3,289 research outputs found

    A specific structure and high richness characterize intestinal microbiota of HIVexposed seronegative individuals

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    Intestinal microbiota facilitates food breakdown for energy metabolism and influences the im-mune response and maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, to date, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha and beta diversity compared to HC, but similar to HIV+. A lower Treg percentage was observed in HESN than HC and HIV+, with enrichment of the genus Butyrivibrio being characteristic of this profile. Interestingly, an increase in Succinivibrio and Prevotella and a re-duction in Bacteroides genus were observed in HESN compared to HC, which is typical of HIV-infected individuals. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.Intestinal microbiota facilitates food breakdown for energy metabolism and influences the im-mune response and maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, to date, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha and beta diversity compared to HC, but similar to HIV+. A lower Treg percentage was observed in HESN than HC and HIV+, with enrichment of the genus Butyrivibrio being characteristic of this profile. Interestingly, an increase in Succinivibrio and Prevotella and a re-duction in Bacteroides genus were observed in HESN compared to HC, which is typical of HIV-infected individuals. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.https://scienti.minciencias.gov.co/cvlac/EnProdArticulo/query.do?cod_producto=73&cod_rh=0000157775https://scholar.google.com.co/citations?hl=en&user=VLZxl1UAAAAJCOL0112548https://orcid.org/0000-0002-7351-873

    Biomimetic Magnetic Nanocarriers Drive Choline Kinase Alpha Inhibitor inside Cancer Cells for Combined Chemo-Hyperthermia Therapy

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    Choline kinase a1 (ChoKa1) has become an excellent antitumor target. Among all the inhibitors synthetized, the new compound Ff35 shows an excellent capacity to inhibit ChoKa1 activity. However, soluble Ff35 is also capable of inhibiting choline uptake, making the inhibitor not selective for ChoKa1. In this study, we designed a new protocol with the aim of disentangling whether the Ff35 biological action is due to the inhibition of the enzyme and/or to the choline uptake. Moreover, we offer an alternative to avoid the inhibition of choline uptake caused by Ff35, since the coupling of Ff35 to novel biomimetic magnetic nanoparticles (BMNPs) allows it to enter the cell through endocytosis without interacting with the choline transporter. This opens the possibility of a clinical use of Ff35. Our results indicate that Ff35-BMNPs nanoassemblies increase the selectivity of Ff35 and have an antiproliferative effect. Also, we demonstrate the effectiveness of the tandem Ff35-BMNPs and hyperthermia.This research was funded by the Ministerio de Economía y Competitividad (CGL2013-46612 and CGL2016-76723 projects), Ramón y Cajal programme (RYC-2014-16901) and the Fondo Europeo de Desarrollo Regional (FEDER). Also, this research was aided by the Andalusian regional government (CTS-236)

    CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome

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    Studies in recent years have established that the principal effects in cardiac cell therapy are associated with paracrine/autocrine factors. We combined several complementary techniques to define human cardiac progenitor cell (CPC) secretome constituted by 914 proteins/genes; 51% of these are associated with the exosomal compartment. To define the set of proteins specifically or highly differentially secreted by CPC, we compared human mesenchymal stem cells and dermal fibroblasts; the study defined a group of growth factors, cytokines and chemokines expressed at high to medium levels by CPC. Among them, IL-1, GROa (CXCL1), CXCL6 (GCP2) and IL-8 are examples whose expression was confirmed by most techniques used. ELISA showed that CXCL6 is significantly overexpressed in CPC conditioned medium (CM) (18- to 26-fold) and western blot confirmed expression of its receptors CXCR1 and CXCR2. Addition of anti-CXCL6 completely abolished migration in CPC-CM compared with anti-CXCR2, which promoted partial inhibition, and anti-CXCR1, which was inefficient. Anti-CXCL6 also significantly inhibited CPC CM angiogenic activity. In vivo evaluation also supported a relevant role for angiogenesis. Altogether, these results suggest a notable angiogenic potential in CPC-CM and identify CXCL6 as an important paracrine factor for CPC that signals mainly through CXCR2.This study was supported by funding from the European Commission (HEALTH-2009_242038) and by grants from the Spanish Ministry of Science and Innovation (SAF2012-34327 and SAF2015-70882-R to AB and BIO2012-37926 and BIO2015-67580-P to JV), the Research Program of the Comunidad Autónoma de Madrid (S2010/BMD-2420) and the Instituto de Salud Carlos III (RETICS-RD12/0019/0018 to AB and RETICS-RD12/0042/0056 to JV).S

    Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and naïve primary health care workers upon COVID-19 vaccination

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    We evaluated the kinetics of antibody responses to Two years into the COVID-19 pandemic and 1 year after the start of vaccination rollout, the world faced a peak of cases associated with the highly contagious Omicron variant of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) and nucleocapsid (N) antigens over five cross-sectional visits (January-November 2021), and the determinants of pre-booster immunoglobulin levels, in a prospective cohort of vaccinated primary health care workers in Catalonia, Spain. Antibodies against S antigens after a full primary vaccination course, mostly with BNT162b2, decreased steadily over time and were higher in pre-exposed (n = 247) than naive (n = 200) individuals, but seropositivity was maintained at 100% (100% IgG, 95.5% IgA, 30.6% IgM) up to 319 days after the first dose. Antibody binding to variants of concern was highly maintained for IgG compared to wild type but significantly reduced for IgA and IgM, particularly for Beta and Gamma. Factors significantly associated with longer-term antibodies included age, sex, occupation, smoking, adverse reaction to vaccination, levels of pre-vaccination SARS-CoV-2 antibodies, interval between disease onset and vaccination, hospitalization, oxygen supply, post COVID and symptomatology. Earlier morning vaccination hours were associated with higher IgG responses in pre-exposed participants. Symptomatic breakthroughs occurred in 9/447 (2.01%) individuals, all among naive (9/200, 4.5%) and generally boosted antibody responses. Additionally, an increase in IgA and/or IgM seropositivity to variants, and N seroconversion at later time points (6.54%), indicated asymptomatic breakthrough infections, even among pre-exposed. Seropositivity remained highly stable over almost a year after vaccination. However, gradually waning of anti-S IgGs that correlate with neutralizing activity, coupled to evidence of an increase in breakthrough infections during the Delta and Omicron predominance, provides a rationale for booster immunization

    Risks of dengue secondary infective biting associated with aedes aegypti in home environments in Monterrey, Mexico

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    Abstract. Secondary dengue virus infections are a major risk for developing dengue hemorrhagic fever. Recent exposure to infectious bites of Aedes aegypti (L.) females in previously diagnosed dengue cases fulfills the epidemiological model of dengue hemorrhagic fever. A study was comprised of 357 (89.2%) dengue and 43 (10.8%) dengue hemorrhagic fever cases confirmed by laboratory tests and clinical manifestations. An entomological survey was done in homes and backyards. Concurrently, a questionnaire was used to assess the impact of healthpromotion campaigns through knowledge of the vector and its epidemiological role. Seventy-six (28.4%) of the 268 (67.0%) total wet or dry oviposition sites were positive for the presence of larvae or pupae, while adult Ae. aegypti were found in 32 (8.0%). One hundred thirty-two (33%) householders who formerly had dengue fever or dengue hemorrhagic fever had knowledge of either larval or adult dengue vector stages. According to gender distribution, 145 (36.2%) and 14 (3.5%) of the males confirmed with cases of dengue and dengue hemorrhagic fever lived in houses with 17.9 and 2% of the Ae. aegypti larval and pupal habitats. Houses with females who had dengue and dengue hemorrhagic fever were 212 (53%) and 29 (7.3%), with containers with immature Ae. aegypti in 19.4 and 7%, respectively. Lack of sustainability of government-targeted health education campaigns is the major problem for involving communities in prevention and control of dengu

    Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

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    This paper presents measurements of the W+μ+νW^+ \rightarrow \mu^+\nu and WμνW^- \rightarrow \mu^-\nu cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

    Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

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    The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

    Standalone vertex finding in the ATLAS muon spectrometer

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    A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

    Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

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    Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson
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