670 resultados para Merlin, Buenaventura
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Letters and doctrinal debates exchanged by Father Buenaventura Merlin and Pastor Santiago Pascoe between 1873 and 1874.
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Neurofibromatosis 2 (NF2) is a dominantly inherited disorder, which predisposes to multiple tumours of the nervous system, typically schwannomas and meningiomas. Biallelic inactivation of the NF2 gene occurs both in sporadic and NF2-related schwannomas and in most meningiomas. The NF2 gene product merlin (or schwannomin) is structurally related to the ERM proteins, ezrin, radixin and moesin, which act as molecular linkers between the actin cytoskeleton and the plasma membrane. Merlin is a tumor suppressor that participates in cell cycle regulation. Merlin s phosphorylation status appears to be associated with its tumour suppressor activity, i.e. non-phosphorylated merlin functions as a tumour suppressor, whereas protein phosphorylation results in loss of functional activity. This thesis study was initiated to investigate merlin s role as a tumor suppressor and growth inhibitor. These studies show, that like many other tumor suppressors, also merlin is targeted to the nucleus at some stages of the cell cycle. Merlin s nuclear localization is regulated by cell cycle phase, contact inhibition and adhesion. In addition, a potential nuclear binding partner for merlin was identified, Human Enhancer of Invasion 10 (HEI10), a cyclin B interacting protein. Many tumor suppressors interact with microtubules and this thesis work shows that also merlin colocalizes with microtubules in mitotic structures. Merlin binds microtubules directly, and increases their polymerization in vitro and in vivo. In addition, primary mouse Schwann cells lacking merlin displays disturbed microtubule cytoskeleton. Fourth part of this thesis work began from the notion that PKA phosphorylates an unidentified site from the merlin N-terminus. Our studies show that serine 10 is a target for PKA and modulation of this residue regulates cytoskeletal organization, lamellipodia formation and cell migration. In summary, this thesis work shows that merlin s role is much more versatile than previously thought. It has a yet unidentified role in the nucleus and it participates in the regulation of both microtubules and the actin cytoskeleton. These studies have led to a better understanding of this enigmatic tumor suppressor, which eventually will aid in the design of specific drugs for the NF2 disease.
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Neurofibromatosis 2 (NF2) is an autosomal dominant disorder manifested by the formation of multiple benign tumors of the nervous system. Affected individuals typically develop bilateral vestibular schwannomas which lead to deafness and balance disorders. The syndrome is caused by inactivation of the NF2 tumor suppressor gene, and mutation or loss of the NF2 product, merlin, is sufficient for tumorigenesis in both hereditary and sporadic NF2-associated tumors. Merlin belongs to the band 4.1 superfamily of cytoskeletal proteins, which also contain the related ezrin, radixin, and moesin (ERM) proteins. The ERM members provide a link between the cell cytoskeleton and membrane by connecting membrane-associated proteins to actin filaments. By stabilizing complexes in the cell cortex, the ERMs modulate morphology, growth, and migration of cells. Despite their structural homology, overlapping subcellular distribution, direct molecular association, and partial overlap of molecular interactions, merlin and ezrin exert opposite effects on cell proliferation. Merlin suppresses cell proliferation, whereas ezrin expression is linked to oncogenic activity. We hypothesized that the regions which differ between the proteins might explain merlin s specificity as a tumor suppressor. We therefore analyzed the regions, which are most diverse between merlin and ezrin; the N-terminal tail and the C-terminus. To determine the properties of the C-terminal region, we studied the two most predominant merlin isoforms together with truncation variants similar to those found in patients. We also focused on the evolutionally conserved C-terminal residues, E545-E547, that harbor disease causing mutations in its corresponding DNA sequence. In addition to inhibiting cell proliferation, merlin regulates cytoskeletal organization. The morphogenic properties of merlin may play a role in tumor suppression, since patient-derived tumor cells demonstrate cytoskeletal abnormalities. We analyzed the mechanisms of merlin-induced extension formation and determined that the C-terminal region of amino acids 538-568 is particularly important for the morphogenic activity. We also characterized the role of C-terminal merlin residues in the regulation of proliferation, phosphorylation, and intramolecular associations. In contrast to previous reports, we demonstrated that both merlin isoforms are able to suppress cell proliferation, whereas C-terminally mutated merlin constructs showed reduced growth inhibition. Phosphorylation serves as a mechanism to regulate the tumor suppressive activity of merlin. The C-terminal serine 518 is phosphorylated in response to both p21-activated kinase (PAK) and protein kinase A (PKA), which inactivates the growth inhibitory function of merlin. However, at least three differentially phosphorylated forms of the protein exist. In this study we demonstrated that also the N-terminus of merlin is phosphorylated by AGC kinases, and that both PKA and Akt phosphorylate merlin at serine 10 (S10). We evaluated the impact of this N-terminal tail phosphorylation, and showed that the phosphorylation state of S10 is an important regulator of merlin s ability to modulate cytoskeletal organization but also regulates the stability of the protein. In summary, this study describes the functional effect of merlin specific regions. We demonstrate that both S10 in the N-terminal tail and residues E545-E547 in the C-terminus are essential for merlin activity and function.
