8 research outputs found

    Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation

    Get PDF
    Objective  Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined. We aimed to determine whether loss of GCN5 in skeletal muscle enhances mitochondrial density and function, and the adaptive response to endurance exercise training.  Methods  We used Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype (WT) littermates. We measured whole-body energy expenditure, as well as markers of mitochondrial density, biogenesis, and function in skeletal muscle from sedentary mice, and mice that performed 20 days of voluntary endurance exercise training.  Results  Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity were comparable between mKO and WT mice. Further, there were no genotype differences in endurance exercise-mediated mitochondrial biogenesis or increases in PGC-1α protein content.  Conclusion  These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle

    Synaptotagmin‐7 enhances calcium‐sensing of chromaffin cell granules and slows discharge of granule cargos

    Full text link
    Synaptotagmin‐7 (Syt‐7) is one of two major calcium sensors for exocytosis in adrenal chromaffin cells, the other being synaptotagmin‐1 (Syt‐1). Despite a broad appreciation for the importance of Syt‐7, questions remain as to its localization, function in mediating discharge of dense core granule cargos, and role in triggering release in response to physiological stimulation. These questions were addressed using two distinct experimental preparations—mouse chromaffin cells lacking endogenous Syt‐7 (KO cells) and a reconstituted system employing cell‐derived granules expressing either Syt‐7 or Syt‐1. First, using immunofluorescence imaging and subcellular fractionation, it is shown that Syt‐7 is widely distributed in organelles, including dense core granules. Total internal reflection fluorescence (TIRF) imaging demonstrates that the kinetics and probability of granule fusion in Syt‐7 KO cells stimulated by a native secretagogue, acetylcholine, are markedly lower than in WT cells. When fusion is observed, fluorescent cargo proteins are discharged more rapidly when only Syt‐1 is available to facilitate release. To determine the extent to which the aforementioned results are attributable purely to Syt‐7, granules expressing only Syt‐7 or Syt‐1 were triggered to fuse on planar supported bilayers bearing plasma membrane SNARE proteins. Here, as in cells, Syt‐7 confers substantially greater calcium sensitivity to granule fusion than Syt‐1 and slows the rate at which cargos are released. Overall, this study demonstrates that by virtue of its high affinity for calcium and effects on fusion pore expansion, Syt‐7 plays a central role in regulating secretory output from adrenal chromaffin cells.Syt‐7 is a high‐affinity calcium sensor expressed on chromaffin cell dense core granules. The purpose of this study was to assess the role of Syt‐7 in regulating the secretory response to cholinergic stimulation. Acetylcholine elicits secretion by elevating cytosolic calcium. The calcium sensitivity of exocytosis in cells lacking Syt‐7 is impaired. Cells that lack Syt‐7 also release peptide hormones at faster rates, implicating a role for Syt‐7 in regulating the exocytotic fusion pore. These data demonstrate that Syt‐7 has an important role in triggering exocytosis in cells and is likely to play a role in controlling hormone output, in situ.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162737/3/jnc14986.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162737/2/jnc14986-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162737/1/jnc14986_am.pd

    Regolith depth, mobility, and variability on Vesta from Dawn's low altitude mapping orbit

    Get PDF
    Regolith, the fragmental debris layer formed from impact events of all sizes, covers the surface of all asteroids imaged by spacecraft to date. Here we use Framing Camera (FC) images [1] acquired by the Dawn spacecraft [2] from its low-altitude mapping orbit (LAMO) of 210 km (pixel scales of ~20 m) to characterize regolith depth, variability, and mobility on Vesta, and to locate areas of especially thin regolith and exposures of competent material. These results will help to evaluate how the surface of this differentiated asteroid has evolved over time, and provide key contextual information for understanding the origin and degree of mixing of the surficial materials for which compositions are estimated [3,4] and the causes of the relative spectral immaturity of the surface [5]. Vestan regolith samples, in the form of howardite meteorites, can be studied in the laboratory to provide complementary constraints on the regolith process [6]

    Anatomie von Kommunikationsrollen. Methoden zur Identifizierung von Akteursrollen in gerichteten Netzwerken.

    Full text link
    Die Identifizierung von generalisierbaren Akteursrollen in sozialen Systemen ist seit jeher ein zentrales Anliegen der Sozialwissenschaften. Dies gilt insbesondere für die Identifizierung von Kommunikationsrollen, um die überaus komplexen Prozesse der interpersonalen und massenmedialen Kommunikation systematisch zu beschreiben und zu verstehen. Der vorliegende Beitrag zeigt auf, welche theoretischen und methodischen Überlegungen bei der Operationalisierung von Akteursrollen in gerichteten Netzwerken zu berücksichtigen sind. Basierend auf einer netzwerkanalytischen Betrachtung werden zum einen Unzulänglichkeiten in bestehenden Operationalisierungen von Kommunikationsrollen aufgezeigt und zum anderen neue Konzepte vorgeschlagen. Die diskutierten Konzepte lassen sich zwei unterschiedlichen Ansätzen zuordnen. Einerseits können Mikrostrukturen wie dyadische und triadische Ego Rollen als Basis für die Operationalisierung verwendet werden und andererseits kann man von der Gesamtstruktur des Netzwerks ausgehen. Für den ersten Fall werden unterschiedliche Aggregationsregeln diskutiert, welche eine Anwendung in komplexeren Netzwerken ermöglichen. Beim zweiten Ansatz, der Berücksichtigung der Gesamtstruktur, werden die Eignung unterschiedlicher Zentralitätsmaße, das Konzept des Blockmodelling und die hierarchische Strukturanalyse besprochen. Zwecks Anschaulichkeit beschränkt sich dieser Beitrag auf Rollen in Kommunikationsnetzwerken. Die vorgestellten Konzepte sind jedoch auch auf andere Netzwerke übertragbar, die aus gerichteten Beziehungen bestehen. ----------------------------------------------------------- The identification of generalizable roles in social systems has been one of the most central issues in social science ever since. Particularly in the field of interpersonal communication, the notion of communication roles has been used to describe and better understand the complex processes in social groups and society. This contribution identifies the theoretical and methodological concepts that have to be considered when roles in directed networks are operationalized. Based on a network analytic approach and critically evaluating the shortcomings of some widely used models, this study aims to propose new concepts for the operationalization of communication roles. These concepts can be divided into two distinctive approaches. One possibility is to use microstructures like dyadic and triadic communication roles as basic units. For this approach, different aggregation rules are discussed which are necessary for their application in more complex networks. The second approach takes the overall structure of a network into ac-count and identifies different roles by applying centrality measures, blockmodelling or hierarchical structure analysis tools. For illustrative reasons, this study limits its focus on the operationalization of communication roles as a prominent object in social science research. The concepts presented, however, are applicable for directed graphs in general
    corecore