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Sample records for class ii binding

  1. Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules

    Science.gov (United States)

    2011-01-20

    Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules Teri L. Kissner, Gordon Ruthel, Shahabuddin Alam...mediated signaling, which activates pro-inflammatory cytokine responses. Recently we reported that staphylococcal enterotoxins (SEA or SEB), which...upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules. PLoS ONE 6(1): e15985. doi:10.1371/journal.pone.0015985 Editor: Jacques Zimmer

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

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    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

  3. High-throughput engineering and analysis of peptide binding to class II MHC.

    Science.gov (United States)

    Jiang, Wei; Boder, Eric T

    2010-07-27

    Class II major histocompatibility complex (MHC-II) proteins govern stimulation of adaptive immunity by presenting antigenic peptides to CD4+ T lymphocytes. Many allelic variants of MHC-II exist with implications in peptide presentation and immunity; thus, high-throughput experimental tools for rapid and quantitative analysis of peptide binding to MHC-II are needed. Here, we present an expression system wherein peptide and MHC-II are codisplayed on the surface of yeast in an intracellular association-dependent manner and assayed by flow cytometry. Accordingly, the relative binding of different peptides and/or MHC-II variants can be assayed by genetically manipulating either partner, enabling the application of directed evolution approaches for high-throughput characterization or engineering. We demonstrate the application of this tool to map the side-chain preference for peptides binding to HLA-DR1 and to evolve novel HLA-DR1 mutants with altered peptide-binding specificity.

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

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    Mittelmann Hans D

    2010-01-01

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

  5. Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D.

    Science.gov (United States)

    Coronado, M A; Ullah, A; da Silva, L S; Chaves-Moreira, D; Vuitika, L; Chaim, O M; Veiga, S S; Chahine, J; Murakami, M T; Arni, R K

    2015-01-01

    Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms, trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental in understanding the functional differences between the class I and II spider PLDs. The crystal structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided insights into the structural determinants for substrate recognition and binding by class II PLDs.

  6. Set Theory Applied to the Mathematical Characterization of HLA Class II Binding Peptides

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    Javier Rodríguez Velásquez, MD, esp.1

    2008-04-01

    Full Text Available Antigen presentation contains the molecularbasis for antigenic identification and immuneresponses. The set theory and experimental datawere used in order to develop an union core regionmathematic characterization through the definitionof 8 laws associated to HLA class II binding.The laws were applied to 4 promiscuous peptides,25 natural peptides sequences of core region: 13binding peptides and 12 no binding peptides; and19 synthetic peptides looking to differentiate peptides.Only one peptide was not rightly characterized.This methodology may be used to choose keypeptides in the development of vaccine.

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

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    Scholl, P.; Diez, A.; Mourad, W.; Parsonnet, J.; Geha, R.S.; Chatila, T. (Harvard Medical School, Boston, MA (USA))

    1989-06-01

    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 {sup 125}I-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 {alpha} and {beta} 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.

  8. 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

    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...... 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...

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

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    Wang, Mingjun; Tang, Sheila T; Stryhn, Anette; Justesen, Sune; Larsen, Mette V; Dziegiel, Morten H; Lewinsohn, David M; Buus, Søren; Lund, Ole; Claesson, Mogens H

    2011-04-01

    Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide-based vaccines. In the present work, bioinformatics technology was employed to predict binding motifs of 9mer peptides derived from M. tuberculosis for the 12 HLA-I supertypes. Subsequently, the predicted peptides were synthesized and assayed for binding to HLA-I molecules in a biochemically based system. The antigenicity of a total of 157 peptides with measured affinity for HLA-I molecules of K(D) ≤ 500 nM were evaluated using peripheral blood T cells from strongly purified protein derivative reactive healthy donors. Of the 157 peptides, eight peptides (5%) were found to induce T-cell responses. As judged from blocking with HLA class I and II subtype antibodies in the ELISPOT assay culture, none of the eight antigenic peptides induced HLA class I restricted CD8(+) T-cell responses. Instead all responses were blocked by pan-HLA class II and anti-HLA-DR antibodies. In addition, CD4(+) T-cell depletion before the 10 days of expansion, resulted in total loss of reactivity in the ELISPOT culture for most peptide specificities. FACS analyses with intracellular interferon-γ staining of T cells expanded in the presence of M. tuberculosis peptides confirmed that the responsive cells were indeed CD4(+). In conclusion, T-cell immunity against HLA-I binding 9mer M. tuberculosis-derived peptides might in many cases turn out to be mediated by CD4(+) T cells and restricted by HLA-II molecules. The use of 9mer peptides recognized by both CD8(+) and CD4(+) T cells might be of importance for the development of future M. tuberculosis peptide-based vaccines.

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

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

    2011-01-01

    Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide...... blocking with HLA class I and II subtype antibodies in the ELISPOT assay culture, none of the eight antigenic peptides induced HLA class I restricted CD8+ T‐cell responses. Instead all responses were blocked by pan‐HLA class II and anti‐HLA‐DR antibodies. In addition, CD4+ T‐cell depletion before the 10......‐cell immunity against HLA‐I binding 9mer M. tuberculosis‐derived peptides might in many cases turn out to be mediated by CD4+ T cells and restricted by HLA‐II molecules. The use of 9mer peptides recognized by both CD8+ and CD4+ T cells might be of importance for the development of future M. tuberculosis peptide...

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

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    Lund Ole

    2009-09-01

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

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

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Lund, Ole

    2007-01-01

    the correct alignment of a peptide in the binding groove a crucial part of identifying the core of an MHC class II binding motif. Here, we present a novel stabilization matrix alignment method, SMM-align, that allows for direct prediction of peptide:MHC binding affinities. The predictive performance...... of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC) and three mouse H2-IA alleles. RESULTS: The predictive performance of the SMM-align method was demonstrated to be superior to that of the Gibbs sampler, TEPITOPE, SVRMHC, and MHCpred methods. Cross validation...... 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...

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

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    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

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

    DEFF Research Database (Denmark)

    Zhang, Hao; Lund, Ole; Nielsen, Morten;

    2010-01-01

    on the highly conserved 3D structure of peptide:MHC complexes. While several such methods have been described before, most are not publicly available and have not been independently tested for their performance. We here implemented and evaluated three prediction methods for MHC class II molecules: statistical...... methods prediction performance showed that these are significantly better than random, but still substantially lower than the best performing sequence based class II prediction methods available. While the approaches presented here were developed independently, we have chosen to present our results...

  15. Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis.

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    Tambunan, Usman Sumo Friend; Wulandari, Evi Kristin

    2010-10-15

    Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate.

  16. The Presence, Persistence and Functional Properties of Plasmodium vivax Duffy Binding Protein II Antibodies Are Influenced by HLA Class II Allelic Variants

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    Torres, Leticia M.; Lima, Barbara A. S.; Sousa, Taís N.; Alves, Jéssica R. S.; Rocha, Roberto S.; Fontes, Cor J. F.; Sanchez, Bruno A. M.; Adams, John H.; Brito, Cristiana F. A.; Pires, Douglas E. V.; Ascher, David B.; Sell, Ana Maria; Carvalho, Luzia H.

    2016-01-01

    Background The human malaria parasite Plasmodium vivax infects red blood cells through a key pathway that requires interaction between Duffy binding protein II (DBPII) and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC). A high proportion of P. vivax-exposed individuals fail to develop antibodies that inhibit DBPII-DARC interaction, and genetic factors that modulate this humoral immune response are poorly characterized. Here, we investigate if DBPII responsiveness could be HLA class II-linked. Methodology/Principal Findings A community-based open cohort study was carried out in an agricultural settlement of the Brazilian Amazon, in which 336 unrelated volunteers were genotyped for HLA class II (DRB1, DQA1 and DQB1 loci), and their DBPII immune responses were monitored over time (baseline, 6 and 12 months) by conventional serology (DBPII IgG ELISA-detected) and functional assays (inhibition of DBPII–erythrocyte binding). The results demonstrated an increased susceptibility of the DRB1*13:01 carriers to develop and sustain an anti-DBPII IgG response, while individuals with the haplotype DRB1*14:02-DQA1*05:03-DQB1*03:01 were persistent non-responders. HLA class II gene polymorphisms also influenced the functional properties of DBPII antibodies (BIAbs, binding inhibitory antibodies), with three alleles (DRB1*07:01, DQA1*02:01 and DQB1*02:02) comprising a single haplotype linked with the presence and persistence of the BIAbs response. Modelling the structural effects of the HLA-DRB1 variants revealed a number of differences in the peptide-binding groove, which is likely to lead to altered antigen binding and presentation profiles, and hence may explain the differences in subject responses. Conclusions/Significance The current study confirms the heritability of the DBPII antibody response, with genetic variation in HLA class II genes influencing both the development and persistence of IgG antibody responses. Cellular studies to increase

  17. In silico designing breast cancer peptide vaccine for binding to MHC class I and II: A molecular docking study.

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    Mahdavi, Manijeh; Moreau, Violaine

    2016-12-01

    Antigenic peptides or cancer peptide vaccines can be directly delivered to cancer patients to produce immunologic responses against cancer cells. Specifically, designed peptides can associate with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells activating anti-tumor effector mechanisms by triggering helper T cell (Th) or cytotoxic T cells (CTL). In general, high binding to MHCs approximately correlates with in vivo immunogenicity. Consequently, a molecular docking technique was run on a library of novel discontinuous peptides predicted by PEPOP from Human epidermal growth factor receptor 2 (HER2 ECD) subdomain III. This technique is expected to improve the prediction accuracy in order to identify the best MHC class I and II binder peptides. Molecular docking analysis through GOLD identified the peptide 1412 as the best MHC binder peptide to both MHC class I and II molecules used in the study. The GOLD results predicted HLA-DR4, HLA-DP2 and TCR as the most often targeted receptors by the peptide 1412. These findings, based on bioinformatics analyses, can be exploited in further experimental analyses in vaccine design and cancer therapy to find possible proper approaches providing beneficial effects.

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

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

    2017-01-01

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

  19. Class II Microcins

    Science.gov (United States)

    Vassiliadis, Gaëlle; Destoumieux-Garzón, Delphine; Peduzzi, Jean

    Class II microcins are 4.9- to 8.9-kDa polypeptides produced by and active against enterobacteria. They are classified into two subfamilies according to their structure and their gene cluster arrangement. While class IIa microcins undergo no posttranslational modification, class IIb microcins show a conserved C-terminal sequence that carries a salmochelin-like siderophore motif as a posttranslational modification. Aside from this C-terminal end, which is the signature of class IIb microcins, some sequence similarities can be observed within and between class II subclasses, suggesting the existence of common ancestors. Their mechanisms of action are still under investigation, but several class II microcins use inner membrane proteins as cellular targets, and some of them are membrane-active. Like group B colicins, many, if not all, class II microcins are TonB- and energy-dependent and use catecholate siderophore receptors for recognition/­translocation across the outer membrane. In that context, class IIb microcins are considered to have developed molecular mimicry to increase their affinity for their outer membrane receptors through their salmochelin-like posttranslational modification.

  20. CD4 binding to major histocompatibility complex class II antigens induces LFA-1-dependent and -independent homotypic adhesion of B lymphocytes.

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    Kansas, G S; Cambier, J C; Tedder, T F

    1992-01-01

    T helper cells recognize processed antigen (Ag) in the context of major histocompatibility complex (MHC) class II antigens present on the surface of B cells and other Ag-presenting cells. This interaction is mediated through the T cell receptor complex with associate recognition of class II molecules by the CD4 molecule. In this study, the binding of a soluble recombinant CD4/Ig heavy chain fusion protein (CD4-gamma 3) or monoclonal antibody (mAb) to class II antigens on human B cells was shown to induce rapid and specific homotypic adhesion of B cells and most B lymphoblastoid cell lines. mAb reactive with CD4 inhibited CD4-gamma 3-induced adhesion and a mutant B lymphoblastoid cell line deficient in class II antigens failed to respond. Induction of homotypic adhesion was dependent on energy metabolism and a functional cytoskeleton, and class II+ pre-B cells did not exhibit adhesion in response to these stimuli, suggesting that cross-linking of class II molecules generated a transmembrane signal and did not simply aggregate cells. In addition, MHC class II-induced adhesion was Fc receptor independent, as 15 mAb of different Ig isotypes reactive with HLA-D or HLA-DQ gene products induced adhesion. Anti-class II mAb and CD4-gamma 3 were able to induce adhesion at concentrations as low as 10 ng/ml and 100 ng/ml, respectively. Suboptimal stimulation of B cell lines through HLA-D antigens induced homotypic adhesion that was dependent on the activation of LFA-1 (CD11a/CD18), and which could be blocked by specific mAb. However, at greater signal strengths, adhesion was not blocked by mAb against the known adhesion receptors, suggesting the induction of a novel adhesion pathway. Consistent with this, homotypic adhesion induced by engagement of MHC class II antigens was observed with LFA-1-deficient B cell lines, and was independent of CD49d or CD18 expression. Thus, the direct engagement of B cell class II antigens by CD4 is likely to generate transmembrane signals which

  1. 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......Major Histocompatibility class II (MHC-II) molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule...... of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC...

  2. Organizing MHC Class II Presentation

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    David R Fooksman

    2014-04-01

    Full Text Available Major histocompatibility complex (MHC class II molecules are ligands for CD4+ T cells and are critical for initiating the adaptive immune response. This review is focused on what is currently known about MHC class II organization at the plasma membrane of antigen presenting cells and how this affects antigen presentation to T cells. The organization and diffusion of class II molecules have been measured by a variety of biochemical and microscopic techniques. Membrane lipids and other proteins have been implicated in MHC class II organization and function. However, when compared with the organization of MHC class I or TCR complexes, much less is known about MHC class II. Since clustering of T cell receptors occurs during activation, the organization of MHC molecules prior to recognition and during synapse formation may be critical for antigen presentation.

  3. 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;

    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...... enzymes. D534A and D534N appeared to be completely inactive. When compared to the wild-type enzyme, the mutant enzymes in general showed only small changes in KM for the substrate, p-nitrophenyl-α-mannoside, but elevated activation constants, KA, for the divalent metal ion (Co2+, Zn2+, Mn2+, or Cd2......+). Some mutant enzyme forms displayed an altered preference for the metal ion compared to that of the wild type-enzyme. Furthermore, the H228Q, H533E, and H533Q enzymes were inhibited at increasing Zn2+ concentrations. The catalytic rate was reduced for all enzymes compared to that of the wild-type enzyme...

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    New strategies applied in the treatment of experimental autoimmune disease models involve blocking or modulation of MHC-peptide-TCR interactions either at the level of peptide-MHC interaction or, alternatively, at the level of T cell recognition. In order to identify useful competitor peptides one...... must be able to assess peptide-MHC interactions. Several well described autoimmune disease models exist in the Lewis rat and thus this particular rat strain provides a good model system to study the effect of competitor peptides. So far no information has been available on the peptide binding...... by chemiluminescence. The assay is sensitive and specific. We have used this assay to determine the binding characteristics of several disease associated T cell determinants and their sequence analogues in the Lewis rat. Notably, most of the autoimmune disease associated peptide sequences tested were found...

  5. Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.

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    Gelber, C; Gemmell, L; McAteer, D; Homola, M; Swain, P; Liu, A; Wilson, K J; Gefter, M

    1997-03-01

    Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.

  6. Tumor susceptibility gene 101 (TSG101 is a novel binding-partner for the class II Rab11-FIPs.

    Directory of Open Access Journals (Sweden)

    Conor P Horgan

    Full Text Available The Rab11-FIPs (Rab11-family interacting proteins; henceforth, FIPs are a family of Rab11a/Rab11b/Rab25 GTPase effector proteins implicated in an assortment of intracellular trafficking processes. Through proteomic screening, we have identified TSG101 (tumor susceptibility gene 101, a component of the ESCRT-I (endosomal sorting complex required for transport complex, as a novel FIP4-binding protein, which we find can also bind FIP3. We show that α-helical coiled-coil regions of both TSG101 and FIP4 mediate the interaction with the cognate protein, and that point mutations in the coiled-coil regions of both TSG101 and FIP4 abrogate the interaction. We find that expression of TSG101 and FIP4 mutants cause cytokinesis defects, but that the TSG101-FIP4 interaction is not required for localisation of TSG101 to the midbody/Flemming body during abscission. Together, these data suggest functional overlap between Rab11-controlled processes and components of the ESCRT pathway.

  7. The bovine class II major histocompatibility complex: Serological definition and further characterization of class II haplotypes.

    NARCIS (Netherlands)

    Nilsson, Ph.R.

    1994-01-01

    In this thesis an analysis of the major histocompatibility complex (MHC) class II in cattle is reported, with emphasis on the development of class II serology. First, the production of class II alloantisera, and the serological definition of bovine MHC class II polymorphism is described. Subsequentl

  8. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

  10. Early failure of Class II resin composite versus Class II amalgam restorations placed by dental students.

    Science.gov (United States)

    Overton, J D; Sullivan, Diane J

    2012-03-01

    Using the information from remake request slips in a dental school's predoctoral clinic, we examined the short-term survival of Class II resin composite restorations versus Class II dental amalgam restorations. In the student clinic, resin composite is used in approximately 58 percent of Class II restorations placed, and dental amalgam is used in the remaining 42 percent. In the period examined, Class II resin composite restorations were ten times more likely to be replaced at no cost to the patient than Class II dental amalgam restorations. A total of eighty-four resin composite restorations and six amalgam restorations were replaced due to an identified failure.

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

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Worning, Peder;

    2004-01-01

    to the 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...

  12. The Relationship between Class I and Class II Methanol Masers

    CERN Document Server

    Ellingsen, S P

    2005-01-01

    The Australia Telescope National Facility Mopra millimetre telescope has been used to search for 95.1-GHz class I methanol masers towards sixty-two 6.6-GHz class II methanol masers. A total of twenty-six 95.1-GHz masers were detected, eighteen of these being new discoveries. Combining the results of this search with observations reported in the literature, a near complete sample of sixty-six 6.6-GHz class II methanol masers has been searched in the 95.1-GHz transition, with detections towards 38 per cent (twenty-five detections ; not all of the sources studied in this paper qualify for the complete sample, and some of the sources in the sample were not observed in the present observations). There is no evidence of an anti-correlation between either the velocity range, or peak flux density of the class I and II transitions, contrary to suggestions from previous studies. The majority of class I methanol maser sources have a velocity range that partially overlaps with the class II maser transitions. The presence...

  13. In silico modification of Zn2+ binding group of suberoylanilide hydroxamic acid (SAHA) by organoselenium compounds as Homo sapiens class II HDAC inhibitor of cervical cancer

    Science.gov (United States)

    Sumo Friend Tambunan, Usman; Bakri, Ridla; Aditya Parikesit, Arli; Ariyani, Titin; Dyah Puspitasari, Ratih; Kerami, Djati

    2016-02-01

    Cervical cancer is the most common cancer in women, and ranks seventh of all cancers worldwide, with 529000 cases in 2008 and more than 85% cases occur in developing countries. One way to treat this cancer is through the inhibition of HDAC enzymes which play a strategic role in the regulation of gene expression. Suberoyl Anilide Hydroxamic Acid (SAHA) or Vorinostat is a drug which commercially available to treat the cancer, but still has some side effects. This research present in silico SAHA modification in Zinc Binding Group (ZBG) by organoselenium compound to get ligands which less side effect. From molecular docking simulation, and interaction analysis, there are five best ligands, namely CC27, HA27, HB28, IB25, and KA7. These five ligands have better binding affinity than the standards, and also have interaction with Zn2+ cofactor of inhibited HDAC enzymes. This research is expected to produce more potent HDAC inhibitor as novel drug for cervical cancer treatment.

  14. MHC Class II epitope predictive algorithms

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lund, Ole; Buus, S

    2010-01-01

    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 have been used to make a graphical...

  15. 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.

  16. 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.

  17. The C-terminal extension peptide of non-photoconvertible water-soluble chlorophyll-binding proteins (Class II WSCPs) affects their solubility and stability: comparative analyses of the biochemical and chlorophyll-binding properties of recombinant Brassica, Raphanus and Lepidium WSCPs with or without their C-terminal extension peptides.

    Science.gov (United States)

    Takahashi, Shigekazu; Uchida, Akira; Nakayama, Katsumi; Satoh, Hiroyuki

    2014-02-01

    Numerous members of the Brassicaceae possess non-photoconvertible water-soluble chlorophyll (Chl)-binding proteins (Class II WSCPs), which function as Chl scavengers during cell disruption caused by wounding, pest/pathogen attacks, and/or environmental stress. Class II WSCPs have two extension peptides, one at the N-terminus and one at the C-terminus. The N-terminal peptide acts as a signal peptide, targeting the protein to the endoplasmic reticulum body, a unique defensive organelle found only in the Brassicaceae. However, the physiological and biochemical functions of the C-terminal extension peptide had not been characterized previously. To investigate the function of the C-terminal extension peptide, we produced expression constructs of recombinant WSCPs with or without the C-terminal extension peptide. The WSCPs used were of Brussels sprouts (Brassica oleracea), Japanese wild radish (Raphanus sativus) and Virginia pepperweed (Lepidium virginicum). The solubility of all of the WSCPs with the C-terminal extension peptide was drastically lower than that of the recombinant WSCPs without the C-terminal extension peptide. In addition, the stability of the reconstituted WSCPs complexes with the C-terminal extension peptide was altered compared with that of the proteins without the C-terminal extension peptide. These finding indicate that the C-terminal extension peptide affects not only the solubility, but also the stability of Class II WSCP. Furthermore, we characterized the Chl-binding properties of the recombinant WSCP from Japanese wild radish (RshWSCP-His) in a 40 % methanol solution. An electrophoretic mobility shift assay revealed that RshWSCP-His required a half-molar ratio of Chls to form a tetramer.

  18. Condylar volume and condylar area in class I, class II and class III young adult subjects

    OpenAIRE

    Saccucci Matteo; D’Attilio Michele; Rodolfino Daria; Festa Felice; Polimeni Antonella; Tecco Simona

    2012-01-01

    Abstract Aim Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. Material and methods 200 Caucasian patients (15–30 years old, 95 male and 105 females) were classified in three groups on the base of ANB angle: skeletal class I (65 patients), skeletal class II (70 patients) and skeletal class III (65 patients). Left and right TMJs of each subject were evaluated independently with CBCT (Iluma). ...

  19. 46 CFR 50.30-15 - Class II pressure vessels.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Class II pressure vessels. 50.30-15 Section 50.30-15... Fabrication Inspection § 50.30-15 Class II pressure vessels. (a) Class II pressure vessels shall be subject to... pressure vessels shall be performed during the welding of the longitudinal joint. At this time the...

  20. 49 CFR 238.317 - Class II brake test.

    Science.gov (United States)

    2010-10-01

    ... locomotives that utilize an electric signal to communicate a service brake application and only a pneumatic... 49 Transportation 4 2010-10-01 2010-10-01 false Class II brake test. 238.317 Section 238.317... Requirements for Tier I Passenger Equipment § 238.317 Class II brake test. (a) A Class II brake test shall...

  1. Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases.

    Science.gov (United States)

    Arase, Hisashi

    2016-01-01

    Misfolded proteins localized in the endoplasmic reticulum are degraded promptly and thus are not transported outside cells. However, misfolded proteins in the endoplasmic reticulum are rescued from protein degradation upon association with major histocompatibility complex (MHC) class II molecules and are transported to the cell surface by MHC class II molecules without being processed to peptides. Studies on the misfolded proteins rescued by MHC class II molecules have revealed that misfolded proteins associated with MHC class II molecules are specific targets for autoantibodies produced in autoimmune diseases. Furthermore, a strong correlation has been observed between autoantibody binding to misfolded proteins associated with MHC class II molecules and the autoimmune disease susceptibility conferred by each MHC class II allele. These new insights into MHC class II molecules suggest that misfolded proteins rescued from protein degradation by MHC class II molecules are recognized as "neo-self" antigens by immune system and are involved in autoimmune diseases as autoantibody targets.

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

    OpenAIRE

    Jean-Simon eFortin; Maryse eCloutier; Jacques eThibodeau

    2013-01-01

    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...

  3. 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......: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 rise to both HLA class I and class II restricted responses by CD8 and CD4 T cells, respectively, whereas...... with this, peptide vaccination did not decrease virus titres in the lungs of intranasally influenza challenged mice. Our data show that HLA class I and class II double binding peptides can be identified by bioinformatics and biochemical technology. By immunization, double binding peptides can give rise...

  4. 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.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1......MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... 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...

  6. Condylar volume and condylar area in class I, class II and class III young adult subjects

    Directory of Open Access Journals (Sweden)

    Saccucci Matteo

    2012-12-01

    Full Text Available Abstract Aim Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. Material and methods 200 Caucasian patients (15–30 years old, 95 male and 105 females were classified in three groups on the base of ANB angle: skeletal class I (65 patients, skeletal class II (70 patients and skeletal class III (65 patients. Left and right TMJs of each subject were evaluated independently with CBCT (Iluma. TMJ evaluation included: condylar volume; condylar area; morphological index (MI. Condylar volumes were calculated by using the Mimics software. The condylar volume, the area and the morphological index (MI were compared among the three groups, by using non-parametric tests. Results The Kruskal-Wallis test and the Mann Whitney test revealed that: no significant difference was observed in the whole sample between the right and the left condylar volume; subjects in skeletal class III showed a significantly higher condylar volume, respect to class I and class II subjects (p 3 in males and 663.5 ± 81.3 mm3 in females; p 2 in males and 389.76 ± 61.15 mm2 in females; p  Conclusion Skeletal class appeared to be associated to the mandibular condylar volume and to the mandibular condylar area in the Caucasian orthodontic population.

  7. The systems biology of MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra

    2012-01-01

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

  8. Angle Class II correction with MARA appliance

    Directory of Open Access Journals (Sweden)

    Kelly Chiqueto

    2013-02-01

    Full Text Available OBJECTIVE: To assess the effects produced by the MARA appliance in the treatment of Angle's Class II, division 1 malocclusion. METHODS: The sample consisted of 44 young patients divided into two groups: The MARA Group, with initial mean age of 11.99 years, treated with the MARA appliance for an average period of 1.11 years, and the Control Group, with initial mean age of 11.63 years, monitored for a mean period of 1.18 years with no treatment. Lateral cephalograms were used to compare the groups using cephalometric variables in the initial and final phases. For these comparisons, Student's t test was employed. RESULTS: MARA appliance produced the following effects: Maxillary growth restriction, no change in mandibular development, improvement in maxillomandibular relationship, increased lower anterior facial height and counterclockwise rotation of the functional occlusal plane. In the upper arch, the incisors moved lingually and retruded, while the molars moved distally and tipped distally. In the lower arch, the incisors proclined and protruded, whereas the molars mesialized and tipped mesially. Finally, there was a significant reduction in overbite and overjet, with an obvious improvement in molar relationship. CONCLUSIONS: It was concluded that the MARA appliance proved effective in correcting Angle's Class II, division 1 malocclusion while inducing skeletal changes and particularly dental changes.OBJETIVO: avaliar os efeitos proporcionados pelo aparelho MARA no tratamento da má oclusão de Classe II, 1ª divisão. MÉTODOS: utilizou-se uma amostra de 44 jovens, divididos em dois grupos - Grupo MARA, com idade inicial média de 11,99 anos e tratado com o aparelho MARA por um período médio de 1,11 ano; e Grupo Controle, com idade inicial média de 11,63 ano e observado por um período médio de 1,18 ano, sem nenhum tratamento. Utilizou-se as telerradiografias em norma lateral para comparar os grupos quanto às variáveis cefalométricas das

  9. 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.

  10. Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases.

    Science.gov (United States)

    Arase, Noriko; Arase, Hisashi

    2015-11-01

    The major function of major histocompatibility complex (MHC) class II molecules is the presentation of peptide antigens to helper T cells. However, when misfolded proteins are associated with MHC class II molecules in the endoplasmic reticulum, they are transported to the cell surface by MHC class II molecules without processing to peptides. Of note, misfolded proteins complexed with MHC class II molecules are specifically recognized by autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins rescued from degradation by MHC class II molecules may be recognized as 'neo-self' antigens by the immune system and be involved in the pathogenicity of autoimmune diseases.

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

    Directory of Open Access Journals (Sweden)

    Zeeshan Iqbal Bhat

    2013-01-01

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

  12. Downregulation of class II transactivator (CIITA) expression by synthetic cannabinoid CP55,940.

    Science.gov (United States)

    Gongora, Celine; Hose, Stacey; O'Brien, Terrence P; Sinha, Debasish

    2004-01-30

    Cannabinoid receptors are known to be expressed in microglia; however, their involvement in specific aspects of microglial immune function has not been demonstrated. Many effects of cannabinoids are mediated by two G-protein coupled receptors, designated CB1 and CB2. We have shown that the CB1 receptor is expressed in microglia that also express MHC class II antigen (J. Neuroimmunol. 82 (1998) 13-21). In our present study, we have analyzed the effect of cannabinoid agonist CP55,940 on MHC class II expression on the surface of IFN-gamma induced microglial cells by flow cytometry. CP55,940 blocked the class II MHC expression induced by IFN-gamma. It has been shown that the regulation of class II MHC genes occurs primarily at the transcriptional level, and a non-DNA binding protein, class II transactivator (CIITA), has been shown to be the master activator for class II transcription. We find that mRNA levels of CIITA are increased in IFN-gamma induced EOC 20 microglial cells and that this increase is almost entirely eliminated by the cannabinoid agonist CP55,940. These data suggests that cannabinoids affect MHC class II expression through actions on CIITA at the transcriptional level.

  13. 25 CFR 522.10 - Individually owned class II and class III gaming operations other than those operating on...

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II and class III gaming... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.10 Individually owned class II and class...

  14. HLA Class I and Class II Associations with ESRD in Saudi Arabian Population

    OpenAIRE

    Nuha Mahmoud Hamdi; Fadel Hassan Al-Hababi; Amr Ekhlas Eid

    2014-01-01

    BACKGROUND: Chronic renal failure (CRF) leads in the majority of instances to end stage renal disease (ESRD) requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population. METHODOLOGY: A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated ...

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

    Science.gov (United States)

    McFarlane, Bruce

    2013-01-01

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

  16. 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.

  17. Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Jonathan Harton

    2016-03-01

    Full Text Available Major histocompatibility complex (MHC class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naïve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II α and β chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail mediates these “non-traditional” class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease.

  18. 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 given...... the public access to frequent, up-to-date performance evaluations of all participating tools. To overcome potential selection bias in the data included in the IEDB, a strategy was implemented that suggests a set of peptides for which different prediction methods give divergent predictions as to their binding...

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

    Science.gov (United States)

    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 the facial axis of the clinical crown)and WALA points (the most prominent point on the soft-tissue ridge)were employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2). In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

  20. The simple class II and class III corrector: three case reports.

    Science.gov (United States)

    Spary, David John; Little, Rachel Ann

    2015-03-01

    This article illustrates three case reports which describe a very simple appliance that is used to correct both class II and class III buccal segments. A class I molar relationship is achieved within 2-6 months. Hundreds of cases have been treated with these appliances over a number of years at Queen's Hospital, Burton upon Trent with great success.

  1. Specific binding of toxin II from Centruroides suffusus suffusus to the sodium channel in electroplaque membranes.

    Science.gov (United States)

    Wheeler, K P; Barhanin, J; Lazdunski, M

    1982-10-26

    The binding of toxin II from the scorpion Centruroides suffusus suffusus (CssII) to electroplaque membranes from Electrophorus electricus was studied with the use of a radiolabeled derivative of the toxin ([125I]CssII). Specific binding of the latter to the membranes required the protonation of a group, either in the membrane or in the toxin itself, with an apparent pKa value of 7.5 and also the presence of a certain minimum concentration of ions, though there was no requirement for a specific ion. At 20 degrees C and pH 6 the second-order rate constant for formation of the [125I]CssII-membrane complex was about 5 X 10(6) M-1 s-1, while the first-order constant for its dissociation was about 2 X 10(-3) s-1. Under equilibrium conditions specific binding of [125I]CssII was a simple saturable function of [125I]CssII concentration, characterized by a dissociation constant of 0.4-0.7 nM and a maximum capacity of 0.9-2.4 pmol of toxin/mg of membrane protein. The latter value was the same as the number of membrane sites that could specifically bind a radiolabeled derivative of tetrodotoxin. Unlabeled CssII displaced bound [125I]CssII with an apparent dissociation constant of about 1 nM. None of 19 other neurotoxins or local anaesthetics known to interact with Na+ channels in excitable cells affected [125I]CssII binding, but it was completely inhibited by toxin gamma from the scorpion Tityus serrulatus serrulatus. These findings suggest that the Na+ channel possesses a distinct class of binding sites to which these two scorpion toxins bind with high affinities. On the other hand, no CssII receptor was detected in crab axonal membranes, indicating that it is not a characteristic feature of all Na+ channels.

  2. 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.

  3. Light-induced activation of class II cyclobutane pyrimidine dimer photolyases.

    Science.gov (United States)

    Okafuji, Asako; Biskup, Till; Hitomi, Kenichi; Getzoff, Elizabeth D; Kaiser, Gebhard; Batschauer, Alfred; Bacher, Adelbert; Hidema, Jun; Teranishi, Mika; Yamamoto, Kazuo; Schleicher, Erik; Weber, Stefan

    2010-05-04

    Light-induced activation of class II cyclobutane pyrimidine dimer (CPD) photolyases of Arabidopsis thaliana and Oryza sativa has been examined by UV/Vis and pulsed Davies-type electron-nuclear double resonance (ENDOR) spectroscopy, and the results compared with structure-known class I enzymes, CPD photolyase and (6-4) photolyase. By ENDOR spectroscopy, the local environment of the flavin adenine dinucleotide (FAD) cofactor is probed by virtue of proton hyperfine couplings that report on the electron-spin density at the positions of magnetic nuclei. Despite the amino-acid sequence dissimilarity as compared to class I enzymes, the results indicate similar binding motifs for FAD in the class II photolyases. Furthermore, the photoreduction kinetics starting from the FAD cofactor in the fully oxidized redox state, FAD(ox), have been probed by UV/Vis spectroscopy. In Escherichia coli (class I) CPD photolyase, light-induced generation of FADH from FAD(ox), and subsequently FADH(-) from FADH, proceeds in a step-wise fashion via a chain of tryptophan residues. These tryptophans are well conserved among the sequences and within all known structures of class I photolyases, but completely lacking from the equivalent positions of class II photolyase sequences. Nevertheless, class II photolyases show photoreduction kinetics similar to those of the class I enzymes. We propose that a different, but also effective, electron-transfer cascade is conserved among the class II photolyases. The existence of such electron transfer pathways is supported by the observation that the catalytically active fully reduced flavin state obtained by photoreduction is maintained even under oxidative conditions in all three classes of enzymes studied in this contribution.

  4. The CLASS blazar survey - II. Optical properties

    NARCIS (Netherlands)

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

    2002-01-01

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

  5. An Investigation of Craniocervical Posture in Class II & Class III Skeletal Patients

    Directory of Open Access Journals (Sweden)

    T. HoseinZadeh-Nik

    2005-02-01

    Full Text Available Statement of Problem: Craniocervical Posture is a factor in the development and function of Craniofacial Structure. Previous studies of different samples have demonstrated associations between craniocervical posture and craniofacial morphology.Purpose: This study aimed lo examine whether any significant association is evident or not between craniocervical posture and the occurrence of Class il & Class III skeletal malocclusions.Materials and Methods: A sample of 76 subjects with Class II & Class III skeletal malocclusion aged 9-i 1 and>18 years were selected. None of them had received orthodontic treatment. Lateral cephalometric radiographs were taken in natural head position (NHP, and craniocervical and craniohorizental angels were traced and determined for analysis of craniocervical posture. Results: According to the craniocervical posture, most class II skeletal patients have flexed heads and class MI skeletal patients have extended heads, as a result malocclusion in these patients seems to become more severe. With increase in age. class II skeletal patients have more flexed their heads and malocclusion become more severe, while with increase in age in class ill skeletal patients, their heads become extended and once again malocclusion thought lo be more severe. In class II skeletal patients, craniocervical posture has a significant correlation with the vertical growth pattern, but shows little correlation with the horizontal growth pattern. In class 111 skeletal patients, craniocervical posture shows no correlation to any of the vertical & horizontal growth patterns, of course the mean of vertical angles is less in these patients and probably in order to make these relation significant in Class III skeletal patients there is need for more samples, in class II & class III skeletal patients, the amount of Na.prep-point A and pog-Na.prep with craniocervical posture shows a significant correlation. Conclusion: Consideration of craniocervical

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

    DEFF Research Database (Denmark)

    Salomonsen, Jan; Marston, Denise; Avila, David;

    2003-01-01

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

  7. Mechanistic understanding and significance of small peptides interaction with MHC class II molecules for therapeutic applications.

    Science.gov (United States)

    Afridi, Saifullah; Hoessli, Daniel C; Hameed, Muhammad Waqar

    2016-07-01

    Major histocompatibility complex (MHC) class II molecules are expressed by antigen-presenting cells and stimulate CD4(+) T cells, which initiate humoral immune responses. Over the past decade, interest has developed to therapeutically impact the peptides to be exposed to CD4(+) T cells. Structurally diverse small molecules have been discovered that act on the endogenous peptide exchanger HLA-DM by different mechanisms. Exogenously delivered peptides are highly susceptible to proteolytic cleavage in vivo; however, it is only when successfully incorporated into stable MHC II-peptide complexes that these peptides can induce an immune response. Many of the small molecules so far discovered have highlighted the molecular interactions mediating the formation of MHC II-peptide complexes. As potential drugs, these small molecules open new therapeutic approaches to modulate MHC II antigen presentation pathways and influence the quality and specificity of immune responses. This review briefly introduces how CD4(+) T cells recognize antigen when displayed by MHC class II molecules, as well as MHC class II-peptide-loading pathways, structural basis of peptide binding and stabilization of the peptide-MHC complexes. We discuss the concept of MHC-loading enhancers, how they could modulate immune responses and how these molecules have been identified. Finally, we suggest mechanisms whereby MHC-loading enhancers could act upon MHC class II molecules.

  8. Receptor-binding radiotracers: a class of potential radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Eckelman, W.C.; Reba, R.C.; Gibson, R.E.; Rzeszotarski, W.J.; Vieras, F.; Mazaitis, J.K.; Francis, B.

    1979-04-01

    To date no radiopharmaceutical is routinely used to study changes in receptor concentration. Frequently changes in receptor concentration, or the appearance of receptors in tumors, indicates a specific pathologic state. With a receptor-binding radiotracer, in vivo studies of these changes will be possible. A reversible bimolecular model and in vitro tests were used to determine equilibrium constants and maximal target-to-blood ratios for new derivatives. Theoretical calculations showed that derivatives binding to the estrogen receptor, the beta adrenoceptor, or the cholinergic receptor are capable of achieving satisfactory target-to-blood ratios. Using in vitro tests, the apparent affinity constant was determined for five iodinated estrogen derivatives and five derivatives of beta blockers. Results of the in vitro study with derivatives of beta blockers. Results of the in vitro study with derivatives of beta blockers, and in vivo displacement studies using propranolol, indicated that the high heart-to-blood ratios (5 to 20) obtained with the new derivatives were not the result of a specific interaction with the receptor. In this instance factors other than receptor binding control the in vivo distribution. The in vitro assay using estrogen receptors showed that of the five derivatives, iodohexestrol and 17-alpha-iodoethynylestradiol bind to the receptor with the highest affinity. In vivo studies confirmed these results; iodohexestrol gave a uterus-to-blood ratio of 10 in immature rats when plasma-protein binding was blocked. With a tritiated muscarinic cholinergic blocking agent, heart-to-blood ratios near the theoretical maximum were obtained. This compound most closely follows the mechanism described by the model. Use of the theoretical model in conjunction with in vitro assays can greatly aid in the design of this new class of receptor-binding radiopharmaceuticals.

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    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......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...... that an additive risk effect (synergism or interaction) exists between the DQB1*0301 and DPA1*0103 alleles which are situated at different HLA class II loci....

  10. HLA class II genes: typing by DNA analysis.

    Science.gov (United States)

    Bidwell, J L; Bidwell, E A; Bradley, B A

    1990-04-01

    A detailed understanding of the structure and function of the human major histocompatibility complex (MHC) has ensued from studies by molecular biologist during the last decade. Virtually all of the HLA genes have now been cloned, and the nucleotide sequences of their different allelic forms have been determined. Typing for these HLA alleles is a fundamental prerequisite for tissue matching in allogeneic organ transplantation. Until very recently, typing procedures have been dominated by serological and cellular methods. The availability of cloned DNA from HLA genes has now permitted the technique of restriction fragment length polymorphism (RFLP) analysis to be applied, with remarkable success and advantage, to phenotyping of both HLA Class I and Class II determinants. For the HLA Class II genes DR and DQ, a simple two-stage RFLP analysis permits the accurate identification of all specificities defined by serology, and of many which are defined by cellular typing. At the present time, however, RFLP typing of HLA Class I genes is not as practicable or as informative as that for HLA Class II genes. The present clinical applications of HLA-DR and DQ RFLP typing are predominantly in phenotyping of living donors, including selection of HLA-matched volunteer bone marrow donors, in allograft survival studies, and in studies of HLA Class II-associated diseases. However, the time taken to perform RFLP analysis precludes its use for the typing of cadaveric kidney donors. Nucleotide sequence data for the alleles of HLA Class II genes have now permitted the development of allele-specific oligonucleotide (ASO) typing, a second category of DNA analysis. This has been greatly facilitated by the ability to amplify specific HLA Class II DNA 'target' sequences using the polymerase chain reaction (PCR) technique. The accuracy of DNA typing techniques should ensure that this methodology will eventually replace conventional HLA phenotyping.

  11. 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.

  12. Exposing the Specific Roles of the Invariant Chain Isoforms in Shaping the MHC Class II Peptidome.

    Science.gov (United States)

    Fortin, Jean-Simon; Cloutier, Maryse; Thibodeau, Jacques

    2013-12-13

    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.

  13. Binding of polycyclic aromatic hydrocarbons by size classes of particulate in Hamilton Harbor water

    Energy Technology Data Exchange (ETDEWEB)

    Leppard, G.G. [National Water Research Inst., Burlington, Ontario (Canada). Aquatic Ecosystem Protection Branch]|[McMaster Univ., Hamilton, Ontario (Canada). Dept. of Biology; Flannigan, D.T. [McMaster Univ., Hamilton, Ontario (Canada). Dept. of Biology; Mavrocordatos, D. [McMaster Univ., Hamilton, Ontario (Canada). Dept. of Biology]|[Univ. of Lausanne (Switzerland). Dept. of Chemistry; Marvin, C.H. [McMaster Univ., Hamilton, Ontario (Canada). Dept. of Chemistry]|[Agriculture and Agri-Food Canada, Vineland Station Ontario (Canada). Pest Management Research Centre; Bryant, D.W.; McCarry, B.E. [McMaster Univ., Hamilton, Ontario (Canada)

    1998-11-15

    In aquatic systems there is considerable transport of organic contaminants on suspended particles that act as carriers and influence the redistribution, bioavailability, and ultimate fate of contaminants. Using methodology not previously applied to the analysis of lake water, the authors demonstrate that polycyclic aromatic hydrocarbons (PAH) in Hamilton Harbor are predominantly sorbed to suspended flocs. Techniques employed were as follows: (i) differential cascade sedimentation and centrifugation to separate suspended particles; (ii) scanning transmission electron microscopy and energy-dispersive spectroscopy to identify flocs and individual particles in the size range of 10{sup {minus}3}--10{sup 3} {micro}m; (iii) gas chromatography-mass spectrometry to identify PAH in extracts prepared from size classes. Heterogeneous flocs larger than 20 {micro}m accounted for roughly 98% of phenanthrene binding, 89% of fluoranthene binding, and 85% of pyrene binding.

  14. 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.

  15. Class II malocclusion therapy using fixed orthodontic appliance

    Directory of Open Access Journals (Sweden)

    Škufca Bojan

    2007-01-01

    Full Text Available Background. Depending on the indication, and the age of a patient, class II division I malocclusion can be treated by a fixed or mobile orthodontic appliance, with or without teeth extraction. Case report. A treatment of a male patient, 15 years old, with dentoalveolar class II division I was described. On the base of clinical findings, study case analysis, analysis of orthopan and profile cephalogram, there were class II division I with protrusion of frontal teeth and mild crowding in lower jaw assessed. The patient was treated by fixed orthodontics appliances (SWA Roth .022" in both jaws for 18 months, with the retention period of the same length. Conclusion. Fixed ortodontic appliances are necessary when bodily movement of the teeth is indicated - in this case for cuspids distalization and retraction of incisors.

  16. Does protein binding modulate the effect of angiotensin II receptor antagonists?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2001-03-01

    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  17. Low major histocompatibility complex class II diversity in European and North American moose.

    OpenAIRE

    1995-01-01

    Major histocompatibility complex (MHC) genes encode cell surface proteins whose function is to bind and present intracellularly processed peptides to T lymphocytes of the immune system. Extensive MHC diversity has been documented in many species and is maintained by some form of balancing selection. We report here that both European and North American populations of moose (Alces alces) exhibit very low levels of genetic diversity at an expressed MHC class II DRB locus. The observed polymorphi...

  18. Ligation of MHC class I and class II molecules can lead to heterologous desensitization of signal transduction pathways that regulate homotypic adhesion in human lymphocytes.

