714 research outputs found

    Visual attention mechanisms in happiness vs. trustworthiness processing of facial expressions

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    A happy facial expression makes a person look (more) trustworthy. Do perceptions of happiness and trustworthiness rely on the same face regions and visual attention processes? In an eye-tracking study, eye movements and fixations were recorded while participants judged the un/happiness or the un/trustworthiness of dynamic facial expressions in which the eyes and/or the mouth unfolded from neutral to happy or vice versa. A smiling mouth and happy eyes enhanced perceived happiness and trustworthiness similarly, with a greater contribution of the smile relative to the eyes. This comparable judgement output for happiness and trustworthiness was reached through shared as well as distinct attentional mechanisms: (a) entry times and (b) initial fixation thresholds for each face region were equivalent for both judgements, thereby revealing the same attentional orienting in happiness and trustworthiness processing. However, (c) greater and (d) longer fixation density for the mouth region in the happiness task, and for the eye region in the trustworthiness task, demonstrated different selective attentional engagement. Relatedly, (e) mean fixation duration across face regions was longer in the trustworthiness task, thus showing increased attentional intensity or processing effort

    Estudio del efecto solvatocrómico en derivados fenólicos naturales

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    Se describen las características espectrofluorimétricas de dos derivados de quercetina aislados de las hojas deFlaveria bidentis, un derivado de 6-prenilpinocembrina, aislado de las raíces de Dalea elegans y un compuesto deestructura antraquinónica aislado de las hojas de Heterophyllaea pustulata. Todos ellos presentan espectros deabsorción con máximos en la región UV-visible acordes con los grupos cromóforos presentes en su estructura. Loscuatro compuestos estudiados presentan fluorescencia nativa. La posición de los máximos de emisión de fluorescenciase modifica en función del disolvente. Los desplazamientos producidos están relacionados con el diferente gradode solvatación de las moléculas en estado excitado según la polaridad del disolvente. La adición de ácidos mineralesprovoca desplazamientos en los máximos de fluorescencia concordantes con los ya descritos para compuestos deestructura similar. Estas modificaciones espectrales tienen un gran interés analítico desde el punto de vista de laidentificación y caracterización de productos naturales de estructura fenólica

    Environmentally friendly analysis of emerging contaminants by pressurized hot water extraction-stir bar sorptive extraction-derivatization and gas chromatography-mass spectrometry

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    This work describes the development, optimiza- tion, and validation of a new method for the simultaneous determination of a wide range of pharmaceuticals (beta- blockers, lipid regulators ... ) and personal care products (fragrances, UV filters, phthalates ... ) in both aqueous and solid environmental matrices. Target compounds were extracted from sediments using pressurized hot water ex- traction followed by stir bar sorptive extraction. The first stage was performed at 1,500 psi during three static extrac- tion cycles of 5 min each after optimizing the extraction temperature (50 – 150 °C) and addition of organic modifiers (% methanol) to water, the extraction solvent. Next, aqueous extracts and water samples were processed using polydime- thylsiloxane bars. Several parameters were optimized for this technique, including extraction and desorption time, ionic strength, presence of organic modifiers, and pH. Fi- nally, analytes were extracted from the bars by ultrasonic irradiation using a reduced amount of solvent (0.2 mL) prior to derivatization and gas chromatography – mass spectrome- try analysis. The optimized protocol uses minimal amounts of organic solvents (<10 mL/sample) and time ( ≈ 8 h/sam- ple) compared to previous ex isting methodologies. Low standard deviation (usually below 10 %) and limits of de- tection (sub-ppb) vouch for the applicability of the method- ology for the analysis of target compounds at trace levels. Once developed, the method was applied to determin

    Type I interferon signaling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice

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    SARS-CoV-2 is a newly emerged coronavirus, causing the global pandemic of respiratory coronavirus disease (COVID-19). The type I interferon (IFN) pathway is of particular importance for anti-viral defence and recent studies identified that type I IFNs drive early inflammatory responses to SARS-CoV-2. Here, we use a mouse model of SARS-CoV-2 infection, facilitating viral entry by intranasal recombinant Adeno-Associated Virus (rAAV) transduction of hACE2 in wildtype (WT) and type I IFN-signalling-deficient (Ifnar1-/- ) mice, to study type I IFN signalling deficiency and innate immune responses during SARS-CoV-2 infection. Our data show that type I IFN signaling is essential for inducing anti-viral effector responses to SARS-CoV-2, control of virus replication and to prevent enhanced disease. Furthermore, hACE2-Ifnar1-/- mice had increased gene expression of the chemokine Cxcl1 and airway infiltration of neutrophils as well as a reduced and delayed production of monocyte-recruiting chemokine CCL2. hACE2-Ifnar1-/- mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C+ to Ly6C- expressing cells. Together, our findings suggest that type I IFN deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. This article is protected by copyright. All rights reserved

    Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems

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    Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus-host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are common human gastrointestinal diseases that share inflammation as a key driver for their development. A general outcome resulting from these chronic inflammatory conditions is increased oxidative stress. Oxidative stress is caused by the generation of reactive oxygen and nitrogen species that are part of the normal inflammatory response, but are also capable of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA strand breaks, point mutations due to DNA adducts, as well as alterations in methylation patterns leading to activation of oncogenes or inactivation of tumor suppressors. There are a number of significant long-term consequences associated with chronic oxidative stress, most notably cancer. Infiltrating immune cells and stromal components of tissue including fibroblasts contribute to dynamic changes occurring in tissue related to disease development. Immune cells can potentiate oxidative stress, and fibroblasts have the capacity to contribute to advanced growth and proliferation of the epithelium and any resultant cancers. Disease models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional human cell and tissue culture systems that recapitulate in vivo growth and differentiation in inflammatory-associated microphysiological environments would enhance our understanding of disease progression and improve our ability to test for disease-prevention strategies. The development of physiologically relevant, human cell-based culture systems is therefore a major focus of our research. These novel models will be of enormous value, allowing us to test hypotheses and advance our understanding of these disorders, and will have a translational impact allowing us to more rapidly develop therapeutic and chemopreventive agents. In summary, this work to develop advanced human cell-based models of inflammatory conditions will greatly improve our ability to study, prevent, and treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster the development of novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions. © 2013 BioMed Central Ltd

    Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one

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    The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe3+, studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe3+. The pFe3+ value 22.0 of P1–iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al3+, Cu2+ and Zn2+ has been studied to evalu- ate the possible use of P1 against a second toxic metal ion (Al3+), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelato

    Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

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    The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions

    Oestradiol-17β plasma concentrations after intramuscular injection of oestradiol benzoate or oestradiol cypionate in llamas (Lama glama)

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    <p>Abstract</p> <p>Background</p> <p>Llamas (<it>Lama glama</it>) are induced ovulators and the process of ovulation depends on dominant follicular size. In addition, a close relationship between behavioural estrus and ovulation is not registered in llamas. Therefore, the exogenous control of follicular development with hormones aims to predict the optimal time to mate. Oestradiol-17β (E<sub>2</sub>) and its esters are currently used in domestic species, including camelids, in synchronization treatments. But, in llamas, there is no reports regarding the appropriate dosages to be used and most protocols have been designed by extrapolation from those recommended for other ruminants. The aim of the present study was to characterize plasma E<sub>2 </sub>concentrations in intact female llamas following a single intramuscular (i.m.) injection of two oestradiol esters: oestradiol benzoate (EB) and oestradiol cypionate (ECP).</p> <p>Methods</p> <p>Twelve non pregnant and non lactating sexually mature llamas were i.m. injected on day 0 with 2.5 mg of EB (EB group, n = 6) or ECP (ECP group, n = 6). Blood samples were collected immediately before injection, at 1, 6, 12, 24 h after treatment and then daily until day 14 post injection. Changes in hormone concentrations with time were analyzed in each group by analysis of variance (ANOVA) using a repeated measures (within-SS) design. Plasma E<sub>2 </sub>concentrations and area under the concentration-time curve (AUC) values were compared between groups by ANOVA. In all cases a Least-Significant Difference test (LSD) was used to determine differences between means. Hormonal and AUC data are expressed as mean ± S.E.M.</p> <p>Results</p> <p>Peak plasma E<sub>2 </sub>concentrations were achieved earlier and were higher in EB group than in ECP group. Thereafter, E<sub>2 </sub>returned to physiological concentrations earlier in EB group (day 5) than in ECP group (day 9). Although plasma E<sub>2 </sub>profiles differed over time among groups there were no differences between them on AUC values.</p> <p>Conclusions</p> <p>The i.m. injection of a single dose of both oestradiol esters resulted in plasma E<sub>2 </sub>concentrations exceeding physiological values for a variable period. Moreover, the plasma E<sub>2 </sub>profiles observed depended on the derivative of oestradiol administered. This basic information becomes relevant at defining treatment protocols including oestrogens in llamas.</p

    Accurate masses and radii of normal stars: modern results and applications

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    This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl

    Specific Marking of hESCs-Derived Hematopoietic Lineage by WAS-Promoter Driven Lentiviral Vectors

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    Genetic manipulation of human embryonic stem cells (hESCs) is instrumental for tracing lineage commitment and to studying human development. Here we used hematopoietic-specific Wiskott-Aldrich syndrome gene (WAS)-promoter driven lentiviral vectors (LVs) to achieve highly specific gene expression in hESCs-derived hematopoietic cells. We first demonstrated that endogenous WAS gene was not expressed in undifferentiated hESCs but was evident in hemogenic progenitors (CD45−CD31+CD34+) and hematopoietic cells (CD45+). Accordingly, WAS-promoter driven LVs were unable to express the eGFP transgene in undifferentiated hESCs. eGFP+ cells only appeared after embryoid body (EB) hematopoietic differentiation. The phenotypic analysis of the eGFP+ cells showed marking of different subpopulations at different days of differentiation. At days 10–15, AWE LVs tag hemogenic and hematopoietic progenitors cells (CD45−CD31+CD34dim and CD45+CD31+CD34dim) emerging from hESCs and at day 22 its expression became restricted to mature hematopoietic cells (CD45+CD33+). Surprisingly, at day 10 of differentiation, the AWE vector also marked CD45−CD31low/−CD34− cells, a population that disappeared at later stages of differentiation. We showed that the eGFP+CD45−CD31+ population generate 5 times more CD45+ cells than the eGFP−CD45−CD31+ indicating that the AWE vector was identifying a subpopulation inside the CD45−CD31+ cells with higher hemogenic capacity. We also showed generation of CD45+ cells from the eGFP+CD45−CD31low/−CD34− population but not from the eGFP−CD45−CD31low/−CD34− cells. This is, to our knowledge, the first report of a gene transfer vector which specifically labels hemogenic progenitors and hematopoietic cells emerging from hESCs. We propose the use of WAS-promoter driven LVs as a novel tool to studying human hematopoietic development
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