Pathway databases and tools for their exploitation: benefits, current limitations and challenges

In past years, comprehensive representations of cell signalling pathways have been developed by manual curation from literature, which requires huge effort and would benefit from information stored in databases and from automatic retrieval and integration methods. Once a reconstruction of the network of interactions is achieved, analysis of its structural features and its dynamic behaviour can take place. Mathematical modelling techniques are used to simulate the complex behaviour of cell signalling networks, which ultimately sheds light on the mechanisms leading to complex diseases or helps in the identification of drug targets. A variety of databases containing information on cell signalling pathways have been developed in conjunction with methodologies to access and analyse the data. In principle, the scenario is prepared to make the most of this information for the analysis of the dynamics of signalling pathways. However, are the knowledge repositories of signalling pathways ready to realize the systems biology promise? In this article we aim to initiate this discussion and to provide some insights on this issue.

Relación precio-calidad de los destinos turísticos españoles de sol y playa

The aim of this article is to estímate price-quality relatíon of Spain resorts from ‘sun and beach’ segment. This study uses initially observed prices, but after obtains net pnces -estimated-, discounting services and characteristics prices. Methodologically, this article is based in hedonic methods, often used in economic analysis. Results show important differences between ‘prices observed’ and ‘adjusted prices’ by services and characteristics. Empirical results obtained in this article should be useful for taking decisions from public and prívate agents

The EU-ADR Web Platform: delivering advanced pharmacovigilance tools

PURPOSE: Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks.METHODS: The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential.RESULTS: The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment.CONCLUSIONS: A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright © 2012 John Wiley & Sons, Ltd.

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration.

Background: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilizehematopoietic stem cells (HSC) and increase their presence in peripheral circulation. Methods: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposureconsisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. Results: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Conclusion: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration.

Background: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilizehematopoietic stem cells (HSC) and increase their presence in peripheral circulation. Methods: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposureconsisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. Results: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Conclusion: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

Els Plans Individualitzats en les regulacions del Departament d’Educació de juny de 2008. Aplicació d’enfocaments multidimensionals en la seva elaboració

Recentment, el Departament d’Educació de la Generalitat de Catalunya ha publicat regulacions sobre els plans individuals per als alumnes considerats més vulnerables. Se n’han determinat els components i les condicions que s’han de donar per al seu inici. Aquest article considera la possibilitat de desenvolupar aquests plans individuals a partir d’enfocaments multidimensionals d’atenció a les necessitats singulars de l’alumnat de les escoles ordinàries, i presenta algunes propostes per abordar aquests procediments des de les perspectives relacionades amb els Plans Educatius Individualitzats en contextos diferents.

Gene Promoter Evolution Targets the Center of the Human Protein Interaction Network

Assessing the contribution of promoters and coding sequences to gene evolution is an important step toward discovering the major genetic determinants of human evolution. Many specific examples have revealed the evolutionary importance of cis-regulatory regions. However, the relative contribution of regulatory and coding regions to the evolutionary process and whether systemic factors differentially influence their evolution remains unclear. To address these questions, we carried out an analysis at the genome scale to identify signatures of positive selection in human proximal promoters. Next, we examined whether genes with positively selected promoters (Prom+ genes) show systemic differences with respect to a set of genes with positively selected protein-coding regions (Cod+ genes). We found that the number of genes in each set was not significantly different (8.1% and 8.5%, respectively). Furthermore, a functional analysis showed that, in both cases, positive selection affects almost all biological processes and only a few genes of each group are located in enriched categories, indicating that promoters and coding regions are not evolutionarily specialized with respect to gene function. On the other hand, we show that the topology of the human protein network has a different influence on the molecular evolution of proximal promoters and coding regions. Notably, Prom+ genes have an unexpectedly high centrality when compared with a reference distribution (P = 0.008, for Eigenvalue centrality). Moreover, the frequency of Prom+ genes increases from the periphery to the center of the protein network (P = 0.02, for the logistic regression coefficient). This means that gene centrality does not constrain the evolution of proximal promoters, unlike the case with coding regions, and further indicates that the evolution of proximal promoters is more efficient in the center of the protein network than in the periphery. These results show that proximal promoters have had a systemic contribution to human evolution by increasing the participation of central genes in the evolutionary process.

Integrative analysis of the Regulatory Region of the FGFR3 Oncogene

The study of transcriptional regulation often needs the integration of diverse yet independent data. In the present work, sequence conservation, predic-tion of transcription factor binding sites (TFBS) and gene expression analysis have been applied to the detection of putative transcription factor (TF) modules in the regulatory region of the FGFR3 oncogene. Several TFs with conserved binding sites in the FGFR3 regulatory region have shown high positive or negative corre-lation with FGFR3 expression both in urothelial carcinoma and in benign nevi. By means of conserved TF cluster analysis, two different TF modules have been iden-tified in the promoter and first intron of FGFR3 gene. These modules contain acti-vating AP2, E2F, E47 and SP1 binding sites plus motifs for EGR with possible repressor function.

