Papel de la proteína Bex-3 en la ubiquitinación del receptor TrkA

Trabajo de Fin de Máster del Máster en Neurociencias, curso 2008-2009.[ES]El presente trabajo trata del papel de la proteína Bex-3 en la ubiquitinación del receptor TrkA[EN]This paper studies the role of Bex protein-3 in the TrkA receptor ubiquitinatio

Enhanced TrkA signaling impairs basal forebrain-dependent behavior

Basal forebrain cholinergic neurons (BFCNs) modulate cognitive functions such as attention, learning and memory. The NGF/TrkA pathway plays an important role in the development and function of BFCNs, although two mouse models conditionally deleting TrkA expression in the central nervous system (CNS) have shown contradictory results. To shed light into this discrepancy, we used a mouse model with a gain-of-function in TrkA receptor signaling. Our results indicate that enhanced TrkA signaling did not alter hippocampal cholinergic innervation, general locomotion or anxiety-related behaviors, but it increases ChAT expression, the number of cholinergic neurons at early postnatal stages and, mutant mice showed impaired motor learning and memory functions. These data demonstrate that proper functioning of the cholinergic system in CNS requires a balanced NGF/TrkA signaling

Evaluación de una intervención de Aprendizaje-Servicio en Educación Musical en la formación de profesorado

El Aprendizaje-Servicio (ApS) es una metodología innovadora en el ámbito educativo que combina el aprendizaje de una materia con la puesta en práctica de los conocimientos a través de la realización de un servicio a la comunidad. Debido a la importancia del ApS este trabajo pretende evaluar un programa de intervención con esta metodología en Educación Musical, en la formación de profesorado. Para ello, se plantea una investigación evaluativa, en la que se comparan los resultados de un grupo control y experimental, seleccionando una muestra total de 93 estudiantes universitarios a los que se les pasa un cuestionario de estrategias de aprendizaje y otro de evaluación de conocimientos musicales, así mismo se comparan las notas finales de ambos grupos. Los resultados reflejan que, partiendo de grupos equivalentes, en las variables de interés existe una mejora en el grupo experimental en la escala de estrategias afectivas, de apoyo y control, así como en las subescalas de componentes afectivos, estrategias de control, tras la aplicación de la intervención. También, se encontraron diferencias significativas en el aprendizaje, a favor del grupo que realizó la intervención. Se recomienda la realización de nuevas investigaciones con ApS en esta y otras áreas para afianzar los resultados y observar la efectividad de esta metodologí

Caracterización Proteómica in vivo de células endoteliales circulantes y células progenitoras de endoteliales an pacientes con síndrome coronario agudo

Comunicaciones a congreso

Nitro-oleic acid regulates T cell activation through post-translational modification of calcineurin

Nitro-fatty acids (NO2-FAs) are unsaturated fatty acid nitration products that exhibit anti-inflammatory actions in experimental mouse models of autoimmune and allergic diseases. These electrophilic molecules interfere with intracellular signaling pathways by reversible post-translational modification of nucleophilic amino-acid residues. Several regulatory proteins have been identified as targets of NO2-FAs, modifying their activity and promoting gene expression changes that result in anti-inflammatory effects. Herein, we report the effects of nitro-oleic acid (NO2-OA) on pro-inflammatory T cell functions, showing that 9- and 10-NOA, but not their oleic acid precursor, decrease T cell proliferation, expression of activation markers CD25 and CD71 on the plasma membrane, and IL-2, IL-4, and IFN-γ cytokine gene expressions. Moreover, we have found that NO2-OA inhibits the transcriptional activity of nuclear factor of activated T cells (NFAT) and that this inhibition takes place through the regulation of the phosphatase activity of calcineurin (CaN), hindering NFAT dephosphorylation, and nuclear translocation in activated T cells. Finally, using mass spectrometry-based approaches, we have found that NO2-OA nitroalkylates CaNA on four Cys (Cys129, 228, 266, and 372), of which only nitroalkylation on Cys372 was of importance for the regulation of CaN phosphatase activity in cells, disturbing functional CaNA/CaNB heterodimer formation. These results provide evidence for an additional mechanism by which NO2-FAs exert their anti-inflammatory actions, pointing to their potential as therapeutic bioactive lipids for the modulation of harmful T cell-mediated immune response

Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential : a molecular and clinicopathological study

Background: The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas. Methods: We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis. Results: Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported. Conclusions: Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions

More, smaller bacteria in response to ocean's warming?

