Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.

U.S.English is a salad bowl. The Representation of Regionalisms in Standard American English

American English exhibits a great dialectal diversity, easily perceived in lexicon; so that questions are raised about which regionalisms are part of the mythical SAE and which are not. A small sample of regionalisms is checked against three standard dictionaries in order to determine the role regionalisms play in SAE.

The Arcuated Lintel and the "Serlian Motif". Imperial Identity, Architectural and Symbolic Interactions in Ancient Rome

Essay on the origin, use and development of the arcuated lintel in ancient Rome and the configuration of the so– called ‘Serlian motif’. These architectural elements will be related to the architecture of prestige on its technical, functional, visual and symbolic sphere. Its depictions, in addition to buildings, can offer a rich repertory of images that speak about the relations between visual culture, religion and power. Furthermore, the analyzed motifs will become important elements of the Western cultural legacy for centuries. The analysis of these events will contribute to the comprehension of the role played by some resources of ancient Rome architecture of prestige and its success

Supremacía del derecho federal sobre el Common Law en materia de requisitos de seguridad y eficacia terapéutica de productos sanitarios. Comentario a Riegel v. Medtronic, Inc. [552 U.S.__ (2008); February 20, 2008]

En Riegel v. Medtronic Inc. (552 U.S.__2008; February 20, 2008), el Sr. Riegel tuvo que ser sometido a un by-pass como consecuencia de la rotura del catéter, fabricado por Medtronic, con el que su médico le practicaba una angioplastia. A pesar de que el catéter había obtenido la autorización de comercialización de la FDA y cumplía los requisitos de seguridad previstos por el sistema regulatorio federal, el Sr. Riegel y su mujer interpusieron una acción de daños contra Medtronic –y no contra el médico- conforme a las reglas de responsabilidad civil objetiva y por negligencia del Common Law neoyorquino. Sin embargo, el Tribunal Supremo federal de los EE.UU., en ponencia del Magistrado Antonin Gregory Scalia, votó, por mayoría de ocho magistrados, rechazar el recurso de la Sra. Riegel y confirmar la sentencia de segunda instancia, desestimatoria de la demanda, porque consideró que la regla de primacía del derecho regulatorio federal sobre seguridad de productos sanitarios [Medical Device Amendments de 1976, 21 U.S.C. Artículo 360k(a)] excluye la aplicabilidad no sólo del derecho regulatorio estatal sobre seguridad de productos sanitarios, sino también del Common Law sobre responsabilidad civil del fabricante.

La nueva formación del profesorado en Francia: la experiencia del I.U.F.M. de la Académie de Grenoble

Se describen las características de la formación inicial de los profesores en Francia a partir del análisis del funcionamiento organizativo y del plan de estudios desarrollado en el Institut Universitaire de Formation des Maîtres de la Académie de Grenoble, y se comparan algunos de los rasgos definitorios del nuevo modelo francés de formación del profesorado con la configuración que ha ido adquiriendo ésta en nuestro país, así como con los cambios institucionales y de planes de estudios que aquí se han venido gestando durante estos últimos años.

Reproductive morphology in Mediterranean Seirospora giraudyi (Ceramiales, Rhodophyta)

This paper presents a detailed description of the reproductive characters of Mediterranean Seirospora giraudyi based on fresh material collected in the northwestern coast of Spain. Vegetative cells are uninucleate. The plant is monoecious. Spermantangial parent’s cells are clustered on modified dwarf determinate filaments, usually situated on adaxial surfaces of branches. One to four spermatia are formed by elongation and proximal divisions of the spermatangial parent cells. Spermatium with a nucleus situated ina mec. The thallus is procarpic. The four-celled carpogonial branch is initially L-shaped, and it is situated on a periaxial supporting fertile axial cell. The mature carpogonial branch is U-shaped and the supporting cell and second periaxial cell enlarge and divide transversely to reproduce a pair uninicleate auxiliary cell. The nucleus in the ferlilized carpogonium divides twice and the carpogonium cleaves vertically into two cells that, turn, cut off a pair of uninucleate connecting cells that fuse with the auxiliary cells on opposite sides; the diploid nuclei in the connecting cells divide at the site of fusion and one of the nuclei enters the auxiliary cell white the other is extruded. Each auxiliary cell gives to a terminal primary gonimolobe initials. Gonimolobes form lax chains of carposporangia. As the gonimoblasts mature, both lobes of the foot cell which is situated on the supporting cell elongate the upper one secondary connecting with the supporting cell, and the lower one with the fertile axial cell. The gonimoblasts are subtended at maturity by one to several clusters of involucral flaments. Seirospora is currently placed in the tribe Euptiloteae; however the reproductive character of S.giraudyi is dentical to those described for the Cañllithamnieae. Molecular studies are needed to confirm the taxonomic position of S.giraudyi as well as that of the other species placed Seirospora

Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and 1H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.

