1,250 research outputs found

    Identification of a new cholesterol-binding site within the IFN-γ receptor that is required for signal transduction.

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    The cytokine interferon-gamma (IFN-γ) is a master regulator of innate and adaptive immunity involved in a broad array of human diseases that range from atherosclerosis to cancer. IFN-γ exerts it signaling action by binding to a specific cell surface receptor, the IFN-γ receptor (IFN-γR), whose activation critically depends on its partition into lipid nanodomains. However, little is known about the impact of specific lipids on IFN-γR signal transduction activity. Here, a new conserved cholesterol (chol) binding motif localized within its single transmembrane domain is identified. Through direct binding, chol drives the partition of IFN-γR2 chains into plasma membrane lipid nanodomains, orchestrating IFN-γR oligomerization and transmembrane signaling. Bioinformatics studies show that the signature sequence stands for a conserved chol-binding motif presented in many mammalian membrane proteins. The discovery of chol as the molecular switch governing IFN-γR transmembrane signaling represents a significant advance for understanding the mechanism of lipid selectivity by membrane proteins, but also for figuring out the role of lipids in modulating cell surface receptor function. Finally, this study suggests that inhibition of the chol-IFNγR2 interaction may represent a potential therapeutic strategy for various IFN-γ-dependent diseases

    The Pioneer Anomaly

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    Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

    Contribution of microscopy for understanding the mechanism of action against trypanosomatids

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    Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

    Evaluación y rehabilitación neuropsicológica en oncología pediátrica.

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    Objetivo. El presente trabajo tiene como objetivo el estudio de los efectos neuropsicológicos a largo plazo del cáncer infantil y sus tratamientos así como plantear propuestas para la rehabilitación cognitiva. Método. El método ha consistido en una revisión sistemática de los resultados en la literatura científica acerca de los efectos de la quimioterapia y la radioterapia sobre el SNC y en las funciones cognitivas y conductuales detectados a través de estudios de neuroimagen como calcificaciones y cambios en la sustancia blanca. Presentamos, además, el protocolo de evaluación neuropsicológica ejemplificado con un diagnóstico frecuente que presenta deterioro generalizado. Proponemos un programa de rehabilitación neuropsicológica basado en el Attention Process Training (APT) de Mateer y Sohlberg. Resultado. La radioterapia craneal y el metotrexato producen alteraciones generalizadas que se reflejan en déficit neuropsicológicos: CI, atención, memoria, habilidades académicas y motoras. Conclusiones. El avance en los tratamientos ha supuesto la disminución del número e intensidad de las secuelas. No obstante, sigue siendo frecuente que en los tumores del SNC y en las leucemias aparezcan alteraciones cognitivas y conductuales. La evaluación neuropsicológica continua y los modelos de sustancia blanca nos ayudan a entender estos efectos a largo plazo. Asimismo, esta evaluación es fundamental para diagnosticar los déficit evitando falsas atribuciones y expectativas inadecuadas. Destacamos la necesidad de una unidad de seguimiento y del trabajo interdisciplinario para promover la calidad de vida de los niños con cáncer

    Restoration of european habitats in mainland, Portugal, using commercial seed mixtures. Considerations for its management and conservation

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    Permanent mountain pastures include meadows and other perennial pastures of high ecological, economic, cultural and scenic value. Increasing desertification limits the maintenance and conservation of its biodiversity and the associated landscape mosaic. A restoration experiment in permanent high altitude grasslands in Beira Alta (Centre East (CE) mainland Portugal) was made, by sowing adequate cultivars of existing grass and legume species. The main objectives addressed were: (1) comparison of floristic composition between reference communities included in the previous habitats and the improved communities; (2) evaluation of the success of sowing adequate cultivars of autochthonous species; (3) evaluation of the establishment of target species in terms of the maintenance of floristic composition of reference. The experiment was carried out in 2014 on nine farms situated in Beira Alta (Guarda District) and the phytosociological method was applied in the floristic surveys. The sown species with highest percentage of soil cover were Trifolium subterraneum, Lolium multiflorum, Ornithopus sativus and Trifolium vesiculosum. In the priority habitat 6220 it was observed a re-establishment of many species in their original composition and a high cover of several cultivars of Trifolium subterraneum. These results highlight the importance of using cultivars of autochthonous species in the improvement of altitude pasturesinfo:eu-repo/semantics/publishedVersio

    The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

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    The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

    Postpartum ovarian vein thrombosis after cesarean delivery: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Postpartum ovarian vein thrombosis is an uncommon complication; incidence varies between 0.002% and 0.05%. It most often occurs during the 2–15 days following delivery.</p> <p>Case presentation</p> <p>A 22-year-old pregnant woman at term presented to hospital with uterine contractions, abdominal pain, nausea and vomiting. After delivery an ovarian vein thrombosis was diagnosed.</p> <p>Conclusion</p> <p>Low-molecular weight heparin with broad-spectrum antibiotics are the accepted therapy in non-complicated cases of postpartum ovarian vein thrombosis.</p
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