Academic literature on the topic 'CD1 proteins'
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Journal articles on the topic "CD1 proteins"
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Huang, Shouxiong, Tan-Yun Cheng, John Altman, and D. Branch Moody. "Comparative lipidomics reveals a global sampling of major cellular membrane lipids by human CD1 proteins (P5006)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 41.4. http://dx.doi.org/10.4049/jimmunol.190.supp.41.4.
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Abstract Human CD1 proteins have differentially shaped grooves and present bacterial or self lipid antigens to T cells, but it is unknown whether the pool of endogenous lipids are differently sampled by each type of CD1 proteins. We used recently established lipidomic approach to analyze the molecules extracted from human CD1a, CD1b, CD1c, and CD1d proteins. In the study, we demonstrated that this highly sensitive and accurate lipidomic approach detected more than one thousand diverse molecules defined by accurate mass retention time values, which represented hundreds of lipid species associated with CD1 proteins. More than fifty percent of these molecules were shared by all four types of CD1 proteins and additional thirty percent shared by two or three CD1 isoforms. Further mass spectrometry analyses of collision-induced dissociation showed that the molecules eluted from all four types of CD1 proteins mainly are lipids from subcellular membranes, including phospholipids of conventional, ether-linked, and lyso forms and sphingolipids. Surprisingly, CD1 isoforms with bigger grooves preferred to lipids with shorter chains, which can be explained by small spacer or scaffold lipids that bind together with antigens. Whereas previous studies argued that one lipid molecule blocks CD1 grooves, analogous to MHC class II-associated CLIP peptide, we conclude that CD1 proteins broadly sample cellular lipids and two small lipids are able to be adapted into a big groove.
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Huang, Shouxiong, Tan-Yun Cheng, David Young, Emilie Layre, Cressida Madigan, John Shires, Vincenzo Cerundolo, John Altman, and Branch Moody. "A CD1 lipidomic analysis determines the structures of human CD1b scaffold lipids and its function to enhance mycobacterial antigen presentation (106.43)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 106.43. http://dx.doi.org/10.4049/jimmunol.188.supp.106.43.
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Abstract Unlike the dominant role of one class II invariant chain peptide (CLIP) in blocking MHC class II, comparative lipidomics analysis shows that human CD1a, CD1b, CD1c and CD1d proteins bind lipids corresponding to hundreds of diverse accurate mass retention time values. Although most ions were observed in association with several CD1 proteins, ligands binding selectively to one CD1 isoform allowed the study of how differing antigen binding grooves influence lipid capture. The CD1b groove is distinguished by its unusually large volume, however, the average mass of compounds eluted from CD1b was similar to that of lipids from other CD1 proteins. Elution of small ligands from the large CD1b groove might be explained, if two small lipids bind simultaneously in the groove. In the context of the known CD1b crystal structures with scaffold lipids seated below the antigen, we also found that ligands selectively associated with CD1b lacked the hydrophilic head group, which is generally needed for antigen recognition, but interferes with scaffold function. Furthermore, we identified the scaffolds as deoxyceramides and diacylglycerols and directly demonstrated a function in augmenting presentation of a mycobacterial antigen, the short chain glucose monomycolate, to T cells. Thus, unlike MHC class II, CD1 proteins capture highly diverse ligands in the secretory pathway. CD1b has a mechanism for binding two small lipids to enhance bacterial antigen presentation and T cell activation.
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Aruffo, A., and B. Seed. "Expression of cDNA clones encoding the thymocyte antigens CD1a, b, c demonstrates a hierarchy of exclusion in fibroblasts." Journal of Immunology 143, no. 5 (September 1, 1989): 1723–30. http://dx.doi.org/10.4049/jimmunol.143.5.1723.
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Abstract The CD1 gene family encodes at least three proteins: CD1a, CD1b, and CD1c, which are coexpressed on cortical thymocytes and a number of T cell leukemias. On thymocytes, CD1a forms noncovalent complexes with CD1b and CD1c, and a disulfide-linked heterodimer with CD8. This report describes the isolation and characterization of cDNA clones encoding the CD1a, CD1b, and CD1c Ag. Cotransfection of the cDNA was used to investigate the formation of intermolecular heterodimers by CD1a with other members of the CD1 gene family and with CD8. No intermolecular heterodimers were observed during transient expression in COS cells. However, an exclusion hierarchy was observed between members of the CD1 gene family when two or more members of the family were cotransfected into COS cells.
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Moody, D. Branch, and Sara Suliman. "CD1: From Molecules to Diseases." F1000Research 6 (October 30, 2017): 1909. http://dx.doi.org/10.12688/f1000research.12178.1.
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The human cluster of differentiation (CD)1 system for antigen display is comprised of four types of antigen-presenting molecules, each with a distinct functional niche: CD1a, CD1b, CD1c, and CD1d. Whereas CD1 proteins were thought solely to influence T-cell responses through display of amphipathic lipids, recent studies emphasize the role of direct contacts between the T-cell receptor and CD1 itself. Moving from molecules to diseases, new research approaches emphasize human CD1-transgenic mouse models and the study of human polyclonal T cells in vivo or ex vivo in disease states. Whereas the high genetic diversity of major histocompatibility complex (MHC)-encoded antigen-presenting molecules provides a major hurdle for designing antigens that activate T cells in all humans, the simple population genetics of the CD1 system offers the prospect of discovering or designing broadly acting immunomodulatory agents.
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Dascher, Christopher C., Kenji Hiromatsu, Jerome W. Naylor, Pamela P. Brauer, Kara A. Brown, James R. Storey, Samuel M. Behar, et al. "Conservation of a CD1 Multigene Family in the Guinea Pig." Journal of Immunology 163, no. 10 (November 15, 1999): 5478–88. http://dx.doi.org/10.4049/jimmunol.163.10.5478.
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Abstract CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene family of the guinea pig (Cavia porcellus). Eight distinct cDNA clones corresponding to CD1 transcripts were isolated from a guinea pig thymocyte cDNA library and completely sequenced. The guinea pig CD1 proteins predicted by translation of the cDNAs included four that can be classified as homologues of human CD1b, three that were homologues of human CD1c, and a single CD1e homologue. These guinea pig CD1 protein sequences contain conserved amino acid residues and hydrophobic domains within the putative Ag binding pocket. A mAb specific for human CD1b cross-reacted with multiple guinea pig CD1 isoforms, thus allowing direct analysis of the structure and expression of at least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This distribution of CD1 staining in guinea pig tissues was thus similar to that seen in other mammals. These data provide the foundation for the development of the guinea pig as an animal model to study the in vivo function of CD1.
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Faraldo-Gómez, José D., and Diana Garzón. "Molecular modeling and simulation studies of CD1 binding proteins (78.3)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 78.3. http://dx.doi.org/10.4049/jimmunol.182.supp.78.3.
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Abstract The presentation of small protein fragments, both foreign and native, on the surface of specialized cells is one of the cornerstones of our immune system. In complex with MHC binding proteins, these protein antigens will be recognized by T-cell membrane receptors either as self or non-self, and an appropriate response will be initiated. In recent years it has become apparent that immune responses may also be induced by a diverse array of lipid antigens. The presentation of these antigens involves a class of binding proteins referred to as CD1, analogous to MHC proteins. The CD1 family includes 5 isoforms of distinct specificity, of which CD1a, CD1b and CD1d have been characterized structurally in complex with diverse lipid antigens. Here we report the results of extensive computer simulation studies of this family, from which we gain insights into the mechanism of lipid binding. We also present a molecular model of CD1c, and based on this, rationalize its specificity for branched mycobacterial lipids.
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Gherardin, Nicholas A., Samuel J. Redmond, Hamish E. G. McWilliam, Catarina F. Almeida, Katherine H. A. Gourley, Rebecca Seneviratna, Shihan Li, et al. "CD36 family members are TCR-independent ligands for CD1 antigen–presenting molecules." Science Immunology 6, no. 60 (June 25, 2021): eabg4176. http://dx.doi.org/10.1126/sciimmunol.abg4176.
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CD1c presents lipid-based antigens to CD1c-restricted T cells, which are thought to be a major component of the human T cell pool. However, the study of CD1c-restricted T cells is hampered by the presence of an abundantly expressed, non–T cell receptor (TCR) ligand for CD1c on blood cells, confounding analysis of TCR-mediated CD1c tetramer staining. Here, we identified the CD36 family (CD36, SR-B1, and LIMP-2) as ligands for CD1c, CD1b, and CD1d proteins and showed that CD36 is the receptor responsible for non–TCR-mediated CD1c tetramer staining of blood cells. Moreover, CD36 blockade clarified tetramer-based identification of CD1c-restricted T cells and improved identification of CD1b- and CD1d-restricted T cells. We used this technique to characterize CD1c-restricted T cells ex vivo and showed diverse phenotypic features, TCR repertoire, and antigen-specific subsets. Accordingly, this work will enable further studies into the biology of CD1 and human CD1-restricted T cells.
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Cheng, Janice M. H., Ashna A. Khan, Mattie S. M. Timmer, and Bridget L. Stocker. "Endogenous and Exogenous CD1-Binding Glycolipids." International Journal of Carbohydrate Chemistry 2011 (April 5, 2011): 1–13. http://dx.doi.org/10.1155/2011/749591.
