the literature hint at functional connections between the expression of MIF and major histocompatibility complex (MHC Class II molecules. Not surprisingly, these relationships have not yet been explored in hepatocytes because MIF and MHC Class II cell surface receptors are commonly expressed by other cell types including various antigen presenting cells of the immune system. On the other hand, mounting evidence suggests that heteromeric MIF receptors share a common molecule with intracellular MHC Class II complexes, viz., CD74, which also serves as the MHC Class II chaperone; and, while it is unclear what cancer-related role(s MHC Class II receptors might play, increasing evidence suggests that MIF and CD74 are also implicated in the biology of hepatocellular carcinoma. These reports are provocative for two reasons: firstly, Ikkβ Δhep mice carrying hepatocyte-targeted deletions of Ikkβ, an IκB kinase complex subunit required for the activation of the transcription factor NF-κB (nuclear factor-κB, have been shown to display heightened susceptibilities to hepatotoxins and chemical hepatocarcinogens; secondly, microarray profiling observations indicate that Ikkβ Δhep hepatocytes constitutively and “ectopically” overexpress genes, particularly CD74, CD44 (a MIF-receptor subunit and MHC Class II I-A/E β and I-A α chains, and gene families that regulate host immune process and immune defense responses. These findings together suggest that Ikkβ Δhep mice might express functional MIF and MHC Class II receptors, leading to increased hepatocellular sensitivity to

  15. The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.

    Science.gov (United States)

    Solomon, Christopher; Southwood, Scott; Hoof, Ilka; Rudersdorf, Richard; Peters, Bjoern; Sidney, John; Pinilla, Clemencia; Marcondes, Maria Cecilia Garibaldi; Ling, Binhua; Marx, Preston; Sette, Alessandro; Mothé, Bianca R

    2010-07-01

    Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus macaque potentially being a more relevant model for AIDS outcomes than the Indian rhesus macaque, the Chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility complex (MHC) composition and function, reducing their greater utilization. In this study, we characterized a total of 50 unique Chinese rhesus macaques from several varying origins for their entire MHC class I allele composition and identified a total of 58 unique complete MHC class I sequences. Only nine of the sequences had been associated with Indian rhesus macaques, and 28/58 (48.3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide binding characteristics with the HLA-B7 supertype, the most frequent supertype in human populations. These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques. PMID:20480161

  16. Soft metal ions, Cd(II) and Hg(II), induce triple-stranded alpha-helical assembly and folding of a de novo designed peptide in their trigonal geometries.

    OpenAIRE

    Li, X; K. Suzuki; Kanaori, K; Tajima, K; Kashiwada, A.; Hiroaki, H; Kohda, D; Tanaka, T

    2000-01-01

    We previously reported the de novo design of an amphiphilic peptide [YGG(IEKKIEA)4] that forms a native-like, parallel triple-stranded coiled coil. Starting from this peptide, we sought to regulate the assembly of the peptide by a metal ion. The replacement of the Ile18 and Ile22 residues with Ala and Cys residues, respectively, in the hydrophobic positions disrupted of the triple-stranded alpha-helix structure. The addition of Cd(II), however, resulted in the reconstitution of the triple-str...

  17. EFFECTS OF BETAHISTINE DIHYDROCHLORIDE AS ADJUVANT TO ENALAPRIL THERAPY OF PATIENTS WITH CHRONIC HEART FAILURE CLASS II-II (NYHA SUFFERING FROM GIDDINESS

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2008-01-01

    Full Text Available Aim. To study adjuvant effect of betahistine dihydrochloride to ACE inhibitors in patients with chronic heart failure (CHF class II-III suffering from giddiness.Material and methods. 61 patients with CHF class II-III, ejection fraction ≤45% (Simpson suffering from giddiness were involved into randomized open parallel study. Patients were randomized to Betahistine dihydrochloride plus basic CHF therapy or only basic therapy groups. Enalapril dose titration was performed in all patients. Quality of life and giddiness severity evaluation, electrocardiogram was performed initially and after treatment. Clinical examination results, drug therapy and adverse event were registered at each visit.Results. The target ACE inhibitor dose (≥20 mg daily was reached in 97 % of patients. It led to significant reduction of dyspnea, edemas, CHF class reduction and life quality increase. Significant differences between investigated groups were not found. Reduction of giddiness severity was shown in both groups. There was a trend to more prominent improvement of life quality (р=0,08 and more frequent achievement of target ACE inhibitor dose in patients treated with betahistine dihydrochloride.Conclusion. The target ACE inhibitor dose can be achieved more than in 90% of patients with CHF class II-III without hypotension symptoms. Adjuvant usage of betahistine dihydrochloride is necessary in patients with CHF still suffering from giddiness after achievement of target ACE inhibitor dose.

  18. New Periodic 6.7 GHz Class II Methanol Maser Associated with G358.460-0.391

    CERN Document Server

    Maswanganye, J P; Goedhart, S; van der Walt, D J; Booth, R S

    2014-01-01

    Eight new class II methanol masers selected from the 6.7 GHz Methanol Multibeam survey catalogues I and II were monitored at 6.7 GHz with the 26m Hartebeesthoek Radio Astronomy Observatory (HartRAO) radio telescope for three years and seven months, from February 2011 to September 2014. The sources were also observed at 12.2 GHz and two were sufficiently bright to permit monitoring. One of the eight sources, namely G358.460-0.391, was found to show periodic variations at 6.7 GHz. The period was determined and tested for significance using the Lomb-Scargle, epoch-folding and Jurkevich methods, and by fitting a simple analytic function. The best estimate for the period of the 6.7 GHz class II methanol maser line associated with G358.460-0.391 is 220.0 $\\pm$ 0.2 day.

  19. Construction of Soluble Mamu-B*1703, a Class I Major Histocompatibility Complex of Chinese Rhesus Macaques, Monomer and Tetramer Loaded with a Simian Immunodeficiency Virus Peptide

    Institute of Scientific and Technical Information of China (English)

    Dongyun Ouyang; Xiaoying Wang; Xianhui He; Lihui Xu; Huanjing Shi; Qi Gao; He Guo

    2009-01-01

    Chinese-descent rhesus macaques have become more prevalent for HIV infection and vaccine investigation than Indian-origin macaques. Most of the currently available data and reagents such as major histocompatibility complex (MHC) class I tetramers, however, were derived from Indian-origin macaques due to the dominant use of these animals in history. Although there are significant differences in the immunogenetic background between the two macaque populations, they share a few of common MHC class I alleles. We reported in this study the procedure for preparation of a soluble Mamu-B*1703 (a MHC class I molecule of Chinese macaques) monomer and tetramer loaded with a dominant simian immunodeficiency virus (SIV) epitope IW9 (IRYPKTFGW) that was identified to be Mamu-B*1701-restricted in Indian macaques. The DNA fragment encoding the Mamu-B*1703 extracellular domain fused with a BirA substrate peptide (BSP) was amplified from a previously cloned cDNA and inserted into a prokaratic expression vector. In the presence of the antigenic peptide IW9 and light chain ?2-microglobulin, the expressed heavy chain was refolded into a soluble monomer. After biotinylation, four monomers were polymerized as a tetramer by phycoerythrin-conjugated streptavidin. The tetramer, having been confirmed to have the right conformation, was a potential tool for investigation of antigen-specific CD8+ T-lymphocytes in SIV vaccine models of Chinese macaques. And our results also suggested that some antigenic peptides reported in Indian-origin macaques could be directly recruited as ligands for construction of Chinese macaque MHC tetramers. Cellular & Molecular Immunology.

  20. Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity.

