69 research outputs found

    Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment

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    During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation

    IMPACT-Global Hip Fracture Audit: Nosocomial infection, risk prediction and prognostication, minimum reporting standards and global collaborative audit. Lessons from an international multicentre study of 7,090 patients conducted in 14 nations during the COVID-19 pandemic

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    Biochronostratigraphy and paleoenvironment analysis of Neogene deposits from the Pelotas Basin (well 2-TG-96-RS), Southernmost Brazil

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    This paper presents the integration of micropaleontological (palynology and foraminifera) and isotopic (87Sr/86Sr) analysis of a selected interval from the well 2-TG-96-RS, drilled on the onshore portion of the Pelotas Basin, Rio Grande do Sul, Brazil. A total of eight samples of the section between 140.20 and 73.50 m in depth was selected for palynological analysis, revealing diversified and abundant palynomorph associations. Species of spores, pollen grains and dinoflagellate cysts are the most common palynomorphs found. Planktic and benthic calcareous foraminifera were recovered from the lowest two levels of the section (140.20 and 134.30 m). Based on the stratigraphic range of the species of dinoflagellate cysts and sporomorphs, a span age from Late Miocene to Early Pliocene is assigned. The relative age obtained from the 87Sr/86Sr ratio in shells of calcareous foraminifers indicates a Late Miocene (Messinian) correspondence, corroborating the biostratigraphic positioning performed with palynomorphs. Paleoenvironmental interpretations based on the quantitative distribution of organic components (palynomorphs, phytoclasts and amorphous organic matter) throughout the section and on foraminiferal associations indicate a shallow marine depositional environment for the section. Two palynologicals intervals were recognized based on palynofacies analysis, related to middle to outer shelf (140.20 to 128.90 m) and inner shelf (115.75 to 73.50 m) conditions

    Murine in vitro cellular models to better understand adipogenesis and its potential applications

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    Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology
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