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In the same way that peptide antigens are presented by major histocompatibility complex (MHC) molecules, glycolipid antigens can also activate the immune response via binding to CD1 proteins on antigen-presenting cells (APCs) and stimulate CD1-restricted T cells. In humans, there are five members of the CD1 family, termed CD1a–e, of which CD1a–d are involved in glycolipid presentation at the cell surface, while CD1e is involved in the intracellular trafficking of glycolipid antigens. Both endogenous (self-derived) and exogenous (non-self-derived) glycolipids have been shown to bind to members of the CD1 family with varying degrees of specificity. In this paper we focus on the key glycolipids that bind to the different members of the CD1 family.
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Li, Sha, Hak-Jong Choi, Sharmila Shanmuganad, and Chyung-Ru Wang. "Phenotypic and functional characterization of group 1 CD1-restricted autoreactive T cells in a transgenic mouse model expressing human group 1 CD1 and a CD1b-specific T cell receptor (36.31)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 36.31. http://dx.doi.org/10.4049/jimmunol.184.supp.36.31.
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Abstract Unlike other MHC molecules, the CD1 family presents self and foreign lipid antigens to multiple T cell subsets. In humans, this family consists of group 1 CD1 molecules CD1a, b and c and group 2 molecule CD1d. While CD1d-restricted NKT cells have been well-studied, our knowledge of the development and function of group 1 CD1-restricted T cells has been limited by the lack of a suitable animal model. We have generated double transgenic mice (hCD1Tg/HJ1Tg) that express the human group 1 CD1 proteins in a pattern similar to that observed in humans in addition to a TCR from a CD1b-restricted autoreactive T cell clone. Like NKT cells, the majority of HJ1Tg T cells that develop in hCD1Tg/HJ1Tg mice express NK markers and exhibit an activated phenotype. In addition, HJ1Tg T cells are highly enriched in the liver. The development of HJ1Tg T cells with the NKT cell phenotype is group 1 CD1-dependent, as NK1.1+ HJ1Tg T cells are absent in HJ1Tg mice that lack the human group 1 CD1 genes. Upon stimulation with group 1 CD1-expressing dendritic cells, HJ1Tg T cells primarily secrete proinflammatory cytokines, including IFN-γ, IL-17A, IL-6 and MCP-1. These cytokine productions can be further enhanced in the presence of TLR agonists, a phenomenon also observed in autoreactive NKT cells. The similarities between the phenotype and functional properties of HJ1Tg T cells and NKT cells suggest that these two autoreactive T cell subsets may play similar immunological roles.
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Gadola, Stephan D., Anastasios Karadimitris, Nathan R. Zaccai, Mariolina Salio, Nicolas Dulphy, Dawn Shepherd, E. Yvonne Jones, and Vincenzo Cerundolo. "Generation of CD1 tetramers as a tool to monitor glycolipid–specific T cells." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 358, no. 1433 (May 29, 2003): 875–77. http://dx.doi.org/10.1098/rstb.2003.1267.
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CD1 molecules are β 2 m–associated HLA class–I–like glycoproteins which have the unique ability to present glycolipid and phospholipid antigens to specific T lymphocytes. To study the biology of CD1 and its role in human disease we developed novel techniques for generation of recombinant CD1/lipid complexes by in vitro refolding. Fluorescent tetrameric complexes made from soluble recombinant CD1d/α–galactosylceramide complexes allowed highly sensitive and specific ex vivo and in vitro detection and functional characterization of novel human T–lymphocyte populations. Furthermore, protein crystals were obtained from soluble recombinant CD1b/β 2 m–proteins loaded either with phosphatidylinositol or ganglioside GM2, which led to the first atomic structure determination of a CD1/lipid complex. The analysis of these crystal structures clarified how CD1b molecules can bind lipid ligands of different size, and revealed a broader spectrum of potential CD1b ligands than previously predicted.
Dissertations / Theses on the topic "CD1 proteins"
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Belkai, Sonia. "Recherche d'acteurs lysosomaux impliqués dans la présentation de lipides mycobactériens par CD1b aux lymphocytes T." Electronic Thesis or Diss., Université de Toulouse (2023-....), 2024. http://www.theses.fr/2024TLSES176.
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Les lipides peuvent être antigéniques et présentés en surface des cellules présentatrices d'antigènes (CPA). Ces lipides, généralement amphiphiles, sont présentés par les protéines CD1 (CD1a à CD1d), des protéines proches structurellement de la protéine du CMH de classe 1, avec pour principale différence le site de liaison des antigènes. Cette présentation mène à une réponse immunitaire spécifique médiée par des lymphocytes T non conventionnels. Mycobacterium tuberculosis (Mtb), agent causal de la tuberculose, possède dans son enveloppe des lipides antigènes présentés par les protéines CD1, et particulièrement par l'isoforme CD1b. Ces lipides sont chargés sur CD1b au niveau du lysosome des cellules dendritiques (CD), dans leur état natif ou après un apprêtement. Cet apprêtement nécessite des protéines de transfert de lipides (LTP), telles que CD1e et les saposines, mais aussi des enzymes (hydrolases), permettant de digérer les parties polaire ou apolaires des lipides. Peu de LTP et hydrolases lysosomales ont à l'heure actuelle été identifiées, il est donc nécessaire de caractériser d'autres acteurs lysosomaux impliqués dans la présentation des antigènes lipidiques mycobactériens par CD1b. Les objectifs de ces travaux étaient de mettre en place des stratégies pour rechercher et identifier ces acteurs. Ainsi, dans le but d'identifier de nouveaux acteurs lysosomaux impliqués dans le transport ou la maturation des glycolipides de Mtb, deux approches complémentaires ont été mises en place. La première, plus globale, nous a conduit à préparer des fractions enrichies en lysosomes provenant de CPA. Pour valider le protocole d'obtention de ces fractions, elles ont été caractérisées morphologiquement ainsi que par la présence de marqueurs protéiques. Elles ont également servi à réaliser des tests de dégradation de lipides mycobactériens in vitro, confirmant l'action des lipases précédemment caractérisées. Enfin, l'analyse protéomique du contenu de ces fractions a contribué à l'élaboration d'une liste de cinq protéines candidates, possiblement impliquées dans l'apprêtement. Parmi elles, certaines n'ont jamais été décrites dans le contexte de présentation de lipides antigènes, et d'autres sont déjà connues pour contribuer à la présentation de lipides par CD1d. La seconde approche a consisté à définir l'interactome de CD1b dans le lysosome, en réalisant une coimmunoprécipitation de CD1b à partir de fractions lysosomales. L'analyse protéomique des partenaires a permis de proposer quatre autres protéines candidates, toutes non décrites à ce jour dans le cadre de la présentation d'antigènes lipidiques. L'expression de certaines de ces protéines candidates, sera par la suite inactivée pour étudier l'impact de cette inactivation sur la présentation des complexes CD1b-lipides. Parmi ces protéines, la protéine NPC1 (" Niemann-Pick disease C1 "), déjà connue pour être impliquée dans la présentation de lipides par l'isoforme CD1d chez la souris, a retenu notre intérêt. Des essais d'inactivation ont été réalisés grâce à un inhibiteur spécifique, avant d'envisager une inactivation de l'expression par utilisation de siRNA ou CRISPR/Cas9. Dans le but d'apprécier les effets de cette inactivation, il est nécessaire de posséder des outils biologiques capables d'évaluer la participation du candidat dans la présentation d'un lipide particulier. Lors de cette étude, deux outils ont été validés : 1) des anticorps recombinants spécifiques de CD1 présentant le sulfoglycolipide diacylé mycobactérien (Ac2SGL), et 2) différents clones lymphocytaires spécifiques de CD1b en complexe avec divers glycolipides mycobactériensLipids can be antigenic and presented on the surface of antigen-presenting cells (APCs). These lipids, generally amphiphilic, are presented by CD1 proteins (CD1a to CD1d), which are structurally similar to class I MHC proteins, with the main difference being in the antigen-binding site. This presentation leads to a specific immune response mediated by unconventional T lymphocytes. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has antigenic lipids in its envelope that are presented by CD1 proteins, particularly by the CD1b isoform. These lipids are loaded onto CD1b in the lysosome of dendritic cells (DCs), either in their native state or after processing. This processing requires lipid transfer proteins (LTPs), such as CD1e and saposins, as well as enzymes (hydrolases) that digest the polar or lipidic parts of the lipids. Few lysosomal LTPs and hydrolases have been identified so far, making it necessary to characterize other lysosomal actors involved in the presentation of mycobacterial lipid antigens by CD1b. The objectives of this work were to develop strategies to search for and identify these actors. To identify new lysosomal actors involved in the transport or maturation of Mtb glycolipids, two complementary approaches were implemented. The first, more global approach, involved preparing lysosome-enriched fractions from APCs. To validate the protocol for obtaining these fractions, they were characterized morphologically and by the presence of protein markers. They were also used to perform in vitro degradation tests of mycobacterial lipids, confirming the action of previously characterized lipases. Finally, proteomic analysis of the contents of these fractions led to the elaboration of a list of five candidate proteins that may be involved in processing. Among them, some have never been described in the context of lipid antigen presentation, while others are already known to contribute to lipid presentation by CD1d. The second approach involved defining the interactome of CD1b in the lysosome by performing co-immunoprecipitation of CD1b from lysosomal fractions. Proteomic analysis of the partners identified four other candidate proteins, none of which have been described to date in the context of lipid antigen presentation. The expression of some of these candidate proteins will subsequently be knocked out to study the impact of this inactivation on the presentation of CD1b-lipid complexes. Among these proteins, NPC1 ("Niemann-Pick disease C1"), already known to be involved in lipid presentation by the CD1d isoform in mice, was considered interesting. Inactivation tests were performed using a specific inhibitor, before considering inactivation of expression using siRNA or CRISPR/Cas9. To evaluate the effects of this inactivation, it is necessary to have biological tools capable of assessing the candidate's role in the presentation of a particular lipid. In this study, two tools were validated: 1) recombinant antibodies specific to CD1 presenting the mycobacterial diacylated sulfoglycolipid (Ac2SGL), and 2) different lymphocyte clones specific to CD1b in complex with various mycobacterial glycolipids
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Haig, Neil Ainslie. "The identification of endogenous lipid antigens associated with CD1 proteins and functional investigation of immune recognition." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526535.