    Science.gov (United States)

    Wagner, N; Engel, P; Vega, M; Tedder, T F

    1994-06-01

    Engagement of lymphocyte MHC class I and class II Ags activates an array of intracellular signal transduction pathways that up-regulates the activity of cell-surface adhesion receptors, resulting in homotypic cell-cell aggregation. In this study, engagement of MHC class I and class II molecules with specific mAbs was shown to also inhibit lymphocyte homotypic adhesion. Two mAbs reactive with class II Ag, homotypic adhesion blocking mAb (HAB)-2, and HAB-3, and one mAb reactive with class I Ag, HAB-4, were generated that inhibited homotypic adhesion of activated lymphocytes and B and T cell lines at concentrations as low as 0.1 microgram/ml. Binding of these mAbs resulted in heterologous desensitization of other surface signal transduction molecules as homotypic adhesion induced through class I, class II, CD19, CD20, CD39, CD40, Leu-13, and PMA was also inhibited. The spontaneous adhesion exhibited by some cell lines was also abrogated by binding of these mAbs. Abs that either induced, blocked, or had no effect on adhesion bound to distinct epitopes on class I, whereas the anti-class II mAbs recognized either distinct or overlapping epitopes. Thus, engagement of distinct epitopes on MHC molecules can result in homologous or heterologous desensitization of cell-surface signaling molecules. The induction or inhibition of homotypic adhesion through class I molecules did not require the presence of the cytoplasmic domain, as deletion of this portion of the class I molecule had no effect. In contrast, the transmembrane region was essential for signal transduction as the mAbs binding to a chimeric molecule in which the transmembrane and cytoplasmic domains of class I were exchanged with those of the HB15 molecule did not induce or inhibit homotypic adhesion. Although this report is the first demonstration that homotypic adhesion can be influenced in a negative manner through MHC molecules, these findings demonstrate a considerable level of cross-talk between MHC molecules

  19. Class II malocclusion nonextraction treatment with growth control

    Directory of Open Access Journals (Sweden)

    Zilda Lúcia Valentim Assunção

    2014-12-01

    Full Text Available The present study reports a case of Angle Class II malocclusion treatment of a male growing patient with 10-mm overjet, excessive overbite and transverse maxillary deficiency. The case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO, with DI equal to or greater than 10, as a requirement for the title of certified by the BBO.

  20. 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

  1. Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold.

    Science.gov (United States)

    Liberman, Joseph A; Salim, Mohammad; Krucinska, Jolanta; Wedekind, Joseph E

    2013-06-01

    PreQ1 riboswitches regulate genes by binding the pyrrolopyrimidine intermediate preQ1 during the biosynthesis of the essential tRNA base queuosine. We report what is to our knowledge the first preQ1-II riboswitch structure at 2.3-Å resolution, which uses a previously uncharacterized fold to achieve effector recognition at the confluence of a three-way helical junction flanking a pseudoknotted ribosome-binding site. The results account for translational control mediated by the preQ1-II riboswitch class and expand the known repertoire of ligand-binding modes used by regulatory RNAs.

  2. Evaluation of mandibular length in subjects with Class I and Class II skeletal patterns using the cervical vertebrae maturation

    OpenAIRE

    Rodrigo Generoso; Elaine Cristina Sadoco; Mônica Costa Armond; Gustavo Hauber Gameiro

    2010-01-01

    The aim of this study was to compare the mandibular size in boys and girls with Class I and Class II skeletal patterns, taking into consideration the bone maturation stage, as defined by the cervical vertebrae maturation. One hundred and sixty cephalometric radiographs were obtained from subjects (aged between 7 and 12 years) with Class I or Class II skeletal patterns, according to the ANB angle and WITS appraisal. The Class I sample consisted of 80 subjects (40 boys, 40 girls). The Class II ...

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

    Science.gov (United States)

    Barreto, Gustavo Mattos

    2013-01-01

    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.

  4. 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.

  5. Multiple regenerative techniques for class II furcation defect

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2012-01-01

    Full Text Available Regeneration of the periodontium is a major goal in the treatment of teeth affected by periodontitis. Periodontal regeneration is quite challenging, especially when it is in the furcation area. There are several techniques used alone or in combination, considered to achieve periodontal regeneration, including bone grafts or substitutes, guided tissue regeneration, root surface modification, and biological mediators. Many factors may account for variability in the response to regenerative therapy in class II furcation. This case report describes the management of a buccal class II furcation defect, with the help of surgical intervention, including the guided tissue regeneration (GTR membrane and bone graft materials. This combined treatment resulted in a healthy periodontium, with radiographic evidence of alveolar bone gain. This case report demonstrates that proper diagnosis, followed by removal of the etiological factors and utilizing combined treatment modalities, restored health and function of the tooth with severe attachment loss, at the 18-month follow-up.

  6. MHC class II genes in the European badger (Meles meles) : Characterization, patterns of variation, and transcription analysis

    NARCIS (Netherlands)

    Sin, Yung Wa; Dugdale, Hannah L.; Newman, Chris; Macdonald, David W.; Burke, Terry

    2012-01-01

    The major histocompatibility complex (MHC) comprises many genes, some of which are polymorphic with numerous alleles. Sequence variation among alleles is most pronounced in exon 2 of the class II genes, which encodes the alpha 1 and beta 1 domains that form the antigen-binding site (ABS) for the pre

  7. 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

  8. Cylindrical bubbles and blobs from a Class II Hydrophobin

    Science.gov (United States)

    Russo, Paul; Pham, Michael; Blalock, Brad

    2012-02-01

    Cerato ulmin is a class II hydrophobin. In aqueous suspensions, it easily forms cylindrical air bubbles and cylindrical oil blobs. The conditions for formation of these unusual structures will be discussed, along with scattering and microscopic investigations of their remarkable stability. Possible applications in diverse fields including polymer synthesis and oil spill remediation will be considered. Acknowledgment is made to Dr. Wayne C. Richards of the Canadian Forest Service for the gift of Cerato ulmin.

  9. Characterization of recombination in the HLA class II region

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, M.; Carrington, M. [National Cancer Institute, Frederick, MD (United States); Noble, J. [Roche Molecular Systems, Almeda, CA (United States)] [and others

    1997-02-01

    Studies of linkage disequilibrium across the HLA class II region have been useful in predicting where recombination is most likely to occur. The strong associations between genes within the 85-kb region from DQB1 to DRB1 are consistent with low frequency of recombination in this segment of DNA. Conversely, a lack of association between alleles of TAP1 and TAP2 ({approximately}15 kb) has been observed, suggesting that recombination occurs here with relatively high frequency. Much of the HLA class II region has now been sequenced, providing the tools to undertake detailed analysis of recombination. Twenty-seven families containing one or two recombinant chromosomes within the 500-kb interval between the DPB1 and DRB1 genes were used to determine patterns of recombination across this region. SSCP analysis and microsatellite typing yielded identification of 127 novel polymorphic markers distributed throughout the class II region, allowing refinement of the site of crossover in 30 class II recombinant chromosomes. The three regions where recombination was observed most frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11 cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further characterization, pending identification of additional informative markers, while four recombinants were localized to other intervals (outliers). Analysis of association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no linkage disequilibrium, supporting the familial recombination data. A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA){sub 12} tandem repeat within the TAP2 gene. 74 refs., 3 figs., 2 tabs.

  10. [Routine application of HLA class II oligotyping. Value of automatization].

    Science.gov (United States)

    Caillat-Zucman, S; Bach, J F

    1992-12-02

    HLA class II typing by DNA amplification and hybridization with allele-specific oligonucleotides has led to an improvement of the overall typing accuracy. In an attempt to apply this procedure to a large-scale analysis, we sought to implement an automation system using the Biomek 1,000 robotic work-station. This system allows a rapid preparation of many consecutive samples and avoids the risk of human errors. It is now routinely used in several laboratories.

  11. Treatment of a Class II deepbite with microimplant anchorage.

    Science.gov (United States)

    Park, Hyo-Sang; Kim, Ji-Yeun; Kwon, Tae-Geon

    2011-03-01

    The goal of this report was to illustrate new treatment mechanics for using microimplants for the treatment of a Class II Division 2 deepbite malocclusion. A 29-year-old woman with a deepbite was treated with the aid of microimplant anchorage. Microimplants placed between the maxillary second premolars and first molars were used as anchorage to apply a distal force to the anterior teeth to correct the Class II canine and molar relationships. A distal force was applied to long hooks that were crimped between the lateral incisors and the canines. By applying a backward force to the long hooks, the maxillary anterior teeth experienced palatal root movement with no change in the vertical and anteroposterior positions of the incisal edges. The distal extrusive movement of the maxillary second molars achieved by disengaging the second molars from the archwire during distal force application and an anterior bite-block bonded on the lingual surface of the maxillary central incisors produced the increase in vertical dimension. The distal force to the long extended hooks from the microimplants was possibly good mechanics for obtaining the palatal root movement and correcting the Class II canine and molar relationships. The anterior bite-block and disengagement of the maxillary second molars during distal force application were effective for increasing the vertical dimension.

  12. MHC Class II haplotypes of Colombian Amerindian tribes.

    Science.gov (United States)

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

    2013-07-01

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

  13. 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.

  14. Copper(II) and nickel(II) binding sites of peptide containing adjacent histidyl residues.

    Science.gov (United States)

    Grenács, Ágnes; Sanna, Daniele; Sóvágó, Imre

    2015-10-01

    Copper(II) and nickel(II) complexes of the terminally protected nonapeptide Ac-SGAEGHHQK-NH2 modeling the metal binding sites of the (8-16) domain of amyloid-β have been studied by potentiometric, UV-vis, CD and ESR spectroscopic methods. The studies on the mutants containing only one of the histidyl residues (Ac-SGAEGAHQK-NH2, Ac-SGAEGHAQK-NH2) have also been performed. The formation of imidazole and amide coordinated mononuclear complexes is characteristic of all systems with a preference of nickel(II) binding to the His14 site, while the involvement of both histidines in metal binding is suggested in the corresponding copper(II) complexes. The formation of bis(ligand) and dinuclear complexes has also been observed in the copper(II)-Ac-SGAEGHHQK-NH2 system. The results provide further support for the copper(II) binding ability of the (8-16) domain of amyloid-β and support the previous assumptions that via the bis(ligand) complex formation copper(II) ions may promote the formation of the oligomers of amyloid-β.

  15. 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

  16. 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.

  17. The shape and size of the sella turcica in skeletal Class I, Class II, and Class III Saudi subjects.

    Science.gov (United States)

    Alkofide, Eman A

    2007-10-01

    The purpose of this study was to describe the shape and measure the size of the sella turcica in Saudi subjects with different skeletal types. Lateral cephalometric radiographs of 180 individuals (90 males and 90 females) with an age range of 11-26 years were taken and distributed according to skeletal classification; 60 Class I, 60 Class II, and 60 Class III. The sella turcica on each radiograph was analysed and measured to determine the shape of the sella, in addition to the linear dimensions of length, depth, and diameter. A Student's t-test was used to calculate differences in linear dimensions, while a one-way analysis of variance was performed to study the relationship between skeletal type and sella size. The results show that the sella turcica presented with a normal morphology in the majority of subjects (67 per cent). No significant differences in linear dimensions between genders could be found. When age was evaluated, significant differences were found between the older (15 years or more) and the younger (11-14 years) age groups at the 0.01 and 0.001 levels for length, depth, and diameter. Sella size of the older age group was larger than in the younger age group. When skeletal type was compared with sella size, a significant difference was found in the diameter of sella between the Class II and Class III subjects (P sella turcica area in Saudi subjects.

  18. Characterization of binding specificities of bovine leucocyte class I molecules: impacts for rational epitope discovery

    DEFF Research Database (Denmark)

    Hansen, Andreas M.; Rasmussen, Michael; Svitek, Nicholas;

    2014-01-01

    The binding of peptides to classical major histocompatibility complex (MHC) class I proteins is the single most selective step in antigen presentation. However, the peptide-binding specificity of cattle MHC (bovine leucocyte antigen, BoLA) class I (BoLA-I) molecules remains poorly characterized...

  19. 78 FR 14013 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Wheelchair Elevator

    Science.gov (United States)

    2013-03-04

    ... Notification; Class II Devices; Wheelchair Elevator AGENCY: Food and Drug Administration, HHS. ACTION: Final... requesting exemption from premarket notification requirements for wheelchair elevator devices commonly known... another, usually in a wheelchair. This order exempts wheelchair elevators, class II devices,...

  20. 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.``

  1. Composition of MHC class II-enriched lipid microdomains is modified during maturation of primary dendritic cells.

    Science.gov (United States)

    Setterblad, Niclas; Roucard, Corinne; Bocaccio, Claire; Abastado, Jean-Pierre; Charron, Dominique; Mooney, Nuala

    2003-07-01

    Dendritic cells (DCs) are the most potent antigen presenting cells. Major histocompatibility complex (MHC) class II molecule expression changes with maturation; immature DCs concentrate MHC class II molecules intracellularly, whereas maturation increases surface expression of MHC class II and costimulatory molecules to optimize antigen presentation. Signal transduction via MHC class II molecules localized in lipid microdomains has been described in B lymphocytes and in the THP-1 monocyte cell line. We have characterized MHC class II molecules throughout human DC maturation with particular attention to their localization in lipid-rich microdomains. Only immature DCs expressed empty MHC class II molecules, and maturation increased the level of peptide-bound heterodimers. Ligand binding to surface human leukocyte antigen (HLA)-DR induced rapid internalization in immature DCs. The proportion of cell-surface detergent-insoluble glycosphingolipid-enriched microdomain-clustered HLA-DR was higher in immature DCs despite the higher surface expression of HLA-DR in mature DCs. Constituents of HLA-DR containing microdomains included the src kinase Lyn and the cytoskeletal protein tubulin in immature DCs. Maturation modified the composition of the HLA-DR-containing microdomains to include protein kinase C (PKC)-delta, Lyn, and the cytoskeletal protein actin, accompanied by the loss of tubulin. Signaling via HLA-DR redistributed HLA-DR and -DM and PKC-delta as well as enriching the actin content of mature DC microdomains. The increased expression of HLA-DR as a result of DC maturation was therefore accompanied by modification of the spatial organization of HLA-DR. Such regulation could contribute to the distinct responses induced by ligand binding to MHC class II molecules in immature versus mature DCs.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Background: Identification of human leukocyte antigen class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the development of new effective peptide-based vaccines. Methodology/Principal Findings: In the present work, bioinformatics was used to predict...... 9mer peptides derived from available influenza A viral proteins with binding affinity for at least one of the 12 HLA-I supertypes. The predicted peptides were then selected in a way that ensured maximal coverage of the available influenza A strains. One hundred and thirty one peptides were...... of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC depleted of CD4(+) or CD8(+) T cells prior to the ELISPOT culture revealed...

  3. The immune function of MHC class II molecules mutated in the putative superdimer interface.

    Science.gov (United States)

    Hayball, John D; Lake, Richard A

    2005-05-01

    Analysis of the crystal structure of human class II (HLA-DR1) molecules suggests that the alphabeta heterodimer may be further ordered as a dimer of heterodimers (superdimer), leading to the hypothesis that T cell receptor dimerisation is a mechanism for initiating signaling events preceding T cell activation. The interface between pairs of molecules is stabilised by both salt bridges, polar and hydrophobic interactions. The residues that form the superdimer interface occur in three areas distinct from the antigen-binding groove. They can be defined as follows: region 1, beta-beta contacts in the helix of the beta1 domain; region 2, alpha-alpha contacts near the alpha 1/alpha2 domain junction and region 3; alpha-beta contacts in the alpha2/beta2 domains adjacent to the plasma membrane. To determine whether salt bridges and polar interactions formed within these regions are involved in the immune function of the murine MHC class II molecule, I-A(b), appropriate residues in both the alpha and beta chain were identified and mutated to uncharged alanine. Cell lines transfected with different combinations of mutated alpha and beta chains were generated and tested for MHC class II expression, peptide binding capabilities, and ability to present antigenic peptide to an OVA-specific T cell hybridoma. With the exception of two residues in region 2, the substitutions tested did not modulate MHC class II expression, or peptide binding function. When tested for ability to present peptide to an antigen-specific T cell hybridoma, with the exception of mutations in region 2, the substitutions did not appear to abrogate the ability of I-A(b) to stimulate the T cells. These results suggest that mutation of residues in region 2 of the putative superdimer interface have a gross effect on the ability of I-A(b) to be expressed on the cell surface. However, abrogation of salt bridges in region 1 and 3 do not influence I-A(b) cell surface expression, peptide binding or ability to

  4. 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.

  5. Signal transduction by HLA class II antigens expressed on activated T cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Martin, P J; Schieven, G L;

    1991-01-01

    Human T cells express HLA class II antigens upon activation. Although activated, class II+ T cells can present alloantigens under certain circumstances, the functional role of class II antigens on activated T cells remains largely unknown. Here, we report that cross-linking of HLA-DR molecules ex...

  6. MHC class II antigen presentation by B cells in health and disease

    NARCIS (Netherlands)

    Souwer, Yuri

    2009-01-01

    MHC class II antigen presentation by B cells is important to activate CD4+ T cells that stimulate the B cell to produce antibodies. Besides this, disruption of MHC class II antigen presentation could play a role in immune escape by tumor cells. This thesis describes MHC class II antigen presentation

  7. 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.

  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....... In addition, down-modulation of CD3 receptors with antibody demonstrated that superantigen-induced signaling events were CD3-dependent. Superantigen signaling was also class II-dependent, in that resting T cells were not responsive to direct enterotoxin stimulation. To address how early signal transducing...

  9. 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.

  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. HLA class I and class II associations with ESRD in Saudi Arabian population.

    Directory of Open Access Journals (Sweden)

    Nuha Mahmoud Hamdi

    Full Text Available BACKGROUND: Chronic renal failure (CRF leads in the majority of instances to end stage renal disease (ESRD requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population. METHODOLOGY: A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated control. Patients and control groups were typed by SSOP lumenix techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18, B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30-DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50, A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02, A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective haplotypes. CONCLUSION: The high Relative Risk (RR observed and its statistical correlation reflect the strength of the described association between HLA antigens and ESRD.

  12. 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

    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...

  13. Structural determinants for ligand capture by a class II preQ1 riboswitch.

    Science.gov (United States)

    Kang, Mijeong; Eichhorn, Catherine D; Feigon, Juli

    2014-02-11

    Prequeuosine (preQ1) riboswitches are RNA regulatory elements located in the 5' UTR of genes involved in the biosynthesis and transport of preQ1, a precursor of the modified base queuosine universally found in four tRNAs. The preQ1 class II (preQ1-II) riboswitch regulates preQ1 biosynthesis at the translational level. We present the solution NMR structure and conformational dynamics of the 59 nucleotide Streptococcus pneumoniae preQ1-II riboswitch bound to preQ1. Unlike in the preQ1 class I (preQ1-I) riboswitch, divalent cations are required for high-affinity binding. The solution structure is an unusual H-type pseudoknot featuring a P4 hairpin embedded in loop 3, which forms a three-way junction with the other two stems. (13)C relaxation and residual dipolar coupling experiments revealed interhelical flexibility of P4. We found that the P4 helix and flanking adenine residues play crucial and unexpected roles in controlling pseudoknot formation and, in turn, sequestering the Shine-Dalgarno sequence. Aided by divalent cations, P4 is poised to act as a "screw cap" on preQ1 recognition to block ligand exit and stabilize the binding pocket. Comparison of preQ1-I and preQ1-II riboswitch structures reveals that whereas both form H-type pseudoknots and recognize preQ1 using one A, C, or U nucleotide from each of three loops, these nucleotides interact with preQ1 differently, with preQ1 inserting into different grooves. Our studies show that the preQ1-II riboswitch uses an unusual mechanism to harness exquisite control over queuosine metabolism.

  14. Characterization and expression of MHC class II alpha and II beta genes in mangrove red snapper (Lutjanus argentimaculatus).

    Science.gov (United States)

    Wang, Tianyan; Tan, Shangjin; Cai, Zhonghua

    2015-12-01

    The major histocompatibility complex (MHC) class II plays a key role in adaptive immunity by presenting foreign peptides to CD4(+) T cells and by triggering the adaptive immune response. While the structure and function of MHC class II have been well characterized in mammalian, limited research has been done on fishes. In this study, we characterized the gene structure and expression of MHC class II α (Lunar-DAA) and II β (Lunar-DAB) of mangrove red snapper (Lutjanus argentimaculatus). Both genes shared, respectively, a high similarity and typical features with other vertebrate MHC class II α and II β. The phylogenetic analysis of the deduced peptides revealed that both Lunar-DAA and Lunar-DAB were located in the teleost subclass. Western blotting analyses indicated that both MHC class II α and II β were expressed ubiquitously in immune-related cells, tissues and organs, and that MHC class II α and II β chains existed mainly as heterodimers. While it was highly expressed in gills, thymus, head kidney (HK), spleen, head kidney macrophage and spleen leucocytes, MHC class II β chain was expressed with a low abundance in skin, intestine, stomach and heart. The highest expression of MHC class II β in thymus confirmed the conclusion that thymus is one of the primary lymphoid organs in fishes. The detection of MHC class II αβ dimers in HK macrophages and spleen leucocytes indicated that HK macrophages and spleen leucocytes play a critical role in the adaptive immunity in fishes. All these results provide valuable information for understanding the structure of MHC class II α and II β and their function in immune responses.

  15. Angiotensin II Inhibits Insulin Binding to Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Su-Jin Oh

    2011-06-01

    Full Text Available BackgroundInsulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.MethodsAfter treating bovine aortic endothelial cells with angiotensin II (ATII, we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR on the cell membranes and in the cytosol.ResultsAfter treatment of 10-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05. ATII receptor blocker (eprosartan dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05. At 200 µM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.ConclusionATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

  16. Yeast surface display of a noncovalent MHC class II heterodimer complexed with antigenic peptide.

    Science.gov (United States)

    Boder, Eric T; Bill, Jerome R; Nields, Andrew W; Marrack, Philippa C; Kappler, John W

    2005-11-20

    Microbial protein display technologies have enabled directed molecular evolution of binding and stability properties in numerous protein systems. In particular, dramatic improvements to antibody binding affinity and kinetics have been accomplished using these tools in recent years. Examples of successful application of display technologies to other immunological proteins have been limited to date. Herein, we describe the expression of human class II major histocompatibility complex allele (MHCII) HLA-DR4 on the surface of Saccharomyces cerevisiae as a noncovalently associated heterodimer. The yeast-displayed MHCII is fully native as assessed by binding of conformationally specific monoclonal antibodies; failure of antibodies specific for empty HLA-DR4 to bind yeast-displayed protein indicates antigenic peptide is bound. This report represents the first example of a noncovalent protein dimer displayed on yeast and of successful display of wild-type MHCII. Results further point to the potential for using yeast surface display for engineering and analyzing the antigen binding properties of MHCII.

  17. Inhibition of Zn(II binding type IA topoisomerases by organomercury compounds and Hg(II.

    Directory of Open Access Journals (Sweden)

    Bokun Cheng

    Full Text Available Type IA topoisomerase activities are essential for resolving DNA topological barriers via an enzyme-mediated transient single strand DNA break. Accumulation of topoisomerase DNA cleavage product can lead to cell death or genomic rearrangement. Many antibacterial and anticancer drugs act as topoisomerase poison inhibitors that form stabilized ternary complexes with the topoisomerase covalent intermediate, so it is desirable to identify such inhibitors for type IA topoisomerases. Here we report that organomercury compounds were identified during a fluorescence based screening of the NIH diversity set of small molecules for topoisomerase inhibitors that can increase the DNA cleavage product of Yersinia pestis topoisomerase I. Inhibition of relaxation activity and accumulation of DNA cleavage product were confirmed for these organomercury compounds in gel based assays of Escherichia coli topoisomerase I. Hg(II, but not As(III, could also target the cysteines that form the multiple Zn(II binding tetra-cysteine motifs found in the C-terminal domains of these bacterial topoisomerase I for relaxation activity inhibition. Mycobacterium tuberculosis topoisomerase I activity is not sensitive to Hg(II or the organomercury compounds due to the absence of the Zn(II binding cysteines. It is significant that the type IA topoisomerases with Zn(II binding domains can still cleave DNA when interfered by Hg(II or organomercury compounds. The Zn(II binding domains found in human Top3α and Top3β may be potential targets of toxic metals and organometallic complexes, with potential consequence on genomic stability and development.

  18. Structure of photosystem II and substrate binding at room temperature

    Science.gov (United States)

    Gul, Sheraz; Fuller, Franklin; Koroidov, Sergey; Brewster, Aaron S.; Tran, Rosalie; Alonso-Mori, Roberto; Kroll, Thomas; Michels-Clark, Tara; Laksmono, Hartawan; Sierra, Raymond G.; Stan, Claudiu A.; Hussein, Rana; Zhang, Miao; Douthit, Lacey; Kubin, Markus; de Lichtenberg, Casper; Long Vo, Pham; Nilsson, Håkan; Cheah, Mun Hon; Shevela, Dmitriy; Saracini, Claudio; Bean, Mackenzie A.; Seuffert, Ina; Sokaras, Dimosthenis; Weng, Tsu-Chien; Pastor, Ernest; Weninger, Clemens; Fransson, Thomas; Lassalle, Louise; Bräuer, Philipp; Aller, Pierre; Docker, Peter T.; Andi, Babak; Orville, Allen M.; Glownia, James M.; Nelson, Silke; Sikorski, Marcin; Zhu, Diling; Hunter, Mark S.; Lane, Thomas J.; Aquila, Andy; Koglin, Jason E.; Robinson, Joseph; Liang, Mengning; Boutet, Sébastien; Lyubimov, Artem Y.; Uervirojnangkoorn, Monarin; Moriarty, Nigel W.; Liebschner, Dorothee; Afonine, Pavel V.; Waterman, David G.; Evans, Gwyndaf; Wernet, Philippe; Dobbek, Holger; Weis, William I.; Brunger, Axel T.; Zwart, Petrus H.; Adams, Paul D.; Zouni, Athina; Messinger, Johannes; Bergmann, Uwe; Sauter, Nicholas K.; Kern, Jan; Yachandra, Vittal K.; Yano, Junko

    2016-01-01

    Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment-protein complex, couples the one-electron photochemistry at the reaction center with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC) (Fig. 1a, Extended Data Fig. 1). Under illumination, the OEC cycles through five intermediate S-states (S0 to S4)1, where S1 is the dark stable state and S3 is the last semi-stable state before O-O bond formation and O2 evolution2,3. A detailed understanding of the O-O bond formation mechanism remains a challenge, and elucidating the structures of the OEC in the different S-states, as well as the binding of the two substrate waters to the catalytic site4-6, is a prerequisite for this purpose. Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage free, room temperature (RT) structures of dark-adapted (S1), two-flash illuminated (2F; S3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S3-enriched) PS II. Although the recent 1.95 Å structure of PS II7 at cryogenic temperature using an XFEL provided a damage-free view of the S1 state, RT measurements are required to study the structural landscape of proteins under functional conditions8,9, and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analog, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states10. Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site10-13. Thus, this approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms. PMID:27871088

  19. Competition from Cu(II), Zn(II) and Cd(II) in Pb(II) binding to Suwannee River Fulvic Acid

    NARCIS (Netherlands)

    Chakraborty, P.; Chakrabarti, C.L.

    2008-01-01

    This is a study of trace metal competition in the complexation of Pb(II) by well-characterized humic substances, namely Suwannee River Fulvic Acid (SRFA) in model solutions. It was found that Cu(II) seems to compete with Pb(II) for strong binding sites of SRFA when present at the same concentration

  20. 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.

  1. 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...... known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues aQ9 and ßN82. Mutagenesis experiments confirmed that replacement of either one of the two......-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting from the structural knowledge provided by this study....

  2. Preferred SLA class I/class II haplotype combinations in German Landrace pigs.

    Science.gov (United States)

    Gimsa, Ulrike; Ho, Chak-Sum; Hammer, Sabine E

    2017-01-01

    Major histocompatibility complex (MHC) molecules are responsible for the antigen presentation to T lymphocytes. High recombination rates in the MHC genes, as observed in humans, are believed to serve the evolutionary goal to achieve a high genetic diversity, allowing for a broad and efficient immune response. In a cohort of 155 pedigreed German Landrace pigs (65 founders and 90 piglets), we found that MHC genes occur in particular class I and class II haplotype combinations. This phenomenon has not been described before, probably because most of the earlier MHC studies in pigs were not pedigree-based. After comparing our data with published genotypes of different European pig breeds and Asian pigs, we hypothesise that the combination of particular but different haplotypes in different geographical regions may have developed under the evolutionary pressure of regionally endemic pathogens. This proposed mechanism ensures an efficient immune response despite low recombination rates.

  3. A growth-related concept for skeletal class II treatment.

    Science.gov (United States)

    Teuscher, U

    1978-09-01

    The use of a combined activator--high-pull headgear appliance for treatment of Class II, Division 1 malocclusion is presented as a preliminary report. The activator itself is equipped with a palatal bar, lower lip pads, and torque-control auxiliaries for the upper incisors. The face-bow is mounted directly on the activator, and the extraoral force vector is equivalent to that of an anterior high-pull vector. During bite registration the veritcal displacement of the mandible is restricted to a minimum, and the anterior displacement should not exceed 6 mm. On the basis of current knowledge of the growth of the bony facial structures, treatment objectives and a specific approach for skeletal Class II correction are defined. Following these objectives, the therapy aims at correcting the malocclusion without diverting the anterior landmarks of the bony face from their specific lines of growth. This is brought about by the corresponding mechanics of the activator-headgear combination. The corrective effect of this appliance may be assumed to be the result of several different factors. The maxillary dentition is restrained in a posterior cranial direction, and an inhibitory effect on the maxilla counter to its line of development is attained. The mandibular dentition is influenced in an anterior downward direction by means of the bite registration, and the occlusion is unlocked during treatment. Any transfer of distally directed headgear forces from the maxilla to the mandible is prevented. Temporary stimulation of condylar growth, possibly combined with temporary posterior deflection of condylar growth, may also be induced. In this way it is possible to take maximum advantage of condylar growth in the sagittal dimension. Thus, not only is the malocclusion corrected but, at the same time, decisive profile improvement is achieved by anterior development of the mandible. From the experience gained so far with a Class II, Division 1 sample undergoing treatment with the

  4. Evaluation of mandibular length in subjects with Class I and Class II skeletal patterns using the cervical vertebrae maturation

    Directory of Open Access Journals (Sweden)

    Rodrigo Generoso

    2010-03-01

    Full Text Available The aim of this study was to compare the mandibular size in boys and girls with Class I and Class II skeletal patterns, taking into consideration the bone maturation stage, as defined by the cervical vertebrae maturation. One hundred and sixty cephalometric radiographs were obtained from subjects (aged between 7 and 12 years with Class I or Class II skeletal patterns, according to the ANB angle and WITS appraisal. The Class I sample consisted of 80 subjects (40 boys, 40 girls. The Class II sample also consisted of 80 subjects (40 boys, 40 girls. On a cross-sectional basis, mandibular length (Co-Gn was compared between groups and genders. The between-stages changes were also evaluated, with the cervical vertebrae analysis used for establishing the bone maturation stages at CS2, CS3, CS4 and CS5. The results were statistically analyzed by the Kruskal-Wallis test. The mandibular length differed between skeletal patterns only at the earlier stages of development. In the Class I pattern, the mandibular lengths of boys were greater than those of girls at stages CS2, CS4 and CS5, whereas in the Class II pattern, the mandibular lengths of boys were greater than those of girls at stages CS2, CS3 and CS4. The present results indicate a sexual dimorphism in the mandibular length at almost all stages of bone maturation, in exception of the CS5 stage in Class II.

  5. Engagement of major histocompatibility complex class I and class II molecules up-regulates intercellular adhesion of human B cells via a CD11/CD18-independent mechanism.

    Science.gov (United States)

    Alcover, A; Juillard, V; Acuto, O

    1992-02-01

    We have studied the role of major histocompatibility complex (MHC) molecules in the regulation of intercellular adhesion of human B cells. We found that molecules able to bind to MHC class II molecules, such as monoclonal antibodies or staphylococcal enterotoxins, induced rapid and sustained homotypic adhesion of Epstein-Barr virus (EBV)-transformed B cell lines as well as peripheral blood B lymphocytes. Moreover, anti-MHC class I monoclonal antibodies also stimulated intercellular adherence. Adhesion induced upon MHC engagement was faster and stronger than that triggered by phorbol esters. It needed active metabolism, but divalent cations were not required. Monoclonal antibodies directed against LFA-1 (CD11a/CD18) or its ligand ICAM-1 (CD54) did not inhibit MHC class II-induced homotypic adhesion of various EBV-transformed B cell lines, nor of a variant of the B cell line Raji expressing very low LFA-1 surface levels. Moreover, EBV-transformed B cells from a severe lymphocyte adhesion deficiency patient, lacking surface CD11/CD18, also aggregated in response to anti-MHC class I or class II monoclonal antibodies. Together these data indicate that engagement of MHC molecules may transduce signals to B cells resulting in up-regulation of intercellular adhesion, via an LFA-1-independent mechanism. This may play a role in the stabilization of T cell/antigen-presenting cell conjugates at the moment of antigen recognition.

  6. 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.

  7. 40 CFR 147.3108 - Plugging Class I, II, and III wells.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Plugging Class I, II, and III wells... Certain Oklahoma Indian Tribes § 147.3108 Plugging Class I, II, and III wells. In addition to the... well: (a) For Class I and III wells: (1) The well shall be filled with mud from the bottom of the...

  8. SED analysis of class I and class II FU Orionis stars

    CERN Document Server

    Gramajo, Luciana V; Gómez, Mercedes

    2014-01-01

    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 an 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 FUORS stage. We modeled the SEDs of 24 of the 26 currently known FUORS, using the radiative transfer code of Whitney et al (2003b). We compare our models with those obtained by Robitaille et al. (2007) 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 $\\sim80\\%$ 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 ~ 1.e-7 Msun/yr vs ~ 1.e-5 Msun/yr for standard YSOs (young stellar o...

  9. Studying the Prevalence and Etiology of Class II Subdivision Malocclusion Utilizing Cone-Beam Computed Tomography

    Science.gov (United States)

    2013-04-24

    II SUBDIVISION MALOCCLUSION UTILIZING CONE-BEAM COMPUTED TOMOGRAPHY A THESIS Presented to the Faculty of the Uniform Services University of...K_Paper _Article _Book _ Poster _Presentation _Other 6. Title: ’Studying the Prevalence and Etiology of Class II Subdivision Malocclusion Utilizing...of any copyrighted material in the thesis manuscript entitled : ’STUDYING THE PREVALENCE AND ETIOLOGY OF CLASS II SUBDIVISION MALOCCLUSION

  10. 40 CFR 144.28 - Requirements for Class I, II, and III wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... annular pressure; (iii) The results from ground-water monitoring wells prescribed in paragraph (g)(1)(iii... drinking water and the well bore is prohibited. (2) The owner or operator of a Class I, II or III injection... water. (ii) For Class II wells: (A) The owner or operator shall not exceed a maximum injection...

  11. NetMHCpan, a method for MHC class I binding prediction beyond humans

    DEFF Research Database (Denmark)

    Hoof, Ilka; Peters, B; Sidney, J;

    2009-01-01

    .0, a method that generates quantitative predictions of the affinity of any peptide-MHC class I interaction. NetMHCpan-2.0 has been trained on the hitherto largest set of quantitative MHC binding data available, covering HLA-A and HLA-B, as well as chimpanzee, rhesus macaque, gorilla, and mouse MHC class I...

  12. Mn(II) binding to human serum albumin: a ¹H-NMR relaxometric study.

    Science.gov (United States)

    Fanali, Gabriella; Cao, Yu; Ascenzi, Paolo; Fasano, Mauro

    2012-12-01

    Human serum albumin (HSA) displays several metal binding sites, participating to essential and toxic metal ions disposal and transport. The major Zn(II) binding site, called Site A, is located at the I/II domain interface, with residues His67, Asn99, His247, and Asp249 contributing with five donor atoms to the metal ion coordination. Additionally, one water molecule takes part of the octahedral coordination geometry. The occurrence of the metal-coordinated water molecule allows the investigation of the metal complex geometry by water (1)H-NMR relaxation, provided that the diamagnetic Zn(II) is replaced by the paramagnetic Mn(II). Here, the (1)H-NMR relaxometric study of Mn(II) binding to HSA is reported. Mn(II) binding to HSA is modulated by Zn(II), pH, and myristate through competitive inhibition and allosteric mechanisms. The body of results indicates that the primary binding site of Zn(II) corresponds to the secondary binding site of Mn(II), i.e. the multimetal binding site A. Excess Zn(II) completely displaces Mn(II) from its primary site suggesting that the primary Mn(II) site corresponds to the secondary Zn(II) site. This uncharacterized site is functionally-linked to FA1; moreover, metal ion binding is modulated by myristate and pH. Noteworthy, water (1)H-NMR relaxometry allowed a detailed analysis of thermodynamic properties of HSA-metal ion complexes.

  13. 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.

  14. Subcellular localization of class II HDAs in Arabidopsis thaliana: nucleocytoplasmic shuttling of HDA15 is driven by light.

    Directory of Open Access Journals (Sweden)

    Malona V Alinsug

    Full Text Available Class II histone deacetylases in humans and other model organisms undergo nucleocytoplasmic shuttling. This unique functional regulatory mechanism has been well elucidated in eukaryotic organisms except in plant systems. In this study, we have paved the baseline evidence for the cytoplasmic and nuclear localization of Class II HDAs as well as their mRNA expression patterns. RT-PCR analysis on the different vegetative parts and developmental stages reveal that Class II HDAs are ubiquitously expressed in all tissues with minimal developmental specificity. Moreover, stable and transient expression assays using HDA-YFP/GFP fusion constructs indicate cytoplasmic localization of HDA5, HDA8, and HDA14 further suggesting their potential for nuclear transport and deacetylating organellar and cytoplasmic proteins. Organelle markers and stains confirm HDA14 to abound in the mitochondria and chloroplasts while HDA5 localizes in the ER. HDA15, on the other hand, shuttles in and out of the nucleus upon light exposure. In the absence of light, it is exported out of the nucleus where further re-exposition to light treatments signals its nuclear import. Unlike HDA5 which binds with 14-3-3 proteins, HDA15 fails to interact with these chaperones. Instead, HDA15 relies on its own nuclear localization and export signals to navigate its subcellular compartmentalization classifying it as a Class IIb HDA. Our study indicates that nucleocytoplasmic shuttling is indeed a hallmark for all eukaryotic Class II histone deacetylases.

  15. Subcellular localization of class II HDAs in Arabidopsis thaliana: nucleocytoplasmic shuttling of HDA15 is driven by light.

    Science.gov (United States)

    Alinsug, Malona V; Chen, Fang Fang; Luo, Ming; Tai, Ready; Jiang, Liwen; Wu, Keqiang

    2012-01-01

    Class II histone deacetylases in humans and other model organisms undergo nucleocytoplasmic shuttling. This unique functional regulatory mechanism has been well elucidated in eukaryotic organisms except in plant systems. In this study, we have paved the baseline evidence for the cytoplasmic and nuclear localization of Class II HDAs as well as their mRNA expression patterns. RT-PCR analysis on the different vegetative parts and developmental stages reveal that Class II HDAs are ubiquitously expressed in all tissues with minimal developmental specificity. Moreover, stable and transient expression assays using HDA-YFP/GFP fusion constructs indicate cytoplasmic localization of HDA5, HDA8, and HDA14 further suggesting their potential for nuclear transport and deacetylating organellar and cytoplasmic proteins. Organelle markers and stains confirm HDA14 to abound in the mitochondria and chloroplasts while HDA5 localizes in the ER. HDA15, on the other hand, shuttles in and out of the nucleus upon light exposure. In the absence of light, it is exported out of the nucleus where further re-exposition to light treatments signals its nuclear import. Unlike HDA5 which binds with 14-3-3 proteins, HDA15 fails to interact with these chaperones. Instead, HDA15 relies on its own nuclear localization and export signals to navigate its subcellular compartmentalization classifying it as a Class IIb HDA. Our study indicates that nucleocytoplasmic shuttling is indeed a hallmark for all eukaryotic Class II histone deacetylases.

  16. Comparative binding energy COMBINE analysis for understanding the binding determinants of type II dehydroquinase inhibitors.

    Science.gov (United States)

    Peón, Antonio; Coderch, Claire; Gago, Federico; González-Bello, Concepción

    2013-05-01

    Herein we report comparative binding energy (COMBINE) analyses to derive quantitative structure-activity relationship (QSAR) models that help rationalize the determinants of binding affinity for inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway. Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2, which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells. These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism. They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor design.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    the public access to frequent, up-to-date performance evaluations of all participating tools. To overcome potential selection bias in the data included in the IEDB, a strategy was implemented that suggests a set of peptides for which different prediction methods give divergent predictions as to their binding...... educated selections between participating tools. Of the four participating servers, NetMHCpan performed the best, followed by ANN, SMM and finally ARB. Availability and implementation: Up-to-date performance evaluations of each server can be found online at http://tools.iedb.org/auto_bench/mhci/weekly. All...

  18. Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (Ii)

    Science.gov (United States)

    2007-05-01

    uveal melanoma cells. Cancer Res. 67: 4499-4506, 2007. 30. Chamuleau ME, Souwer Y, Van Ham SM, Zevenbergen A, Westers TM, Berkhof J, Meijer CJ, van...MHC class I, class II, CD80, CD4, CD8, and immunoglobulin) or fixed and stained for Ii as described (20). Western blots . Ii Western blots were done...as described (20). Blots for MHC II were done as for Ii with the following modifications: cell lysates were loaded onto SDS-PAGE gels using nonreducing

  19. Expression of HLA Class I and HLA Class II by Tumor Cells in Chinese Classical Hodgkin Lymphoma Patients

    NARCIS (Netherlands)

    Huang, Xin; van den Berg, Anke; Gao, Zifen; Visser, Lydia; Nolte, Ilja; Vos, Hans; Hepkema, Bouke; Kooistra, Wierd; Poppema, Sibrand; Diepstra, Arjan

    2010-01-01

    Background: In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. HLA expression (in relation to EBV) in Asian cHL patients has no

  20. DIFFERENT ROLES OF CLASS-I AND CLASS-II CLOSTRIDIUM-HISTOLYTICUM COLLAGENASE IN RAT PANCREATIC-ISLET ISOLATION

    NARCIS (Netherlands)

    WOLTERS, GHJ; VOSSCHEPERKEUTER, GH; LIN, HC; VANSCHILFGAARDE, R

    1995-01-01

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

  1. Characterization and evolution of MHC class II B genes in Galápagos marine iguanas (Amblyrhynchus cristatus).

    Science.gov (United States)

    Glaberman, Scott; Moreno, Maria A; Caccone, Adalgisa

    2009-08-01

    Major histocompatibility complex (MHC) class II molecules play a key role in the adaptive immune system of vertebrates. Class II B genes appear to evolve in a very different manner in mammals and birds. Orthology is commonly observed among mammal loci, while genes tend to cluster phylogenetically within bird species. Here we present class II B data from a representative of another major group of amniotes, the squamates (i.e. lizards, snakes, amphisbaenians), with the ultimate goal of placing mammalian and avian MHC evolution into a broader context. In this study, eight class II B cDNA sequences were obtained from the Galápagos marine iguana (Amblyrhynchus cristatus) which were divided into five locus groups, Amcr-DAB1 through -DAB5, based on similarities along most of the coding and noncoding portions of the transcribed gene. All marine iguana sequences were monophyletic with respect to class II genes from other vertebrates indicating that they originated from a common ancestral locus after squamates split from other reptiles. The beta-1 domain, which is involved in antigen binding, exhibited signatures of positive selection as well as interlocus gene conversion in both long and short tracts-a pattern also observed in birds and fish, but not in mammals. On the other hand, the beta-2 domain was divergent between gene groups, which is characteristic of mammals. Based on these results, we preliminarily show that squamate class II B genes have been shaped by a unique blend of evolutionary forces that have been observed in differing degrees in other vertebrates.

  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. Prediction of peptide binding to a major histocompatibility complex class I molecule based on docking simulation.

    Science.gov (United States)

    Ishikawa, Takeshi

    2016-10-01

    Binding between major histocompatibility complex (MHC) class I molecules and immunogenic epitopes is one of the most important processes for cell-mediated immunity. Consequently, computational prediction of amino acid sequences of MHC class I binding peptides from a given sequence may lead to important biomedical advances. In this study, an efficient structure-based method for predicting peptide binding to MHC class I molecules was developed, in which the binding free energy of the peptide was evaluated by two individual docking simulations. An original penalty function and restriction of degrees of freedom were determined by analysis of 361 published X-ray structures of the complex and were then introduced into the docking simulations. To validate the method, calculations using a 50-amino acid sequence as a prediction target were performed. In 27 calculations, the binding free energy of the known peptide was within the top 5 of 166 peptides generated from the 50-amino acid sequence. Finally, demonstrative calculations using a whole sequence of a protein as a prediction target were performed. These data clearly demonstrate high potential of this method for predicting peptide binding to MHC class I molecules.

  5. II-Q restriction endonucleases--new class of type II enzymes.

    Science.gov (United States)

    Degtyarev, S K; Rechkunova, N I; Kolyhalov, A A; Dedkov, V S; Zhilkin, P A

    1990-10-11

    Unique restriction endonucleases Bpu 10l and Bsil have been isolated from Bacillus pumilas and Bacillus sphaericus, respectively. The recognition sequences and cleavage points of these enzymes have been determinated as 5'-CC1TNAGC-3'/3'-GGANT1CG-5' for Bpu 10l and 5'-C1TCGTG-3'/3'-GAGCA1C-5' for Bsil. Restriction endonucleases Bpu 10l and Bsil represent a new class of enzymes which recognize non-palindromic nucleotide sequences and hydrolize DNA within the recognition sequence. Bpu 10l and Bsil recognition sequences may be regarded as quasipalindromic and the enzymes may be designated as type II-Q restriction endonucleases.

  6. 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.

  7. 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.

