633 research outputs found

    Victimización escolar y satisfacción con la vida en adolescentes del distrito de Puente Piedra, Lima, 2022

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    En esta investigación se buscó determinar la relación entre victimización escolar y satisfacción con la vida en adolescentes del distrito de Puente Piedra, Lima, 2022. El diseño fue no experimental, con un modelo descriptivo correlacional. La muestra lo conformaron 381 adolescentes, 199 fueron hombres y 182 mujeres, cuyas edades oscilaban entre 12 a 17 años. Para la recopilación de información se utilizaron los instrumentos de victimización entre iguales (VE-I) y la escala de satisfacción con la vida (SWLS). Los resultados mostraron que existe una correlación inversa y significativa entre las variables estudiadas. (Rho=-.244**), mostrando un tamaño de efecto pequeño. Concluyendo que, a mayor victimización escolar, menor es la percepción de satisfacción con la vida en los estudiante

    Moisture sorption properties and storage stability conditions of a nutraceutical system microencapsulated by spray drying

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    The adsorption isotherms of a nutraceutical system microencapsulated by spray drying were determined at 20, 35 and 40 °C. Experimental data of the isotherms were fitted using the GAB and Caurie models and the integral thermodynamic functions (enthalpy and entropy) were estimated by the Clausius-Clapeyron equation. The Kelvin and Halsey equations were adequate for calculation of pore radius which varied from 0.67 to 8.15 nm. The point of maximum stability (minimum integral entropy) was found between 3.61 and 3.81 kg H2O/100 kg d.s. (corresponding to water activity, aW, of 0.19-0.37). Enthalpy-entropy compensation for the microcapsules showed two isokinetic temperatures. The first isokinetic temperature was observed at low moisture contents (< 3.81 kg H2O/100 kg d.s.) and was controlled by changes in the entropy of water, whereas the second isokinetic temperature was considered to be enthalpy-driven (3.81-20 kg H2O/100 kg d.s.). Keywords: sorption isotherms, pore radius, minimum integral entropy, enthalphy-entropy compensation, water activity

    Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit

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    Biochemistry; Molecular medicineBioquímica; Medicina molecularBioquímica; Medicina molecularImbalanced mitochondrial dNTP pools are known players in the pathogenesis of multiple human diseases. Here we show that, even under physiological conditions, dGTP is largely overrepresented among other dNTPs in mitochondria of mouse tissues and human cultured cells. In addition, a vast majority of mitochondrial dGTP is tightly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial respiratory chain. NDUFA10 shares a deoxyribonucleoside kinase (dNK) domain with deoxyribonucleoside kinases in the nucleotide salvage pathway, though no specific function beyond stabilizing the complex I holoenzyme has been described for this subunit. We mutated the dNK domain of NDUFA10 in human HEK-293T cells while preserving complex I assembly and activity. The NDUFA10E160A/R161A shows reduced dGTP binding capacity in vitro and leads to a 50% reduction in mitochondrial dGTP content, proving that most dGTP is directly bound to the dNK domain of NDUFA10. This interaction may represent a hitherto unknown mechanism regulating mitochondrial dNTP availability and linking oxidative metabolism to DNA maintenance.We thank Dr, Luke Formosa (Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia) for his valuable advice and assistance on NDUFA10 molecular studies and Dr. Francesc Canals and his team (Proteomics Laboratory, Vall d’Hebron Institute of Oncology [VHIO], Universitat Autònoma de Barcelona, Barcelona, Spain) for their assistance with LC-MS/MS analyses. This work was supported by the Spanish Ministry of Industry, Economy and Competitiveness [grants BFU2014-52618-R, SAF2017-87506, and PID2020-112929RB-I00 to Y.C.], by the Spanish Instituto de Salud Carlos III [grants PI21/00554 and PMP15/00025 to R.M.], co-financed by the European Regional Development Fund (ERDF), and by an NHMRC Project grant to M.R. (GNT1164459)

    CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells

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    The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1low cells present a migratory and invasive phenotype, while EWSR1::FLI1high cells are more proliferative. In this work, we described how the CD44 standard isoform (CD44s), a transmembrane protein involved in cell adhesion and migration, is overexpressed in the EWSR1::FLI1low phenotype. The functional characterization of CD44s (proliferation, clonogenicity, migration, and invasion ability) was performed in three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, and CADO-ES1). As a result, CD44s expression reduced cell proliferation in all the cell lines tested without affecting clonogenicity. Additionally, CD44s increased cell migration in A673 and MHH-ES1, without effects in CADO-ES1. As hyaluronan is the main ligand of CD44s, its effect on migration ability was also assessed, showing that high molecular weight hyaluronic acid (HMW-HA) blocked cell migration while low molecular weight hyaluronic acid (LMW-HA) increased it. Invasion ability was correlated with CD44 expression in A673 and MHH-ES1 cell lines. CD44s, upregulated upon EWSR1::FLI1 knockdown, regulates cell migration and invasion in Ewing sarcoma cells.This project was funded by Instituto de Salud Carlos III, grant numbers PI20CIII/00020, DTS18CIII/00005, Asociación Pablo Ugarte, grant numbers TRPV205/18; Asociación Candela Riera, Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant numbers TVP333-19, TVP-1324/15; ASION, grant number TVP141/17. Enrique Fernández-Tabanera is supported by Asociación Candela Riera, Asociación Todos Somos Iván & Fundación Sonrisa de Alex, Saint T. Cervera is supported by Asociación Pablo Ugarte and Raquel M. Melero is supported by a CIBERER contract.S