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Hassan, Namir. "Interactions of the leukocyte cell-surface proteins CD5 and CD6." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398158.
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Wong, Chung Kai. "The DIX domain protein Ccd1 inhibits JNK activation by axin and dishevelled through distinct mechanisms /." View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?BICH%202004%20WONG.
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Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2004.Includes bibliographical references (leaves 60-68). Also available in electronic version. Access restricted to campus users.
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Martins, Soraia Alexandra Araújo. "CD81 interacting proteins." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16139.
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Mestrado em Biomedicina MolecularFertilization is a multistep and complex process culminating in the merge of gamete membranes, cytoplasmic unity and fusion of genome. CD81 is a tetraspanin protein that participates in sperm-oocyte interaction, being present at the oocyte surface. CD81 has also been implicated in other biological processes, however its specific function and molecular mechanisms of action remain to be elucidated. The interaction between CD81 and its binding partner proteins may underlie the CD81 involvement in a variety of cellular processes and modulate CD81/interactors specific functions. Interestingly, in a Yeast two Hybrid system previously performed in our lab, CD81 has emerged as a putative interactor of the Amyloid Precursor Protein (APP). In the work here described, bioinformatics analyses of CD81 interacting proteins were performed and the retrieved information used to construct a protein-protein interaction network, as well as to perform Gene Ontology enrichment analyses. CD81 expression was further evaluated in CHO, GC-1 and SH-SY5Y cell lines, and in human sperm cells. Additionally, its subcellular localization was analyzed in sperm cells and in the neuronal-like SH-SY5Y cell line. Subsequently, coimmunoprecipitation assays were performed in CHO and SH-SY5Y cells to attempt to prove the physical interaction between CD81 and APP. A functional interaction between these two proteins was accessed thought the analyses of the effects of CD81 overexpression on APP levels. A co-localization analysis of CD81 and some interactors proteins retrieved from the bioinformatics analyses, such as APP, AKT1 and cytoskeleton-related proteins, was also performed in sperm cells and in SH-SY5Y cells. The effects of CD81 in cytoskeleton remodeling was evaluated in SH-SY5Y cells through monitoring the effects of CD81 overexpression in actin and tubulin levels, and analyzing the colocalization between overexpressed CD81 and F-actin. Our results showed that CD81 is expressed in all cell lines tested, and also provided the first evidence of the presence of CD81 in human sperm cells. CD81 immunoreactivity was predominantly detected in the sperm head, including the acrosome membrane, and in the midpiece, where it co-localized with APP, as well as in the post-acrosomal region. Furthermore, CD81 co-localizes with APP in the plasma membrane and in cellular projections in SH-SY5Y cells, where CD81 overexpression has an influence on APP levels, also visible in CHO cells. The analysis of CD81 interacting proteins such as AKT1 and cytoskeletonrelated proteins showed that CD81 is involved in a variety of pathways that may underlie cytoskeleton remodeling events, related to processes such as sperm motility, cell migration and neuritogenesis. These results deepen our understanding on the functions of CD81 and some of its interactors in sperm and neuronal cells.
A fecundação é um processo complexo e faseado que culmina na fusão celular das membranas dos gametas, do citoplasma e do genoma. A CD81 é uma proteína tetraspanina que participa na interacção espermatozóide-oócito, estando presente na superfície do oócito. A CD81 também tem sido associada a outros processos biológicos, contudo a sua função específica e os seus mecanismos de acção não estão elucidados. A ligação entre a CD81 e as suas proteínas interactoras fundamenta o envolvimento da CD81 numa variedade de processos celulares e funções específicas. O desenvolvimento de um sistema de Dois Híbrido em Leveduras, anteriormente realizado no nosso laboratório, mostrou que a CD81 potencialmente interage com a Proteína Percursora de Amilóide (PPA). No presente trabalho, foi realizada a análise bioinformática das proteínas interactoras da CD81. A informação obtida permitiu a construção de uma rede de interações proteína-proteína, bem como a análise de enrequecimento de Ontologia de Genes. Adicionalmente, a expressão da CD81 foi avaliada nas linhas celulares CHO, GC-1 e SH-SY5Y e em espermatozóides humanos. A sua localização subcelular foi também analisada em espermatozóides humanos e na linha de neuroblastoma SH-SY5Y. Foram ainda realizados ensaios de coimunoprecipitacão nas linhas celulares CHO e SH-SY5Y, com a tentativa de provar a intercação física entre a CD81 e a PPA. A interação funcional entre estas duas proteínas foi estudada através da análise do efeito da sobreexpressão da CD81 nos níveis de PPA. Foram também realizados estudos de colocalização entre a CD81 e algumas proteínas interactoras, nos espermatozóides humanos e na linha celular SH-SY5Y. Os interatores analisados, PPA, AKT1 e proteínas relacionadas com o citoesqueleto, foram obtidos da análise bioinformática previamente realizada. O efeito da CD81 na remodelação do citoesqueleto foi avaliado através da monitorização dos efeitos da sobre-expressão da CD81 nos níveis de actina e tubulina, bem como através da análise da colocalização entre a CD81 sobre-expressa e a F-actina. Os nossos resultados mostram que a CD81 está expressa em todas as linhas celulares testadas, providenciando a primeira evidência da presença da CD81 em espermatozóides humanos. A marcação da CD81 foi predominantemente detectada na cabeça do espermatozóde e na peça intermédia, onde colocaliza com a PPA, bem como na região pós-acrossómica. Em adição, a CD81 colocaliza com a PPA na membrana plasmática e nas projecções celulares das células SH-SY5Y, onde a sobre-expressão da CD81 influencia os níveis de PPA, efeito também observado nas células CHO. A análise de proteínas interactoras da CD81, como a AKT1 e proteínas relacionadas com o citoesqueleto, evidenciou que a CD81 está envolvida na remodelação do citoesqueleto, nomeadamente na motilidade dos espermatozóides, na migração celular e na neuritogénese. Estes resultados permitiram aprofundar o conhecimento das funções da CD81 e de alguns dos seus interactores, em espermatozóides e em células neuronais.
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Simões, Inês Tadeu dos Anjos. "Characterization of the in vivo immunomodulatory properties of CD5 and CD6." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/593499.
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Our goal in this doctoral thesis was to study the immunomodulatory effects of CD5 and CD6, two proteins expressed on the lymphocytes membrane. These two proteins belong to the Scavenger Receptors Cystein- Rich superfamily, characterized by the presence of one or more cysteine rich domains. The interaction between CD6 and ALCAM, its principal ligand, is well established but recently more ligands of CD6 have been described. On the other hand, to date there is no consensus about the CD5 ligand/s, although several candidates have been proposed. Previous work carried out with CD5 and CD6-deficient mice revealed the role as negative modulators of the T/B cell receptor signaling. It was observed how its blockade/absence led to a hyper-activation post T cell activation by increment of cell proliferation and calcium mobilization.
We decided to generate a transgenic mouse that would expresses high levels of the extracellular region of human CD5 constitutively, in order to block the interactions mediated by membrane-bound CD5 with its ligand/s. This “functional knockout" would resemble what would happen in a clinical application, by injecting the soluble recombinant protein to humans. These mice presented indeed soluble human CD5 in serum, which resulted in immunophenotypical changes that were reproduced in wild-type mice after repeated administration of exogenous rshCD5 protein. The transgenic mice did not reveal any gross alterations in major lymphocyte subpopulations. However, a decrease in T and B cell subsets with regulatory function, as well as an increment in NKT cells were observed. They also presented more severe disease outcome to two different induced experimental autoimmune disease models and a better anti- tumor response against murine melanoma cells (B16-F0) and a genetically modified line of thymoma tumor cells (EG7-OVA). We have observed that this effect is due to the increase in number and activity of the effector cells of the immune system as well as the lowering of the regulatory T cells in the tumor draining lymph nodes. On the other hand, wild-type mice challenged with melanoma showed an improved anti-tumor response as well as changes in the tumor draining lymph node after therapeutic administration of the protein. In addition, in this model, a decrease in IL-6 expression levels was observed, and the loss of efficacy obtained with CD5 administration by depleting NK cells.