  8. Synthesis, characterization, DNA binding, DNA cleavage, protein binding and cytotoxic activities of Ru(II) complexes.

    Science.gov (United States)

    Thota, Sreekanth; Vallala, Srujana; Yerra, Rajeshwar; Rodrigues, Daniel Alencar; Raghavendra, Nulgumnalli Manjunathaiah; Barreiro, Eliezer J

    2016-01-01

    We report on the synthesis of novel Ru(II) compounds (Ru-1 to Ru-8) bearing R-pdc, 4-Cl-pbinh ligands (where R=4-CF3, 4-F, 4-OH pdc=3-phenyl-5-(1H-pyrrol-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide, pbinh=phenoxybenzylidene isonicotinyl hydrazides) and their in vitro antitumor activity toward the cell lines murine leukemia L1210, human lymphocyte CEM, human epithelial cervical carcinoma HeLa, BEL-7402 and Molt4/C8. Some of the complexes exhibited more potent antiproliferative activity against cell lines than the standard drug cisplatin. Ruthenium complex Ru-2 displayed potent cytotoxicity with than that of cisplatin. DNA-binding, DNA cleavage and protein binding properties of ruthenium complexes with these ligands are reported. Interactions of these ruthenium complexes with DNA revealed an intercalative mode of binding between them. Synchronous fluorescence spectra proved that the interaction of ruthenium complexes with bovine serum albumin (BSA) resulted in a conformational change of the latter.

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

    Directory of Open Access Journals (Sweden)

    Bernd Rupp

    Full Text Available 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 molecule. Non-receptiveness hinders the efficient loading of new antigens onto the empty MHC II. However, the mechanisms driving the formation of the peptide inaccessible state are not well understood. Here, a combined approach of experimental site-directed mutagenesis and computational modeling is used to reveal structural features underlying "non-receptiveness." Molecular dynamics simulations of the human MHC II HLA-DR1 suggest a straightening of the α-helix of the β1 domain during the transition from the open to the non-receptive state. The movement is mostly confined to a hinge region conserved in all known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues αQ9 and βN82. Mutagenesis experiments confirmed that replacement of either one of the two residues by alanine renders the protein highly susceptible. Notably, loading enhancement was also observed when the mutated MHC II molecules were expressed on the surface of fibroblast cells. Altogether, structural features underlying the non-receptive state of empty HLA-DR1 identified by theoretical means and experiments revealed highly conserved residues critically involved in the receptiveness of MHC II. The atomic details of rearrangements of the peptide-binding groove upon peptide loss provide insight into structure and dynamics of empty MHC II molecules and may foster rational approaches to interfere with non-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting

  10. 77 FR 60625 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2012-10-04

    ... National Indian Gaming Commission 25 CFR Parts 542 and 543 RIN 3141-AA-37 Minimum Internal Control... while tribes and operations transition to the new Class II Minimum Internal Control Standards that were... part 543, Minimum Internal Control Standards Class II Gaming, with comprehensive and updated...

  11. 76 FR 53817 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2011-08-30

    ... National Indian Gaming Commission 25 CFR Parts 542 and 543 Minimum Internal Control Standards for Class II... delay of the effective date on the final rule for Minimum Internal Control Standards for Class II Gaming... sections of established Minimum Internal Control Standards and replaced them with a new part titled...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

    Livas, Christos

    2015-01-01

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

  14. 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...

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  16. Insect Cells Encode a Class II α-Mannosidase with Unique Properties*

    OpenAIRE

    Kawar, Ziad; Karaveg, Khanita; Moremen, Kelley W.; Jarvis, Donald L.

    2001-01-01

    Previously, we cloned and characterized an insect (Sf9) cell cDNA encoding a class II α-mannosidase with amino acid sequence and biochemical similarities to mammalian Golgi α-mannosidase II. Since then, it has been demonstrated that other mammalian class II α-mannosidases can participate in N-glycan processing. Thus, the present study was performed to evaluate the catalytic properties of the Sf9 class II α-mannosidase and to more clearly determine its relationship to mammalian Golgi α-mannosi...

  17. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Coeliac disease (CD is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1, DQ6(1, DR11(5, DQ7(3, DQ2 and DR15(2 were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2 was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1 and DQ6(1 in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5 in the group of relatives (RR=0.363,PF=0.232. These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.

  18. Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

    2010-03-08

    Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

  19. Phenotypic Diversity in Caucasian Adults with Moderate to Severe Class II Malocclusion

    Science.gov (United States)

    Moreno Uribe, Lina M.; Howe, Sara C.; Kummet, Colleen; Vela, Kaci C.; Dawson, Deborah V.; Southard, Thomas E.

    2014-01-01

    INTRODUCTION Class II malocclusion affects about 15 % of the US population and is characterized by a convex profile and occlusion disharmonies. The specific etiological mechanisms resulting in the range of Class II dento-skeletal combinations observed is not yet understood. Most studies describing the class II phenotypic diversity have utilized moderate sample sizes or have focused on younger individuals that later in life may outgrow their class II discrepancies; such a focus may also preclude the visualization of adult class II features. The majority have utilized simple correlation methods resulting in phenotypes that may not be generalizable to different samples and thus may not be suitable for studies of malocclusion etiology. The purpose of this study is to address these knowledge gaps by capturing the maximum phenotypic variation present in a large Caucasian sample of class II individuals selected with strict eligibility criteria and rigorously standardized multivariate reduction analyses. METHODS Sixty-three lateral cephalometric variables were measured from pre-treatment records of 309 Class II Caucasian adults (82 males, 227 females; ages 16–60 years). Principal component analysis (PCA) and cluster analysis were used to generate comprehensive phenotypes in an effort to identify the most homogeneous groups of individuals reducing heterogeneity and improving the power of future malocclusion etiology studies. RESULTS PCA resulted in 7 principal components that accounted for 81% of the variation. The first three components represented variation on mandibular rotation, upper incisor angulation and mandibular length, respectively. The cluster analysis identified 5 distinct Class II phenotypes. CONCLUSIONS A comprehensive spectrum of Class II phenotypic definitions was obtained that could be generalized to other samples advancing our efforts to the identification of etiological factors underlying Class II malocclusion. PMID:24582022

  20. MHC class I epitope binding prediction trained on small data sets

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Nielsen, Morten; Lamberth, K.;

    2004-01-01

    prediction methods exist only for alleles were the binding pattern have been deduced from peptide motifs. Using empirical knowledge of important anchor positions within the binding peptides dramatically reduces the number of peptides needed for reliable predictions. We here present a general method...... for predicting peptides binding to specific MHC class I alleles. The method combines advanced automatic scoring matrix generation with empirical position specific differential anchor weighting. The method leads to predictions with a comparable or higher accuracy than other established prediction servers, even...

  1. Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

    Science.gov (United States)

    Kasper, Katherine J; Zeppa, Joseph J; Wakabayashi, Adrienne T; Xu, Stacey X; Mazzuca, Delfina M; Welch, Ian; Baroja, Miren L; Kotb, Malak; Cairns, Ewa; Cleary, P Patrick; Haeryfar, S M Mansour; McCormick, John K

    2014-05-01

    Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

  2. Binding of transcobalamin II by human mammary epithelial cells.

    Science.gov (United States)

    Adkins, Y; Lönnerdal, B

    2001-01-01

    The presence of nutrient binders in milk may have an important role during milk production and may influence the nutrient's bioavailability to the infant. Human milk and plasma contain at least two types of vitamin B12 binders: transcobalamin II (TCII) and haptocorrin (Hc). Vitamin B12 in milk is exclusively bound to Hc (Hc-B12). In plasma, the major vitamin B12 binding protein that is responsible for delivering absorbed vitamin B12 to most tissues and cells is TCII (TCII-B12). Currently, little is known about the route of secretion of vitamin B12 into human milk. It is possible that a receptor-mediated pathway is involved, since maternal vitamin B12 supplementation increases the amount of the vitamin secreted into human milk if the mother's vitamin B12 consumption is low, but remains unchanged if her intake is adequate. In this study, we investigated the process by which the mammary gland acquires vitamin B12 from maternal circulation, whether as a free vitamin or as a Hc-B12 or TCII-B12 complex. TCII was purified from plasma incubated with [57Co]vit B12 (B12*), while Hc was purified from whey incubated with B12*. Both proteins were separated by fast protein liquid chromatography using gel filtration and anion-exchange columns. Purity of the separated proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies were carried out on a monolayer of normal human mammary epithelial cells (HMEC) at 4 degrees C using free B12* and TCII-B12* and Hc-B12* complexes. Minimal binding of free B12* and Hc-B12* to HMEC was observed; however, HMEC exhibited a high affinity for the TCII-B12* complex. This study suggests that a specific cell surface receptor for the TCII-B12 complex exists in the mammary gland. It is possible that once vitamin B12 is in the mammary gland it is transferred to Hc (which may be synthesized by the mammary gland) and then secreted into milk as a Hc-B12 complex.

  3. Class II antigen-associated invariant chain mRNA in mouse small intestine.

    Science.gov (United States)

    Ouellette, A J; Frederick, D; Hagen, S J; Katz, J D

    1991-09-30

    MHC class II antigen-associated invariant (Ii) chain mRNA appears in mouse small intestine during postnatal development. Ii chain cDNA hybridizes to RNA from epithelial sheets dissociated from the lamina propria with EDTA. Of several mouse organs tested, only bone marrow and spleen contain higher levels of Ii chain mRNA than small bowel. Ii chain mRNA is not detected in stomach, colon, duodenum, testis, liver, submandibular gland, or L-cell RNA; brain contains a cross-reactive but uncharacterized sequence. cDNA amplification using primers specific for both Ii31 and Ii41 chain mRNAs showed that both forms occur in small intestine. These results support the conclusion that regulation of the class II Ii chain gene is associated with the ontogeny of intestinal immunity.

  4. Molecular requirements for MHC class II alpha-chain engagement and allelic discrimination by the bacterial superantigen streptococcal pyrogenic exotoxin C.

    Science.gov (United States)

    Kasper, Katherine J; Xi, Wang; Rahman, A K M Nur-Ur; Nooh, Mohammed M; Kotb, Malak; Sundberg, Eric J; Madrenas, Joaquín; McCormick, John K

    2008-09-01

    Superantigens (SAgs) are microbial toxins that bind to both TCR beta-chain variable domains (Vbetas) and MHC class II molecules, resulting in the activation of T cells in a Vbeta-specific manner. It is now well established that different isoforms of MHC II molecules can play a significant role in the immune response to bacterial SAgs. In this work, using directed mutational studies in conjunction with functional analyses, we provide a complete functional map of the low-affinity MHC II alpha-chain binding interface of the SAg streptococcal pyrogenic exotoxin C (SpeC) and identify a functional epitope in the beta-barrel domain that is required for the activation of T cells. Using cell lines that exclusively express individual MHC II isoforms, our studies provide a molecular basis for the selectivity of SpeC-MHC II recognition, and provide one mechanism by how SAgs are capable of distinguishing between different MHC II alleles.

  5. The Oropharyngeal Airway in Young Adults with Skeletal Class II and Class III Deformities: A 3-D Morphometric Analysis.

    Directory of Open Access Journals (Sweden)

    Yasas Shri Nalaka Jayaratne

    Full Text Available 1 To determine the accuracy and reliability of an automated anthropometric measurement software for the oropharyngeal airway and 2 To compare the anthropometric dimensions of the oropharyngeal airway in skeletal class II and III deformity patients.Cone-beam CT (CBCT scans of 62 patients with skeletal class II or III deformities were used for this study. Volumetric, linear and surface area measurements retroglossal (RG and retropalatal (RP compartments of the oropharyngeal airway was measured with the 3dMDVultus software. Accuracy of automated anthropometric pharyngeal airway measurements was assessed using an airway phantom.The software was found to be reasonably accurate for measuring dimensions of air passages. The total oropharyngeal volume was significantly greater in the skeletal class III deformity group (16.7 ± 9.04 mm3 compared with class II subjects (11.87 ± 4.01 mm3. The average surface area of both the RG and RP compartments were significantly larger in the class III deformity group. The most constricted area in the RG and RP airway was significantly larger in individuals with skeletal class III deformity. The anterior-posterior (AP length of this constriction was significantly greater in skeletal class III individuals in both compartments, whereas the width of the constriction was not significantly different between the two groups in both compartments. The RP compartment was larger but less uniform than the RG compartment in both skeletal deformities.Significant differences were observed in morphological characteristics of the oropharyngeal airway in individuals with skeletal class II and III deformities. This information may be valuable for surgeons in orthognathic treatment planning, especially for mandibular setback surgery that might compromise the oropharyngeal patency.

  6. Inflammatory bowel disease associations with HLA Class II genes

    Energy Technology Data Exchange (ETDEWEB)

    Castro, R. [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Yang, H.; Targan, S. [Roche Molecular Systems, Inc., Alameda, CA (United States)] [and others

    1994-09-01

    A PCR-SSOP assay has been used to analyze HLA-Class II DRB1 and DQB1 alleles in 378 Caucasians from a population in Southern California. The data has been analyzed separately for the Ashkenasi Jews and non-Jewish patients (n=286) and controls (n=92). Two common clinical forms of inflammatory bowel disease (IBD) have been studied: ulcerative colitis (UC) and Crohn`s disease (CD). In CD, we observed a susceptible effect with the rare DR1 allele - DRB*0103 [O.R.=4.56; 95% CI (0.96, 42.97); p=0.03]; a trend for an increase in DRB1*0103 was also observed in UC patients. A susceptible effect with DRB1*1502 [O.R.=5.20; 95% CI (1.10, 48.99); p=0.02] was observed in non-Jewish UC patients. This susceptible effect was restricted to UC ANCA-positive (antineutrophil cytoplasmic antibodies) patients. In addition, a significant association with DRB1*1101-DQB1*0301 [O.R.=9.46; 95% CI (1.30, 413.87); p=0.01] was seen with UC among non-Jewish patients: this haplotype was increased with CD among non-Jewish patients. Two protective haplotypes were detected among CD non-Jewish patients: DRB1*1301-DQB1*0603 [O.R.=0.34; 95% CI (0.09, 1.09); p=0.04], and DRB*0404-DQB1*0302 [O.R.=<0.08; 95% CI (0.0, 0.84); p=0.01]. When the same data were analyzed at the serology level, we observed a positive association in UC with DR2 [O.R.6.77; 95% CI (2.47, 22.95); p=2 x 10{sup -4}], and a positive association in CD with DR1 [O.R.=2.63; 95% CI (1.14, 6.62); p=0.01] consistent with previous reports. Thus, some IBD disease associations appear to be common to both UC and CD, while some are unique to one disease.

  7. Low major histocompatibility complex class II diversity in European and North American moose.

    Science.gov (United States)

    Mikko, S; Andersson, L

    1995-05-09

    Major histocompatibility complex (MHC) genes encode cell surface proteins whose function is to bind and present intracellularly processed peptides to T lymphocytes of the immune system. Extensive MHC diversity has been documented in many species and is maintained by some form of balancing selection. We report here that both European and North American populations of moose (Alces alces) exhibit very low levels of genetic diversity at an expressed MHC class II DRB locus. The observed polymorphism was restricted to six amino acid substitutions, all in the peptide binding site, and four of these were shared between continents. The data imply that the moose have lost MHC diversity in a population bottleneck, prior to the divergence of the Old and New World subspecies. Sequence analysis of mtDNA showed that the two subspecies diverged at least 100,000 years ago. Thus, viable moose populations with very restricted MHC diversity have been maintained for a long period of time. Both positive selection for polymorphism and intraexonic recombination have contributed to the generation of MHC diversity after the putative bottleneck.

  8. On the Relationship of UC H II Regions and Class II Methanol Masers: I. Source Catalogs

    CERN Document Server

    Hu, Bo; Wu, Yuanwei; Bartkiewicz, Anna; Rygl, Kazi; Reid, Mark J; Urquhart, James S; Zheng, Xingwu

    2016-01-01

    We conducted VLA C-configuration observations to measure positions and luminosities of Galactic Class II 6.7 GHz methanol masers and their associated ultra-compact H II regions. The spectral resolution was 3.90625 kHz and the continuum sensitivity reached 45 \\uJypb. We mapped 372 methanol masers with peak flux densities of more than 2 Jy selected from the literature, 367 of them were detected. Absolute positions have nominal uncertainties of 0.3 arcsec. In this first paper on the data analysis, we present three catalogs, the first gives information on the strongest feature of 367 methanol maser sources, and the second on all detected maser spots. The third catalog present derived data of the 279 radio continuum sources found in the vicinity of maser sources. Among them, 140 show evidence of physical association with maser sources. Our catalogs list properties including distance, flux density, radial velocity and the distribution of masers on the Galactic plane is then provided as well. We found no significant...

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

    Directory of Open Access Journals (Sweden)

    Carmen L Mueller Storrer

    2014-01-01

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

  10. 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...... sealing of the restorations was performed after finishing. One operator placed 99 restorations (33 sets). Evaluation was performed with slightly modified USPHS criteria at baseline, 2, 3, 10 and 27 years. Results: Postoperative sensitivity was observed in 5 patients. Three participants with 11......: Class II restorations of the three conventional resin composites showed an acceptable success rate during the 27 year evaluation....

  11. Class II direct composite resin restorations with beta-quartz glass-ceramic inserts.

    Science.gov (United States)

    Rada, R E

    1993-11-01

    With the increasing demand for esthetic posterior restorations, numerous techniques have been developed. The direct resin restoration has probably been used most extensively in Class II situations. Problems with Class II direct resin restorations include difficulty in developing proximal contact, occlusal wear, and polymerization shrinkage. Beta-quartz glass-ceramic inserts have been developed in an attempt to reduce the incidence of these potential problems. They can be placed in a one-appointment technique, are relatively inexpensive, and can readily be utilized by the clinician adept in placing Class II composite resin restorations.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  13. A Single Residue Switch for Mg2+-dependent Inhibition Characterizes Plant Class II Diterpene Cyclases from Primary and Secondary Metabolism*

    Science.gov (United States)

    Mann, Francis M.; Prisic, Sladjana; Davenport, Emily K.; Determan, Mara K.; Coates, Robert M.; Peters, Reuben J.

    2010-01-01

    Class II diterpene cyclases mediate the acid-initiated cycloisomerization reaction that serves as the committed step in biosynthesis of the large class of labdane-related diterpenoid natural products, which includes the important gibberellin plant hormones. Intriguingly, these enzymes are differentially susceptible to inhibition by their Mg2+ cofactor, with those involved in gibberellin biosynthesis being more sensitive to such inhibition than those devoted to secondary metabolism, which presumably limits flux toward the potent gibberellin phytohormones. Such inhibition has been suggested to arise from intrasteric Mg2+ binding to the DXDD motif that cooperatively acts as the catalytic acid, whose affinity must then be modulated in some fashion. While further investigating class II diterpene cyclase catalysis, we discovered a conserved basic residue that seems to act as a counter ion to the DXDD motif, enhancing the ability of aspartic acid to carry out the requisite energetically difficult protonation of a carbon-carbon double bond and also affecting inhibitory Mg2+ binding. Notably, this residue is conserved as a histidine in enzymes involved in gibberellin biosynthesis and as an arginine in those dedicated to secondary metabolism. Interchanging the identity of these residues is sufficient to switch the sensitivity of the parent enzyme to inhibition by Mg2+. These striking findings indicate that this is a single residue switch for Mg2+ inhibition, which not only supports the importance of this biochemical regulatory mechanism in limiting gibberellin biosynthesis, but the importance of its release, presumably to enable higher flux, into secondary metabolism. PMID:20430888

  14. Histochemical analysis of the role of class I and class II Clostridium histolyticum collagenase in the degradation of rat pancreatic extracellular matrix for islet isolation

    NARCIS (Netherlands)

    VosScheperkeuter, GH; vanSuylichem, PTR; Wolters, GHJ; vanSchilfgaarde, R

    1997-01-01

    To understand why class II Clostridium histolyticum collagenase is much more effective than class I in the isolation of rat pancreatic islets, we analyzed the role of these collagenases in pancreatic tissue dissociation. Crude collagenase was purified and then fractionated into class I and II with d

  15. Identifying Affinity Classes of Inorganic Materials Binding Sequences via a Graph-Based Model.

    Science.gov (United States)

    Du, Nan; Knecht, Marc R; Swihart, Mark T; Tang, Zhenghua; Walsh, Tiffany R; Zhang, Aidong

    2015-01-01

    Rapid advances in bionanotechnology have recently generated growing interest in identifying peptides that bind to inorganic materials and classifying them based on their inorganic material affinities. However, there are some distinct characteristics of inorganic materials binding sequence data that limit the performance of many widely-used classification methods when applied to this problem. In this paper, we propose a novel framework to predict the affinity classes of peptide sequences with respect to an associated inorganic material. We first generate a large set of simulated peptide sequences based on an amino acid transition matrix tailored for the specific inorganic material. Then the probability of test sequences belonging to a specific affinity class is calculated by minimizing an objective function. In addition, the objective function is minimized through iterative propagation of probability estimates among sequences and sequence clusters. Results of computational experiments on two real inorganic material binding sequence data sets show that the proposed framework is highly effective for identifying the affinity classes of inorganic material binding sequences. Moreover, the experiments on the structural classification of proteins (SCOP) data set shows that the proposed framework is general and can be applied to traditional protein sequences.

  16. A Case of Probable MHC Class II Deficiency with Disseminated BCGitis.

    Science.gov (United States)

    Alyasin, Soheyla; Abolnezhadian, Farhad; Khoshkhui, Maryam

    2015-09-01

    Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency disease characterized by abnormality of MHC class II molecules surface expression on peripheral blood lymphocytes and monocytes. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections but the immunodeficiency is not as severe as SCID (severe combined immunodeficiency), as evidenced by failure to develop disseminated infection after BCG vaccination. Therefore, MHC II deficiency with BCGosis, that is disseminated BCGitis, is not reported commonly. We report an interesting case of BCGosis after vaccination that was diagnosed to have probable MHC II deficiency.

  17. Structure of the human angiotensin II type 1 (AT1) receptor bound to angiotensin II from multiple chemoselective photoprobe contacts reveals a unique peptide binding mode.

    Science.gov (United States)

    Fillion, Dany; Cabana, Jérôme; Guillemette, Gaétan; Leduc, Richard; Lavigne, Pierre; Escher, Emanuel

    2013-03-22

    Breakthroughs in G protein-coupled receptor structure determination based on crystallography have been mainly obtained from receptors occupied in their transmembrane domain core by low molecular weight ligands, and we have only recently begun to elucidate how the extracellular surface of G protein-coupled receptors (GPCRs) allows for the binding of larger peptide molecules. In the present study, we used a unique chemoselective photoaffinity labeling strategy, the methionine proximity assay, to directly identify at physiological conditions a total of 38 discrete ligand/receptor contact residues that form the extracellular peptide-binding site of an activated GPCR, the angiotensin II type 1 receptor. This experimental data set was used in homology modeling to guide the positioning of the angiotensin II (AngII) peptide within several GPCR crystal structure templates. We found that the CXC chemokine receptor type 4 accommodated the results better than the other templates evaluated; ligand/receptor contact residues were spatially grouped into defined interaction clusters with AngII. In the resulting receptor structure, a β-hairpin fold in extracellular loop 2 in conjunction with two extracellular disulfide bridges appeared to open and shape the entrance of the ligand-binding site. The bound AngII adopted a somewhat vertical binding mode, allowing concomitant contacts across the extracellular surface and deep within the transmembrane domain core of the receptor. We propose that such a dualistic nature of GPCR interaction could be well suited for diffusible linear peptide ligands and a common feature of other peptidergic class A GPCRs.

  18. 78 FR 14015 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Powered Patient Transport

    Science.gov (United States)

    2013-03-04

    ... Notification; Class II Devices; Powered Patient Transport AGENCY: Food and Drug Administration, HHS. ACTION... requesting exemption from premarket notification requirements for powered patient transport devices commonly... FDA's powered patient transport regulations, including attendant-operated portable...

  19. N-Sulfonyl hydroxamate derivatives as inhibitors of class II fructose-1,6-diphosphate aldolase.

    Science.gov (United States)

    Gavalda, Sabine; Braga, Rémi; Dax, Chantal; Vigroux, Alain; Blonski, Casimir

    2005-12-15

    Dihydroxyacetone-phosphate and phosphonate derivatives were synthesized bearing a N-sulfonyl hydroxamate moiety. The phosphate derivatives represent competitive inhibitors for the class II-FBP aldolase catalyzed reaction, while the phosphonate isosteres are comparatively weaker inhibitors.

  20. 40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... facility; (vii) Dated records of the quantity (in kilograms) of raw materials and feedstock chemicals used...) Recordkeeping and reporting. Any person who produces, imports, exports, transforms, or destroys class II... total of expended and unexpended production allowances, consumption allowances, export...

  1. Major histocompatibility complex class I binding predictions as a tool in epitope discovery

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lund, Ole; Buus, Søren;

    2010-01-01

    Over the last decade, in silico models of the major histocompatibility complex (MHC) class I pathway have developed significantly. Before, peptide binding could only be reliably modelled for a few major human or mouse histocompatibility molecules; now, high-accuracy predictions are available...... for any human leucocyte antigen (HLA) -A or -B molecule with known protein sequence. Furthermore, peptide binding to MHC molecules from several non-human primates, mouse strains and other mammals can now be predicted. In this review, a number of different prediction methods are briefly explained...

  2. 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.

  3. HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman, India.

    Science.gov (United States)

    Chaaithanya, Itta Krishna; Muruganandam, Nagarajan; Anwesh, Maile; Rajesh, Reesu; Ghosal, Sruti R; Kartick, Chinnaiah; Prasad, Kadiyala Nageswara; Muthumani, Karuppiah; Vijayachari, Paluru

    2013-10-01

    A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July-August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT-PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA-DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA-DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide-binding pockets of HLA-DQB1 molecules were investigated. The frequencies of HLA-DRB1 alleles were not significantly different, whereas lower frequency of HLA-DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR)  = 0, 95% confidence interval (95% CI) 0·0-0·331; Peto's OR = 0·1317, 95% CI 0·0428-0·405). Significantly lower frequency of glutamic acid at position 86 of peptide-binding pocket 1 coding HLA-DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125-0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA-DQ molecules are known to bind more CHIKV peptides than HLA-DRB1 molecules. The results suggest that HLA-DQB1 alleles and critical amino acid differences in the peptide-binding pockets of HLA-DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV.

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

    OpenAIRE

    2014-01-01

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

  5. Marginal and internal adaptation of class II restorations after immediate or delayed composite placement

    OpenAIRE

    Dietschi, Didier; Monasevic, Manuela; Krejci, Ivo; Davidson, Carel

    2002-01-01

    Direct class II composite restorations still represent a challenge, particularly when proximal limits extend below the CEJ. The aim of this in vitro study was to evaluate the influence of the type of adhesive and the delay between adhesive placement and composite insertion on restoration adaptation. Direct class II MOD box-shaped composite restorations (n=8 per group) were placed on intact human third molars, with proximal margins 1mm above or under CEJ. All cavities were filled with a horizo...

  6. 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...

  7. The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts

    OpenAIRE

    1996-01-01

    The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules nd lysosomal hydrolases were studied in I-Cell Disease (ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC class II- invariant chain complexes colocalized with the lysosomal hydrolase cathepsin D in buds and vesicles that lacked markers of clathrin-coated vesicle-mediated transport. ...

  8. Oral Impacts on Quality of Life in Adult Patients with Class I, II and III Malocclusion

    OpenAIRE

    Javed, Omair; Bernabé, Eduardo

    2016-01-01

    PURPOSE: To compare the social impact of malocclusion on quality of life between adult patients with Angle Class I, II and III malocclusion.MATERIALS AND METHODS: A total of 222 adult patients (139, 42 and 41 with Angle Class I, II and III malocclusion, respectively) were recruited voluntarily from those attending the Orthodontic Clinic of Khyber College of Dentistry in Pesh awar, Pakistan. Participants were asked to complete the Urdu version of the short form of the Oral Health Impact Profil...

  9. Conformational lability in the class II MHC 310 helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange

    Science.gov (United States)

    Painter, Corrie A.; Negroni, Maria P.; Kellersberger, Katherine A.; Zavala-Ruiz, Zarixia; Evans, James E.; Stern, Lawrence J.

    2011-01-01

    HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 310 helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange. PMID:22084083

  10. Conformational lability in the class II MHC 310 helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange.

    Science.gov (United States)

    Painter, Corrie A; Negroni, Maria P; Kellersberger, Katherine A; Zavala-Ruiz, Zarixia; Evans, James E; Stern, Lawrence J

    2011-11-29

    HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 3(10) helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange.

  11. Evaluation and Comparison of Intermaxillary Tooth Size Discrepancy among Class I, Class II Division 1, and Class III Subjects Using Bolton’s Analysis: An in vitro Study

    OpenAIRE

    Prasanna, A Lakshmi; Venkatramana, V; Aryasri, A Srikanth; Katta, Anil Kumar; K. Santhanakrishnan; Maheshwari, Uma

    2015-01-01

    Aim: The aim of the present study was to evaluation and comparison of intermaxillary tooth size discrepancy among Class I, Class II division 1, and Class III subjects using Bolton’s analysis. Materials and Methods: The pre-treatment casts were selected from the records of patients attending the Department of Orthodontics of Meenakshi Ammal Dental College, Chennai. The sample consists of 180 pre-treatment casts with both sexes evenly distributed with 60 casts in each type of malocclusion, i.e....

  12. Class II genes of miniature swine. II. Molecular identification and characterization of B (beta) genes from the SLAc haplotype.

    Science.gov (United States)

    Pratt, K; Sachs, D H; Germana, S; el-Gamil, M; Hirsch, F; Gustafsson, K; LeGuern, C

    1990-01-01

    Genomic clones corresponding to class II beta genes of the SLAc haplotype of miniature swine have been isolated and characterized. These genes have been grouped into seven non-overlapping clusters on the basis of restriction mapping. Ordering of exons within each cluster was accomplished by hybridization of Southern blots of restriction fragments with exon-specific probes. The two clusters (clusters 2 and 3) encoding the DRB and DQB genes were identified on the basis of hybridization with locus-specific 3' untranslated cDNA probes. Cluster 4 contained exons of both DOB and DQB genes, the basis for which remains to be determined. The remaining four clusters (1, 5, 6, 7) were identified as containing DP, DR, and DO coding sequences, respectively, on the basis of sequence analysis. The porcine class II region appears very similar to that of man in number and nature of the class II genes identified and in the intron/exon organization of corresponding genes.

  13. Discovery of Two New Class II Methanol Maser Transitions in G345.01+1.79

    CERN Document Server

    Ellingsen, S P; Cragg, D M; Godfrey, P D

    2012-01-01

    We have used the Swedish ESO Submillimetre Telescope (SEST) to search for new class II methanol maser transitions towards the southern source G345.01+1.79. Over a period of 5 days we observed 11 known or predicted class II methanol maser transitions. Emission with the narrow line width and characteristic velocity of class II methanol masers (in this source) was detected in 8 of these transitions, two of which have not previously been reported as masers. The new class II methanol maser transitions are the 13(-3)-12(-4)E transition at 104.1 GHz and the 5(1)-4(2)E transition at 216.9 GHz. Both of these are from transition series for which there are no previous known class II methanol maser transitions. This takes the total number of known class II methanol maser series to 10, and the total number of transitions (or transition groups) to 18. The observed 104.1 GHz maser suggests the presence of two or more regions of masing gas with similar line of sight velocities, but quite different physical conditions. Althou...

  14. 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.

  15. Aspects of Protein, Chemistry, Part II: Oxygen-Binding Proteins

    Science.gov (United States)

    Nixon, J. E.

    1977-01-01

    Compares differences in function and behavior of two oxygen-binding proteins, myoglobin found in muscle and hemoglobin found in blood. Describes the mechanism of oxygen-binding and allosteric effect in hemoglobin; also describes the effect of pH on the affinity of hemoglobin for oxygen. (CS)

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

    Science.gov (United States)

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

    2012-11-01

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

  17. 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

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

    Science.gov (United States)

    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

    2016-01-29

    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 cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.

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

    DEFF Research Database (Denmark)

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

    1991-01-01

    adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human......, but not the class I-negative parental line, 221, showed homotypic aggregation in response to an HLA-G specific mAb (87G) and a broad reacting class I-specific mAb (IOT2). Both cell lines responded with aggregation to anti-class II mAb (TU35). The anti-class I mAb, W6/32, had no effect on all cell lines tested...... and two anti-beta 2-microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature-sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase...

  20. Do orthodontists recommend Class II treatment according to evidence-based knowledge?

    Directory of Open Access Journals (Sweden)

    Soraia Azevedo Almeida

    Full Text Available AbstractIntroductionThe adequate indications for the timing of treatment for Class II malocclusion are mandatory for the ethical and efficient practice of orthodontics, but clinicians are reluctant to accept new information that contradicts their preferred method of treatment.ObjectiveThe aim of this investigation was to assess the agreement regarding the indications for Class II malocclusion interceptive therapy between a group of international opinion-makers on early treatment and a group of orthodontists and to compare their treatment indications with the current evidence-based knowledge.Material and methodAn electronic survey containing photographs of mild, moderate and severe Class II malocclusions in children was sent to two panels of experts. Panel 1 (n=28 was composed of international orthodontists who had authored world-class publications on early orthodontic treatment, and Panel 2 (n=261 was composed of clinical orthodontists. Based on a 5-point Likert-type scale, the orthodontists selected their therapy option for each of the 9 Class II malocclusion cases.ResultThe Class II malocclusion treatment recommendations of Panel 2 were significantly different from those offered by Panel 1 with a skew of at least 1 scale point toward earlier treatment. The Class II malocclusion treatment recommendations of the members of Panel 1 members were in accordance with contemporary evidence-based knowledge.ConclusionClass II malocclusion overtreatment appears to be the tendency among clinical orthodontists but not among orthodontists who are academically involved with early treatment. There is a gap between the scientific knowledge and the practices of orthodontists.

  1. [Type-I and -II estradiol binding sites in the endometrium during blastocyst implantation].

    Science.gov (United States)

    Bernal, A; Calzada, L; Hicks, J J; Velázquez, A

    1989-04-01

    The properties of type I and occupied and unoccupied type II cytosolic estrogen binding sites in the rat endometrium were analyzed on day five of pregnancy; the samples studied correspond to blastocyst receptive endometrium (implantation sites), nonreceptive endometrium and ovariectomized uterine horn endometrium, from the same pregnancy rats. The occupied binding site type II was analyzed by exchange assays. Dissociation constant obtained from experiments carried out at 4 or 25 degrees C are similar for each one of the binding site at the three different endometrium samples; the binding capacity (femtomoles/mg protein) from the sites type I and type II and the ratio between occupied (by endogenous estradiol) and unoccupied site type II, seems to be characteristic for each one of the three analyzed endometrium.

  2. Synthesis, characterization and DNA binding/cleavage, protein binding and cytotoxicity studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes of aminonaphthoquinone.

    Science.gov (United States)

    Kosiha, A; Parthiban, C; Elango, Kuppanagounder P

    2017-03-01

    The Co(II), Ni(II), Cu(II) and Zn(II) complexes of an aminonaphthoquinone ligand (L) have been prepared and characterized using analytical and spectral techniques. The structures of L and its Zn(II) complex are confirmed by single crystal X-ray diffraction study. The results indicate that Co(II), Ni(II) and Zn(II) complexes possess tetrahedral geometry while Cu(II) complex exhibits square planar structure. The interaction of L and its complexes with CT-DNA reveal that they could interact with CT-DNA through intercalation. The DNA cleavage studies of the L and its complexes indicate that the Cu(II) and Ni(II) complexes cleave the circular form of the DNA relatively to a greater extent than the other complexes. The results of the interaction of these compounds with bovine serum albumin (BSA) indicate that the complexes exhibit a strong binding to BSA over the L. The in vitro anticancer activities indicate that these compounds exhibit substantial activity against human breast (MCF7) and lung cancer (A549) cell lines. The characteristics of apoptosis in cell morphology have been observed using AO/EB and DAPI staining and the results suggest that an apoptotic mode of cell death with these compounds. The overall results and discussion indicate that coordination of metal ions with the ligand enhances the biological activity.

  3. 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.

  4. Comparison Between the Sonic-Sys System and Inlay in II Class

    OpenAIRE

    Feder, T.; Mierzwinska-Nastalska, E; Adamczyk-Sosinska, E.; Gladkowski, J.; Siedlecki, M.

    2002-01-01

    In everyday dental practice we often face the problem of class II restorations. Large caries create serious problems with regard to obtaining correct contact points, marginal fit (expecially in the gingival area) and good resin polymerisation. In such cases usage of the Sonic-Sys system and inlays seems to be the best solution. The aim of this poster is to present a manual of the Sonic-Sys system, as well as comparison of the Empress II and Sonic-Sys system inlays in class II restorations....

  5. 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.

  6. 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.

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

    Science.gov (United States)

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

    2005-01-01

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

  8. Linkage relationships in the bovine MHC region. High recombination frequency between class II subregions.

    Science.gov (United States)

    Andersson, L; Lundén, A; Sigurdardottir, S; Davies, C J; Rask, L

    1988-01-01

    Class II genes of the bovine major histocompatibility complex (MHC) have been investigated by Southern blot analysis using human DNA probes. Previous studies revealed the presence of bovine DO beta, DQ alpha, DQ beta, DR alpha, and DR beta genes, and restriction fragment length polymorphisms for each of these genes were documented. In the present study, the presence of three additional class II genes, designated DZ alpha, DY alpha, and DY beta, are reported. DZ alpha was assumed to correspond to the human DZ alpha gene while the other two were designated DY because their relationship to human class II genes could not be firmly established. The linkage relationships among bovine class II genes and two additional loci, TCP1B and C4, were investigated by family segregation analysis and analysis of linkage disequilibrium. The results clearly indicated that all these loci belong to the same linkage group. This linkage group is divided into two subregions separated by a fairly high recombination frequency. One region includes the C4, DQ alpha, DQ beta, DR alpha, and DR beta loci and the other one is composed of the DO beta, DY alpha, DY beta, and TCP1B loci. No recombinant was observed within any of these subregions and there was a strong or fairly strong linkage disequilibrium between loci within groups. In contrast, as many as five recombinants among three different families were detected in the interval between these subregions giving a recombination frequency estimate of 0.17 +/- 0.07. The fairly high recombination frequency observed between class II genes in cattle is strikingly different from the corresponding recombination estimates in man and mouse. The finding implies either a much larger molecular distance between some of the bovine class II genes or alternatively the presence of a recombinational "hot spot" in the bovine class II region.

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

    Directory of Open Access Journals (Sweden)

    Darwin Vaz de Lima

    2013-04-01

    Full Text Available 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 evaluation was 6.12 years. To verify the influence of the severity of initial Class II molar relationship in stability of molar relationship, the sample was divided into two groups, one presenting a ½-cusp or ¾-cusp Class II molar relationship, and the other with full-cusp Class II molar relationship. In dental casts from initial, final and postretention stages, molar, first and second premolars and canine relationships were measured. Data obtained were analyzed by dependent ANOVA, Tukey and Pearson's correlation tests, as well as independent t test between the two groups divided by severity of initial molar relationship. RESULTS: There was a non-statistically significant 0.12 mm relapse of molar relationship. The initial severity of Class II molar relationship was not correlated to relapse in the post-retention period. When compared, the two groups showed no difference in relapse of molar relationship. CONCLUSION: It was concluded that correction of Class II molar relationship is stable and initial severity does not influence relapse of molar relationship.

  10. HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Jesionek-Kupnicka, Dorota; Bojo, Marcin; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna; Jabłońska, Joanna; Kalinka-Warzocha, Ewa; Kordek, Radzisław; Młynarski, Wojciech; Robak, Tadeusz; Warzocha, Krzysztof; Lech-Maranda, Ewa

    2016-06-01

    The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.

  11. DNA binding and biological activity of mixed ligand complexes of Cu(II, Ni(II and Co(II with quinolones and N donor ligand

    Directory of Open Access Journals (Sweden)

    S.M M Akram

    2015-10-01

    Full Text Available  AbstractMixed ligand complexes of  Cu(II, Ni(II and Co(II have been synthesized by using levofloxacin and bipyridyl and characterized using spectral and analytical techniques. The binding behavior of the Ni(II and Cu(II complexes with herring sperm DNA(Hs-DNA were determined using electronic absorption titration, viscometric measurements and cyclic voltammetry measurements. The binding constant calculated  for Cu(II and Ni(II complexes are 2.0 x 104 and 4.0 x 104 M-1 respectively. Detailed analysis reveals that these metal complexes interact with DNA through intercalative binding mode. The nuclease activity of  Cu(II and Ni(II complexes with ct-DNA was carried out using agarose gel electrophoresis technique. The antioxidant activities for the synthesized complexes have been tested and the antibacterial activity for Ni(II complex was also checked.Key words: Intercalation, hypochromism, red shift and  peak potential.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

    Directory of Open Access Journals (Sweden)

    Katherine J Kasper

    2014-05-01

    Full Text Available Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS, how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6 mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

  14. Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner

    Science.gov (United States)

    Kasper, Katherine J.; Zeppa, Joseph J.; Wakabayashi, Adrienne T.; Xu, Stacey X.; Mazzuca, Delfina M.; Welch, Ian; Baroja, Miren L.; Kotb, Malak; Cairns, Ewa; Cleary, P. Patrick; Haeryfar, S. M. Mansour; McCormick, John K.

    2014-01-01

    Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC –II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms. PMID:24875883

  15. Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity.

    Science.gov (United States)

    Merelo, Paz; Ram, Hathi; Pia Caggiano, Monica; Ohno, Carolyn; Ott, Felix; Straub, Daniel; Graeff, Moritz; Cho, Seok Keun; Yang, Seong Wook; Wenkel, Stephan; Heisler, Marcus G

    2016-10-18

    A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD-ZIP) transcription factors are key mediators in the regulation of adaxial-abaxial patterning. Their expression is restricted adaxially during early development by the abaxially expressed microRNA (MIR)165/166, yet the mechanism that restricts MIR165/166 expression to abaxial leaf tissues remains unknown. Here, we show that class III and class II HD-ZIP proteins act together to repress MIR165/166 via a conserved cis-element in their promoters. Organ morphology and tissue patterning in plants, therefore, depend on a bidirectional repressive circuit involving a set of miRNAs and its targets.

  16. A Class I and Class II Methanol Maser Survey of Extended Green Objects (EGOs) from the GLIMPSE Survey

    CERN Document Server

    Cyganowski, C J; Hunter, T R; Churchwell, E

    2009-01-01

    We present the results of a high angular resolution Very Large Array (VLA) Class I 44 GHz and Class II 6.7 GHz methanol maser survey of a sample of ~20 massive young stellar object (MYSO) outflow candidates selected on the basis of extended 4.5 micron emission in Spitzer Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE) images. These 4.5 micron-selected candidates are referred to as extended green objects (EGOs), for the common coding of this band as green in three-color IRAC images. The detection rate of 6.7 GHz Class II methanol masers, which are associated exclusively with massive YSOs, towards EGOs is greater than ~64%--nearly double the detection rate of surveys using other MYSO selection criteria. The detection rate of Class I 44 GHz methanol masers, which trace molecular outflows, is ~89% towards EGOs associated with 6.7 GHz methanol masers. The two types of methanol masers exhibit different spatial distributions: 6.7 GHz masers are centrally concentrated and usually coincide with 24 m...

  17. A novel HURRAH protocol reveals high numbers of monomorphic MHC class II loci and two asymmetric multi-locus haplotypes in the Pere David's deer.

    Directory of Open Access Journals (Sweden)

    Qiu-Hong Wan

    Full Text Available The Père David's deer is a highly inbred, but recovered, species, making it interesting to consider their adaptive molecular evolution from an immunological perspective. Prior to this study, genomic sequencing was the only method for isolating all functional MHC genes within a certain species. Here, we report a novel protocol for isolating MHC class II loci from a species, and its use to investigate the adaptive evolution of this endangered deer at the level of multi-locus haplotypes. This protocol was designated "HURRAH" based on its various steps and used to estimate the total number of MHC class II loci. We confirmed the validity of this novel protocol in the giant panda and then used it to examine the Père David's deer. Our results revealed that the Père David's deer possesses nine MHC class II loci and therefore has more functional MHC class II loci than the eight genome-sequenced mammals for which full MHC data are currently available. This could potentially account at least in part for the strong survival ability of this species in the face of severe bottlenecking. The results from the HURRAH protocol also revealed that: (1 All of the identified MHC class II loci were monomorphic at their antigen-binding regions, although DRA was dimorphic at its cytoplasmic tail; and (2 these genes constituted two asymmetric functional MHC class II multi-locus haplotypes: DRA1*01 ∼ DRB1 ∼ DRB3 ∼ DQA1 ∼ DQB2 (H1 and DRA1*02 ∼ DRB2 ∼ DRB4 ∼ DQA2 ∼ DQB1 (H2. The latter finding indicates that the current members of the deer species have lost the powerful ancestral MHC class II haplotypes of nine or more loci, and have instead fixed two relatively weak haplotypes containing five genes. As a result, the Père David's deer are currently at risk for increased susceptibility to infectious pathogens.

