243 research outputs found

    Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation.

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    Cultured cardiac myocytes from adult Sprague-Dawley rats express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man6P) receptors and respond to IGF-I with a dose-dependent accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2]. Specific binding of [125I]IGF-I to isolated membranes from cultured cardiac myocytes amounted to 1-1.2%. Binding of [125I]IGF-I was inhibited by unlabeled IGF-I at nanomolar concentrations and insulin at much higher concentrations. These data suggest that IGF-I binds to its own receptor on rat cardiac myocytes. Competitive binding studies using isolated membranes from cardiac myocytes and [125I]IGF-II showed 2-4% specific binding. Binding of [125I]IGF-II was inhibited by IGF-II and much less potently by IGF-I and insulin. Immunoglobulin G (IgG) 3637 (an IgG directed against the IGF-II/Man6P receptor) partially inhibited binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity cross-linking studies with [125I]IGF-II and cardiac myocyte membranes and subsequent analysis of the ligand-receptor complex using SDS-PAGE and autoradiography showed a radiolabeled band of approximately 250 kilodalton (kDa). The formation of the [125I]IGF-II-receptor complex was inhibited by incubation with IGF-II and IgG 3637 but not by insulin or nonimmune IgG. Western blotting of protein extracts from cultured cardiac myocytes was performed using IgG 3637 and an immunoperoxidase technique for the visualization of the IGF-II/Man6P receptor protein. A specific band at 220 kDa under nonreducing conditions was detected on the blots, providing further evidence for the expression of the IGF-II/Man6P receptor by cardiac myocytes. The effect of IGFs on the accumulation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo-[3H]inositol-labeled cultured cardiac myocytes. IGF-I (50 ng/ml) stimulated the accumulation both of Ins(1,4,5)P3 and Ins(1,4)P2 after 30 sec by 43% and 63%. IGF-II (up to 500 ng/ml) had no significant effect on inositol phosphate accumulation under the same conditions. However, in the presence of millimolar concentrations of Man6P, IGF-II (500 ng/ml) also increased Ins(1,4,5)P3 accumulation by 59%. We conclude that cardiac myocytes from adult rats express IGF receptors and respond to IGFs with the accumulation of Ins(1,4,5)P3 and Ins(1,4)P2. This effect seems to be mediated by an IGF-I receptor-specific pathway

    "Einer von drei Sozialpädagogen arbeitet nach dem Studium mit alten Menschen" : Alternswissenschaft ist für eine zukunftsorientierte Universität essenziell ; im Gespräch: Prof. Dr. Gisela Zenz und Prof. Dr. Günther Böhme mit Ulrike Jaspers und Anne Hardy

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    Als Sie vor über drei Jahren das Forum »Alterswissenschaften und Alterspolitik« ins Leben gerufen haben, wollten Sie eine fächerübergreifende Zusammenarbeit in der Altersforschung initiieren. Was ist daraus geworden? Zenz: Wir haben zunächst einmal mit der öffentlichen Vorstellung von Frankfurter Forschungsprojekten begonnen. Im Rahmen einer Vortragsreihe sind immer wieder Wissenschaftler aus unterschiedlichen Disziplinen zusammengekommen – aus Sportwissenschaft und Psychologie, Biologie und Hirnforschung, Ökonomie und Soziologie, Psychiatrie und Pädagogik. Dabei sind auch Fachhochschul- und Praxisprojekte einbezogen worden, um Beispiel vom Frankfurter Bürgerinstitut. Und immer haben wir Wert darauf gelegt, dass neben den etablierten Professoren der »wissenschaftliche Nachwuchs« zu Wort kam. ..