    Science.gov (United States)

    Jannin, Vincent; Chevrier, Stéphanie; Michenaud, Matthieu; Dumont, Camille; Belotti, Silvia; Chavant, Yann; Demarne, Frédéric

    2015-11-10

    Lipid-based formulations can be effective drug delivery systems for poorly water-soluble chemical entities, provided they are designed with careful selection of the excipients, based on their role in the delivery system and in relation to drug properties. The primary factor leading to increased bioavailability is the administration of the drug in a pre-dissolved state thereby avoiding the dissolution limiting step. All model drugs tested (piroxicam, curcumin and nifedipine) belong to the same chemical space--small BCS class II molecules with logP ranging from 2 to 3. These drugs, exhibiting low to medium logP, are not soluble in lipophilic lipid-based excipients (e.g., vegetable oils). Water-soluble and water-dispersible surfactants are able to dissolve the target dose of each drug in the dosage form and efficiently keep it in solution during dispersion. In vitro digestion testing was necessary to discriminate formulations and enable selection of the most robust one. For each molecule, the system with the best performance during dispersion/digestion tests did not comprise the surfactant which delivered the highest solvent capacity for the drug. This study demonstrates the potential of surfactant-based formulations - i.e., Type IV systems from the lipid formulation classification system - for this type of hydrophobic drug. PMID:26364710

  1. Impact of physical activity and fitness in class II and III obese individuals: a systematic review.

    Science.gov (United States)

    Baillot, A; Audet, M; Baillargeon, J P; Dionne, I J; Valiquette, L; Rosa-Fortin, M M; Abou Chakra, C N; Comeau, E; Langlois, M F

    2014-09-01

    The objective of this systematic review was to appraise current knowledge on the impact of physical activity (PA) and physical fitness (PF) on the health of class II and III obese subjects and bariatric surgery (BS) patients. All original studies were searched using four databases (Medline®, Scopus®, CINAHL and Sportdiscus). Two independent investigators selected studies assessing the impact of PA or PF on specific health outcomes (anthropometric parameters, body composition, cardiometabolic risk factors, PF, wellness) in adults with a body mass index ≥35 kg m(-2) or in BS patients. Conclusions were drawn based on a rating system of evidence. From 3,170 papers identified, 40 papers met the inclusion criteria. The vast majority of studies were recently carried out with a predominance of women. Less than one-third of these studies were experimental and only three of them were of high quality. Each study reported at least one beneficial effect of PA or PF. However, a lack of high-quality studies and heterogeneity in designs prevented us from finding high levels of evidence. In conclusion, although results support the importance of PA and PF to improve the health of this population, higher-quality trials are required to strengthen evidence-based recommendations. PMID:24712685

  2. Techniques used to Enhance Bioavailability of BCS Class II Drugs: A Review

    Directory of Open Access Journals (Sweden)

    Honey Kansara

    2015-03-01

    Full Text Available Traditionally, nearly 40% of the new chemical entities (NCEs identified by pharmaceutical industry screening programs have failed to be developed because of poor water-solubility, which makes their formulation difficult or even impossible. The solubility issues complicating the delivery of these new drugs also affect the delivery of many existing drugs. The various traditional and novel techniques that that can be used for solubility enhancement of BCS Class II drugs are briefly discussed in this article. The Traditional techniques that has been discussed in this article includes use of co-solvents, Hydrotropy, Micronization, change in dielectric constant of solvent, amorphous forms, chemical modification of drug, use of surfactants, inclusion complex, alteration of pH of solvent, use of hydrates or solvates, use of soluble prodrugs, application of ultrasonic waves, functional polymer technology, controlled precipitation technology, evaporative precipitation in aqueous solution, use of precipitation inhibitors, solvent deposition, precipitation, selective adsorption on insoluble carriers. Novel drug delivery technologies developed in recent years for solubility enhancement of insoluble drugs are size reduction technologies, lipid based delivery system, micellar technologies, porous micro particle technology. Solid Dispersion Technique and various types of solid dispersion systems have also been explained briefly.

  3. Discovery of periodic class II methanol masers associated with G339.986-0.425 region

    CERN Document Server

    Maswanganye, J P; Goedhart, S; Gaylard, M J

    2015-01-01

    Ten new class II methanol masers from the 6.7-GHz Methanol Multibeam survey catalogues III and IV were selected for a monitoring programme at both 6.7 and 12.2 GHz with the 26m Hartebeesthoek Radio Astronomy Observatory (HartRAO) radio telescope for two years and nine months, from August 2012 to May 2015. In the sample, only masers associated with G339.986-0.425 were found to show periodic variability at both 6.7 and 12.2 GHz. The existence of periodic variation was tested with four independent methods. The analytical method gave the best estimation of the period, which was 246 $\\pm$ 1 days. The time series of G339.986-0.425 show strong correlations across velocity channels and between the 6.7 and 12.2 GHz masers. The time delay was also measured across channels and shows structure across the spectrum which is continuous between different maser components.

  4. SOLUBILITY ENHANCEMENT OF FENOFIBRATE, A BCS CLASS II DRUG, BY SELF EMULSIFYING DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    M.Sunitha Reddy

    2011-11-01

    Full Text Available The present work was aimed at the enhancement of solubility of Fenofibrate a BCS class II drug by Self Emulsifying Drug Delivery systems (SEDDS. The solubility of Fenofibrate in various excipients was determined. The excipients were screened for maximum solubility and compatibility. SEDDS formulations of Fenofibrate were developed using different Oils, Surfactants and Co-Surfactant combinations. Pseudoternary phase diagrams were drawn using Triplot software and by applying Pseudoternary phase diagrams, microemulsification area was evaluated.Formulations were screened based on visual observances and phase diagrams. Seven formulations were selected for further evaluations like stability, effect of dilution, freeze-thawing, emulsion droplet size and zeta potential. Among the seven formulations three were optimized and In-Vitro dissolution was performed. The dissolution rate of SEDDS was compared with plain Fenofibrate (API. The study confirmed that the solubility and dissolution rate of Fenofibrate were remarkably increased when compared to that of plain drug. Hence SEDDS formulations can be a potential alternative to traditional oral drug delivery systems of Fenofibrate to improve its bioavailability.

  5. 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. PMID:26429320

  6. Expression of major histocompatibility complex class II antigens in porcine leptospiral nephritis.

    Science.gov (United States)

    Radaelli, E; Del Piero, F; Aresu, L; Sciarrone, F; Vicari, N; Mattiello, S; Tagliabue, S; Fabbi, M; Scanziani, E

    2009-09-01

    Class II major histocompatibility complex (MHCII) is required for the presentation of antigens to CD4 helper T cells. During nephritis, not only primary antigen presenting cells such as histiocytes and lymphocytes, but also cytokine-stimulated tubular epithelial cells express MHCII. Leptospirosis in fattening pigs is characterized by several degrees of nephritis, from absence of lesions to severe multifocal tubulo-interstitial inflammation. Renal tissue from 20 8-month-old pigs with spontaneous nephritis and 6 control pigs without renal lesions were investigated for leptospirosis by indirect immunohistochemistry (IHC) and polymerase chain reaction (PCR). IHC for MHCII also was performed on renal samples. Serum samples were tested for different serovars of Leptospira interrogans. Control pigs were free of interstitial nephritis and negative for leptospirosis by all tests. In pigs with nephritis, serology was positive for serovar Pomona in 19/20 pigs. In 16 of these 19 pigs, leptospiral renal infection was confirmed by PCR and/or indirect IHC. Nephritic lesions were classified histologically into perivascular lymphocytic (4 pigs), lymphofollicular (6 pigs), lymphohistiocytic (8 pigs), and neutrophilic (2 pigs) pattern. MHCII expression by histiocytes and lymphocytes was observed in all lesions. Prominent MHCII expression in regenerating tubular epithelium was observed in lymphofollicular and lymphohistiocytic nephritis. No tubular colocalization between leptospiral and MHCII antigen was observed. Results suggest that during leptospiral nephritis, MHCII contributes to the intensity of the inflammatory response. Furthermore de novo MHCII expression in regenerating tubules may play a role in the defence mechanism against leptospiral tubular colonization. PMID:19179617