  18. RNAs nonspecifically inhibit RNA polymerase II by preventing binding to the DNA template.

    Science.gov (United States)

    Pai, Dave A; Kaplan, Craig D; Kweon, Hye Kyong; Murakami, Kenji; Andrews, Philip C; Engelke, David R

    2014-05-01

    Many RNAs are known to act as regulators of transcription in eukaryotes, including certain small RNAs that directly inhibit RNA polymerases both in prokaryotes and eukaryotes. We have examined the potential for a variety of RNAs to directly inhibit transcription by yeast RNA polymerase II (Pol II) and find that unstructured RNAs are potent inhibitors of purified yeast Pol II. Inhibition by RNA is achieved by blocking binding of the DNA template and requires binding of the RNA to Pol II prior to open complex formation. RNA is not able to displace a DNA template that is already stably bound to Pol II, nor can RNA inhibit elongating Pol II. Unstructured RNAs are more potent inhibitors than highly structured RNAs and can also block specific transcription initiation in the presence of basal transcription factors. Crosslinking studies with ultraviolet light show that unstructured RNA is most closely associated with the two large subunits of Pol II that comprise the template binding cleft, but the RNA has contacts in a basic residue channel behind the back wall of the active site. These results are distinct from previous observations of specific inhibition by small, structured RNAs in that they demonstrate a sensitivity of the holoenzyme to inhibition by unstructured RNA products that bind to a surface outside the DNA cleft. These results are discussed in terms of the need to prevent inhibition by RNAs, either though sequestration of nascent RNA or preemptive interaction of Pol II with the DNA template.

  19. PowerScope a Class II corrector – A case report

    Directory of Open Access Journals (Sweden)

    Joby Paulose

    2016-01-01

    Full Text Available Managing mild to moderate Class II malocclusion is a one of the common and major challenges to orthodontists. Class II discrepancies with mandibular deficiency during active growth are usually treated by myofunctional appliances. Fixed functional appliances evolved due to the noncompliance with conventional myofunctional appliances. This case report illustrates the efficiency of PowerScope in correction of skeletal Class II with mandibular deficiency in a patient aged 13 years who has reported to the department with a chief complaint of forwardly placed upper front teeth. This case with functional jaw retrusion was treated initially with MBT 0.022” prescription followed by PowerScope. Pre-, mid- and post-treatment cephalograms were obtained, and cephalometric analysis was performed. Stable and successful results were obtained with a substantial improvement in facial profile, skeletal jaw relationship, and overall esthetic appearance of the patient. A significant forward displacement of the mandible was the principal element for successful correction of Class II malocclusion. PowerScope provides the best results for Class II management, thus enables us to treat such cases by a nonextraction approach rather than contemplating extractions.

  20. Structural evidence for conformational changes of Delta class glutathione transferases after ligand binding.

    Science.gov (United States)

    Wongsantichon, Jantana; Robinson, Robert C; Ketterman, Albert J

    2012-05-01

    We report four new crystal structures for Delta class glutathione transferases from insects. We compare these new structures as well as several previously reported structures to determine that structural transitions can be observed with ligand binding. These transitions occurred in the regions around the active site entrance, including alpha helix 2, C-terminus of alpha helix 4 including the loop to helix 5 and the C-terminus of helix 8. These structural movements have been reported or postulated to occur for several other glutathione transferase classes; however, this is the first report showing structural evidence of all these movements occurring, in this case in Delta class glutathione transferases. These fluctuations also can be observed occurring within a single structure as there is ligand bound in only one subunit and each subunit is undergoing different conformational transitions. The structural comparisons show reorganizations occur both pre- and post-GSH ligand binding communicated through the subunit interface of the quaternary assembly. Movements of these positions would allow 'breathing' of the active site for substrate entrance, topological rearrangement for varying substrate specificity and final product release.

  1. Identification of the minimal copper(II)-binding alpha-synuclein sequence.

    Science.gov (United States)

    Jackson, Mark S; Lee, Jennifer C

    2009-10-05

    Parkinson's disease has been long linked to environmental factors, such as transition metals and recently to alpha-synuclein, a presynaptic protein. Using tryptophan-containing peptides, we identified the minimal Cu(II)-binding sequence to be within the first four residues, MDV(F/W), anchored by the alpha-amino terminus. In addition, mutant peptide 1-10 (Lys --> Arg) verified that neither Lys6 nor Lys10 are necessary for Cu(II) binding. Interestingly, Trp4 excited-state decay kinetics measured for peptides and proteins reveal two quenching modes, possibly arising from two distinct Cu(II)-polypeptide structures.

  2. Wild-type phosphoribosylpyrophosphate synthase (PRS) from Mycobacterium tuberculosis: a bacterial class II PRS?

    Science.gov (United States)

    Breda, Ardala; Martinelli, Leonardo K B; Bizarro, Cristiano V; Rosado, Leonardo A; Borges, Caroline B; Santos, Diógenes S; Basso, Luiz A

    2012-01-01

    The 5-phospho-α-D-ribose 1-diphosphate (PRPP) metabolite plays essential roles in several biosynthetic pathways, including histidine, tryptophan, nucleotides, and, in mycobacteria, cell wall precursors. PRPP is synthesized from α-D-ribose 5-phosphate (R5P) and ATP by the Mycobacterium tuberculosis prsA gene product, phosphoribosylpyrophosphate synthase (MtPRS). Here, we report amplification, cloning, expression and purification of wild-type MtPRS. Glutaraldehyde cross-linking results suggest that MtPRS predominates as a hexamer, presenting varied oligomeric states due to distinct ligand binding. MtPRS activity measurements were carried out by a novel coupled continuous spectrophotometric assay. MtPRS enzyme activity could be detected in the absence of 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 determination of

  3. 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

  4. Quantitative distribution of angiotensin II binding sites in rat brain by autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Saavedra, J.M.; Israel, A.; Plunkett, L.M.; Kurihara, M.; Shigematsu, K.; Correa, F.M.

    1986-07-01

    Angiotensin II binding sites were localized and quantified in individual brain nuclei from single rats by incubation of tissue sections with 1 nM /sup 125/I-(Sar1)-angiotensin II, (/sup 3/H)-Ultrofilm autoradiography, computerized microdensitometry and comparison with /sup 125/I-standards. High angiotensin II binding was present in the circumventricular organs (organon vasculosum laminae terminalis, organon subfornicalis and area postrema), in selected hypothalamic nuclei (nuclei suprachiasmatis, periventricularis and paraventricularis) and in the nucleus tractus olfactorii lateralis, the nucleus preopticus medianus, the dorsal motor nucleus of the vagus and the nucleus tractus solitarii. High affinity (KA from 0.3 to 1.5 X 10(9) M-1) angiotensin II binding sites were demonstrated in the organon subfornicalis, the nucleus tractus solitarii and the area postrema after incubation of consecutive sections from single rat brains with /sup 125/I-(Sar1)-angiotensin II in concentrations from 100 pM to 5 nM. These results demonstrate and characterize brain binding sites for angiotensin II of variable high affinity binding both inside and outside the blood-brain barrier.

  5. Inhibition of RNA Polymerase II Transcription in Human Cells by Synthetic DNA-Binding Ligands

    Science.gov (United States)

    Dickinson, Liliane A.; Gulizia, Richard J.; Trauger, John W.; Baird, Eldon E.; Mosier, Donald E.; Gottesfeld, Joel M.; Dervan, Peter B.

    1998-10-01

    Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole--imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located with RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.

  6. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false What are the minimum technical hardware standards applicable to Class II gaming systems? 547.7 Section 547.7 Indians NATIONAL INDIAN GAMING COMMISSION... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class...

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

    Directory of Open Access Journals (Sweden)

    Keith T Ballingall

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

  8. Cu(II) binding by a pH-fractionated fulvic acid

    Science.gov (United States)

    Brown, G.K.; Cabaniss, S.E.; MacCarthy, P.; Leenheer, J.A.

    1999-01-01

    The relationship between acidity, Cu(II) binding and sorption to XAD resin was examined using Suwannee River fulvic acid (SRFA). The work was based on the hypothesis that fractions of SRFA eluted from an XAD column at various pH's from 1.0 to 12.0 would show systematic variations in acidity and possibly aromaticity which in turn would lead to different Cu(II) binding properties. We measured equilibrium Cu(II) binding to these fractions using Cu2+ ion-selective electrode (ISE) potentiometry at pH 6.0. Several model ligands were also examined, including cyclopentane-1,2,3,4-tetracarboxylic acid (CP-TCA) and tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THF-TCA), the latter binding Cu(II) much more strongly as a consequence of the ether linkage. The SRFA Cu(II) binding properties agreed with previous work at high ionic strength, and binding was enhanced substantially at lower ionic strength, in agreement with Poisson-Boltzmann predictions for small spheres. Determining Cu binding constants (K(i)) by non-linear regression with total ligand concentrations (L(Ti)) taken from previous work, the fractions eluted at varying pH had K(i) similar to the unfractionated SRFA, with a maximum enhancement of 0.50 log units. We conclude that variable-pH elution from XAD does not isolate significantly strong (or weak) Cu(II)-binding components from the SRFA mixture. Copyright (C) 1999 Elsevier Science B.V.

  9. A specific binding site recognizing a fragment of angiotensin II in bovine adrenal cortex membranes.

    Science.gov (United States)

    Bernier, S G; Fournier, A; Guillemette, G

    1994-12-12

    We have characterized a specific binding site for angiotensin IV in bovine adrenal cortex membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.24 +/- 0.03 nM). The binding site is saturable and relatively abundant (maximal binding capacity around 0.5 pmol/mg protein). Non-equilibrium kinetic analyses at 37 degrees C revealed a calculated kinetic Kd of 47 pM. The binding site is pharmacologically distinct from the classic angiotensin receptors AT1 or AT2. Competitive binding studies with bovine adrenal cortex membranes demonstrated the following rank order of effectiveness: angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) = angiotensin II-(3-7) (Val-Tyr-Ile-His-Pro) > angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) > or = angiotensin II-(4-7) (Tyr-Ile-His-Pro) > angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) > angiotensin II-(1-6) (Asp-Arg-Val-Tyr-Ile-His) > angiotensin II-(4-8) (Tyr-Ile-His-Pro-Phe) > > > angiotensin II-(3-6) (Val-Tyr-Ile-His), angiotensin II-(4-6) (Tyr-Ile-His), L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'(1-H-tetrazol-5-yl)[1,1'-biphenyl]-4-y l) methyl]-3-H-imidazo[4,5-beta]pyridine H2O) and PD 123319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)4,5,6 ,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid). The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of 125I-angiotensioffn IV to bovine adrenal cortex membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. 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.

  11. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8(+) T cell-mediated protection...... against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4(+) T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute...

  13. Targeting the MHC Class II antigen presentation pathway in cancer immunotherapy.

    Science.gov (United States)

    Thibodeau, Jacques; Bourgeois-Daigneault, Marie-Claude; Lapointe, Réjean

    2012-09-01

    The success of immunotherapy relies on the participation of all arms of the immune system and the role of CD4+ T lymphocytes in preventing tumor growth is now well established. Understanding how tumors evade immune responses holds the key to the development of cancer immunotherapies. In this review, we discuss how MHC Class II expression varies in cancer cells and how this influences antitumor immune responses. We also discuss the means that are currently available for harnessing the MHC Class II antigen presentation pathway for the development of efficient vaccines to activate the immune system against cancer.

  14. HLA class II haplotypes distinctly associated with vaso-occlusion in children with sickle cell disease.

    Science.gov (United States)

    Mahdi, Najat; Al-Ola, Khadija; Al-Subaie, Abeer M; Ali, Muhallab E; Al-Irhayim, Zaid; Al-Irhayim, A Qader; Almawi, Wassim Y

    2008-04-01

    We investigated the association of HLA class II alleles and haplotypes with sickle cell anemia vaso-occlusive crisis (VOC). DRB1*100101 was positively associated, while DRB1*140101, DRB1*150101, and DQB1*060101 were negatively associated, with VOC. Both susceptible (DRB1*100101-DQB1*050101) and protective (DRB1*110101-DQB1*030101 and DRB1*150101-DQB1*060101) haplotypes were identified, indicating that HLA class II haplotypes influence VOC risk.

  15. Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic

    DEFF Research Database (Denmark)

    Andersen, M L M; Ruhwald, Morten; Nissen, M H;

    2003-01-01

    Thirty self-peptides were selected on the basis of their predicted binding to H-2b molecules. The binding of peptides was ascertained experimentally by biochemical (KD measurements) and cellular [major histocompatibility complex class I (MHC-I) stabilization] assays. A weak, but significant, corr...

  16. Domain structures and molecular evolution of class I and class II major histocompatibility gene complex (MHC) products deduced from amino acid and nucleotide sequence homologies.

    Science.gov (United States)

    Ohnishi, K

    1984-01-01

    Domain structures of class I and class II MHC products were analyzed from a viewpoint of amino acid and nucleotide sequence homologies. Alignment statistics revealed that class I (transplantation) antigen H chains consist of four mutually homologous domains, and that class II (HLA-DR) antigen beta and alpha chains are both composed of three mutually homologous ones. The N-terminal three and two domains of class I and class II (both beta and alpha) gene products, respectively, all of which being approximately 90 residues long, were concluded to be homologous to beta2-microglobulin (beta2M). The membrane-embedded C-terminal shorter domains of these MHC products were also found to be homologous to one another and to the third domain of class I H chains. Class I H chains were found to be more closely related to class II alpha chains than to class II beta chains. Based on these findings, an exon duplication history from a common ancestral gene encoding a beta2M-like primodial protein of one-domain-length up to the contemporary MHC products was proposed.

  17. Investigation of Cu(II) Binding to Bovine Serum Albumin by Potentiometry with an Ion Selective Electrode

    Science.gov (United States)

    Jie Liu

    2004-01-01

    A laboratory project that investigates Cu(II) bind to bovine serum albumin (BSA) in an aqueous solution is developed to assist undergraduate students in gaining better understanding of the interaction of ligands with biological macromolecule. Thus, students are introduced to investigation of Cu(II) binding to BSA by potentiometry with the Cu(II)…

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k-3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323......-339) immunodominant peptide to the I-Ad-restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3...

  19. 46 CFR 50.30-10 - Class I, I-L and II-L pressure vessels.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Class I, I-L and II-L pressure vessels. 50.30-10 Section... PROVISIONS Fabrication Inspection § 50.30-10 Class I, I-L and II-L pressure vessels. (a) Classes I, I-L and II-L pressure vessels shall be subject to shop inspection at the plant where they are...

  20. Spectral and thermodynamic properties of Ag(I), Au(III), Cd(II), Co(II), Fe(III), Hg(II), Mn(II), Ni(II), Pb(II), U(IV), and Zn(II) binding by methanobactin from Methylosinus trichosporium OB3b.

    Science.gov (United States)

    Choi, Dong W; Do, Young S; Zea, Corbin J; McEllistrem, Marcus T; Lee, Sung-W; Semrau, Jeremy D; Pohl, Nicola L; Kisting, Clint J; Scardino, Lori L; Hartsel, Scott C; Boyd, Eric S; Geesey, Gill G; Riedel, Theran P; Shafe, Peter H; Kranski, Kim A; Tritsch, John R; Antholine, William E; DiSpirito, Alan A

    2006-12-01

    Methanobactin (mb) is a novel chromopeptide that appears to function as the extracellular component of a copper acquisition system in methanotrophic bacteria. To examine this potential physiological role, and to distinguish it from iron binding siderophores, the spectral (UV-visible absorption, circular dichroism, fluorescence, and X-ray photoelectron) and thermodynamic properties of metal binding by mb were examined. In the absence of Cu(II) or Cu(I), mb will bind Ag(I), Au(III), Co(II), Cd(II), Fe(III), Hg(II), Mn(II), Ni(II), Pb(II), U(VI), or Zn(II), but not Ba(II), Ca(II), La(II), Mg(II), and Sr(II). The results suggest metals such as Ag(I), Au(III), Hg(II), Pb(II) and possibly U(VI) are bound by a mechanism similar to Cu, whereas the coordination of Co(II), Cd(II), Fe(III), Mn(II), Ni(II) and Zn(II) by mb differs from Cu(II). Consistent with its role as a copper-binding compound or chalkophore, the binding constants of all the metals examined were less than those observed with Cu(II) and copper displaced other metals except Ag(I) and Au(III) bound to mb. However, the binding of different metals by mb suggests that methanotrophic activity also may play a role in either the solubilization or immobilization of many metals in situ.

  1. Endo-S-c-di-GMP Analogues-Polymorphism and Binding Studies with Class I Riboswitch

    Directory of Open Access Journals (Sweden)

    Herman O. Sintim

    2012-11-01

    Full Text Available C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become drug leads for the development of anti-biofilm compounds. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogues, which have both phosphate and sugar moieties simultaneously modified (called endo-S-c-di-GMP analogues. We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the polymorphism of c-di-GMP can be tuned with conservative modifications to the phosphate and sugar moieties (conformational steering. Binding studies with Vc2 RNA (a class I c-di-GMP riboswitch revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class I riboswitch.

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

    OpenAIRE

    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...

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

    LENUS (Irish Health Repository)

    Mandall, Nicky A

    2010-03-01

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

  4. Crystallographic and Computational Studies of a Class II MHC Complex with a Nonconforming Peptide: HLA-DRA/DRB3*0101

    Science.gov (United States)

    Parry, Christian S.; Gorski, Jack; Stern, Lawrence J.

    2003-03-01

    The stable binding of processed foreign peptide to a class II major histocompatibility (MHC) molecule and subsequent presentation to a T cell receptor is a central event in immune recognition and regulation. Polymorphic residues on the floor of the peptide binding site form pockets that anchor peptide side chains. These and other residues in the helical wall of the groove determine the specificity of each allele and define a motif. Allele specific motifs allow the prediction of epitopes from the sequence of pathogens. There are, however, known epitopes that do not satisfy these motifs: anchor motifs are not adequate for predicting epitopes as there are apparently major and minor motifs. We present crystallographic studies into the nature of the interactions that govern the binding of these so called nonconforming peptides. We would like to understand the role of the P10 pocket and find out whether the peptides that do not obey the consensus anchor motif bind in the canonical conformation observed in in prior structures of class II MHC-peptide complexes. HLA-DRB3*0101 complexed with peptide crystallized in unit cell 92.10 x 92.10 x 248.30 (90, 90, 90), P41212, and the diffraction data is reliable to 2.2ÅWe are complementing our studies with dynamical long time simulations to answer these questions, particularly the interplay of the anchor motifs in peptide binding, the range of protein and ligand conformations, and water hydration structures.

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

    Science.gov (United States)

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

    2006-09-15

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

  6. Anti-cofactor autoantibodies in systemic lupus erythematosus: prevalence, clinical and HLA class II associations.

    Science.gov (United States)

    Sebastiani, Gian Domenico; Morozzi, Gabriella; Bellisai, Francesca; Fineschi, Irene; Bacarelli, Maria Romana; Simpatico, Antonella; Font, Josep; Cervera, Ricard; Houssiau, Frederic; Fernandez-Nebro, Antonio; De Ramon Garrido, Enrique; De Pità, Ornella; Smolen, Josef; Galeazzi, Mauro

    2008-01-01

    The aim of our study was to evaluate the clinical and HLA-class II allele associations of some anti-cofactor antibodies in a homogeneous group of European patients with SLE. One hundred thirty-six patients with SLE, fulfilling four or more of the ACR 1997 revised criteria for the classification of the disease, coming from 7 European countries, were enrolled consecutively. Anti-prothrombin (anti-PT), anti-annexin V (anti-AnnV), anti-protein C (anti-Cprot) and anti-protein S (anti-Sprot) were determined by using commercial ELISA kits. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 loci was performed by using PCR-SSOP method, carried out using digoxygenin (DIG) labeled probes. The prevalence of anti-AnnV, anti-PT, anti-Cprot and anti-Sprot was 19%, 10.4%, 4.4% and 8.1%, respectively. Twenty-seven % of anti-AnnV positive patients reported migraine vs 5.5% of anti-AnnV negatives (p = 0.003, but p not significant, odds ratio (OR) = 6.4, 95% confidence interval (CI) = 2-21). Anti-PT, anti-AnnV and anti-Sprot were positively associated with some HLA alleles, but pc was not significant. In this study we have shown that some HLA alleles carry the risk to produce antibodies against phospholipid-binding proteins, but these association need confirmation in other studies, because they have never been reported and appear to be weak associations.

  7. Characterization and Inhibition of a Class II Diterpene Cyclase from Mycobacterium tuberculosis

    Science.gov (United States)

    Mann, Francis M.; Prisic, Sladjana; Hu, Huayou; Xu, Meimei; Coates, Robert M.; Peters, Reuben J.

    2009-01-01

    Mycobacterium tuberculosis remains a widespread and devastating human pathogen, whose ability to infiltrate macrophage host cells from the human immune system is an active area of investigation. We have recently reported the discovery of a novel diterpene from M. tuberculosis, edaxadiene, whose ability to arrest phagosomal maturation in isolation presumably contributes to this critical process in M. tuberculosis infections. (Mann, F. M., Xu, M., Chen, X., Fulton, D. B., Russell, D. G., and Peters, R. J. (2009) J. Am. Chem. Soc., in press). Here, we present characterization of the class II diterpene cyclase that catalyzes the committed step in edaxadiene biosynthesis, i.e. the previously identified halimadienyl-diphosphate synthase (HPS; EC 5.5.1.16). Intriguingly, our kinetic analysis suggests a potential biochemical regulatory mechanism that triggers edaxadiene production upon phagosomal engulfment. Furthermore, we report characterization of potential HPS inhibitors: specifically, two related transition state analogs (15-aza-14,15-dihydrogeranylgeranyl diphosphate (7a) and 15-aza-14,15-dihydrogeranylgeranyl thiolodiphosphate (7b)) that exhibit very tight binding. Although arguably not suitable for clinical use, these nevertheless provide a basis for pharmaceutical design against this intriguing biosynthetic pathway. Finally, we provide evidence indicating that this pathway exists only in M. tuberculosis and is not functional in the closely related Mycobacterium bovis because of an inactivating frameshift in the HPS-encoding gene. Thus, we hypothesize that the inability to produce edaxadiene may be a contributing factor in the decreased infectivity and/or virulence of M. bovis relative to M. tuberculosis in humans. PMID:19574210

  8. GPS-MBA: computational analysis of MHC class II epitopes in type 1 diabetes.

    Science.gov (United States)

    Cai, Ruikun; Liu, Zexian; Ren, Jian; Ma, Chuang; Gao, Tianshun; Zhou, Yanhong; Yang, Qing; Xue, Yu

    2012-01-01

    As a severe chronic metabolic disease and autoimmune disorder, type 1 diabetes (T1D) affects millions of people world-wide. Recent advances in antigen-based immunotherapy have provided a great opportunity for further treating T1D with a high degree of selectivity. It is reported that MHC class II I-A(g7) in the non-obese diabetic (NOD) mouse and human HLA-DQ8 are strongly linked to susceptibility to T1D. Thus, the identification of new I-A(g7) and HLA-DQ8 epitopes would be of great help to further experimental and biomedical manipulation efforts. In this study, a novel GPS-MBA (MHC Binding Analyzer) software package was developed for the prediction of I-A(g7) and HLA-DQ8 epitopes. Using experimentally identified epitopes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted and improved. By extensive evaluation and comparison, the GPS-MBA performance was found to be much better than other tools of this type. With this powerful tool, we predicted a number of potentially new I-A(g7) and HLA-DQ8 epitopes. Furthermore, we designed a T1D epitope database (TEDB) for all of the experimentally identified and predicted T1D-associated epitopes. Taken together, this computational prediction result and analysis provides a starting point for further experimental considerations, and GPS-MBA is demonstrated to be a useful tool for generating starting information for experimentalists. The GPS-MBA is freely accessible for academic researchers at: http://mba.biocuckoo.org.

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

    Directory of Open Access Journals (Sweden)

    Kuszynski Charles

    2011-07-01

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

  10. Quantitative determination of angiotensin II binding sites in rat brain and pituitary gland by autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Israel, A.; Correa, F.M.A.; Niwa, M.; Saavedra, J.M. (National Inst. of Mental Health, Bethesda, MD (USA))

    1984-11-26

    Rat brain and pituitary angiotensin II (AII) binding sites were quantitated by incubation of tissue sections with /sup 125/I-(Sar/sup 1/) AII, Ultrofilm radioautography, computerized densitometry, and comparison with /sup 125/I-standards at appropriate film exposure times. The highest number of AII binding sites was found in anterior pituitary and the circumventricular organs, organon subfornicalis and organon vasculosum laminae terminalis.

  11. Triazolopyridyl ketones as a novel class of antileishmanial agents. DNA binding and BSA interaction.

    Science.gov (United States)

    Adam, Rosa; Bilbao-Ramos, Pablo; López-Molina, Sonia; Abarca, Belén; Ballesteros, Rafael; González-Rosende, M Eugenia; Dea-Ayuela, M Auxiliadora; Alzuet-Piña, Gloria

    2014-08-01

    A new series of triazolopyridyl pyridyl ketones has been synthetized by regioselective lithiation of the corresponding [1,2,3]triazolo[1,5-a]pyridine at 7 position followed by reaction with different electrophiles. The in vitro antileishmanial activity of these compounds was evaluated against Leishmaniainfantum, Leishmaniabraziliensis, Leishmaniaguyanensis and Leishmaniaamazonensis. Compounds 6 and 7 were found to be the most active leishmanicidal agents. Both of them showed activities at micromolar concentration against cultured promastigotes of Leishmania spp. (IC₅₀=99.8-26.8 μM), without cytotoxicity on J774 macrophage cells. These two compounds were also tested in vivo in a murine model of acute infection by L. infantum. The triazolopyridine derivative 6 was effective against both spleen and liver parasites forms, while 7 was inactive against liver parasites. Mechanistic aspects of the antileishmanial activity were investigated by means of DNA binding studies (UV-titration and viscosimetry). Results have revealed that these active ligands are able to interact strongly with DNA [Kb=1.14 × 10(5)M(-1) (6) and 3.26 × 10(5)M(-1) (7)]. Moreover, a DNA groove binding has been proposed for both 6 and 7. To provide more insight on the mode of action of compounds 6 and 7 under biological conditions, their interaction with bovine serum albumin (BSA) was monitored by fluorescence titrations and UV-visible spectroscopy. The quenching constants and binding parameters were determined. Triazolopyridine ketones 6 and 7 have exhibited significant affinity towards BSA [Kb=2.5 × 10(4)M(-1) (6) and 1.9 × 10(4)M(-1) (7)]. Finally, to identify the binding location of compounds 6 and 7 on the BSA, competitive binding experiments were carried out, using warfarin, a characteristic marker for site I, and ibuprofen as one for site II. Results derived from these studies have indicated that both compounds interact at BSA site I and, to a lesser extent, at site II.

  12. Extraction of maxillary first permanent molars in patients with Class II Division 1 malocclusion.

    NARCIS (Netherlands)

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

    2007-01-01

    INTRODUCTION: Our objectives were to assess treatment outcomes in Class II Division 1 patients who were treated orthodontically with extraction of the maxillary first permanent molars and to describe the changes in their facial profiles. METHODS: This was a prospective, longitudinal, 1-group outcome

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  14. 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

  15. 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

  16. 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)

  17. 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.

  18. 77 FR 58473 - Minimum Technical Standards for Class II Gaming Systems and Equipment

    Science.gov (United States)

    2012-09-21

    ... supported the NPRM's removal of language asserting that ``TGRAs also regulate Class II gaming,'' but... primary regulators of tribal gaming. Response: The Commission declines to insert the requested language... are eliminated from operation through attrition and/or market forces. One commenter noted...

  19. 78 FR 5800 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-01-28

    ... administrative order assessing a civil penalty against any person who has violated applicable emergency planning... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity... resolve violations of the Clean Water Act (CWA) and the Emergency Planning and Community Right-to-Know...

  20. 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.

  1. Influence of composite resin consistency and placement technique on proximal contact tightness of Class II restorations.

    NARCIS (Netherlands)

    Loomans, B.A.C.; Opdam, N.J.M.; Roeters, F.J.M.; Bronkhorst, E.M.; Plasschaert, A.J.M.

    2006-01-01

    PURPOSE: To investigate the influence of composite resin consistency and placement technique on proximal contact tightness of Class II composite resin restorations. MATERIALS AND METHODS: A manikin model (KaVo Dental) was used with an artificial first molar in which a standardized MO preparation was

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

    DEFF Research Database (Denmark)

    Morling, N; Friis, J; Fugger, L;

    1991-01-01

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

  3. 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.

  4. A Cephalometric Comparison of Twin Block and Bionator Appliances in Treatment of Class II Malocclusion

    Science.gov (United States)

    Ahmadian-Babaki, Fatemeh; Araghbidi-Kashani, S. Mehdi

    2017-01-01

    Background Class II malocclusion is one of the most common orthodontic problems. In cases of class II malocclusion with mandibular deficiency, functional appliances often are used with the intent of stimulating mandibular growth. Bionator and twin block are two of the more popular functional appliances. The aim of this study was to compare the treatment outcomes of these two appliances using cephalometric radiographs. Material and Methods Cephalometric radiographs of 33 patients who had class II division I malocclusion, before and after treatment were digitalized. The mean changes in twin block and bionator groups were compared using independent t test. Results Twin block and bionator showed no statistically significant differences in cephalometric parameters except for ANB, NA-Pog, Basal and Ar-Go-Me angles. Conclusions There were no statistically significant differences in dentoalveolar and mandibular position between twin block and bionator (p>0.1). Twin block was more efficient in inhibition of forward movement of maxilla (p<0.1). Key words:Functional, Class II malocclusion, Cephalometrics, Twin block, Bionator, Treatment. PMID:28149473

  5. 40 CFR 82.70 - Nonessential Class II products and exceptions.

    Science.gov (United States)

    2010-07-01

    ... limited to household, industrial, automotive and pesticide uses; (2) Except— (i) Medical devices listed in...; (iii) Lubricants, coatings or cleaning fluids used for aircraft maintenance, which contain class II... books, books with coated, dense or paper and tightly bound documents; (vii) Portable fire...

  6. Comparison of Activator-Headgear and Twin Block Treatment Approaches in Class II Division 1 Malocclusion

    Science.gov (United States)

    Mroz Tranesen, Kate; Birkeland, Kari; Katic, Visnja; Pavlic, Andrej; Vandevska-Radunovic, Vaska

    2017-01-01

    The purpose was to compare the treatment effects of functional appliances activator-headgear (AH) and Twin Block (TB) on skeletal, dental, and soft-tissue structures in class II division 1 malocclusion with normal growth changes in untreated subjects. The sample included 50 subjects (56% females) aged 8–13 years with class II division 1 malocclusion treated with either AH (n = 25) or TB (n = 25) appliances. Pre- and posttreatment lateral cephalograms were evaluated and compared to 50 untreated class II division 1 cases matched by age, gender, ANB angle, and skeletal maturity. A paired sample, independent samples tests and discriminant analysis were performed for intra- and intergroup analysis. Treatment with both appliances resulted in significant reduction of skeletal and soft-tissue facial convexity, the overjet, and the prominence of the upper lip in comparison to untreated individuals (p < 0.001). Retroclination of maxillary incisors and proclination of mandibular incisors were seen, the latter being significantly more evident in the TB group (p < 0.05). Increase of effective mandibular length was more pronounced in the TB group. In conclusion, both AH and TB appliances contributed successfully to the correction of class II division 1 malocclusion when compared to the untreated subjects with predominantly dentoalveolar changes. PMID:28203569

  7. [Features of the hormonal status in patients with temporomandibular joint dysfunction and class II malocclusion].

    Science.gov (United States)

    Gus, L A; Arsenina, O I; Komolov, I S

    2015-01-01

    The article presents data on androgen levels in female patients with temporomandibular joint (TMJ) dysfunction of varying degree and class II malocclusion. The study revealed significant correlation between degenerative and inflammatory TMJ changes and androgens level in patients with stigmas of connective tissue dysplasia (p<0.05), probably due to indirect proinflammatory action of androgens as they stimulate inflammatory mediators expression.

  8. 40 CFR 147.250 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... State of California, except those on Indian lands, is the program administered by the California... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class II wells. 147.250 Section 147.250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  11. Identification of the Minimal Copper(II)-binding α-Synuclein Sequence

    OpenAIRE

    Jackson, Mark S.; Lee, Jennifer C.

    2009-01-01

    Parkinson’s disease has been long linked to environmental factors, such as transition metals and recently to α-synuclein, a presynaptic protein. Using tryptophan-containing peptides, we identified the minimal Cu(II)-binding sequence to be within the first four residues, MDV(F/W), anchored by the α-amino terminus. In addition, mutant peptide 1–10 (Lys→Arg) verified that neither Lys6 or Lys10 are necessary for Cu(II) binding. Interestingly, Trp4 excited-state decay kinetics measured for peptide...

  12. Rationale for referring class II patients for early orthodontic treatment As razões para indicação de tratamento precoce em pacientes de classe II

    Directory of Open Access Journals (Sweden)

    José Augusto Mendes Miguel

    2005-09-01

    Full Text Available The tendency of indicating early treatment (before growth spurt when dealing with Angle Class II cases has been noticed, although there is no definite scientific evidence to justify such decision. The aim of this study was to identify the advantages and disadvantages to this approach and which appliances are used for this purpose. For that purpose, a questionnaire containing full records of a Class II patient was sent to two professors of each Orthodontic graduate program in Brazil (n=96, total 192, from which 107 were properly answered. Results demonstrated that the most used appliances were the headgear (80.4%, maxillary splint (50% and Bionator (44.4%. The benefits most often quoted were increase of patient self-esteem (78.5% and reduction in the incidence of incisors trauma (63.6%, while the main disadvantage was saturation of patient compliance (73.8%. Considering early Class II treatment, there is still no unanimity as to treating in one or two stages or in selection of appliances. However, the orthodontists should consider the physical situation of the patient, severity of cases and susceptibility of trauma to the maxillary incisors. It is crucial that updated information is given to parents, in order to justify this approach.A tendência de indicação de tratamento precoce (antes de surto de crescimento para casos de Classe II de Angle tem sido observada, embora não haja evidência científica para embasar tal decisão. O objetivo deste estudo foi identificar as vantagens e desvantagens da indicação e quais aparelhos são usados no tratamento. Foram enviados questionários (n=192 com a documentação completa de um paciente Classe II para dois professores de cada curso de especialização em Ortodontia no Brasil, os quais 107 foram respondidos. Os resultados demonstraram que os aparelhos mais usados foram: Extra-oral (80,4%, Thurow (50,0% e Bionator (44,4%. Foram citados como maiores vantagens: aumento de auto-estima do paciente (78

  13. 56-month clinical performance of Class I and II resin composite restorations

    Directory of Open Access Journals (Sweden)

    Flavia Bittencourt Pazinatto

    2012-06-01

    Full Text Available OBJECTIVE: This study evaluated the 56-month clinical performance of Class I and II resin composite restorations. Filtek P60 was compared with Filtek Z250, which are both indicated for posterior restorations but differ in terms of handling characteristics. The null hypothesis tested was that there is no difference in the clinical performance of the two resin composites in posterior teeth. MATERIAL AND METHODS: Thirty-three patients were treated by the same operator, who prepared 48 Class I and 42 Class II cavities, which were restored with Single Bond/Filtek Z250 or Single Bond/Filtek P60 restorative systems. Restorations were evaluated by two independent examiners at baseline and after 56 months, using the modified USPHS criteria. Data were analyzed statistically using Chi-square and Fisher's Exact tests (a=0.05. RESULTS: After 56 months, 25 patients (31 Class I and 36 Class II were analyzed. A 3% failure rate occurred due to secondary caries and excessive loss of anatomic form for P60. For both restorative systems, there were no significant differences in secondary caries and postoperative sensitivity. However, significant changes were observed with respect to anatomic form, marginal discoloration, and marginal adaptation. Significant decreases in surface texture were observed exclusively for the Z250 restorations. CONCLUSIONS: Both restorative systems can be used for posterior restorations and can be expected to perform well in the oral environment.

  14. Thermal Study of a Newly Synthesized Cu(II Complex Binding to Bovine β-Lactoglobulin

    Directory of Open Access Journals (Sweden)

    Adeleh Divsalar

    2013-01-01

    Full Text Available We have investigated the interactions between β-lactoglobulin, BLG, and new synthesized Cu(II complex (2,2′-dibipyridine Cu(II chloride using isothermal titration calorimetry (ITC methods at different temperatures of 298 and 310 K. The heats of BLG + Cu(II interactions are reported and analyzed in terms of the extended solvation theory for calculation of binding and thermodynamic parameters of the interaction. The results suggested that binding of Cu(II complex on BLG resulted in significant changes on the tertiary structure and conformation of protein via increasing of hydrophobicity and inducing partially unfolded structure in BLG which has a good agreement with the solvation parameters recovered by the extended solvation model suggesting destabilization of the protein.

  15. Binding of the Covalent Flavin Assembly Factor to the Flavoprotein Subunit of Complex II.

    Science.gov (United States)

    Maklashina, Elena; Rajagukguk, Sany; Starbird, Chrystal A; McDonald, W Hayes; Koganitsky, Anna; Eisenbach, Michael; Iverson, Tina M; Cecchini, Gary

    2016-02-05

    Escherichia coli harbors two highly conserved homologs of the essential mitochondrial respiratory complex II (succinate:ubiquinone oxidoreductase). Aerobically the bacterium synthesizes succinate:quinone reductase as part of its respiratory chain, whereas under microaerophilic conditions, the quinol:fumarate reductase can be utilized. All complex II enzymes harbor a covalently bound FAD co-factor that is essential for their ability to oxidize succinate. In eukaryotes and many bacteria, assembly of the covalent flavin linkage is facilitated by a small protein assembly factor, termed SdhE in E. coli. How SdhE assists with formation of the covalent flavin bond and how it binds the flavoprotein subunit of complex II remain unknown. Using photo-cross-linking, we report the interaction site between the flavoprotein of complex II and the SdhE assembly factor. These data indicate that SdhE binds to the flavoprotein between two independently folded domains and that this binding mode likely influences the interdomain orientation. In so doing, SdhE likely orients amino acid residues near the dicarboxylate and FAD binding site, which facilitates formation of the covalent flavin linkage. These studies identify how the conserved SdhE assembly factor and its homologs participate in complex II maturation.

  16. In vitro DNA binding studies of the sweetening agent saccharin and its copper(II) and zinc(II) complexes.

    Science.gov (United States)

    Icsel, Ceyda; Yilmaz, Veysel T

    2014-01-05

    The interactions of fish sperm DNA (FS-DNA) with the sodium salt of sweetener saccharin (sacH) and its copper and zinc complexes, namely [M(sac)2(H2O)4]·2H2O (M=Cu(II) or Zn(II)) were studied by using UV-Vis titration, fluorometric competition, thermal denaturation, viscosity and gel electrophoresis measurements. The intrinsic binding constants (Kb) obtained from absorption titrations were estimated to be 2.86 (±0.06)×10(4)M(-1) for Na(sac), 6.67 (±0.12)×10(4)M(-1) for Cu-sac and 4.01 (±0.08)×10(4)M(-1) for Zn-sac. The Cu-sac complex binds to FS-DNA via intercalation with a KA value of 50.12 (±0.22)×10(4)M(-1) as evidenced by competitive binding studies with ethidium bromide. Moreover, competition experiments with Hoechst 33258 are indicative of a groove binding mode of Na(sac) and Zn-sac with binding constants of 3.13 (±0.16)×10(4)M(-1) and 5.25 (±0.22)×10(4)M(-1), respectively. The spectroscopic measurements indicate a moderate DNA binding affinity of Na(sac) and its metal complexes. The suggested binding modes are further confirmed by the thermal denaturation and viscosity measurements. In addition, Cu-sac and Zn-sac show weak ability to damage to pBR322 supercoiled plasmid DNA.

  17. Treatment of Class II open bite in the mixed dentition with a removable functional appliance and headgear.

    Science.gov (United States)

    Ngan, P; Wilson, S; Florman, M; Wei, S H

    1992-05-01

    Early diagnosis of patients exhibiting open bites that are complicated by skeletal Class II and vertical growth problems can facilitate subsequent treatment. Eight patients with Class II skeletal open bite were treated with the high-pull activator appliance and compared to reasonably matched controls to determine the effects of the appliance. The high-pull activator was found to reduce forward growth of the maxilla and increase mandibular alveolar height, transforming the Class II molar relationship into a Class I molar relationship. The overjet and open bite were decreased, and, in addition, the appliance reduced the amount of forward and downward movement of the maxillary molars, providing vertical control of the maxilla during Class II orthopedic correction. These results demonstrated that open bite complicated by a Class II vertical growth pattern can be treated during the mixed dentition with favorable results by a combination of a removable functional appliance and high-pull headgear.

  18. 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......OBJECTIVES: It was the aim of the study to analyze by the FE method stresses generated in tooth and restoration by occlusal loading of Class I and Class II restorations of resin composite. On the basis of available information on the influence of the modulus of elasticity, the research hypothesis...

  19. Copper(II) binding to alpha-synuclein, the Parkinson's protein.

    Science.gov (United States)

    Lee, Jennifer C; Gray, Harry B; Winkler, Jay R

    2008-06-04

    Variations in tryptophan fluorescence intensities confirm that copper(II) interacts with alpha-synuclein, a protein implicated in Parkinson's disease. Trp4 fluorescence decay kinetics measured for the F4W protein show that Cu(II) binds tightly (Kd 100 nM) near the N-terminus at pH 7. Work on a F4W/H50S mutant indicates that a histidine imidazole is not a ligand in this high-affinity site.

  20. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    Science.gov (United States)

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-04

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters.

  1. Binding of kinetically inert metal ions to RNA: the case of platinum(II).

    Science.gov (United States)

    Chapman, Erich G; Hostetter, Alethia A; Osborn, Maire F; Miller, Amanda L; DeRose, Victoria J

    2011-01-01

    In this chapter several aspects of Pt(II) are highlighted that focus on the properties of Pt(II)-RNA adducts and the possibility that they influence RNA-based processes in cells. Cellular distribution of Pt(II) complexes results in significant platination of RNA, and localization studies find Pt(II) in the nucleus, nucleolus, and a distribution of other sites in cells. Treatment with Pt(II) compounds disrupts RNA-based processes including enzymatic processing, splicing, and translation, and this disruption may be indicative of structural changes to RNA or RNA-protein complexes. Several RNA-Pt(II) adducts have been characterized in vitro by biochemical and other methods. Evidence for Pt(II) binding in non-helical regions and for Pt(II) cross-linking of internal loops has been found. Although platinated sites have been identified, there currently exists very little in the way of detailed structural characterization of RNA-Pt(II) adducts. Some insight into the details of Pt(II) coordination to RNA, especially RNA helices, can be gained from DNA model systems. Many RNA structures, however, contain complex tertiary folds and common, purine-rich structural elements that present suitable Pt(II) nucleophiles in unique arrangements which may hold the potential for novel types of platinum-RNA adducts. Future research aimed at structural characterization of platinum-RNA adducts may provide further insights into platinum-nucleic acid binding motifs, and perhaps provide a rationale for the observed inhibition by Pt(II) complexes of splicing, translation, and enzymatic processing.

  2. Structural Basis of Differential Ligand Recognition by Two Classes of bis-(3-5)-cyclic Dimeric Guanosine Monophosphate-binding Riboswitches

    Energy Technology Data Exchange (ETDEWEB)

    K Smith; C Shanahan; E Moore; A Simon; S Strobel

    2011-12-31

    The bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) signaling pathway regulates biofilm formation, virulence, and other processes in many bacterial species and is critical for their survival. Two classes of c-di-GMP-binding riboswitches have been discovered that bind this second messenger with high affinity and regulate diverse downstream genes, underscoring the importance of RNA receptors in this pathway. We have solved the structure of a c-di-GMP-II riboswitch, which reveals that the ligand is bound as part of a triplex formed with a pseudoknot. The structure also shows that the guanine bases of c-di-GMP are recognized through noncanonical pairings and that the phosphodiester backbone is not contacted by the RNA. Recognition is quite different from that observed in the c-di-GMP-I riboswitch, demonstrating that at least two independent solutions for RNA second messenger binding have evolved. We exploited these differences to design a c-di-GMP analog that selectively binds the c-di-GMP-II aptamer over the c-di-GMP-I RNA. There are several bacterial species that contain both types of riboswitches, and this approach holds promise as an important tool for targeting one riboswitch, and thus one gene, over another in a selective fashion.

  3. Structure/Function/Dynamics of Photosystem II Plastoquinone Binding Sites

    Science.gov (United States)

    Lambreva, Maya D.; Russo, Daniela; Polticelli, Fabio; Scognamiglio, Viviana; Antonacci, Amina; Zobnina, Veranika; Campi, Gaetano; Rea, Giuseppina

    2014-01-01

    Photosystem II (PSII) continuously attracts the attention of researchers aiming to unravel the riddle of its functioning and efficiency fundamental for all life on Earth. Besides, an increasing number of biotechnological applications have been envisaged exploiting and mimicking the unique properties of this macromolecular pigment-protein complex. The PSII organization and working principles have inspired the design of electrochemical water splitting schemes and charge separating triads in energy storage systems as well as biochips and sensors for environmental, agricultural and industrial screening of toxic compounds. An intriguing opportunity is the development of sensor devices, exploiting native or manipulated PSII complexes or ad hoc synthesized polypeptides mimicking the PSII reaction centre proteins as bio-sensing elements. This review offers a concise overview of the recent improvements in the understanding of structure and function of PSII donor side, with focus on the interactions of the plastoquinone cofactors with the surrounding environment and operational features. Furthermore, studies focused on photosynthetic proteins structure/function/dynamics and computational analyses aimed at rational design of high-quality bio-recognition elements in biosensor devices are discussed. PMID:24678671

  4. 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

    from pathogens or cancer proteomes involve either reverse immunology or high-throughput mass spectrometry (HTMS). Reverse immunology approaches involve pre-screening of proteomes by computational algorithms, followed by experimental validation of selected targets ( [Mora et al., 2006], [De Groot et al......). 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......). Computational algorithms are essential steps in high-throughput identification of T-cell epitope candidates using both reverse immunology and HTMS approaches. Peptide binding to MHC molecules is the single most selective step in defining T cell epitope and the accuracy of computational algorithms for prediction...

