La poesía desde la oralidad: una propuesta didáctica para secundaria

En el presente trabajo final de máster se plasma una investigación didáctica y una propuesta de intervención sobre la enseñanza del género lírico en el marco del desarrollo de la competencia literaria y con especial atención al desarrollo de la competencia de comunicación oral en la etapa de educación secundaria. La finalidad de este proyecto es mejorar y desarrollar estrategias didácticas que potencien estas competencias. Para tratar el tema se han llevado a cabo tres actividades de investigación: un cuestionario para el profesorado de la materia de Lengua, de cara a conocer así su visión sobre estos ámbitos; el análisis de los escritos producidos por los alumnos, y, por último, el diseño y desarrollo curricular de una propuesta didáctica innovadora. Estas actividades están diseñadas para un grupo de 4º ESO, y se pretende innovar en el proceso de enseñanza y aprendizaje tanto de la competencia oral como en el de la didáctica de la poesía. Para ello, además de tener en cuenta un canon de tipo clásico, atendiendo a los criterios de actualidad y de competencia emocional, se introduce el ámbito musical, la música rap, como forma innovadora y vehículo para la enseñanza del género lírico. Los resultados ponen de manifiesto la dificultad de enseñanza en este campo así como la relevancia de facilitar la aproximación de los adolescentes a la poesía mediante estrategias más participativas e innovadoras.<br /

Functional specialization of different PI3K isoforms for the control of neuronal architecture, synaptic plasticity, and cognition

Neuronal connectivity and activity-dependent synaptic plasticity are fundamental properties that support brain function and cognitive performance. Phosphatidylinositol 3-kinase (PI3K) intracellular signaling controls multiple mechanisms mediating neuronal growth, synaptic structure, and plasticity. However, it is still unclear how these pleiotropic functions are integrated at molecular and cellular levels. To address this issue, we used neuron-specific virally delivered Cre expression to delete either p110α or p110β (the two major catalytic isoforms of type I PI3K) from the hippocampus of adult mice. We found that dendritic and postsynaptic structures are almost exclusively supported by p110α activity, whereas p110β controls neurotransmitter release and metabotropic glutamate receptor–dependent long-term depression at the presynaptic terminal. In addition to these separate functions, p110α and p110β jointly contribute to N-methyl-d-aspartate receptor–dependent postsynaptic long-term potentiation. This molecular and functional specialization is reflected in different proteomes controlled by each isoform and in distinct behavioral alterations for learning/memory and sociability in mice lacking p110α or p110β.This work was supported by the Spanish Ministry of Science and Innovation grants SAF2017-86983-R and PID2020-117651RB (to J.A.E.), Spanish Ministry of Science and Innovation grants SAF2017-89116R-P (FEDER/EU) and PID2020-116184RB (to M.G.), Carlos III Institute of Health-Fondo de Investigación Sanitaria grant PRB3 (IPT17/0019–ISCIII-SGEFI/ERDF, ProteoRed) and CIBERCV (to J.A.L.), Spanish Ministry of Economy postdoctoral contract IJCI-2015-25507 (to M.I.C.), Marie Curie cofund UAM-UE (EU project 713366) Intertalentum Postdoctoral Program (to V.B.), and Spanish Ministry of Science and Innovation predoctoral contracts (to C.S.-C., A.F.-R., and S.L.-G.). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033)

HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy

The role of HCV on the HIV reservoir is controversial since the reduction on HIV-DNA levels after HCV eradication with IFNα/RBV treatment seems to be the result of drugs instead of HCV clearance. We assessed whether HCV eradication can decrease HIV-DNA content in HIV/HCV-coinfected patients treated with direct-acting antivirals, DAAs (IFNα/RBV-free regimens). Cell-associated HIV-DNA was measured by ddPCR in 25 HIV-monoinfected and 25 HIV/HCV-coinfected patients. There were no differences in HIV-DNA levels between groups neither at baseline nor at 12 weeks after DAAs treatment completion. Our results indicate that HCV does not appear to influence the HIV reservoir size and suggest the lack of an anti-HIV action for DAAs.This work was supported by projects PI14/00518, RD16/0025/0013 integrated into the State Plan for Scientific and Technical Research and Innovation from the General Sub-Directorate for research assessment and promotion, Spanish Carlos III Institute of Health (ISCIII) co-funded by the European Regional Development Fund (ERDF). Maria A Navarrete-Muñoz was funded by the Spanish Directorate General for Research and Technological of the “Comunidad de Madrid” [grant: IND2018/BMD9651]. Norma Rallón is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III [grant: CPII19/00025].S

Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors

Impaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may contribute to take up this drug. The aim of this study was to investigate whether OCT3 could contribute to the uptake of sorafenib and other tyrosine kinase inhibitors (TKIs) and whether OCT3 determination can predict HCC response to sorafenib. Cells overexpressing OCT3 were used to determine the ability of this carrier to transport sorafenib. Immunostaining of OCT3 was performed in HCC samples obtained in the TRANSFER study. Considering the intensity of staining and the number of OCT3-positive cells, tumors were classified as having absent, weak, moderate, or strong OCT3 expression and were also categorized according to the presence or absence of PM staining. Functional in vitro studies revealed that OCT3 is also able to mediate sorafenib uptake. Other TKIs, such as regorafenib, lenvatinib, and cabozantinib can also interact with this transporter. In silico studies suggested that the expression of OCT3 is better preserved in HCC than that of OCT1. In HCC samples, OCT3 was expressed at the PM of cancer cells, and its presence, detected in 26% of tumors, was associated with better outcomes in patients treated with sorafenib. In conclusion, analysis by immunohistochemistry of OCT3 in the PM of tumor cells may help to predict the response of HCC patients to sorafenib and potentially to other TKIs.Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III Junta de Castilla y Leo

Proton Radiographs Using Position-Sensitive Silicon Detectors and High-Resolution Scintillators

7 pags., 11 figs., 1 tab.Proton therapy is a cancer treatment technique currently in growth since it offers advantages with respect to conventional X-ray and ¿ -ray radiotherapy. In particular, better control of the dose deposition allowing to reach higher conformity in the treatments causing less secondary effects. However, in order to take full advantage of its potential, improvements in treatment planning and dose verification are required. A new prototype of proton computed tomography scanner is proposed to design more accurate and precise treatment plans for proton therapy. Our prototype is formed by double-sided silicon strip detectors and scintillators of LaBr3(Ce) with high energy resolution and fast response. Here, the results obtained from an experiment performed using a 100-MeV proton beam are presented. Proton radiographs of polymethyl methacrylate (PMMA) samples of 50-mm thickness with spatial patterns in aluminum were taken. Their properties were studied, including reproduction of the dimensions, spatial resolution, and sensitivity to different materials. Structures of up to 2 mm are well resolved and the sensitivity of the system was enough to distinguish the thicknesses of 10 mm of aluminum or PMMA. The spatial resolution of the images was 0.3 line pairs per mm (MTF-10%). This constitutes the first step to validate the device as a proton radiography scanner.This work has been supported by the PRONTO-CM B2017/BMD-3888 project funded by Comunidad de Madrid (Spain). The research leading to these results has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 654002 (ENSAR2) and grant agreement No [730983] (INSPIRE). This work has been partly supported by the Spanish Funding Agency for Research (AEI) through the PID2019-104390GBI00 and PID2019-104714GB-C21 projects. A.N. Nerio acknowledges the fundings from the Erasmus Mundus Joint Master Degree on Nuclear Physics co-funded by the Erasmus+Programme of the European Union

Desarrollo de herramientas docentes y materiales prácticos para la enseñanza virtual de asignaturas de Fisiología Humana para alumnos de Grado y Máster

Memoria ID-139. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

Beta-delayed proton emission from ²¹Mg

16 pags.; 9 figs.; 6 tabs.© 2015, SIF, Springer-Verlag Berlin Heidelberg. Beta-delayed proton emission from 21Mg has been measured at ISOLDE, CERN, with a detection setup consisting of two charged-particle telescopes surrounding the decay point. Altogether 27 βp branches were measured with center-of-mass energies between 0.4–7.2 MeV. Seven new βp branches were observed. Beta-delayed protons were used to determine the half-life of 21Mg as 118.6 ± 0.5 ms. From a line shape fit of the βp branches we extract the widths, spins, and parities of the resonances of 21Na. An improved interpretation of the decay scheme in accordance with the results obtained in reaction studies is presented.This work has been supported by the European Commision within the Seventh Framework Programme “European Nuclear Science and Applications Research”, contract no. 262010 (ENSAR), and by the Spanish research agency under number FPA2012-32443.Peer Reviewe

Desarrollo de herramientas para mejorar la calidad del Programa de Doctorado en Fisiopatología y Farmacología

Memoria ID2022-203 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control

Producción CientíficaThe mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214-1 and CC214-2. In vitro studies confirmed the superior ability of CC214-1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214-1 was more efficient in inhibiting na€ıve T cell activation and the expression of Tcell activation markers. In addition, CC214-1 induced specific tolerance against alloantigens, while preserving anti-cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214-2 significantly improved mice survival and decreased GvHD-induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214-1 on T lymphocytes and illustrates the role of CC214-2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.Gerencia Regional de Salud de Castilla y León (Proyecto GRS 726/A13

Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly

De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancementRamon y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723)Peer reviewe