We also generated another murine model expressing elevated levels of human soluble CD6 in a constitutive way, with the objective of blocking the heterophillic and homophillic interactions of CD6 and its ligands. These mice had a decrease in the spleen and lymph nodes total cell number. Their B cells have reduced proliferative capacity and the regulatory T cell less suppressive activity aside to a reduction of their number. We observed an increment of the anti-tumor response to different tumor cell lines, but their autoimmune response was not exacerbated, as it was expected. These results were reproduced when recombinant soluble human CD6 was injected repeatedly into wild-type mice.
The results obtained demonstrate that counteracting the function of membrane-bound CD5/CD6 with sCD5/CD6 may enhance current immunotherapies for cancer, as well as be used in other possible applications such as in acute or chronic infections (CD5 recognizes fungal and viral components, and CD6 bacterial components) and vaccines.El objetivo de esta tesis doctoral ha sido el estudio de los efectos inmunomoduladores de CD5 y CD6, dos proteínas expresadas en la membrana de los linfocitos. Estas dos proteínas pertenecen a la superfamilia de receptores "Scavenger Receptor Cystein-Rich", caracterizada por la presencia de uno o varios dominios ricos en cisteínas. En cuanto a CD6, están descritos varios ligandos, sin embargo, a día de hoy no existe un consenso acerca del ligando/s de CD5.Trabajos previos llevados a cabo con ratones deficientes para CD5/CD6, pusieron de manifiesto sus papeles como moduladores negativos de la señal del receptor de células T/B. Decidimos generar un ratón que expresara niveles elevados de la región extracelular de CD5 humano constitutivamente, con el objetivo de bloquear las interacciones mediadas por el CD5 de membrana con su ligando/s. Observamos que estos ratones presentaron una respuesta autoinmune exacerbada pero mejor respuesta anti-tumoral frente a células murinas de melanoma y linfoma. Este efecto se debió al aumento de número y actividad de las células efectoras del sistema inmune, así como a la bajada de las células T reguladoras en los ganglios drenantes del tumor. Por otro lado, ratones silvestres a los que se les indujo melanoma mostraron una respuesta anti-tumoral mejorada, así como cambios en el ganglio drenante, tras la administración de la proteína de forma terapéutica. Además, la eficacia obtenida con la administración de CD5 se perdió al deplecionar las células NK. Además, se generó otro modelo murino que expresara niveles elevados de CD6 soluble humano de manera constitutiva, con el mismo objetivo. Estos ratones presentaron una bajada en cuanto al número de células en bazo y nódulos linfáticos debido a la capacidad proliferativa reducida de los linfocitos B. Además de una disminución en número, las células T reguladoras presentaron una menor actividad supresora. Así, observamos un aumento de la respuesta anti-tumoral frente a diferentes líneas tumorales, pero su respuesta autoinmune no se encontraba exacerbada. Estos resultados se reprodujeron cuando se inyectó CD6 soluble a ratones silvestres. Los resultados obtenidos denotan la importancia de CD5 y CD6 en la respuesta inmune, y su posible aplicación en combinación con las actuales terapias inmunomoduladoras.
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Yap, Jessica. "Identification of Plasmodium falciparum protein kinase substrates and interacting proteins." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/644.
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Characterization of PfPKA and PfPK5 substrates, as well as the proteins they interact with, will help us to develop innovative therapies targeting binding sites.; Malaria is a devastating disease that results in almost one million deaths annually. Most of the victims are children under the age of five in Sub-Saharan Africa. Malaria parasite strains throughout developing countries are continually building resistance to available drugs. Current therapies such as mefloquine, chloroquine, as well as artemisinin are becoming less effective, and this underscores the urgency for therapeutics directed against novel drug targets. In order to identify new drug targets, the molecular biology of the malaria parasite Plasmodium needs to be elucidated. Plasmodium exhibits a unique cell cycle in which it undergoes multiple rounds of DNA synthesis and mitosis without cytokinesis. Thus, cell cycle regulatory proteins are likely to be promising pathogen-specific drug targets. It is expected that fluctuating activity of key proteins, such as protein kinases, play an essential role in regulating the noncanonical life cycle of Plasmodium. Consequently, malarial kinases are a prime target for therapy. One way to better understand the role of malarial kinases in Plasmodium cell cycle regulation is to identify putative protein kinase substrates and interacting proteins. Two malarial kinases that have been implicated in regulating malaria parasite cell cycle stages were investigated in this study: P. falciparum CDK-like Protein Kinase 5 (PfPK5) and cAMP-Dependent Protein Kinase A (PfPKA). A transgenic P. falciparum line was created for the expression of epitope-tagged PfPK5 for pull-down analysis. Phospho-substrate antibodies were used to identify physiological substrates of both PfPK5 and PfPKA. Immunoblotting with these antibodies identified several potential substrates. Identities of the PfPKA physiological substrates were determined from the global P. falciparum phosphoproteome dataset that has recently been generated in our laboratory.B.S.
Bachelors
Burnett School of Biomedical Sciences
Molecular and Microbiology
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Nishimura, Hiroyuki. "Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4-CD8-) thymocytes." Kyoto University, 1997. http://hdl.handle.net/2433/202184.
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Carrat, Christophe. "Etude des mécanismes de présentation des lipides mycobactériens par les protéines CD1." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30293.
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Les antigènes lipidiques sont présentés aux lymphocytes T par les protéines CD1 (CD1a à CD1d), exprimées à la surface des cellules présentatrices d'antigènes (CPA), telles que les cellules dendritiques. Dans le cadre de la tuberculose, dont l'agent étiologique est Mycobacterium tuberculosis (Mtb), un certain nombre d'antigènes lipidiques ont été décrits depuis une vingtaine d'années et sont, pour la plupart, présentés par l'isoforme CD1b. Plus récemment, il a été montré que ces antigènes peuvent être apprêtés par des enzymes lysosomales de la CPA, à l'instar de ce qui est connu pour la présentation de peptides par le complexe majeur d'histocompatibilité. L'apprêtement des antigènes lipidiques fait intervenir des protéines de transfert de lipides, telle que la protéine CD1e, une cinquième isoforme soluble nécessaire à la présentation des phosphatidyl-myo-inositol mannosides (PIM). Cependant, les mécanismes de l'apprêtement des antigènes lipidiques ainsi que les épitopes réellement présentés par CD1b à la surface des CPA sont à l'heure actuelle encore mal connus. Afin d'identifier les épitopes lipidiques présentés par CD1b lors d'une infection par Mtb, nous avons développé une stratégie innovante permettant d'isoler les complexes CD1b: lipides présents en surface des CPA, en s'affranchissant de l'utilisation de détergents, proscrits ici. Cette stratégie repose sur la construction d'une CPA comportant une forme clivable de la protéine CD1b, exprimant CD1e ou non. Les conditions de clivage et de purification de ces complexes ont été mises au point au cours de ce travail. Les lipides sont ensuite extraits et analysés par HPLC couplée à la spectrométrie de masse. Cette approche a permis l'analyse des lipides endogènes présents dans CD1b. Elle a ensuite été validée par des expériences de stimulation des CPA par des lipides mycobactériens purifiés. Afin d'améliorer la détection des épitopes par spectrométrie de masse, des optimisations des conditions de stimulation des CPA sont actuellement en cours. Le second axe développé au cours de ma thèse a porté sur l'étude des enzymes impliquées dans l'apprêtement des antigènes lipidiques. Les glycolipides mycobactériens peuvent être le substrat d'enzymes lysosomales. Les PIM en sont l'exemple le mieux caractérisé, car des enzymes intervenant dans l'hydrolyse de la partie saccharidique et de la partie hydrophobe du lipide ont été identifiées. Pour déterminer de nouvelles activités enzymatiques impliquées dans l'apprêtement des glycolipides de Mtb, nous avons cherché à générer une fraction lysosomale issue de CPA pour réaliser des tests de dégradation in vitro. [...]Lipid antigens are presented to T cells by CD1 proteins (CD1a to CD1d), expressed at the surface of antigen presenting cells (APC), such as dendritic cells. Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB). Mtb lipid antigens have been described over the last twenty years and are, most of them being presented by the CD1b isoform. Recent studies in humans have shown that specific T cell responses to Mtb lipid antigens play a role in the immune response to infection, and contribute to the creation of a reservoir of memory cells. More recently, it has been shown that these antigens can be processed by lysosomal enzymes in APC, similarly to that described for the presentation of peptides by the major histocompatibility complex. Lipid antigens processing involves lipid transfer proteins, such as CD1e, a fifth soluble isoform of CD1 necessary for the presentation of phosphatidyl-myo-inositol mannosides (PIM). However, the mechanisms of lipid antigen processing as well as the repertoire of epitopes presented by CD1b at the surface of APC are still poorly understood. In order to identify the lipid epitopes presented by CD1b during Mtb infection, we developed an innovative strategy to isolate the CD1b:lipid complexes at the surface of APC, by avoiding the use of detergents. This strategy is based on the construction of APC cell lines. Different APC were constructed, that may or may not express CD1e. The conditions of CD1b cleavage and purification, as well as the extraction of the lipids and their analysis by mass spectrometry were set up and optimized. The lipids are then extracted and analyzed by HPLC coupled to mass spectrometry. In a first step, this approach was used to study the endogenous lipids presented by CD1b. It was then validated by APC stimulation experiments with purified mycobacterial lipids. Detecting Mtb epitopes during infection requires a high sensitivity in mass spectrometry. Therefore, optimizations of the APC stimulation efficiency are in progress. The second axis developed during my PhD focused on the study of enzymes involved in lipid antigen processing. Mycobacterial glycolipids may be the substrates of lysosomal enzymes. Among them, the PIM family is the best characterized example, with enzymes involved in the hydrolysis of both the saccharide and the lipid part. To characterize new enzymatic activities involved in processing of Mtb glycolipids, we sought to generate a lysosomal fraction from APC to perform in vitro digestion tests. Digestion tests for tetra-acylated PIM2 yielded di and tri-acylated PIM2 generated by lipase activities.[...]