  5. Insulin-like growth factor II: complexity of biosynthesis and receptor binding

    DEFF Research Database (Denmark)

    Gammeltoft, S; Christiansen, Jan; Nielsen, F C;

    1991-01-01

    Insulin-like growth factor II (IGF-II) belongs to the insulin family of peptides and acts as a growth factor in many fetal tissues and tumors. The gene expression of IGF-II is initiated at three different promoters which gives rise to multiple transcripts. In a human rhabdomyosarcoma cell line...... the 4.8-kb mRNA is translated to IGF-II. The cell line secretes two forms of immunoreactive and bioactive IGF-II to the medium of molecular size 10 kd and 7.5 kd which may be involved in autocrine control of cell growth. IGF-II binds to two receptors on the surface of many cell types: the IGF-I receptor...... and the mannose-6-phosphate (Man-6-P)/IGF-II receptor. There is consensus that the cellular effects of IGF-II are mediated by the IGF-I receptor via activation of its intrinsic tyrosine kinase. The Man-6-P/IGF-II receptor is involved in endocytosis of lysosomal enzymes and IGF-II. In selected cell types, however...

  6. The puzzle posed by COMMD1, a newly discovered protein binding Cu(II).

    Science.gov (United States)

    Sarkar, Bibudhendra; Roberts, Eve A

    2011-01-01

    Copper is critically important for cellular metabolism. It plays essential roles in developmental processes, including angiogenesis. The liver is central to mammalian copper homeostasis: biliary excretion is the major route of excretion for ingested copper and serves to regulate the total amount of copper in the organism. An extensive network of proteins manipulates copper disposition in hepatocytes, but comparatively little is known about this protein system. Copper exists in two oxidation states: most extracellular copper is Cu(II) and most, if not all, intracellular copper is Cu(I). Typical intracellular copper-binding proteins, such as the Cu-transporting P-type ATPases ATP7B (Wilson ATPase) and ATP7A (Menkes ATPase), bind copper as Cu(I). Accordingly, the recent discovery that the ubiquitous protein COMMD1 binds Cu(II) exclusively raises the question as to what role Cu(II) may play in intracellular processes. This issue is particularly important in the liver and brain. In humans, Wilson’s disease, due to mutations in ATP7B, exhibits progressive liver damage from copper accumulation; in some Bedlington terriers, mutations in COMMD1 are associated with chronic copper-overloaded liver disease, clinically distinct from Wilson’s disease. It seems unlikely that Cu(II), which generates reactive oxygen species through the Fenton reaction, has a physiological role intracellularly; however, Cu(II) might be the preferred state of copper for elimination from the cell, such as by biliary excretion. We argue that COMMD1 participates in the normal disposition of copper within the hepatocyte and we speculate about that role. COMMD1 may contribute to the mechanism of biliary excretion of copper by virtue of binding Cu(II). Additionally, or alternatively, COMMD1 may be an important component of an intracellular system for utilizing Cu(II), or for detecting and detoxifying it.

  7. Class II treatment by extraction of maxillary first molars or Herbst appliance: dentoskeletal and soft tissue effects in comparison

    NARCIS (Netherlands)

    Booij, J.W.; Goeke, J.; Bronkhorst, E.M.; Katsaros, C.; Ruf, S.

    2013-01-01

    AIM: To compare dentoskeletal and soft tissue treatment effects of two alternative Class II division 1 treatment modalities (maxillary first permanent molar extraction versus Herbst appliance). METHODS: One-hundred-fifty-four Class II division 1 patients that had either been treated with extractions

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  9. 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...

  10. 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

    tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  12. 75 FR 70271 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-17

    ... wound therapy into class II (special controls) under section 513(f)(2) of the Federal Food, Drug, and... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Non-Powered Suction Apparatus Device Intended for...

  13. 76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-04-14

    ... into class II (special controls) under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use;...

  14. Má oclusão Classe II, 2ª Divisão de Angle, com sobremordida acentuada Angle Class II, Division 2, malocclusion with deep overbite

    Directory of Open Access Journals (Sweden)

    Paulo Renato Carvalho Ribeiro

    2010-02-01

    Full Text Available Este relato de caso descreve o tratamento ortodôntico de uma paciente adulta, portadora de uma má oclusão Classe II, 2ª Divisão de Angle, com sobremordida e curva de Spee acentuadas e que apresentava vestibuloversão do dente 12 e algumas recessões gengivais. A paciente foi tratada com exodontia dos primeiros pré-molares superiores e máximo controle de ancoragem. Esse caso foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, representando a categoria 6, ou seja, uma má oclusão com sobremordida acentuada, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.This case report describes the orthodontic treatment of an adult patient, who presented a Angle Class II, Division 2, malocclusion, with overbite, severe curve of Spee, right maxillary lateral incisor proclined and gengival recessions. The patient was treated with extraction of the first premolars and maximum anchorage control. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO representing the category 6, deep overbite malocclusion, as part of the requirements for obtaining the title of Diplomate by BBO.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-09-18

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

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

    Directory of Open Access Journals (Sweden)

    Dirceu Barnabé Raveli

    2016-09-01

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

  17. Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules

    Science.gov (United States)

    Park, Yoon-Kyung; Jung, Sundo; Park, Se-Ho

    2016-01-01

    In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-Aq in a murine CIA model. We found that recombinant I-Aq/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-Aq/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis. [BMB Reports 2016; 49(6): 331-336 PMID:26779996

  18. Sculpting MHC class II-restricted self and non-self peptidome by the class I Ag-processing machinery and its impact on Th-cell responses.

    Science.gov (United States)

    Spencer, Charles T; Dragovic, Srdjan M; Conant, Stephanie B; Gray, Jennifer J; Zheng, Mu; Samir, Parimal; Niu, Xinnan; Moutaftsi, Magdalini; Van Kaer, Luc; Sette, Alessandro; Link, Andrew J; Joyce, Sebastian

    2013-05-01

    It is generally assumed that the MHC class I antigen (Ag)-processing (CAP) machinery - which supplies peptides for presentation by class I molecules - plays no role in class II-restricted presentation of cytoplasmic Ags. In striking contrast to this assumption, we previously reported that proteasome inhibition, TAP deficiency or ERAAP deficiency led to dramatically altered T helper (Th)-cell responses to allograft (HY) and microbial (Listeria monocytogenes) Ags. Herein, we tested whether altered Ag processing and presentation, altered CD4(+) T-cell repertoire, or both underlay the above finding. We found that TAP deficiency and ERAAP deficiency dramatically altered the quality of class II-associated self peptides suggesting that the CAP machinery impacts class II-restricted Ag processing and presentation. Consistent with altered self peptidomes, the CD4(+) T-cell receptor repertoire of mice deficient in the CAP machinery substantially differed from that of WT animals resulting in altered CD4(+) T-cell Ag recognition patterns. These data suggest that TAP and ERAAP sculpt the class II-restricted peptidome, impacting the CD4(+) T-cell repertoire, and ultimately altering Th-cell responses. Together with our previous findings, these data suggest multiple CAP machinery components sequester or degrade MHC class II-restricted epitopes that would otherwise be capable of eliciting functional Th-cell responses.

  19. A Class of Asymmetric Gapped Hamiltonians on Quantum Spin Chains and its Characterization II

    Science.gov (United States)

    Ogata, Yoshiko

    2016-06-01

    We give a characterization of the class of gapped Hamiltonians introduced in Part I (Ogata, A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015). The Hamiltonians in this class are given as MPS (Matrix product state) Hamiltonians. In Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), we list up properties of ground state structures of Hamiltonians in this class. In this Part II, we show the converse. Namely, if a (not necessarily MPS) Hamiltonian H satisfies five of the listed properties, there is a Hamiltonian H' from the class by Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), satisfying the following: The ground state spaces of the two Hamiltonians on the infinite interval coincide. The spectral projections onto the ground state space of H on each finite intervals are approximated by that of H' exponentially well, with respect to the interval size. The latter property has an application to the classification problem with open boundary conditions.

  20. A Class of Asymmetric Gapped Hamiltonians on Quantum Spin Chains and its Characterization II

    Science.gov (United States)

    Ogata, Yoshiko

    2016-12-01

    We give a characterization of the class of gapped Hamiltonians introduced in Part I (Ogata, A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015). The Hamiltonians in this class are given as MPS (Matrix product state) Hamiltonians. In Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), we list up properties of ground state structures of Hamiltonians in this class. In this Part II, we show the converse. Namely, if a (not necessarily MPS) Hamiltonian H satisfies five of the listed properties, there is a Hamiltonian H' from the class by Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), satisfying the following: The ground state spaces of the two Hamiltonians on the infinite interval coincide. The spectral projections onto the ground state space of H on each finite intervals are approximated by that of H' exponentially well, with respect to the interval size. The latter property has an application to the classification problem with open boundary conditions.

  1. Extracellular polymeric substances for Zn (II) binding during its sorption process onto aerobic granular sludge.

    Science.gov (United States)

    Wei, Dong; Li, Mengting; Wang, Xiaodong; Han, Fei; Li, Lusheng; Guo, Jie; Ai, Lijie; Fang, Lulu; Liu, Ling; Du, Bin; Wei, Qin

    2016-01-15

    The aim of this study was to evaluate the interaction between extracellular polymeric substances (EPS) and Zn (II) during the sorption process of Zn (II) onto aerobic granular sludge. Batch results showed that the adsorption rate of Zn (II) onto aerobic granular sludge was better fitted with pseudo-second order kinetics model, and the adsorption isotherm data agreed well with Freundlich equation. Extracellular polymeric substances (EPS) for Zn (II) binding during sorption process was investigated by using a combination of three-dimensional excitation-emission matrix (3D-EEM), synchronous fluorescence spectra, two-dimensional correlation spectroscopy (2D-COS) and Fourier transform infrared spectroscopy (FTIR). Results implied that the main composes of EPS, including polysaccharide (PS) and protein (PN), decreased from 5.92±0.13 and 23.55±0.76 mg/g SS to 4.11±0.09 and 9.55±0.68 mg/g SS after the addition of different doses of Zn (II). 3D-EEM showed that the intensities of PN-like substances and humic-like substances were obviously decreased during the sorption process. According to synchronous fluorescence spectra, the quenching mechanism between PN-like substances and Zn (II) was mainly caused by a static quenching process. Additionally, 2D-COS indicated that PN-like substances were more susceptible to Zn (II) binding than humic-like substances. It was also found that the main functional groups for complexation of Zn (II) and EPS were OH groups, N-H groups and C=O stretching vibration. The findings of this study are significant to reveal the fate of heavy metal during its sorption process onto aerobic granular sludge through EPS binding, and provide useful information on the interaction between EPS and heavy metal.

  2. 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

  3. 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...

  4. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development

    DEFF Research Database (Denmark)

    Nielsen, J; Christiansen, J; Lykke-Andersen, J;

    1999-01-01

    Insulin-like growth factor II (IGF-II) is a major fetal growth factor. The IGF-II gene generates multiple mRNAs with different 5' untranslated regions (5' UTRs) that are translated in a differential manner during development. We have identified a human family of three IGF-II mRNA-binding proteins.......5 followed by a decline towards birth, and, similar to IGF-II, IMPs are especially expressed in developing epithelia, muscle, and placenta in both mouse and human embryos. The results imply that cytoplasmic 5' UTR-binding proteins control IGF-II biosynthesis during late mammalian development....

  5. CCD surface photometry of radio galaxies: Pt. 1. FR class I and II sources

    Energy Technology Data Exchange (ETDEWEB)

    Owen, F.N.; Laing, R.A.

    1989-05-01

    CCD surface photometry of 47 radio galaxies in the R-band is reported. The goal of the programme is to study the relationship of the properties of the parent galaxies to the radio structure and, in particular, to look for differences between Fanaroff and Riley (FR) class I and II sources. In order to clarify some ambiguous cases in the FR classification, we define Classical Double, Twin Jet and Fat Double sources. We describe our definitions of these three classes and their relation to the FR classification. (author).

  6. Degradation, Promoter Recruitment and Transactivation Mediated by the Extreme N-Terminus of MHC Class II Transactivator CIITA Isoform III.

    Directory of Open Access Journals (Sweden)

    Yves B Beaulieu

    Full Text Available Multiple relationships between ubiquitin-proteasome mediated protein turnover and transcriptional activation have been well documented, but the underlying mechanisms are still poorly understood. One way to induce degradation is via ubiquitination of the N-terminal α-amino group of proteins. The major histocompatibility complex (MHC class II transactivator CIITA is the master regulator of MHC class II gene expression and we found earlier that CIITA is a short-lived protein. Using stable and transient transfections of different CIITA constructs into HEK-293 and HeLa cell lines, we show here that the extreme N-terminal end of CIITA isoform III induces both rapid degradation and transactivation. It is essential that this sequence resides at the N-terminal end of the protein since blocking of the N-terminal end with an epitope-tag stabilizes the protein and reduces transactivation potential. The first ten amino acids of CIITA isoform III act as a portable degron and transactivation sequence when transferred as N-terminal extension to truncated CIITA constructs and are also able to destabilize a heterologous protein. The same is observed with the N-terminal ends of several known N-terminal ubiquitination substrates, such as Id2, Cdt1 and MyoD. Arginine and proline residues within the N-terminal ends contribute to rapid turnover. The N-terminal end of CIITA isoform III is responsible for efficient in vivo recruitment to the HLA-DRA promoter and increased interaction with components of the transcription machinery, such as TBP, p300, p400/Domino, the 19S ATPase S8, and the MHC-II promoter binding complex RFX. These experiments reveal a novel function of free N-terminal ends of proteins in degradation-dependent transcriptional activation.

  7. Quantitative predictions of peptide binding to MHC class I molecules using specificity matrices and anchor-stratified calibrations

    DEFF Research Database (Denmark)

    Lauemøller, S L; Holm, A; Hilden, J;

    2001-01-01

    predictions, we have measured the MHC class I binding of a large number of peptides. In an attempt to further improve predictions and to include sequence dependency, we subdivided the panel of peptides according to whether the peptides had zero, one or two primary anchor residues. This allowed us to define......Peptides are key immune targets. They are generated by fragmentation of antigenic proteins, selected by major histocompatibility complex (MHC) molecules and subsequently presented to T cells. One of the most selective requirements is that of peptide binding to MHC. Accurate descriptions...... and predictions of peptide-MHC interactions are therefore important. Quantitative matrices representing MHC class I specificity can be used to search any query protein for the presence of MHC binding peptides. Assuming that each peptide residue contributes to binding in an additive and sequence independent manner...

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

    Science.gov (United States)

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

    2007-11-10

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

  9. A Unique Cause of Proteinuria in Pregnancy: Class II Lupus Nephritis with Concomitant Minimal Change Disease

    Science.gov (United States)

    Kunjal, Ryan; Adam-Eldien, Rabie; Makary, Raafat; Jo-Hoy, Francois; Heilig, Charles W.

    2016-01-01

    We report the case of a 22-year-old African American female who presented to another facility for routine follow-up in the 34th week of pregnancy with lower extremity swelling and nephrotic-range proteinuria. Although she was normotensive, it was initially thought that she had preeclampsia. She was monitored carefully and delivery was induced at 37 weeks of gestation. She was transferred to our hospital, where she was diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria. Renal biopsy revealed a surprising finding of minimal change disease (MCD) concomitant with class II lupus nephritis (LN). She was managed with pulses and then tapering doses of steroid therapy with dramatic resolution of the nephrotic syndrome. This case demonstrates not only the rare de novo occurrence of SLE in pregnancy, but the unique finding of MCD coexisting with class II LN. We propose that altered T cell activity may be the link between these seemingly distinct entities.

  10. Simvastatin inhibits interferon-γ-induced MHC class II up-regulation in cultured astrocytes

    Directory of Open Access Journals (Sweden)

    Glazenburg Lisa

    2006-07-01

    Full Text Available Abstract Based on their potent anti-inflammatory properties and a preliminary clinical trial, statins (HMG-CoA reductase inhibitors are being studied as possible candidates for multiple sclerosis (MS therapy. The pathogenesis of MS is unclear. One theory suggests that the development of autoimmune lesions in the central nervous system may be due to a failure of endogenous inhibitory control of MHC class II expression on astrocytes, allowing these cells to adapt an interferon (IFN-γ-induced antigen presenting phenotype. By using immunocytochemistry in cultured astrocytes derived from newborn Wistar rats we found that simvastatin at nanomolar concentrations inhibited, in a dose-response fashion, up to 70% of IFN-γ-induced MHC class II expression. This effect was reversed by the HMG-CoA reductase product mevalonate. Suppression of the antigen presenting function of astrocytes might contribute to the beneficial effects of statins in MS.

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

    Directory of Open Access Journals (Sweden)

    Habib Ollah Ghanbari

    2014-06-01

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

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

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    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.

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

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    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.

  14. Target recognition, resistance, immunity and genome mining of class II bacteriocins from Gram-positive bacteria.

    Science.gov (United States)

    Kjos, Morten; Borrero, Juan; Opsata, Mona; Birri, Dagim J; Holo, Helge; Cintas, Luis M; Snipen, Lars; Hernández, Pablo E; Nes, Ingolf F; Diep, Dzung B

    2011-12-01

    Due to their very potent antimicrobial activity against diverse food-spoiling bacteria and pathogens and their favourable biochemical properties, peptide bacteriocins from Gram-positive bacteria have long been considered promising for applications in food preservation or medical treatment. To take advantage of bacteriocins in different applications, it is crucial to have detailed knowledge on the molecular mechanisms by which these peptides recognize and kill target cells, how producer cells protect themselves from their own bacteriocin (self-immunity) and how target cells may develop resistance. In this review we discuss some important recent progress in these areas for the non-lantibiotic (class II) bacteriocins. We also discuss some examples of how the current wealth of genome sequences provides an invaluable source in the search for novel class II bacteriocins.

  15. 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.

  16. Binding and activation of halocarbons by iron(II) and ruthenium(II)

    Energy Technology Data Exchange (ETDEWEB)

    Kulawiec, R.J.; Faller, J.W.; Crabtree, R.H. (Yale Univ., New Haven, CT (USA))

    1990-03-01

    A series of cyclopentadienylruthenium(II) and -iron(II) complexes contain intact iodoalkanes, p-iodotoluene, or chelating (P, X) (o-halophenyl)diphenylphosphine (X = Cl, Br) ligands. The halocarbons coordinate via {sigma}-donation of a halogen lone pair and retain their carbon-halogen bonds. The complexes are synthesized from the halocarbon, metal halide, and silver(I) ion. Full characterization shows that they are Ru(II) complexes of intact halocarbons rather than Ru(IV) products of oxidative addition. The crystal and molecular structure of one such complex, (Cp(CO)(PPh{sub 3})Ru(IC{sub 6}H{sub 4}-p-CH{sub 3}))PF{sub 6}, is reported (P{bar 1}, a = 10.976 (3) {angstrom}, b = 11.329 (3) {angstrom}, c = 13.666 (4) {angstrom}, {beta} = 102.62 (3){degree}, Z = 2, R{sub 1} = 0.054, R{sub 2} = 0.065).

  17. Preventing postoperative tooth sensitivity in class I, II and V restorations.

    Science.gov (United States)

    Christensen, Gordon J

    2002-02-01

    Postoperative tooth sensitivity in Class I, II and V resin-based composite restorations continues to be an unpredictable problem in dentistry. In spite of meticulous use of dentin bonding agents, dentists and patients are faced with the sensitivity problem and the frustrating need to remove restorations and occasionally accomplish endodontic therapy on teeth that were not sensitive before the restorations were placed. Practitioners have developed numerous preventive methods to overcome the sensitivity challenge, which I have described in this article.

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

    OpenAIRE

    J. W. Booij; Christos Livas

    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.

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

    Directory of Open Access Journals (Sweden)

    J. W. Booij

    2016-01-01

    Full Text Available 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.

  20. Class II, Division 1 Angle malocclusion with severe proclination of maxillary incisors

    Directory of Open Access Journals (Sweden)

    Kátia Montanha

    2016-02-01

    Full Text Available Protrusion of maxillary incisors is a common complaint among patients seeking orthodontic treatment. This report addresses the correction of Class II Angle malocclusion with excessively bucally proclined maxillary incisors, in an adolescent female patient, through the use of extraoral and fixed appliances. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as part of the requirements for obtaining the title of certified by the BBO.

  1. Treatment of a Class II division 1 anterior open bite malocclusion.

    Science.gov (United States)

    Ong, H B

    2001-06-01

    A case report of an 11-year-old Caucasian female who presented with a Class II div I anterior open bite malocclusion. Overjet is 6 mm and the anterior open bite 2 mm. There was a history of digit sucking till she was eight years old. She was successfully treated by non-extraction with pre-adjusted Edgewise appliances and high-pull headgear for a period of 27 months.

  2. Class II transactivator (CIITA enhances cytoplasmic processing of HIV-1 Pr55Gag.

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    Kristen A Porter

    Full Text Available BACKGROUND: The Pr55(gag (Gag polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs. In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol (Gag-Pol levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.

  3. Anteroposterior and vertical changes in skeletal class II patients treated with modified Thurow appliance.

    Science.gov (United States)

    Pithon, Matheus Melo; dos Santos, Rogério Lacerda; Sampaio, Gêisa Aiane de Morais; de Meneses, Izaura Helena Chaves; Coqueiro, Raildo Silva

    2014-01-01

    The aim of this study was to evaluate the post-treatment anteroposterior and vertical alterations in skeletal Class II malocclusion with different maxillary patterns in patients treated with modified Thurow appliance. Forty-five patients (22 girls and 23 boys) with skeletal Class II and angle SN.GoGn ≤ 35 and different maxillary patterns (n = 15), as follows: retrusive (SNA84°) maxilla; mean age 9 years at pre-treatment (T1) and 9 years and 10 months at post-treatment (T2), were treated with modified Thurow cervical traction appliance, with expander screw and extraoral face bow with 10° to 20° fold in relation to the intraoral arch. Force of 500 gf was applied and use for 12 to 14 h/day, with fortnightly adjustments. Analysis of variance ANOVA followed by post-hoc Tukey and Kruskal-Wallis test, followed by Mann-Whitney were used (α = 5%). In changes obtained from stage T1 to T2, no statistically significant differences were found among the groups Protrusive, normal and retrusive maxilla for the variables SNB, SN.GoGn, 1.NA, overjet, overbite and Class II discrepancy (right and left) (p>0.05). Angular measurements SNA and ANB in the protrusive maxilla group were significantly greater than in the normal and retrusive maxilla groups (p0.05). Within the limits of this study, it may be concluded that the modified Thurow cervical traction appliance was efficient for the correction of skeletal Class II irrespective of the maxillary pattern. The mandible had no significant rotation during treatment.

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

    OpenAIRE

    Kuszynski Charles; Gangaplara Arunakumar; Upadhyaya Bijaya; Massilamany Chandirasegaran; Reddy Jay

    2011-01-01

    Abstract Background Tetramers are useful tools to enumerate the frequencies of antigen-specific T cells. However, unlike CD8 T cells, CD4 T cells - especially self-reactive cells - are challenging to detect with major histocompatibility complex (MHC) class II tetramers because of low frequencies and low affinities of their T cell receptors to MHC-peptide complexes. Here, we report the use of fluorescent multimers, designated MHC dextramers that contain a large number of peptide-MHC complexes ...

  5. Synthesis, Characterization and DNA-Binding Properties of The Novel Mononuclear Zn(II, Cd(II, and Mn(II Complexes with Pantoprazole.

    Directory of Open Access Journals (Sweden)

    Wessam N. El-Sayed

    2016-04-01

    Full Text Available A   novel   mononuclear   Mn(II,   Zn(II   and   Cd(II   complexes of pantoprazole   (PA   was synthesized  and characterized  by elemental analysis,  molar conductivity,  magnetic susceptibility   measurements,   IR,  UV-visible  spectral  studies,  and  thermal  analysis.  The electronic spectra along with magnetic data suggest octahedral geometry for Mn(II, Zn(II and Cd(II complexes.  PA acts as an anionic bi-dentate ligand being coordinated by (S=O oxygen and benzimdazolyl nitrogen atoms. The interaction of the complexes with calf thymus DNA (CT-DNA was monitored by blue shift and hyperchromism in the UV-vis spectra. The observed  intrinsic  binding  constants  together  with  structural  analysis  of  the  complexes indicate  the groove  binding. The binding constants were determined at 303°K, 308°K and 313°K.  A thermodynamic analysis showed that the reaction is spontaneous with ΔG being negative. The enthalpy ΔH and the entropy ΔS of reactions were all determined.

  6. HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations.

    Science.gov (United States)

    Fort, M; de Stefano, G F; Cambon-Thomsen, A; Giraldo-Alvarez, P; Dugoujon, J M; Ohayon, E; Scano, G; Abbal, M

    1998-04-01

    HLA class II alleles were identified in 181 healthy unrelated Ethiopian children of both sexes and in 350 European controls from the South of France. The Ethiopian individuals belonged to the two major ethnic groups of the country: Oromo (N=83) and Amhara (N=98). In both panels, genetic polymorphism of HLA class II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and DQB1 loci. Allelic and phenotypic frequencies were compared with those of European controls and other African populations. Construction of HLA class II three-locus haplotypes was also performed. The study revealed some differences between the two groups. Characteristic features of Central and North African populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11 presented one of the lowest gene frequencies in both Ethiopian ethnic groups in contrast to Europeans and West Africans. Furthermore, this decrease was more marked than those observed using serological techniques in other geographically close East African countries. Oromo and Amhara only showed minor differences in spite of their different origins and histories. One significant difference consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West African people. Some new or rare haplotypes were also observed in the Oromo group. Our results underline the distinctive features of the Ethiopian populations among the few HLA genotyping data available for East African groups and emphasise the major interest of such investigations in this region of Africa.

  7. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series.

    Science.gov (United States)

    Verma, Pushpendra Kumar; Srivastava, Ruchi; Gupta, K K; Chaturvedi, T P

    2013-09-01

    Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR), root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  8. Cephalometric changes in Class II division 1 patients treated with two maxillary premolars extraction

    Directory of Open Access Journals (Sweden)

    Marisana Piano Seben

    2013-08-01

    Full Text Available OBJECTIVE: The purpose of this study was to evaluate the cephalometric alterations in patients with Angle Class II division 1 malocclusion, orthodontically treated with extraction of two maxillary premolars. METHODS: The sample comprised 68 initial and final lateral cephalograms of 34 patients of both gender (mean initial age of 14.03 years and mean final age of 17.25 years, treated with full fixed appliances and extraction of the first maxillary premolars. In order to evaluate the alterations due the treatment between initial and final phases, the dependent t test was applied to the studied cephalometric variables. RESULTS: The dentoskeletal alterations due to extraction of two maxillary premolars in the Class II division 1 malocclusion were: maxillary retrusion, improvement of the maxillomandibular relation, increase of lower anterior face height, retrusion of the maxillary incisors, buccal inclination, protrusion and extrusion of the mandibular incisors, besides the reduction of overjet and overbite. The tissue alterations showed decrease of the facial convexity and retrusion of the upper lip. CONCLUSIONS: The extraction of two maxillary premolars in Class II division 1 malocclusion promotes dentoskeletal and tissue alterations that contribute to an improvement of the relation between the bone bases and the soft tissue profile.

  9. Class II malocclusion treatment using high-pull headgear with a splint: a systematic review

    Directory of Open Access Journals (Sweden)

    Helder B. Jacob

    2013-04-01

    Full Text Available OBJECTIVE: To systematically review the scientific evidence pertaining to the effectiveness of high-pull headgear in growing Class II subjects. METHODS: A literature survey was performed by electronic database search. The survey covered the period from January 1966 to December 2008 and used Medical Subject Headings (MeSH. Articles were initially selected based on their titles and abstracts; the full articles were then retrieved. The inclusion criteria included growing subjects between 8 to 15 years of age, Class II malocclusion treatment with high-pull headgear, and a control group with Class II malocclusion. References from selected articles were hand-searched for additional publications. Selected studies were evaluated methodologically. RESULTS: Four articles were selected; none were randomized controlled trials. All of the articles clearly formulated their objectives and used appropriate measures. The studies showed that high-pull headgear treatment improves skeletal and dental relationship, distal displacement of the maxilla, vertical eruption control and upper molars distalization. One of the studies showed a slight clockwise rotation of the palatal plane; the others showed no significant treatment effect. The mandible was not affected by the treatment. CONCLUSION: While there is still a lack of strong evidence demonstrating the effects of high-pull headgear with a splint, other studies indicate that the AP relations improve due to distalization of the maxilla and upper molars, with little or no treatment effects in the mandible. Greater attention to the design should be given to improve the quality of such trials.

  10. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2013-01-01

    Full Text Available Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR, root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  11. Treatment timing of MARA and fixed appliance therapy of Class II malocclusion.

    Science.gov (United States)

    Ghislanzoni, Luis Tomas Huanca; Baccetti, Tiziano; Toll, Douglas; Defraia, Efisio; McNamara, James A; Franchi, Lorenzo

    2013-06-01

    The objective of this study is to evaluate the effect of timing on Mandibular Anterior Repositioning Appliance (MARA) and fixed appliance treatment of Class II malocclusion in a prospective clinical trial. The treated sample consisted of 51 consecutively treated patients at prepubertal (n = 21), pubertal (n = 15), and postpubertal (n = 15) stages of development. Control groups for the three treated groups were generated from growth data of untreated Class II subjects. Lateral cephalograms were digitized and superimposed via cephalometric software at T1 (pre-treatment) and T2 (after comprehensive treatment). The T1-T2 changes in the treated groups were compared to those in their corresponding control groups with Mann-Whitney tests with Bonferroni correction. Mandibular elongation was greater at the pubertal stage (Co-Gn +2.6 mm, with respect to controls). Headgear effect on the maxilla was greater in the pre-peak sample (Co-A -1.9 mm, with respect to controls). Dentoalveolar compensations (proclination of lower incisors, extrusion and mesialization of lower molars, and reduction in the overbite) were significant in the pre-peak and post-peak groups. Optimal timing for Class II treatment with MARA appliance is at the pubertal growth spurt, with enhanced mandibular skeletal changes and minimal dentoalveolar compensations.

  12. The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.

    Science.gov (United States)

    Andersson, Lisa S; Swinburne, June E; Meadows, Jennifer R S; Broström, Hans; Eriksson, Susanne; Fikse, W Freddy; Frey, Rebecka; Sundquist, Marie; Tseng, Chia T; Mikko, Sofia; Lindgren, Gabriella

    2012-03-01

    Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p (raw) = 2.34 × 10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.

  13. Metal-ion dependent catalytic properties of Sulfolobus solfataricus class II α-mannosidase

    DEFF Research Database (Denmark)

    Nielsen, Jonas Willum; Poulsen, Nina Rødtness; Johnsson, Anna Margit Susanne;

    2012-01-01

    The active site for the family GH38 class II α-mannosidase is constituted in part by a divalent metal ion, mostly Zn(2+), as revealed in the crystal structures of enzymes from both animal and bacterial sources. The metal ion coordinates to the bound substrate and side chains of conserved amino acid...... residues. Recently, evidence has accumulated that class II α-mannosidase is active in complex with a range of divalent metal ions. In the present work, with employment of the class II α-mannosidase, ManA, from the hyperthermophilic archaeon Sulfolobus solfataricus, we explored the influence of the divalent...... metal ion on the associated steady-state kinetic parameters, K(M) and k(cat), for various substrates. With p-nitrophenyl-α-d-mannoside as a substrate, the enzyme showed activity in the presence of Co(2+), Cd(2+), Mn(2+), and Zn(2+), whereas Ni(2+) and Cu(2+) were inhibitory and nonactivating. Co(2...

  14. Variation in Class II malocclusion: comparison of Mexican mestizos and American whites.

    Science.gov (United States)

    Phelan, Tom; Buschang, Peter H; Behrents, Rolf G; Wintergerst, Ana M; Ceen, Richard F; Hernandez, Angeles

    2004-04-01

    This study compared the skeletal and dental characteristics of Class II Division 1 white Americans and Mexicans. It was designed specifically to the evaluate ethnic, age, and sex differences of 101 whites and 107 Mexican mestizos, with approximately equal numbers in each subgroup. Three-way analyses of variance were used to simultaneously evaluate the effects of age, sex, ethnicity, and their interactions. Although Mexicans and whites in the United States had similar maxillomandibular relationships, Mexicans showed greater protrusion of the jaws and teeth. Mexican subjects with Class II malocclusions also showed less divergence of the cranial base (SN-FH angle) and greater vertical tendencies (MPA, Y-axis, and palatal plane angle) than their white counterparts. In comparison with children (mean age 9.0 years), young adults (mean age 20.1 years) had significantly larger craniofacial dimensions, jaws that were positioned more forward, and teeth that were more protruded. Sex differences pertained only to size (men were larger) and maxillary incisor angulation (men were more protrusive). The findings pertaining to the ethnic differences have important clinical implications regarding treatment decisions for Mexican and white patients. In addition, this study provides a foundation for future studies pertaining to Class II malocclusion in Mexicans.

  15. Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells.

    Science.gov (United States)

    Herouet, C; Cottin, M; LeClaire, J; Enk, A; Rousset, F

    2000-01-01

    Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.

  16. DNA binding, DNA cleavage, and cytotoxicity studies of two new copper (II) complexes.

    Science.gov (United States)

    Kashanian, Soheila; Khodaei, Mohammad Mehdi; Roshanfekr, Hamideh; Shahabadi, Nahid; Rezvani, Alireza; Mansouri, Ghobad

    2011-05-01

    The DNA binding behavior of [Cu(phen)(phen-dione)Cl]Cl (1) and [Cu(bpy)(phen-dione)Cl]Cl (2) was studied with a series of techniques including UV-vis absorption, circular dichroism spectroscopy, and viscometric methods. Cytotoxicity effect and DNA unwinding properties were also investigated. The results indicate that the Cu(II) complexes interact with calf-thymus DNA by both partially intercalative and hydrogen binding. These findings have been further substantiated by the determination of intrinsic binding constants spectrophotometrically, 12.5 × 10(5) and 5 × 10(5) for 1 and 2, respectively. Our findings suggest that the type of ligands and structure of complexes have marked effect on the binding affinity of complexes involving CT-DNA. Circular dichroism results show that complex 1 causes considerable increase in base stacking of DNA, whereas 2 decreases the base stacking, which is related to more extended aromatic area of 1,10-phenanthroline in 1 rather than bipyridine in 2. Slow decrease in DNA viscosity indicates partially intercalative binding in addition to hydrogen binding on the surface of DNA. The second binding mode was also confirmed by additional tests: interaction in denaturation condition and acidic pH. Also, these new complexes induced cleavage in pUC18 plasmid DNA as indicated in gel electrophoresis and showed excellent antitumor activity against K562 (human chronic myeloid leukemia) cells.

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

    DEFF Research Database (Denmark)

    McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany

    2016-01-01

    N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate...... cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen derived peptides maintain a canonical...

  18. Binding mode analyses and pharmacophore model development for stilbene derivatives as a novel and competitive class of α-glucosidase inhibitors.

    Science.gov (United States)

    Lee, Yuno; Kim, Songmi; Kim, Jun Young; Arooj, Mahreen; Kim, Siu; Hwang, Swan; Kim, Byeong-Woo; Park, Ki Hun; Lee, Keun Woo

    2014-01-01

    Stilbene urea derivatives as a novel and competitive class of non-glycosidic α-glucosidase inhibitors are effective for the treatment of type II diabetes and obesity. The main purposes of our molecular modeling study are to explore the most suitable binding poses of stilbene derivatives with analyzing the binding affinity differences and finally to develop a pharmacophore model which would represents critical features responsible for α-glucosidase inhibitory activity. Three-dimensional structure of S. cerevisiae α-glucosidase was built by homology modeling method and the structure was used for the molecular docking study to find out the initial binding mode of compound 12, which is the most highly active one. The initial structure was subjected to molecular dynamics (MD) simulations for protein structure adjustment at compound 12-bound state. Based on the adjusted conformation, the more reasonable binding modes of the stilbene urea derivatives were obtained from molecular docking and MD simulations. The binding mode of the derivatives was validated by correlation analysis between experimental Ki value and interaction energy. Our results revealed that the binding modes of the potent inhibitors were engaged with important hydrogen bond, hydrophobic, and π-interactions. With the validated compound 12-bound structure obtained from combining approach of docking and MD simulation, a proper four featured pharmacophore model was generated. It was also validated by comparison of fit values with the Ki values. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from stilbene derivatives.

  19. Macrocyclic nickel(II) complexes: Synthesis, characterization, superoxide scavenging activity and DNA-binding

    Science.gov (United States)

    Ramadan, Abd El-Motaleb M.

    2012-05-01

    A new series of nickel(II) complexes with the tetraaza macrocyclic ligand have been synthesized as possible functional models for nickel-superoxide dismutase enzyme. The reaction of 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde (AMPC) with itself in the presence of nickel(II) ion yields, the new macrocyclic cationic complex, [NiL(NO3)2], containing a ligand composed of the self-condensed AMPC (4 mol) bound to a single nickel(II) ion. A series of metathetical reactions have led to the isolation of a number of newly complexes of the types [NiL]X2; X = ClO4 and BF4, [NiLX2], X = Cl and Br (Scheme 1). Structures and characterizations of these complexes were achieved by several physicochemical methods namely, elemental analysis, magnetic moment, conductivity, and spectral (IR and UV-Vis) measurements. The electrochemical properties and thermal behaviors of these chelates were investigated by using cyclic voltammetry and thermogravimetric analysis (TGA and DTG) techniques. A distorted octahedral stereochemistry has been proposed for the six-coordinate nitrato, and halogeno complexes. For the four-coordinate, perchlorate and fluoroborate, complex species a square-planar geometry is proposed. The measured superoxide dismutase mimetic activities of the complexes indicated that they are potent NiSOD mimics and their activities are compared with those obtained previously for nickel(II) complexes. The probable mechanistic implications of the catalytic dismutation of O2rad - by the synthesized nickel(II) complexes are discussed. The DNA-binding properties of representative complexes [NiLCl2] and [NiL](PF4)2 have been investigated by the electronic absorption and fluorescence measurements. The results obtained suggest that these complexes bind to DNA via an intercalation binding mode and the binding affinity for DNA follows the order: [NiLCl2] □ [NiL](PF4)2.

  20. Type-II Dirac fermions in the PtSe2 class of transition metal dichalcogenides

    Science.gov (United States)

    Huang, Huaqing; Zhou, Shuyun; Duan, Wenhui

    2016-09-01

    Recently, a new "type-II" Weyl fermion, which exhibits exotic phenomena, such as an angle-dependent chiral anomaly, was discovered in a new phase of matter where electron and hole pockets contact at isolated Weyl points [Nature (London) 527, 495 (2015), 10.1038/nature15768]. This raises an interesting question about whether its counterpart, i.e., a type-II Dirac fermion, exists in real materials. Here, we predict the existence of symmetry-protected type-II Dirac fermions in a class of transition metal dichalcogenide materials. Our first-principles calculations on PtSe2 reveal its bulk type-II Dirac fermions which are characterized by strongly tilted Dirac cones, novel surface states, and exotic doping-driven Lifshitz transition. Our results show that the existence of type-II Dirac fermions in PtSe2-type materials is closely related to its structural P 3 ¯m 1 symmetry, which provides useful guidance for the experimental realization of type-II Dirac fermions and intriguing physical properties distinct from those of the standard Dirac fermions known before.

  1. A extração de segundos molares superiores para o tratamento da Classe II Extraction of upper second molars for treatment of Angle Class II malocclusion

    Directory of Open Access Journals (Sweden)

    Maurício Barbieri Mezomo

    2010-06-01

    Full Text Available Este trabalho tem por objetivo apresentar uma abordagem alternativa para o tratamento ortodôntico das más oclusões de Classe II. Através de uma revisão da literatura, verificou-se que a extração de segundos molares superiores demonstrou ser uma alternativa viável para o tratamento desse tipo de má oclusão. Essa opção terapêutica possibilita maior rapidez na distalização dos primeiros molares com menor necessidade de cooperação por parte do paciente. Porém, a análise do grau de formação, posição intraóssea e morfologia do terceiro molar deve ser cuidadosamente realizada para proporcionar o correto posicionamento do mesmo no lugar do segundo molar extraído. Dois casos clínicos apresentarão a sequência do diagnóstico e tratamento com essa mecânica, exibindo resultados adequados dos pontos de vista funcional e estético.The purpose of this article is to present an alternative approach to the orthodontic treatment of Angle Class II malocclusion. According to a literature review it was observed that the extraction of upper second molars has proven to be a viable alternative for the treatment of this type of malocclusion. This therapeutic option enables faster first molar retraction and requires less patient compliance. However, the level of development, intraosseous position and morphology of the third molar should be carefully evaluated to ensure its correct positioning in place of the extracted second molar. Two clinical case reports will demonstrate that the sequence of diagnosis and treatment used with this mechanics yields satisfactory functional and aesthetic results.

  2. pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-{beta} peptide

    Energy Technology Data Exchange (ETDEWEB)

    Ghalebani, Leila, E-mail: leila.ghalebani@ki.se [Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm (Sweden); Wahlstroem, Anna, E-mail: anna.wahlstrom@dbb.su.se [Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm (Sweden); Danielsson, Jens, E-mail: jensd@dbb.su.se [Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm (Sweden); Waermlaender, Sebastian K.T.S., E-mail: seb@dbb.su.se [Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm (Sweden); Graeslund, Astrid, E-mail: astrid@dbb.su.se [Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm (Sweden)

    2012-05-11

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

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

    Directory of Open Access Journals (Sweden)

    Lisa K. Denzin

    2013-12-01

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

  4. Creation of a putative third metal binding site in type II dihydroorotases significantly enhances enzyme activity.

    Science.gov (United States)

    Huang, Yen-Hua; Huang, Cheng-Yang

    2015-01-01

    Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides. DHOase is divided into two types (I and II). Type II DHOase generally contains a binuclear metal center in its active site. Recently, the crystal structure of DHOase domain in human CAD protein (huDHOase) has revealed three metal ions in the protein's active site. However, whether type II DHOase can have the critical third metal ion, as observed in huDHOase, remains unknown. In the present study, the putative third metal binding site in type II enzymes, such as the prokaryotic Salmonella enterica serovar Typhimurium LT2 DHOase (StDHOase) and the eukaryotic Saccharomyces cerevisiae DHOase (ScDHOase), was created and identified. StDHOase T198E and ScDHOase T208E mutants had higher activities compared with their wild-type enzymes. The need for a higher DHOase stability and activity may drive creation of the third metal ion binding site in huDHOase, which can be achieved by mutating a highly conserved position T in type II dihydroorotases to E, similar to that in huDHOase.

  5. Copper(II) Binding to α-Synuclein, the Parkinson’s Protein

    OpenAIRE

    Lee, Jennifer C.; Gray, Harry B.; Winkler, Jay R.

    2008-01-01

    Variations in tryptophan fluorescence intensities confirm that copper(II) interacts with α-synuclein, a protein implicated in Parkinson’s disease. Trp4 fluorescence decay kinetics measured for the F4W protein show that Cu(II) binds tightly (K d ∼ 100 nM) near the N-terminus at pH 7. Work on a F4W/H50S mutant indicates that a histidine imidazole is not a ligand in this high-affinity site.

  6. pRB is required for interferon-gamma-induction of the MHC class II abeta gene.

    Science.gov (United States)

    Zhu, X; Pattenden, S; Bremner, R

    1999-09-02

    pRB is required for IFN-gamma-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRB-dependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB+/+ mouse embryonic fibroblasts (MEFs), but deficient in RB-/- MEFs. Inducibility is restored in RB-/- MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was specifically required for induction of the Abeta, but not Aalpha or other MHC cII genes including Ebeta, Ii and H2-Malpha. Finally, IFN-gamma-induction of class II transactivator (CIITA), was pRB-independent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

  7. A primary survey on bryophyte species reveals two novel classes of nucleotide-binding site (NBS genes.

    Directory of Open Access Journals (Sweden)

    Jia-Yu Xue

    Full Text Available Due to their potential roles in pathogen defense, genes encoding nucleotide-binding site (NBS domain have been particularly surveyed in many angiosperm genomes. Two typical classes were found: one is the TIR-NBS-LRR (TNL class and the other is the CC-NBS-LRR (CNL class. It is seldom known, however, what kind of NBS-encoding genes are mainly present in other plant groups, especially the most ancient groups of land plants, that is, bryophytes. To fill this gap of knowledge, in this study, we mainly focused on two bryophyte species: the moss Physcomitrella patens and the liverwort Marchantia polymorpha, to survey their NBS-encoding genes. Surprisingly, two novel classes of NBS-encoding genes were discovered. The first novel class is identified from the P. patens genome and a typical member of this class has a protein kinase (PK domain at the N-terminus and a LRR domain at the C-terminus, forming a complete structure of PK-NBS-LRR (PNL, reminiscent of TNL and CNL classes in angiosperms. The second class is found from the liverwort genome and a typical member of this class possesses an α/β-hydrolase domain at the N-terminus and also a LRR domain at the C-terminus (Hydrolase-NBS-LRR, HNL. Analysis on intron positions and phases also confirmed the novelty of HNL and PNL classes, as reflected by their specific intron locations or phase characteristics. Phylogenetic analysis covering all four classes of NBS-encoding genes revealed a closer relationship among the HNL, PNL and TNL classes, suggesting the CNL class having a more divergent status from the others. The presence of specific introns highlights the chimerical structures of HNL, PNL and TNL genes, and implies their possible origin via exon-shuffling during the quick lineage separation processes of early land plants.

  8. 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 3,139,729 bp. 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.

