149 research outputs found

    Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response.

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    Communication through cell-cell contacts and extracellular vesicles (EVs) enables immune cells to coordinate their responses against diverse types of pathogens. The function exerted by EVs in this context depends on the proteins and nucleic acids loaded into EVs, which elicit specific responses involved in the resolution of infection. Several mechanisms control protein and nucleic acid loading into EVs; in this regard, acetylation has been described as a mechanism of cellular retention during protein sorting to exosomes. HDAC6 is a deacetylase involved in the control of cytoskeleton trafficking, organelle polarity and cell migration, defense against Listeria monocytogenes (Lm) infection and other immune related functions. Here, we show that the protein content of dendritic cells (DCs) and their secreted EVs (DEVs) vary during Lm infection, is enriched in proteins related to antiviral functions compared to non-infected cells and depends on HDAC6 expression. Analyses of the post-translational modifications revealed an alteration of the acetylation and ubiquitination profiles upon Lm infection both in DC lysates and DEVs. Functionally, EVs derived from infected DCs upregulate anti-pathogenic genes (e.g. inflammatory cytokines) in recipient immature DCs, which translated into protection from subsequent infection with vaccinia virus. Interestingly, absence of Listeriolysin O in Lm prevents DEVs from inducing this anti-viral state. In summary, these data underscore a new mechanism of communication between bacteria-infected DC during infection as they alert neighboring, uninfected DCs to promote antiviral responses.This study was supported by grant PDI-2020-120412RB-I00, PDC2021-121797-I00, BIO2015-67580-P and PGC2018-097019-BI00 from the Spanish Ministry of Economy and Competitiveness (MINECO), grant S2017/BMD-3671-INFLAMUNE-CM from the Comunidad de Madrid, a grant from the Ramón Areces Foundation “Ciencias de la Vida y la Salud” (XIX Concurso-2018), “la Caixa” Banking Foundation (grants HR17-00016 and HR17-00247), BIOIMID (PIE13/041) and PRB3 (IPT17/0019 - ISCIII-SGEFI/ ERDF, ProteoRed) from Instituto de Salud Carlos III, CIBER Cardiovascular (CB16/11/00272), and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). IF-D is supported by a Fellowship from the Spanish Ministry of Science, Innovation, and Universities (FPU15/02539). DC-F is supported by a Fellowship from “la Caixa” Foundation (LCF/BQ/DR19/11740010). 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 (CEX2020- 001041-S). Funding agencies did not intervene in the design of the studies, with no copyright over the study.S

    DataSheet_1_Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response.pdf [Dataset]

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    Supplementary Figure 1. Isolated EVs present typical size and topology. Supplementary Figure 2. Protein profiling from total cell lysates and their derived EVs from WT and KO-HDAC6 BMDCs. Supplementary Figure 3. Enrichment in acetylated and ubiquitinated DC proteins upon Lm infection. Supplementary Figure 4. Ubiquitination in K-48 and K-63 state in T lymphoblast total cell lysates and their derived EVs. Supplementary Figure 5. Pore filtration methods restrain Lm and do not induce strong antipathogenic responses. Supplementary Figure 6. IFN-β is detected following Lm infection. Table S1. List of antibodies used for Western-blot and Flow Cytometry and the used dilution. Table S2. List of primers, with their corresponding sequence, used for qPCR. Table S3: Protein quantification in total cell lysates Table S4: IPA analysis of total cell lysates: canonical pathways and diseases and functions category Table S5: Protein quantification in EVs Table S6: IPA analysis of EVs: diseases and functions category Table S7: Ubiquitinated and acetylated peptides in total cell lysates and EVs Table S8: Enrichment analysis of ubiquitinated and acetylated proteinsPeer reviewe

    Preparación del sector judicial para la inteligencia artificial en América Latina

