1000 resultados para AB-hydrolase domain 6
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Colbertinus
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Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199-314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73 +/- 12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-gamma secretion, ratios of IFN-gamma/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNF alpha/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5-88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-gamma/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens.
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NOR-1/NR4A3 is an orphan member of the nuclear hormone receptor superfamily. NOR-1 and its close relatives Nurr1 and Nur77 are members of the NR4A subgroup of nuclear receptors. Members of the NR4A subgroup are induced through multiple signal transduction pathways. They have been implicated in cell proliferation, differentiation, T-cell apoptosis, chondrosarcomas, neurological disorders, inflammation, and atherogenesis. However, the mechanism of transcriptional activation, coactivator recruitment, and agonist-mediated activation remain obscure. Hence, we examined the molecular basis of NOR-1-mediated activation. We observed that NOR-1 trans-activates gene expression in a cell- and target-specific manner; moreover, it operates in an activation function (AF)-1-dependent manner. The N-terminal AF-1 domain delimited to between amino acids 1 and 112, preferentially recruits the steroid receptor coactivator (SRC). Furthermore, SRC-2 modulates the activity of the AF-1 domain but not the C-terminal ligand binding domain (LBD). Homology modeling indicated that the NOR-1 LBD was substantially different from that of hRORbeta, a closely related AF-2-dependent receptor. In particular, the hydrophobic cleft characteristic of nuclear receptors was replaced with a very hydrophilic surface with a distinct topology. This observation may account for the inability of this nuclear receptor LBD to efficiently mediate cofactor recruitment and transcriptional activation. In contrast, the N-terminal AF-1 is necessary for cofactor recruitment and can independently conscript coactivators. Finally, we demonstrate that the purine anti-metabolite 6-mercaptopurine, a widely used antineoplastic and anti-inflammatory drug, activates NOR-1 in an AF-1-dependent manner. Additional 6-mercaptopurine analogs all efficiently activated NOR-1, suggesting that the signaling pathways that modulate proliferation via inhibition of de novo purine and/or nucleic acid biosynthesis are involved in the regulation NR4A activity. We hypothesize that the NR4A subgroup mediates the genotoxic stress response and suggest that this subgroup may function as sensors that respond to genotoxicity.
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[Histoire romaine (latin). 1518-1533]
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[Histoire romaine (latin). 1518-1533]
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Référence bibliographique : Toledano, Marieschi, 33b
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Référence bibliographique : Toledano, Marieschi, 31b
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Référence bibliographique : Toledano, Marieschi, 4c
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Référence bibliographique : Toledano, Marieschi, 25d
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Référence bibliographique : Toledano, Marieschi, 3i
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Comprend : Fol. Diijr° - Sit nomen Domini benedictum in seculum (Fuga, à 4 v.) - Fol. Ej r° - Morior ego, si non habuero (Fuga, à 5 v.) - Fol. Ej r° - Fuga à 5 v. - Fol. Ej v° - Fuga à 2 v. - Fol. Ej v° - Fuga à 5 v. - Fol. Eij r° - Fuga à 5 v. - Fol. Eij v° - Fuga à 2 v. - Fol. Eiij v° - Fuga à 2 v. - Fol. Eiv r° - Fuga à 5 v. - Fol. Eiv v° - Fuga à 2 v. - Fol. F j r° - Canon à 3 v. - Fol. I j v° - Elegantia super Languir me fault (à 2 v.) - Fol. I ij v° - C'est à grant tort (Aliud exemplum, à 2 v.) - Fol. iiij v° - Fuga à 4 v. - Fol. Kiij r° - In omnibus requiem (à 1 v.) - Fol. Kiij v° - Salve sancta parens (à 1 v. (le début d'une autre voix sur la même portée en ms.)) - Fol. Liij r° - Vanitas vanitatum (à 4 v.) - Fol. Liij v° - Dixit Dominus (à 4 v.) - Fol. Liiij r° - Dixit Dominus (à 5 v. et faux-bourdon) - Fol. Liiij v° - O vos omnes (à 4 v.) - Fol. N j r° - Omnis arbor (à 2 v.) - Fol. N j v° - Pleni sunt coeli (à 2 v.) - Fol. Nij v° - Pleni sunt coeli (à 2 v.) - Fol. Niij r° - Christus spes mea (à 3 v.) - Fol. Niij r° - Et expecto resurectionem mortuorum (à 3 v.) - Fol. Niij v° - Pleni sunt coeli (à 3 v.) - Fol. Niiij v° - A solis ortu cardine ([Hymne], à 4 v.) - Fol. O j v° - [Canon] à 4 v. - Fol. O j v° - Revertere (à 4 v.) - Fol. O j v° - Adolescens graditur (à 5 v.) - Fol. Oij r° - Dominus mihi adiutor (Fuga, à 5 v.) - Fol. Oij v° - Surrexit Christus hodie (à 5 v.) - Fol. Oiij v° - Christus pro nobis passus est (à 5 v.) - Fol. Oiiij v° - Agnus Dei (à 6 v.) - Fol. Pj v° - [Pièce sans texte] (à 6 v.) - Fol. Pij v° - Sumite psalmum (Fuga, à 6 v.) - Fol. Pij v° - Nobilis est (Fuga, à 6 v.) - Fol. Piij r° - Ambulate dum lucem habetis (Fuga, à 7 v.) - Fol. Piij r° - Sancta Trinitas (Fuga, à 7 v.) - Fol. Piij v° - Omnis consummationis vidi finem (Canon, à 8 v. dont 4 notées)
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Brown sediment with clasts ranging from small to medium in size. Grain shape ranges from angular to sub-rounded. Water escape structures and lineations are abundant throughout the sample. Some comet structures can also be seen. There were minor amounts of grain crushing also present.
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El marcaje de proteínas con ubiquitina, conocido como ubiquitinación, cumple diferentes funciones que incluyen la regulación de varios procesos celulares, tales como: la degradación de proteínas por medio del proteosoma, la reparación del ADN, la señalización mediada por receptores de membrana, y la endocitosis, entre otras (1). Las moléculas de ubiquitina pueden ser removidas de sus sustratos gracias a la acción de un gran grupo de proteasas, llamadas enzimas deubiquitinizantes (DUBs) (2). Las DUBs son esenciales para la manutención de la homeostasis de la ubiquitina y para la regulación del estado de ubiquitinación de diferentes sustratos. El gran número y la diversidad de DUBs descritas refleja tanto su especificidad como su utilización para regular un amplio espectro de sustratos y vías celulares. Aunque muchas DUBs han sido estudiadas a profundidad, actualmente se desconocen los sustratos y las funciones biológicas de la mayoría de ellas. En este trabajo se investigaron las funciones de las DUBs: USP19, USP4 y UCH-L1. Utilizando varias técnicas de biología molecular y celular se encontró que: i) USP19 es regulada por las ubiquitin ligasas SIAH1 y SIAH2 ii) USP19 es importante para regular HIF-1α, un factor de transcripción clave en la respuesta celular a hipoxia, iii) USP4 interactúa con el proteosoma, iv) La quimera mCherry-UCH-L1 reproduce parcialmente los fenotipos que nuestro grupo ha descrito previamente al usar otros constructos de la misma enzima, y v) UCH-L1 promueve la internalización de la bacteria Yersinia pseudotuberculosis.
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The disruption of the human immunolobulin E–high affinity receptor I (IgE–FcεRI) protein–protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A–B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 660 μM) is displayed by the peptide containing a 2,2′-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A–B loop epitope in IgE.