  9. Model membrane interaction and DNA-binding of antimicrobial peptide Lasioglossin II derived from bee venom.

    Science.gov (United States)

    Bandyopadhyay, Susmita; Lee, Meryl; Sivaraman, J; Chatterjee, Chiradip

    2013-01-01

    Lasioglossins, a new family of antimicrobial peptide, have been shown to have strong antimicrobial activity with low haemo-lytic and mast cell degranulation activity, and exhibit cytotoxic activity against various cancer cells in vitro. In order to understand the active conformation of these pentadecapeptides in membranes, we have studied the interaction of Lasioglossin II (LL-II), one of the members of Lasioglossins family with membrane mimetic micelle Dodecylphosphocholine (DPC) by fluorescence, Circular Dichroism (CD) and two dimensional (2D) (1)H NMR spectroscopy. Fluorescence experiments provide evidence of interaction of the N-terminal tryptophan residue of LL-II with the hydrophobic core of DPC micelle. CD results show an extended chain conformation of LL-II in water which is converted to a partial helical conformation in the presence of DPC micelle. Moreover we have determined the first three-dimensional NMR structure of LL-II bound to DPC micelle with rmsd of 0.36Å. The solution structure of LL-II shows hydrophobic and hydrophilic core formation in peptide pointing towards different direction in the presence of DPC. This amphipathic structure may allow this peptide to penetrate deeply into the interfacial region of negatively charged membranes and leading to local membrane destabilization. Further we have elucidated the DNA binding ability of LL-II by agarose gel retardation and fluorescence quenching experiments.

  10. Treatment of Class II, Division 2 in the late growth period.

    Science.gov (United States)

    Eberhard, H; Hirschfelder, U

    1998-01-01

    The "Deckbiss" with skeletal Class II jaw relationship sometimes presents a considerable therapeutic problem, particularly in the late growth period (DP3U), as regards the coordination of dental and skeletal treatment objectives. An effective treatment approach was demonstrated: a modified Herbst appliance used simultaneously with fixed appliances in the maxilla. The sample comprised 12 male (14.0 +/- 0.9 years old) and 10 female (12.3 +/- 0.4 years old) patients. Correction of the distal occlusion was achieved in all patients by means of the Herbst appliance, which was removed after an average time period of 6.4 +/- 0.2 months. In the mandible the multibracket appliances were then immediately inserted, and Class II elastics were used for retention. Maximum anchorage was required in the maxilla as well as in the mandible. Complete diagnostic records were made at the beginning of the treatment as well as 6 and 12 months later, in order to document skeletal and dental changes. A dental and skeletal Class I relationship was achieved in all cases. A significant improvement was recorded in the vertical jaw base relationship; this was still stable after a period of 12 months. In the dental area in particular, a so-called high-pull headgear effect (intrusion and distalization 16, 26) and intrusion of teeth 34, 44 were registered. Only a minor protrusion of the mandibular incisors was observed. Reinforcement of the bands reduced the failure rate significantly. The Herbst appliance does not represent a standard treatment for Class II. Its indication range is limited.

  11. Variations in cyclic mandibular movements during treatment of Class II malocclusions with removable functional appliances.

    Science.gov (United States)

    Thieme, Kirsten M; Nägerl, Hans; Hahn, Wolfram; Ihlow, Dankmar; Kubein-Meesenburg, Dietmar

    2011-12-01

    The aim of the study was to establish whether juveniles with a Class II malocclusion change the neuromuscular control of mandibular movements during the course of orthodontic treatment with removable functional appliances (RFAs). Neuromuscular control can be indirectly evaluated by recording cyclic planar mandibular movements which were freely carried out by the patients (28 girls, 14 boys, aged 11.1 ± 1.1 years at the start of treatment) and measured with an ultrasonic device before, during, and after Class II functional appliance therapy, with either an activator or a bite jumping plate. The cyclic movements represented simultaneous rotations of the mandible around a maxillary and mandibular fixed axis (MFHA) and could be characterized by μ(α)-diagrams (μ = swing angle of MFHA, α = mouth opening angle) and path length (L) of the MFHA. The μ(α)-diagrams clearly divided into four parts: movement representing protrusion, mouth opening, and two parts of backward closing as known from Posselt diagrams. Parameters from the Posselt and μ(α)-diagrams were checked by one-factor analysis of variance on a 5 per cent significance level for group dependency. For one-third of the patients investigated, no significant changes were seen in any parameter pre- or post-therapy. However, patients showing an initially large mouth opening capacity or a very short condylar path changed their neuromuscular control to that of Class I subjects. Analysis of μ(α)-diagrams provides the possibility of assessing changes in the neuromuscular control of the mandible during Class II treatment.

  12. The murine cytomegalovirus immunoevasin gp40 binds MHC class I molecules to retain them in the early secretory pathway.

    Science.gov (United States)

    Janßen, Linda; Ramnarayan, Venkat Raman; Aboelmagd, Mohamed; Iliopoulou, Maro; Hein, Zeynep; Majoul, Irina; Fritzsche, Susanne; Halenius, Anne; Springer, Sebastian

    2016-01-01

    In the presence of the murine cytomegalovirus (mCMV) gp40 (m152) protein, murine major histocompatibility complex (MHC) class I molecules do not reach the cell surface but are retained in an early compartment of the secretory pathway. We find that gp40 does not impair the folding or high-affinity peptide binding of the class I molecules but binds to them, leading to their retention in the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, most likely by retrieval from the cis-Golgi to the ER. We identify a sequence in gp40 that is required for both its own retention in the early secretory pathway and for that of class I molecules.

  13. Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding

    DEFF Research Database (Denmark)

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

    1996-01-01

    size are distributed into positional scanning combinatorial peptide libraries (PSCPL) to develop a highly efficient, universal and unbiased approach to address MHC specificity. The PSCPL approach appeared qualitatively and quantitatively superior to other currently used strategies. The average effect...... of any amino acid in each position was quantitated, allowing a detailed description of extended peptide binding motifs including primary and secondary anchor residues. It also identified disfavored residues which were found to be surprisingly important in shaping MHC class I specificity. Assuming...

  14. Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials

    Directory of Open Access Journals (Sweden)

    Otten Celine

    2008-06-01

    Full Text Available 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 incanus, to investigate characteristic features of MHC selection. This study is the first investigation of MHC selection in free-ranging Neotropical marsupials. In addition, the evolutionary history of MHC lineages within the group of marsupials was examined. Results G. microtarsus showed extensive levels of MHC diversity within and among individuals as 47 MHC-DAB alleles and high levels of sequence divergence were detected at a minimum of four loci. Positively selected codon sites were identified, of which most were congruent with human antigen binding sites. The diversity in M. incanus was rather low with only eight observed alleles at presumably two loci. However, these alleles also revealed high sequence divergence. Again, positive selection was identified on specific codon sites, all congruent with human ABS and with positively selected sites observed in G. microtarsus. In a phylogenetic comparison alleles of M. incanus interspersed widely within alleles of G. microtarsus with four alleles being present in both species. Conclusion Our investigations revealed extensive MHC class II polymorphism in a natural marsupial population, contrary to previous assumptions. Furthermore, our study confirms for the first time in marsupials the presence of three characteristic features common at MHC loci of eutherian mammals, birds and fish: large allelic sequence divergence, positive selection on specific sites and trans-specific polymorphism.

  15. Comparison of the binding of the dyes Sudan II and Sudan IV to bovine hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haoyu; Xia, Qing; Liu, Rutao, E-mail: rutaoliu@sdu.edu.cn

    2014-04-15

    Sudan dyes are widely used in industry, and sometimes illegally used as food additives despite their potential toxicity. In this work, the interactions of Sudan II and Sudan IV with bovine hemoglobin (BHb) were investigated by fluorescence, synchronous fluorescence, resonance light scattering (RLS), UV–vis absorption, circular dichroism (CD), and molecular modeling techniques. Binding of Sudan dyes to BHb could cause static quenching of the fluorescence, indicating changes in the microenvironment of tryptophan and tyrosine residues. The binding constants estimated for Sudan II and IV were 1.84×10{sup 4} L mol{sup −1} and 2.54×10{sup 4} L mol{sup −1}, respectively, at 293 K (20 °C). Each protein molecule bound one Sudan molecule approximately. Sudan II and IV were held at the hydrophobic cavity of BHb mainly by hydrophobic interaction. The decrease of α-helix and the increase of β-sheet seen in the CD spectra revealed a conformational alteration of the protein. From all the results, we conclude that Sudan IV has a stronger impact on the structure and function of BHb than that of Sudan II. -- Highlights: • Spectroscopic results show interaction details of Sudan II and IV with BHb. • The interaction of BHb with Sudan dyes is spontaneous with a 1:1 stoichiometry. • Sudan II and IV are located at the hydrophobic cavity of the BHb, and form complexes via hydrophobic interaction. • A stronger influence of bovine hemoglobin is caused by Sudan IV than that of Sudan II.

  16. Analytical methods to determine the comparative DNA binding studies of curcumin-Cu(II) complexes.

    Science.gov (United States)

    Rajesh, Jegathalaprathaban; Rajasekaran, Marichamy; Rajagopal, Gurusamy; Athappan, Periakaruppan

    2012-11-01

    DNA interaction studies of two mononuclear [1:1(1); 1:2(2)] copper(II) complexes of curcumin have been studied. The interaction of these complexes with CT-DNA has been explored by physical methods to propose modes of DNA binding of the complexes. Absorption spectral titrations of complex 1 with CT-DNA shows a red-shift of 3 nm with the DNA binding affinity of K(b), 5.21×10(4)M(-1) that are higher than that obtained for 2 (red-shift, 2 nm; K(b), 1.73×10(4)M(-1)) reveal that the binding occurs in grooves as a result of the interaction is via exterior phosphates. The CD spectra of these Cu(II) complexes show a red shift of 3-10nm in the positive band with increase in intensities. This spectral change of induced CD due to the hydrophobic interaction of copper complexes with DNA is the characteristic of B to A conformational change. The EB displacement assay also reveals the same trend as observed in UV-Vis spectral titration. The addition of complexes 1 and 2 to the DNA bound ethidium bromide (EB) solutions causes an obvious reduction in emission intensities indicating that these complexes competitively bind to DNA with EB. The positive shift of both the E(pc) and E(0)' accompanied by reduction of peak currents in differential pulse voltammogram (DPV), upon adding different concentrations of DNA to the metal complexes, are obviously in favor of strong binding to DNA. The super coiled plasmid pUC18 DNA cleavage ability of Cu(II) complexes in the presence of reducing agent reveals the single strand DNA cleavage (ssDNA) is observed. The hydroxyl radical (HO()) and the singlet oxygen are believed to be the reactive species responsible for the cleavage.

  17. Semi-longitudinal Study of the Mcnamara Cephalometric Triangle in Class II and Class III Subjects Grouped by Cervical Vertebrae Maturation Stage.

    Science.gov (United States)

    Arriola-Guillén, Luis E; Fitzcarrald, Fernando D; Flores-Mir, Carlos

    2015-12-01

    The aim was to compare the McNamara cephalometric triangle values in untreated normodivergent Class II and Class III malocclusion subjects of Latin American origin grouped by cervical vertebrae maturation stage to an untreated Class I malocclusion normodivergent control group. The study was conducted on a sample of 610 pretreatment lateral cephalograms (250 male, 360 female), examined and grouped according to their anteroposterior skeletal relationship (Class I, II or III), cervical vertebrae maturation stage (Pre Pubertal Peak P1 = CS1 and CS2, Pubertal Peak P2= CS3 and CS4, and Post Pubertal Peak P3 = CS5 and CS6) and sex. Co-A, Co-Gn and ENA-Me were measured in each lateral cephalogram. ANOVA and Tukey HSD post-hoc tests were performed to determine differences between the groups. The results showed that in males, the greatest maxillary and mandibular dimensional increases occurred during the P3 stage (CS5 to CS6), while in females, they occurred in the P2 stage (CS3 to CS4). The Co-A and Co-Gn showed significant differences between the malocclusion classes (pClass II subjects and the mandibular lengths in Class III subjects were already higher at the beginning of the period evaluated (P1). A worsening trend for the Class II and III malocclusions was identified during the period evaluated. Finally, changes in the McNamara cephalometric triangle values were markedly different in the three normodivergent skeletal malocclusion classes. In these Latin American subjects the pubertal growth spurt occurred at different times with respect to the Caucasian and Asian norms.

  18. 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.

  19. 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.

  20. Energy-optimised pharmacophore approach to identify potential hotspots during inhibition of Class II HDAC isoforms.

    Science.gov (United States)

    Ganai, Shabir Ahmad; Shanmugam, Karthi; Mahadevan, Vijayalakshmi

    2015-01-01

    Histone deacetylases (HDACs) are conjugated enzymes that modulate chromatin architecture by deacetylating lysine residues on the histone tails leading to transcriptional repression. Pharmacological interventions of these enzymes with small molecule inhibitors called Histone deacetylase inhibitors (HDACi) have shown enhanced acetylation of the genome and are hence emerging as potential targets at the clinic. Type-specific inhibition of Class II HDACs has shown enhanced therapeutic benefits against developmental and neurodegenerative disorders. However, the structural identity of class-specific isoforms limits the potential of their inhibitors in precise targeting of their enzymes. Diverse strategies have been implemented to recognise the features in HDAC enzymes which may help in identifying isoform specificity factors. This work attempts a computational approach that combines in silico docking and energy-optimised pharmacophore (E-pharmacophore) mapping of 18 known HDAC inhibitors and has identified structural variations that regulate their interactions against the six Class II HDAC enzymes considered for the study. This combined approach establishes that inhibitors possessing higher number of aromatic rings in different structural regions might function as potent inhibitors, while inhibitors with scarce ring structures might point to compromised potency. This would aid the rationale for chemical optimisation and design of isoform selective HDAC inhibitors with enhanced affinity and therapeutic efficiency.

  1. Identification and characterization of a novel angiotensin binding site in cultured vascular smooth muscle cells that is specific for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV.

    Science.gov (United States)

    Hall, K L; Hanesworth, J M; Ball, A E; Felgenhauer, G P; Hosick, H L; Harding, J W

    1993-03-19

    This study demonstrates the existence of a previously unrecognized class of angiotensin binding sites on vascular smooth muscle that exhibit high affinity and specificity for the hexapeptide (3-8) fragment of angiotensin II (AngIV). Binding of [125I]AngIV is saturable, reversible and describes a pharmacologic profile that is distinct and separate from the classic AT1 or AT2 angiotensin receptors. Saturation binding studies utilizing cultured vascular smooth muscle cells obtained from bovine aorta (BVSM) revealed that [125I]AngIV bound to a single high affinity site with an associated Hill coefficient of 0.99 +/- 0.003, exhibiting a KD = 1.85 +/- 0.45 nM and a corresponding Bmax = 960 +/- 100 fmol mg-1 protein. Competition binding curves in BVSM demonstrated the following rank order effectiveness: AngIV > AngII(3-7) > AngIII > Sar1,Ile8 AngII > AngII > AngII(1-7) > AngII(4-8), DuP 753, PD123177. The presence of the non-hydrolyzable GTP analog GTP gamma S, had no effect on [125I]AngIV binding affinity in BVSM. The presence of this novel angiotensin binding site on smooth muscle in high concentration suggests the possibility that this system may play an important, yet unrecognized role in vascular control.

  2. MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression.

    Science.gov (United States)

    Galbas, Tristan; Steimle, Viktor; Lapointe, Réjean; Ishido, Satoshi; Thibodeau, Jacques

    2012-07-01

    IL-10 is vastly studied for its anti-inflammatory properties on most immune cells. However, it has been reported that IL-10 activates B cells, up-regulates their MHC class II molecules and prevents apoptosis. As MARCH1 was shown to be responsible for the intracellular sequestration of MHC class II molecules in dendritic cells and monocytes in response to IL-10, we set out to clarify the role of this ubiquitin ligase in B cells. Here, we demonstrate in mice that splenic follicular B cells represent the major cell population that up-regulate MHC II molecules in the presence of IL-10. Activation of these cells through TLR4, CD40 or the IL-10 receptor caused the down-regulation of MARCH1 mRNA. Accordingly, B cells from MARCH1-deficient mice do not up-regulate I-A(b) in response to IL-10. In all, our results demonstrate that IL-10 can have opposite effects on MARCH1 regulation in different cell types.

  3. HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

    Science.gov (United States)

    De Leo, C; Castelan, N; Lopez, M; Gonzalez, N; Weckmann, A L; Melin-Aldana, H; Vargas-Alarcon, G; Bordes, J; Alarcon-Segovia, D; Granados, J; Ramirez, E; Lisker, R

    1997-12-01

    We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

  4. FAD binding by ApbE protein from Salmonella enterica: a new class of FAD-binding proteins.

    Science.gov (United States)

    Boyd, Jeffery M; Endrizzi, James A; Hamilton, Trinity L; Christopherson, Melissa R; Mulder, David W; Downs, Diana M; Peters, John W

    2011-02-01

    The periplasmic protein ApbE was identified through the analysis of several mutants defective in thiamine biosynthesis and was implicated as having a role in iron-sulfur cluster biosynthesis or repair. While mutations in apbE cause decreased activity of several iron-sulfur enzymes in vivo, the specific role of ApbE remains unknown. Members of the AbpE family include NosX and RnfF, which have been implicated in oxidation-reduction associated with nitrous oxide and nitrogen metabolism, respectively. In this work, we show that ApbE binds one FAD molecule per monomeric unit. The structure of ApbE in the presence of bound FAD reveals a new FAD-binding motif. Protein variants that are nonfunctional in vivo were generated by random and targeted mutagenesis. Each variant was substituted in the environment of the FAD and analyzed for FAD binding after reconstitution. The variant that altered a key tyrosine residue involved in FAD binding prevented reconstitution of the protein.

  5. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-07-21

    ... HUMAN SERVICES Food and Drug Administration (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  6. 75 FR 54637 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-09-08

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document for Certain Percutaneous Transluminal Coronary Angioplasty (PTCA) Catheters; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY:...

  7. Treatment of Class II malocclusion with bialveolar protrusion by means of unusual extractions and anchorage mini-implant

    OpenAIRE

    Jong-Moon Chae

    2012-01-01

    INTRODUCTION: Patients with dental Class II bialveolar protrusion are generally treated by extracting the four first premolars or two first and two second premolars, and retracting the anterior teeth. This case report describes the treatment of an adult patient with bialveolar protrusion, a Class II canine and molar relationship, and lip protrusion. METHODS: In this patient, the maxillary right second molar (1.7) had to be extracted due to extensive caries. To create sufficient space to retra...

  8. A single residue change leads to a hydroxylated product from the class II diterpene cyclization catalyzed by abietadiene synthase

    Science.gov (United States)

    Criswell, Jared; Potter, Kevin; Shephard, Freya; Beale, Michael H.; Peters, Reuben J.

    2012-01-01

    Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate. While this reaction typically is terminated via methyl deprotonation to yield copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead. Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a copalyl diphosphate intermediate. Here it is shown that substitution of aspartate for a conserved histidine in the class II active site of abietadiene synthase leads to selective production of 8α-hydroxy-CPP instead, demonstrating striking plasticity. PMID:23167845

  9. The D2 period of collagen II contains a specific binding site for the human discoidin domain receptor, DDR2.

    Science.gov (United States)

    Leitinger, Birgit; Steplewski, Andrzej; Fertala, Andrzej

    2004-12-03

    The human discoidin domain receptors (DDRs), DDR1 and DDR2, are expressed widely and, uniquely among receptor tyrosine kinases, activated by the extracellular matrix protein collagen. This activation is due to a direct interaction of collagen with the DDR discoidin domain. Here, we localised a specific DDR2 binding site on the triple-helical region of collagen II. Collagen II was found to be a much better ligand for DDR2 than for DDR1. As expected, DDR2 binding to collagen II was dependent on triple-helical collagen and was mediated by the DDR2 discoidin domain. Collagen II served as a potent stimulator of DDR2 autophosphorylation, the first step in transmembrane signalling. To map the DDR2 binding site(s) on collagen II, we used recombinant collagen II variants with specific deletions of one of the four repeating D periods. We found that the D2 period of collagen II was essential for DDR2 binding and receptor autophosphorylation, whereas the D3 and D4 periods were dispensable. The DDR2 binding site on collagen II was further defined by recombinant collagen II-like proteins consisting predominantly of tandem repeats of the D2 or D4 period. The D2 construct, but not the D4 construct, mediated DDR2 binding and receptor autophosphorylation, demonstrating that the D2 period of collagen II harbours a specific DDR2 recognition site. The discovery of a site-specific interaction of DDR2 with collagen II gives novel insight into the nature of the interaction of collagen II with matrix receptors.

  10. Identification of genes encoding photoconvertible (Class I) water-soluble chlorophyll-binding proteins from Chenopodium ficifolium.

    Science.gov (United States)

    Takahashi, Shigekazu; Abe, Eriko; Nakayama, Katsumi; Satoh, Hiroyuki

    2015-01-01

    Photoconvertible water-soluble chlorophyll-binding proteins, called Class I WSCPs, have been detected in Chenopodiaceae, Amaranthaceae and Polygonaceae plant species. To date, Chenopodium album WSCP (CaWSCP) is the only cloned gene encoding a Class I WSCP. In this study, we identified two cDNAs encoding Chenopodium ficifolium Class I WSCPs, CfWSCP1, and CfWSCP2. Sequence analyses revealed that the open reading frames of CfWSCP1 and CfWSCP2 were 585 and 588 bp, respectively. Furthermore, both CfWSCPs contain cystein2 and cystein30, which are essential for the chlorophyll-binding ability of CaWSCP. Recombinant CfWSCP1 and CfWSCP2, expressed in Escherichia coli as hexa-histidine fusion proteins (CfWSCP1-His and CfWSCP2-His), formed inclusion bodies; however, we were able to solubilize these using a buffer containing 8 M urea and then refold them by dialysis. The refolded CfWSCP1-His and CfWSCP2-His could bind chlorophylls and exhibited photoconvertibility, confirming that the cloned CfWSCPs are further examples of Class I WSCPs.

  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

    2016-01-01

    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

  12. A tensor analysis to evaluate the effect of high-pull headgear on Class II malocclusions.

    Science.gov (United States)

    Ngan, P; Scheick, J; Florman, M

    1993-03-01

    The inaccuracies inherent in cephalometric analysis of treatment effects are well known. The objective of this article is to present a more reliable research tool in the analysis of cephalometric data. Bookstein introduced a dilation function by means of a homogeneous deformation tensor as a method of describing changes in cephalometric data. His article gave an analytic description of the deformation tensor that permits the rapid and highly accurate calculation of it on a desktop computer. The first part of this article describes the underlying ideas and mathematics. The second part uses the tensor analysis to analyze the cephalometric results of a group of patients treated with high-pull activator (HPA) to demonstrate the application of this research tool. Eight patients with Class II skeletal open bite malocclusions in the mixed dentition were treated with HPA. A control sample consisting of eight untreated children with Class II who were obtained from The Ohio State University Growth Study was used as a comparison group. Lateral cephalograms taken before and at the completion of treatment were traced, digitized, and analyzed with the conventional method and tensor analysis. The results showed that HPA had little or no effect on maxillary skeletal structures. However, reduction in growth rate was found with the skeletal triangle S-N-A, indicating a posterior tipping and torquing of the maxillary incisors. The treatment also induced additional deformation on the mandible in a downward and slightly forward direction. Together with the results from the conventional cephalometric analysis, HPA seemed to provide the vertical and rotational control of the maxilla during orthopedic Class II treatment by inhibiting the downward and forward eruptive path of the upper posterior teeth. The newly designed computer software permits rapid analysis of cephalometric data with the tensor analysis on a desktop computer. This tool may be useful in analyzing growth changes for

  13. Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs.

    Directory of Open Access Journals (Sweden)

    Jonathan Massey

    Full Text Available A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 "graded" controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032. When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011. Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.

  14. Purification and characterization of a class II α-Mannosidase from Moringa oleifera seed kernels.

    Science.gov (United States)

    Tejavath, Kiran Kumar; Nadimpalli, Siva Kumar

    2014-10-01

    α-Mannosidase (EC. 3.2.1.114) belonging to class II glycosyl hydrolase family 38 was purified from Moringa oleifera seeds to apparent homogeneity by conventional protein purification methods followed by affinity chromatography on Con A Sepharose and size exclusion chromatography. The purified enzyme is a glycoprotein with 9.3 % carbohydrate and exhibited a native molecular mass of 240 kDa, comprising two heterogeneous subunits with molecular masses of 66 kDa (α-larger subunit) and 55 kDa (β-smaller subunit). Among both the subunits only larger subunit stained for carbohydrate with periodic acid Schiff's staining. The optimum temperature and pH for purified enzyme was 50 °C and pH 5.0, respectively. The enzyme was stable within the pH range of 3.0-7.0. The enzyme was inhibited by EDTA, Hg(2+), Ag(2+), and Cu(2+). The activity lost by EDTA was completely regained by addition of Zn(2+). The purified enzyme was characterized in terms of the kinetic parameters K m (1.6 mM) and V max (2.2 U/mg) using para-nitrophenyl-α-D-mannopyranoside as substrate. The enzyme was very strongly inhibited by swainsonine (SW) at 1 μM concentration a class II α-Mannosidase inhibitor, but not by deoxymannojirimycin (DMNJ). Chemical modification studies revealed involvement of tryptophan at active site. The inhibition by SW and requirement of the Zn(2+) as a metal ion suggested that the enzyme belongs to class II α-Mannosidase.

  15. 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......Objective. The aim of this 30 year randomized controlled study was to evaluate, by intrain-dividual comparisons, the durability of three conventional resin composites in Class IIrestorations. Methods. Each of 30 participants, 21 female and 9 male (mean age 30 years, range 20–43),received at least...... 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 the...

  16. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha.

    Science.gov (United States)

    Qian, David Z; Kachhap, Sushant K; Collis, Spencer J; Verheul, Henk M W; Carducci, Michael A; Atadja, Peter; Pili, Roberto

    2006-09-01

    Hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a critical role in transcriptional gene activation involved in tumor angiogenesis. A novel class of agents, the histone deacetylase (HDAC) inhibitors, has been shown to inhibit tumor angiogenesis and HIF-1 alpha protein expression. However, the molecular mechanism responsible for this inhibition remains to be elucidated. In the current study, we investigated the molecular link between HIF-1 alpha inhibition and HDAC inhibition. Treatment of the VHL-deficient human renal cell carcinoma cell line UMRC2 with the hydroxamic HDAC inhibitor LAQ824 resulted in a dose-dependent inhibition of HIF-1 alpha protein via a VHL-independent mechanism and reduction of HIF-1 alpha transcriptional activity. HIF-1 alpha inhibition by LAQ824 was associated with HIF-1 alpha acetylation and polyubiquitination. HIF-1 alpha immunoprecipitates contained HDAC activity. Then, we tested different classes of HDAC inhibitors with diverse inhibitory activity of class I versus class II HDACs and assessed their capability of targeting HIF-1 alpha. Hydroxamic acid derivatives with known activity against both class I and class II HDACs were effective in inhibiting HIF-1 alpha at low nanomolar concentrations. In contrast, valproic acid and trapoxin were able to inhibit HIF-1 alpha only at concentrations that are effective against class II HDACs. Coimmunoprecipitation studies showed that class II HDAC4 and HDAC6 were associated with HIF-1 alpha protein. Inhibition by small interfering RNA of HDAC4 and HDAC6 reduced HIF-1 alpha protein expression and transcriptional activity. Taken together, these results suggest that class II HDACs are associated with HIF-1 alpha stability and provide a rationale for targeting HIF-1 alpha with HDAC inhibitors against class II isozymes.

  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

    Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8+ T cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presentation...

  18. 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...

  19. Genetic variation and balancing selection at MHC class II exon 2 in cultured stocks and wild populations of orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Meng, Z N; Yang, S; Fan, B; Wang, L; Lin, H R

    2012-11-12

    Major histocompatibility complex (MHC) molecules play vital roles in triggering adaptive immune responses and are considered the most variable molecules in vertebrates. Recently, many studies have focused on the polymorphism and evolution mode of MHC in both model and non-model organisms. Here, we analyzed the MHC class II exon 2-encoding β chain in comparison with the mitochondrial Cytb gene and our previously published microsatellite data set in three cultured stocks and four wild populations of the orange-spotted grouper (Epinephelus coioides) in order to investigate its genetic variation and mechanism of evolution. We detected one to four alleles in one individual, suggesting that at least two loci exist in the orange-spotted grouper, as well as a particularly high level of allelic diversity at the MHC loci. Furthermore, the cultured stocks exhibited reduced allelic diversity compared to the wild counterparts. We found evidence of balancing selection at MHC class II exon 2, and codon sites under positive selection were largely correspondent to the protein-binding region. In addition, MHC class II exon 2 revealed significant differences between population differentiation patterns from the neutral mitochondrial Cytb and microsatellites, which may indicate local adaptation at MHC loci in orange-spotted grouper originating from the South China Sea and Southeast Asia.

  20. The angiotensin hexapeptide 3-8 fragment potently inhibits [125I]angiotensin II binding to non-AT1 or -AT2 recognition sites in bovine adrenal cortex.

    Science.gov (United States)

    Jarvis, M F; Gessner, G W; Ly, C Q

    1992-08-25

    In the present studies, ligand competition experiments were conducted to examine the ability of angiotensin II peptide agonists and nonpeptide AT1- and AT2-selective receptor antagonists to inhibit the binding of [125I]angiotensin II to bovine adrenal cortical membranes. Angiotensin II, angiotensin III, the All-(3-8) hexapeptide fragment of angiotensin II, and the AT1-selective receptor antagonist L-158,809, inhibited [125I]angiotensin II binding in a biphasic fashion indicative of a ligand interaction at more than one recognition site. Approximately 20% of low affinity [125I]angiotensin II binding was inhibited only by high micromolar concentrations of L-158,809. RG 13647 (1(-1,4-benzodioxan-2-methyl)-5-diphenylacetyl-4,5,6,7-tetra hydro-1H-imidazo- [4,5,c]-pyridine-6-carboxylic acid) represents a potent and AT2-selective analog of PD 123177 and showed weak activity in competing for [125I]angiotensin II binding with an IC50 value of 100 microM. When subsequent competition studies were conducted in the presence of 1 microM L-158,809 to block [125I]angiotensin II to the AT1 receptor subtype, the angiotensin II agonists produced monophasic inhibition curves with AII-(3-8) showing the greatest activity (IC50 = 6 nM) followed by angiotensin III (IC50 = 15 nM) much greater than angiotensin II (IC50 = 110 nM). RG 13647 was not found to significantly inhibit this portion of [125I]angiotensin II binding. These data demonstrate that bovine adrenal cortex contains both the AT1 receptor subtype, as well as, a novel class of [125I]angiotensin II recognition sites which may be analogous to the recently described angiotensin IV (AT4) receptor.

  1. DNA polymorphism of HLA class II genes in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Morling, Niels; Dalhoff, K; Fugger, L;

    1992-01-01

    We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary......) associated DRB Bgl II 9.1 kilobase (kb) fragment (RR = 2.9; P less than 0.05, 'corrected' P greater than 0.05), the DQA1*0501 associated DQA Taq I 4.8 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05), the DQB1*0201 (DQw2) associated DQB Hin dIII 11.5 kb fragment (RR = 3.1; P less...

  2. Angle Class II, subdivision, with agenesis of mandibular second molars and extrusion of maxillary second molars

    Directory of Open Access Journals (Sweden)

    Rubens Rodrigues Tavares

    2015-04-01

    Full Text Available This clinical case reports the treatment of an Angle Class II malocclusion in a young woman with a balanced face affected by agenesis of second and third mandibular molars and subsequent extrusion of second maxillary molars. The atypical and peculiar occlusal anomaly led to individualized treatment proposed in order to normalize dental malpositions, with subsequent rehabilitation of edentulous areas by means of a multidisciplinary approach. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO in partial fulfillment of the requirements for obtaining the title of certified by the BBO.

  3. 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

  4. Effects of pulp capping materials on fracture resistance of Class II composite restorations

    OpenAIRE

    2015-01-01

    Objective: The aim of this study was to investigate the effect of cavity design and the type of pulp capping materials on the fracture resistance of Class II composite restorations. Materials and Methods: Sixty freshly extracted, sound molar teeth were selected for the study. A dovetail cavity on the mesio-occlusal and a slot cavity on disto-occlusal surfaces of each tooth were prepared, and the teeth were divided 4 groups which one of them as a control group. The pulp capping materials (Ther...

  5. Post-transplant anti-HLA class II antibodies as risk factor for late kidney allograft failure.

    Science.gov (United States)

    Campos, E F; Tedesco-Silva, H; Machado, P G; Franco, M; Medina-Pestana, J O; Gerbase-DeLima, M

    2006-10-01

    The purpose of this study was to prospectively analyze the relationship between the post-transplant anti-HLA class I and/or class II panel reactive antibodies and graft failure due to chronic allograft nephropathy (CAN). We studied 512 first kidney recipients transplanted at a single center, with a graft functioning for at least 3 years. A single blood sample was collected from each patient for antibody evaluation. The median posttransplant time after blood collection was 4.4 years and did not differ between patients with (n = 91) or without anti-HLA antibodies (n = 421). Female gender, pregnancies and blood transfusions were associated with the presence of anti-HLA class I antibodies. Graft function deterioration was associated with anti-HLA class II antibodies. Multivariate analysis showed independent association for creatinine levels (RR = 7.5), acute rejection (RR = 2.6), recipient male gender (RR = 3.6) and anti-HLA class II antibodies (RR = 2.9) and CAN-associated graft loss. In conclusion, the presence of anti-HLA class II antibodies conferred a risk for graft loss before a decline in renal function and increased the risk of graft failure in patients who already had a decline in graft function. Thus, anti-HLA class II antibody monitoring is a useful tool for the management of long-term kidney recipients.

  6. ACTN3 R577X Genotypes Associate with Class II and Deep Bite Malocclusions

    Science.gov (United States)

    Zebrick, Brian; Teeramongkolgul, Teesit; Nicot, Romain; Horton, Michael J.; Raoul, Gwenael; Ferri, Joel; Vieira, Alexandre R.; Sciote, James J.

    2014-01-01

    Introduction α-actinins are myofibril anchor proteins which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p = 0.002). Conclusion ACTN3 577XX is overrepresented in skeletal class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions. PMID:25439211

  7. ELK1 uses different DNA binding modes to regulate functionally distinct classes of target genes.

    Directory of Open Access Journals (Sweden)

    Zaneta Odrowaz

    Full Text Available Eukaryotic transcription factors are grouped into families and, due to their similar DNA binding domains, often have the potential to bind to the same genomic regions. This can lead to redundancy at the level of DNA binding, and mechanisms are required to generate specific functional outcomes that enable distinct gene expression programmes to be controlled by a particular transcription factor. Here we used ChIP-seq to uncover two distinct binding modes for the ETS transcription factor ELK1. In one mode, other ETS transcription factors can bind regulatory regions in a redundant fashion; in the second, ELK1 binds in a unique fashion to another set of genomic targets. Each binding mode is associated with different binding site features and also distinct regulatory outcomes. Furthermore, the type of binding mode also determines the control of functionally distinct subclasses of genes and hence the phenotypic response elicited. This is demonstrated for the unique binding mode where a novel role for ELK1 in controlling cell migration is revealed. We have therefore uncovered an unexpected link between the type of binding mode employed by a transcription factor, the subsequent gene regulatory mechanisms used, and the functional categories of target genes controlled.

  8. Effect of Common Buffers and Heterocyclic Ligands on the Binding of Cu(II at the Multimetal Binding Site in Human Serum Albumin

    Directory of Open Access Journals (Sweden)

    Magdalena Sokołowska

    2010-01-01

    Full Text Available Visible-range circular dichroism titrations were used to study Cu(II binding properties of Multimetal Binding Site (MBS of Human Serum Albumin (HSA. The formation of ternary MBS-Cu(II-Buffer complexes at pH 7.4 was positively verified for sodium phosphate, Tris, and Hepes, the three most common biochemical buffers. The phosphate > Hepes > Tris order of affinities, together with strong spectral changes induced specifically by Tris, indicates the presence of both Buffer-Cu(II and Buffer-HSA interactions. All complexes are strong enough to yield a nearly 100% ternary complex formation in 0.5 mM HSA dissolved in 100 mM solutions of respective buffers. The effects of warfarin and ibuprofen, specific ligands of hydrophobic pockets I and II in HSA on the Cu(II binding to MBS were also investigated. The effects of ibuprofen were negligible, but warfarin diminished the MBS affinity for Cu(II by a factor of 20, as a result of indirect conformational effects. These results indicate that metal binding properties of MBS can be modulated directly and indirectly by small molecules.

  9. 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...

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

    NARCIS (Netherlands)

    R.B. Baleeiro (Renato); K.H. Wiesmüller (Karl Heinz); L. Dähne (Lars); J. Lademann (Jürgen); J.A. Barbuto (José); P. 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 e

  11. HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.

    Directory of Open Access Journals (Sweden)

    Anders Näsman

    Full Text Available HPV-DNA positive (HPVDNA+ oropharyngeal squamous cell carcinoma (OSCC has better clinical outcome than HPV-DNA negative (HPVDNA- OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS, disease-specific survival (DSS and overall survival (OS in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT or radiotherapy (RT alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

  12. 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

  13. 77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-03-19

    ... March 19, 2012 Part II Department of Health and Human Services Food and Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls... SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration...

  14. Synthesis, crystal structure and electrochemical and DNA binding studies of oxygen bridged-copper(II) carboxylate

    Science.gov (United States)

    Iqbal, Muhammad; Ali, Saqib; Tahir, Muhammad Nawaz; Muhammad, Niaz; Shah, Naseer Ali; Sohail, Manzar; Pandarinathan, Vedapriya

    2015-08-01

    A new binuclear O-bridged Cu(II) complex with 4-chlorophenyl acetate and 2,2‧-bipyridine has been synthesized and characterized using FT-IR, powder and single crystal XRD and electrochemical solution studies. The results revealed that the two penta-coordinated Cu(II) centers are linked by two carboxylate ligands in end-on bonding fashion. The coordination geometry is slightly distorted square pyramidal (SP) with bridging oxygen atoms occupying the apical position and other ligands lying in the equatorial plane. The striking difference in Cu-O bond distance of the bridging oxygen atom in the complex may be responsible for the SP geometry of Cu(II) ion. The complex gave rise to metal centered irreversible electro-activity where one electron Cu(II)/Cu(III) oxidation process and a single step two electron Cu(II)/Cu(0) reduction process was observed. The redox processes were found predominantly adsorption controlled. The values of diffusion coefficient and heterogeneous rate constant for oxidation process were 6.98 × 10-7 cm2 s-1 and 4.60 × 10-5 cm s-1 while the corresponding values for reduction were 5.30 × 10-8 cm2 s-1 and 5.41 × 10-6 cm s-1, respectively. The formal potential and charge transfer coefficient were also calculated. The DNA-binding ability was explored through cyclic voltammetry and UV-Visible spectroscopy. Diminution in the value of Do for oxidation indicated the binding of the complex with DNA corresponding to Kb = 8.58 × 104 M-1. UV-Visible spectroscopy yielded ε = 49 L mol-1 cm-1 and Kb = 2.96 × 104 M-1. The data of both techniques support each other. The self-induced redox activation of the complex, as indicated by cyclic voltammetry heralds its potential applications in redox catalysis and anticancer activity.

  15. The metallomics approach: use of Fe(II) and Cu(II) footprinting to examine metal binding sites on serum albumins.

    Science.gov (United States)

    Duff, Michael R; Kumar, Challa V

    2009-11-01

    Metal binding to serum albumins is examined by oxidative protein-cleavage chemistry, and relative affinities of multiple metal ions to particular sites on these proteins were identified using a fast and reliable chemical footprinting approach. Fe(ii) and Cu(ii), for example, mediate protein cleavage at their respective binding sites on serum albumins, in the presence of hydrogen peroxide and ascorbate. This metal-mediated protein-cleavge reaction is used to evaluate the binding of metal ions, Na(+), Mg(2+), Ca(2+), Al(3+), Cr(3+), Mn(2+), Co(2+), Ni(2+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Ce(3+) to albumins, and the relative affinities (selectivities) of the metal ions are rapidly evaluated by examining the extent of inhibition of protein cleavage. Four distinct systems Fe(II)/BSA, Cu(II)/BSA, Fe(II)/HSA and Cu(II)/HSA are examined using the above strategy. This metallomics approach is novel, even though the cleavage of serum albumins by Fe(II)/Cu(II) has been reported previously by this laboratory and many others. The protein cleavage products were analyzed by SDS PAGE, and the intensities of the product bands quantified to evaluate the extent of inhibition of the cleavage and thereby evaluate the relative binding affinities of specific metal ions to particular sites on albumins. The data show that Co(II) and Cr(III) showed the highest degree of inhibition, across the table, followed by Mn(II) and Ce(III). Alakali metal ions and alkaline earth metal ions showed very poor affinity for these metal sites on albumins. Thus, metal binding profiles for particular sites on proteins can be obtained quickly and accurately, using the metallomics approach.

  16. The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes.

    Science.gov (United States)

    Fanger, N A; Cosman, D; Peterson, L; Braddy, S C; Maliszewski, C R; Borges, L

    1998-11-01

    The MHC class I binding proteins leukocyte immunoglobulin-like receptor (LIR)-1 and -2 recognize a similar broad spectrum of HLA-A, -B and -C alleles but are differentially expressed in lymphocytes, monocytes, and dendritic cells. In monocytes, phosphorylation of LIR-1 and LIR-2 results in the binding of the tyrosine phosphatase SHP-1. Coligation of either LIR with Fcgamma receptor I (CD64) inhibits tyrosine phosphorylation of the associated Fc receptor gamma chain and Syk molecules, as well as intracellular calcium mobilization. These findings suggest that LIR-1 and LIR-2 function as unique MHC class I receptors involved in the inhibition or down-modulation of monocyte activation signals, particularly those mediated through the receptors for IgG, IgE and IgA.

  17. Signalling via MHC class II molecules modifies the composition of GEMs in APC.

    Science.gov (United States)

    Setterblad, N; Becart, S; Charron, D; Mooney, N

    2001-01-01

    Major histocompatibility complex (MHC) class II molecules are responsible for peptide presentation to helper T lymphocytes and as such play an essential role in the immune response. These molecules transmit intracellular signals leading to diverse consequences in B lymphocytes including proliferation and apoptosis. Recent studies have revealed that glycolipid enriched membrane microdomains (GEMs) behave as signalling platforms for a variety of lymphocyte receptors. We have quantified human leucocyte antigen (HLA)-DR molecules localized in GEMs in human B lymphocytes. Use of a model imitating the interaction of HLA-DR with a T-cell receptor (TCR) modified the constituents of the HLA-DR-enriched GEMs. Confocal microscopy demonstrated a recruitment of HLA-DR and the ganglioside GM1 at the site of HLA-DR interaction with the stimulating ligand. Moreover, cholesterol depletion efficiently impaired this recruitment. Co-localizing proteins detected in HLA-DR-enriched GEMs include protein kinase C (PKC)-delta and actin. These data reveal that MHC class II antigens are localized in GEMs in mature human B lymphocytes and indicates that the formation of the immunological synapse regulates the composition of HLA-DR enriched GEMs in the antigen presenting cell (APC).

  18. 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.

  19. Comparison of 2 modifications of the twin-block appliance in matched Class II samples.

    Science.gov (United States)

    Parkin, N A; McKeown, H F; Sandler, P J

    2001-06-01

    The purpose of this study was to compare the skeletal and dental changes contributing to Class II correction with 2 modifications of the Twin-block appliance: Twin-block appliances that use a labial bow (TB1) and Twin-block appliances that incorporate high-pull headgear and torquing spurs on the maxillary central incisors (TB2). After pretreatment equivalence was established, a total of 36 consecutively treated patients with the TB1 modification were compared with 27 patients treated with the TB2 modification. Both samples were treated in the same hospital department and the same technician made all the appliances. The cephalostat, digitizing package, and statistical methods were common to both groups. The results demonstrated that the addition of headgear to the appliance resulted in effective vertical and sagittal control of the maxillary complex and thus maximized the Class II skeletal correction in the TB2 sample. Use of the torquing springs resulted in less retroclination of the maxillary incisors in the TB2 sample when compared with the TB1 sample; however, this difference did not reach the level of statistical significance.

  20. Transverse craniofacial dimensions in Angle Class II, Division 1 malocclusion according to breathing mode

    Directory of Open Access Journals (Sweden)

    Agda Rísia David Pinto Coelho

    2010-03-01

    Full Text Available The aim of this longitudinal study was to assess the relation between the transverse craniofacial dimensions of subjects with Class II, Division 1 malocclusion and the breathing mode presented by them. Forty Angle Class II, Division 1 malocclusion subjects of both genders participated in the study, 23 of which were predominantly nose breathers and 17 were predominantly mouth breathers. The mean age ranged from 10 years and 9 months to 14 years - Age range 1; and from 13 years and 4 months to 16 years and 6 months - Age range 2. Measurements of six transverse craniofacial dimensions were performed in P-A teleradiographs: Total Sphenoid, Total Zygomatic, Total Nasal Cavity, Total Maxilla, Total Mastoid and Total Antegonion. The transversal craniofacial dimensions were measured and compared in both groups at age ranges 1 and 2. The longitudinal assessment of age ranges 1 and 2 showed that there was no statistically significant influence of the breathing mode on the craniofacial dimensions evaluated, or on the alteration of these dimensions. Breathing mode had no influence on craniofacial development in the sample studied.

