5 research outputs found

    Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams

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    The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for "printing" memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval

    PDA-Based Glyconanomicelles for Hepatocellular Carcinoma Cells Active Targeting Via Mannose and Asialoglycoprotein Receptors

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    Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the fourth most common cause of cancer-related mortality worldwide. Sorafenib is the first-line molecular therapy for patients in an advanced stage of HCC. However, the recommended clinical dose of Sorafenib is associated with several complications, which derive from its lack of cell specificity and its very low water solubility. To circumvent these drawbacks, in the present study we developed two sugar-coated polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose and asialoglycoprotein receptors (MR and ASGPR, respectively). The strategies allowed the inducement of apoptosis and reduction of cell proliferation at a nanomolar, instead of micromolar, range in liver cancer cells. The study showed that, contrary to literature data, Sorafenib included into the pMicMan (Man = mannose) vector (targeting MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR). Indeed, pMicMan increased the endosomal incorporation with an increased intracellular Sorafenib concentration that induced apoptosis and reduced cell proliferation at a low concentration range (10-20 nM).Financial support was provided by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78580-C2-1-R to N.K.) and the Institute of Health Carlos III (ISCIII) (PI13/00021, PI16/00090, and PI19/01266 to J.M.) both cofinanced by the European Regional Development Fund (ERDF) from FEDER and the European Social Fund (ESF), as well by the Andalusian Ministry of Economy, Science and Innovation (P07-FQM-2774 to N.K., CV20-04221 to N.K. P20_00882 to N.K. and CTS-6264 to J.M.), the PAIDI Program from the Andalusian Government (FQM-313 to N.K., CV20-04221 to N.K., P20_00882 to N.K., P20_00882 to N.K., and CTS-0664 to J.M.), the Andalusian Ministry of Health (PI-00025-2013, and PI-0198-2016 to J.M.), and the CSIC (CSIC–COV19-047). We thank the Biomedical Research Network Center for Liver and Digestive Diseases founded by the ISCIII and cofinanced by FEDER “A way to achieve Europe” and ERDF for their financial support. The COST action CA-18132 “Functional Glyconanomaterials for the Development of Diagnostic and Targeted Therapeutic Probe” is also acknowledged. E.R.B., C.C.A., and P. de la C.-O. were supported by FPU predoctoral fellowship (FPU15/04267, FPU17/00190, and FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E.N.-V. was supported by the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii.Peer reviewe

    Revolution: Museo de las estrellas un paseo por la fama : Hollywood

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    Convocatoria proyectos de innovación de Extremadura 2020/2021Se describe un proyecto llevado a cabo entre 13 centros educativos extremeños que consistió en desarrollar cinco unidades de trabajo gamificadas, cinco historias detectivescas con misterios por resolver, donde se ponían a prueba las habilidades de lógica, la capacidad de observación, de concentración y de atención de los alumnos. Los objetivos principales de la propuesta fueron: promover la puesta en práctica de proyectos intercentros; impulsar pedagogías activas; desarrollar la competencia digital a través del uso de las pedagogías emergentes lo que ha permitido llevar a cabo una enseñanza presencial, híbrida y virtual y atender a la diversidadExtremaduraES

    Compilación de Proyectos de Investigacion de 1984-2002

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    Instituto Politecnico Nacional. UPIICS
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