72 research outputs found

    Schritt für Schritt zum Bibliothekskonzept – Entwicklung einer Toolbox

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    Die Arbeit mit dem Titel "Schritt für Schritt zum Bibliothekskonzept: Entwicklung einer Toolbox" hat das Ziel im Rahmen des Qualitätsmodell "Ausgezeichnete Bibliothek für kleine Bibliotheken" eine Toolbox zur Konzeptentwicklung zu erstellen. Diese Toolbox soll den Konzeptentwicklungsprozess vereinfachen. Die zentrale Fragestellung ist, in wie weit kann der Erstellungsprozess eines Bibliothekskonzeptes für kleinere Bibliotheken komprimiert und vereinfacht werden. Die Antwort erhält man durch die detaillierte Analyse verschiedener Konzeptentwicklungsmodelle und verschiedener Konzepte ausgewählter Bibliotheken und zum anderen durch die Befragung der ausgewählten Bibliotheken. Die Toolbox als Ergebnis leitet den Konzeptentwickler durch den Prozess und bietet Orientierung und Hilfestellungen an.The scientific paper titled „Step by Step to the Library Concept: Development of a Toolbox”, has the objective to create a toolbox for the process of formation in the framework of the quality model “Ausgezeichnete Bibliothek für kleine Bibliotheken”. This toolbox is to simplify the concept process of formation. The central question is: how can the process of formation of a library concept be condensed and simplified for smaller libraries? You get the answer to that question on the one hand by a detailed analysis of different concept models of formation and different conceptions of selected libraries and on the other hand by surveying these exclusive libraries. As a result this toolbox leads the developer of concept through the process and offers orientation and support

    Sulfur sequestration promotes multicellularity during nutrient limitation

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    The behaviour of Dictyostelium discoideum depends on nutrients. When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism. This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species-generated as a consequence of nutrient limitation-lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron-sulfur cluster. The regulated sequestration of sulfur maintains D. discoideum in a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes

    Dynamic Cardiolipin Synthesis Is Required for CD8<sup>+</sup> T Cell Immunity

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    Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity

    Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation

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    How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range of functions, the polyamine spermidine is needed to hypusinate the translation factor eukaryotic initiation factor 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes the efficient expression of a subset of mitochondrial proteins involved in the TCA cycle and oxidative phosphorylation (OXPHOS). Several of these proteins have mitochondrial targeting sequences (MTSs) that in part confer an increased dependency on eIF5AH. In macrophages, metabolic switching between OXPHOS and glycolysis supports divergent functional fates stimulated by activation signals. In these cells, hypusination of eIF5A appears to be dynamically regulated after activation. Using in vivo and in vitro models, we show that acute inhibition of this pathway blunts OXPHOS-dependent alternative activation, while leaving aerobic glycolysis-dependent classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis

    Enhancing Biological and Biomechanical Fixation of Osteochondral Scaffold: A Grand Challenge

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    Osteoarthritis (OA) is a degenerative joint disease, typified by degradation of cartilage and changes in the subchondral bone, resulting in pain, stiffness and reduced mobility. Current surgical treatments often fail to regenerate hyaline cartilage and result in the formation of fibrocartilage. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bones in the early stage of OA and have shown potential in restoring the joint's function. In this approach, the use of three-dimensional scaffolds (with or without cells) provides support for tissue growth. Commercially available osteochondral (OC) scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, some controversial results are often reported from both clinical trials and animal studies. The objective of this chapter is to report the scaffolds clinical requirements and performance of the currently available OC scaffolds that have been investigated both in animal studies and in clinical trials. The findings have demonstrated the importance of biological and biomechanical fixation of the OC scaffolds in achieving good cartilage fill and improved hyaline cartilage formation. It is concluded that improving cartilage fill, enhancing its integration with host tissues and achieving a strong and stable subchondral bone support for overlying cartilage are still grand challenges for the early treatment of OA

    Role of the Mitochondrial Pyruvate Carrier in Macrophages

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    Völkerrechtlicher Schutz gefährdeter Tiere und Pflanzen vor übermässiger Ausbeutung durch den internationalen Handel : (das Washingtoner Artenschutzabkommen von 1973) /

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    Originally presented as the author's thesis, ZĂĽrich.Bibliography: p. 141-147

    Physical indicators of cartilage health: the relevance of compliance, thickness, swelling and fibrillar texture

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    This study uses a bovine patella model to compare the relative merits of on-bone compliance and thickness measurements, free-swelling behaviour, and structural imaging with differential interference contrast (DIC) light microscopy to assess the biomechanical normality of the cartilage matrix. The results demonstrate that across a spectrum of cartilage tissues from immature, mature, through to mildly degenerate, and all with intact articular surfaces, there is a consistent pattern of increased free swelling of the isolated general matrix with age and degeneration. High swelling was always associated with major structural alterations of the general matrix that were readily imaged using DIC light microscopy. Conversely, for all tissue groups, no relationship was observed between thickness vs. compliance and compliance vs. general matrix swelling. Only in the proximal aspects of the normal mature and degenerate tissues was there a correlation between thickness and general matrix swelling. Free-swelling measurements combined with fibrillar texture imaging using DIC light microscopy are therefore recommended as providing a reliable and quick method of assessing the biomechanical condition of the cartilage general matrix
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