    Reference Scenarios and Key Performance Indicators for 5G Ultra-dense Networks

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    The so-called 5G will revolutionize the way we live, and work. In order to demonstrate the profound changes, we can expect to experience within the next 5 to 10 years, we present use cases for the planned research within the TeamUp5G project. Some use cases are strongly linked to the network layer and aim at developing solutions capable of optimizing the main promising benefits of 5G: extremely low latency and extremely high bandwidth (e.g., handle video streams, traffic congestion, user profiles), in the most efficient way possible. Other use cases focus on commercial applications that make use of middleware applications to enhance their performance. The latter fall into two main areas: real-time virtual reality and live video streaming, which are extremely demanding in terms of latency and bandwidth to provide an acceptable QoE/QoS to multiple users. The use cases presented are built assuming that 5G is essential for their support with appropriate QoE/QoS. Key performance indicators and their range of variation are also identified.info:eu-repo/semantics/acceptedVersio

    An Ultrahigh CO2-Loaded Silicalite-1 Zeolite: Structural Stability and Physical Properties at High Pressures and Temperatures

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    [EN] We report the formation of an ultrahigh CO2-loaded pure-SiO2, silicalite-1 structure at high pressure (0.7 GPa) from the interaction of empty zeolite and fluid CO, medium. The CO2-filled structure was characterized in situ by means of synchrotron powder X-ray diffraction. Rietveld refinements and Fourier recycling allowed the location of 16 guest carbon dioxide molecules per unit cell within the straight and sinusoidal channels of the porous framework to be analyzed. The complete filling of pores by CO, molecules favors structural stability under compression, avoiding pressure-induced amorphization below 20 GPa, and significantly reduces the compressibility of the system compared to that of the parental empty one. The structure of CO2-loaded silicalite-1 was also monitored at high pressures and temperatures, and its thermal expansivity was estimated.The authors thank the Spanish Ministerio de Economia y Competitividad (MINECO), the Spanish Research Agency (AEI), and the European Fund for Regional Development (FEDER) for their financial support (MAT2016-75586-C4-1-P, MAT2016-75586-C4-3-P, MAT2015-71842-P; Severo Ochoa SEV-2012-0267; and MAT2015-71070-REDC (MALTA Consolider)). D.S.-P. and J.R-F. acknowledge MINECO for a Ramon y Cajal (RyC-2014-15643) and a Juan de la Cierva (IJCI-2014-20513) contract, respectively. A.K. acknowledges the support of the University of Valencia through the Grant UV-INV-EPC17-548561. Portions of this work were performed at GeoSoilEnviroCARS (Sector 13), Advanced Photon Source (APS), and Argonne National Laboratory. GeoSoilEnviroCARS is supported by the National Science Foundation, Earth Sciences (EAR-1128799), and the Department of Energy, GeoSciences (DE-FG02-94ER14466). This research used resources from the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory (DE-AC02-06CH11357). Use of the COMPRES-GSECARS gas loading system was supported by COMPRES under NSF Cooperative Agreement EAR 11-57758. CO2 gas was also loaded at Diamond Light Source. The authors thank the synchrotron facility ALBA-CELLS for beamtime allocation at MSPD line.Marqueno, T.; Santamaria-Perez, D.; Ruiz-Fuertes, J.; Chulia-Jordan, R.; Jorda Moret, JL.; Rey Garcia, F.; Mcguire, C.... (2018). An Ultrahigh CO2-Loaded Silicalite-1 Zeolite: Structural Stability and Physical Properties at High Pressures and Temperatures. Inorganic Chemistry. 57(11):6447-6455. https://doi.org/10.1021/acs.inorgchem.8b00523S64476455571

    EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping

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    Molecular classification of medulloblastoma is critical for the treatment of this brain tumor. Array-based DNA methylation profiling has emerged as a powerful approach for brain tumor classification. However, this technology is currently not widely available. We present a machine-learning decision support system (DSS) that enables the classification of the principal molecular groups—WNT, SHH, and non-WNT/non-SHH—directly from quantitative PCR (qPCR) data. We propose a framework where the developed DSS appears as a user-friendly web-application—EpiGe-App—that enables automated interpretation of qPCR methylation data and subsequent molecular group prediction. The basis of our classification strategy is a previously validated six-cytosine signature with subgroup-specific methylation profiles. This reduced set of markers enabled us to develop a methyl-genotyping assay capable of determining the methylation status of cytosines using qPCR instruments. This study provides a comprehensive approach for rapid classification of clinically relevant medulloblastoma groups, using readily accessible equipment and an easy-to-use web-application.The study was supported by Associations of Parents and Families of Children with Cancer and by funding of the Spanish Ministry of for Science, Innovation and University (grant PI20/00519; PI CL) and the Foundation La Marató TV3 (grant 201921-30; PI CL). We acknowledge the multidisciplinary team who helped in the molecular analyses and care of patients, and the BioBank Hospital Sant Joan de Déu of the Spanish BioBank Network for sample procurement. We also acknowledge Marta Fortuny for communication strategy advice and Eduard Puig for legal assistance and data protection regulations. Authors acknowledge the SJD Fundraising Team.Peer ReviewedArticle signat per 23 autors/es: Soledad Gómez-González, Joshua Llano, Marta Garcia, Alicia Garrido-Garcia, Mariona Suñol, Isadora Lemos, Sara Perez-Jaume, Noelia Salvador, Nagore Gene-Olaciregui, Raquel Arnau Galán, Vicente Santa-María, Marta Perez-Somarriba, Alicia Castañeda, José Hinojosa, Ursula Winter, Francisco Barbosa Moreira, Fabiana Lubieniecki, Valeria Vazquez, Jaume Mora, Ofelia Cruz, Andrés Morales La Madrid, Alexandre Perera, Cinzia Lavarino.Postprint (published version

    RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition

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    Long INterspersed Element class 1 (LINE-1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition-competent LINE-1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE-1 repressors and when mutated cause the autoinflammatory disorder Aicardi-Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE-1 retrotransposition. It has therefore been suggested that increased LINE-1 activity may be the cause of aberrant innate immune activation in AGS. Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE-1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE-1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE-1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE-1-derived nucleic acids driving autoinflammation in AGS.M.B.-G. is funded by a “Formacion Profesorado Universitario” (FPU) PhD fellowship from the Government of Spain (MINECO, Ref FPU15/03294), and this paper is part of her thesis project (“Epigenetic control of the mobility of a human retrotransposon”). R.V.-A. is funded by a PFIS Fellowship from the Government of Spain (ISCiii, FI16/00413). O.M. is funded by an EMBO Long-Term Fellowship (ALTF 7-2015), the European Commission FP7 (Marie Curie Actions, LTFCOFUND2013, GA-2013-609409) and the Swiss National Science Foundation (P2ZHP3_158709). S.R.H. is funded by the Government of Spain (MINECO, RYC-2016-21395 and SAF2015-71589-P). A.P.J’s laboratory is supported by the UK Medical Research Council (MRC University Unit grant U127527202). J.L.G.P’s laboratory is supported by CICEFEDER- P12-CTS-2256, Plan Nacional de I+D+I 2008-2011 and 2013-2016 (FISFEDER- PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research Council (ERC-Consolidator ERC-STG-2012-233764), by an International Early Career Scientist grant from the Howard Hughes Medical Institute (IECS-55007420), by The Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund (ISFF2) and by a private donation from Ms Francisca Serrano (Trading y Bolsa para Torpes, Granada, Spain)

    Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

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    Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients

    Evolution of antibodies against SARS-CoV-2 over seven months: experience of the Nationwide Seroprevalence ENE-COVID Study in Spain [preprint]

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    Objectives To analyse temporal trends in SARS-CoV-2 anti-nucleocapsid IgG throughout the four rounds of the nationwide seroepidemiologic study ENE-COVID (April-November 2020), and to compare the fourth-round results of two immunoassays detecting antibodies against nucleocapsid and to S protein receptor-binding domain (RBD). Methods A chemiluminescent microparticle immunoassay (CMIA) was offered to all participants in the first three rounds (Abbott; anti-nucleocapsid IgG). In the fourth round we offered this test and a chemiluminescence immunoassay (CLIA) (Beckman; anti-RBD IgG) to i) a randomly selected sub-cohort, ii) participants who were IgG-positive in any of the three first rounds; and iii) participants who were IgG-positive in the fourth round by point-of-care immunochromatography. Results Immunoassays involving 10,153 participants (82.2% of people invited to donate samples) were performed in the fourth round. A total of 2595 participants (35.1% of participants with immunoassay results in the four rounds) were positive for anti-nucleocapsid IgG in at least one round. Anti-nucleocapsid IgG became undetectable in 43.3% of participants with positive first-round results. Pneumonia was more frequent in participants with anti-nucleocapsid IgG in all four rounds (11.2%) than those in which IgG became undetectable (2.4%). In fourth round, anti-nucleocapsid and anti-RBD IgG were detected in 5.5% and 5.4% participants of the randomly selected sub-cohort, and in 26.6% and 25.9% participants with at least one previous positive result, respectively. Agreement between techniques was 90.3% (kappa: 0.72). Conclusions The response of IgG to SARS-CoV-2 is heterogeneous and conditioned by infection severity. A substantial proportion of the SARS-CoV-2 infected population may have negative serologic results in the post-infection months.N
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