422 research outputs found

    RUNX3 Regulates Intercellular Adhesion Molecule 3 (ICAM-3) Expression during Macrophage Differentiation and Monocyte Extravasation

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    The adhesion molecule ICAM-3 belongs to the immunoglobulin gene superfamily and functions as a ligand for the β2 integrins LFA-1, Mac-1 and αdβ2. The expression of ICAM-3 is restricted to cells of the hematopoietic lineage. We present evidences that the ICAM-3 gene promoter exhibits a leukocyte-specific activity, as its activity is significantly higher in ICAM-3+ hematopoietic cell lines. The activity of the ICAM-3 gene promoter is dependent on the occupancy of RUNX cognate sequences both in vitro and in vivo, and whose integrity is required for RUNX responsiveness and for the cooperative actions of RUNX with transcription factors of the Ets and C/EBP families. Protein analysis revealed that ICAM-3 levels diminish upon monocyte-derived macrophage differentiation, monocyte transendothelial migration and dendritic cell maturation, changes that correlate with an increase in RUNX3. Importantly, disruption of RUNX-binding sites led to enhanced promoter activity, and small interfering RNA-mediated reduction of RUNX3 expression resulted in increased ICAM-3 mRNA levels. Altogether these results indicate that the ICAM-3 gene promoter is negatively regulated by RUNX transcription factors, which contribute to the leukocyte-restricted and the regulated expression of ICAM-3 during monocyte-to-macrophage differentiation and monocyte extravasation

    El diseño de las instituciones en el Estado Sandinista (1979-1982): la revolución como fuente de derecho

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    While the institutions of the new revolutionary state were emerging in Nicaragua, an element which would remain constant throughout the 1980s was taking shape: the pre-eminence of the executive power and the loss of the initial support of the Sandinista National Liberation Front (FSLN). At the same time, the understanding between Nicaragua and the US, which was already complicated within the context of the Cold War, worsened during this period. This paper aims to elucidate the various factors which caused the imbalance in the distribution of powers within Sandinista institutions.A medida que se iban perfilando en Nicaragua las instituciones del nuevo Estado revolucionario, se fue consolidando una constante que permanecería toda la década de 1980: la preeminencia del poder ejecutivo sobre los demás y la pérdida de los grandes apoyos iniciales del Frente Sandinista de Liberación Nacional (FSLN). Asimismo, el entendimiento entre Nicaragua y EE.UU., ya difícil en el contexto de la Guerra Fría, empeoró durante este período. El presente trabajo pretende dilucidar los diversos factores que generaron el desequilibrio de poderes del diseño institucional sandinista

    Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying

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    The main aim of this work was to evaluate the effect of high-intensity ultrasound (US) on the drying kinetics of orange peel as well as its influence on the microstructural changes induced during drying. Convective drying kinetics of orange peel slabs were carried out at a relative humidity of 26.5±0.9%, 40 °C and 1 m/s with (AIR+US) and without (AIR) ultrasound application. In order to identify the US effect on water transport, drying kinetics were analyzed by taking the diffusion theory into account. Fresh, AIR and AIR+US dried samples were analyzed using Cryo-Scanning Electron Microscopy. Results showed that the drying kinetics of orange peel were significantly improved by US application, which involved a significant (p<0.05) improvement of mass transfer coefficient and effective moisture diffusivity. The effects on mass transfer properties were confirmed with microstructural observations. In the cuticle surface of flavedo, the pores were obstructed by the spread of the waxy components, this fact evidencing US effects on the air solid interfaces. Furthermore, the cells of the albedo were disrupted by US, as it created large intercellular air spaces facilitating water transfer through the tissue.The authors would like to acknowledge the financial support of MICINN and CEE (European Regional Development Fund) from projects Ref. DPI2009-14549-C04-04, PSE-060000-2009-003, and FP6-2004-FOOD-23140 HIGHQ RTE.García Pérez, JV.; Ortuño Cases, C.; Puig Gómez, CA.; Cárcel Carrión, JA.; Pérez Munuera, IM. (2012). Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying. Food and Bioprocess Technology. 5(6):2256-2265. https://doi.org/10.1007/s11947-011-0645-0S2256226556Alandes, L., Perez-Munuera, I., Llorca, E., Quiles, A., & Hernando, I. (2009). 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    Functional impact and evolution of a novel human polymorphic inversion that disrupts a gene and creates a fusion transcript

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    Since the discovery of chromosomal inversions almost 100 years ago, how they are maintained in natural populations has been a highly debated issue. One of the hypotheses is that inversion breakpoints could affect genes and modify gene expression levels, although evidence of this came only from laboratory mutants. In humans, a few inversions have been shown to associate with expression differences, but in all cases the molecular causes have remained elusive. Here, we have carried out a complete characterization of a new human polymorphic inversion and determined that it is specific to East Asian populations. In addition, we demonstrate that it disrupts the ZNF257 gene and, through the translocation of the first exon and regulatory sequences, creates a previously nonexistent fusion transcript, which together are associated to expression changes in several other genes. Finally, we investigate the potential evolutionary and phenotypic consequences of the inversion, and suggest that it is probably deleterious. This is therefore the first example of a natural polymorphic inversion that has position effects and creates a new chimeric gene, contributing to answer an old question in evolutionary biology