  7. 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

  8. HLA class II genes in chronic hepatitis C virus-infection and associated immunological disorders.

    Science.gov (United States)

    Congia, M; Clemente, M G; Dessi, C; Cucca, F; Mazzoleni, A P; Frau, F; Lampis, R; Cao, A; Lai, M E; De Virgiliis, S

    1996-12-01

    To investigate the factors that may confer susceptibility or protection to hepatitis C virus (HCV) infection and to HCV-associated immunological disorders, we designed two studies on 420 Sardinian transfusion-dependent thalassemia patients followed in our department in Cagliari since 1974. The first one was an epidemiological survey aimed to evaluate the prevalence of HCV infection and HCV-associated immunological disorders. In the second study, the distribution of different HLA class II genes was examined by DNA analysis in 116 HCV positive patients, 30 HCV negative patients, and 606 healthy controls. Three hundred fourteen patients became infected with HCV (74.7%) after 5.6 +/- 2.8 years of regular transfusion program. Mixed cryoglobulinemia, purpura, arthritis, proteinuria, decreased complement levels, rheumatoid factor and anti-GOR, smooth muscle antibody (SMA), anti-nuclear antibody (ANA), and liver, kidney microsome (LKM) autoantibodies were significantly more represented in HCV positive patients than in negative ones (P patients who despite 10.3 +/- 2.2 years in a regular blood transfusion program did not show any evidence of HCV infection (Pc < .0092). Our results represent clear evidence for a relationship between HCV infection and immune extrahepatic abnormalities. A gene(s) located in the human major histocompatibility complex (MHC) region may play an important role in conferring protection against HCV infection. PMID:8938157

  9. Clues to tRNA Evolution from the Distribution of Class II tRNAs and Serine Codons in the Genetic Code.

    Science.gov (United States)

    Bernhardt, Harold S

    2016-01-01

    We have previously proposed that tRNA(Gly) was the first tRNA and glycine was the first amino acid incorporated into the genetic code. The next two amino acids incorporated would have been the other two small hydrophilic amino acids serine and aspartic acid, which occurred through the duplication of the tRNA(Gly) sequence, followed by mutation of its anticodon by single C to U transition mutations, possibly through spontaneous deamination. Interestingly, however, tRNA(Ser) has a different structure than most other tRNAs, possessing a long variable arm; because of this tRNA(Ser) is classified as a class II tRNA. Also, serine codons are found not only in the bottom right-hand corner of the genetic code table next to those for glycine and aspartic acid, but also in the top row of the table, next to those for two of the most hydrophobic amino acids, leucine and phenylalanine. In the following, I propose that the class II tRNA structure of tRNA(Ser) and the arrangement of serine codons in the genetic code provide clues to the early evolution of tRNA and the genetic code. In addition, I address Di Giulio's recent criticism of our proposal that tRNA(Gly) was the first tRNA, and discuss how early peptides produced from a restricted amino acid alphabet of glycine, serine and aspartic acid might have possessed proteolytic activity, which is possibly important for the early recycling of amino acid monomers. PMID:26927183

  10. 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,...

  11. Mutations in the HLA class II genes leading to loss of expression of HLA-DR and HLA-DQ in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Jordanova, ES; Philippo, K; Giphart, MJ; Schuuring, E; Kluin, PM

    2003-01-01

    Loss of expression of human leukocyte antigen (HLA) class II molecules on tumor cells affects the onset and modulation of the immune response through lack of activation of CD4(+) T lymphocytes. Previously, we showed that the frequent loss of expression of HLA class II in diffuse large B-cell lymphom

  12. Cervical vertebral column morphology related to craniofacial morphology and head posture in preorthodontic children with Class II malocclusion and horizontal maxillary overjet

    DEFF Research Database (Denmark)

    Arntsen, Torill; Sonnesen, Ane Liselotte

    2011-01-01

    In preorthodontic children with Class II malocclusion and horizontal maxillary overjet, cervical column morphology was examined and related to craniofacial morphology and head posture for the first time.......In preorthodontic children with Class II malocclusion and horizontal maxillary overjet, cervical column morphology was examined and related to craniofacial morphology and head posture for the first time....

  13. Human leukocyte antigen-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies

    NARCIS (Netherlands)

    Kremer, A.N.; Meijden, E.D. van der; Honders, M.W.; Pont, M.J.; Goeman, J.J.; Falkenburg, J.H.F.; Griffioen, M.

    2014-01-01

    Hematological malignancies often express surface HLA class II, making them attractive targets for CD4+ T cell therapy. We previously demonstrated that HLA class II ligands can be divided into DM-resistant and DM-sensitive antigens. In contrast to presentation of DM-resistant antigens, presentation o

  14. 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 report...... panel of 43 peptides of different lengths and sequences. The DQ8 molecules showed a different pattern of peptide binding compared to a previously studied DQ2 molecule. Peptides derived from thyroid peroxidase, HLA-DQ(alpha1*0301), HLA-DQ(alpha1*0302), retinol receptor and p21ras were among the high...

  15. Exceptional hyperthyroidism and a role for both major histocompatibility class I and class II genes in a murine model of Graves' disease.

    Directory of Open Access Journals (Sweden)

    Sandra M McLachlan

    Full Text Available Autoimmune hyperthyroidism, Graves' disease, can be induced by immunizing susceptible strains of mice with adenovirus encoding the human thyrotropin receptor (TSHR or its A-subunit. Studies in two small families of recombinant inbred strains showed that susceptibility to developing TSHR antibodies (measured by TSH binding inhibition, TBI was linked to the MHC region whereas genes on different chromosomes contributed to hyperthyroidism. We have now investigated TSHR antibody production and hyperthyroidism induced by TSHR A-subunit adenovirus immunization of a larger family of strains (26 of the AXB and BXA strains. Analysis of the combined AXB and BXA families provided unexpected insight into several aspects of Graves' disease. First, extreme thyroid hyperplasia and hyperthyroidism in one remarkable strain, BXA13, reflected an inability to generate non-functional TSHR antibodies measured by ELISA. Although neutral TSHR antibodies have been detected in Graves' sera, pathogenic, functional TSHR antibodies in Graves' patients are undetectable by ELISA. Therefore, this strain immunized with A-subunit-adenovirus that generates only functional TSHR antibodies may provide an improved model for studies of induced Graves' disease. Second, our combined analysis of linkage data from this and previous work strengthens the evidence that gene variants in the immunoglobulin heavy chain V region contribute to generating thyroid stimulating antibodies. Third, a broad region that encompasses the MHC region on mouse chromosome 17 is linked to the development of TSHR antibodies (measured by TBI. Most importantly, unlike other strains, TBI linkage in the AXB and BXA families to MHC class I and class II genes provides an explanation for the unresolved class I/class II difference in humans.