Asentamientos rurales y estructuración de la Layetania interior (Barcelona): romanización e impacto de los programas de organización territorial

This paper presents the results of the first phase of archaeological and historical study developed in the Vallès Oriental. It has done a complete study of the archaeological information available from the several documentary sources (bibliography, IPAC, etc.). This has lead to an interpretative update on the forms of occupation and settlement dynamics developed in the study area during the 5th BC to 1st century AD. Preliminary results of the archaeomorphological analysis focused primarily on the road network are also presented. The first results highlight the importance of territorial organization programs of the late 2nd BC and 1st century BC. In this sense, it has been documented a close relationship between the road network and the distribution of rural settlements in late-Republican and Augustan periods. The use of databases in the management of archaeological information, and especially the application of GIS in the analysis and interpretation of data, suggest new interpretive approaches.

La Corona immarcescible : pintures de l'antiguitat tardana de la necròpolis alta d'Oxirinc (Mínia, Egipte)

La primera publicació de l’Institut enceta la Sèrie Documenta, que respon a la voluntat de promoure i editar estudis que donin a conèixer i emmarquin científicament nous elements de la cultura material de l’antiguitat clàssica.Aquest llibre estudia un conjunt de pintura mural dels segles V o VI que decorava les parets d’una casa funerària, convertida després en oratori, i que fou descoberta a la necròpolis alta de l’antiga ciutat d’Oxirinc (Mínia, Egipte). El cicle pictòric presenta una sobrietat simbolista que evoluciona després en una iconografia rica en figures i colors.Tot això, completat per la gens menyspreable qualitat artística de les representacions pictòriques, fa d’aquest conjunt una peça arqueològica molt singular.L’estudi inclou un primer capítol a càrrec del Dr. Josep Padró, de la Universitat de Barcelona, Maite Mascort i Hassan Ibrahim Amer, on es sintetitzen els treballs arqueològics i històrics realitzats, des de l’any 1992, a l’antiga Oxirin. Tot seguit, la Dra. Eva Subías, investigadora de la Universitat Rovira i Virgili i col·laboradora de l’Institut des del primer moment, ens ofereix l’estudi històricoartístic del cicle mural. Finalment, Concepció Piedrafita ens dóna la lectura i traducció dels textos grecs presents en les pintures.L’obra inclou una presentació a càrrec de Josep Guitart, director de l’Institut Català d’Arqueologia Clàssica i una traducció dels textos al francès.

Desenvolupament d’una aplicación web per a l’oci nocturn de Girona

Desenvolupament d’ una eina en forma de pàgina web que reculli tota la informació relacionada amb l’oci nocturn de la província de Girona i que permeti als usuaris conèixer tota aquesta activitat de la província en un sol lloc web

Desenvolupament d’una eina per a l’escriptura de nous exercicis de l’ACME

L'ACME és una plataforma d'e-learning utilitzada a la Universitat de Girona que permet la correcció automètica d'un gran nombre d'exercicis de tipologies variades via web. Actualments'utilitza com a eina de seguiment del treball diari dels alumnes en moltes carreresi facultats de la Universitat de Girona, que els permet consolidar la matèria explicada aclasse.Actualment tots els fitxers que contenen la implementació dels exercicis definits a l'ACMEestan en format LATEXi segueixen uns formats d'escriptura concrets, no estàndards i moltsdefiits per a la seva posterior lectura i interpretació. Aquesta alta especificitat i mancad'estandardització fa difícil l'aprenentatge de l'escriptura per part dels professors que volenfer servir l'ACME. La majoria d'ells es limiten a escriure exercicis nous a partir d'exercicisantics, desconeixen per complet si amb la tipologia d'exercici que utilitzen estan fent servirtot el potencial, o no, que permet l'eina. És en aquest punt que neix aquest ProjecteFinal de Carrera amb la intenció de desenvolupar una eina que permeti facilitar, millorar iampliar la metodologia d'escriptura de nous exercicis a l'ACME.L'objectiu d'aquest Projecte Final de Carrera era desenvolupar una metodologia d'escripturad'exercicis diferent, innovadora i a l'abast de qualsevol professor per poder crear noustipus d'exercicis amb facilitat i sense haver de necessitar coneixements sobre programació

Modelación y conceptualización del paisaje romano en el Ager Tarraconensis: Tarraco y la centuriación del territorio

Se presentan los resultados de la investigación arqueomorfológica desarrollada en los últimos años en el ager Tarraconensis. El análisis de las formas del paisaje realizado muestra una compleja morfología agraria caracterizada por la presencia de diversas tramas centuriadas, fosilizadas en la morfología moderna del territorio. Por otra parte, las posibilidades abiertas por el análisis digital son importantes en relación con la fiabilidad del registro planimétrico, la precisión de las restituciones y la posibilidad de integrar gran diversidad de fuentes en un mismo entorno. Se han realizado también modelos topográficos en tres dimensiones, a partir de documentos fotográficos y cartográficos anteriores a las grandes reformas territoriales de los años sesenta generándose documentos que permiten una mejor aproximación al conocimiento del territorio antiguo. Asimismo los análisis de visibilidad aportan sugerentes hipótesis sobre como se concibió y planificó la actuación de los agrimensores romanos, así como sobre la articulación entre la estructura urbana y el territorio, y las tramas centuriadas entre sí. La integración de datos en la zona estudiada demuestra la profunda estructuración del territorio, relacionada específicamente con la promoción de Tarraco a colonia en época de César. Desde esta perspectiva se aporta nueva información sobre la implantación de la ciudad en el paisaje del ager Tarraconensis en época tardo-republicana.