68 research outputs found

    CCL2-Expressing Astrocytes Mediate the Extravasation of T Lymphocytes in the Brain. Evidence from Patients with Glioma and Experimental Models In Vivo

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    CCL2 is a chemokine involved in brain inflammation, but the way in which it contributes to the entrance of lymphocytes in the parenchyma is unclear. Imaging of the cell type responsible for this task and details on how the process takes place in vivo remain elusive. Herein, we analyze the cell type that overexpresses CCL2 in multiple scenarios of T-cell infiltration in the brain and in three different species. We observe that CCL2+ astrocytes play a part in the infiltration of T-cells in the brain and our analysis shows that the contact of T-cells with perivascular astrocytes occurs, suggesting that may be an important event for lymphocyte extravasation

    ABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and non-cholesterol sterols

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    Context Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin. Objective The aim of this work was to study the prevalence of ABCG5/G8 genetic variants in mutation-negative FH, as defects in these genes relate to intestinal hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part the mechanism of hypercholesterolemia. Design, setting, and patients We sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls. Surrogate markers of cholesterol absorption (5?-cholestanol, ?-sitosterol, campesterol, stigmasterol, and sitostanol) were quantified by high-performance liquid chromatography?tandem mass spectrometry in both studied groups. Results We found 8 mutation-negative FH patients (3.73%) with a pathogenic mutation in ABCG5/G8 genes. We observed significantly higher concentration of surrogate markers of cholesterol absorption in mutation-negative FH than in controls. In addition, we found significantly higher concentrations of cholesterol absorption markers in mutation-negative FH with ABCG5/G8 defects than in mutation-negative, ABCG5/G8-negative FH. A gene score reflecting the number of common single nucleotide variants associated with hypercholesterolemia was significantly higher in cases than in controls (P = .032). Subjects with a gene score above the mean had significantly higher 5?-cholestanol and stigmasterol than those with a lower gene score. Conclusions Mutation-negative FH subjects accumulate an excess of rare and common gene variations in ABCG5/G8 genes. This variation is associated with increased intestinal absorption of cholesterol, as determined by surrogate makers, suggesting that these loci contribute to hypercholesterolemia by enhancing intestinal cholesterol absorption.This study was supported by grants from the Spanish Ministry of Economy and Competitiveness PI15/01983, PI13/02507, PI12/01321, CIBERCV, CIBEROBN, and Cuenca Villoro Foundation. These projects are co-financed by Instituto de Salud Carlos III and the European Regional Development Fund (ERDF) of the European Union “A way to make Europe.

    Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus study

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    Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ‚Č•3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health

    Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (II). Innovación docente en Filosofía

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    El PIMCD "Precariedad, exclusi√≥n social y diversidad funcional (discapacidad): l√≥gicas y efectos subjetivos del sufrimiento social contempor√°neo (II). Innovaci√≥n docente en Filosof√≠a" se ocupa de conceptos generalmente eludidos por la tradici√≥n te√≥rica (contando como n√ļcleos aglutinantes los de la precariedad laboral, la exclusi√≥n social y diversidad funcional o discapacidad), cuyo an√°lisis propicia nuevas pr√°cticas en la ense√Īanza universitaria de filosof√≠a, adoptando como meta principal el aprendizaje centrado en el estudiantado, el dise√Īo de nuevas herramientas de ense√Īanza y el fomento de una universidad inclusiva. El proyecto cuenta con 26 docentes de la UCM y otros 28 docentes de otras 17 universidades espa√Īolas (UV, UNED, UGR, UNIZAR, UAH, UC3M, UCA, UNIOVI, ULL, EHU/UPV, UA, UAM, Deusto, IFS/CSIC, UCJC, URJC y Univ. Pontificia de Comillas), que permitir√°n dotar a las actividades programadas de un alcance id√≥neo para consolidar la adquisici√≥n de competencias argumentativas y dial√©cticas por parte de lxs estudiantes implicados en el marco de los seminarios previstos. Se integrar√°n en el PIMCD, aparte de PDI, al menos 26 estudiantes de m√°ster y doctorado de la Facultad de Filosof√≠a, a lxs que acompa√Īar√°n durante el desarrollo del PIMCD 4 Alumni de la Facultad de Filosof√≠a de la UCM, actualmente investigadores post-doc y profesorxs de IES, cuya experiencia ser√° beneficiosa para su introducci√≥n en la investigaci√≥n. Asimismo, el equipo cuenta con el apoyo de varixs profesorxs asociadxs, que en algunos casos son tambi√©n profesores de IES. Varixs docentes externos a la UCM participantes en el PIMCD poseen una dilatada experiencia en la coordinaci√≥n de proyectos de innovaci√≥n de otras universidades, lo que redundar√° en beneficio de las actividades a desarrollar. La coordinadora y otrxs miembros del PIMCD pertenecen a la Red de Innovaci√≥n Docente en Filosofia (RIEF), puesta en marcha desde la Universitat de Val√®ncia (http://rief.blogs.uv.es/encuentros-de-la-rief/), a la que mantendremos informada de las actividades realizadas en el proyecto. Asimismo, lxs 6 miembros del PAS permitir√°n difundir debidamente las actividades realizadas en el PIMCD entre lxs estudiantes Erasmus IN del curso 2019/20 en la Facultad de Filosof√≠a, de la misma manera que orientar en las tareas de maquetaci√≥n y edici√≥n que puedan ser necesarias de cara a la publicaci√≥n de lxs resultados del PIMCD y en las tareas de pesquisa bibliogr√°fica necesarias para el desarrollo de los objetivos propuestos. Han manifestado su inter√©s en los resultados derivados del PIMCD editoriales especializadas en la difusi√≥n de investigaciones predoctorales como √Āpeiron y CTK E-Books

    ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider

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    Estudios sobre la detección de luz de centelleo en la TPC de argón líquido ProtoDUNE Dual Phase y su capacidad para el disparo de supernovas en DUNE

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    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física Teórica. Fecha de lectura: 15-12-2021The Deep Underground Neutrino Experiment (DUNE) is a long-baseline neutrino oscillation experiment that aims at addressing key questions in neutrino physics in the next decades. Its scientific program includes the detection of the neutrino flux from a core-collapse supernova. The DUNE far detector will have four 17-kt mass liquid-argon (LAr) time-projection chamber (TPC) modules. ProtoDUNE Dual Phase (DP), a dual-phase LAr TPC with 300 t of active mass and 6 m of drift distance, was operated with cosmic muons in 2019-2020 as part of an R&D program at the CERN Neutrino Platform to demonstrate the feasibility of the technology at such a large scale. In a LAr TPC, the photon detection system (PDS) provides fun- damental timing information and trigger capabilities. The PDS of ProtoDUNE-DP, which consisted of 36 photomultiplier tubes (PMTs), counted on a dedicated light calibration system (LCS) to monitor the PMT response. In this dissertation, the characterization and validation of the ProtoDUNE-DP PDS and LCS components before their installation will be reviewed, highlighting the results of general interest for experiments that use liquid noble gasses as target medium. The results from the stable performance of both systems in the detector during 15 months will be presented next as well as the studies on the scintillation light detection in ProtoDUNE-DP, where the collection of light produced in LAr at 7 m from the photosensors has been achieved for the first time. It is worth pointing out that the excellent LAr purity and the large size of the detector have enabled to develop a unique data-driven investigation on aspects that are critical for LAr- based experiments but that are not completely understood. The analyses cover the characterization of the low-energy background detected by the PDS, the quantification of the electric field impact on the light yield, the evaluation of the Rayleigh scattering affecting the light propagation, and the analysis of the PMT detection efficiency. The effect of the VUV reflectivity of the detector materials will be also discussed. In addition, the estimation of the cosmic muon flux crossing the TPC and the study of the observed light yield by the PDS will be reported. Finally, the results from the simulation-based study of the supernova burst trigger capability with the PDS of a 12.1-kt active mass dual-phase LAr TPC as the one proposed for DUNE will be summarized. Several configurations of reflective foils installed in the TPC to enhance the light collection will be compare

    Studies on the scintillation light detection in the ProtoDUNE Dual Phase liquid-argon TPC and its capability for the supernova trigger in DUNE

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    The Deep Underground Neutrino Experiment (DUNE) is a long-baseline neutrino oscillation experiment that aims at addressing key questions in neutrino physics in the next decades. Its scientific program includes the detection of the neutrino flux from a core-collapse supernova. The DUNE far detector will have four 17-kt mass liquid-argon (LAr) time-projection chamber (TPC) modules. ProtoDUNE Dual Phase (DP), a dual-phase LAr TPC with 300 t of active mass and 6 m of drift distance, was operated with cosmic muons in 2019-2020 as part of an R&D program at the CERN Neutrino Platform to demonstrate the feasibility of the technology at such a large scale. In a LAr TPC, the photon detection system (PDS) provides fundamental timing information and trigger capabilities. The PDS of ProtoDUNE-DP, which consisted of 36 photomultiplier tubes (PMTs), counted on a dedicated light calibration system (LCS) to monitor the PMT response. In this dissertation, the characterization and validation of the ProtoDUNE-DP PDS and LCS components before their installation will be reviewed, highlighting the results of general interest for experiments that use liquid noble gasses as target medium. The results from the stable performance of both systems in the detector during 15 months will be presented next as well as the studies on the scintillation light detection in ProtoDUNE-DP, where the collection of light produced in LAr at 7 m from the photosensors has been achieved for the first time. It is worth pointing out that the excellent LAr purity and the large size of the detector have enabled to develop a unique data-driven investigation on aspects that are critical for LAr-based experiments but that are not completely understood. The analyses cover the characterization of the low-energy background detected by the PDS, the quantification of the electric field impact on the light yield, the evaluation of the Rayleigh scattering affecting the light propagation, and the analysis of the PMT detection efficiency. The effect of the VUV reflectivity of the detector materials will be also discussed. In addition, the estimation of the cosmic muon flux crossing the TPC and the study of the observed light yield by the PDS will be reported. Finally, the results from the simulation-based study of the supernova burst trigger capability with the PDS of a 12.1-kt active mass dual-phase LAr TPC as the one proposed for DUNE will be summarized. Several configurations of reflective foils installed in the TPC to enhance the light collection will be compared

    T cells express CCL2 receptor.

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    <p>Expression of CCR2 in T-cells in human glioma (top panel) and monkey brain (bottom panel). CD3<sup>+</sup> T-cells (green) express CCR2 in their surface (magenta). Nucleus is stained with DAPI (blue).</p
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