El siguiente paso en el desarrollo de los repositorios: integración con la infraestructura institucional de gestión de la información científica

Dídac Martínez, Director de l'Àrea de Serveis Universitaris de la UPC, va esmentar en la seva introducció una sèrie de 10 prioritats per aldesenvolupament dels dipòsits institucionals, de les quals la desena era la integració dels repositoris en la infraestructura institucional de gestió de la informació científica. A més de citar diverses iniciatives de integració en aquest sentit -tant per investigació com per a continguts docents- a la Universitat Politècnica de Catalunya, la presentació va esmentar NARCIS com a model, un sistema CRIS d'àmbit nacional desenvolupat a Holanda per una sèrie d'universitats (que comparteixen Metis com a sistema CRIS institucional), NWO i el KNAW.

Curriculum Vitae Normalizado. Jornada técnica sobre CRIS y repositorios

Izascun Lacunza y David Arellano, FECYT, presentaron el proyecto CVN para la creación de un modelo normalizado de CV de investigador a partir de los datos almacenados en los sistemas CRIS institucionales. El modelo CVN se encuentra en la actualidad implementado en 32 universidades españolas, dando servicio a más de 18.500 investigadores de dichas instituciones, lo que supone un 14% del total de investigadores del Sistema Español de Ciencia y Tecnología (SECT), y hay planes para extender su implantación a más universidades y a más personal científico en aquéllas en las que ya está en marcha.

SICA2 : la experiencia de integración CRIS/RI en el ámbito regional de Andalucía

El proyecto SICA2, presentado por Beatriz Barros y Miguel Ángel Aguirre, de la Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía, supone una innovadora extensión del concepto de CRIS universitario a un ámbito regional para el conjunto de las universidades andaluzas. El sistema de recogida y validación de la información científica en tiempo real se basa en una primera fase SICA que organiza la investigación en unidades mínimas o 'Grupos PAIDI' y que ya implementó el estándar CVN para las nueve universidades andaluzas que forman parte del proyecto. Esta segunda fase de integración tiene además prevista su prolongación en el repositorio institucional Reposit-AN de ámbito igualmente regional que se alimentará de los metadatos procedentes del sistema CRIS de la Junta de Andalucía y se presentará oficialmente a final de año.

Experiencias de interoperabilidad entre CRIS y repositorios en Catalunya

Toni Prieto, Técnico IC del Servicio de Bibliotecas y Documentación (SBD) de la UPC, en su presentación 'Experiencias de interoperabilidad entre CRIS y repositorios en Catalunya', describió la integración del repositorio UPCommons y del CRIS DRAC (Descriptor de la Recerca i l'Activitat Acadèmica) de la UPC. El resultado de esta integración es un esquema integrado de archivo CRIS/IR en dos fases, envío y revisión, en el que los metadatos se introducen en DRAC -para posteriormente ser transferidos, validados y enriquecidos si procede- y el archivo de texto completo asociado se realiza en UPCommons. De manera similar funciona la integración de GIR (Gestió Integral de la Recerca, basado en Universitas XXI Investigación) y el repositorio O2 en la UOC, permitiendo la asignación del identificador handle de un ítem en O2 a una referencia en GIR. Ambos sistemas, DRAC en la UPC y GIR en la UOC, están integrados en el Proyecto CVN de generación de CVs normalizados. Se mencionaron asimismo experiencias posteriores de integración CRIS/IR actualmente en curso en la Universitat de Barcelona y en la U Pompeu Fabra, y se mostró el impacto significativo de la estrategia de integración de sistemas sobre el ritmo de incorporación de contenidos a UPCommons.