  16. Expansion design for a radioactive sources handling laboratory type II class B; Diseno de ampliacion para un laboratorio de manejo de fuentes radiactivas tipo II clase B

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez S, P. S. [Universidad Mexiquense del Bicentenario, Av. Industria Poniente s/n, Parque Industrial Dona Rosa, 52000 Lerma, Estado de Mexico (Mexico); Monroy G, F.; Alanis, J., E-mail: salvador-21@live.com.mx [ININ, Carretera Mexico-Touca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2013-10-15

    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)

  17. 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

  18. MHC class II-associated invariant chain linkage of antigen dramatically improves cell-mediated immunity induced by adenovirus vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Mandrup Jensen, Camilla Maria; Orskov, Cathrine; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Sørensen, Maria Rathmann

    2008-01-01

    potent and versatile Ag delivery vehicles available. However, the impact of chronic infections like HIV and hepatitis C virus underscore the need for further improvements. In this study, we show that the protective immune response to an adenovirus-encoded vaccine Ag can be accelerated, enhanced......, broadened, and prolonged by tethering of the rAg to the MHC class II-associated invariant chain (Ii). Thus, adenovirus-vectored vaccines expressing lymphocytic choriomeningitis virus (LCMV)-derived glycoprotein linked to Ii increased the CD4+ and CD8+ T cell stimulatory capacity in vitro and in vivo....... Furthermore, mice vaccinated with a single dose of adenovirus-expressing LCMV-derived glycoprotein linked to Ii were protected against lethal virus-induced choriomeningitis, lethal challenge with strains mutated in immunodominant T cell epitopes, and systemic infection with a highly invasive strain. In...

  19. A step-by-step overview of the dynamic process of epitope selection by major histocompatibility complex class II for presentation to helper T cells [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Scheherazade Sadegh-Nasseri

    2016-06-01

    Full Text Available T cell antigen receptors (TCRs expressed on cytotoxic or helper T cells can only see their specific target antigen as short sequences of peptides bound to the groove of proteins of major histocompatibility complex (MHC class I, and class II respectively. In addition to the many steps, several participating proteins, and multiple cellular compartments involved in the processing of antigens, the MHC structure, with its dynamic and flexible groove, has perfectly evolved as the underlying instrument for epitope selection. In this review, I have taken a step-by-step, and rather historical, view to describe antigen processing and determinant selection, as we understand it today, all based on decades of intense research by hundreds of laboratories.

  20. Correlação entre a assimetria clínica e a assimetria radiográfica na Classe II, subdivisão Correlation between photographic asymmetry and radiographic asymmetry in patients with Class II subdivision malocclusion

    OpenAIRE

    Angela Rita Pontes Azevedo; Guilherme Janson; José Fernando Castanha Henriques

    2004-01-01

    O objetivo deste estudo foi avaliar a correlação entre a assimetria clínica e a assimetria radiográfica nos pacientes com Classe II, subdivisão. A amostra consistiu de 42 indivíduos com má oclusão de Classe II, subdivisão completa, com idade média de 15,21 anos. A assimetria clínica foi avaliada medindo-se a diferença relativa da posição espacial dos pontos do tecido mole entre os lados direito e esquerdo em fotografias frontais. A assimetria radiográfica foi avaliada medindo-se a diferença r...

  1. Bio-oss in Treatment of Furcation Class II Deffects and Comparison with Coronally Positioned Flap

    Directory of Open Access Journals (Sweden)

    Ak.Khoshkhoo Nejad

    2004-09-01

    Full Text Available Statement of Problem: Among periodontal defects, the furcation involvement represents one of the most chalenging scenarios due to the difficulty of achieving a predictable improvement regardless of the type of periodontal therapy. Moreover, the presence of furcation involvement has been demonstrated to considerably affect tooth prognosis. Thus, treatment of furcation defects is a challenge in clinical periodontics. The aim of periodontal treatment is not only to control infection but also to regenerate periodontal tissues lost as a consequence of periodontal disease.Purpose: The purpose of this study was to compare Bio-oss (Bo, an anorganic bovine bone Xenograft, in combination with coronally positioned flap to open flap debridment surgery with coronally positiond flap alone in human mandibular class II furcation defects.Materials and Methods: In this clinical trial and interventional study 24 furcations, which provided 12 pairs of similar periodontal defects were evaluated. Each defect was randomly assigned to treatment with Bio-Oss in combination coronally positioned flap or open flap debridment and coronally positioned flap alone. Following basic therapy, baseline measurements were recorded including probing depth (PDD, clinical attachment level (CAL,gingival recession (REC, keratinized gingiva (KG and closed horizontal probing depth(CHPD. After 6 months, all sites were re-entered and hard tissue measurements were recorded.Hard tissue measurements were performed during surgery to determine open horizontal probing depth (OHPD and open vertical probing depth (OVPD. The data was analyzed using t-test paired sample.Results: Vertical probing depth reduction of 3.17±1.32 mm and horizontal probing depth reduction of 4.42±1.02 mm were noted for the BO group, with 2.87±0.83 mm and 2.31±0.49 mm reductions, respectively, noted for CPF alone. Both surgical procedures resulted in statistically significant probing depth reduction and gain clinical

  2. HLA class II antigens and haplotypes associated with susceptibility of leukemias and myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Genetical and environmental factors play an interactive role in the development of acute and chronic leukemias. HLA antigens have been considered as possible genetic risk factors. The aim of this work was to investigate a possible association between HLA class II polymorphisms and leukemias and myelodysplastic syndrome. In the present study we investigated HLA class II antigens, DR/DQ and DR51/DR52/DR53 haplotypes in 100 patients: 7 suffering from myelodysplastic syndrome (MDS,37 from acute lymphoblastic leukemia(ALL,32 from acute myeloid leukemia (AML and 24 from chronic myeloid leukemia(CML. A panel of 210 healthy unrelated individuals of the same origin, from Vojvodina, served as controls. HLA phenotyping was performed by two color fluorescence method. In patients suffering from MDS was found a positive association with DR7(RR=2.598,EF=0.175 and DQ7(3(RR=4.419, EF=0.632, while negative association was found for DR15(2(RR=0.405, PF=0.172 and DQ6(1 (RR=0.889, PF=0,936.Positive association was found in the group of patients with ALL for DR7(RR=2.391,EF=0.688 and DQ2(RR=1.62, EF=0.15,while negative association was found with DQ5(1(RR=0.075, PF=0.324. In the group of patients with AML, there were positive associations with DR11(5(RR=1.732,EF=0.211,DQ2(RR= 1.594, EF=0.151 and DQ7(3 (RR=2.547,EF=0.266,while possible protective antigen was DQ5(1 (RR=0.107,RF=0.701. Higher RR than 1 and EF>0.15, in patients suffering from CML was found for DQ6(1(RR=1.661,EF=0.232, while negative association was found for DR4 (RR=0.182,PF=0.155.Possible protective haplotype in this study was DR3DQ8(3 for patients suffering from AML(RR=0.007, PF=0.501.The distribution of DR53-DR53 haplotypes showed significant difference in male patients with ALL(6% vs 0.09%, while DR52-DR52 haplotype was significantly less frequent in male patients with CML (4% vs 20.47% and female patients with MDS (1% vs 18.57%, respectively, in comparison to controls. We deduced that DR7 antigen in

  3. Expansion design for a Laboratory of Radioactive Sources Handling type II, class B; Diseno de ampliacion para un Laboratorio de Manejo de Fuentes Radiactivas tipo II, clase B

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez S, P. S.

    2014-07-01

    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)

  4. HLA Class II Allele and Haplotype Frequencies in Iranian Patients with Leukemia

    Directory of Open Access Journals (Sweden)

    Farideh Khosravi

    2007-09-01

    Full Text Available Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML" and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033. Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%. According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls .In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.

  5. Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Paola Cruz-Tapias

    2012-01-01

    Full Text Available The prevalence and genetic susceptibility of autoimmune diseases (ADs may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53 was found to be a risk factor for systemic lupus erythematosus (SLE, Sjögren's syndrome (SS, and type 1 diabetes mellitus (T1D. DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05 influences autoimmune hepatitis (AIH, rheumatoid arthritis (RA, and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42 is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

  6. 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 at...... baseline and then annually for 10 years. The overall performance of the experimental restorations was tested after intra-individual comparison and their ranking was tested using Friedman's two-way ANOVA. The level of significance was set at 5%. Results: Four patient drop-outs with 8 restorations (4TEC, 4TC...