Heterotrophic bacteria play a major role in organic matter cycling in the ocean. Although the high abundances and relatively fast growth rates of coastal surface bacterioplankton make them suitable sentinels of global change, past analyses have largely overlooked this functional group. Here, time series analysis of a decade of monthly observations in temperate Atlantic coastal waters revealed strong seasonal patterns in the abundance, size and biomass of the ubiquitous flow-cytometric groups of low (LNA) and high nucleic acid (HNA) content bacteria. Over this relatively short period, we also found that bacterioplankton cells were significantly smaller, a trend that is consistent with the hypothesized temperature-driven decrease in body size. Although decadal cell shrinking was observed for both groups, it was only LNA cells that were strongly coherent, with ecological theories linking temperature, abundance and individual size on both the seasonal and interannual scale. We explain this finding because, relative to their HNA counterparts, marine LNA bacteria are less diverse, dominated by members of the SAR11 clade. Temperature manipulation experiments in 2012 confirmed a direct effect of warming on bacterial size. Concurrent with rising temperatures in spring, significant decadal trends of increasing standing stocks (3% per year) accompanied by decreasing mean cell size (-1% per year) suggest a major shift in community structure, with a larger contribution of LNA bacteria to total biomass. The increasing prevalence of these typically oligotrophic taxa may severely impact marine food webs and carbon fluxes by an overall decrease in the efficiency of the biological pump.Versión del editor5,064

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP.

Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanoresponse of Imp7 by forming a YAP/Imp7 complex that responds to mechanical cues through the Hippo kinases MST1/2. Furthermore, YAP behaves as a dominant cargo of Imp7, restricting the Imp7 binding and the nuclear translocation of other Imp7 cargoes such as Smad3 and Erk2. Thus, the nuclear import process is an additional regulatory layer indirectly regulated by mechanical cues, which activate a preferential Imp7 cargo, YAP, which competes out other cargoes, resulting in signaling crosstalk.We thank Miguel Sánchez for text editing. We thank Erika R. Geisbrecht, Kenneth Irvine, and Ariberto Fassati for kindly providing reagents. This study was supported by grants from the Spanish Ministry of Science and Innovation (MICIIN)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (ARDF/FEDER) “A way to make Europe” (PID2020-118658RB-I00, SAF2017-83130-R, IGP-SO grant MINSEV1512-07-2016, CSD2009-0016 and BFU2016-81912-REDC), Comunidad Autónoma de Madrid (Tec4Bio-CM, S2018/NMT¬4443), Fundació La Marató de TV3 (201936-30-31), “La Caixa” Foundation (HR20-00075) and AECC (PROYE20089DELP) all to M.A.d.P. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 641639. M.G.G. and L.S. are sponsored by FPU fellowships (FPU15/ 03776 and FPU18/05394, respectively). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MICIIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence CEX2020- 001041-S.S

Moving music, moving through music

Este proyecto pretende acercar la música en vivo a pacientes infantiles hospitalizados, a través de alumnado universitario de los grados de Maestro en Educación Infantil/Primaria, de la Facultad de Educación de la UCM. Con ello, se pretende aportar bienestar a niños y familias, así como desarrollar competencias éticas y cívicas en los alumnos universitarios y desarrollar el patrimonio musical español a través de actividades musicales diseñadas en las clases. El proyecto formará parte de la actividad docente reglada de una de las asignaturas del quinto semestre del Grado de Maestro en Educación Infantil de la UCM que se impartirá durante el primer cuatrimestre del curso académico 2019-2020. La evaluación incluirá indicadores y técnicas de recolección de datos cuantitativos y cualitativos y medirá también el impacto de los beneficiarios del servicio, como familias y personal sanitario, contribuyendo así a una evaluación más holística. La difusión de la experiencia se hará durante y después del proyecto, en congresos y jornadas académicas a través de videos que representen la experiencia vivida por los estudiantes, profesores y los beneficiarios del servicio, así como a través de publicaciones de artículos en revistas científicas internacionales. Se considera que el presente proyecto supondrá un beneficio y aprendizaje doble tanto para las familias y niños, como para los estudiantes universitarios, ya que se espera que se produzca un crecimiento tanto personal como formativo como consecuencias de las vivencias experimentadas a lo largo del proyecto

An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004–2020)

Objectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004–2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all firstblood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008–2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillin-resistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend.This research was supported by CIBER—Consorcio Centro de Investigación Biomédica en Red (CB21/13/00095, CB21/13/00006, CB21/13/00054, CB21/13/00068, CB21/13/00084, CB21/13/00099 groups of CIBERINFEC; CB06/06/0058 group of CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU. This research was also supported by Personalized and precision medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), and by the Antibiotic Resistance and Staphylococcus aureus Surveillance Programs of the National Center for Microbiology, Instituto de Salud Carlos III.S