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Gohring, John Thomas Fan Xudong. "Detection of CD4 and CD8 t-lymphocytes and HER2 breast cancer biomarker using the opto-fluidic ring resonator biosensor." Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/6661.
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Title from PDF of title page (University of Missouri--Columbia, viewed on March 10, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Thesis advisor: Dr. Xudong Fan. Includes bibliographical references.
Books on the topic "CD1 proteins"
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Pontus, Aspenstrøm, ed. The pombe Cdc 15 homology proteins. Austin, Tex: Landes Bioscience, 2009.
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Anderluh, Gregor, and Robert Gilbert, eds. MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-8881-6.
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Metzner, Karin. Zur CD8+-T-Lymphozyten: Interleukin-16 und Identifikation und Charakterisierung anderer sezernierter Proteine. [s.l.]: [s.n.], 1997.
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Pumphrey, Nicholas Jonathan. Delineating the signalling potential of the cytoplasmic tail of CD31, and related protein CD66a. Birmingham: University of Birmingham, 2000.
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B, Kastan M., and Imperial Cancer Research Fund (Great Britain), eds. Checkpoint controls and cancer. Plainview, NY: Cold Spring Harbor Laboratory Press, 1997.
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A, Schreiber, ed. Primate phylogeny from a human perspective: A study based on the immunological technique of comparative determinant analysis (CDA). Stuttgart: G. Fischer, 1996.
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Workshop on Mechanisms and Specificity of HIV Entry into Host Cells (1989 San Francisco, Calif.). Mechanisms and specificity of HIV entry into host cells. New York: Plenum Press, 1991.
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Gilbert, Robert, and Gregor Anderluh. MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Ingramcontent, 2014.
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Gilbert, Robert, and Gregor Anderluh. MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Springer, 2016.
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Gilbert, Robert, and Gregor Anderluh. MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Springer London, Limited, 2014.
Find full textBook chapters on the topic "CD1 proteins"
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Porcelli, Steven A., and D. Branch Moody. "Antigen Processing and Presentation by CD1 Family Proteins." In Antigen Presenting Cells, 129–56. Weinheim, FRG: Wiley-VCH Verlag GmbH & Co. KGaA, 2006. http://dx.doi.org/10.1002/3527607021.ch5.
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Walsh, Gary. "Proteins and Proteomics." In Proteins, 1–23. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2015. http://dx.doi.org/10.1002/9781119117599.ch1.
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Kontermann, Roland E. "Half-Life Modulating Strategies-An Introduction." In Therapeutic Proteins, 1–21. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2012. http://dx.doi.org/10.1002/9783527644827.ch1.
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Medway, Christopher, and Kevin Morgan. "CD2-Associated Protein (CD2AP)." In Genetic Variants in Alzheimer's Disease, 201–8. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-7309-1_11.
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Anderluh, Gregor, Matic Kisovec, Nada Kraševec, and Robert J. C. Gilbert. "Distribution of MACPF/CDC Proteins." In MACPF/CDC Proteins - Agents of Defence, Attack and Invasion, 7–30. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-8881-6_2.
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Stirpe, Fiorenzo. "Introduction and History." In Ribosome-inactivating Proteins, 1–10. Oxford: John Wiley & Sons, Ltd., 2014. http://dx.doi.org/10.1002/9781118847237.ch1.
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Tobias, Peter S. "Lipopolysaccharide-Binding Protein and CD14." In Innate Immunity, 255–65. Totowa, NJ: Humana Press, 2003. https://doi.org/10.1007/978-1-59259-320-0_14.
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Holm, Liisa, and Andreas Heger. "Automated Sequence-Based Approaches for Identifying Domain Families." In Protein Families, 1–24. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118743089.ch1.
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Patterson, Cam, and Jörg Höhfeld. "Molecular Chaperones and the Ubiquitin-Proteasome System." In Protein Degradation, 1–30. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2008. http://dx.doi.org/10.1002/9783527620210.ch1.
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Kragt, Astrid, Rob Benne, and Ben Distel. "Ubiquitin: A New Player in the Peroxisome Field." In Protein Degradation, 1–20. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2007. http://dx.doi.org/10.1002/9783527620227.ch1.
Full textConference papers on the topic "CD1 proteins"
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Milanović, Žiko, Marko Antonijević, Dušica Simijonović, Jelena Đorović Jovanović, and Marijana Stanojević Pirković. "Investigating the potential inhibitory effect of the megaphone (molecule) on nasopharyngeal cancer growth factor receptors." In 2nd International Conference on Chemo and Bioinformatics. Institute for Information Technologies, University of Kragujevac, 2023. http://dx.doi.org/10.46793/iccbi23.682m.
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Nasopharyngeal cancer (NPC) is a type of cancer that originates in the nasopharynx, which is the upper part of the throat behind the nasal cavity. Like other cancers, the growth and progression of nasopharyngeal cancer are influenced by various proteins involved in cell signaling, growth regulation, and tumor development such as Epidermal Growth Factor Receptor (EGFR), Vascular Endothelial Growth Factor (VEGF), Fibroblast growth factor receptor (FGFR) and Cyclin D1 (CD1). Megaphone ((1′R,5′R,7R,8S)-7-Hydroxy-3,4,5,5′-methoxy-5′,6′-dihydro-2′H-8,1′-neolign-8′-en-2′-one, MG) is the main component of the alcohol extract of the ground root of Aniba megaphylla, which in vitro inhibits the growth of cells derived from human nasopharyngeal carcinoma. Due to the lack of literature data, the main goal of this study was to examine the first step of the mechanisms of anti-carcinogenic activity by examining the inhibitory potential of MG against the above-mentioned cancer cell growth factor receptors.
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Wernet, P., E. M. Scheider, P. Sarin, P. Chandra, H. H. Brackmann, M. Kessler, and H. Egli. "Demonstration of HIV-encoded Proteins in Cultured and in Uncultured CD 4 Positive Mononuclear Cells from Hemophilia Patients Employing Monoclonal Antibodies against p 15, p 24, GP 41, GP 120, and Reverse Transcriptase." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644683.
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In the light of the large percentage of hemophilia patients with antibodies to HIV the identification of a specific virus infection in comparison to HIV antibody negative hemophilia patients has reached crucial importance. The low success rates of direct virus culture techniques together with the as yet low AIDS-di-sease rate observed in these patients separate these patients from the other main risk groups. Within this context, we studied the expression of CD3, CD4, CD8, and HLA class II antigens on fixed cells after PHA stimulation and Interleukin 2 propagation as well as on untreated blood mononuclear cells from healthy individuals and from hemophilia patients by fluorescence activated flow cytometry. Monoclonal antibodies thought to be specific for p 15, p 24, GP 41, GP 120, and for reverse transcriptase revealed a certain number of positive cells on all defined subpopulations analysed. From cell specimen of HIV antibody positive hemophilia patients cells with specific HIV antigens could be enriched by in vitro cultivation. Importantly the expression of virus-encoded antigens preceedes a cytopathic effect for several daVs. Current analyses aim at the prognostic relevance of low amounts of such viral HIV proteins selectively detectable by moAbs.directed to either p 24, GP 41, GP 120, and RT. The reliability, high sensitivity and monoclonal antibody dependent specificity of this newly developed method for the demonstration of HIV specific proteins make it applicable also for longitudinal surveys of hemophilia patients to assess a potential state of viremia or virus antigen processing in their mononuclear cells.
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Lima, Maríllia Raphaella Cabral Fonseca de, Guilherme Antonio de Souza Silva, Leonardo Carvalho de Oliveira Cruz, Georon Ferreira de Sousa, Bárbara Rafaela da Silva Barros, Rodrigo Cesar Abreu de Aquino, and Cristiane Moutinho Lagos de Melo. "PERFIL DA RESPOSTA IMUNOLÓGICA, EFICÁCIA E EFEITOS COLATERAIS DAS VACINAS EM USO CONTRA A COVID-19 NO BRASIL." In XXVII Semana de Biomedicina Inovação e Ciência. Editora IME, 2021. http://dx.doi.org/10.51161/9786588884119/24.