El camino hacia la integración de sistemas de gestión de la información científica : el TCD (Trinity College Dublin) como estudio de caso. CERIF y euroCRIS

Pablo de Castro, Director de GrandIR, describió la visión que el Grupo euroCRIS tiene de la infraestructura integrada de gestión de la información científica, compuesta por un sistema CRIS institucional, un repositorio de publicaciones y un repositorio de datos y software, y presentó el modelo de infraestructura integrada del Trinity College Dublin (TCD) como estudio de caso internacional. El sistema CRIS del TCD (TCD Research Support System o RSS), desde su primera versión en 2002, está basado en el estándar CERIF, un modelo de descripción de la actividad científica que está adquiriendo una progresiva relevancia como base de los sistemas CRIS en Europa, particularmente en el Reino Unido. Se citaron en la presentación los ensayos para incorporar CERIF al modelo de datos del software ePrints de repositorios, habilitándolo así para soportar parte de las tareas de recolección de información que realiza un CRIS, y la progresiva cobertura de CERIF a ámbitos tales como la gestión de datos de investigación.

La paulatina incorporación del estándar CERIF al diseño de sistemas integrados de gestión científica

Núria Cuní y Juan Pedro Belchi, representantes del Consorcio Sigma Gestión Universitaria, miembro institucional de euroCRIS, hablaron de sus previsiones para la incorporación de CERIF al desarrollo de su módulo Argos para sistemas CRIS universitarios, previa descripción de la aplicación de Argos a la integración de diversos sistemas institucionales en la Universitat Pompeu Fabra. El trabajo de implantación de Argos en la UPF incluyó la puesta a punto del estándar CVN, y en la presentación se relacionó dicho proyecto CVN con la adaptación progresiva del modelo de datos de Argos hacia CERIF.

A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

egr-4, a target of EGFR signaling, is required for the formation of the brian primordial and head regeneration in planarians

During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/β-catenin and Hh signaling pathways in re-establishing anterior-posterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain- and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phases - an early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration.

Identification of in vitro HSC fate regulators by differential lipid raft clustering.

Most hematopoietic stem cells (HSC) in the bone marrow reside in a quiescent state and occasionally enter the cell cycle upon cytokine-induced activation. Although the mechanisms regulating HSC quiescence and activation remain poorly defined, recent studies have revealed a role of lipid raft clustering (LRC) in HSC activation. Here, we tested the hypothesis that changes in lipid raft distribution could serve as an indicator of the quiescent and activated state of HSCs in response to putative niche signals. A semi-automated image analysis tool was developed to map the presence or absence of lipid raft clusters in live HSCs cultured for just one hour in serum-free medium supplemented with stem cell factor (SCF). By screening the ability of 19 protein candidates to alter lipid raft dynamics, we identified six factors that induced either a marked decrease (Wnt5a, Wnt3a and Osteopontin) or increase (IL3, IL6 and VEGF) in LRC. Cell cycle kinetics of single HSCs exposed to these factors revealed a correlation of LRC dynamics and proliferation kinetics: factors that decreased LRC slowed down cell cycle kinetics, while factors that increased LRC led to faster and more synchronous cycling. The possibility of identifying, by LRC analysis at very early time points, whether a stem cell is activated and possibly committed upon exposure to a signaling cue of interest could open up new avenues for large-scale screening efforts.

Systematic review of evidence and consensus on diverticulitis: an analysis of national and international guidelines.

AIM: The study aimed to analyse the currently available national and international guidelines for areas of consensus and contrasting recommendations in the treatment of diverticulitis and thereby to design questions for future research. METHOD: MEDLINE, EMBASE and PubMed were systematically searched for guidelines on diverticular disease and diverticulitis. Inclusion was confined to papers in English and those < 10 years old. The included topics were classified as consensus or controversy between guidelines, and the highest level of evidence was scored as sufficient (Oxford Centre of Evidence-Based Medicine Level of Evidence of 3a or higher) or insufficient. RESULTS: Six guidelines were included and all topics with recommendations were compared. Overall, in 13 topics consensus was reached and 10 topics were regarded as controversial. In five topics, consensus was reached without sufficient evidence and in three topics there was no evidence and no consensus. Clinical staging, the need for intraluminal imaging, dietary restriction, duration of antibiotic treatment, the protocol for abscess treatment, the need for elective surgery in subgroups of patients, the need for surgery after abscess treatment and the level of the proximal resection margin all lack consensus or evidence. CONCLUSION: Evidence on the diagnosis and treatment of diverticular disease and diverticulitis ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.