    Retrieval of the Vacuolar H+-ATPase from Phagosomes Revealed by Live Cell Imaging

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    The vacuolar H+-ATPase, or V-ATPase, is a highly-conserved multi-subunit enzyme that transports protons across membranes at the expense of ATP. The resulting proton gradient serves many essential functions, among them energizing transport of small molecules such as neurotransmitters, and acidifying organelles such as endosomes. The enzyme is not present in the plasma membrane from which a phagosome is formed, but is rapidly delivered by fusion with endosomes that already bear the V-ATPase in their membranes. Similarly, the enzyme is thought to be retrieved from phagosome membranes prior to exocytosis of indigestible material, although that process has not been directly visualized., we fed the cells yeast, large particles that maintain their shape during trafficking. To track pH changes, we conjugated the yeast with fluorescein isothiocyanate. Cells were labeled with VatM-GFP, a fluorescently-tagged transmembrane subunit of the V-ATPase, in parallel with stage-specific endosomal markers or in combination with mRFP-tagged cytoskeletal proteins.We find that the V-ATPase is commonly retrieved from the phagosome membrane by vesiculation shortly before exocytosis. However, if the cells are kept in confined spaces, a bulky phagosome may be exocytosed prematurely. In this event, a large V-ATPase-rich vacuole coated with actin typically separates from the acidic phagosome shortly before exocytosis. This vacuole is propelled by an actin tail and soon acquires the properties of an early endosome, revealing an unexpected mechanism for rapid recycling of the V-ATPase. Any V-ATPase that reaches the plasma membrane is also promptly retrieved.Thus, live cell microscopy has revealed both a usual route and alternative means of recycling the V-ATPase in the endocytic pathway

    An in-depth look at prior art in fast round-robin arbiter circuits

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    Arbiters are found where shared resources exist such as busses, switching fabrics, processing elements. Round-robin is a fair arbitration method, where requestors get near-equal shares of a common resource or service. Round-robin arbitration (RRA) finds use in network switches/routers and processor boards/systems as well as many other applications that have concurrency. Today's electronic systems require arbiters with hundreds of ports (e.g., switching fabrics with virtual I/O queues) and clock speeds near the limits of even the latest microelectronics fabrication processes/libraries. Achieving high clock speeds in the presence of large number of ports is only possible with highly parallel arbiter architectures. This paper presents an in-depth literature survey of previous work on this problem. It looks at RRA work in the literature in a bigger context, then defines the typical RRA problem (RRA_typical), and specifically investigates work on fast architectures that solve the RRA_typical problem. There are five such works that are really competitive. This report takes a very in-depth look at these works. It explains each architecture and how/why it works from a unique perspective that cannot be found in the original publication of that architecture. It also proposes improvements to these architectures. We wrote generators for the improved versions of these architectures. We will share a summary of synthesis results in this report – although a detailed account of how these results were obtained and their analysis is the subject of another (upcoming) publicatio

    evidence for a moderator effect

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    Background: While ethnic discrimination emphasizes boundaries between different cultures, the concept of transculturality focuses on the fact that cultures can merge and that individuals integrate novel cultural elements into their identity. This is an exploratory study that investigates the interplay between perceived ethnic discrimination, psychological adjustment and transcultural identity. Methods: Structured interviews were conducted using a sample of 46 adolescents with a Turkish migratory background and 45 adolescents who were native born Germans. Results: Correlational and multiple regression analyses revealed that perceived discrimination was clearly associated with a poorer psychological adjustment among adolescents with a migratory background. Transcultural identity moderated this relationship. That is, adolescents who showed higher levels of transcultural identity displayed a better psychological adjustment when compared to adolescents who showed lower levels of transcultural identity—provided that they did not feel discriminated against. This is congruent with the idea that transcultural identity can involve considerable benefits for personality. However, when adolescents perceived higher rates of discrimination, higher levels of transcultural identity came attached to a poorer psychological adjustment. Conclusions: The findings suggest that perceived discrimination has negative effects on the well-being of immigrant adolescents—particularly for those who describe their identity as transcultural. The findings are discussed considering specific characteristics of transcultural identity, and how they stand in opposition to discrimination
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