Activation of p53 by nutlin-3a induces apoptosis and cellular senescence in human glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite concerted efforts to improve current therapies and develop novel clinical approaches, patient survival remains poor. As such, increasing attention has focused on developing new therapeutic strategies that specifically target the apoptotic pathway in order to improve treatment responses. Recently, nutlins, small-molecule antagonists of MDM2, have been developed to inhibit p53-MDM2 interaction and activate p53 signaling in cancer cells. Glioma cell lines and primary cultured glioblastoma cells were treated with nutlin-3a. Nutlin-3a induced p53-dependent G1- and G2-M cell cycle arrest and apoptosis in glioma cell lines with normal TP53 status. In addition, nutlin-arrested glioma cells show morphological features of senescence and persistent induction of p21 protein. Furthermore, senescence induced by nutlin-3a might be depending on mTOR pathway activity. In wild-type TP53 primary cultured cells, exposure to nutlin-3a resulted in variable degrees of apoptosis as well as cellular features of senescence. Nutlin-3a-induced apoptosis and senescence were firmly dependent on the presence of functional p53, as revealed by the fact that glioblastoma cells with knockdown p53 with specific siRNA, or cells with mutated or functionally impaired p53 pathway, were completely insensitive to the drug. Finally, we also found that nutlin-3a increased response of glioma cells to radiation therapy. The results provide a basis for the rational use of MDM2 antagonists as a novel treatment option for glioblastoma patients.

Deposition and characterization of lines printed through laser-induced forward transfer

The possibility of printing two-dimensional micropatterns of biomolecule solutions is of great interest in many fields of research in biomedicine, from cell-growth and development studies to the investigation of the mechanisms of communication between cells. Although laser-induced forward transfer (LIFT) has been extensively used to print micrometric droplets of biological solutions, the fabrication of complex patterns depends on the feasibility of the technique to print micron-sized lines of aqueous solutions. In this study we investigate such a possibility through the analysis of the influence of droplet spacing of a water and glycerol solution on the morphology of the features printed by LIFT. We prove that it is indeed possible to print long and uniform continuous lines by controlling the overlap between adjacent droplets. We show how, depending on droplet spacing, several printed morphologies are generated, and we offer, in addition, a simple explanation of the observed behavior based on the jetting dynamics characteristic of the LIFT of liquids.

Activation of p53 by nutlin-3a induces apoptosis and cellular senescence in human glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite concerted efforts to improve current therapies and develop novel clinical approaches, patient survival remains poor. As such, increasing attention has focused on developing new therapeutic strategies that specifically target the apoptotic pathway in order to improve treatment responses. Recently, nutlins, small-molecule antagonists of MDM2, have been developed to inhibit p53-MDM2 interaction and activate p53 signaling in cancer cells. Glioma cell lines and primary cultured glioblastoma cells were treated with nutlin-3a. Nutlin-3a induced p53-dependent G1- and G2-M cell cycle arrest and apoptosis in glioma cell lines with normal TP53 status. In addition, nutlin-arrested glioma cells show morphological features of senescence and persistent induction of p21 protein. Furthermore, senescence induced by nutlin-3a might be depending on mTOR pathway activity. In wild-type TP53 primary cultured cells, exposure to nutlin-3a resulted in variable degrees of apoptosis as well as cellular features of senescence. Nutlin-3a-induced apoptosis and senescence were firmly dependent on the presence of functional p53, as revealed by the fact that glioblastoma cells with knockdown p53 with specific siRNA, or cells with mutated or functionally impaired p53 pathway, were completely insensitive to the drug. Finally, we also found that nutlin-3a increased response of glioma cells to radiation therapy. The results provide a basis for the rational use of MDM2 antagonists as a novel treatment option for glioblastoma patients.

Fama y verdad en la épica quinientista española. El virgilianismo político y la tradición castellana del siglo xv

Fame and truth in Spanish XVth century epic. !e political vergilianism and the castilian tradition of the XVth century. The starting premise of this essay is that the Spanish Golden Age epic must be read from a historical perspective that takes into account the Hispanic literary tradition ofthe XVth century. In particular, it argues that epic should be approached from a theoretical perspective that explores its relationship with history in order to illuminate the diferences between Italian and Spanish epic theory and practice in the XVth century. The relationship between the discourses of epic and history can be explained through the imitation of the Vergilian model, specifically the Aeneid´s ideological representation of empire. However, it is also necessary to consider theoretical aspects in the light of the diferent uses of classical literature by Italian humanists and Castilian writers of the XV th century. Thus, its primary thesis is that although XVI th century Spanish epic shares the general principles of the Western Epic tradition, it should be approached from a specifically perspective Hispanic, in the light of the «political vergilianism» already enshrined in authors like Enrique de Villena and Juan de Mena, which is essential to appreciate how epic genre serves as memory for the present

AR 117: viviendas en Alcázar de San Juan

Postprint (published version)

La Transmisión textual de las Mémories de Philippe de Commynes en las traducciones de Felipe (1636) y Juan de Vitrián (1643)

Análisis de las traducciones de Felipe Vitrián (1936) y de Juan Vitrián (1643) de la obra de Philippe de Commynes “Mémoires”