  7. Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion

    DEFF Research Database (Denmark)

    Odum, Niels; Yoshizumi, H; Okamoto, Y;

    1992-01-01

    Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was...... antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was......, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through...

  8. Overlapping Synthetic Peptides Encoding TPD52 as Breast Cancer Vaccine in Mice: Prolonged Survival1

    OpenAIRE

    Mirshahidi, Saied; Kramer, Victor G; James B Whitney; Essono, Sosthène; Lee, Sandra; Dranoff, Glenn; Anderson, Karen S.; Ruth M Ruprecht

    2009-01-01

    Peptide-based vaccines, one of several anti-tumor immunization strategies currently under investigation, can elicit both MHC Class I-restricted (CD8+) and Class II-restricted (CD4+) responses. However, the need to identify specific T-cell epitopes in the context of MHC alleles has hampered the application of this approach. We have tested overlapping synthetic peptides (OSP) representing a tumor antigen as a novel approach that bypasses the need for epitope mapping, since OSP contain all possi...

  9. Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Faber, O K;

    1989-01-01

    Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated...... fasting plasma C-peptide value less than 0.20 nmol/l, a glucagon stimulated plasma C-peptide value less than 0.32 nmol/l, and a urinary C-peptide value less than 3.1 nmol/l, or less than 0.54 nmol/mmol creatinine/24 h, or less than 5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C-peptide......) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved...

  10. 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 Grant ostatní: 6th Framework Programme(XE) GOCE-2003-010284 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

  11. Contrasting Epidemic Histories Reveal Pathogen-Mediated Balancing Selection on Class II MHC Diversity in a Wild Songbird

    OpenAIRE

    Hawley, Dana M; Fleischer, Robert C

    2012-01-01

    The extent to which pathogens maintain the extraordinary polymorphism at vertebrate Major Histocompatibility Complex (MHC) genes via balancing selection has intrigued evolutionary biologists for over half a century, but direct tests remain challenging. Here we examine whether a well-characterized epidemic of Mycoplasmal conjunctivitis resulted in balancing selection on class II MHC in a wild songbird host, the house finch (Carpodacus mexicanus). First, we confirmed the potential for pathogen-...

  12. Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials

    OpenAIRE

    Otten Celine; Meyer-Lucht Yvonne; Püttker Thomas; Sommer Simone

    2008-01-01

    Abstract Background Research on the genetic architecture and diversity of the MHC has focused mainly on eutherian mammals, birds and fish. So far, studies on model marsupials used in laboratory investigations indicated very little or even no variation in MHC class II genes. However, natural levels of diversity and selection are unknown in marsupials as studies on wild populations are virtually absent. We used two endemic South American mouse opossums, Gracilinanus microtarsus and Marmosops in...

  13. Assessment of divine proportion in the cranial structure of individuals with Angle Class II malocclusion on lateral cephalograms

    OpenAIRE

    Marcos André dos Santos da Silva; Edmundo Médici Filho; Julio Cezar de Melo Castilho; Cássia T. Lopes de Alcântara Gil

    2012-01-01

    INTRODUCTION: The study of the Divine Proportion (Φ = 1.618) began with the Greeks, having as main researchers the mathematician Pythagoras and the sculptor Phidias. In Dentistry, Ricketts (1981-82) was an early to study this issue. OBJECTIVE: This study proposed to evaluate how some cephalometric measures are presented in relation to the Divine Proportion, with the total of 52 proportions, formed by 28 cephalometric landmarks. METHODS: Lateral cephalograms of 40 Class II adults patients...

  14. Absence of major histocompatibility complex class II mediated immunity in pipefish, Syngnathus typhle: evidence from deep transcriptome sequencing

    OpenAIRE

    Haase, David; Roth, Olivia; Kalbe, Martin; Schmiedeskamp, Gisela; Scharsack, Jörn P; Rosenstiel, Philip; Reusch, Thorsten B. H.

    2013-01-01

    The major histocompatibility complex (MHC)-mediated adaptive immune system is the hallmark of gnathostome immune defence. Recent work suggests that cod-like fishes (Gadidae) lack important components of the MHC class II mediated immunity. Here, we report a putative independent loss of functionality of this pathway in another species, the pipefish Syngnathus typhle, that belongs to a distantly related fish family (Syngnathidae). In a deep transcriptome sequencing approach comprising several in...

  15. HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc Patients.

    Directory of Open Access Journals (Sweden)

    Tatiana S Rodriguez-Reyna

    Full Text Available Human leukocyte antigen (HLA polymorphism studies in Systemic Sclerosis (SSc have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications.We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population.Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02, and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients.This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as

  16. Radiosynthesis of (tetrazoyl-11C)irbesartan, a non-peptidic angiotensin II antagonist

    International Nuclear Information System (INIS)

    With the aim of visualizing myocardial angiotensin II receptors (ATI subtypes), [tetrazoyl-11C]2-n-butyl-1-[(2'-(1H-tetrazole-5-yl)-1,1'-biphenyl-4-yl)methyl]-4-spirocyclo-pentane-2-imidazoline-5-one ([tetrazoyl-11C]irbesartam (SR47436/BMS-186295)) 11 was synthesized in one pot in four steps from [11C]hydrogen cyanide. The labelling process which yielded [tetrazoyl-11C]irbesartan is described in detail and could be applied to the labelling of other ligands which possess the (1H-tetrazole-5-yl) moiety. Positron emission tomography (PET) studies were performed in dogs. Heart, lung and blood time-activity curves did not change. Therefore this new radioligand is not suitable for studying myocardial angiotensin II receptors with PET. (authors)

  17. Class II-targeted antigen is superior to CD40-targeted antigen at stimulating humoral responses in vivo.

    Science.gov (United States)

    Frleta, D; Demian, D; Wade, W F

    2001-02-01

    We examined the efficacy of using monoclonal antibodies to target antigen (avidin) to different surface molecules expressed on antigen presenting cells (APC). In particular, we targeted CD40 to test whether the "adjuvant" properties of CD40 signaling combined with targeted antigen would result in enhanced serologic responses. We targeted avidin to class II as a positive control and to CD11c as a negative control. These surface proteins represent an ensemble of surface molecules that signal upon ligation and that are expressed on professional APC, in particular dendritic cells (DC). We observed that targeting class II molecules on APC was superior to targeting CD40, or CD11c. However, CD40 and CD11c could function as targets for antigen bound monoclonal antibodies under certain conditions. Interestingly, inclusion of anti-CD40 mAb with the targeting anti-class II-targeted antigens negatively affects humoral response, suggesting that CD40 signaling under certain conditions may suppress processing and/or presentation of targeted antigen. PMID:11360928

  18. Cephalometric assessment of vertical control in the treatment of class II malocclusion with a combined maxillary splint

    Directory of Open Access Journals (Sweden)

    Ivana Uglik Garbui

    2010-03-01

    Full Text Available Vertical control is one of the primary objectives sought by orthodontists when treating malocclusions in hyperdivergent individuals. This investigation aimed at assessing vertical control, by cephalometric measurements, during the treatment of Angle Class II Division 1 malocclusion. Thirty cases, selected from the files of the São Leopoldo Mandic Dental Research Center, Brazil, of subjects with Angle Class II Division 1 malocclusion and facial hyperdivergence, were used in this study. The patients were treated using a combined extraoral appliance during a mean treatment time of 1.1 years. Pre- and posttreatment cephalometric measurements were compared to assess vertical control. The results were submitted to ANOVA (p = 5%. The ANOVA test revealed no statistically significant difference between the pretreatment and posttreatment values of OP (Occlusal plane angle and SN.MP. While there was a decrease in Y-axis, FMA, and PP.MP, there was an increase in SN.PP, Co-Go, AFH, PFH, and FHI. It was concluded that the divergence in the facial lower third of the patients did not increase, suggesting that the combined extraoral appliance with the line of force application directed to the resistance center of the maxilla was effective in treating Angle Class II malocclusion in hyperdivergent subjects.