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    Fil: Aguerre, Carolina. Universidad de San Andrés. Centro de Estudios de Tecnología y Sociedad; Argentina.Fil: Amunátegui, Carlos. Pontificia Universidad Católica de Chile; Chile.Fil: Aranguis, Matias. Pontificia Universidad Católica de Chile. Programa Derecho, Ciencia y Tecnología; Chile.Fil: Bustos Frati, Gonzalo. Universidad de San Andrés. Centro de Estudios de Tecnología y Sociedad; Argentina.Fil: Castaño, Daniel. Universidad Externado de Colombia. Centro de Ética Digital; Colombia.Fil: Mendoza Enriquez, Olivia Andrea. Centro de Investigación y Docencia Económicas. División de Estudios Jurídicos; México.Fil: Moreno González, Jimena. Centro de Investigación y Docencia Económicas; México.Fil: Gorgone, Bruno. Universidad de San Andrés. Centro de Estudios de Tecnología y Sociedad; Argentina.Fil: Lens, Julio. Universidad Católica del Uruguay; Uruguay.Fil: Madrid, Raúl. Pontificia Universidad Católica de Chile. Programa de Derecho, Ciencia y Tecnología; Chile.Fil: Maqueo Ramírez, María Solange. Centro de Investigación y Docencia Económicas. División de Estudios Jurídicos; México.Fil: Rentería Marín, César. Centro de Investigación y Docencia Económicas; México.Fil: Segredo, Sandra. Universidad Católica del Uruguay; Uruguay.Fil: Vargas, Fernando. Universidad de Montevideo; Uruguay."Con el objetivo de aprovechar los beneficios de la inteligencia artificial (IA), sectores judiciales de diversos países de América Latina se encuentran implementando (o en proceso de implementación) de estas tecnologías en sus procesos o servicios. En este contexto, el CETyS está llevando adelante una investigación cuyo propósito es evaluar la preparación, necesidades, obstáculos y oportunidades del sector judicial a la hora de adoptar responsablemente tecnologías de IA. La investigación involucra la identificación del uso actual de IA y tecnologías digitales relacionadas por el sector judicial; una evaluación de su potencial aplicación para abordar sus necesidades y desafíos clave; y también el debate sobre cuestiones críticas en el diseño y la implementación relacionadas con la equidad, la responsabilidad y la independencia judicial. El proyecto se destaca también porque propone y elabora un marco analítico que permite a otros agentes judiciales o actores interesados realizar el mismo trabajo de diagnóstico, evaluación y adopción de estrategias de IA en sus procesos y servicios públicos de forma responsable, desde una perspectiva regional. El marco funciona como un mapa con indicadores propios de la región sobre las normativas y actores públicos de la gobernanza digital (con énfasis en la IA); los procesos de modernización judicial; un diagnóstico y desarrollo de capacidades para su adopción; las condiciones existentes para el despliegue de IA en el ámbito judicial; y referencias a sus oportunidades y riesgos.

    Plant characterization of genetically modified maize hybrids MON-89Ø34-3 × MON-88Ø17-3, MON-89Ø34-3 × MON-ØØ6Ø3-6, and MON-ØØ6Ø3-6: alternatives for maize production in Mexico

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    Environmental risk assessment (ERA) of genetically modified (GM) crops is a process to evaluate whether the biotechnology trait(s) in a GM crop may result in increased pest potential or harm to the environment. In this analysis, two GM insect-resistant (IR) herbicide-tolerant maize hybrids (MON-89Ø34-3 9 MON-88Ø17-3 and MON-89Ø34-3 9 MON-ØØ6Ø3-6) and one herbicide-tolerant GM hybrid (MON-ØØ6Ø3-6) were compared with conventional maize hybrids of similar genetic backgrounds. Two sets of studies, Experimental Phase and Pilot Phase, were conducted across five ecological regions (ecoregions) in Mexico during 2009–2013, and data were subject to meta-analysis. Results from the Experimental Phase studies, which were used for ERA, indicated that the three GM hybrids were not different from conventional maize for early stand count, days-tosilking, days-to-anthesis, root lodging, stalk lodging, or final stand count. Statistically significant differences were observed for seedling vigor, ear height, plant height, grain moisture, and grain yield, particularly in the IR hybrids; however, none of these phenotypic differences are expected to contribute to a biological or ecological change that would result in an increased pest potential or ecological risk when cultivating these GM hybrids. Overall, results from the Experimental Phase studies are consistent with those from other world regions, confirming that there are no additional risks compared to conventional maize. Results from Pilot Phase studies indicated that, compared to conventional maize hybrids, no differences were detected for the agronomic and phenotypic characteristics measured on the three GM maize hybrids, with the exception of grain moisture and grain yield in the IR hybrids. Since MON-89Ø34- 3 9 MON-88Ø17-3 and MON-89Ø34-3 9 MONØØ6Ø3- 6 confer resistance to target insect pests, they are an alternative for farmers in Mexico to protect the crop from insect damage. Additionally, the herbicide tolerance conferred by all three GM hybrids enables more cost-effective weed management

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

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    An embedding technique to determine ττ backgrounds in proton-proton collision data

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    An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

    Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

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    Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at s \sqrt{s} = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at s \sqrt{s} = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at s=\sqrt{s} = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at s=\sqrt{s} = 7 TeV, as well as with theoretical predictions

    Search for dark matter in events with a leptoquark and missing transverse momentum in proton-proton collisions at 13 TeV

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    A search is presented for dark matter in proton-proton collisions at a center-of-mass energy of root s= 13 TeV using events with at least one high transverse momentum (p(T)) muon, at least one high-p(T) jet, and large missing transverse momentum. The data were collected with the CMS detector at the CERN LHC in 2016 and 2017, and correspond to an integrated luminosity of 77.4 fb(-1). In the examined scenario, a pair of scalar leptoquarks is assumed to be produced. One leptoquark decays to a muon and a jet while the other decays to dark matter and low-p(T) standard model particles. The signature for signal events would be significant missing transverse momentum from the dark matter in conjunction with a peak at the leptoquark mass in the invariant mass distribution of the highest p(T) muon and jet. The data are observed to be consistent with the background predicted by the standard model. For the first benchmark scenario considered, dark matter masses up to 500 GeV are excluded for leptoquark masses m(LQ) approximate to 1400 GeV, and up to 300 GeV for m(LQ) approximate to 1500 GeV. For the second benchmark scenario, dark matter masses up to 600 GeV are excluded for m(LQ) approximate to 1400 GeV. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe
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