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.

Rellevància de la competència transversal Capacitat d'aprenentatge i responsabilitat en l'àmbit de Ciències de la Salut

Se determina la relevancia y la modalidad de trabajo (Presencial, semipresencial o no presencial) del conjunto de las cinco sub-competencias (Capacidad de análisis y de síntesis - Aplicar conocimientos a la práctica - Resolver problemas y tomar deci-siones - Capacitado para adaptarse a nuevas situaciones - Asumir responsabilida-des), ligadas a la competencia transversal Capacidad de aprendizaje y responsabili-dad, en los estudios de grado de Ciencias de la Salud de la UB y URL.

Rellevància de la competència transversal Capacitat d'aprenentatge i responsabilitat en l'àmbit de Ciències de la Salut

Se determina la relevancia y la modalidad de trabajo (Presencial, semipresencial o no presencial) del conjunto de las cinco sub-competencias (Capacidad de análisis y de síntesis - Aplicar conocimientos a la práctica - Resolver problemas y tomar deci-siones - Capacitado para adaptarse a nuevas situaciones - Asumir responsabilida-des), ligadas a la competencia transversal Capacidad de aprendizaje y responsabili-dad, en los estudios de grado de Ciencias de la Salud de la UB y URL.

Rellevància de la competència transversal Capacitat d'aprenentatge i responsabilitat en l'àmbit de Ciències de la Salut

Se determina la relevancia y la modalidad de trabajo (Presencial, semipresencial o no presencial) del conjunto de las cinco sub-competencias (Capacidad de análisis y de síntesis - Aplicar conocimientos a la práctica - Resolver problemas y tomar deci-siones - Capacitado para adaptarse a nuevas situaciones - Asumir responsabilida-des), ligadas a la competencia transversal Capacidad de aprendizaje y responsabili-dad, en los estudios de grado de Ciencias de la Salud de la UB y URL.

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male SpragueDawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokineticpharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Forecasting coal resources and reserves in heterogeneous coal zones using 3D facies models (As Pontes Basin, NW Spain)

Forecasting coal resources and reserves is critical for coal mine development. Thickness maps are commonly used for assessing coal resources and reserves; however they are limited for capturing coal splitting effects in thick and heterogeneous coal zones. As an alternative, three-dimensional geostatistical methods are used to populate facies distributionwithin a densely drilled heterogeneous coal zone in the As Pontes Basin (NWSpain). Coal distribution in this zone is mainly characterized by coal-dominated areas in the central parts of the basin interfingering with terrigenous-dominated alluvial fan zones at the margins. The three-dimensional models obtained are applied to forecast coal resources and reserves. Predictions using subsets of the entire dataset are also generated to understand the performance of methods under limited data constraints. Three-dimensional facies interpolation methods tend to overestimate coal resources and reserves due to interpolation smoothing. Facies simulation methods yield similar resource predictions than conventional thickness map approximations. Reserves predicted by facies simulation methods are mainly influenced by: a) the specific coal proportion threshold used to determine if a block can be recovered or not, and b) the capability of the modelling strategy to reproduce areal trends in coal proportions and splitting between coal-dominated and terrigenousdominated areas of the basin. Reserves predictions differ between the simulation methods, even with dense conditioning datasets. Simulation methods can be ranked according to the correlation of their outputs with predictions from the directly interpolated coal proportion maps: a) with low-density datasets sequential indicator simulation with trends yields the best correlation, b) with high-density datasets sequential indicator simulation with post-processing yields the best correlation, because the areal trends are provided implicitly by the dense conditioning data.

Cómo definir tu estrategia de marca personal en los medios sociales

Definir una estratègia per a la nostra marca personal com a forma d’aproximació dels nostres valors, atributs i objectius cap al nostre públic objectiu és el plantejament d’aquest projecte. Amb aquesta finalitat es desenvoluparà una estratègia de comunicació digital, per l’actor català Albert Carbó, que comprengui les seves necessitats per arribar a complir amb els seus objectius.

Innovar, renovar, avaluar

[eng] The new educational context in which we are involved and the facilities of the TIC (Communication Information Technologies) have led to the necessary modification of didactic approach that during years has been used for Pharmaceutical Technology teaching. However, changes/updating and innovation require a simultaneous reflection in order to avoid excessive dispersion of the approach and to channel adequately the pedagogic and didactic effort. On the other hand, it is necessary to evaluate the above initiatives to determinate if these one are on the right track. The Pharmaceutical Technology Teaching Innovation Group of the University of Barcelona has been formed and consolidated in this point of view. In this work, a review of studies carried on by the group, in the exposed purposes, from the beginning of their activities is presented. [spa] El nuevo contexto docente en el que estamos inmersos así como las posibilidades de las TIC (Tecnologías de la Información y de la Comunicación) han conllevado la necesaria modificación de los planteamientos didácticos que durante años han servido de base para las enseñanzas de la Tecnología Farmacéutica. Sin embargo, la renovación/actualización e innovación precisan de una simultánea reflexión a fin de evitar una excesiva dispersión del enfoque y para encauzar adecuadamente el esfuerzo pedagógico y didáctico. Por otra parte, es necesario evaluar dichas iniciativas para determinar si están bien encaminadas. El Grupo de Innovación Docente de Tecnología Farmacéutica de la Universidad de Barcelona se ha creado y consolidado desde esta óptica. En este trabajo se presentan un conjunto de estudios que el grupo ha llevado a cabo, con los fines expuestos, desde el comienzo de sus actividades.