  19. Changes in skeletal and dental relationship in Class II Division I malocclusion after rapid maxillary expansion: a prospective study

    Directory of Open Access Journals (Sweden)

    Carolina Baratieri

    2014-06-01

    Full Text Available OBJECTIVE: To assess skeletal and dental changes immediately after rapid maxillary expansion (RME in Class II Division 1 malocclusion patients and after a retention period, using cone beam computed tomography (CBCT imaging. METHODS: Seventeen children with Class II, Division 1 malocclusion and maxillary skeletal transverse deficiency underwent RME following the Haas protocol. CBCT were taken before treatment (T1, at the end of the active expansion phase (T2 and after a retention period of 6 months (T3. The scanned images were measured anteroposteriorly (SNA, SNB, ANB, overjet and MR and vertically (N-ANS, ANS-Me, N-Me and overbite. RESULTS: Significant differences were identified immediately after RME as the maxilla moved forward, the mandible moved downward, overjet increased and overbite decreased. During the retention period, the maxilla relapsed backwards and the mandible was displaced forward, leaving patients with an overall increase in anterior facial height. CONCLUSION: RME treatment allowed more anterior than inferior positioning of the mandible during the retention period, thus significantly improving Class II dental relationship in 75% of the patients evaluated.

  20. Platelet-rich plasma in the treatment of Class II furcation defects: a histometrical study in dogs

    Directory of Open Access Journals (Sweden)

    Fabrícia Ferreira Suaid

    2012-04-01

    Full Text Available OBJECTIVE: This study was designed to evaluate the potential adjunctive benefits of platelet-rich plasma (PRP when used with guided-tissue regeneration (GTR and bioactive glass (BG in the treatment of Class II furcation lesions. MATERIAL AND METHODS: Bilateral Class II furcation lesions were surgically created and allowed to become chronic in the mandibular third premolars of 9 dogs. The defects were randomly assigned to: A GTR+BG and B GTR+BG+PRP. Similar defects were created in the maxillary third premolars and received the same treatments after 45 days. Dogs were sacrificed 90 days after the first treatment. The histometric parameters evaluated were: connective tissue adaptation, new cementum, new bone, mineralized bone area, non-mineralized bone area, and residual BG particle area. RESULTS: Data analysis showed a superior length of new cementum and a greater mineralized bone area for group B in both periods (p<0.05. The non-mineralized bone area was greater in the control group (p<0.05 in both periods. CONCLUSION: Within the limits of this study, it can be concluded that the use of PRP in the treatment of Class II furcation defects may enhance the amount of new cementum and provide a more mineralized bone in a shorter period of time.

  1. Finite Element Analysis of the Effect of Proximal Contour of Class II Composite Restorations on Stress Distribution

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Moghaddas

    2013-01-01

    Full Text Available Introduction: The aim of this study was to evaluate the effect of proximal contour of class II composite restorations placed with straight or contoured matrix band using composite resins with different modulus of elasticity on stress distribution by finite element method. Methods: In order to evaluate the stress distribution of class II composite restorations using finite element method, upper right first molar and second premolar were modeled. Proximal boxes were designed and restored with universal Z250 and packable P60 composite resins (3M ESPE using two matrix systems: flat Tofflemire matrix and precurved sectional matrix. Finally models were evaluated under loads of 200 and 400 Newton at 90 degrees angle and the results were graphically illustrated in the form of Von Misses stresses. Results: In general the stress obtained under 400 Newton load was significantly greater than the stress of models under 200 Newton load. Von Misses stress distribution pattern of two different Z250 and P60 composites were very similar in all modes of loading and proximal contour. In all analyzed models there was a significant difference between models restored with Tofflemire matrix with flat contour and models restored with sectional matrix with curved contour. This difference was greater in first molar than second premolar. Conclusion: Use of a contoured matrix band results in less stress in class II composite resin restorations.

  2. Work Analysis of the nuclear power plant control room operators (II): The classes of situation

    International Nuclear Information System (INIS)

    This report presents a work analysis of nuclear power plant control room operators focused on the classes of situation they can meet during their job. Each class of situation is first described in terms of the process variables states. We then describe the goals of the operators and the variables they process in each class of situation. We report some of the most representative difficulties encountered by the operators in each class of situation. Finally, we conclude on different topics: the nature of the mental representations, the temporal dimension, the monitoring activity, and the role of the context in the work of controlling a nuclear power plant

  3. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII.

    Directory of Open Access Journals (Sweden)

    Simon D van Haren

    Full Text Available The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+ T cell-dependent process. Activation of FVIII-specific CD4(+ T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found - these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides or two to three donors (12 peptides. Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.

  4. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  5. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  6. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  7. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  8. The great diversity of major histocompatibility complex class II genes in Philippine native cattle.

    Science.gov (United States)

    Takeshima, S N; Miyasaka, T; Polat, M; Kikuya, M; Matsumoto, Y; Mingala, C N; Villanueva, M A; Salces, A J; Onuma, M; Aida, Y

    2014-12-01

    Bovine leukocyte antigens (BoLA) are extensively used as markers for bovine disease and immunological traits. However, none of the BoLA genes in Southeast Asian breeds have been characterized by polymerase chain reaction (PCR)-sequence-based typing (SBT). Therefore, we sequenced exon 2 of the BoLA class II DRB3 gene from 1120 individual cows belonging to the Holstein, Sahiwal, Simbrah, Jersey, Brahman, and Philippine native breeds using PCR-SBT. Several cross-breeds were also examined. BoLA-DRB3 PCR-SBT identified 78 previously reported alleles and five novel alleles. The number of BoLA-DRB3 alleles identified in each breed from the Philippines was higher (71 in Philippine native cattle, 58 in Brahman, 46 in Holstein × Sahiwal, and 57 in Philippine native × Brahman) than that identified in breeds from other countries (e.g., 23 alleles in Japanese Black and 35 in Bolivian Yacumeño cattle). A phylogenetic tree based on the DA distance calculated from the BoLA-DRB3 allele frequency showed that Philippine native cattle from different Philippine islands are closely related, and all of them are closely similar to Philippine Brahman cattle but not to native Japanese and Latin American breeds. Furthermore, the BoLA-DRB3 allele frequency in Philippine native cattle from Luzon Island, located in the Northern Philippines was different from that in cattle from Iloilo, Bohol, and Leyte Islands, which are located in the Southern Philippines. Therefore, we conclude that Philippine native cattle can be divided into two populations, North and South areas. Moreover, a neutrality test revealed that Philippine native cattle from Leyte showed significantly greater genetic diversity, which may be maintained by balancing selection. This study shows that Asian breeds have high levels of BoLA-DRB3 polymorphism. This finding, especially the identification of five novel BoLA-DRB3 alleles, will be helpful for future SBT studies of BoLA-DRB3 alleles in East Asian cattle. PMID:25606401

  9. The great diversity of major histocompatibility complex class II genes in Philippine native cattle

    Directory of Open Access Journals (Sweden)