L’obra de Guillaume de Machaut en el Manuscrit Mòdena, Biblioteca Estense, a.M.5.24

Entre finals del segle XIV i principis del XV es data la redacció del Manuscrit Mòdena, Biblioteca Estense, .M.5.24, un dels principals manuscrits del moment que han arribat als nostres dies, essent un element culminant pel que fa a penetració de l’art polifònic francès a la Itàlia d’inicis del ‘400. En ell es copien quatre peces de Guillaume de Machaut i l’únic poema de l’autor francès musicat per un altre compositor. En els treballs sobre el manuscrit molt sovint s’obvien aquestes quatre peces, i l’estudi sobre Machaut es fa quasi exclusivament des de les fonts franceses. Aquest treball pretén respondre, sobretot, a dues preguntes: Què ens poden explicar aquestes peces sobre el procés d’afrancesament de la música italiana? Què ens poden explicar sobre la difusió de l’obra de Machaut pel vell continent?

Glyceraldehyde-3-phosphate dehydrogenase as a moonlighting protein in bacteria

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a housekeeping protein that is present in virtually all organisms, where it performs metabolic functions essential for survival. GAPDH plays an essential role in the process of energy production, and is also involved in numerous biological processes. GAPDH belongs to a subset of proteins called moonlighting proteins, in which different functions are associated with a single polypeptide chain. The multifunctionality of GAPDH has been described in pathogenic and probiotic microorganisms, in mammals and in plants. In this review, we summarize the moonlighting role of GAPDH in bacteria.

Glyceraldehyde-3-phosphate dehydrogenase as a moonlighting protein in bacteria

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a housekeeping protein that is present in virtually all organisms, where it performs metabolic functions essential for survival. GAPDH plays an essential role in the process of energy production, and is also involved in numerous biological processes. GAPDH belongs to a subset of proteins called moonlighting proteins, in which different functions are associated with a single polypeptide chain. The multifunctionality of GAPDH has been described in pathogenic and probiotic microorganisms, in mammals and in plants. In this review, we summarize the moonlighting role of GAPDH in bacteria.

Glyceraldehyde-3-phosphate dehydrogenase as a moonlighting protein in bacteria

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a housekeeping protein that is present in virtually all organisms, where it performs metabolic functions essential for survival. GAPDH plays an essential role in the process of energy production, and is also involved in numerous biological processes. GAPDH belongs to a subset of proteins called moonlighting proteins, in which different functions are associated with a single polypeptide chain. The multifunctionality of GAPDH has been described in pathogenic and probiotic microorganisms, in mammals and in plants. In this review, we summarize the moonlighting role of GAPDH in bacteria.

Alteritzar la singularitat: veus per a una pedagogia de l'experiència

Parte de la investigación en torno a la realidad educativa que se ha desarrollado durante los últimos años se caracteriza por intentar encontrar formas de interpretación orientadas a significar los procesos formativos centrados en las vivencias singulares de los agentes que participan de la educación así como en la posibilidad que éstas ofrecen de devenir experiencia, eso es,vivencia concienciada. A raíz de las mismas podemos observar como la biografía apunta a ser una de las más emblemáticas formalizaciones del proceso de narración de vivencias. Pero, aún cuando la misma se perfila como una de las narraciones que más promueven la interpretación e intercambio de vivencias, posibilitando la reflexión e, incluso, formación mediada, la biografía todavía presenta como forma teorética algunos escollos. Los cuales, pueden ser utilizados como preguntas base para formular una voz de las pedagogías de la experiencia. Justamente, interrogarse y repensar su factibilidad es el tema que se ensaya en el presente artículo.

Maria Josepa Arnall i Juan, in memoriam

This article reviews the life and career of Dr. Maria Josepa Arnall i Juan (1948-2002), head professor of Historiographic Science and Techniques at the University of Barcelona. Dr. Arnall was distinguished both on a personal and professional level. She performed a magnificent task as a researcher and teacher, and possessed a great work ethic, as evidenced by her rich and rigorous scientific output, described in the article. She played an active role in collaboration with the Archivists Association of Catalonia helping to train Catalan archivists. The memory of her as a person and a professional, as well as her important and valuable work, remain as her legacy

En torno al cardenal Don Gil Álvarez de Albornoz y el platero sienés Andrea Petrucci: el relicario de la mano de Santa Lucía y el cáliz de San Segundo

Este artículo trata de la complicada y hasta ahora inédita historia de la llegada a España de dos obras cumbres de la orfebrería sienesa del s. XIV en plata con esmaltes translúcidos: el relicario de la mano de Santa Lucía en la catedral de Toledo y el cáliz de San Segundo en la catedral de Ávila. La importación de estos dos importantísimos objetos devocionales y litúrgicos, ambos firmados por el platero sienés Andrea Petrucci, está relacionada con la estancia en Italia del cardenal don Gil de Albornoz, arzobispo de Toledo y posteriormente cardenal de San Clemente y Santa Sabina y legado papal. El mecenazgo del cardenal castellano y de su círculo en Italia explica la comisión y adquisición de estas piezas, cuyos accidentados itinerarios desembocarían finalmente en Toledo y en Ávila.

epiCentre!: rehabilitació de Ca n'Oliver com a centre d'art

Award-winning