977 research outputs found

    Las matemáticas a través de la robótica y programación en educación infantil

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    Una de las tendencias de la innovación educativa hoy en día, es la inclusión de la robótica y los inicios de la programación en las aulas, incluso desde Educación Infantil. Después de indagar en las posibilidades y los beneficios para el aprendizaje de nuestros alumnos y alumnas, se ha planteado una propuesta didáctica de iniciación a estas nuevas disciplinas, en la que se van a destacar los contenidos matemáticos que aparecen en la misma. En esta adaptación de la escuela a la realidad social, además de formación al profesorado y aparatos electrónicos, hay que plantearse cómo aprovechar el contexto, aunque sea adverso. Esta propuesta puede implementarse en cualquier aula de infantil. <br /

    The multifaceted roles of gasdermins in cancer biology and oncologic therapies

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    The involvement of the Gasdermin (GSDM) protein family in cancer and other pathologies is one of the hottest topics in biomedical research. There are six GSDMs in humans (GSDMA, B, C, D, GSDME/DFNA5 and PJVK/DFNB59) and, except PJVK, they can trigger cell death mostly by pyroptosis (a form of lytic and pro-inflammatory cell death) but also other mechanisms. The exact role of GSDMs in cancer is intricate, since depending on the biological context, these proteins have diverse cell-death dependent and independent functions, exhibit either pro-tumor or anti-tumor functions, and promote either sensitization or resistance to oncologic treatments. In this review we provide a comprehensive overview on the multifaceted roles of the GSDMs in cancer, and we critically discuss the possibilities of exploiting GSDM functions as determinants of anti-cancer treatment and as novel therapeutic targets, with special emphasis on innovative GSDM-directed nano-therapies. Finally, we discuss the issues to be resolved before GSDM-mediated oncologic therapies became a reality at the clinical levelThis study was supported by the Ministerio de Ciencia e Innovaci´on (PID2019-104644RB-I00 -GMB-), the Instituto de Salud Carlos III (CIBERONC, CB16/12/00295 –GMB-; partly supported by FEDER funds) and by the Fundaci´on Científica de la AECC (FC_AECC PROYE19036MOR -GMB-

    The multifaceted roles of gasdermins in cancer biology and oncologic therapies

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    The involvement of the Gasdermin (GSDM) protein family in cancer and other pathologies is one of the hottest topics in biomedical research. There are six GSDMs in humans (GSDMA, B, C, D, GSDME/DFNA5 and PJVK/ DFNB59) and, except PJVK, they can trigger cell death mostly by pyroptosis (a form of lytic and proinflammatory cell death) but also other mechanisms. The exact role of GSDMs in cancer is intricate, since depending on the biological context, these proteins have diverse cell-death dependent and independent functions, exhibit either pro-tumor or anti-tumor functions, and promote either sensitization or resistance to oncologic treatments. In this review we provide a comprehensive overview on the multifaceted roles of the GSDMs in cancer, and we critically discuss the possibilities of exploiting GSDM functions as determinants of anti-cancer treatment and as novel therapeutic targets, with special emphasis on innovative GSDM-directed nano-therapies. Finally, we discuss the issues to be resolved before GSDM-mediated oncologic therapies became a reality at the clinical level.This study was supported by the Ministerio de Ciencia e Innovación (PID2019-104644RB-I00 -GMB-), the Instituto de Salud Carlos III (CIBERONC, CB16/12/00295 –GMB-; partly supported by FEDER funds) and by the Fundación Científica de la AECC (FC_AECC PROYE19036MOR -GMB-).S

    Evaluation of surrounding ring of two different extrashort implants design in crestal bone maintanence: A histologic study in dogs.

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    This is the peer reviewed versión of the following article : " Evaluation of surrounding ring of two different extrashort implants design in crestal bone maintanence: A histologic study in dogs.", which has been published in final form at " FOR PEER REVIEW (DOI)". This article May be used for non-comercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."Odontologí

    Tracing the spatial imprint of Oldowan technological behaviors: A view from DS (Bed I, Olduvai Gorge, Tanzania)

