55 research outputs found

    Cortistain is expressed in a distinct subset of cortical interneurons

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    Cortistatin is a presumptive neuropeptide that shares 11 of its 14 amino acids with somatostatin. In contrast to somatostatin, administration of cortistatin into the rat brain ventricles specifically enhances slow wave sleep, apparently by antagonizing the effects of acetylcholine on cortical excitability. Here we show that preprocortistatin mRNA is expressed in a subset of GABAergic cells in the cortex and hippocampus that partially overlap with those containing somatostatin. A significant percentage of cortistatin-positive neurons is also positive for parvalbumin. In contrast, no colocalization was found between cortistatin and calretinin, cholecystokinin, or vasoactive intestinal peptide. During development there is a transient increase in cortistatin-expressing cells in the second postnatal week in all cortical areas and in the dentate gyrus. A transient expression of preprocortistatin mRNA in the hilar region at P16 is paralleled by electrophysiological changes in dentate granule cells. Together, these observations suggest mechanisms by which cortistatin may regulate cortical activity

    Sistema neurodifuso con defuzificación basado en relaciones booleanas (DBR) aplicado a series de tiempo Mackey-Glass

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    This paper presents a Neuro-Fuzzy system with defuzzification based on Boolean relations (DBR) for the prediction of Mackey-Glass chaotic time series. Initially, the Back-propagation training algorithm and use of DBR as a defuzzification method are explained. Later, time series is modeled with sixteen fuzzy If-Then rules, using the technique described. The results show a reduction in training time and computational calculations, compared with conventional Neuro-Fuzzy Networks.En este artículo se presenta un sistema neurodifuso con defuzificación basaba en relaciones booleanas (DBR) para la predicción de la serie de tiempo caótica Mackey-Glass. Inicialmente, se explica el algoritmo de entrenamiento retropropagación y la utilización del DBR como método de defuzificación. Posteriormente, se modela la serie de tiempo con dieciséis reglas difusas Si-Entonces, usando la técnica descrita. Los resultados obtenidos muestran una reducción del tiempo de entrenamiento y cálculo computacional, en comparación con las redes neurodifusas convencionales

    Diseño de un controlador proporcional derivativo difuso para un conversor reductor-elevador empleando el defuzificador basado en relaciones booleanas

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    En este documento se presenta el diseño de un sistema de control para la regulación del voltaje de salida de un conversor de corriente continua del tipo reductor-elevador. En particular para el diseño del controlador se emplea un esquema de control no lineal conocido como defusificador basado en relaciones booleanas. Para el desarrollo del trabajo, en primer lugar se revisa el modelo del conversor evidenciando la no linealidad del sistema. Posteriormente se diseña un controlador proporcional derivativo, el cual incorpora en su arquitectura el defusificador basado en relaciones booleanas. Este controlador es optimizado de acuerdo con el criterio de la integral del error cuadrado ponderado en el tiempo. Los resultados obtenidos en simulación muestran el comportamiento del sistema con el controlador diseñado. Con los resultados se analiza el desempeño del sistema considerando el criterio de optimización y el consumo de potencia

    Imaging the Kirkendall effect in pyrite (FeS2) thin films: cross-sectional microstructure and chemical features

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    This investigation provides novel data on the structure and chemical composition of pyrite thin films and new hints concerning their formation mechanism. From TEM-HAADF data, it has been found that the films are composed of two different layers: one is very compact and the other one is quite porous with many voids separating a few groups of grains. This porous layer is always in direct contact with the substrate, and its thickness is quite similar to that of the original Fe film. The average size of pyrite grains is equal in both layers, what suggests that the same process is responsible for their formation. Concentration profiles of sulfur, iron and some impurities (mainly sodium and oxygen from the glass substrate) through both layers are given in this work, and thus chemical inhomogeneities of the films are proved by the obtained stoichiometric ratios (S/Fe). Moreover, Na from sodalime glass substrates mainly accumulates at the pyrite grain boundaries and barely dopes them. The obtained results support the hypothesis that the iron sulfuration process essentially induces the diffusion of iron atoms, what leads to the porous layer formation as a manifestation of the Kirkendall Effect. Therefore, it seems that the same mechanisms that operate in the synthesis of surface hollow structures at the nanoscale are also active in the formation of pyrite thin films ranging from several tens to hundreds of nanometersMembers of MIRE Group acknowledge the financial support of the Spanish MICINN under project RTI2018-099794-B-I00. E. Flores acknowledges the intramural CSIC project 2D-MeSes funding and the service from the MiNa Laboratory at IMN, and funding from CM (project SpaceTec, S2013/ICE2822), MINECO (project CSIC13-4E1794) and EU (FEDER,FSE). Financial support through the project UMA18-FEDERJA-041 is gratefully acknowledge

