Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells

A Tool for Developing Correct Programs by Refinement

This report reviews the requirements for tool support of refinement, and reports on the design and implementation of a new tool to support refinement based on these requirements. The main features of the new tool are close integration of refinement and proof in a single tool, good management of the refinement context, an extensible theory base that allows the tool to be adapted to new application domains, and a flexible user interface

Application of Volcano Plots in Analyses of mRNA Differential Expressions with Microarrays

Volcano plot displays unstandardized signal (e.g. log-fold-change) against noise-adjusted/standardized signal (e.g. t-statistic or -log10(p-value) from the t test). We review the basic and an interactive use of the volcano plot, and its crucial role in understanding the regularized t-statistic. The joint filtering gene selection criterion based on regularized statistics has a curved discriminant line in the volcano plot, as compared to the two perpendicular lines for the "double filtering" criterion. This review attempts to provide an unifying framework for discussions on alternative measures of differential expression, improved methods for estimating variance, and visual display of a microarray analysis result. We also discuss the possibility to apply volcano plots to other fields beyond microarray.Comment: 8 figure

Protein kinases modulate store-operated channels in pulmonary artery smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>This study investigates whether protein kinase G (PKG), protein kinase A (PKA) and protein kinase C (PKC) are involved in the regulatory mechanisms of store-operated channel (SOC) in pulmonary arteries.</p> <p>Methods</p> <p>Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat intralobar pulmonary arteries. Whole cell, cell-attached and inside-out patch-clamp electrophysiology were used to monitor SOCs in isolated PASMCs.</p> <p>Results</p> <p>Initially the Ca²⁺-ATPase inhibitor cyclopiazonic acid (CPA, 10 μM) initiated a whole cell current that was reduced by the SOC blocker SKF-96365 (10 μM). Subsequent work using both cell-attached and whole cell configurations revealed that the PKG and PKA inhibitors, KT5823 (3 μM) and H-89 (10 μM), also stimulated SOC activity; this augmentation was attenuated by the SOC blockers SKF-96365 (10 μM) and Ni²⁺(0.1 mM). Finally using the inside-out configuration, the PKC activator phorbol 12-myristate 13-acetate (PMA, 10 μM) was confirmed to modestly stimulate SOC activity although this augmentation appeared to be more substantial following the application of 10 μM inositol 1,4,5-triphosphate (Ins(1,4,5)P₃).</p> <p>Conclusions</p> <p>SOC activity in PASMCs was stimulated by the inhibition of PKG and PKA and the activation of PKC. Our findings suggest that the SOC could be a substrate of these protein kinases, which therefore would regulate the intracellular concentration of calcium and pulmonary arteriopathy via SOC.</p

Photometric observations of the radio bright B[e]/X-ray binary CI Cam

We present multiwavelength (optical, IR, radio) observations of CI Cam, the optical counterpart to the transient X-ray source XTE J0421+560. Pre-outburst quiescent observations reveal the presence of a dusty envelope around the system. Pronounced short term variability is observed at all wavebands from U-K, but no indication of prior flaring of a similar magnitude to the 1998 April outburst is found in these data. Data obtained during the 1998 April X-ray flare reveal pronounced optical-radio flaring. The optical flux was observed to quickly return to quiescent levels, while the radio flare was of much longer duration. The optical component is likely to result from a combination of free-free/free-bound emission, emission line and thermal dust emission, caused by re-radiation of the X-ray flux, while the behaviour of the multiwavelength radio data is consistent with emission from expanding ejecta emitting via the synchrotron mechanism. Post-outburst (1998 August-1999 March) U-M broadband photometric observations reveal that while the optical (UBV) flux remains at pre-outburst quiescent levels, near IR (JHKLM) fluxes exceed the pre-outburst fluxes by ~0.5 magnitudes. Modelling the pre- and post-outburst spectral energy distribution of CI Cam reveals that the structure and/or composition of the dusty component of the circumstellar envelope appears to have changed. Due to a lack of information on the precise chemical composition of the dust within the system several explanations for this behaviour are possible, such as the production of new dust at the inner edge of the envelope, or modification of the composition of the dust due to X-ray irradiation

Love, rights and solidarity: studying children's participation using Honneth's theory of recognition

Recent attempts to theorize children’s participation have drawn on a wide range of ideas, concepts and models from political and social theory. The aim of this article is to explore the specific usefulness of Honneth’s theory of a ‘struggle for recognition’ in thinking about this area of practice. The article identifies what is distinctive about Honneth’s theory of recognition, and how it differs from other theories of recognition. It then considers the relevance of Honneth’s conceptual framework to the social position of children, including those who may be involved in a variety of ‘participatory’ activities. It looks at how useful Honneth’s ideas are in direct engagement with young people’s praxis, drawing on ethnographic research with members of a children and young people’s forum. The article concludes by reflecting on the implications of this theoretical approach and the further questions which it opens up for theories of participation and of adult–child relations more generally

Quantum Cryptography

Quantum cryptography is a new method for secret communications offering the ultimate security assurance of the inviolability of a Law of Nature. In this paper we shall describe the theory of quantum cryptography, its potential relevance and the development of a prototype system at Los Alamos, which utilises the phenomenon of single-photon interference to perform quantum cryptography over an optical fiber communications link.Comment: 36 pages in compressed PostScript format, 10 PostScript figures compressed tar fil

Ursinus College Bulletin Vol. 9, No. 9, June 1893

A digitized copy of the June 1893 Ursinus College Bulletin.https://digitalcommons.ursinus.edu/ucbulletin/1087/thumbnail.jp