    Skin manifestations in COVID-19: prevalence and relationship with disease severity

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    Background: Data on the clinical patterns and histopathology of SARS-CoV-2 related skin lesions, as well as on their relationship with the severity of COVID-19 are limited. Methods and Materials: Retrospective analysis of a prospectively collected cohort of patients with SARS-CoV-2 infection in a teaching hospital in Barcelona, Spain, from 1 April to 1 May 2020. Clinical, microbiological and therapeutic characteristics, clinicopathological patterns of skin lesions, and direct immunofluorescence and immunohistochemical findings in skin biopsies were analyzed. Results: Fifty-eight out of the 2761 patients (2.1%) either consulting to the emergency room or admitted to the hospital for COVID-19 suspicion during the study period presented COVID-19 related skin lesions. Cutaneous lesions could be categorized into six patterns represented by the acronym "GROUCH": Generalized maculo-papular (20.7%), Grover's disease and other papulo-vesicular eruptions (13.8%), livedo Reticularis (6.9%), Other eruptions (22.4%), Urticarial (6.9%), and CHilblain-like (29.3%). Skin biopsies were performed in 72.4%, including direct immunofluorescence in 71.4% and immunohistochemistry in 28.6%. Patients with chilblain-like lesions exhibited a characteristic histology and were significantly younger and presented lower rates of systemic symptoms, radiological lung infiltrates and analytical abnormalities, and hospital and ICU admission compared to the rest of patients. Conclusion: Cutaneous lesions in patients with COVID-19 appear to be relatively rare and varied. Patients with chilblain-like lesions have a characteristic clinicopathological pattern and a less severe presentation of COVID-19

    Dia2 Controls Transcription by Mediating Assembly of the RSC Complex

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    Background: Dia2 is an F-box protein found in the budding yeast, S. cerevisiae. Together with Skp1 and Cul1, Dia2 forms the substrate-determining part of an E3 ubiquitin ligase complex, otherwise known as the SCF. Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex. Principal Findings: We identified components of the RSC chromatin remodelling complex as genetic interactors with Dia2, suggesting an additional role for Dia2 in the regulation of transcription. We show that Dia2 is involved in controlling assembly of the RSC complex. RSC belongs to a group of ATP-dependent nucleosome-remodelling complexes that controls the repositioning of nucleosomes. The RSC complex is expressed abundantly and its 17 subunits are recruited to chromatin in response to both transcription activation and repression. In the absence of Dia2, RSC-mediated transcription regulation was impaired, with concomitant abnormalities in nucleosome positioning. Conclusions: Our findings imply that Dia2 is required for the correct assembly and function of the RSC complex. Dia2, by controlling the RSC chromatin remodeller, fine-tunes transcription by controlling nucleosome positioning during transcriptional activation and repression

    The Role of the Yap5 Transcription Factor in Remodeling Gene Expression in Response to Fe Bioavailability

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    The budding yeast Saccharomyces cerevisiae has developed several mechanisms to avoid either the drastic consequences of iron deprivation or the toxic effects of iron excess. In this work, we analysed the global gene expression changes occurring in yeast cells undergoing iron overload. Several genes directly or indirectly involved in iron homeostasis showed altered expression and the relevance of these changes are discussed. Microarray analyses were also performed to identify new targets of the iron responsive factor Yap5. Besides the iron vacuolar transporter CCC1, Yap5 also controls the expression of glutaredoxin GRX4, previously known to be involved in the regulation of Aft1 nuclear localization. Consistently, we show that in the absence of Yap5 Aft1 nuclear exclusion is slightly impaired. These studies provide further evidence that cells control iron homeostasis by using multiple pathways

    Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

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    A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

    Measurement of the relative rate of prompt χc0, χc1 and χc2 production at √s=7TeV

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    Prompt production of charmonium χc0, χc1 and χc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of √s=7TeV. The χc mesons are identified through their decay to J/ψγ, with J/ψ→μ+mu− using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fb−1 collected by the LHCb detector, is used to measure the relative prompt production rate of χc1 and χc2 in the rapidity range 2.0<y<4.5 as a function of the J/ψ transverse momentum from 3 to 20 GeV/c. First evidence for χc0 meson production at a hadron collider is also presented

    Study of DJ meson decays to D+π−, D0π+ and D∗+π− final states in pp collisions

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    A study of D+π−, D0π+ and D∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D1(2420)0 resonance is observed in the D∗+π− final state and the D∗2(2460) resonance is observed in the D+π−, D0π+ and D∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D∗+π−, D+π− and D0π+ final states
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