    A Roadmap until 2030 and first action plan for the Peruvian agri-food sector, focusing on Andean native crops : results from the 3rd and 4th Futures Workshops of the Pecolo Project

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    PECOLO, or Native crops for sustainable and innovative food futures in Peru and Colombia, was a collaborative project involving the University of Turku, Finland (UTU), Universidad Nacional Agraria La Molina, Peru (UNALM) and Universidad el Bosque, Colombia (UEB). From UTU, Finland Futures Research Centre (FFRC) coordinated the project. In addition, the Functional Foods Forum and Department of Biochemistry of the University of Turku were also participating in the project. One of the key focus areas of the PECOLO project was the development of innovation environments around native Andean crops. Futures research and foresight methodologies were used as novel tools for developing innovation environments in cooperation with academic, public and private sector organizations and NGOs. This is the second of two publications concerning Peru that have been produced based on the results of the PECOLO project’s four-stage futures process. The first, A Scenario for the Desirable Future of the Peruvian Agri-Food Sector 2030, Focusing on Andean Native Crops: Results from the 1st and 2nd Futures Workshops of the PECOLO Project , describes the methods and results of the first two steps of the futures process. The outcome was a futures table describing a set of three alternative futures for the Peruvian agri-food sector that reconsider the potential of Andean crops, as well as a scenario narrative for the most desirable future. This second publication covers the work that took place during the project’s third and fourth futures workshops. The third workshop established a vision for 2030 based on the desirable scenario of the second workshop, and a roadmap for the Peruvian agri-food sector with a special focus on Andean native crops. The fourth and final workshop elaborated concrete actions that can and should be taken by stakeholders in the first implementation period, from 2020–2022, in order to begin to move toward these common goals. The PECOLO project was funded by the Ministry for Foreign Affairs of Finland between 2017–2019 under the HEI-ICI Programme (Higher Education Institutions – Institutional Capacity-building Instrument)

    A Scenario for the desirable future of the Peruvian agrifood sector 2030, focusing on Andean native crops : results from the 1st and 2nd futures workshops of the PECOLO project

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    The Andean region is exceptionally rich in biodiversity, harbouring an important centre of domestication of global food crops, such as potato, quinoa, corn, peanut and tomato. Such biodiversity provides a great potential to discover or, reintroduce, nutritionally rich local varieties and utilize them to develop innovative food applications. Utilization of native plant crops provide promising solutions to address the wider sustainability goals, such as rediscovering crops more resilient to the changing climate and providing local source of nutritious food. Diversification of the local diets with local grains enables better nutrition and can also contribute to food security in areas where food production is threatened by climate change. ‘Native crops for sustainable and innovative food futures in Peru and Colombia (PECOLO)’ is a collabo-ration project between University of Turku, Finland (UTU), Universidad Nacional Agraria La Molina, Peru (UNALM) and Universidad el Bosque, Colombia (UEB). From UTU, Finland Futures Research Centre (FFRC) of University of Turku coordinates the project. In addition, Functional Foods Forum and Department of Biochemistry of University of Turku participate in the project. The PECOLO project has a special focus on the development of innovation environments around Andean native crops. Futures research and foresight methodologies are used as novel tools for developing innovation environments in cooperation with academic, public and private sector organizations and NGOs. In addition to the development of innovation environments, the project has capacity-building and mobility components in specialized topics in food science such as nutrition and functional foods, and in sustainability issues along the food value chain, such as environmental impacts of food production, sustainable diets and food waste and loss. This publication is the first of the two publications for Peru that will be published as an outcome of the PECOLO project’s four step futures process around Andean native crops. The publication covers the methods and the results of the 1st workshop, which focused on horizon scanning of the current state of the agri-food sector, as well as the methods and the results of the 2nd workshop, which focused on development of scenarios for the Peruvian agri-food sector with a special focus on Andean native crops. The second PECOLO publication (published later in 2019) will present the roadmaps and action plans for the agri-food sector stakeholders in Peru and Colombia

    Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

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    Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

    A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility.

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    Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18-4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene.A.O. is partially funded by FIS PI19/00640 supported by FEDER funds and the Spanish Network on Rare Diseases (CIBERER). M.d.l.H. is partially funded by FIS PI20/00110 supported by FEDER funds.S
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