3,984 research outputs found

    (In)Visible signatures of the minimal dark abelian gauge sector

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    In this paper we study the present and future sensitivities of the rare meson decay facilities KOTO, LHCb and Belle II to a light dark sector of the minimal dark abelian gauge symmetry where a dark Higgs SS and a dark photon ZDZ_D have masses 10\lesssim 10 GeV. We have explored the interesting scenario where SS can only decay to a pair of ZDZ_D's and so contribute to visible or invisible signatures, depending on the life-time of the latter. Our computations show that these accelerator experiments can access the dark Higgs (mass and scalar mixing) and the dark photon (mass and kinetic mixing) parameters in a complementary way. We have also discussed how the CMS measurement of the SM Higgs total decay width and their limit on the Higgs invisible branching ratio can be used to extend the experimental reach to dark photon masses up to 10\sim 10 GeV, providing at the same time sensitivity to the gauge coupling associated with the broken dark abelian symmetry.Comment: 33 pages, 11 figure

    The RNA binding protein Csx1 promotes sexual differentiation in schizosaccharomyces pombe

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    Sexual differentiation is a highly regulated process in the fission yeast Schizosaccharomyces pombe and is triggered by nutrient depletion, mainly nitrogen source. One of the key regulatory proteins in fission yeast sexual differentiation is the transcription factor Ste11. Ste11 regulates the transcription of many genes required for the initial steps of conjugation and meiosis, and its deficiency leads to sterility. Ste11 activity is mainly regulated at two levels: phosphorylation and abundance of its mRNA. Csx1 is an RNA binding protein that we have previously described to bind and regulate the turnover rate of the mRNA encoding the transcription factor Atf1 in the presence of oxidative stress. We have observed that Csx1-deficient cells have defects in sexual differentiation and are partially sterile. We investigated how Csx1 is regulating this process in S. pombe. Csx1 associates with ste11 + mRNA and cells lacking Csx1 are sterile with a reduced amount of ste11 + mRNA. Overexpression of ste11 + mRNA completely rescues the mating deficiencies of csx1Δ cells. Here, we present a novel mechanism of ste11 + mRNA positive regulation through the activity of Csx1, an RNA binding protein that also have key functions in the response to oxidative stress in fission yeast. This finding opens interesting question about the possible coordination of sexual differentiation and oxidative stress response in eukaryotes and the role of RNA binding proteins in the adaptation to environmental signals.Spanish Ministry of Science and Innovation (BFU2006-01767, BFU2009-09116); Madrid GovernmentPeer Reviewe

    Regulatory landscape of the Hox transcriptome

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    Precise regulation of Hox gene activity is essential to achieve proper control of animal embryonic development and to avoid generation of a variety of malignancies. This is a multilayered process, including complex polycistronic transcription, RNA processing, microRNA repression, long noncoding RNA regulation and sequence-specific translational control, acting together to achieve robust quantitative and qualitative Hox protein output. For many such mechanisms, the Hox cluster gene network has turned out to serve as a paradigmatic model for their study. In this review, we discuss current knowledge of how the different layers of post-transcriptional regulation and the production of a variety of noncoding RNA species control Hox output, and how this shapes formation of developmental systems that are reproducibly patterned by complex Hox networks.Fundação para a Ciência e a Tecnologia grants: ( PTDC/BEX-BID/0899/2014, SFRH/BD/51876/2012); Santa Casa da Misericordia de Lisboa grant: (SCML-MC-60-2014);info:eu-repo/semantics/publishedVersio

    Eye drop Self-medication: Comparative Questionnaire-based study of two Latin American cities.