Capsid modified replicating adenovirus to selectively target colon cancer

Résumé: Pratiquement tous les cancers du colon contiennent des mutations dans la voie de signalisation de Wnt qui active constitutivement cette voie. Cette activation mène à la stabilisation de la β-catenine. La β-catenin est transportée dans le noyau ou elle active des gènes cible en interagissant avec le facteur de transcription de TCF/LEF. Des adénovirus qui peuvent sélectivement se répliquer dans les cellules tumorales sont les agents qui peuvent permettre la déstruction de la tumeur mais pas le tissu normal. In vitro, les adénovirus avec des sites d'attachement du facteur de transcription TCF dans les promoteurs de l'adénovirus montrent une sélectivité et une activité dans une large sélection de lignées cellulaires de cancer du colon. Au contraire, in vivo, quand les adénovirus modifiés sont injectés dans la circulation, ils sont moins efficaces à cause de leur fixation par le foie et à cause de l'absence d'expression du récepteur du Coxsackie-Adénovirus (CAR). Le but de ma thèse était de modifier la protéine principale de capside de l'adénovirus, fibre, pour augmenter l'infection des tumeurs du cancer du colon. La fibre de l'adénovirus est responsable de l'attachement aux cellules et de l'entrée virale. J'ai inséré un peptide RGD dans la boucle HI de la fibre qui dirige sélectivement le virus aux récepteurs des integrines. Les integrines sont surexprimées par les cellules du cancer du colon et l'endothélium des vesseaux de la tumeur. Le virus re-ciblé, vKH6, a montré une activité accrue dans toutes les lignées cellulaires de cancer du colon, tandis que la sélectivité était maintenue. In vivo, vKH6 était supérieur au virus avec une capside de type sauvage en retardant la croissance de la tumeur. Le virus s'est répliqué plus vite et dispersé graduellement dans la tumeur. Cet effet a été montré par hybridation in situ et par PCR quantitative. Cependant, la monothérapie avec le virus n'a pu retarder la croissance des cellules tumorales SW620 greffées que de 2 semaines, mais à cause des régions non infectées la tumeur n'a pas pu être éliminée. Bien que la combinaison avec les chimiothérapies conventionnelles soit d'intérêt potentiel, presque toutes interfèrent avec la réplication virale. Les drogues antiangiogéniques sont des agents anti-tumoraux efficaces et prometteurs. Ces drogues n'interfèrent pas avec le cycle de vie de l'adénovirus. RAD001 est un dérivé de la rapamycine et il inhibe mTOR, une protéine kinase de la voie de PI3K. RAD001 empêche la croissance des cellules et il a aussi des effets anti-angiogénique et immunosuppressifs. RAD001 in vitro n'affecte pas l'expression des gènes viraux et la production virale. La combinaison de VKH6 et RAD001 in vivo a un effet additif en retardant la croissance de la tumeur. Des nouveaux peptides plus efficaces dans le ciblage de l'adénovirus sont nécessaires pour augmenter l'infection des tumeurs. J'ai créé un système de recombinaison qui permettra la sélection de nouveaux peptides dans le contexte du génome de l'adénovirus. Summary Virtually all colon cancers have mutations in the Wnt signalling pathway which result in the constitutive activation of the pathway. This activation leads to stabilization of β-catenin. β-catenin enters the nucleus and activates its target genes through interaction with the TCF transcription factor. Selectively replicating adenoviruses are promising novel agents that can destroy the tumour but not the surrounding normal tissue. In vitro, adenoviruses with TCF binding sites in the early viral promoters show selectivity and activity in a broad panel of viruses but in vivo they are less effective due to the lack of expression of the Coxsackie-Adenovirus receptor (CAR). The aim of my thesis was to modify the major capsid protein of the adenovirus, fibre, to increase the infection of colon tumours. Fibre of adenovirus is responsible for the binding to cells and for the viral uptake. I inserted an RGD binding peptide into the HI loop of fibre that selectively targets the virus to integrins that are overexpressed on tumour cells and on tumour endothelium. The retargeted virus, vKH6, showed increased activity in all colon cancer cell lines while selectivity was maintained. In vivo, vKH6 is superior to a matched virus with a wild type capsid in delaying tumour growth. vKH6 replicates and gradually spreads within the tumour as shown by in situ hybridization and Q-PCR. The virus alone can delay the growth of SW620 xenografts by 2 weeks but due to uninfected tumour regions the tumour cannot be cured. Although combination with conventional chemotherapeutics is of potential interest, almost all of them interfere with the viral replication. Growing evidence supports that anti-angiogenic drugs are effective and promising anti-tumour agents. These drugs interfere less with the viral life cycle. RAD001 is a rapamycin derivative and it blocks mTOR, a protein kinase in the PI3K pathway. RAD001 inhibits cell growth and has strong anti-angiogenic and immunosuppressive effects. RAD001 in vitro does not affect viral gene expression and viral burst size. In vivo vKH6 and RAD001 have an additive effect in delaying tumour growth, but tumour growth is still not completely inhibited. To further increase tumour infection new tumour specific targeting peptides are needed. I created an adenovirus display library that will allow the selection of targeting peptides. This system may also facilitate the production of fibre modified viruses.