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Introdução: Com a pandemia da COVID-19, doença causada pelo vírus SARS-CoV- 2¹, o desenvolvimento de uma vacina eficaz ocorreu em tempo recorde, exibindo bons resultados. As vacinas foram criadas com métodos variados, como: vetor viral recombinante, subunidade de proteína, vírus inativados e ácidos nucleicos. No Brasil, a vacinação foi iniciada em 17 de janeiro de 2021, com uso emergencial da CoronaVac e da AstraZeneca. Objetivos: Descrever o perfil da resposta imunológica, eficácia e efeitos colaterais das vacinas contra COVID-19 utilizadas no Brasil. Métodos: Foram selecionados artigos disponíveis na plataforma PubMed. Os critérios de inclusão foram artigos no idioma inglês, publicados nos anos de 2020-2021 com os seguintes descritores: Vacinação; COVID-19; Eficácia; Efeitos Colaterais; e Resposta Imunológica. Resultados/Discussão: A vacina de RNAm da Pfizer induziu elevados títulos de anticorpos neutralizantes para SARS-CoV-2 e resposta T CD4+/CD8+, com eficácia de 95% após a segunda dose, e os efeitos colaterais mais comuns foram fadiga e cefaléia². A AstraZeneca, vacina de adenovírus modificado, apresentou resposta imunológica humoral e celular, além de eficácia de 90% após a segunda dose, possuindo como efeitos adversos mais comuns mialgia, fadiga, cefaléia, dor no local da injeção e febre.³ A Janssen, vacina adenoviral (Ad26) de dose única, demonstrou produção de anticorpos neutralizantes, e resposta celular T CD4+/CD8+, apresentando eficácia variando de 67% a 85% de acordo com a gravidade do caso. Seus os principais efeitos adversos foram dor no local da injeção, cefaléia e fadiga.4 A Sputnik V, vacina adenoviral de imunização heteróloga (Ad26 primeira dose e Ad5 segunda dose), apresentou forte resposta humoral e de células T CD4+/CD8+, e eficácia de 91,4% após a segunda dose, sendo as principais reações adversas astenia, mialgia, artralgia, febre e cefaléia. A CoronaVac, vacina de vírus inteiro inativado, induziu a produção de anticorpos contra o SARS-CoV-2, além de uma resposta celular de linfócitos T produtores de IFN-γ, apresentou eficácia que variou entre 83,7% e 100% após a segunda dose, dependendo da gravidade, e a principal reação adversa foi a dor no local da aplicação.5 Conclusões: O perfil de resposta imunológica é, principalmente, produção de anticorpos neutralizantes e resposta T CD4+/CD8+. As eficácias das vacinas em uso no Brasil variam entre 66% - 91,4% após a imunização completa e o principal efeito colateral foi a cefaléia.
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Valadão, Robson Cabral. "FORMAS DE DEFESA DO SISTEMA IMUNOLÓGICO CONTRA DIFERENTES TIPOS DE MICRORGANISMOS." In II Congresso Brasileiro de Imunologia On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/ii-conbrai/6938.
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Introdução: O sistema imunológico precisa estar alerta contra a diversidade de microrganismos que entram em contato com o corpo humano e impedir que haja reações maléficas. Nossa primeira barreira imunológica, a pele, possui componentes moleculares e celulares envolvidos na imunidade inata. Caso essa primeira defesa falhe, muitas vezes pela ação do próprio microrganismo que já possui meios de driblar o ataque do nosso sistema, entra em cena outros componentes moleculares e celulares mais específicos, diversificados e potentes. Cada tipo de microrganismo causa uma reação diferenciada, seja a nível molecular ou celular. Objetivo: explanar como ocorre essa atuação específica do sistema imunológico frente a essa variedade de patógenos e seus próprios componentes de defesa. Metodologia: Foi utilizado como método uma revisão bibliográfica de artigos que tratam do tema na plataforma Scielo. Resultados: Para bactérias extracelulares temos as barreiras naturais, como pele e mucosas, imunidade inata com proteína C reativa, sistema complemento, células NK, neutrófilos, macrófagos, anticorpos, citocinas produzidas por células T e quimiocinas. Bactérias intracelulares podem estimular tanto células T CD4 quanto células T CD8. Os vírus, na fase inicial, a defesa é feita através da imunidade inata por macrófagos, células NK e interferons, dando sequência, a ativação da imunidade adaptativa, células T CD8 com sua função de citotoxicidade, tentando provocar lise celular e posteriormente opsonização do que restar da carga viral por meio dos anticorpos, sendo ativos pela participação também das células T CD4. Os protozoários escapam do sistema imune, principalmente do inato, por seus mecanismos de conservação para o parasitismo. Ativando então a imunidade adaptativa por APCs, atuando tanto células T CD4 quanto T CD8. Helmintos, devido ao tamanho e a diversidade metabólica, ativam múltiplos mecanismos da resposta imunológica, principalmente com produção de IgE e ação de eosinófilos. Conclusão: Os fungos ativam principalmente os fagócitos, que tendam destruí-los pela produção de NO e de outras citocinas. As morfologias, os tamanhos, seus componentes moleculares ligado a membrana e fisiologias diversas desses microrganismos impulsionaram nosso sistema imunológico a se adaptar e adquirir novos componentes, ao logo da evolução, justamente na tentativa de impedir qualquer invasão indesejada.
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Lee, Solhwi, and Se Jin Im. "1095 CD51 as a newly identified immunomodulatory protein: investigating expression and function on CD8 T cells." In SITC 38th Annual Meeting (SITC 2023) Abstracts. BMJ Publishing Group Ltd, 2023. http://dx.doi.org/10.1136/jitc-2023-sitc2023.1095.
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Anurangi, P. A. L. A., D. Amaratunga, and S. D. Viswakula. "Testing For Group Differences in Proteomics Data with Left Censored Data and a Limited Sample Size." In SLIIT International Conference on Advancements in Sciences and Humanities 2023. Faculty of Humanities and Sciences, SLIIT, 2023. http://dx.doi.org/10.54389/kykw4210.
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This research study aims to assess how a specific treatment influences the levels of three proteins when left-censored observations are present in a limited sample size. The dataset contained paired data gathered from 20 subjects categorized into 4 groups with increasing dosages, collected before and after administrating the treatment. The primary objective of this study is to evaluate whether there is an increase in response with increasing dosage for each of the proteins. To check the adherence of data to standard distribution, Cumulative Distribution Function (CDF) plots were used. To obtain summary statistics, Regression on Order Statistics (ROS), Maximum Likelihood Estimate (MLE) and Kaplan-Meier (KM) methods were utilized. ROS assumed to be the estimate that generally works well for the dataset as KM was unable to estimate the median for highly censored data and MLE produced unrealistic values for mean in some cases. Various matched paired tests were used to assess differences between before treatment and after treatment. The censored sign test, censored sign rank test, Peto Prentice test, and censored paired test all produced consistent conclusions across different alternative hypotheses, confirming higher protein concentrations after treatment. To evaluate mean differences, censored ANOVA, permutation tests, Peto Peto test, and Kruskal Wallis test were employed. No method demonstrated clear superiority over others. Jonckheere Terpstra test revealed the presence of group trend across increasing dosages. Multiple detection limits did not significantly impact the conclusions drawn from the study, and their consideration did not pose additional burdens. In conclusion, the treatment had a significant effect on protein levels, with dose variations influencing the outcome.
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Andrade, Vitor Soares Machado de, MATHEUS DA SILVA WIZIACK, PEDRO RAFAEL BEZERRA MACEDO, ANA CAROLINE RIBEIRO LIMA BORGES, and LARISSA SOARES DE ANDRADE. "A RELAÇÃO IMUNOLÓGICA DA VACINA CONTRA O COVID-19 COM DESFECHOS DE MIOCARDITE." In II Congresso Brasileiro de Imunologia On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/ii-conbrai/5942.
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Introdução: A miocardite é uma doença inflamatória cardíaca desencadeada por infecções virais. Hodiernamente, tem-se percebido um aumento da incidência de casos de miocardite após a vacinação contra o COVID-19 (10 a cada 100000 pessoas). No entanto, esse aumento foi mais relatado em vacinas que utilizaram como base tecnológica o mRNA, como Pfizer/BioNTech e Moderna. Objetivos: Descrever mecanismos imunológicos envolvidos nos desfechos de miocardite após a vacinação contra o COVID-19. Material e Métodos:: Trata-se de uma revisão sistemática, na qual foram selecionados artigos científicos publicados na Biblioteca Virtual de Saúde (BVS), entre os anos de 2020 a 2022, a partir das palavras chaves “vacina”, “covid-19”, “miocardite” e “pericardite”, unidas pelo operador boleano \"AND\". Posteriormente, selecionou-se os artigos que respondessem a seguinte pergunta norteadora “qual a relação imunológica da vacina contra o covid-19 com desfechos de miocardite?”, totalizando 9 artigos. Resultados: A sequência de mRNA inoculada pela vacina promove a formação de proteínas spike do coronavírus nas células hospedeiras. Esses peptídeos são apresentados por células apresentadoras de antígeno, que ativam a imunidade adaptativa: resposta celular (ativação dos linfócitos T CD4+ e CD8+) e humoral (ativação de linfócitos B e produção de anticorpos anti-SARS-CoV-2). Contudo, a imunidade inata também é ativada de forma anormal devido a exposição à proteína spike secretada pela célula hospedeira ou pela exposição ao ácido nucleico viral, provocando uma resposta hiperimune que inclui ativação de linfócitos natural killer (NK) e macrófagos, bem como liberação exacerbada de citocinas. Sugere-se que essa alteração esteja correlacionada ao comprometimento miocárdico. Além disso, uma resposta imune contra autoantígenos em cardiomiócitos é outro possível mecanismo, visto que a presença de mimetismo entre a proteína spike e os autoantígenos cardíacos podem gerar anticorpos anti-SARS-Cov-2 contra proteínas cardíacas. Conclusão Portanto, os mecanismos imunológicos da vacina sobre a incidência de miocardite podem estar relacionados com a tempestade de citocinas e mimetismo da spike com autoantígenos cardíacos. Apesar dessa relação, os benefícios da vacinação contra COVID-19 ultrapassam o raro risco de miocardite para todas as faixas etárias, entretanto, são necessárias mais investigações sobre os mecanismos imunológicos desse quadro.