The Dialogic Turn in Educational Psychology

The increasing presence of and claim for dialogue in today"s society has already had an impact on the theory and practice of learning. Whereas in the past individual and cognitive elements were seen as crucial to learning, since about two decades ago, scientific literature indicates that culture, interaction and dialogue are the key factors. In addition, the research project of highest scientific rank and with most resources dedicated to the study of school education in the Framework Program of the European Union: INCLUD-ED shows that the practices of successful schools around Europe are in line with the dialogic approach to learning. This article presents the dialogic turn in educational psychology, consisting of moving from symbolic conceptions of mind and internalist perspectives that focus on mental schemata of previous knowledge, to theories that see intersubjectivity and communication as the primary factors in learning. The paper deepens on the second approach.

Pass-through in dollarized countries: should Ecuador abandon the U.S. Dollar?

In this article we examine the convenience of dollarization for Ecuador today. As Ecuador is strongly integrated financially and commercially with the United States, the exchange rate pass-through should be zero. However, we sustain that rising rates of imports from trade partners other than the United States and subsequent real effective exchange rate depreciations are causing the pass-through to move away from zero. Here, in the framework of the Vector Error Correction Model, we analyse the impulse response function and variance decomposition of the inflation variable. We show that the developing economy of Ecuador is importing inflation from its main trading partners, most of them emerging countries with appreciated currencies. We argue that if Ecuador recovered both its monetary and exchange rate instruments it would be able to fight against inflation. We believe such an analysis could be extended to other countries with pegged exchange rate regimes.

El Món funerari antic, tardoantic i altomedieval a la ciutat de Girona: u n estat de la qüestió

Article que estudia els cementiris antics i altomedievals de la ciutat de Girona ubicats a l'entorn immediat de la ciutat, a la riba esquerra del riu Onyar i intra muros

Instal·lació wiki S.A.U.

Estudi d'una solució i implantació d'un sistema centralitzat per gestionar el coneixement de l'equip del servei d'atenció a l'usuari de l'empresa TIC a la que treballem. Basant-nos a la nostra experiència, considerem que la majoria de les tasques a desenvolupar es poden transmetre de manera eficient com a coneixement explícit dins d'un format documental, amb una evident millora en cas de recolzar-se en recursos multimèdia, per això hem seleccionat l'entorn wiki com a una eina apropiada per a aquesta finalitat.

The determinants of capital intensity in Japan and the U.S

We estimate the determinants of capital intensity in Japan and the US, characterized by striking different paths. We augment an otherwise standard Constant Elasticity of Substitution (CES) model with demand-side considerations, which we find especially relevant in the US. In this augmented setting, the elasticity of substitution between capital and labor is placed around 0.85 in Japan, and 0.30 in the US. We also find evidence of biased technical change, which is capital-saving in Japan but labor-saving in the US. These differences help us explain the diverse experience in the capital deepening process of these economies, and lead us to conclude that demand-side drivers may also be relevant to account for different growth experiences. A close look at the nature of technological change is also needed before designing one-size-fits-all industrial, economic growth, and/or labor market policies.

Debat sobre la desigualtat sexe/gènere i propostes u(dis)tòpiques: veus de dones

Realitat de les dones que viuen a Girona que tenen en comú, per una banda, la seva condició de dona, i per una altra banda, la de viure en una societat marcada per una diferència sexual i de gènere que es tradueix en desigualtat social. La tipologia de dones és molt diversa i inclou les que treballen a casa, les que treballen fora de casa, les feministes, les que no ho són, etc

Introducción de la simulación de alta fidelidad en el Grado de Enfermería U.B.

Simulación es la creación de una situación donde experimentar un evento con el fin de practicar, evaluar o adquirir conocimientos de sistemas o actuaciones humanas.La simulación de alta fidelidad se introduce en el curso 2012-2013 como proyecto piloto en el grado de Enfermería de la UB, está dirigida a alumnos de 4º de grado de Enfermería, pretende reforzar contenidos de la asignatura “Pràcticum” en el entorno del aula de alta simulación, potenciando la toma de decisiones en equipo ante situaciones de riesgo vital. La experiencia permite analizar, evaluar y reflexionar sobre la práctica, posibilita la mejora o replanteamiento del aprendizaje sin riesgo para el paciente. Durante la observación, alumnos y docentes cumplimentan la plantilla del caso: reflexiones y chequeo de la práctica simulada. Terminada la simulación, la reflexión final o "debriefing" pone en común aspectos emocionales, de interrelación y formativos, susceptibles de mejorar. La metodología permite evaluar competencias básicas y específicas, utilizando un marco de valoración.