  1. Morphological changes of the facial skeleton in Class II/1 patients treated with orthodontic functional appliances

    Directory of Open Access Journals (Sweden)

    Dana Festila

    2014-01-01

    Full Text Available Aim: The aim of this study was to investigate, using lateral cephalometry, the skeletal changes in maxillary bones induced through functional jaw orthopedic therapy. 30 patients with class II division 1 malocclusion and average age of 10.4 years were included in the study. Material and Methods: Cephalometric data were analyzed with the following methods: Burstone, McNamara, Rickets, Tweed and Wits and treatment changes were evaluated overlapping the lateral cephalograms on cranial base with sella registered. Results: The results showed reduced over-jet in average with 2.46 mm, mandibular advancement with a mean value of 2.72 mm and increasing of the total mandibular length with a mean value of 4.17 mm. Although we found an inhibiting in the anterior development of the maxilla with an average of 1.57 degree, the decrease of the anterior-posterior discrepancy was due especially to the mandible. Conclusions: It can be concluded that functional appliances were effective in correcting class II malocclusion. Changes of the position and mandible′s length determined improved facial profile but did not correct it completely because of the chin that moved not only anterior but also downward, as a result of vertical ramus growth.

  2. Genomic analysis identifies class II mismatches in serologically DR-compatible human renal allografts.

    Science.gov (United States)

    Bushell, A; Wood, K J; Morris, P J

    1988-11-01

    Many studies, including those from our own center, have shown that matching the donor and recipient for HLA-DR antigens has a beneficial effect on the outcome of cadaveric renal transplantation. However, cases of irreversible graft rejection are sometimes seen in patients who have received an HLA-DR-compatible kidney, suggesting that serologic compatibility for HLA-DR may not always ensure reduced alloreactivity toward the graft. We have examined a number of recipients and their serologically DR-compatible cadaveric donors by Southern blotting and hybridization with locus specific HLA class II probes in order to determine whether in these patients there were class II mismatches that had been undetected by serology. The results show that the analysis of DR beta restriction fragment patterns does little more than complement and confirm the serologic identification of HLA-DR. Hybridization with DQ alpha and DQ beta probes, however, significantly extends the number of DQ specificities that can be detected and suggests that DQ mismatches in DR-compatible donor-recipient pairs may be more common than previously supposed, although it is not possible to draw any conclusions on the influence of DQ incompatibilities in the presence of DR compatibility on graft outcome.

  3. 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.

  4. Search for class II methanol masers at 23.1 GHz

    CERN Document Server

    Cragg, D M; Caswell, J L; Ellingsen, S P; Godfrey, P D

    2004-01-01

    In the early days of methanol maser discoveries the 9(2)-10(1) A+ transition at 23.1 GHz was found to exhibit maser characteristics in the northern star-forming region W3(OH), and probable maser emission in two other sources. Attention subsequently turned to the 6.6-GHz 5(1)-6(0) A+ methanol maser transition, which has proved a valuable tracer of early high-mass star formation. We have undertaken a new search for 23.1-GHz methanol masers in 50 southern star formation regions using the Parkes radiotelescope. The target sources all exhibit class II methanol maser emission at 6.6 GHz, with 20 sources also displaying maser features in the 107.0-GHz 3(1)-4(0) A+ methanol line. Strong emission at 23.1 GHz in NGC 6334F was confirmed, but no emission was detected in the remaining sources. Thus the 23.1-GHz methanol masers are rare. A maser model in which methanol molecules are pumped to the second torsionally excited state by radiation from warm dust can account for class II maser activity in all the transitions in w...

  5. IMPORTANCE OF RESEARCH HLA ANTIBODIES CLASS I AND II, AND MICA ANTIBODIES IN KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2011-01-01

    Full Text Available The purpose of this study was to investigate the occurrence of HLA and MICA antibodies in patients from the waiting list for kidney transplantation and their influence on the course of post-transplant period. Determination of HLA antibodies class I and II, and MICA antibodies was performed on a platform of Luminex (xMAP-tech- nology using sets LABScreen ONE LAMBDA (U.S.. A total of 156 patients from the waiting list for kidney transplantation. Revealed the presence of HLA and MICA antibodies in the serum of 31.4% of patients. Regraf- ted patients increased the content of antibodies to the antigens of HLA system was noted in 88.2% of cases, 47% met the combination of antibodies to the I, II classes and MICA. In patients awaiting first kidney transplantation, HLA and MICA antibodies were determined in 23.7% of cases. The presence of pretransplant HLA and MICA antibodies had a significant influence on the course of post-transplant period. Patients with the presence of HLA and MICA in 50% of cases delayed graft function. Sessions of plasmapheresis can reduce the concentration of HLA and MICA antibodies on average by 61.1%. 

  6. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens;

    2014-01-01

    sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast......JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV...... for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR...

  7. 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.

  8. Mycobacterium tuberculosis class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III exhibits DNA regulated modes of interaction with the sliding DNA β-clamp.

    Science.gov (United States)

    Khanam, Taran; Rai, Niyati; Ramachandran, Ravishankar

    2015-10-01

    The class-II AP-endonuclease (XthA) acts on abasic sites of damaged DNA in bacterial base excision repair. We identified that the sliding DNA β-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. A novel 239 QLRFPKK245 motif in the DNA-binding domain of XthA was found to be important for the interactions. Likewise, the peptide binding-groove (PBG) and the C-terminal of β-clamp located on different domains interact with XthA. The β-clamp-XthA complex can be disrupted by clamp binding peptides and also by a specific bacterial clamp inhibitor that binds at the PBG. We also identified that β-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the β-clamp onto DNA is required for activity stimulation. A reduction in XthA activity stimulation was observed in the presence of β-clamp binding peptides supporting that direct interactions between the proteins are necessary to cause stimulation. Finally, we found that in the absence of DNA, the PBG located on the second domain of the β-clamp is important for interactions with XthA, while the C-terminal domain predominantly mediates functional interactions in the substrate's presence.

  9. Collagen binding specificity of the discoidin domain receptors: Binding sites on collagens II and III and molecular determinants for collagen IV recognition by DDR1

    OpenAIRE

    Xu, Huifang; Raynal, Nicolas; Stathopoulos, Stavros; Myllyharju, Johanna; Farndale, Richard W.; Leitinger, Birgit

    2011-01-01

    The discoidin domain receptors, DDR1 and DDR2 are cell surface receptor tyrosine kinases that are activated by triple-helical collagen. While normal DDR signalling regulates fundamental cellular processes, aberrant DDR signalling is associated with several human diseases. We previously identified GVMGFO (O is hydroxyproline) as a major DDR2 binding site in collagens I–III, and located two additional DDR2 binding sites in collagen II. Here we extend these studies to the homologous DDR1 and the...

  10. 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.

  11. Treatment of Class II high angle malocclusions with the Herbst appliance: a cephalometric investigation.

    Science.gov (United States)

    Schiavoni, R; Grenga, V; Macri, V

    1992-11-01

    The purpose of this study was to examine the results of treatment of Class II malocclusions by using two different designs of the Herbst appliance. Cephalometric records from lateral headplates of 19 consecutively treated Class II cases were evaluated. The headplates were taken before and after the treatment stage in which the Herbst appliance was used. The patients were divided into two groups: the first group, normohypodivergent, was treated with the Herbst appliance attached to bands; the second group, hyperdivergent, was treated with the Herbst appliance attached to acrylic splints in which a high-pull headgear was also used. The results were compared between these groups and with a control group age-matched from Bolton standards to match the changes in the Herbst samples against what might be expected in case of normal growth during similar periods of time. The results of the investigation revealed the following: (1) 9 months of treatment resulted in Class I dental arch relationships in all 19 cases; (2) the Herbst appliance attached to bands did not significantly modify the vertical growth pattern of the normohypodivergent patients; and (3) in hyperdivergent patients, the use of a Herbst appliance attached to acrylic splints in conjunction with the use of a high-pull headgear allowed a better control of the vertical dimension, as assessed by the cephalometric parameters (FA, FMA, Go-Gn-SN). The clinician should be aware of the different dentofacial changes induced in the vertical plane by different designs of the Herbst appliance to better program treatment strategy.

  12. MAXILLARY INCISOR TRAUMA IN PATIENTS WITH CLASS II DIVISION 1 DENTAL MALOCCLUSION: ASSOCIATED FACTORS

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    Elif Yaman DOSDOĞRU

    2017-01-01

    Full Text Available Purpose: The aim of this study was to assess the association between the presence of maxillary incisor trauma (MIT with age, gender, dentition type, the degree of overjet (OJ, lip form, respiratory type and dental arch form in patients with Class II division 1 dental malocclusion. Subjects and Methods: 256 patients (mean age: 15.80 ± 2.2 were included in this study. The patients’ gender, dentition type, superior lip form, dental arch form and respiratory type were recorded. Participants were divided into four groups according to the severity of OJ: 3.5 mm II ≤ 6 mm with incompetent lip, 6 mmClass II division 1 malocclusion.

  13. 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.

  14. DNA-Damage Response RNA-Binding Proteins (DDRBPs): Perspectives from a New Class of Proteins and Their RNA Targets.

    Science.gov (United States)

    Dutertre, Martin; Vagner, Stéphan

    2016-09-29

    Upon DNA damage, cells trigger an early DNA-damage response (DDR) involving DNA repair and cell cycle checkpoints, and late responses involving gene expression regulation that determine cell fate. Screens for genes involved in the DDR have found many RNA-binding proteins (RBPs), while screens for novel RBPs have identified DDR proteins. An increasing number of RBPs are involved in early and/or late DDR. We propose to call this new class of actors of the DDR, which contain an RNA-binding activity, DNA-damage response RNA-binding proteins (DDRBPs). We then discuss how DDRBPs contribute not only to gene expression regulation in the late DDR but also to early DDR signaling, DNA repair, and chromatin modifications at DNA-damage sites through interactions with both long and short noncoding RNAs.

  15. Selection and trans-species polymorphism of major histocompatibility complex class II genes in the order Crocodylia.

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    Weerachai Jaratlerdsiri

    Full Text Available Major Histocompatibility Complex (MHC class II genes encode for molecules that aid in the presentation of antigens to helper T cells. MHC characterisation within and between major vertebrate taxa has shed light on the evolutionary mechanisms shaping the diversity within this genomic region, though little characterisation has been performed within the Order Crocodylia. Here we investigate the extent and effect of selective pressures and trans-species polymorphism on MHC class II α and β evolution among 20 extant species of Crocodylia. Selection detection analyses showed that diversifying selection influenced MHC class II β diversity, whilst diversity within MHC class II α is the result of strong purifying selection. Comparison of translated sequences between species revealed the presence of twelve trans-species polymorphisms, some of which appear to be specific to the genera Crocodylus and Caiman. Phylogenetic reconstruction clustered MHC class II α sequences into two major clades representing the families Crocodilidae and Alligatoridae. However, no further subdivision within these clades was evident and, based on the observation that most MHC class II α sequences shared the same trans-species polymorphisms, it is possible that they correspond to the same gene lineage across species. In contrast, phylogenetic analyses of MHC class II β sequences showed a mixture of subclades containing sequences from Crocodilidae and/or Alligatoridae, illustrating orthologous relationships among those genes. Interestingly, two of the subclades containing sequences from both Crocodilidae and Alligatoridae shared specific trans-species polymorphisms, suggesting that they may belong to ancient lineages pre-dating the divergence of these two families from the common ancestor 85-90 million years ago. The results presented herein provide an immunogenetic resource that may be used to further assess MHC diversity and functionality in Crocodylia.

  16. Selection and trans-species polymorphism of major histocompatibility complex class II genes in the order Crocodylia.

    Science.gov (United States)

    Jaratlerdsiri, Weerachai; Isberg, Sally R; Higgins, Damien P; Miles, Lee G; Gongora, Jaime

    2014-01-01

    Major Histocompatibility Complex (MHC) class II genes encode for molecules that aid in the presentation of antigens to helper T cells. MHC characterisation within and between major vertebrate taxa has shed light on the evolutionary mechanisms shaping the diversity within this genomic region, though little characterisation has been performed within the Order Crocodylia. Here we investigate the extent and effect of selective pressures and trans-species polymorphism on MHC class II α and β evolution among 20 extant species of Crocodylia. Selection detection analyses showed that diversifying selection influenced MHC class II β diversity, whilst diversity within MHC class II α is the result of strong purifying selection. Comparison of translated sequences between species revealed the presence of twelve trans-species polymorphisms, some of which appear to be specific to the genera Crocodylus and Caiman. Phylogenetic reconstruction clustered MHC class II α sequences into two major clades representing the families Crocodilidae and Alligatoridae. However, no further subdivision within these clades was evident and, based on the observation that most MHC class II α sequences shared the same trans-species polymorphisms, it is possible that they correspond to the same gene lineage across species. In contrast, phylogenetic analyses of MHC class II β sequences showed a mixture of subclades containing sequences from Crocodilidae and/or Alligatoridae, illustrating orthologous relationships among those genes. Interestingly, two of the subclades containing sequences from both Crocodilidae and Alligatoridae shared specific trans-species polymorphisms, suggesting that they may belong to ancient lineages pre-dating the divergence of these two families from the common ancestor 85-90 million years ago. The results presented herein provide an immunogenetic resource that may be used to further assess MHC diversity and functionality in Crocodylia.

  17. Genetic variation of the major histocompatibility complex (MHC class II B gene in the threatened Hume's pheasant, Syrmaticus humiae.

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    Weicai Chen

    Full Text Available Major histocompatibility complex (MHC genes are the most polymorphic genes in vertebrates and encode molecules that play a crucial role in pathogen resistance. As a result of their diversity, they have received much attention in the fields of evolutionary and conservation biology. Here, we described the genetic variation of MHC class II B (MHCIIB exon 2 in a wild population of Hume's pheasant (Syrmaticus humiae, which has suffered a dramatic decline in population over the last three decades across its ranges in the face of heavy exploitation and habitat loss. Twenty-four distinct alleles were found in 73 S. humiae specimens. We found seven shared alleles among four geographical groups as well as six rare MHCIIB alleles. Most individuals displayed between one to five alleles, suggesting that there are at least three MHCIIB loci of the Hume's pheasant. The dN ⁄ dS ratio at putative antigen-binding sites (ABS was significantly greater than one, indicating balancing selection is acting on MHCIIB exon 2. Additionally, recombination and gene conversion contributed to generating MHCIIB diversity in the Hume's pheasant. One to three recombination events and seventy-five significant gene conversion events were observed within the Hume's pheasant MHCIIB loci. The phylogenetic tree and network analysis revealed that the Hume's pheasant alleles do not cluster together, but are scattered through the tree or network indicating a trans-species evolutionary mode. These findings revealed the evolution of the Hume's pheasant MHC after suffering extreme habitat fragmentation.

  18. Copper(II) ions and the Alzheimer's amyloid-β peptide: Affinity and stoichiometry of binding

    Science.gov (United States)

    Tõugu, Vello; Friedemann, Merlin; Tiiman, Ann; Palumaa, Peep

    2014-10-01

    Deposition of amyloid beta (Aβ) peptides into amyloid plaques is the hallmark of Alzheimer's disease. According to the amyloid cascade hypothesis this deposition is an early event and primary cause of the disease, however, the mechanisms that cause this deposition remain elusive. An increasing amount of evidence shows that the interactions of biometals can contribute to the fibrillization and amyloid formation by amyloidogenic peptides. From different anions the copper ions deserve the most attention since it can contribute not only toamyloid formation but also to its toxicity due to the generation of ROS. In this thesis we focus on the affinity and stoichiometry of copper(II) binding to the Aβ molecule.

  19. Characterization of the internal calcium(II) binding sites in dissolved insulin hexamer using europium(III) fluorescence.

    Science.gov (United States)

    Alameda, G K; Evelhoch, J L; Sudmeier, J L; Birge, R R

    1985-03-26

    The fluorescence of Eu(III) is used to study the nature of the Ca(II) binding sites in the central cavity of the two-zinc(II) insulin hexamer. The dependence of the Eu(III) fluorescence lifetime upon Eu(III) stoichiometry indicates that there are three identical Eu(III) binding sites present in the two-zinc(II) insulin hexamer in solution. Addition of excess Ca(II) causes a decrease in the Eu(III) fluorescence intensity, confirming that Ca(II) competes for the observed Eu(III) sites. The solvent dependence of the Eu(III) fluorescence lifetime (H2O vs. D2O) indicates that four OH groups are coordinated to each Eu(III) in the hexamer. Substitution of Co(II) for Zn(II) causes a decrease in the Eu(III) fluorescence lifetime. Calculations based on Förster energy-transfer theory predict that the Co(II) [or Zn(II) in vivo] and Eu(III) [or Ca(II) in vivo] binding sites are separated by 9.6 +/- 0.5 A. Variation of the metal stoichiometries indicates that all three Eu(III) [or Ca(II) in vivo] sites are equidistant from the Zn(II) sites. We conclude that these sites are identical with the three central Zn(II) sites present in insulin hexamer crystals soaked in excess Zn(II) [Emdin, S. O., Dodson, G., Cutfield, J. M., & Cutfield, S. M. (1980) Diabetologia 19, 174-182] and suggest that these central sites are occupied by Ca(II) in vivo.

  20. A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes.

    Science.gov (United States)

    Dijkstra, Johannes Martinus; Katagiri, Takayuki; Hosomichi, Kazuyoshi; Yanagiya, Kazuyo; Inoko, Hidetoshi; Ototake, Mitsuru; Aoki, Takashi; Hashimoto, Keiichiro; Shiina, Takashi

    2007-04-01

    Most of the previously studied teleost MHC class I molecules can be classified into two broad lineages: "U" and "Z/ZE." However, database reports on genes in cyprinid and salmonid fishes show that there is a third major lineage, which lacks detailed analysis so far. We designated this lineage "L" because of an intriguing linkage characteristic. Namely, one zebrafish L locus is closely linked with MHC class II loci, despite the extensively documented nonlinkage of teleost class I with class II. The L lineage consists of highly variable, nonclassical MHC class I genes, and has no apparent orthologues outside teleost fishes. Characteristics that distinguish the L lineage from most other MHC class I are (1) absence of two otherwise highly conserved tryptophan residues W51 and W60 in the alpha1 domain, (2) a low GC content of the alpha1 and alpha2 exons, and (3) an HINLTL motif including a possible glycosylation site in the alpha3 domain. In rainbow trout (Oncorhynchus mykiss) we analyzed several intact L genes in detail, including their genomic organization and transcription pattern. The gene Onmy-LAA is quite different from the genes Onmy-LBA, Onmy-LCA, Onmy-LDA, and Onmy-LEA, while the latter four are similar and categorized as "Onmy-LBA-like." Whereas the Onmy-LAA gene is organized like a canonical MHC class I gene, the Onmy-LBA-like genes are processed and lack all introns except intron 1. Onmy-LAA is predominantly expressed in the intestine, while the Onmy-LBA-like transcripts display a rather homogeneous tissue distribution. To our knowledge, this is the first description of an MHC class I lineage with multiple copies of processed genes, which are intact and transcribed. The present study significantly improves the knowledge of MHC class I variation in teleosts.

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

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    Pía Villanueva

    2009-09-01

    Full Text Available OBJETIVO: determinar los patrones de articulación de fones consonánticos en sujetos de habla española chilena clases I, II y III esqueletal; comparar las diferencias fonéticas que existan entre clases esqueletales. MÉTODOS: se seleccionaron 54 individuos que cumplían con los criterios de inclusión determinados mediante un examen clínico intraoral y a través del análisis de Ricketts, y se conformaron los grupos de estudio de pacientes clases esqueletales I, II y III. Se les realizó un examen fonoarticulatorio estandarizado para determinar los fones modificados y el patrón articulatorio compensatorio realizado. RESULTADOS: se observaron cambios en el punto de articulación de fones consonánticos en las tres clases esqueletales, con diferencias significativas en los grupos de fones anteriores y medios entre pacientes clases I y II, sólo en el grupo de los fones anteriores entre pacientes I y III. Entre pacientes clases II y III no se observaron diferencias significativas. Se reportan modificaciones y compensaciones cualitativamente distintas entre las clases esqueletales. CONCLUSIONES: en relación a pacientes clase I, los pacientes clase II o III, presentan distinto grado de modificación en el punto de articulación de fones consonánticos. Las diferencias observadas se relacionan con los patrones esqueletales propios de cada clase.PURPOSE: to determine the consonant phonemes articulation patterns in Chilean skeletal class I, II and III Spanish speakers and compare their phonetic differences. METHODS: fifty-four skeletal class I, II and III subjects were selected, based on intraoral clinical examination and Ricketts cephalometric analysis, constituting the study groups. A standardized phonoarticulatory test was applied to each patient to determine the modified phonemes and their compensatory patterns. RESULTS: the findings indicate changes in articulation in all three groups. Significant differences were found in anterior and medium

  2. Mercury(II) binds to both of chymotrypsin's histidines, causing inhibition followed by irreversible denaturation/aggregation.

    Science.gov (United States)

    Stratton, Amanda; Ericksen, Matthew; Harris, Travis V; Symmonds, Nick; Silverstein, Todd P

    2017-02-01

    The toxicity of mercury is often attributed to its tight binding to cysteine thiolate anions in vital enzymes. To test our hypothesis that Hg(II) binding to histidine could be a significant factor in mercury's toxic effects, we studied the enzyme chymotrypsin, which lacks free cysteine thiols; we found that chymotrypsin is not only inhibited, but also denatured by Hg(II). We followed the aggregation of denatured enzyme by the increase in visible absorbance due to light scattering. Hg(II)-induced chymotrypsin precipitation increased dramatically above pH 6.5, and free imidazole inhibited this precipitation, implicating histidine-Hg(II) binding in the process of chymotrypsin denaturation/aggregation. Diethylpyrocarbonate (DEPC) blocked chymotrypsin's two histidines (his40 and his57 ) quickly and completely, with an IC50 of 35 ± 6 µM. DEPC at 350 µM reduced the hydrolytic activity of chymotrypsin by 90%, suggesting that low concentrations of DEPC react with his57 at the active site catalytic triad; furthermore, DEPC below 400 µM enhanced the Hg(II)-induced precipitation of chymotrypsin. We conclude that his57 reacts readily with DEPC, causing enzyme inhibition and enhancement of Hg(II)-induced aggregation. Above 500 µM, DEPC inhibited Hg(II)-induced precipitation, and [DEPC] >2.5 mM completely protected chymotrypsin against precipitation. This suggests that his40 reacts less readily with DEPC, and that chymotrypsin denaturation is caused by Hg(II) binding specifically to the his40 residue. Finally, we show that Hg(II)-histidine binding may trigger hemoglobin aggregation as well. Because of results with these two enzymes, we suggest that metal-histidine binding may be key to understanding all heavy metal-induced protein aggregation.

  3. Re-directing CD4+ T cell responses with the flanking residues of MHC class II-bound peptides: the core is not enough

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    David Kenneth Cole

    2013-07-01

    Full Text Available Recombinant αβ T cell receptors (TCRs recognise short peptides presented at the cell surface in complex with MHC molecules. There are two main subsets of αβ T cells: CD8+ T cells that recognise mainly cytosol-derived peptides in the context of MHC class I (pMHC-I, and CD4+ T cells that recognise peptides usually derived from exogenous proteins presented by MHC class II (pMHC-II. Unlike the more uniform peptide lengths (usually 8-13mers bound in the MHC-I closed groove, MHC-II presented peptides are of a highly variable length. The bound peptides consist of a core bound 9mer (reflecting the binding motif for the particular MHC-II type but with variable peptide flanking residues (PFRs that can extend from both the N- and C-terminus of the MHC-II binding groove. Although pMHC-I and pMHC-II play a virtually identical role during T cell responses (T cell antigen presentation and are very similar in overall conformation, there exist a number of subtle but important differences that may govern the functional dichotomy observed between CD8+ and CD4+ T cells. Here, we provide an overview of the impact of structural differences between pMHC-I and pMHC-II and the molecular interactions with the TCR including the functional importance of MHC-II peptide flanking residues. We consider how factors such as anatomical location, inflammatory milieu and particular types of APC might, in theory, contribute to the quantitative (i.e. pMHC ligand frequency as well as qualitative (i.e. variable PFR nature of peptide epitopes, and hence offer a means of control and influence of a CD4+ T cell response. Lastly, we review our recent findings showing how modifications to these flanking regions modify CD4+ T cell antigen recognition. These findings may have novel applications for the development of CD4+ T cell peptide vaccines and diagnostics.

  4. MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data.

    Science.gov (United States)

    Papassavas, E C; Spyropoulou-Vlachou, M; Papassavas, A C; Schipper, R F; Doxiadis, I N; Stavropoulos-Giokas, C

    2000-06-01

    In the present study, DNA typing for HLA-A, C, B, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, and DPB1 was performed for 246 healthy, unrelated Greek volunteers of 20-59 years of age. Phenotype, genotype frequencies, Hardy-Weinberg equilibrium fit, and 3-locus haplotype frequencies for HLA-A, C, B, HLA-A, B, DRB1, HLA-DRB1, DQA1, DQB1, and HLA-DRB1, DQB1, DPB1 were calculated. Furthermore, linkage disequilibrium, deltas, relative deltas and p-values for significance of the deltas were defined. The population studied is in Hardy-Weinberg equilibrium, and many MHC haplotypes are in linkage disequilibrium. The most frequent specificities were HLA-A*02 (phenotype frequency = 44.3%) followed by HLA-A*24 (27.2%), HLA-B*51 (28.5%), HLA-B*18 (26.8%) and HLA-B*35 (26.4%) and HLA-Cw*04 (30.1%) and HLA-Cw*12 (26.8%). The most frequent MHC class II alleles were HLA-DRB1*1104 (34.1%), HLA-DQB1*0301 (54.5%) and HLA-DPB1*0401 with a phenotype frequency of 59.8%. The most prominent HLA-A, C, B haplotypes were HLA-A*24, Cw*04, B*35, and HLA-A*02, Cw*04, B*35, each of them observed in 21/246 individuals. The most frequent HLA-A, B, DRB1 haplotype was HLA-A*02, B*18, DRB1*1104 seen in 20/246 individuals, while the haplotype HLA-DRB1*1104, DQB1*0301, DPB1*0401 was found in 49/246 individuals. Finally, the haplotype DRB1*1104, DQA1*0501, DQB1*0301 was observed in 83/246 individuals. These results can be used for the estimation of the probability of finding a suitable haplotypically identical related or unrelated stem cell donor for patients of Greek ancestry. In addition, they can be used for HLA and disease association studies, genetic distance studies in the Balkan and Mediterranean area, paternity cases, and matching probability calculations for the optimal allocation of kidneys in Greece.

  5. Ca(II) Binding Regulates and Dominates the Reactivity of a Transition-Metal-Ion-Dependent Diesterase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Pedroso, Marcelo M; Larrabee, James A; Ely, Fernanda; Gwee, Shuhui E; Mitić, Nataša; Ollis, David L; Gahan, Lawrence R; Schenk, Gerhard

    2016-01-18

    The diesterase Rv0805 from Mycobacterium tuberculosis is a dinuclear metallohydrolase that plays an important role in signal transduction by controlling the intracellular levels of cyclic nucleotides. As Rv0805 is essential for mycobacterial growth it is a promising new target for the development of chemotherapeutics to treat tuberculosis. The in vivo metal-ion composition of Rv0805 is subject to debate. Here, we demonstrate that the active site accommodates two divalent transition metal ions with binding affinities ranging from approximately 50 nm for Mn(II) to about 600 nm for Zn(II) . In contrast, the enzyme GpdQ from Enterobacter aerogenes, despite having a coordination sphere identical to that of Rv0805, binds only one metal ion in the absence of substrate, thus demonstrating the significance of the outer sphere to modulate metal-ion binding and enzymatic reactivity. Ca(II) also binds tightly to Rv0805 (Kd ≈40 nm), but kinetic, calorimetric, and spectroscopic data indicate that two Ca(II) ions bind at a site different from the dinuclear transition-metal-ion binding site. Ca(II) acts as an activator of the enzymatic activity but is able to promote the hydrolysis of substrates even in the absence of transition-metal ions, thus providing an effective strategy for the regulation of the enzymatic activity.

  6. Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

    Science.gov (United States)

    Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

    2016-01-01

    Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This

  7. Probing the Evolution of Massive Young Stellar Objects using Weak Class II 6.7GHz Methanol Maser Emission

    Science.gov (United States)

    Ludwig, Bethany Ann; Cunningham, Nichol

    2017-01-01

    We present results from an investigation of class II 6.7GHz methanol masers towards four Massive Young Stellar Objects (MYSOs). The sources, selected from the Red MSX Source (RMS) Survey (Lumsden et al. 2013), were previously understood to be non-detections for class II methanol maser emission in the methanol multi-beam (MMB) Survey (Caswell et al. 2010.) Class II methanol masers are a well-known sign post of massive star forming regions and may be utilized to probe their relatively poorly understood formation. It is possible that these non-detections are simply weak masers that are potentially associated with a younger evolutionary phase of MYSOs as hypothesized by Olmi et al. (2014). The sources were chosen to sample various stages of evolution, having similar 21 to 8 micron flux ratios and bolometric luminosities as other MYSOs with previous class II methanol maser detections. We observed all 4 MYSOs with ATCA (~2" resolution) at 10 times deeper sensitivity than previously obtained with the MMB survey and have a spectral resolution of 0.087kms^-1 . The raw data is reduced using the program Miriad (Sault, R. J., et al., 1995) and deconvolutioned using the program CASA (McMullin, J. P., et al. 2007.) We determine one of the four observed MYSOs is harboring a weak class II methanol maser. We discuss the possibility of sensitivity limitations on the remaining sources as well as environmental and evolutionary differences between the sources.

  8. The band gap of II-Vi ternary alloys in a tight-binding description

    Energy Technology Data Exchange (ETDEWEB)

    Olguin, Daniel; Blanquero, Rafael [Instituto Politecnico Nacional, Mexico, D.F (Mexico); De Coss, Romeo [Instituto Politecnico Nacional, Yucatan (Mexico)

    2001-02-01

    We present tight-binding calculations for the band gap of II-Vi pseudobinary ternary alloys. We use an sp{sup 3} s* tight-binding Hamiltonian which include spin-orbit coupling. The band gap composition dependence is calculated using a extended version of the virtual crystal approximation, which introduce an empirical correction factor that takes into account the non-linear dependence of the band gap with the composition. The results compare quite well with the experimental data, both for the ternary alloys with wide band gap and for the narrow band gap ones. [Spanish] Presentamos el calculo de la banda de energia prohibida de aleaciones ternarias de compuestos II-VI. El calculo, que incluye interaccion espin-orbita, se hace con el metodo de enlace fuerte, utilizando una base ortogonal de cinco orbitales atomicos por atomo (sp{sup 3} s*), en conjunto con la aproximacion del cristal virtual. En la aproximacion del cristal virtual, incluimos un factor de correccion que toma en cuenta la no linealidad de la banda de energia prohibida como funcion de la concentracion. Con esta correccion nuestros resultados reproducen aceptablemente los datos experimentales hallados en la literatura.

  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

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    Flávia Artese

    2009-06-01

    Full Text Available A má oclusão Classe II de Angle é caracterizada por uma discrepância dentária anteroposterior, que geralmente está acompanhada por alterações esqueléticas. O tratamento ortodôntico precoce permite a correção da discrepância esquelética por controle de crescimento (primeira fase, o que favorece a correção do posicionamento dentário, mais tardiamente (segunda fase. Este relato descreve o tratamento de um caso de má oclusão Classe II, divisão 2, de Angle, em duas fases, e foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO. O caso foi avaliado como representante da Categoria 1, ou seja, má oclusão Classe II de Angle tratada sem extrações dentárias e com controle de crescimento.Angle Class II malocclusion is characterized by an anteroposterior dental discrepancy which is generally accompanied by skeletal disharmonies. Early orthodontic treatment allows the correction of skeletal discrepancies using growth control (first phase which favors later correction of tooth positioning (second phase. This case report describes an Angle Class II, division 2, malocclusion treated in two phases and was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as part of the requirements for BBO certification. It was evaluated as a Category 1 case, i.e., Class II malocclusion treated without extractions, with growth control.

  10. HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations.

    Science.gov (United States)

    Vargas-Alarcón, Gilberto; Granados, Julio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Canto-Cetina, Thelma; Coral-Vázquez, Ramón Mauricio; Areces, Cristina; Gómez-Prieto, Pablo; Arnaiz-Villena, Antonio

    2011-01-01

    We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.

  11. A modified orthodontic protocol for advanced periodontal disease in Class II division 1 malocclusion.

    Science.gov (United States)

    Janson, Marcos; Janson, Guilherme; Murillo-Goizueta, Oscar Edwin Francisco

    2011-04-01

    An interdisciplinary approach is often the best option for achieving a predictable outcome for an adult patient with complex clinical problems. This case report demonstrates the combined periodontal/orthodontic treatment for a 49-year-old woman presenting with a Class II Division 1 malocclusion with moderate maxillary anterior crowding, a 9-mm overjet, and moderate to severe bone loss as the main characteristics of the periodontal disease. The orthodontic treatment included 2 maxillary first premolar extractions through forced extrusion. Active orthodontic treatment was completed in 30 months. The treatment outcomes, including the periodontal condition, were stable 17 months after active orthodontic treatment. The advantages of this interdisciplinary approach are discussed. Periodontally compromised orthodontic patients can be satisfactorily treated, achieving most of the conventional orthodontic goals, if a combined orthodontic/periodontic approach is used.

  12. Tratamento da classe II divisão 1 na dentição mista

    OpenAIRE

    Angelino, André de Brito

    2016-01-01

    Introdução: Os indivíduos portadores da má oclusão de Classe II Divisão 1 possuem diversas etiologias e podem ser encontrados em todas as etnias. As suas características clínicas e radiográficas se agravam com o crescimento e uma vez não tratada, continuam com esta má oclusão por toda sua vida. Para o tratamento ortodôntico na dentição mista recorre-se a dispositivos como aparelhos extra-orais, aparelhos funcionais fixos e removíveis. Objetivo: O objetivo deste trabalho é fazer uma revisão...

  13. Agenesis of maxillary lateral incisor in an Angle Class II, Division 1 malocclusion patient

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    Guilherme Thiesen

    2015-10-01

    Full Text Available The present case report describes the orthodontic treatment of a patient with agenesis of maxillary left lateral incisor and Angle Class II, Division 1 malocclusion. The patient also presented with maxillary midline deviation and inclination of the occlusal plane in the anterior region. Treatment objectives were: correction of sagittal relationship between the maxilla and the mandible; correction of midline deviation, so as to cause maxillary and mandibular midlines to coincide; correction of overbite and leveling of the occlusal plane, so as to create ideal conditions for esthetic rehabilitation of anterior teeth. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as a requirement for the title of certified by the BBO.

  14. Genetic variation in V gene of class II Newcastle disease virus.

    Science.gov (United States)

    Hao, Huafang; Chen, Shengli; Liu, Peng; Ren, Shanhui; Gao, Xiaolong; Wang, Yanping; Wang, Xinglong; Zhang, Shuxia; Yang, Zengqi

    2016-01-01

    The genetic variation and molecular evolution of the V gene of the class II Newcastle disease virus (NDV) isolates with genotypes I-XVIII were determined using bioinformatics. Results indicated that low homology existed in different genotype viruses, whereas high homology often for the same genotypes, exception may be existed within genotypes I, V, VI, and XII. Sequence analysis showed that the genetic variation of V protein was consistent with virus genotype, and specific signatures on the V protein for nine genotypes were identified. Phylogenetic analysis demonstrated that the phylogenetic trees were highly consistent between the V and F genes, with slight discrepancies in the sub-genotypes. Evolutionary rate analyses based on V and F genes revealed the evolution rates varied in genotypes. These data indicate that the genetic variation of V protein is genotype-related and will help in elucidating the molecular evolution of NDV.

  15. Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules.

    Science.gov (United States)

    Grødeland, Gunnveig; Bogen, Bjarne

    2015-06-01

    There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.

  16. 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.

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

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    Ji-Sung Jang

    2014-01-01

    Full Text Available Idiopathic condylar resorption (ICR, also known as idiopathic condylysis or condylar atrophy, is multifactorial pathology leading to severe mandibular retrognathism. The etiology has been shown to be multifactorial, such as avascular necrosis, traumatic injuries, hormone and autoimmune disease and it is largely difficult to distinguish the exact cause in each individual. In spite of the remarkable morphological alteration, surgical intervention is not readily recruited due to the possibility of recurrence of resorption. In order to restore balanced facial profile and occlusion. In this report, we present a camouflage treatment for skeletal Class II with ICR and facial asymmetry involving total arch movement, for the improvement facial profile and reconstruction of occlusion.

  18. Orthodontic Protocol Using Mini-Implant for Class II Treatment in Patient with Special Needs

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    Fernando Pedrin Carvalho Ferreira

    2016-01-01

    Full Text Available Improving facial and dental appearance and social interaction are the main factors for special needs (SN patients to seek orthodontic treatment. The cooperation of SN patients and their parents is crucial for treatment success. Objective. To show through a case report the satisfactory results, both functional and esthetic, in patients with intellectual disability, congenital nystagmus, and severe scoliosis. Materials Used. Pendulum device with mini-implants as anchorage unit. Results. Improvement of facial and dental esthetics, correction of Class II malocclusion, and no root resorption shown in the radiographic follow-up. Conclusion. Knowing the limitations of SN patients, having a trained team, motivating and counting on the cooperation of parents and patients, and employing quick and low-cost orthodontic therapy have been shown to be the essential factors for treatment success.

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

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    Ru-Sen Feng

    2013-01-01

    Full Text Available Hydrophobically modified associating polyacrylamide (HAPAM has good compatibility with the Daqing heavy alkylbenzene sulfonate surfactant. The HAPAM alkali/surfactant/polymer (ASP system can generate ultralow interfacial tension in a wide range of alkali/surfactant concentrations and maintain stable viscosity and interfacial tension for 120 days. The HAPAM ASP system has good injectivity for the Daqing class II reservoirs (100–300 × 10−3 μm2 and can improve oil recovery by more than 25% on top of water flooding. In the presence of both the alkali and the surfactant, the surfactant interacts with the associating groups of the polymer to form more micelles, which can significantly enhance the viscosity of the ASP system. Compared with using HPAM (Mw = 2.5 MDa, using HAPAM can reduce the polymer use by more than 40%.

  20. Prediction of HLA class II alleles using SNPs in an African population.

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    Fasil Tekola Ayele

    Full Text Available Despite the importance of the human leukocyte antigen (HLA gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs. However, the utility of these methods in African populations has not been systematically evaluated.In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1 alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.

  1. 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.

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

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    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.

  3. Marginal and internal adaptation of class II restorations after immediate or delayed composite placement.

    Science.gov (United States)

    Dietschi, Didier; Monasevic, Manuela; Krejci, Ivo; Davidson, Carel

    2002-01-01

    Direct class II composite restorations still represent a challenge, particularly when proximal limits extend below the CEJ. The aim of this in vitro study was to evaluate the influence of the type of adhesive and the delay between adhesive placement and composite insertion on restoration adaptation. Direct class II MOD box-shaped composite restorations (n=8 per group) were placed on intact human third molars, with proximal margins 1mm above or under CEJ. All cavities were filled with a horizontal layering technique, immediately after adhesive placement (IP) or after a 24h delay (DP). A filled three-component adhesive (OptiBond FL: OB) and a single-bottle, unfilled one (Prime & Bond 2.1: PB) were tested. Marginal adaptation was assessed before and after each phase of mechanical loading (250000 cycles at 50 N, 250000 cycles at 75 N and 500000 cycles at 100 N); internal adaptation was evaluated after test completion. Gold-plated resin replicas were observed in the SEM and restoration quality evaluated in percentages of continuity (C) at the margins and within the internal interface, after sample section. Adaptation to beveled enamel proved satisfactory in all groups. After loading, adaptation to gingival dentin degraded more in PB-IP (C=55.1%) than PB-DP (C=86.9%) or OB-DP (C=89%). More internal defects were observed in PB samples (IP: C=79.2% and DP: C=86.3%) compared to OB samples (IP: C=97.4% and DP: C=98.3%). The filled adhesive (OB) produced a better adaptation than the 'one-bottle' brand (PB), hypothetically by forming a stress-absorbing layer, limiting the development of adhesive failures. Postponing occlusal loading (such as the indirect approach) improved also restoration adaptation.

  4. 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

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    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.

  5. Stability of Class II treatment with the Bionator followed by fixed appliances

    Directory of Open Access Journals (Sweden)

    Manoela Favaro FRANCISCONI

    2013-12-01

    Full Text Available Objective: This prospective study assessed the stability of Class II treatment with the Bionator, followed by fixed appliances, 10 years after treatment. Material and Methods: The experimental group comprised 23 patients of both sexes (10 boys, 13 girls at a mean initial age of 11.74 years (late mixed or early permanent dentitions, treated for a mean period of 3.55 years who were evaluated at three stages: initial (T1, final (T2 and long-term posttreatment (T3. A total of 69 lateral cephalograms were evaluated and 69 dental casts were measured using the PAR index. The difference between initial and final PAR indexes, the percentage of occlusal improvement obtained with therapy and the percentage of relapse were calculated, using the PAR index. The variables were compared by repeated measures analysis of variance (ANOVA followed by Tukey tests. Results: The significant improvement in apical base relationship, the palatal inclination of the maxillary incisors and the labial inclination of the mandibular incisors, and the significant improvement in molar relationship and reduction of overjet and overbite, obtained with treatment, remained stable in the long-term posttreatment period. There was also significant improvement in the occlusal relationships which remained stable in the long-term posttreatment period. The percentage of occlusal improvement obtained was of 81.78% and the percentage of relapse was of 4.90%. Conclusions: Treatment of Class II division 1 malocclusions with the Bionator associated with fixed appliances showed to be stable in the long-term posttreatment period.

  6. Influence of different restorative techniques on marginal seal of class II composite restorations

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    Sinval Adalberto Rodrigues Junior

    2010-02-01

    Full Text Available OBJECTIVE: To evaluate the gingival marginal seal in class II composite restorations using different restorative techniques. MATERIAL AND METHODS: Class II box cavities were prepared in both proximal faces of 32 sound human third molars with gingival margins located in either enamel or dentin/cementum. Restorations were performed as follows: G1 (control: composite, conventional light curing technique; G2: composite, soft-start technique; G3: amalgam/composite association (amalcomp; and G4: resin-modified glass ionomer cement/composite, open sandwich technique. The restored specimens were thermocycled. Epoxy resin replicas were made and coated for scanning electron microscopy examination. For microleakage evaluation, teeth were coated with nail polish and immersed in dye solution. Teeth were cut in 3 slices and dye penetration was recorded (mm, digitized and analyzed with Image Tool software. Microleakage data were analyzed statistically by non-parametric Kruskal-Wallis and Mann-Whitney tests. RESULTS: Leakage in enamel was lower than in dentin (p<0.001. G2 exhibited the lowest leakage values (p<0.05 in enamel margins, with no differences between the other groups. In dentin margins, groups G1 and G2 had similar behavior and both showed less leakage (p<0.05 than groups G3 and G4. SEM micrographs revealed different marginal adaptation patterns for the different techniques and for the different substrates. CONCLUSION: The soft-start technique showed no leakage in enamel margins and produced similar values to those of the conventional (control technique for dentin margins.

  7. New susceptibility variants to narcolepsy identified in HLA class II region.

    Science.gov (United States)

    Miyagawa, Taku; Toyoda, Hiromi; Hirataka, Akane; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Imai, Makoto; Fujimura, Yota; Tamura, Yoshiyuki; Ikegami, Azusa; Wada, Yamato; Moriya, Shunpei; Furuya, Hirokazu; Kato, Mitsuhiro; Omata, Naoto; Kojima, Hiroto; Kashiwase, Koichi; Saji, Hiroh; Khor, Seik-Soon; Yamasaki, Maria; Wada, Yuji; Ishigooka, Jun; Kuroda, Kenji; Kume, Kazuhiko; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Hirata, Koichi; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-02-01

    Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

  8. KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif.

    Directory of Open Access Journals (Sweden)

    Arnaud D Colantonio

    2011-03-01

    Full Text Available Molecular interactions between killer immunoglobulin-like receptors (KIRs and their MHC class I ligands play a central role in the regulation of natural killer (NK cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02, a common MHC class I molecule in the rhesus macaque with a canonical Bw6 motif, as a ligand for Mamu-KIR3DL05. Mamu-A1*00201 tetramers folded with certain SIV peptides, but not others, directly stained primary NK cells and Jurkat cells expressing multiple allotypes of Mamu-KIR3DL05. Differences in binding avidity were associated with polymorphisms in the D0 and D1 domains of Mamu-KIR3DL05, whereas differences in peptide-selectivity mapped to the D1 domain. The reciprocal exchange of the third predicted MHC class I-contact loop of the D1 domain switched the specificity of two Mamu-KIR3DL05 allotypes for different Mamu-A1*00201-peptide complexes. Consistent with the function of an inhibitory KIR, incubation of lymphocytes from Mamu-KIR3DL05(+ macaques with target cells expressing Mamu-A1*00201 suppressed the degranulation of tetramer-positive NK cells. These observations reveal a previously unappreciated role for D1 polymorphisms in determining the selectivity of KIRs for MHC class I-bound peptides, and identify the first functional KIR-MHC class I interaction in the rhesus macaque. The modulation of KIR-MHC class I interactions by viral peptides has important implications to pathogenesis, since it suggests that the immunodeficiency viruses, and potentially other types of viruses and tumors, may acquire changes in epitopes that increase the affinity of certain MHC class I ligands for inhibitory KIRs to prevent the activation of specific NK cell subsets.

