508 research outputs found

    Rank ectopic expression in the presence of Neu and PyMT oncogenes alters mammary epithelial cell populations and their tumorigenic potential

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    Determination of the mammary epithelial cell that serves as the cell of origin for breast cancer is key to understand tumor heterogeneity and clinical management. In this study, we aimed to decipher whether Rank expression in the presence of PyMT and Neu oncogenes might affect the cell of origin of mammary gland tumors. We observed that Rank expression in PyMT+/- and Neu(+/-) mammary glands alters the basal and luminal mammary cell populations already in preneoplasic tissue, which may interfere with the tumor cell of origin restricting their tumorigenesis ability upon transplantation assays. In spite of this, Rank expression eventually promotes tumor aggressiveness once tumorigenesis is established

    Citrato de cafeína: ¿por qué usarlo en los recién nacidos?

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    ResumenEl citrato de cafeína, es uno de los medicamentos más comúnmente usado en cualquier unidad de cuidados intensivos neonatales; es una metilxantina e inhibidor de los receptores de adenosina. Desde hace más de 30 años es bien conocida su eficacia en el tratamiento de la apnea del prematuro, actualmente se le reconocen otros beneficios como disminución en la incidencia de displasia broncopulmonar, disminución de la falla a la extubación y ser un factor de neuroprotección entre otros. El objetivo del presente artículo fue realizará una revisión sobre las propiedades farmacológicas, mecanismos de acción, dosis adecuadas, niveles séricos y efectos terapéuticos de la cafeína en los recién nacidos.AbstractCaffeine, a methylxantine and nonspecific inhibitor of adenosine receptors, is commonly prescribed in the Neonatal Intensive Care Units. The efficacy of caffeine in an episode of apnea of prematurity has been known for over thirty years, but now it has been found that caffeine have others beneficial actions, such as reduction in the incidence of bronchopulmonary dysplasia, less extubation failure, the need for patent ductus arteriosus treatment, and neuroprotective role. The objective is this review was to update the current knowledge of pharmacologic properties, the mechanisms of action, caffeine dosing and therapeutic effects, in the neonatal population

    Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands

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    Rank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with lineage tracing techniques, we found that loss of luminal Rank reduces the luminal progenitor pool and leads to aberrant alveolar-like differentiation with high protein translation capacity in virgin mammary glands. These Rank-deleted luminal cells are unable to expand during the first pregnancy, leading to lactation failure and impairment of protein synthesis potential in the parous stage. The unfit parous Rank-deleted luminal cells in the alveoli are progressively replaced by Rank-proficient cells early during the second pregnancy, thereby restoring lactation. Transcriptomic analysis and functional assays point to the awakening of basal bipotency after pregnancy by the induction of Rank/NF-kappa B signaling in basal parous cell to restore lactation and tissue homeostasis. Rocha and co-authors show that loss of luminal Rank signaling causes abnormal alveolar differentiation and lactation failure. Subsequent pregnancies activate bipotency in basal cells, replacing unfit luminal cells, and restoring lactation

    Aqueous and Ethanolic Valeriana officinalis Extracts Change the Binding of Ligands to Glutamate Receptors

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    The effects of two valerian extracts (aqueous and hydroalcoholic) were investigated through [3H]Glutamate ([3H]Glu) and [3H]Fluorowillardine ([3H]FW) receptor binding assays using rat synaptic membranes in presence of different receptor ligands. In addition, the extract stability was monitored spectrophotometrically. Both extracts demonstrated interaction with ionotropic glutamate receptors (iGluRs). However, the extracts displayed considerable differences in receptor selectivity. The hydroalcoholic extract selectively interacted with quisqualic acid (QA), group I metabotropic glutamate receptor (mGluR) ligand, while the aqueous extract did not alter the binding of QA. The stability of the extracts was examined during several weeks. Freshly prepared extract inhibited 38–60% of [3H]FW binding (AMPA). After 10 days, the aqueous extract inhibited 85% of [3H]FW binding while the hydroalcoholic extract markedly potentiated (200%) [3H]FW binding to AMPA receptors. Thus, our results showed that factors such as extraction solvent and extract stability determine the selectivity for glutamate receptor (GluR) interactions

    Golimumab as rescue therapy for refractory immune-mediated uveitis: a three-center experience

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    OBJECTIVE: To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM) for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. METHODS: Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks) during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. RESULTS: Eight men and 5 women (22 affected eyes) with a median age of 30 years (range 20-38) and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%). GLM therapy achieved complete control of inflammation in 12/13 patients (92.3%) after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P = 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 µ, P = 0.05) at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. CONCLUSIONS: GLM is a new and promising therapeutic option for patients with severe and refractory uveitis

    FCNC Top Quark Decays in Extra Dimensions

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    The flavor changing neutral top quark decay t -> c X is computed, where X is a neutral standard model particle, in a extended model with a single extra dimension. The cases for the photon, X= \gamma,andaStandardModelHiggsboson,X=H,areanalyzedindetailinanonlinear, and a Standard Model Higgs boson, X = H, are analyzed in detail in a non-linearR_\xi gauge. We find that the branching ratios can be enhanced by the dynamics originated in the extra dimension. In the limit where 1/R >> ->, we have found Br(t -> c \gamma) \simeq 10^{-10} for 1/R = 0.5 TeV. For the decay t -> c H, we have found Br(t -> cH) \simeq 10^{-10} for a low Higgs mass value. The branching ratios go to zero when 1/R -> \infty.Comment: Accepted to be published in the Europ. Phys. Jour. C; 16 pages, 2 figure

    Diseño y desarrollo de aplicaciones de aprendizaje ubicuo

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    En la Universidad Nacional de Santiago del Estero se está llevando a cabo el desarrollo del proyecto de investigación titulado "Sistemas de información web personalizados, basados en ontologías, para soporte al aprendizaje ubicuo". El mismo tiene como objetivo principal desarrollar aplicaciones basadas en ontologías que den soporte al aprendizaje ubicuo. En este artículo se presentan los objetivos, los resultados alcanzados y la formación de recursos humanos concretada en el marco del proyecto.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

    Diseño y desarrollo de aplicaciones de aprendizaje ubicuo

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    En la Universidad Nacional de Santiago del Estero se está llevando a cabo el desarrollo del proyecto de investigación titulado "Sistemas de información web personalizados, basados en ontologías, para soporte al aprendizaje ubicuo". El mismo tiene como objetivo principal desarrollar aplicaciones basadas en ontologías que den soporte al aprendizaje ubicuo. En este artículo se presentan los objetivos, los resultados alcanzados y la formación de recursos humanos concretada en el marco del proyecto.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

    Diseño y desarrollo de aplicaciones de aprendizaje ubicuo

    Get PDF
    En la Universidad Nacional de Santiago del Estero se está llevando a cabo el desarrollo del proyecto de investigación titulado "Sistemas de información web personalizados, basados en ontologías, para soporte al aprendizaje ubicuo". El mismo tiene como objetivo principal desarrollar aplicaciones basadas en ontologías que den soporte al aprendizaje ubicuo. En este artículo se presentan los objetivos, los resultados alcanzados y la formación de recursos humanos concretada en el marco del proyecto.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI
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