    S.N. Takeshima

    2014-12-01

    Full Text Available Bovine leukocyte antigens (BoLA are extensively used as markers for bovine disease and immunological traits. However, none of the BoLA genes in Southeast Asian breeds have been characterized by polymerase chain reaction (PCR-sequence-based typing (SBT. Therefore, we sequenced exon 2 of the BoLA class II DRB3 gene from 1120 individual cows belonging to the Holstein, Sahiwal, Simbrah, Jersey, Brahman, and Philippine native breeds using PCR-SBT. Several cross-breeds were also examined. BoLA-DRB3 PCR-SBT identified 78 previously reported alleles and five novel alleles. The number of BoLA-DRB3 alleles identified in each breed from the Philippines was higher (71 in Philippine native cattle, 58 in Brahman, 46 in Holstein × Sahiwal, and 57 in Philippine native × Brahman than that identified in breeds from other countries (e.g., 23 alleles in Japanese Black and 35 in Bolivian Yacumeño cattle. A phylogenetic tree based on the DA distance calculated from the BoLA-DRB3 allele frequency showed that Philippine native cattle from different Philippine islands are closely related, and all of them are closely similar to Philippine Brahman cattle but not to native Japanese and Latin American breeds. Furthermore, the BoLA-DRB3 allele frequency in Philippine native cattle from Luzon Island, located in the Northern Philippines was different from that in cattle from Iloilo, Bohol, and Leyte Islands, which are located in the Southern Philippines. Therefore, we conclude that Philippine native cattle can be divided into two populations, North and South areas. Moreover, a neutrality test revealed that Philippine native cattle from Leyte showed significantly greater genetic diversity, which may be maintained by balancing selection. This study shows that Asian breeds have high levels of BoLA-DRB3 polymorphism. This finding, especially the identification of five novel BoLA-DRB3 alleles, will be helpful for future SBT studies of BoLA-DRB3 alleles in East Asian cattle.

  10. Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Rana J EI Wafai

    2011-01-01

    Full Text Available Type-1 diabetes mellitus (T1DM is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting β-cells of the pancreas. HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1], especially DR and DQ, show strong association with T1DM. In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12 on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes. The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP technique and to investigate the asso-ciation of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis in Lebanese T1DM patients. The study was conduc-ted on 39 Lebanese T1DM patients. Results of HLA typing showed an increased frequency of the HLA-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 alleles, sugges-ting risk association and thus can be considered as susceptibility alleles. On the other hand, strong protection against the disease was conferred by the HLA-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 alleles. RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population. Analysis of the two polymorphisms showed no detectable association between the two genes. However, a significant negative association of the G allele with the DQB1FNx010201 allele was ob-served. This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.

  11. Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients

    Directory of Open Access Journals (Sweden)

    Godard MP

    2012-11-01

    Full Text Available Michael P Godard,1 Samantha A Whitman,2 Yao-Hua Song,3 Patrice Delafontaine41Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO, USA; 2Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA; 3Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China; 4Tulane University School of Medicine, Section of Cardiology, New Orleans, LA, USABackground: Heart failure (HF, a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1 and insulin-like growth factor-binding protein-5 (IGFB-5 appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single–skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure.Materials and methods: To investigate these molecules during “early” events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size.Results: There were more (P < 0.05 single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7% compared to the control subjects (13% ± 2%. IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05, respectively. Strikingly

  12. Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris.

    Science.gov (United States)

    Ahmed, A R; Wagner, R; Khatri, K; Notani, G; Awdeh, Z; Alper, C A; Yunis, E J

    1991-01-01

    Previous studies demonstrated that HLA-DR4 was markedly increased among Ashkenazi Jewish patients with pemphigus vulgaris (PV), almost entirely as the common Jewish extended haplotype [HLA-B38, SC21, DR4, DQw8] or as the haplotype HLA-B35, SC31, DR4, DQw8, and that HLA-DR4, DQw8 was distributed among patients in a manner consistent with dominant expression of a class II (D-region or D-region-linked) susceptibility gene. In the present study of major histocompatibility complex (MHC) haplotypes in 25 non-Jewish PV patients, DR4, DQw8 was found in 12 of the patients and DRw6, DQw5 was found in 15. Only 3 patients had neither. Only 1 of the DR4, DQw8 haplotypes was [HLA-B38, SC21, DR4, DQw8] and 2 were HLA-B35, SC31, DR4, DQw8; most were the presumed fragments (SC31, DR4, DQw8) or (SC21, DR4, DQw8) or DR4, DQw8 with some other complotype. Of the patients with DRw6, DQw5, all were DRw14, DQw5, and 6 had a rare Caucasian haplotype, HLA-Bw55, SB45, DRw14, DQw5. Four of 6 of these were found in patients of Italian extraction, as was the 1 normal example. The non-Jewish patients were of more Southern European extraction than our controls. This suggests that there are two major MHC susceptibility alleles in American patients with PV. The more ancient apparently arose on a haplotype in the Jews, HLA-B38(35), SC21(SC31), DR4, DQw8, and spread to other populations largely as D-region segments. The other arose in or near Italy on the haplotype HLA-Bw55, SB45, DRw14, DQw5 and has also partially fragmented so that many patients carry only DRw14, DQw5. The available data do not permit the specific localization of either the DR4, DQw8- or the DRw14, DQw5-linked susceptibility genes. Images PMID:1675792

  13. Identification of peptides from foot‐and‐mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA‐1*0401 and SLA‐2*0401

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Harndahl, M.; Nielsen, Morten;

    2013-01-01

    within the structural proteins of foot‐and‐mouth disease virus (FMDV), strain A24 were analyzed as candidate T‐cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA‐1*0401 and SLA‐2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted...... FMDV peptides bound to SLA‐2*0401, whereas five of the nine predicted FMDV peptides bound to SLA‐1*0401. These methods provide the characterization of T‐cell epitopes in response to pathogens in more detail. The development of such approaches to analyze vaccine performance will contribute to a more...

  14. Estudo cefalométrico comparativo dos espaços naso e bucofaríngeo nas más oclusões Classe I e Classe II, Divisão 1, sem tratamento ortodôntico, com diferentes padrões de crescimento A Comparative cephalometric study of the naso and oropharyngeal space in malocclusions Class I and Class II Division 1, without orthodontic treatment with different growth patterns

    Directory of Open Access Journals (Sweden)

    Nadyr M. Penteado Virmond Alcazar

    2004-08-01

    Full Text Available A finalidade deste estudo foi comparar os espaços aéreos naso e bucofaríngeo em indivíduos com má oclusão Classe I e Classe II, divisão 1, segundo Angle, do gênero masculino e feminino, com idade média de 11 anos e 6 meses, com padrão de crescimento normal e vertical, não tratados ortodonticamente. A amostra desse estudo foi dividida em dois grupos: 40 pacientes apresentando Classe I e 40 pacientes com Classe II, divisão 1, cada grupo subdividido de acordo com o padrão de crescimento facial: normal e vertical. Os espaços aéreos naso e bucofaríngeo foram avaliados segundo a análise de McNamara Jr., pelas medidas NFa-NFp e BFa-BFp. A análise dos resultados obtidos revelou que, a medida do espaço bucofaríngeo para Classe I com padrão de crescimento vertical e para o espaço nasofaríngeo para Classe II com padrão normal de crescimento apresentaram-se semelhantes à medida padrão da amostra de McNamara Jr.. As outras medidas apresentaram-se estatisticamente menores. Na comparação entre os grupos, o espaço nasofaríngeo no grupo Classe I com padrão de crescimento vertical, apresentou-se menor do que nos grupos Classe I e grupo Classe II divisão 1, ambos com padrão de crescimento normal. O espaço bucofaríngeo não sofreu alteração significante de um grupo para outro. Em relação à hipertrofia da tonsila faringeana, apenas o grupo Classe I com padrão de crescimento vertical apresentou obstrução; para hipertrofia das tonsilas palatinas, apenas o grupo Classe I com padrão de crescimento vertical e Classe II com padrão de crescimento normal apresentou hipertrofia das tonsilas palatinas.The aim of this study is to compare the naso and oropharyngeal air space in people with malocclusion class I and class II division 1, according to Angle, with mean age from 8 to 15 years old with normal and vertical growth pattern not treated orthodontically. This study was divided into two groups: 40 patients with class I, and 40

  15. Analysis of Gag-specific Cytotoxic T Lymphocytes in Simian Immunodeficiency Virus–infected Rhesus Monkeys by Cell Staining with a Tetrameric Major Histocompatibility Complex Class I–Peptide Complex

    OpenAIRE

    Kuroda, Marcelo J.; Schmitz, Jörn E.; Barouch, Dan H.; Craiu, Abie; Allen, Todd M.; Sette, Alessandro; Watkins, David I.; Forman, Meryl A.; Letvin, Norman L.