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    A broad spectrum of ocular symptoms are treated by self-medication with commercial eye-drops.  This behavior threatens individuals' visual health. In Latin America, evidence is poor. Objective:  To  detect,  characterize  and  compare  patterns  of  ophthalmic  self-medication  between  Córdoba (Argentina) and Barranquilla (Colombia).Design:  Analytic, cross-sectional and comparative population-based study. Setting: Two private tertiary care ophthalmology centers from Córdoba, Argentina, and Barranquilla, Colombia.Participants:  Patients 18 years of age or older who consulted for the first time in this two institutions duringAugust-November 2009, were included. A number of 570 patients were enrrolled.Methods:  Data collected through a semi-structured questionnaire. Main outcome measure: To determine thefrequency of self-medication with eyedrops on a specific population of two cities in Latin America.Results:  Comparable  rates  of  ocular  self-medication  were  found  (25.6%  and  25.7%  for  Cordoba  and Barranquilla, respectively). The percentage of men and women who self-medicated was not significantly different between both samples. The major source of eye drops recommendation in the Argentineans patients was the pharmacist (31%); while the social source was predominant in Colombian individuals (53%). In Cordoba, the most frequently used product was a non-steroidal anti-inflammatory drop in combination with a vasoconstrictive agent (32%); while in Barranquilla, antibiotic eye drops were preferred (33%). Self-medication was higher between the ages of 31 and 50 years old in Argentinean citizens (28%) and between 18 to 31 years old in the Colombiancommunity (39%). This habit was found mostly in patients who completed university studies in Cordoba (33%); in Barranquilla, individuals with lower educational level practice more this behavior (36%).Conclusion:  In both populations, patients commonly treat ocular conditions by self-medicating. Currently, anincreasing number of eye drops are obtainable without prescription and a high percentage of self-medicated patients in both samples ignore the possible side effects of the used medication.Fil: Marquez, Gabriel. Fundación VER; ArgentinaFil: Hildegard Piñeros-Heilbron. Fundación Oftalmológica del Caribe; ColombiaFil: Sanchez, Victoria M.. Fundación VER; ArgentinaFil: Torres, Victor Eduardo Roque. Fundación VER; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Gramajo, Ana L.. Fundación VER; ArgentinaFil: Juarez, Claudio P.. Fundación VER; Argentina. Fundación Oftalmológica del Caribe; ColombiaFil: Peña, Fernando. Fundación Oftalmológica del Caribe; ColombiaFil: Luna, José D.. Fundación VER; Argentin

    Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM) of Piperine

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    In this article we introduce a proof of concept strategy: Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM) to expedite the discovery of drug metabolites. The use of a bioactive natural product, piperine, that has a well curated metabolite profile but has an unpredictable computational metabolism (Biotransformer v3.0) was selected. We developed an electrochemical reaction to oxidise piperine into a range of metabolites, which were detected by LC-MS. In turn, a series of chemically plausible metabolites were predicted based on ion-fragmentation patterns. These metabolites were docked into the active site of CYP3A4 using Autodock4.2 From the clustered low-energy profile of piperine in the active site it can be inferred that the most likely metabolic position of piperine (based on intermolecular distances to the Fe-oxo active site) is the benzo[d][1,3]dioxole motif. The metabolic profile was confirmed by literature comparison and the electrochemical reaction delivered plausible metabolites vide infra. Thus, demonstrating the power of the hyphenated technique of tandem electrochemical detection and computational evaluation of binding poses. Taken together, we outline a novel approach where diverse data sources are combined to predict and confirm a metabolic outcome for a bioactive structure

    Birds breathe at an aerodynamic resonance

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    We present a dynamical model for the avian respiratory system and report the measurement of its variables in normal breathing canaries (Serinus canaria). Fitting the parameters of the model, we are able to show that the birds in our study breathe at an aerodynamic resonance of their respiratory system. For different respiratory regimes, such as singing, where rapid respiratory gestures are used, the nonlinearities of the model lead to a shift in its resonances toward higher frequency values.Fil: Fainstein, Facundo. Universidad de Buenos Aires; ArgentinaFil: Geli, Sebastián M.. Universidad de Buenos Aires; ArgentinaFil: Amador, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Goller, Franz. Westfälische Wilhelms Universität; AlemaniaFil: Mindlin, Bernardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentin

    Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM) of Piperine

    Get PDF
    In this article, we introduce a proof-of-concept strategy, Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM), to expedite the discovery of drug metabolites. The use of a bioactive natural product, piperine, that has a well-curated metabolite profile but an unpredictable computational metabolism (Biotransformer v3.0) was selected. We developed an electrochemical reaction to oxidize piperine into a range of metabolites, which were detected by LC-MS. A series of chemically plausible metabolites were predicted based on ion fragmentation patterns. These metabolites were docked into the active site of CYP3A4 using Autodock4.2. From the clustered low-energy profile of piperine in the active site, it can be inferred that the most likely metabolic position of piperine (based on intermolecular distances to the Fe-oxo active site) is the benzo[d][1,3]dioxole motif. The metabolic profile was confirmed by comparison with the literature, and the electrochemical reaction delivered plausible metabolites, vide infra, thus, demonstrating the power of the hyphenated technique of tandem electrochemical detection and computational evaluation of binding poses. Taken together, we outline a novel approach where diverse data sources are combined to predict and confirm a metabolic outcome for a bioactive structure
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