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Nurhidayati, Dwi Yuni, Yuliati Yuliati, Almira Fahrinda, Tri Yudhani Mardining Raras, Hidayat Sujuti, and Sumarno Reto Prawiro. "Effect of Ag38kDa recombinant protein antibodies of Mycobacterium tuberculosis and Rifampicin on CD4 and CD8 lymphocytes: Ex vivo study." In THE 4TH INTERNATIONAL CONFERENCE ON LIFE SCIENCE AND TECHNOLOGY (ICoLiST). AIP Publishing, 2023. http://dx.doi.org/10.1063/5.0117952.
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Jovičić Milić, Sandra S., Marko Antonijević, Đorđe S. Petrović, Verica V. Jevtić, and Danijela Lj Stojković. "Investigation of the anticancer activity of 2-amino-6-methylbenzothiazole and corresponding Pd(II) complex using molecular docking simulations." In 2nd International Conference on Chemo and Bioinformatics. Institute for Information Technologies, University of Kragujevac, 2023. http://dx.doi.org/10.46793/iccbi23.535jm.
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In our prior investigations, it has been established that compound di(2-amino-6-methylbenzothiazole)dichloridopalladate(II) (C1) exhibits promising efficacy in inhibiting the growth of colon carcinoma, thereby demonstrating potential as an anticancer agent. To elucidate the underlying mechanism of action against cancer, a comprehensive investigation involving DNA binding analysis and a series of assays to evaluate the inhibitory potential of compound C1 against key proteins involved in cancer metabolism were conducted. The significant inhibitory potential of C1 towards Bcl-2, Ki-67, and CDK-4 was determined. In order to investigate the underlying mechanism behind the anticancer properties and to assess the inhibition of various proteins involved in different metabolic pathways of C1, molecular docking simulations were conducted. The investigation revealed that the observed lack of similarity between the experimental outcomes and the inhibition of Bcl-2 and CDK-4 by C1 and 2-amino-6-methylbenzothiazole (L1) suggests that the metabolic pathways involving these proteins do not contribute to the anticancer properties of C1. The observed correlation between the inhibition of Ki-67 and the experimental outcomes was found to be significant. The inhibition of Ki-67 in cell cycle regulation is a promising approach to the development of anticancer drugs. Further research is required to explore the potential application of C1 as a Ki-67 inhibitor.
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Draghiciu, L., S. Mihaila, C. Parvulescu, and A. Albu. "Electrical tests for acetylcholinesterase and activation with CD3 (antigen) and anti- CD3 (antibody) with proteins." In 2023 International Semiconductor Conference (CAS). IEEE, 2023. http://dx.doi.org/10.1109/cas59036.2023.10303684.
Full textReports on the topic "CD1 proteins"
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Banai, Menachem, and Gary Splitter. Molecular Characterization and Function of Brucella Immunodominant Proteins. United States Department of Agriculture, July 1993. http://dx.doi.org/10.32747/1993.7568100.bard.
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The BARD project was a continuation of a previous BARD funded research project. It was aimed at characterization of the 12kDa immunodominant protein and subsequently the cloning and expression of the gene in E. coli. Additional immunodominant proteins were sought among genomic B. abortus expression library clones using T-lymphocyte proliferation assay as a screening method. The 12kDa protein was identified as the L7/L12 ribosomal protein demonstrating in the first time the role a structural protein may play in the development of the host's immunity against the organism. The gene was cloned from B. abortus (USA) and B. melitensis (Israel) showing identity of the oligonucleotide sequence between the two species. Further subcloning allowed expression of the protein in E. coli. While the native protein was shown to have DTH antigenicity its recombinant analog lacked this activity. In contrast the two proteins elicited lymphocyte proliferation in experimental murine brucellosis. CD4+ cells of the Th1 subset predominantly responded to this protein demonstrating the development of protective immunity (g-IFN, and IL-2) in the host. Similar results were obtained with bovine Brucella primed lymphocytes. UvrA, GroE1 and GroEs were additional Brucella immunodominant proteins that demonstrated MHC class II antigenicity. The role cytotoxic cells are playing in the clearance of brucella cells was shown using knock out mice defective either in their CD4+ or CD8+ cells. CD4+ defective mice were able to clear brucella as fast as did normal mice. In contrast mice which were defective in their CD8+ cells could not clear the organisms effectively proving the importance of this subtype cell line in development of protective immunity. The understanding of the host's immune response and the expansion of the panel of Brucella immunodominant proteins opened new avenues in vaccine design. It is now feasible to selectively use immunodominant proteins either as subunit vaccine to fortify immunity of older animals or as diagnostic reagents for the serological survaillance.
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Lapidot, Moshe, and Vitaly Citovsky. molecular mechanism for the Tomato yellow leaf curl virus resistance at the ty-5 locus. United States Department of Agriculture, January 2016. http://dx.doi.org/10.32747/2016.7604274.bard.
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Tomato yellow leaf curl virus (TYLCV) is a major pathogen of tomato that causes extensive crop loss worldwide, including the US and Israel. Genetic resistance in the host plant is considered highly effective in the defense against viral infection in the field. Thus, the best way to reduce yield losses due to TYLCV is by breeding tomatoes resistant or tolerant to the virus. To date, only six major TYLCV-resistance loci, termed Ty-1 to Ty-6, have been characterized and mapped to the tomato genome. Among tomato TYLCV-resistant lines containing these loci, we have identified a major recessive quantitative trait locus (QTL) that was mapped to chromosome 4 and designated ty-5. Recently, we identified the gene responsible for the TYLCV resistance at the ty-5 locus as the tomato homolog of the gene encoding messenger RNA surveillance factor Pelota (Pelo). A single amino acid change in the protein is responsible for the resistant phenotype. Pelo is known to participate in the ribosome-recycling phase of protein biosynthesis. Our hypothesis was that the resistant allele of Pelo is a “loss-of-function” mutant, and inhibits or slows-down ribosome recycling. This will negatively affect viral (as well as host-plant) protein synthesis, which may result in slower infection progression. Hence we have proposed the following research objectives: Aim 1: The effect of Pelota on translation of TYLCV proteins: The goal of this objective is to test the effect Pelota may or may not have upon translation of TYLCV proteins following infection of a resistant host. Aim 2: Identify and characterize Pelota cellular localization and interaction with TYLCV proteins: The goal of this objective is to characterize the cellular localization of both Pelota alleles, the TYLCV-resistant and the susceptible allele, to see whether this localization changes following TYLCV infection, and to find out which TYLCV protein interacts with Pelota. Our results demonstrate that upon TYLCV-infection the resistant allele of pelota has a negative effect on viral replication and RNA transcription. It is also shown that pelota interacts with the viral C1 protein, which is the only viral protein essential for TYLCV replication. Following subcellular localization of C1 and Pelota it was found that both protein localize to the same subcellular compartments. This research is innovative and potentially transformative because the role of Peloin plant virus resistance is novel, and understanding its mechanism will lay the foundation for designing new antiviral protection strategies that target translation of viral proteins. BARD Report - Project 4953 Page 2
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Grafi, Gideon, and Brian Larkins. Endoreduplication in Maize Endosperm: An Approach for Increasing Crop Productivity. United States Department of Agriculture, September 2000. http://dx.doi.org/10.32747/2000.7575285.bard.
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The focus of this research project is to investigate the role of endoreduplication in maize endosperm development and the extent to which this process contributes to high levels of starch and storage protein synthesis. Although endoreduplication has been widely observed in many cells and tissues, especially those with high levels of metabolic activity, the molecular mechanisms through which the cell cycle is altered to produce consecutive cycles of S-phase without an intervening M-phase are unknown. Our previous research has shown that changes in the expression of several cell cycle regulatory genes coincide with the onset of endoreduplication. During this process, there is a sharp reduction in the activity of the mitotic cyclin-dependent kinase (CDK) and activation of the S-phase CDK. It appears the M-phase CDK is stable, but its activity is blocked by a proteinaceous inhibitor. Coincidentally, the S-phase checkpoint protein, retinoblastoma (ZmRb), becomes phosphorylated, presumably releasing an E2F-type transcriptional regulator which promotes the expression of genes responsible for DNA synthesis. To investigate the role of these cell cycle proteins in endoreduplication, we have created transgenic maize plants that express various genes in an endosperm-specific manner using a storage protein (g-zein) promoter. During the first year of the grant, we constructed point mutations of the maize M-phase kinase, p34cdc2. One alteration replaced aspartic acid at position 146 with asparagine (p3630-CdcD146N), while another changed threonine 161 to alanine (p3630-CdcT161A). These mutations abolish the activity of the CDK. We hypothesized that expression of the mutant forms of p34cdc2 in endoreduplicating endosperm, compared to a control p34cdc2, would lead to extra cycles of DNA synthesis. We also fused the gene encoding the regulatory subunit of the M- phase kinase, cyclin B, under the g-zein promoter. Normally, cyclin B is expected to be destroyed prior to the onset of endoreduplication. By producing high levels of this protein in developing endosperm, we hypothesized that the M-phase would be extended, potentially reducing the number of cycles of endoreduplication. Finally, we genetically engineered the wheat dwarf virus RepA protein for endosperm-specific expression. RepA binds to the maize retinoblastoma protein and presumably releases E2F-like transcription factors that activate DNA synthesis. We anticipated that inactivation of ZmRb by RepA would lead to additional cycles of DNA synthesis.