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    DS (David’s site) is one of the new archaeological sites documented in the same paleolandscape in which FLK 22 was deposited at about 1.85 Ma in Olduvai Gorge. Fieldwork in DS has unearthed the largest vertically-discrete archaeological horizon in the African Pleistocene, where a multi-cluster anthropogenic accumulation of fossil bones and stone tools has been identified. In this work we present the results of the techno-economic study of the lithic assemblage recovered from DS. We also explore the spatial magnitude of the technological behaviors documented at this spot using powerful spatial statistical tools to unravel correlations between the spatial distributional patterns of lithic categories. At DS, lavas and quartzite were involved in different technological processes. Volcanic materials, probably transported to this spot from a close source, were introduced in large numbers, including unmodified materials, and used in percussion activities and in a wide variety of reduction strategies. A number of volcanic products were subject to outward fluxes to other parts of the paleolandscape. In contrast, quartzite rocks were introduced in smaller numbers and might have been subject to a significantly more intense exploitation. The intra-site spatial analysis has shown that specialized areas cannot be identified, unmodified materials are not randomly distributed, percussion and knapping categories do not spatially overlap, while bipolar specimens show some sort of spatial correlation with percussion activities

    The Origin of The Acheulean: The 1.7 Million-Year-Old Site of FLK West, Olduvai Gorge (Tanzania)

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    The appearance of the acheulean is one of the hallmarks of human evolution. It represents the emergence of a complex behavior, expressed in the recurrent manufacture of large-sized tools, with standardized forms, implying more advance forethought and planning by hominins than those required by the precedent Oldowan technology. The earliest known evidence of this technology dates back to c. 1.7 Ma. and is limited to two sites (Kokiselei [Kenya] and Konso [Ethiopia]), both of which lack functionally-associated fauna. The functionality of these earliest Acheulean assemblages remains unknown. Here we present the discovery of another early Acheulean site also dating to c. 1.7 Ma from Olduvai Gorge. This site provides evidence of the earliest steps in developing the Acheulean technology and is the oldest acheulean site in which stone tools occur spatially and functionally associated with the exploitation of fauna. Simple and elaborate large-cutting tools (LCT) and bifacial handaxes co-exist at FLK West, showing that complex cognition was present from the earliest stages of the acheulean. Here we provide a detailed technological study and evidence of the use of these tools on the butchery and consumption of fauna, probably by early Homo erectus sensu lato

    Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation

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    Gasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors. Different in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples. GSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers. Our findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome. The online version contains supplementary material available at 10.1186/s13046-022-02497-w

    Cartografía crítica de recursos educativos y pedagógicos en instituciones y entidades culturales del ámbito de las artes visuales en la Comunidad de Madrid como herramienta para la formación del profesorado

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    Investigar recursos educativos y pedagógicos en los museos y salas de arte de la Comunidad de Madrid, y establecer como estrategias de acercamiento institucional Educación/Arte para desarrollar un recurso on line disponible en la web, destinado especialmente a la formación de profesorado y estudiantes de arte interesados en educación para creación de una comunidad de aprendizaje

    Novel regulatory mechanism of establishment genes of conjugative plasmids

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    The principal route for dissemination of antibiotic resistance genes is conjugation by which a conjugative DNA element is transferred from a donor to a recipient cell. Conjugative elements contain genes that are important for their establishment in the new host, for instance by counteracting the host defense mechanisms acting against incoming foreign DNA. Little is known about these establishment genes and how they are regulated. Here, we deciphered the regulation mechanism of possible establishment genes of plasmid p576 from the Gram-positive bacterium Bacillus pumilus. Unlike the ssDNA promoters described for some conjugative plasmids, the four promoters of these p576 genes are repressed by a repressor protein, which we named Reg. Reg also regulates its own expression. After transfer of the DNA, these genes are de-repressed for a period of time until sufficient Reg is synthesized to repress the promoters again. Complementary in vivo and in vitro analyses showed that different operator configurations in the promoter regions of these genes lead to different responses to Reg. Each operator is bound with extreme cooperativity by two Regdimers. The X-ray structure revealed that Reg has a Ribbon-Helix-Helix core and provided important insights into the high cooperativity of DNA recognition

    European Journalism Observatory- a platform for training and professional networks in the Faculty of Information Sciences

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    The launching of a Spanish platform within the Observatory will serve as a training laboratory for undergraduate and graduate students of the Faculty of Information Sciences at the same time as for establishing a professional media network in and outside Spain. The European Journalism Observatory (EJO) is a network of 14 non-profit media research institutes in 11 countries where Spain continue to be the missing element. All researchers in the EJO network actively strive to transfer their knowledge to the media industry as well as interested publics outside the scientific community, as a platform to enable online availability of at least a portion of many publications in several languages
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