    1998-01-01

    A tetrameric recombinant major histocompatibility complex (MHC) class I–peptide complex was used as a staining reagent in flow cytometric analyses to quantitate and define the phenotype of Gag-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of simian immunodeficiency virus macaque (SIVmac)-infected rhesus monkeys. The heavy chain of the rhesus monkey MHC class I molecule Mamu-A*01 and β2-microglobulin were refolded in the presence of an SIVmac Gag synthetic peptide (p11C, C–M)...

  16. Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion, and enhanced bioactivity against cancer cells

    Science.gov (United States)

    Yoong, Sia Lee; Lau, Wei Liang; Liu, Ang Yu; Prendergast, D'arcy; Ho, Han Kiat; Yu, Victor Chun Kong; Lee, Chengkuo; Ang, Wee Han; Pastorin, Giorgia

    2015-08-01

    Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study, multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep) across cellular barriers without compromising their bioactivity. The peptide was conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)-functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep), respectively. Both conjugates were shown to be internalized by breast cancer MCF-7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have escaped from endosomes and be in the vicinity of mitochondria. The WST-1 cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed that MWCNT-peptide conjugates were significantly more effective in curbing cancer cell growth compared to a commercially available cell permeable HKII fusion peptide. In addition, both nanoconjugates displayed an enhanced ability in eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the mere HKII peptide. Importantly, hexokinase II release from mitochondria was demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells, highlighting that the structure and bioactivity of HKII(pep) were not compromised after covalent conjugation to MWCNTs.Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study

  17. Changes of hyoid bone position following treatment of class II div1 malocclusion with Farmand functional appliance

    Directory of Open Access Journals (Sweden)

    Yassaei S

    2007-01-01

    Full Text Available Background and Aim: Unlike other bones of the head and neck, hyoid bone has no bony articulations. It is connected to mandible, cranium and pharynx through muscles and ligaments. During treatment with functional appliance in patients with class II div1 malocclusion, mandible is positioned in inferior and anterior direction. Regarding the relation between hyoid and mandibular bone, alterations of hyoid bone position can be a result of functional appliance therapy. The aim of this study was to evaluate the changes of hyoid bone position following treatment with Farmand functional appliance in patients with class II div 1 malocclusion. Materials and Methods: In this before-after clinical trial, 28 patients with class II div 1 malocclusion which were under treatment with Farmand functional appliance for 11 months were selected. Facial growth in vertical, normal or horizontal direction was determined by cephalometric measurement. Data were analyzed with Paired-t test to compare the differences of mean values pre and post treatment. Variance analysis was used to compare the three growth patterns. P<0.05 was considered as the limit of significance. Results: Hyoid bone shifted significantly forward in horizontal dimension (P<0.01 and non-significantly upward in vertical dimension. There was no significant difference among the three studied groups with respect to hyoid bone position alterations in horizontal dimension but significant difference was observed between horizontal and vertical growth pattern in vertical dimension (P<0.05. There was significant correlation between decrease of ANB angle and forward movement of hyoid bone. Conclusion: Based on the results of this study, treatment with Farmand functional appliance (Fa II leads to significant alterations in the position and anterior displacement of the hyoid bone.

  18. The Composition of Metals Bound to Class III Metallothionein (Phytochelatin and Its Desglycyl Peptide) Induced by Various Metals in Root Cultures of Rubia tinctorum.

    Science.gov (United States)

    Maitani, T.; Kubota, H.; Sato, K.; Yamada, T.

    1996-04-01

    The induction of phytochelatins (PCs) and their desglycyl peptides (both are referred to as class III metallothionein [CIIIMT]) by exposure to various metals (Ag+, As3+, As5+, Cd2+, Cu2+, Ga3+, Hg2+, In3+, Ni2+, Pb2+, Pd2+, Se4+, and Zn2+) and the metal composition in the CIIIMTs were investigated in root cultures of Rubia tinctorum L. All of these metal species induced PCs to various degrees when analyzed by the postcolumn derivatization high-performance liquid chromatography method. The desglycyl peptides of PCs often were also present. However, only Ag, Cd, and Cu were bound to the CIIIMTs that they induced when analyzed by the high-performance liquid chromatography-inductively coupled plasma-atomic emission spectrometry method. Cu was also bound to the CIIIMTs induced by Ag+, As3+, and Cd2+. After Ag+ exposure, an Fe peak that may be of Fe-CIIIMT was also observed. However, most of the metal species studied were not bound to the CIIIMTs that they induced. PMID:12226248

  19. A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    Full Text Available For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III based on the protein sequence and structure. For Rift Valley fever virus (RVFV, the glycoprotein Gc (Class II fusion protein mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus, Class II (Andes virus, or Class III (vesicular stomatitis virus fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

  20. Pediocin-like antimicrobial peptides (class IIa bacteriocins) and their immunity proteins: biosynthesis, structure, and mode of action.

    Science.gov (United States)

    Fimland, Gunnar; Johnsen, Line; Dalhus, Bjørn; Nissen-Meyer, Jon

    2005-11-01

    Pediocin-like antimicrobial peptides (AMPs) form a group of lactic acid bacteria produced, cationic membrane-permeabilizing peptides with 37 to 48 residues. Upon exposure to membrane-mimicking entities, their hydrophilic, cationic, and highly conserved N-terminal region forms a three-stranded antiparallel beta-sheet supported by a conserved disulfide bridge. This N-terminal beta-sheet region is followed by a central amphiphilic alpha-helix and this in most (if not all) of these peptides is followed by a rather extended C-terminal tail that folds back onto the central alpha-helix, thereby creating a hairpin-like structure in the C-terminal half. There is a flexible hinge between the beta-sheet N-terminal region and the hairpin C-terminal region and one thus obtains two domains that may move relative to each other. The cationic N-terminal beta-sheet domain mediates binding of the pediocin-like AMPs to the target-cell surface through electrostatic interactions, while the more hydrophobic and amphiphilic C-terminal hairpin domain penetrates into the hydrophobic part of the target-cell membrane, thereby mediating leakage through the membrane. The hinge provides the structural flexibility that enables the C-terminal hairpin domain to dip into the hydrophobic part of the membrane. Despite extensive sequence similarities, these AMPs differ markedly in their target-cell specificity, and results obtained with hybrid AMPs indicate that the membrane-penetrating hairpin-like C-terminal domain is the major specificity determinant. Bacteria that produce pediocin-like AMPs also produce a 11-kDa cognate immunity protein that protects the producer. The immunity proteins are well-structured, 4-helix bundle cytosolic proteins. They show a high degree of specificity in that they largely recognize and confer immunity only to their cognate AMP and in some cases to a few AMPs that are closely related to their cognate AMP. The C-terminal half of the immunity proteins contains a domain that