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Palmer, Guy H., Eugene Pipano, Terry F. McElwain, Varda Shkap, and Donald P. Knowles, Jr. Development of a Multivalent ISCOM Vaccine against Anaplasmosis. United States Department of Agriculture, July 1993. http://dx.doi.org/10.32747/1993.7568763.bard.
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Anaplasmosis is an arthropod+borne disease of cattle caused by the rickettsia Anaplasma marginale and an impediment to efficient production of healthy livestock in both Israel and the United States. Our research focuses on development of a recombinant membrane surface protein (MSP) immunogen to replace current vaccines derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Briefly, we accomplished the following in our BARD supported research: i) characterization of the intramolecular and intermolecular relationships of the native Major Surface Proteins (MSP) in the outer membrane; ii) expression, purification, and epitope characterization of the recombinant MSP-2, MSP-3, MSP-4, and MSP-5 proteins required to construct the recombinant ISCOM; iii) demonstration that the outer membrane-Quil A induces CD4+ T lymphocytes specific for the outer membrane polypeptides; iv) identification of CD4+ T lymphocytes that recognize outer membrane polypeptide epitopes conserved among other wise antigenically distinct strains; v) determination that immunization with the outer membrane-Quil A construct does not affect the ability of ticks to acquire or transmit A. marginale; and vi) demonstration that the outer membrane-Quil A construct induces complete protection against rickettsemia upon homologous challenge and significant protection against challenge with antigenically distinct strains, including tick transmission. Importantly, the level of protection against homologous challenge in the MSP vaccinates was comparable to that induced by live blood-based vaccines and demonstrates that development of a new generation of vaccines is feasible.
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Li, Yuan, Benjamin Metcalf, Sopio Chochua, Zhongya Li, Robert Gertz, Hollis Walker, Paulina Hawkins, Theresa Tran, Lesley McGee, and Bernard W. Beall. Validation of β-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences [Supporting data]. Centers for Disease Control and Prevention (U.S.), November 2017. http://dx.doi.org/10.15620/cdc/147467.
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The datafiles, R scripts, MIC tables, and other files were used to evaluate the prediction performance of a penicillin-binding protein (PBP) typing system and two methods (Random Forest (RF) and Mode MIC (MM) previously developed by this research team. This data and these files support the finding of the paper "Validation of β-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences" at https://doi.org/10.1186%2Fs12864-017-4017-7 or at https://stacks.cdc.gov/view/cdc/47684.
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Futcher, A. B. General Methods for Identifying Gl-phase Substrates of Cdk Protein Kinases. Fort Belvoir, VA: Defense Technical Information Center, June 1998. http://dx.doi.org/10.21236/ada366953.
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Futcher, A. B. General Methods for Identifying G1-phase Substrates of Cdk Protein Kinases. Fort Belvoir, VA: Defense Technical Information Center, June 1999. http://dx.doi.org/10.21236/ada374137.
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Futcher, A. B., and Daniel R. Marshak. General Methods for Identifying G1-Phase Substrates of Cdk Protein Kinases. Fort Belvoir, VA: Defense Technical Information Center, June 1996. http://dx.doi.org/10.21236/ada323678.
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Porat, Ron, Gregory T. McCollum, Amnon Lers, and Charles L. Guy. Identification and characterization of genes involved in the acquisition of chilling tolerance in citrus fruit. United States Department of Agriculture, December 2007. http://dx.doi.org/10.32747/2007.7587727.bard.
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Citrus, like many other tropical and subtropical fruit are sensitive to chilling temperatures. However, application of a pre-storage temperature conditioning (CD) treatment at 16°C for 7 d or of a hot water brushing (HWB) treatment at 60°C for 20 sec remarkably enhances chilling tolerance and reduces the development of chilling injuries (CI) upon storage at 5°C. In the current research, we proposed to identify and characterize grapefruit genes that are induced by CD, and may contribute to the acquisition of fruit chilling tolerance, by two different molecular approaches: cDNA array analysis and PCR cDNA subtraction. In addition, following the recent development and commercialization of the new Affymetrix Citrus Genome Array, we further performed genome-wide transcript profiling analysis following exposure to CD and chilling treatments. To conduct the cDNA array analysis, we constructed cDNA libraries from the peel tissue of CD- and HWB-treated grapefruit, and performed an EST sequencing project including sequencing of 3,456 cDNAs from each library. Based on the obtained sequence information, we chose 70 stress-responsive and chilling-related genes and spotted them on nylon membranes. Following hybridization the constructed cDNA arrays with RNA probes from control and CD-treated fruit and detailed confirmations by RT-PCR analysis, we found that six genes: lipid-transfer protein, metallothionein-like protein, catalase, GTP-binding protein, Lea5, and stress-responsive zinc finger protein, showed higher transcript levels in flavedo of conditioned than in non-conditioned fruit stored at 5 ᵒC. The transcript levels of another four genes: galactinol synthase, ACC oxidase, temperature-induced lipocalin, and chilling-inducible oxygenase, increased only in control untreated fruit but not in chilling-tolerant CD-treated fruit. By PCR cDNA subtraction analysis we identified 17 new chilling-responsive and HWB- and CD-induced genes. Overall, characterization of the expression patterns of these genes as well as of 11 more stress-related genes by RNA gel blot hybridizations revealed that the HWB treatment activated mainly the expression of stress-related genes(HSP19-I, HSP19-II, dehydrin, universal stress protein, EIN2, 1,3;4-β-D-glucanase, and SOD), whereas the CD treatment activated mainly the expression of lipid modification enzymes, including fatty acid disaturase2 (FAD2) and lipid transfer protein (LTP). Genome wide transcriptional profiling analysis using the newly developed Affymetrix Citrus GeneChip® microarray (including 30,171 citrus probe sets) revealed the identification of three different chilling-related regulons: 1,345 probe sets were significantly affected by chilling in both control and CD-treated fruits (chilling-response regulon), 509 probe sets were unique to the CD-treated fruits (chilling tolerance regulon), and 417 probe sets were unique to the chilling-sensitive control fruits (chilling stress regulon). Overall, exposure to chilling led to expression governed arrest of general cellular metabolic activity, including concretive down-regulation of cell wall, pathogen defense, photosynthesis, respiration, and protein, nucleic acid and secondary metabolism. On the other hand, chilling enhanced various adaptation processes, such as changes in the expression levels of transcripts related to membranes, lipid, sterol and carbohydrate metabolism, stress stimuli, hormone biosynthesis, and modifications in DNA binding and transcription factors.
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Leitner, Gabriel, and Naomi Balaban. Novel Immunotherapeutic Agent for the Treatment and Prevention of Staphylococcal Mastitis in Dairy Cows. United States Department of Agriculture, January 2009. http://dx.doi.org/10.32747/2009.7709880.bard.
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Staphylococci are the most common and costly mammary disease of dairy cattle worldwide. TRAP, a membrane associated 167AA protein, is highly conserved among staphylococci. The aims of this study were to test the safety and efficacy of recombinant TRAP (rTRAP) vaccine in dairy animals. The vaccine was safe as 2-3 subcutaneous injections of rTRAP (54–100μg) with adjuvant ISA 206 to cows and goats did not lead to any abnormal symptoms of sensitivity to the vaccine. The rTRAP vaccine was immunogenic and caused the induction of a humoral immune response that remained high for at least 160 days post second immunization. rTRAP vaccine also elicited a cell-mediated immune response (memory CD4+ and CD8+ T cells), as determined by lymphocyte proliferation assays. The rTRAP vaccine was efficacious as at parturition, only 13.5% heifers in the immunized group were infected with Staphylococcus chromogenes as compared to 42.9% in the non immunized group. Additionally, when cows were immunized in mid-lactation, the difference between somatic cell count (SCC) in immunized and control animals was profound (45±7 vs. 470±194, respectively). At the same time, the difference in milk yield was also evident (48.3±1.4 vs. 44.3±0.9 l/day, respectively). Put together, these studies indicate the value of the rTRAP vaccine in preventing new udder infections by staphylococci, which significantly lead to lowered SCC and some increase in milk yield. TRAP is conserved among all strains and species and is constitutively expressed in any strain of S. aureus or CNS tested so far, including those isolated from cows. TRAP may thus serve as a universal anti-staphylococcus vaccine.