2,223 research outputs found

    Las gramáticas dialogadas del español en el Siglo de Oro: el caso de Ambrosio de Salazar

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    El Espexo general de la gramática en diálogos –manual de español publicado en Francia en 1614– se ha estudiado habitualmente bajo la óptica de la historiografía lingüística atendiendo a su aportación doctrinal dentro de la tradición gramaticográfica española. De forma menos sistemática se ha aludido a sus planteamientos metodológicos, casi siempre a través de valoraciones negativas, que ya surgían incluso desde el momento de aparición del manual en el ambiente de enseñanza del español del país vecino (Oudin, Marcos Fernández)

    Risks of Tailings Dams Failure

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    Risk and Reliability in Geotechnical Engineerin

    Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation

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    BACKGROUND Survivors of critical illness are at increased risk of fractures. This may be due to increased osteoclast formation during critical illness, leading to trabecular bone loss. Such bone loss has also been observed in Paget's disease, and has been related to deficient autophagy. Deficient autophagy has also been documented in vital organs and skeletal muscle of critically ill patients. The objective of this study was to investigate whether deficient autophagy can be linked to critical illness-induced bone loss. METHODS Osteoclasts grown in vitro and their precursor cells isolated from peripheral blood of critically ill patients and from matched healthy volunteers were analysed for the expression of autophagy genes (SQSTM1, Atg3 and Atg7), and proteins (p62, Atg-5, and microtubule-associated protein light chain 3-II (LC3-II)) and for autophagy and epigenetic signalling factors via PCR arrays and were treated with the autophagy inducer rapamycin. The effect of rapamycin was also investigated at the tissue level in an in vivo rabbit model of critical illness. RESULTS Many more osteoclasts formed in vitro from the blood precursor cells isolated from critically ill patients, which accumulated p62, and displayed reduced expression of Atg5, Atg7, and LC3-II compared to healthy controls, suggesting deficient autophagy, whilst addition of rapamycin reduced osteoclast formation. PCR arrays revealed a down-regulation of histone methyltransferases coupled with an up-regulation of negative regulators of autophagy. Critically ill rabbits displayed a reduction in trabecular and cortical bone, which was rescued with rapamycin. CONCLUSIONS Deficient autophagy in osteoclasts and their blood precursor cells at least partially explained aberrant osteoclast formation during critical illness and was linked to global histone hypomethylation. Treatment with the autophagy activator Rapamycin reduced patient osteoclast formation in vitro and reduced the amount of bone loss in critically ill rabbits in vivo. These findings may help to develop novel therapeutic targets to prevent critical illness-induced bone loss

    Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis

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    In human cells, the RIPK1-RIPK3-MLKL-PGAM5-Drp1 axis drives tumor necrosis factor (TNF)-induced necroptosis through mitochondrial fission, but whether this pathway is conserved among mammals is not known. To answer this question, we analyzed the presence and functionality of the reported necroptotic axis in mice. As in humans, knockdown of receptorinteracting kinase-3 (RIPK3) or mixed lineage kinase domain like (MLKL) blocks TNF-induced necroptosis in L929 fibrosarcoma cells. However, repression of either of these proteins did not protect the cells from death, but instead induced a switch from TNF-induced necroptosis to receptor-interacting kinase-1 (RIPK1) kinase-dependent apoptosis. In addition, although mitochondrial fission also occurs during TNF-induced necroptosis in L929 cells, we found that knockdown of phosphoglycerate mutase 5 (PGAM5) and dynamin 1 like protein (Drp1) did not markedly protect the cells from TNF-induced necroptosis. Depletion of Pink1, a reported interactor of both PGAM5 and Drp1, did not affect TNF-induced necroptosis. These results indicate that in these murine cells mitochondrial fission and Pink1 dependent processes, including Pink-Parkin dependent mitophagy, apparently do not promote necroptosis. Our data demonstrate that the core components of the necrosome (RIPK1, RIPK3 and MLKL) are crucial to induce TNF-dependent necroptosis both in human and in mouse cells, but the associated mechanisms may differ between the two species or cell types

    MarBEF, databases, and the legacy of John Gray

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    Within the European Network of Excellence (NoE) on Marine Biodiversity and Ecosystem Functioning (MarBEF), marine biodiversity scientists from across Europe have been brought together to focus on 3 broad themes. Theme 1 describes large-scale (and long-term) distribution patterns of marine biodiversity, Theme 2 examines the consequences of changes in marine biodiversity for the functioning of marine ecosystems, and Theme 3 explores and disseminates the socio-economic consequences of changes in marine biodiversity and biodiversity-mediated processes. Within MarBEF Theme 1, a large collaborative effort has produced an integrated database of species occurrence information (MacroBen), which contains data of quantitative samples of soft-sediment benthic infauna collected in European continental waters, from the Arctic to the Black Sea. Papers in this Theme Section describe initial studies based on the database. The late Prof. John S. Gray led activities within MarBEF Theme 1 for the first 2.5 yr, during which time the majority of the work described in this Theme Section was set in motion, and he continued to be involved in the work until his untimely death. We dedicate this body of work to his memory.

    El canon literario de las gramáticas: los dictámenes de Jean Chapelain en la "Nouvelle méthode espagnole" de Lancelot (1660)

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    Este trabajo se centra en las autoridades y ejemplificación literarias de la gramática española, a través del análisis de la Nouvelle méthode pour apprendre facilement et en peu de temps la langue espagnole (NME) de Claude Lancelot (1660). En particular, nos fijamos en cómo permean en ella los juicios literarios de la época, a través de la correspondencia mantenida con el hispanista Jean Chapelain. Tras un examen detenido de la NME, se concluye que la erudición del gramático de Port-Royal se ve avalada y reforzada por (i) los consejos procedentes de la crítica literaria, (ii) la consulta de crestomatías poéticas (Arte poética española, Rengifo 1592) y (iii) el aprovechamiento de otras gramáticas (La Parfaicte Methode, Charpentier 1596). Lancelot reserva, no obstante, un pequeño espacio para sus propios juicios estéticos: por un lado, de su selección destacan algunos autores religiosos como Rivadeneyra, fray Luis de Granada o Juan de Ávila y, por otro, alaba el éxito de Gracián.This paper examines the use of authors and literary exemplification in the Spanish grammar, through the case of Nouvelle méthode pour apprendre facilement et en peu de temps la langue espagnole (NME) by Claude Lancelot (1660). Specifically, we focus on the influence of literary criticism, which is often detectable in the history of Spanish grammar. We conserve traces of this influence: two letters sent by Jean Chapelain to the grammarian of Port Royal. After analyzing the NME, we can conclude that Lancelot is well advised, not only by the literary criticism but also by poetic sources (Arte poética española, Rengifo 1592) and grammatical sources (La Parfaicte Methode, Charpentier 1596). Apart from these influences, Lancelot makes room for his own esthetic ideas: he likes religious authors as Rivadeneyra, Fray Luis de Granada or Juan de Ávila, and he knows about Gracián’s success
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