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El estudio se realizó en la comunidad de San Buenaventura perteneciente al municipio de Boaco, en el período comprendido entre octubre de 2003 y octubre de 2004. Se elaboró un estudio de factibilidad para el establecimiento de un taller de multiplicación artesanal de Beauveria bassiana para el manejo de broca del café en el municipio de Boaco, con el objetivo de determinar la rentabilidad del mismo. El estudio contiene cinco etapas: estudio de mercado, estudio técnico, evaluación financiera, evaluación económica y social y evaluación de impacto ambiental. Los resultados obtenidos indican que únicamente existe un taller de multiplicación artesanal como oferente del producto en la zona, y que para el año 2007 la demanda insatisfecha del producto será del 80%. El estudio financiero demostró la rentabilidad del proyecto al obtenerse un Valor Actual Neto (VAN) de 305,461.65 córdobas, con una Tasa Interna de Retorno (TIR) de 48.51% y una relación beneficio costo de 1.79 córdobas. Se sensibilizó el proyecto utilizando dos situaciones: Aumento del 30% en los costos de operación y disminución del 30% en los ingresos; los resultados obtenidos demuestran que bajo estas condiciones el proyecto seguiría generando utilidades. Se determinó la existencia de aportes económicos y sociales a la zona de influencia del proyecto obteniéndose un Valor Actual Neto Económico (VANE) de 542,021.42 córdobas; y en el flujo económico con ahorro por el uso de Beauveria bassiana como controlador biológico de la broca del café el VANE resultó de 1,089,936.07 córdobas. La evaluación ambiental indica que no existen impactos negativos en el medio ambiente por el uso de producto biológicos a base de Beauveria bassiana
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Resumen: Este trabajo trata clara y brevemente el pensamiento de San Buenaventura acerca de la unión entre cuerpo y alma, y su teoría de la composición hilemórfica del alma como una respuesta frente a la disputa entre las posturas aristotélica y platónica y frente a los planteos de Averroes acerca del intelecto agente.
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Trabalho de projeto apresentado à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Publicidade e Marketing.
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Recueil de dessins à la plume, modèles d'écriture, d'architecture ; Oraison dominicale et alphabets en plusieurs langues ; dessins de l'église cathédrale et de Saint-Rémy de Reims, de Notre-Dame de Paris, et autres monuments parisiens ; dessins d'instruments géographiques et astronomiques, d'instruments de musique, etc. ; — (fol. 193) « Ensuivent plusieurs portraicts tracés en escriture. »
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Recueil de dessins à la plume, modèles d'écriture, d'architecture ; Oraison dominicale et alphabets en plusieurs langues ; dessins de l'église cathédrale et de Saint-Rémy de Reims, de Notre-Dame de Paris, et autres monuments parisiens ; dessins d'instruments géographiques et astronomiques, d'instruments de musique, etc. ; — (fol. 193) « Ensuivent plusieurs portraicts tracés en escriture. »
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[Vente. Art. 1846-02-02 - 1846-02-05. Paris]
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[Vente. Art. 1846-06-16 - 1846-06-22. Paris]
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[Vente (Art). 1846-11-24 - 1846-11-28. Paris]
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Contient : Histoire du Saint-Graal, par ROBERT DE BORON. « [C]hil ki se tient et juge au plus peceor de tous, mande salus... » [Le Saint Graal, éd. Hucher, II, 3, note] ; « ... et commenche messire ROBERS en tel manière [Ibid., III, 303], comme vos poerés oïr, s'il est ki le vos die. Or nous consaut Sainte Marie. Explicit li commencemens de l'estoire del s. Graal, et chi après vient l'estoire de Merlin. Dieu nous maint tous à boine fin. Amen. » [Cf. l'explicit dans le ms. franç. 95] ; Histoire de Merlin, par ROBERT DE BORON. « Mout fut iriés li anemis, quant nostre sires ot estei en enfer... » ; «... si come li contes le vous devisera cha avant. Explicit l'enserrement de Merlin. Diex nous maint tous à boine fin. Amen »