β-catenin signalling in Glioblastoma multiforme and Glioma-initiating cells

Glioblastoma multiforme (GBM) is a commonly occurring brain tumor with a poor prognosis. GBM can develop both “de novo” or evolve from a previous astrocytoma and is characterized by high proliferation and infiltration into the surrounding tissue. Following treatment (surgery, radiotherapy, and chemotherapy), tumors often reappear. Glioma-initiating cells (GICs) have been identified in GBM and are thought to be responsible for tumors initiation, their continued growth, and recurrence. β-catenin, a component of the cell-cell adhesion complex and of the canonical Wnt pathway, regulates proliferation, adhesion, and migration in different cell types. β-catenin and components of the Wnt canonical pathway are commonly overexpressed in GBM. Here, we review previous work on the role of Wnt/β-catenin signalling in glioma initiation, proliferation, and invasion. Understanding the molecular mechanisms regulating GIC biology and glioma progression may help in identifying novel therapeutic targets for GBM treatment.

Características agronômicas de seis genótipos de maracujazeiro-azedo cultivados no Distrito Federal

Este trabalho teve como objetivo avaliar as características agronômicas de seis genótipos de maracujazeiro-azedo cultivados no Distrito Federal. O experimento foi desenvolvido na área experimental da Fazenda Água Limpa da Universidade de Brasília, no DF. Utilizou-se o delineamento em blocos casualizados, com quatro repetições, seis tratamentos e sete plantas por parcela. Foram avaliados os genótipos: Rubi Gigante, EC-3-0, EC-L-7, RC-3, Redondão e Gigante Amarelo. Os parâmetros analisados, durante seis meses (17 colheitas), foram: produtividade total estimada, quantidade de frutos e coloração da casca. O genótipo Rubi Gigante teve a maior produtividade (16,69 t/ha-1), enquanto o RC-3 a menor (2,92 t/ha-1). Foram observados resultados semelhantes quanto às variáveis: produtividade total e quantidade de frutos de tamanho: primeira, 1B e 1A em relação aos seis genótipos. Não houve diferença significativa a 5%, pelo teste de Tukey, para: % de frutos de coloração amarela, rosa e roxa; massa fresca de frutos amarelos e rosas; quantidade de frutos rosas e roxos, e também quantidade de frutos de tamanho 2A e 3A em relação a todos os genótipos avaliados. Os genótipos Rubi Gigante, Redondão, EC-3-0 e EC-L-7 podem ser recomendados para o cultivo no DF e região geoeconômica, se confirmarem a superioridade quando avaliados por um maior período e em diferentes condições ambientais.

Pas caart van de Oost zee. Detalji.

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