  9. A Randomized 10-year Prospective Follow-up of Class II Nanohybrid and Conventional Hybrid Resin Composite Restorations

    DEFF Research Database (Denmark)

    van Dijken, Jan Wv; Pallesen, Ulla

    2014-01-01

    Purpose: To evaluate the 10-year durability of a nanohybrid resin composite in Class II restorations in a randomized controlled intraindividual comparison with its conventional hybrid resin composite predecessor. Materials and Methods: Each of 52 participants received at least two Class II...... restorations that were as similar as possible. The cavities were chosen at random to be restored with a nanohybrid resin composite (Excite/Tetric EvoCeram (TEC); n = 61) and a conventional hybrid (Excite/Tetric Ceram (TC); n = 61). The restorations were evaluated with slightly modified USPHS criteria...... investigated resin composites. Conclusion: The nanohybrid and the conventional hybrid resin composite showed good clinical effectiveness in extensive Class II restorations during the 10-year study....

  10. Klammt open elastic activator and twin blocks in Class II malocclusion treatment.

    Directory of Open Access Journals (Sweden)

    Eduardo Maikel Curbeira Hernández

    2009-04-01

    Full Text Available Background: Klammt open elastic activator and twin blocks have been two of the most worldwide studied functional appliances; however, there are different opinions about their effect on the cranium-facial complex. Objective: To determine the efficacy of these appliances in the functional treatment in Class II division I syndrome in early mixed teething. Methods: Prospective, cuasi experimental, “before-after” study without control group, including all children between 6 and 9 years of Area II in Cienfuegos municipality. After applying inclusion criteria, 20 patients were selected through simple randomized sampling and distributed in two groups, one for each technique. Lateral cranium teleradiographies were taken at the beginning and after a year of treatment, and lineal and/or angular measurements of Steiner, Ricketts, McNamara and Legan Burstone cephalograms were applied. Results: Favourable changes in cranium lateral radiographies measurements were obtained mainly from therapy with twin blocks. There was a decrease in the angle formed by the joint planes nasion-point A and nasion-point B and facial convexity, increase in mandible length and inferior facial height. Nasolabial angle and labial protuberance didn´t increase significantly. Conclusions: treated patients positively modified their bio-typology, and growth trend showed positive variations during functional therapy.

  11. N-containing Ag(I) and Hg(II) complexes: a new class of antibiotics.

    Science.gov (United States)

    Sabounchei, Seyyed Javad; Shahriary, Parisa

    2013-01-01

    Several classes of antimicrobial compounds are presently available; microorganism's resistance to these drugs constantly emerges. In order to prevent this serious medical problem, the elaboration of new types of antibacterial agents or the expansion of bioactivity of the naturally known biosensitive compounds is a very interesting research problem. The synthesis and characterization of metal complexes with organic bioactive ligands is one of the promising fields for the search. The biological activities of the metal complexes differ from those of either the ligand or the metal ion. The results obtained thus far have led to the conclusion that structural factors, which govern antimicrobial activities, are strongly dependent on the central metal ion. A review of papers dealing with the Ag(I) and Hg(II) complexes of N donor ligands is presented. These metal complexes of N-chelating ligands have attracted considerable attention because of their interesting physicochemical properties and pronounced biological activities. This review will mainly focus on the preparation procedures and antibacterial properties of free organic ligands and the corresponding complexes. Finally, a research about antimicrobial properties of new Hg(II) complexes with 5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione (L) and various halogen ions, HgL2X2 (X = Cl¯ (49), Br¯ (50), and I¯ (51)), is reported. Noteworthy antimicrobial activities, evaluated by minimum inhibitory concentration, for these complexes were observed.

  12. DNA-binding, cytotoxicity, cellular uptake, apoptosis and photocleavage studies of Ru(II) complexes.

    Science.gov (United States)

    N Deepika; C Shobha Devi; Y Praveen Kumar; K Laxma Reddy; P Venkat Reddy; D Anil Kumar; Surya S Singh; S Satyanarayana

    2016-07-01

    Two Ru(II) complexes [Ru(phen)2bppp](ClO4)2 (1) and [Ru(phen)27-Br-dppz](ClO4)2 (2) [phen=1,10 phenanthroline, 7-Br-dppz=7-fluorodipyrido[3,2-a:2',3'-c]phenazine, bppp=11-bromo-pyrido[2',3':5,6]pyrazino[2,3-f] [1,10]phenanthroline] have been synthesized and characterized by elemental analysis, ES-MS, (1)H-NMR, (13)C-NMR and IR. The in vitro cytotoxicity of the complexes examined against a panel of cancer cell lines (HeLa, Du145 and A549) by MTT method, both complexes show prominent anticancer activity against various cancer cells. Live cell imaging study and flow cytometric analysis demonstrate that both the complexes 1 and 2 could cross the cell membrane accumulating in the nucleus. Further, flow cytometry experiments showed that the cytotoxic Ru(II) complexes 1 and 2 induced apoptosis of HeLa tumor cell lines. Photo induced DNA cleavage studies have been performed and results indicate that both the complexes efficiently photo cleave pBR322 DNA. The binding properties of two complexes toward CT-DNA were investigated by various optical methods and viscosity measurements. The experimental results suggested that both Ru(II) complexes can intercalate into DNA base pairs. The complexes were docked into DNA-base pairs using the GOLD docking program.

  13. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells.

    Science.gov (United States)

    Matsuzaki, Junko; Tsuji, Takemasa; Luescher, Immanuel; Old, Lloyd J; Shrikant, Protul; Gnjatic, Sacha; Odunsi, Kunle

    2014-04-01

    Tumor antigen-specific CD4(+) T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4(+) T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157-170 peptide vaccination in patients with ovarian cancer. Although both subsets recognized exogenous NY-ESO-1 protein pulsed on DP04(+) target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4(+) T cells more efficiently recognized the short 8-9-mer peptides than the non-tumor-recognizing CD4(+) T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways, such as the proteasomal degradation and transporter-associated with antigen-processing-mediated peptide transport, were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacologic inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrate that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple nonclassical antigen-processing pathways. Harnessing the direct tumor-recognizing ability of CD4(+) T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment.

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

    Science.gov (United States)

    Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Capodaglio, Paolo; Brunani, Amelia; Fanari, Paolo; Salvadori, Alberto; Malatesta, Davide

    2015-01-01

    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.

  15. 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.

  16. Characterization and antifungal activity of gazyumaru (Ficus microcarpa) latex chitinases: both the chitin-binding and the antifungal activities of class I chitinase are reinforced with increasing ionic strength.

    Science.gov (United States)

    Taira, Toki; Ohdomari, Atsuko; Nakama, Naoya; Shimoji, Makiko; Ishihara, Masanobu

    2005-04-01

    Three chitinases, designated gazyumaru latex chitinase (GLx Chi)-A, -B, and -C, were purified from the latex of gazyumaru (Ficus microcarpa). GLx Chi-A,-B, and -C are an acidic class III (33 kDa, pI 4.0), a basic class I (32 kDa, pI 9.3), and a basic class II chitinase (27 kDa, pI > 10) respectively. GLx Chi-A did not exhibit any antifungal activity. At low ionic strength, GLx Chi-C exhibited strong antifungal activity, to a similar extent as GLx Chi-B. The antifungal activity of GLx Chi-C became weaker with increasing ionic strength, whereas that of GLx Chi-B became slightly stronger. GLx Chi-B and -C bound to the fungal cell-walls at low ionic strength, and then GLx Chi-C was dissociated from them by an escalation of ionic strength, but this was not the case for GLx Chi-B. The chitin-binding activity of GLx Chi-B was enhanced by increasing ionic strength. These results suggest that the chitin-binding domain of basic class I chitinase binds to the chitin in fungal cell walls by hydrophobic interaction and assists the antifungal action of the chitinase.

  17. Selective binding of 2'-F-c-di-GMP to Ct-E88 and Cb-E43, new class I riboswitches from Clostridium tetani and Clostridium botulinum respectively.

    Science.gov (United States)

    Luo, Yiling; Zhou, Jie; Wang, Jingxin; Dayie, T Kwaku; Sintim, Herman O

    2013-06-01

    C-di-GMP is a second messenger in bacteria and partly regulates bacterial physiology by binding to class I and II riboswitches. Four class I c-di-GMP riboswitch aptamer candidates, Ct-E88, Cb-17B, Cb-E43 and Cd-630 RNAs, selected from a GEMM RNA sequence motif in the Rfam database, were expressed and experimentally verified to bind to c-di-GMP. The two newly characterized c-di-GMP riboswitches, Ct-E88 and Cb-E43, bound c-di-GMP with nanomolar Kd whereas the affinities of Cb-17B and Cd-630 for c-di-GMP were at least a 100-fold weaker. Interestingly, whereas the three riboswitches (Vc2, Et-E88 and Cb-E43) bound c-di-GMP with similar Kd values, 2'-modified analogs of c-di-GMP differentially bound to these three class I aptamers. For example, 2'-F-c-di-GMP bound Vc2 with a Kd value of 102 nM whereas the Kd value of 2'-F-c-di-GMP-Ct-E88 is 43 μM (422× higher than that for Vc2 RNA), revealing that there are differences in the binding sites of functional class I c-di-GMP riboswitches.

  18. Nickel(II), copper(II) and zinc(II) metallo-intercalators: structural details of the DNA-binding by a combined experimental and computational investigation.

    Science.gov (United States)

    Lauria, Antonino; Bonsignore, Riccardo; Terenzi, Alessio; Spinello, Angelo; Giannici, Francesco; Longo, Alessandro; Almerico, Anna Maria; Barone, Giampaolo

    2014-04-28

    We present a thorough characterization of the interaction of novel nickel(II) (1), copper(II) (2) and zinc(II) (3) Schiff base complexes with native calf thymus DNA (ct-DNA), in buffered aqueous solution at pH 7.5. UV-vis absorption, circular dichroism (CD) and viscometry titrations provided clear evidence of the intercalative mechanism of the three square-planar metal complexes, allowing us to determine the intrinsic DNA-binding constants (K(b)), equal to 1.3 × 10(7), 2.9 × 10(6), and 6.2 × 10(5) M(-1) for 1, 2 and 3, respectively. Preferential affinity, of one order of magnitude, toward AT compared to GC base pair sequences was detected by UV-vis absorption titrations of 1 with [poly(dG-dC)]2 and [poly(dA-dT)]2. Structural details of the intercalation site of the three metal complexes within [dodeca(dA-dT)]2 were obtained by molecular dynamics (MD) simulations followed by density functional theory/molecular mechanics (DFT/MM) calculations. The calculations revealed that three major intermolecular interactions contribute to the strong affinity between DNA and the three metal complexes: (1) the electrostatic attraction between the two positively charged triethylammoniummethyl groups of the metal complexes and the negatively charged phosphate groups of the DNA backbone; (2) the intercalation of the naphthalene moiety within the four nitrogen bases of the intercalation site; (3) the metal coordination by exocyclic donor atoms of the bases, specifically the carbonyl oxygen and amine nitrogen atoms. Remarkably, the Gibbs formation free energy calculated for the intercalation complexes of 1, 2 and 3 with [dodeca(dA-dT)]2 in the implicit water solution is in agreement with the experimental Gibbs free energy values obtained from the DNA-binding constants as ΔG° = -RT ln(K(b)). In particular, the DNA-binding affinity trend, 1 > 2 > 3, is reproduced. Finally, the first shell coordination distances calculated for the intercalation complex 3/[dodeca(dA-dT)]2 are in

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    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 for T cell...... antigen recognition. This could be demonstrated both in cell-free systems using purified reagents and in cellular systems. Thus, MHC class II and APN may act in concert to generate the final T cell epitopes....

  20. IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments

    Directory of Open Access Journals (Sweden)

    Vardjan Nina

    2012-06-01

    Full Text Available Abstract Background In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ can express major histocompatibility complex (MHC class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT astrocytes and in astrocytes devoid of IFs. Methods The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor546-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software. Results Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor546-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-γ-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-γ-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent. Conclusions Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a

  1. Distalization of maxillary arch and correction of Class II with mini-implants: A report of two cases

    Directory of Open Access Journals (Sweden)

    Pawankumar Dnyandeo Tekale

    2015-01-01

    Full Text Available This article reports the successful use of mini-screws in the maxilla to treat two patients of age 21-year and 17-year-old girls. Both the patients had a skeletal Class II malocclusion with protrusive maxillary teeth and angels Class II mal-occlusion. Temporary anchorage devices (TADs in the posterior dental region between maxillary second premolar and maxillary first molar teeth on both sides were used as anchorage for the retraction and intrusion of her maxillary anterior teeth. Those appliances, combined with a compensatory curved maxillary archwire, eliminated spacing, deep bite, forwardly placed and proclined upper front teeth and the protrusive profile, corrected the molar relationship from Class II to Class I. With no extra TADs in the anterior region for intrusion, the treatment was workable and simple. The patient received a satisfactory occlusion and an attractive smile. This technique requires minimal compliance and is particularly useful for correcting Class II patients with protrusive maxillary front teeth and dental deep bite.

  2. Dynamic changes in binding of immunoglobulin heavy chain 3' regulatory region to protein factors during class switching.

    Science.gov (United States)

    Chatterjee, Sanjukta; Ju, Zhongliang; Hassan, Rabih; Volpi, Sabrina A; Emelyanov, Alexander V; Birshtein, Barbara K

    2011-08-19

    The 3' regulatory region (3' RR) of the Igh locus works at long distances on variable region (V(H)) and switch region (I) region promoters to initiate germ line (non-coding) transcription (GT) and promote class switch recombination (CSR). The 3' RR contains multiple elements, including enhancers (hs3a, hs1.2, hs3b, and hs4) and a proposed insulator region containing CTCF (CCCTC-binding factor) binding sites, i.e. hs5/6/7 and the downstream region ("38"). Notably, deletion of each individual enhancer (hs3a-hs4) has no significant phenotypic consequence, suggesting that the 3' RR has considerable structural flexibility in its function. To better understand how the 3' RR functions, we identified transcription factor binding sites and used chromatin immunoprecipitation (ChIP) assays to monitor their occupancy in splenic B cells that initiate GT and undergo CSR (LPS±IL4), are deficient in GT and CSR (p50(-/-)), or do not undergo CSR despite efficient GT (anti-IgM+IL4). Like 3' RR enhancers, hs5-7 and the 38 region were observed to contain multiple Pax5 binding sites (in addition to multiple CTCF sites). We found that the Pax5 binding profile to the 3' RR dynamically changed during CSR independent of the specific isotype to which switching was induced, and binding focused on hs1.2, hs4, and hs7. CTCF-associated and CTCF-independent cohesin interactions were also identified. Our observations are consistent with a scaffold model in which a platform of active protein complexes capable of facilitating GT and CSR can be formed by varying constellations of 3' RR elements.

  3. The Caulobacter crescentus chromosome replication origin evolved two classes of weak DnaA binding sites.

    Science.gov (United States)

    Taylor, James A; Ouimet, Marie-Claude; Wargachuk, Richard; Marczynski, Gregory T

    2011-10-01

    The Caulobacter crescentus replication initiator DnaA and essential response regulator CtrA compete to control chromosome replication. The C. crescentus replication origin (Cori) contains five strong CtrA binding sites but only two apparent DnaA boxes, termed G-boxes (with a conserved second position G, TGATCCACA). Since clusters of DnaA boxes typify bacterial replication origins, this discrepancy suggested that C. crescentus DnaA recognizes different DNA sequences or compensates with novel DNA-binding proteins. We searched for novel DNA sites by scanning mutagenesis of the most conserved Cori DNA. Autonomous replication assays showed that G-boxes and novel W-boxes (TCCCCA) are essential for replication. Further analyses showed that C. crescentus DnaA binds G-boxes with moderate and W-boxes with very weak affinities significantly below DnaA's capacity for high-affinity Escherichia coli-boxes (TTATCCACA). Cori has five conserved W-boxes. Increasing W-box affinities increases or decreases autonomous replication depending on their strategic positions between the G-boxes. In vitro, CtrA binding displaces DnaA from proximal G-boxes and from distal W-boxes implying CtrA-DnaA competition and DnaA-DnaA cooperation between G-boxes and W-boxes. Similarly, during cell cycle progression, CtrA proteolysis coincides with DnaA binding to Cori. We also observe highly conserved W-boxes in other replication origins lacking E. coli-boxes. Therefore, strategically weak DnaA binding can be a general means of replication control.

  4. Crystal structures and inhibitor binding properties of plant class V chitinases: the cycad enzyme exhibits unique structural and functional features.

    Science.gov (United States)

    Umemoto, Naoyuki; Kanda, Yuka; Ohnuma, Takayuki; Osawa, Takuo; Numata, Tomoyuki; Sakuda, Shohei; Taira, Toki; Fukamizo, Tamo

    2015-04-01

    A class V (glycoside hydrolase family 18) chitinase from the cycad Cycas revoluta (CrChiA) is a plant chitinase that has been reported to possess efficient transglycosylation (TG) activity. We solved the crystal structure of CrChiA, and compared it with those of class V chitinases from Nicotiana tabacum (NtChiV) and Arabidopsis thaliana (AtChiC), which do not efficiently catalyze the TG reaction. All three chitinases had a similar (α/β)8 barrel fold with an (α + β) insertion domain. In the acceptor binding site (+1, +2 and +3) of CrChiA, the Trp168 side chain was found to stack face-to-face with the +3 sugar. However, this interaction was not found in the identical regions of NtChiV and AtChiC. In the DxDxE motif, which is essential for catalysis, the carboxyl group of the middle Asp (Asp117) was always oriented toward the catalytic acid Glu119 in CrChiA, whereas the corresponding Asp in NtChiV and AtChiC was oriented toward the first Asp. These structural features of CrChiA appear to be responsible for the efficient TG activity. When binding of the inhibitor allosamidin was evaluated using isothermal titration calorimetry, the changes in binding free energy of the three chitinases were found to be similar to each other, i.e. between -9.5 and -9.8 kcal mol(-1) . However, solvation and conformational entropy changes in CrChiA were markedly different from those in NtChiV and AtChiC, but similar to those of chitinase A from Serratia marcescens (SmChiA), which also exhibits significant TG activity. These results provide insight into the molecular mechanism underlying the TG reaction and the molecular evolution from bacterial chitinases to plant class V chitinases.

  5. Treatment of class II and class III maloccolusion by using churro jumper: an efficient, inexpensive and uncomplicated fixed flexible functional technique

    OpenAIRE

    Mani, Shubhangi Amit; Mote, Nilesh; Pawar, Kunal Dilip; Mishra, Prashantkumar; Mishra, Richa Anil; Rai, Rajlaxmi Rajaram

    2016-01-01

    Functional orthopedic treatment seeks to improve skeletal and dental relationship of the jaws. The challenging task is to correctly position jaws antero-posteriorly and vertically with correct overbite, overjet and Centric relation. The Churro Jumper is an efficient, inexpensive and uncomplicated fixed flexible functional appliance. It is used to evaluate the efficacy of the Churro Jumper appliance in treatment of skeletal Class II malocclusion with retrognathic mandible. Churro Jumper contri...

  6. Collagen binding specificity of the discoidin domain receptors: binding sites on collagens II and III and molecular determinants for collagen IV recognition by DDR1.

    Science.gov (United States)

    Xu, Huifang; Raynal, Nicolas; Stathopoulos, Stavros; Myllyharju, Johanna; Farndale, Richard W; Leitinger, Birgit

    2011-01-01

    The discoidin domain receptors, DDR1 and DDR2 are cell surface receptor tyrosine kinases that are activated by triple-helical collagen. While normal DDR signalling regulates fundamental cellular processes, aberrant DDR signalling is associated with several human diseases. We previously identified GVMGFO (O is hydroxyproline) as a major DDR2 binding site in collagens I-III, and located two additional DDR2 binding sites in collagen II. Here we extend these studies to the homologous DDR1 and the identification of DDR binding sites on collagen III. Using sets of overlapping triple-helical peptides, the Collagen II and Collagen III Toolkits, we located several DDR2 binding sites on both collagens. The interaction of DDR1 with Toolkit peptides was more restricted, with DDR1 mainly binding to peptides containing the GVMGFO motif. Triple-helical peptides containing the GVMGFO motif induced DDR1 transmembrane signalling, and DDR1 binding and receptor activation occurred with the same amino acid requirements as previously defined for DDR2. While both DDRs exhibit the same specificity for binding the GVMGFO motif, which is present only in fibrillar collagens, the two receptors display distinct preferences for certain non-fibrillar collagens, with the basement membrane collagen IV being exclusively recognised by DDR1. Based on our recent crystal structure of a DDR2-collagen complex, we designed mutations to identify the molecular determinants for DDR1 binding to collagen IV. By replacing five amino acids in DDR2 with the corresponding DDR1 residues we were able to create a DDR2 construct that could function as a collagen IV receptor.

  7. HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

    Science.gov (United States)

    Lou, H; Li, H C; Kuwayama, M; Yashiki, S; Fujiyoshi, T; Suehara, M; Osame, M; Yamashita, M; Hayami, M; Gurtsevich, V; Ballas, M; Imanishi, T; Sonoda, S

    1998-11-01

    The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

  8. Conformational Change Observed in the Active Site of Class C β-Lactamase MOX-1 upon Binding to Aztreonam.

    Science.gov (United States)

    Oguri, Takuma; Ishii, Yoshikazu; Shimizu-Ibuka, Akiko

    2015-08-01

    We solved the crystal structure of the class C β-lactamase MOX-1 complexed with the inhibitor aztreonam at 1.9Å resolution. The main-chain oxygen of Ser315 interacts with the amide nitrogen of aztreonam. Surprisingly, compared to that in the structure of free MOX-1, this main-chain carboxyl changes its position significantly upon binding to aztreonam. This result indicates that the interaction between MOX-1 and β-lactams can be accompanied by conformational changes in the B3 β-strand main chain.

  9. Natural acquired inhibitory antibodies to Plasmodium vivax Duffy binding protein (PvDBP-II) equally block erythrocyte binding of homologous and heterologous expressed PvDBP-II on the surface of COS-7 cells.

    Science.gov (United States)

    Valizadeh, Vahideh; Zakeri, Sedigheh; Mehrizi, Akram A; Mirkazemi, Sedigheh; Djadid, Navid D

    2016-02-01

    The binding domain of Plasmodium vivax Duffy binding protein (PvDBP-II) is a promising blood-stage vaccine candidate for vivax malaria. For the development of a successful vivax malaria vaccine based on DBP-II, the antigenic diversity and also naturally occurring functional antibodies to different PvDBP-II variant types in the various populations must be determined. However, similar to other blood-stage antigens, allelic variation within the PvDBP-II is a fundamental challenge for the development of a broadly efficient vaccine. The present study was performed to define whether the polymorphisms in PvDBP-II influence the nature of functional inhibitory activity of naturally acquired or induced anti-DBP-II antibodies in mice. In this investigation, five genetically distinct variants of PvDBP-II were transiently expressed on the COS-7 cell surface. Erythrocyte-binding inhibition assay (EBIA) was performed using human sera infected with corresponding and non-corresponding P. vivax variants as well as by the use of mice sera immunized with different expressed recombinant PvDBP-IIs. EBIA results showed that the inhibitory percentage varied between 50 and 63 % by using sera from infected individuals, and in case of mouse antisera, inhibition was in the range of 76-86 %. Interestingly, no significant difference was detected in red blood cell binding inhibition when different PvDBP-II variants on the COS-7 cell surfaces were incubated with heterologous and homologous sera infected with PvDBP-II variants. This suggests that the detected polymorphisms in all five forms of PvDBP-II may not affect functional activity of anti-DBP-II antibodies. In conclusion, our results revealed that there are functional cross-reactive antibody responses to heterologous PvDBP-II variants that might provide a broader inhibitory response against all, or at least the majority of strains compared to single allele of this protein that should be considered in development of PvDBP-II-based vaccine.

  10. Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer.

    Science.gov (United States)

    Surmann, Eva-Maria; Voigt, Anita Y; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Ferrone, Soldano; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2015-03-01

    Besides being expressed on professional antigen-presenting cells, HLA class II antigens are expressed on various tumors of non-lymphoid origin, including a subset of colorectal cancers (CRC). Information about the regulation of HLA class II antigen expression is important for a better understanding of their role in the interactions between tumor and immune cells. Whether lack of HLA class II antigen expression in tumors reflects the selective immune destruction of HLA class II antigen-expressing tumor cells is unknown. To address this question, we tested whether lack of HLA class II antigen expression in CRC was associated with immune cell infiltration. We selected microsatellite-unstable (MSI-H) CRC, because they show pronounced tumor antigen-specific immune responses and, in a subset of tumors, lack of HLA class II antigen expression due to mutations inactivating HLA class II-regulatory genes. We examined HLA class II antigen expression, mutations in regulatory genes, and CD4-positive T cell infiltration in 69 MSI-H CRC lesions. Mutations in RFX5, CIITA, and RFXAP were found in 13 (28.9%), 3 (6.7%), and 1 (2.2%) out of 45 HLA class II antigen-negative tumors. CD4-positive tumor-infiltrating lymphocyte counts were significantly higher in HLA class II antigen-negative tumors harboring mutations in HLA class II-regulatory genes (107.4 T cells per 0.25 mm(2)) compared to tumors without mutations (55.5 T cells per 0.25 mm(2), p = 0.008). Our results suggest that the outgrowth of tumor cells lacking HLA class II antigen expression due to mutations of regulatory genes is favored in an environment of dense CD4-positive T cell infiltration.

  11. Cyclic ferrocenylnaphthalene diimide derivative as a new class of G-quadruplex DNA binding ligand.

    Science.gov (United States)

    Islam, Md Monirul; Sato, Shinobu; Shinozaki, Shingo; Takenaka, Shigeori

    2017-01-15

    To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (10(6)M(-1) order) with diminished binding to dsDNA (10(4)M(-1) order) in 100mM AcOH-AcOK buffer (pH 5.5) containing 100mM KCl. Interestingly, 1 showed an approximately 50-fold higher selectivity to mixed hybrid-type telomeric G-quadruplex DNA (K=3.4×10(6)M(-1) and a 2:1 stoichiometry) than dsDNA (K=7.5×10(4)M(-1)) did. Furthermore, 1 showed higher thermal stability to G-quadruplex DNAs than it did to dsDNA with a preference for c-kit and c-myc G-quadruplex DNAs over telomeric and thrombin binding aptamers. Additionally, 1 exhibited telomerase inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.4μM. Compound 2 showed a preference for G-quadruplex; however, the binding affinity magnitude and preference were improved in 1 because the former had a cyclic structure.

  12. The designed protein M(II)-Gly-Lys-His-Fos(138-211) specifically cleaves the AP-1 binding site containing DNA.

    Science.gov (United States)

    Harford, C; Narindrasorasak, S; Sarkar, B

    1996-04-09

    A new specific DNA cleavage protein, Gly-Lys-His-Fos(138-211), was designed, expressed, and characterized. The DNA-binding component of the design uses the basic and leucine zipper regions of the leucine zipper Fos, which are represented by Fos(138-211). The DNA cleavage moiety was provided by the design of the amino-terminal Cu(II)-, Ni(II)-binding site GKH at the amino terminus of Fos(138-211). Binding of Cu(II) or Ni(II) by the protein activates its cleavage ability. The GKH motif was predicted to form a specific amino-terminal Cu(II)-, Ni(II)-binding motif as previously defined [Predki, P. F., Harford, C., Brar, P., & Sarkar, B. (1992) Biochem. J. 287, 211 -215]. This prediction was verified as the tripeptide, GKH, and the expressed protein, GKH-Fos(138-211), were both shown to be capable of binding Cu(II) and Ni(II). The designed protein upon heterodimerization with Jun(248-334) was shown to bind to and cleave several forms of DNA which contained an AP-1 binding site. The cleavage was shown to be specific. This design demonstrates the versatility of the amino-terminal Cu(II)-, Ni(II)-binding motif and the variety of motifs which can be generated. The site of cleavage by GKH-Fos(138-211) on DNA provides further information regarding the bending of DNA upon binding to Fos-Jun heterodimers.

  13. Uso do aparelho de Thurow no tratamento da má oclusão esquelética de Classe II The use of Thurow's appliance in the treatment of skeletal class II malocclusion

    Directory of Open Access Journals (Sweden)

    Maíra Massuia de Souza

    2005-08-01

    Full Text Available O objetivo deste trabalho foi realizar uma revisão de literatura em relação ao tratamento da má oclusão esquelética de Classe II com a utilização do splint maxilar removível associado à tração alta, realçando sua influência no crescimento ósseo e seus benefícios. Através do relato do caso clínico será mostrada a confecção e os efeitos do aparelho de Thurow quando utilizado no período da dentadura mista, para a correção da Classe II esqueléticaThe aim of this study was to review the literature concerning the treatment of Class II malocclusion with removable maxillary splint associated to the high traction, enhancing its influence in the bony growth and its benefits. This clinical case will show the fabrication and the effects of Thurow's appliance, when it's used in the mixed dentition for the correction skeletal class II malocclusion.

  14. HLA class I and class II conserved extended haplotypes and their fragments or blocks in Mexicans: implications for the study of genetic diversity in admixed populations.

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    Joaquín Zúñiga

    Full Text Available Major histocompatibility complex (MHC genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C, and class II (HLA-DRB1, -DQB1 genes using high-resolution sequence based typing (SBT method and we structured the blocks and conserved extended haplotypes (CEHs in 234 non-related admixed Mexican individuals (468 haplotypes by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs and HLA-B that correlated with the frequency of most probable ancestral HLA-C/-B and -DRB1/-DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations.

  15. Protein-binding, cytotoxicity in vitro and cell cycle arrest of ruthenium(II) polypyridyl complexes

    Science.gov (United States)

    Liu, Si-Hong; Zhu, Jian-Wei; Xu, Hui-Hua; Wang, Yan; Liu, Ya-Min; Liang, Jun-Bo; Zhang, Gui-Qiang; Cao, Di-Hua; Lin, Yang-Yang; Wu, Yong; Guo, Qi-Feng

    2016-05-01

    The cytotoxic activity of two Ru(II) complexes against A549, BEL-7402, HeLa, PC-12, SGC-7901 and SiHa cell lines was investigated by MTT method. Complexes 1 and 2 show moderate cytotoxicity toward BEL-7402 cells with an IC50 value of 53.9 ± 3.4 and 39.3 ± 2.1 μM. The effects of the complexes inducing apoptosis, cellular uptake, reactive oxygen species and mitochondrial membrane potential in BEL-7402 cells have been studied by fluorescence microscopy. The percentages of apoptotic and necrotic cells and cell cycle arrest were studied by flow cytometry. The BSA-binding behaviors were investigated by UV/visible and fluorescent spectra.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC...

  17. An alternate mode of binding of the polyphenol quercetin with serum albumins when complexed with Cu(II)

    Energy Technology Data Exchange (ETDEWEB)

    Singha Roy, Atanu; Tripathy, Debi Ranjan; Ghosh, Arup Kumar [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India); Dasgupta, Swagata, E-mail: swagata@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India)

    2012-11-15

    Polyphenols find wide use as antioxidants, cancer chemopreventive agents and metal chelators. The latter activity has proved interesting in many aspects. We have probed the binding characteristics of the polyphenol quercetin-Cu(II) complex with human serum albumin (HSA) and bovine serum albumin (BSA). Fluorescence studies reveal that the quercetin-Cu(II) complex can quench the fluorescence of the serum albumins. The binding constant (K{sub b}) values are of the order of 10{sup 5} M{sup -1} which increased with rise in temperature in case of HSA and BSA interacting with the quercetin-Cu(II) complex. Displacement studies reveal that both the ligands bind to site 1 (subdomain IIA) of the serum albumins. However, thermodynamic parameters calculated from temperature dependent studies indicated that the mode of interaction of the complexes with the proteins differs. Both {Delta}H Degree-Sign and {Delta}S Degree-Sign were positive for the interaction of the quercetin-Cu(II) complex with both proteins but the value of {Delta}H Degree-Sign was negative in case of the interaction of quercetin with the proteins. This implies that after chelation with metal ions, the polyphenol alters its mode of interaction which could have varying implications on its other physicochemical activities. - Research Highlights: Black-Right-Pointing-Pointer Mode of binding of quercetin with SAs is altered after complexation with Cu(II). Black-Right-Pointing-Pointer Hydrophobic forces play a key role in the binding of the copper complex with SAs. Black-Right-Pointing-Pointer Negative {Delta}G Degree-Sign values indicate the spontaneity of the binding processes. Black-Right-Pointing-Pointer Quercetin and its copper complex bind at the same site of the SAs.

  18. Marginal sealing ability of silorane and methacrylate resin composites in class II cavities: A scanning electron microscopic study

    Directory of Open Access Journals (Sweden)

    Jyothi Kashi Nanjundasetty

    2013-01-01

    Intergroup comparison of subgroup A did not show statistically significant difference, whereas subgroup B showed statistically significant difference for microleakage between group I and group II (P = 0.003, group III and group II (P = 0.002. Conclusion: Silorane resin composite and methacrylate resin with liner showed significantly less microleakage in class II cavities along the gingival margin placed below CEJ compared to methacrylate resin without liner. All the study groups showed less microleakage and microgap formation along the gingival margin placed above CEJ.

  19. Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity

    DEFF Research Database (Denmark)

    Merelo, Paz; Ram, Hathi; Caggiano, Monica Pia

    2016-01-01

    A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD-...

  20. A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.

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    Susan Pereira Ribeiro

    Full Text Available Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8. Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.

  1. Cu(II) bis(thiosemicarbazone) radiopharmaceutical binding to serum albumin: further definition of species dependence and associated substituent effects

    Energy Technology Data Exchange (ETDEWEB)

    Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: magreen@purdue.edu

    2009-07-15

    Introduction: The pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) radiopharmaceutical appears to exhibit only nonspecific binding to HSA and animal serum albumins. Methods: To further probe the structural basis for the species dependence of this albumin binding interaction, we examined protein binding of these three radiopharmaceuticals in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat and elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results: Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions: The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate.

  2. Development of a simultaneous high resolution typing method for three SLA class II genes, SLA-DQA, SLA-DQB1, and SLA-DRB1 and the analysis of SLA class II haplotypes.

    Science.gov (United States)

    Le, MinhThong; Choi, Hojun; Choi, Min-Kyeung; Cho, Hyesun; Kim, Jin-Hoi; Seo, Han Geuk; Cha, Se-Yeon; Seo, Kunho; Dadi, Hailu; Park, Chankyu

    2015-06-15

    The characterization of the genetic variations of major histocompatibility complex (MHC) is essential to understand the relationship between the genetic diversity of MHC molecules and disease resistance and susceptibility in adaptive immunity. We previously reported the development of high-resolution individual locus typing methods for three of the most polymorphic swine leukocyte antigens (SLA) class II loci, namely, SLA-DQA, SLA-DQB1, and SLA-DRB1. In this study, we extensively modified our previous protocols and developed a method for the simultaneous amplification of the three SLA class II genes and subsequent analysis of individual loci using direct sequencing. The unbiased and simultaneous amplification of alleles from the all three hyper-polymorphic and pseudogene containing genes such as MHC genes is extremely challenging. However, using this method, we demonstrated the successful typing of SLA-DQA, SLA-DQB1, and SLA-DRB1 for 31 selected individuals comprising 26 different SLA class II haplotypes which were identified from 700 animals using the single locus typing methods. The results were identical to the known genotypes from the individual locus typing. The new method has significant benefits over the individual locus typing, including lower typing cost, use of less biomaterial, less effort and fewer errors in handling large samples for multiple loci. We also extensively characterized the haplotypes of SLA class II genes and reported three new haplotypes. Our results should serve as a basis to investigate the possible association between polymorphisms of MHC class II and differences in immune responses to exogenous antigens.

  3. Synthesis, Cytotoxic Activity, and DNA Binding Properties of Copper (II Complexes with Hesperetin, Naringenin, and Apigenin

    Directory of Open Access Journals (Sweden)

    Mingxiong Tan

    2009-01-01

    Full Text Available Complexes of copper (II with hesperetin, naringenin, and apigenin of general composition [CuL2(H2O2]⋅nH2O (1–3 have been synthesized and characterized by elemental analysis, UV-Vis, FT-IR, ESI-MS, and TG-DTG thermal analysis. The free ligands and the metal complexes have been tested in vitro against human cancer cell lines hepatocellular carcinoma (HepG-2, gastric carcinomas (SGC-7901, and cervical carcinoma (HeLa. Complexes 1 and 3 were found to exhibit growth inhibition of SGC-7901 and HepG2 cell lines with respect to the free ligands; the inhibitory rate of complex 1 is 43.2% and 43.8%, while complex 3 is 46% and 36%, respectively. The interactions of complex 1 and its ligand Hsp with calf thymus DNA were investigated by UV-Vis, fluorescence, and CD spectra. Both complex 1 and Hsp were found to bind DNA in intercalation modes, and the binding affinity of complex 1 was stronger than that of free ligand.

  4. MHC class II up-regulation and co-localization with Fas in experimental models of immune-mediated bone marrow failure

    Science.gov (United States)

    Erie, Andrew J.; Samsel, Leigh; Takaku, Tomoiku; Desierto, Marie J.; Keyvanfar, Keyvan; McCoy, J. Philip; Young, Neal S.; Chen, Jichun

    2011-01-01

    Objective To test the hypothesis that gamma interferon (IFN-γ) promotes MHC class II expression on bone marrow (BM) cell targets that facilitates T cell-mediated BM destruction in immune-mediated BM failure. Materials and Methods Allogeneic lymph node (LN) cells were infused into MHC or minor histocompatibility antigen (minor-H) mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas co-localization was detected by ImageStream Imaging Flow Cytometry and other cell-cell associations were visualized by confocal microscopy. T cell-mediated BM cell apoptosis and effects of IFN-γ on MHC class II-Fas co-localization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry. Results BM failure animals had significantly up-regulated MHC class II expression on CD4−CD8−CD11b−CD45R− residual BM cells and significantly increased MHC class II-Fas co-localization on BM CD150+ and CD34+ hematopoietic cells. MHC class II+Fas+ BM cells were closely associated with CD4+ T cells in the BM of affected animals, and they were significantly more responsive to T-cell mediated cell apoptosis relative to MHC class II−Fas− BM cells. Infusion of IFN-γ-deficient LN cells into minor-H mismatched recipients resulted in no MHC class II-Fas up-regulation and no clinically overt BM failure. Treatment with recombinant IFN-γ significantly increased both MHC class II-Fas co-expression and co-localization on normal BM cells. Conclusion Elevation of the inflammatory cytokine IFN-γ stimulated MHC class II expression and MHC class II-Fas co-localization, which may facilitate T-cell mediated cell destruction. PMID:21635935

  5. Marginal Integrity of Bulk Versus Incremental Fill Class II Composite Restorations.

    Science.gov (United States)

    Al-Harbi, F; Kaisarly, D; Bader, D; El Gezawi, M

    2016-01-01

    Bulk-fill composites have been introduced to facilitate the placement of deep direct resin composite restorations. This study aimed at analyzing the cervical marginal integrity of bulk-fill vs incremental and open-sandwich class II resin composite restorations after thermomechanical cycling using replica scanning electron microscopy (SEM) and ranking according to the World Dental Federation (FDI) criteria. Box-only class II cavities were prepared in 91 maxillary premolars with the gingival margin placed 1 mm above and below the cemento-enamel junction. Eighty-four premolars were divided into self-etch and total-etch groups, then subdivided into six restorative subgroups (n=7): 1-Tetric Ceram HB (TC) was used incrementally and in the open-sandwich technique with 2-Tetric EvoFlow (EF) and 3-Smart Dentin Replacement (SD). Bulk-fill restoratives were 4-SonicFill (SF), 5-Tetric N-Ceram Bulk Fill (TN), and 6-Tetric EvoCeram Bulk Fill (TE). In subgroups 1-5, Tetric N-Bond self-etch and Tetric N-Bond total-etch adhesives were used, whereas in subgroup 6, AdheSE self-etch and ExciTE F total etch were used. One more group (n=7) was restored with Filtek P90 Low Shrink Posterior Restorative (P9) only in combination with its self-etch P90 System Adhesive. Materials were manipulated and light cured (20 seconds, 1600 mW/cm(2)), and restorations were artificially aged by thermo-occlusal load cycling. Polyvinyl-siloxane impressions were taken and poured with epoxy resin. Resin replicas were examined by SEM (200×) for marginal sealing, and percentages of perfect margins were analyzed. Moreover, samples were examined using loupes (3.5×) and explorers and categorized according to the FDI criteria. Results were statistically analyzed (SEM by Kruskal-Wallis test and FDI by chi-square test) without significant differences in either the replica SEM groups (p=0.848) or the FDI criteria groups (p>0.05). The best SEM results at the enamel margin were in TC+EF/total-etch and SF

  6. 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

  7. Structural fold, conservation and Fe(II) binding of the intracellular domain of prokaryote FeoB

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Kuo-Wei; Chang, Yi-Wei; Eng, Edward T.; Chen, Jai-Hui; Chen, Yi-Chung; Sun, Yuh-Ju; Hsiao, Chwan-Deng; Dong, Gang; Spasov, Krasimir A.; Unger, Vinzenz M.; Huang, Tai-huang (Yale-MED); (Perutz Lab); (AS); (NTHU-Taiwan)

    2010-09-17

    FeoB is a G-protein coupled membrane protein essential for Fe(II) uptake in prokaryotes. Here, we report the crystal structures of the intracellular domain of FeoB (NFeoB) from Klebsiella pneumoniae (KpNFeoB) and Pyrococcus furiosus (PfNFeoB) with and without bound ligands. In the structures, a canonical G-protein domain (G domain) is followed by a helical bundle domain (S-domain), which despite its lack of sequence similarity between species is structurally conserved. In the nucleotide-free state, the G-domain's two switch regions point away from the binding site. This gives rise to an open binding pocket whose shallowness is likely to be responsible for the low nucleotide-binding affinity. Nucleotide binding induced significant conformational changes in the G5 motif which in the case of GMPPNP binding was accompanied by destabilization of the switch I region. In addition to the structural data, we demonstrate that Fe(II)-induced foot printing cleaves the protein close to a putative Fe(II)-binding site at the tip of switch I, and we identify functionally important regions within the S-domain. Moreover, we show that NFeoB exists as a monomer in solution, and that its two constituent domains can undergo large conformational changes. The data show that the S-domain plays important roles in FeoB function.

  8. The Cd(II)-binding abilities of recombinant Quercus suber metallothionein: bridging the gap between phytochelatins and metallothioneins.

    Science.gov (United States)

    Domènech, Jordi; Orihuela, Rubén; Mir, Gisela; Molinas, Marisa; Atrian, Sílvia; Capdevila, Mercè

    2007-08-01

    In this work, we have analyzed both at stoichiometric and at conformational level the Cd(II)-binding features of a type 2 plant metallothionein (MT) (the cork oak, Quercus suber, QsMT). To this end four peptides, the wild-type QsMT and three constructs previously engineered to characterize its Zn(II)- and Cu(I)-binding behaviour, were heterologously produced in Escherichia coli cultures supplemented with Cd(II), and the corresponding complexes were purified up to homogeneity. The Cd(II)-binding ability of these recombinant peptides was determined through the chemical, spectroscopic and spectrometric characterization of the recovered clusters. Recombinant synthesis of the four QsMT peptides in cadmium-rich media rendered complexes with a higher metal content than those obtained from zinc-supplemented cultures and, consequently, the recovered Cd(II) species are nonisostructural to those of Zn(II). Also of interest is the fact that three out of the four peptides yielded recombinant preparations that included S(2-)-containing Cd(II) complexes as major species. Subsequently, the in vitro Zn(II)/Cd(II) replacement reactions were studied, as well as the in vitro acid denaturation and S(2-) renaturation reactions. Finally, the capacity of the four peptides for preventing cadmium deleterious effects in yeast cells was tested through complementation assays. Consideration of all the results enables us to suggest a hairpin folding model for this typical type 2 plant Cd(II)-MT complex, as well as a nonnegligible role of the spacer in the detoxification function of QsMT towards cadmium.

  9. Natural polyphenols binding to amyloid: a broad class of compounds to treat different human amyloid diseases.

    Science.gov (United States)

    Ngoungoure, Viviane L Ndam; Schluesener, Jan; Moundipa, Paul F; Schluesener, Hermann

    2015-01-01

    Polyphenols are a large group of phytonutrients found in herbal beverages and foods. They have manifold biological activities, including antioxidative, antimicrobial, and anti-inflammatory properties. Interestingly, some polyphenols bind to amyloid and substantially ameliorate amyloid diseases. Misfolding, aggregation, and accumulation of amyloid fibrils in tissues or organs leads to a group of disorders, called amyloidoses. Prominent diseases are Alzheimer's, Parkinson's, and Huntington's disease, but there are other, less well-known diseases wherein accumulation of misfolded protein is a prominent feature. Amyloidoses are a major burden to public health. In particular, Alzheimer's disease shows a strong increase in patient numbers. Accelerated development of effective therapies for amyloidoses is a necessity. A viable strategy can be the prevention or reduction of protein misfolding, thus reducing amyloid build-up by restoring the cellular aggretome. Amyloid-binding polyphenols affect amyloid formation on various levels, e.g. by inhibiting fibril formation or steering oligomer formation into unstructured, nontoxic pathways. Consequently, preclinical studies demonstrate reduction of amyloid-formation by polyphenols. Amyloid-binding polyphenols might be suitable lead structures for development of imaging agents for early detection of disease and monitoring amyloid deposition. Intake of dietary polyphenols might be relevant to the prevention of amyloidoses. Nutraceutical strategies might be a way to reduce amyloid diseases.

  10. Major histocompatibility (MH) class II ß gene polymorphism influences disease resistance of common carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Rakus, K.L.; Wiegertjes, G.F.; Jurecka, P.M.; Walker, P.D.; Pilarczyk, A.; Irnazarow, I.

    2009-01-01

    Genes of the major histocompatibility complex (MHC) are crucial elements of adaptive immunity. High polymorphism renders the MHC genes highly suitable for studies on association with disease resistance. In common carp (Cyprinus carpio L.), there are two paralogous groups of MH class II B genes, Cyca

  11. 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...

  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 147.303 - 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...

  14. 40 CFR 147.253 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)<