Autoevaluación intercativa y lúdica de Tecnología Farmacéutica

[eng] The individual work of the student, in the European space for higher education, takes a particular relevance. At the same time, in this context, a complex challenge is presented to the professors, in the educational and formative work aimed at the students as well as in the organization of educational plans. Among the different activities that the system of ECTS comprises, we can highlight the preparation and accomplishment of examinations. This fact means to integrate into the learning process the individual and autonomous work that the students have to carry out to acquire the knowledge and to surpass the evaluation test. To achieve this objective, a database including multiple choice questions with three possible answers has been developed (similar to those composing part of the Pharmaceutical Technology test). This database has a design that facilitates its use by professors and students interested in this area and allows as the interactive evaluation of obligatory and optional subjects from the formal point of view, as a corporate recreational environment to make their employment more attractive for the students. The edition of the Web page of the Pharmaceutical Technology Teaching Innovation Group of the UB has been used to place this database within everybody"s reach. [spa] El trabajo individual del alumno adquiere, dentro del marco europeo de educación superior, una particular relevancia. Al mismo tiempo, en este contexto, a los profesores se nos presenta un reto complejo, tanto en nuestra labor docente y formativa del alumno, como en la organización de los planes docentes. De las distintas actividades que engloba el crédito europeo podemos destacar la preparación y realización de exámenes, hecho que supone integrar en el proceso de aprendizaje el trabajo individual y autónomo que realiza el estudiante para adquirir los conocimientos y superar las pruebas de evaluación. Para conseguir este objetivo se ha planteado la elaboración de una base de preguntas con tres respuestas posibles (del tipo de las que componen parte de los exámenes de Tecnología Farmacéutica), en forma de base de datos con un formato que facilite su utilización por parte de profesores y alumnos interesados en este ámbito y que permita tanto la evaluación interactiva de las asignaturas troncales y optativas desde el punto de vista formal, como su aplicación en un entorno lúdico corporativo para hacer más atrayente su empleo por los estudiantes. Se ha aprovechado la edición de la página Web del Grupo de Innovación Docente de Tecnología Farmacéutica de la UB para ponerlo al alcance de todos.

Revegetació de talussos d'una explotació carbonífera mitjançant materials de rebuig

En aquest treball s'avalua la rehabilitació dels talussos d'una explotació minera carbonífera utilitzant materials de rebuig de la pròpia explotació i provinents d'activitats ramaderes (purins de porc) o urbanes (llots de depuradora), en un ambient àrid del Baix Segre. Les variables analitzades foren el tipus i recobriment vegetals, la penetromia i la salinitat del substrat, i la salinitat, els nitrats i els sediments dels efluents. Els resultats indiquen que és possible rehabilitar els runams en aquests medis, assolint recobriments vegetals fins al 50 % sense que se'n derivin efectes ambientals negatius importants. Taxes altes puntuals d'erosió poden controlar-se amb un disseny adient dels talussos. L'aplicació superficial de purí no té efectes antiencrostants. La moderada salinitat dels substrats condiciona l'establiment de vegetació halòfila.

Espeleotoponímia de motivació paleontològica i antracotoponímia de les Illes Balears

En aquest treball es recopilen i estudien, des d’una perspectiva etnopaleontològica, les aportacions i influencies exercides pels fòssils en relació al patrimoni onomàstic toponímic relacionat amb cavitats càrstiques de l’àmbit geogràfic de les Illes Balears. Generalment es tracta de microtopònims moderns o recents, en vies de popularització i/o tradicionalització (neotopònims), establerts pels científics que estudien les coves i/o esportistes del món de l’espeleologia (topocultismes). Es poden distingir entre espeleotopònims de primer ordre (quan es refereixen a cavitats completes) i de segon ordre (quan es refereixen a un sector d’una cavitat). També es realitza una primera aproximació als topònims referits a mines d’extracció de carbó fòssil (antracotopònims).

Toponímia de motivació paleontològica de les Illes Balears

En aquest treball es recopilen i estudien, des d’una perspectiva etnopaleontològica, les aportacions i influencies exercides pels fòssils en relació al patrimoni onomàstic toponímic dins l’àmbit geogràfic de les Illes Balears. Aquests patrimoni paleontotoponímic inclou topònims tradicionals i neotopònims (espeleotopònims) de motivació paleontològica, topònims relacionats amb creences o llegendes sobre els fòssils i topònims relacionats amb l’extracció de carbó fòssil (antracotopònims). També es realitza una aproximació a la utilitat de la toponímia com a ciència auxiliar de la paleontologia.

The First World War and Coal Trade Geography in Latin America and the Caribbean, 1890-1930

This paper aims to illustrate the dynamics of coal trade between Latin America and its main trade partners, i.e., the USA, Great Britain, and Germany, before and after the enormous disruption caused by the First World War. The coal trade was used as an indicator of modernization for Latin American countries, given that oil was at that time of secondary importance. Energy imports have determined the possibilities of each Latin American country in its process of development. Here, we address this question and place special emphasis on supply channels, concluding that the trade link with main suppliers was of key significance. Although this was very clear by the end of the period, the process had started well before the First World War, at least for the majority of LA&C countries. These points are developed through a gravity model applied to the bilateral coal trade. The importance of the market supplier share is addressed through cluster methodologies.

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.