991 resultados para 7136-129


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T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions.

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Mammalian group-II phospholipases A2 (PLA2) of inflammatory fluids display bactericidal properties, which are dependent on their enzymatic activity. This study shows that myotoxins II (Lys49) and III (Asp49), two group-II PLA2 isoforms from the venom of Bothrops asper, are lethal to a broad spectrum of bacteria. Since the catalytically inactive Lys49 myotoxin II isoform has similar bactericidal effects to its catalytically active Asp49 counterpart, a bactericidal mechanism that is independent of an intrinsic PLA2 activity is demonstrated. Moreover, a synthetic 13-residue peptide of myotoxin II, comprising residues 115-129 (common numbering system) near the C-terminal loop, reproduced the bactericidal effect of the intact protein. Following exposure to the peptide or the protein, accelerated uptake of the hydrophobic probe N-phenyl-N-naphthylamine was observed in susceptible but not in resistant bacteria, indicating that the lethal effect was initiated on the bacterial membrane. The outer membrane, isolated lipopolysaccharide (LPS), and lipid A of susceptible bacteria showed higher binding to the myotoxin II-(115-129)-peptide than the corresponding moieties of resistant strains. Bacterial LPS chimeras indicated that LPS is a relevant target for myotoxin II-(115-129)-peptide. When heterologous LPS of the resistant strain was present in the context of susceptible bacteria, the chimera became resistant, and vice versa. Myotoxin II represents a group-II PLA2 with a direct bactericidal effect that is independent of an intrinsic enzymatic activity, but adscribed to the presence of a short cluster of basic/hydrophobic amino acids near its C-terminal loop.

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Scène initiale : vignettes du chapitre 16, sur quatre registres. Au registre inférieur, on voit le défunt coiffé d'un cône d'encens accompagné de son épouse ; ils sont tous les deux assis. Au deuxième registre, le disque solaire émergeant du Noun est adoré par quatre babouins. Au troisième régistre, deux déesses symbolisant l'Orient et l'Occident adorent le disque solaire, lequel est surmonté d'une barque où sont assises plusieurs divinités. Enfin, le registre supérieur, lacunaire, laisse deviner le défunt accomplissant un acte de piété.Colonnes de texte :Colonnes 1 à 5 : chapitre 18. Chaque séquence est surmontée d'une vignette présentant le défunt en adoration devant quatre divinités.Col. 6, lignes x+ 1-7 et vignette (fragmentaire) : chapitre 21, titre en lacune ("Formule pour donner une bouche au défunt"). On voit le défunt officier devant une divinité assise.Col. 6, l. x+8-22 et vignette : chapitre 23, avec titre rubriqué : "Formule pour ouvrir la bouche d'un homme pour son usage dans la nécropole". Le vignette montre le défunt officier devant un double de lui-même.

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Servicios registrales

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Brown sediment with clasts ranging from small to medium in size. Clast shape ranges from angular to sub-rounded in shape. Lineations and rotation structures can be seen throughout the sample. Some comet structures and grain stacking can also be seen.

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Brown sediment with multiple domains. There are two finer grained domains that contain a few small clasts. These two can be distinguished based on the abundance of clay material(darker brown). The coarse grained sediment contains clasts ranging from small to medium in size, and angular to sub-rounded in shape. This domain contains lineations, rotation structures, comet structures, and some edge-to-edge grain crushing.

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Brown sediment with two main domains; a fine grained one rich in organic material and a coarse grained domain. The fine grained domain appears in several areas of the sample, and in one area alternates with the coarser domain. The coarse grained domain contains clasts ranging from small to medium in size, and angular to sub-rounded in shape. Grain crushing and lineations can commonly be seen in this domain.

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Brown sediment with clasts ranging from small to medium in size. Clast shape ranges from angular to sub-rounded. Rotation structures are abundant in this sample. Edge-to-edge grain crushing, comet structures, and lineations can also be seen in this sample.

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Las enfermedades causadas por priones, llamadas encefalopatías espongiformes transmisibles, son el producto de la conversión espontánea de la proteína celular PrPC inofensiva en su forma patógena, la PrPSc. Todavía se desconoce cómo se lleva a cabo esta conversión, aunque se conocen mutaciones que pueden inducirla debido a la interacción con las partículas priónicas. También se han reportado polimorfismos que aumentan la susceptibilidad al desarrollo de este tipo de enfermedades, entre ellos, el M129V en el gen PRNP, el cual se asocia con el aumento de la susceptibilidad cuando el incluye el genotipo homocigoto para metionina. De acuerdo con lo anterior, el objetivo de este estudio fue analizar la distribución del polimorfismo M129V en la población colombiana y compararla con algunas poblaciones reportadas previamente en la literatura. El fragmento que alberga la variante M129V fue amplificado por PCR, en 202 individuos colombianos, no relacionados, de ambos géneros, y se llevó a cabo análisis por RFLPs mediante el uso de la enzima de restricción NspI. Las frecuencias génicas y genotípicas y el ajuste al equilibrio de Hardy-Weinberg fueron calculadas utilizando el software GENEPOP. Al no encontrarse estudios en la población colombiana en cuanto a la distribución del polimorfismo de estudio, es necesario realizar trabajos que determinen el riesgo de la población colombiana a desarrollar enfermedades causadas por priones.