83 research outputs found
A framework for experience management in public organisations
El proyecto Pellucid desarrolló una plataforma adaptable y personalizable para habilitar
gestión de la experiencia en las organizaciones públicas. Un marco para la gestión de la experiencia
se ha desarrollado en base a la generación de ‘pistas activas’ que se presentan al usuario
según el contexto de trabajo. El contexto de trabajo abarca tanto la posición en el proceso de trabajo
y características específicas del dominio. El documento presenta este marco y describe la
proceso de ingeniería que se llevó a cabo siguiendo la metodología CommonKADS.The Pellucid project developed an adaptable and customisable platform for enabling
experience management in public organisations. A framework for experience management
has been developed based on the generation of ‘active hints’ that are presented to the user
according to working context. Working context encompasses both position in the work process
and domain-specific characteristics. The paper presents this framework and describes the
engineering process that was undertaken following the CommonKADS methodology
A framework for experience management in public organisations
The Pellucid project developed an adaptable and customisable platform for enabling experience management in public organisations. A framework for experience management has been developed based on the generation of ‘active hints’ that are presented to the user according to working context. Working context encompasses both position in the work process and domain-specific characteristics. The paper presents this framework and describes the engineering process that was undertaken following the CommonKADS methodology.Keywords: Knowledge Management, Experience Management, E-Government, Workflow Management Systems, CommonKADS
Combinatorial ECM Arrays Identify Cooperative Roles for Matricellular Proteins in Enhancing the Generation of TH+ Neurons From Human Pluripotent Cells
The development of efficient cell culture strategies for the generation of dopaminergic neurons is an important goal for transplantation-based approaches to treat Parkinson’s disease. To identify extracellular matrix molecules that enhance differentiation and might be used in these cell cultures we have used micro-contact printed arrays on glass slides presenting 190 combinations of 19 extracellular matrix molecules selected on the basis of their expression during embryonic development of the ventral midbrain. Using long-term neuroepithelial stem cells (Lt-NES), this approach identified a number of matricellular proteins that enhanced differentiation, with the combination of Sparc, Sparc-like (Sparc-l1) and Nell2 increasing the number of tyrosine hydroxylase+ neurons derived from Lt-NES cells and, critically for further translation, human pluripotent stem cells
RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme.We would like to thank the Functional Genomics, Microscopy, and Cytometry core facilities of IRB Barcelona, and the UB. We thank C. Caelles for the 3AOX-luc construct. We thank Angel Nebreda for his scientific suggestions. EJA is supported by "La Caixa" PhD fellowship programme, and JU is a Juan de la Cierva Researcher (MICINN). JM is a Howard Hughes investigator. The work of A. C. and S.F-R is supported by the Ramon y Cajal award to AC (Spanish Ministry of Education) and the ERC (336343). JM was supported by HHMI. RRG and XS are ICREA Research Professors (Institucio Catalana de Recerca i Estudis Avancats). Support and structural funds were provided by the Associacion Espanola Contra el Cancer (AECC), Fundacion BBVA, Generalitat de Catalunya (2009 SGR 1429), and Spanish Ministerio de Ciencia e Innovacion (MICINN) (SAF2010-21171) to RRG
Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells.
Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development. Cell types and gene expression were generally conserved across species, but with clear differences in cell proliferation, developmental timing, and dopaminergic neuron development. Additionally, we developed a method to quantitatively assess the fidelity of dopaminergic neurons derived from human pluripotent stem cells, at a single-cell level. Thus, our study provides insight into the molecular programs controlling human midbrain development and provides a foundation for the development of cell replacement therapies.All authors were supported by EU FP7 grant DDPDGENES. S.L. was supported by European Research Council grant 261063 (BRAINCELL), Knut and Alice Wallenberg Foundation grant 2015.0041, Swedish Research Council (STARGET), and the Swedish Foundation for Strategic Research (RIF14-0057). A.Z. was supported by the Human Frontier Science Program. E.A. was supported by Swedish Research Council (VR projects: 2011-3116 and 2011-3318), Swedish Foundation for Strategic Research (SRL program), and Karolinska Institutet (SFO Thematic Center in Stem cells and Regenerative Medicine). E.A. and R.A.B. were supported by the EU FP7 grant NeuroStemcellRepair. R.A.B. was also supported by an NIHR Biomedical Research Centre award to the University of Cambridge/Addenbrookes Hospital. iCell dopaminergic neurons were a generous gift from Cellular Dynamics International. Single-cell RNA-seq servic0es were provided by the Eukaryotic Single-cell Genomics facility and the National Genomics Infrastructure at Science for Life Laboratory.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.cell.2016.09.02
Paleofitogeografía de los pinares en las montañas periféricas de la cuenca del Duero
En las dos últimas décadas se han obtenido numerosos resultados procedentes de diferentes trabajos paleobotánicos (Cuaternario final) realizados en los territorios montanos periféricos de la depresión del Duero. Las metodologías empleadas han sido diversas y tienen que ver con los diferentes tipos de yacimientos y de muestras biológicas seleccionadas para su estudio; entre ellas destacan las técnicas de microscopía óptica para la identificación de maderas subfósiles, la morfología comparada de macrorrestos y los estudios dendrocronológicos en árboles longevos y maderas subfósiles. En esta comunicación se reúnen y resumen los trabajos más importantes, haciéndose una síntesis de las conclusiones obtenidas en los trabajos paleofitogeográficos realizados hasta el momento; se hace hincapié en la información proporcionada por los macrorrestos (maderas, estróbilos) así como por la recogida en los registros dendrocronológicos (con extensión a la dendroecología). Otro de los objetivos de la comunicación es la síntesis de las conclusiones obtenidas en los trabajos paleofitogeográficos realizados hasta el momento. Uno de esos resultados es que el comportamiento de los pinares a lo largo del Holoceno presenta diferentes modalidades en cada una de las cordilleras que bordean la cuenca del Duero; desde casos con marcada estabilidad a otros en que se muestran variaciones temporales apreciables (con patrones de heterogeneidad en función de un eje N-S y/o O-E
FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth
The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report that BCa cells are dependent on a mechanism to supply precursors for intracellular lipid production derived from extracellular sources and that the endothelial lipase (LIPG) fulfils this function. LIPG expression allows the import of lipid precursors, thereby contributing to BCa proliferation. LIPG stands out as an essential component of the lipid metabolic adaptations that BCa cells, and not normal tissue, must undergo to support high proliferation rates. LIPG is ubiquitously and highly expressed under the control of FoxA1 or FoxA2 in all BCa subtypes. The downregulation of either LIPG or FoxA in transformed cells results in decreased proliferation and impaired synthesis of intracellular lipids
Clinical Practice Guidelines for Management of Schizophrenia : evaluation Using AGREE II
Introducción
Colombia se encuentra en estos momentos en la realización de guías de práctica clínica para el tratamiento de diversas patologías. Las guías de práctica clínica representan una herramienta al alcance del clínico para la toma de decisiones sobre sus pacientes. En psiquiatría se dispone internacionalmente de práctica clínica para esquizofrenia, no obstante no se dispone de una guía colombiana ni de una apreciación de las guías desarrolladas en el mundo sobre esta patología.
Método
En el marco del desarrollo de la Guía de práctica clínica sobre esquizofrenia para Colombia se realiza una búsqueda sistemática sobre GPC en diversas bases y se evalúan empleando la herramienta AGREE II por parte de 2 personas entrenadas para ello. Se presentan los resultados de esta fase de manera global y por dominios.
Resultados
Se encontraron 164 resultados de posibles guías, de las cuales se evalúan finalmente 7 mediante AGREE II. Por dominios y calificación global la guía realizada por el National Institute for Health and Care Excellence (NICE) obtuvo el mejor puntaje. De las guías evaluadas, únicamente dos eran de América Latina y la mayoría (cuatro) de Europa. Solamente una de las guías evaluadas utilizó el abordaje GRADE para evaluar la calidad de la evidencia y formular las recomendaciones.
