30 research outputs found

    “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels

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    ON THE TOPOLOGY GENERATED BY SEMI-REGULAR SETS

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    In this paper we study compactness properties of spaces whose topologies are generated by the family of semi-open sets or the family of semi-regular sets of a given topological space (X, tau). In addition, we obtain characterizations of extremally disconnected spaces and show that the concepts of semi-compactness and semi-countable compactness coincide. We also prove that the family of semi-regular sets of a space constitutes a topology iff the corresponding semi-regularization space is locally indiscrete

    Establishing an extra-large segmental Tibial Defect Ovine Animal Model for bone regeneration

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    Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression

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    Natural-resistance associated macrophage protein 1 (Nramp1) encodes a transmembrane phagolysosomal protein exerting resistance toward infections with intracellular pathogens by a mechanism not fully elucidated so far. We used the murine macrophagecell line RAW264.7, stably transfected with functional (RAW-37) or nonfunctional (RAW-21) Nramp1, to study for differences in the expression of NO, a central antimicrobial effector molecule of macrophages. Following stimulation with IFN- and LPS, Nramp1-expressing cells exhibit higher enzymatic activity of inducible NO synthase (iNOS) and increased cytoplasmic iNOS-mRNA levels than RAW-21 cells. Time-course experiments showed that iNOS-mRNA levels remain increased in RAW-37 cells after prolonged cytokine stimulation while they decrease in RAW-21 cells. Reporter gene assays with iNOS-promoter luciferase constructs demonstrated an increased and prolonged promoter activity in Nramp1-resistant vs susceptible cells. This was paralleled by increased IFN regulatory factor 1 (IRF-1) expression and binding affinity to the iNOS promoter in RAW-37 cells, which may be related to enhanced STAT-1 binding affinity in these cells. A point mutation within the IRF-1 binding site of the iNOS promoter abolished the differences in iNOS transcription between RAW-21 and RAW-37 cells. Cells carrying functional Nramp1express increased amounts of NO, which may be related to STAT-1-mediated stimulation of IRF-1 expression with subsequent prolonged activation of iNOS transcription. Enhanced NO expression may partly underlie the protection against infection with intracellular pathogens by Nramp1 functionality
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