Conclusión
La diversidad de guías encontrados sobre esquizofrenia no permite una fácil adopción ni adaptación de alguna guía por el médico psiquiatra de acuerdo con los parámetros que se han planteado para Colombia.Q4Artículo original3-12Introduction
Colombia is developing multiple national practice guidelines from a range of diseases. Clinical practice guidelines represent a very useful tool to be able to take decision over a patient care that is widely available for the clinician. In psychiatry there are a good number of international clinical guidelines for the treatment of schizophrenia nevertheless there is no article that evaluate them scientifically
Methods
In the settings of developing a Colombian schizophrenia practice guideline, a systematic search was performed in multiple databases and the results were then evaluated by two trained persons. We present the results globally and by domains.
Results
We found 164 matches for possible guidelines. After screening 7 guidelines were evaluated with the AGREE II instrument. Globally and by the different domains, the National Institute for Health and Care Excellence (NICE) was the guideline that got the best score. From the guidelines that were reviewed, 4 were from Europe and only 2 were from Latin America. None of the guidelines used GRADE methodology for the recommendations.
Conclusion
The diversity of the schizophrenia treatment guidelines does not allow an easy adoption of the recommendation by a psychiatrist in Colombia
Vitamin E delivery systems increase resistance to oxidative stress in red deer sperm cells: hydrogel and nanoemulsion carriers
This article belongs to the Special Issue Nanoantioxidants.Oxidative stress has become a major concern in the field of spermatology, and one of the possible solutions to this acute problem would be the use of antioxidant protection; however, more studies are required in this field, as highly contradictory results regarding the addition of antioxidants have been obtained. Vitamin E is a powerful biological antioxidant, but its low stability and high hydrophobicity limit its application in spermatology, making the use of organic solvents necessary, which renders spermatozoa practically motionless. Keeping this in mind, we propose the use of hydrogels (HVEs) and nanoemulsions (NVEs), alone or in combination, as carriers for the controlled release of vitamin E, thus, improving its solubility and stability and preventing oxidative stress in sperm cells. Cryopreserved sperm from six stags was thawed and extended to 30 × 106 sperm/mL in Bovine Gamete Medium (BGM). Once aliquoted, the samples were incubated as follows: control, free vitamin E (1 mM), NVEs (9 mM), HVEs (1 mM), and the combination of HVEs and NVEs (H + N), with or without induced oxidative stress (100 µM Fe2+/ascorbate). The different treatments were analyzed after 0, 2, 5, and 24 h of incubation at 37 °C. Motility (CASA®), viability (YO-PRO-1/IP), mitochondrial membrane potential (Mitotracker Deep Red 633), lipid peroxidation (C11 BODIPY 581/591), intracellular reactive oxygen species production (CM-H2DCFDA), and DNA status (SCSA®) were assessed. Our results show that the deleterious effects of exogenous oxidative stress were prevented by the vitamin E-loaded carriers proposed, while the kinematic sperm parameters (p ˂ 0.05) and sperm viability were always preserved. Moreover, the vitamin E formulations maintained and preserved mitochondrial activity, prevented sperm lipid peroxidation, and decreased reactive oxygen species (ROS) production (p ˂ 0.05) under oxidative stress conditions. Vitamin E formulations were significantly different as regards the free vitamin E samples (p < 0.001), whose sperm kinematic parameters drastically decreased. This is the first time that vitamin E has been formulated as hydrogels. This new formulation could be highly relevant for sperm physiology preservation, signifying an excellent approach against sperm oxidative damage.Grants AGL2017-85603-P, PID2020-120281RB-I00 and PID2020-117788RB-I00 funded by MCIN/AEI/10.13039/501100011033 and, as appropriate, by ERDF A way of making Europe, by the European Union or by the European Union NextGenerationEU/PRTR. A.J.-C. was supported by a UCLM scholarship and P.J.S.-M was supported by a JCCM scholarship.Peer reviewe
The genomic history of the Iberian Peninsula over the past 8000 years
We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula.We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming.We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry.We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean
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