Protein tyrosine phosphorylation is involved in osmoregulation of ionic conductances

Using the human Intestine 407 cell line as a model, we investigated a possible role for tyrosine kinase(s) in regulating the ion efflux pathways induced by hyposmotic stimulation (regulatory volume decrease, RVD). Pretreatment of 125I(-)-and 86Rb(+)-loaded cells with the phosphotyrosine phosphatase inhibitor sodium orthovanadate (200 microM) potentiated isotope efflux triggered by mild hypotonicity (10-20%) but did not further increase the efflux in response to more vigorous osmotic stimulation (30% hypotonicity). The tyrosine kinase inhibitors herbimycin A and genistein largely reduced the osmoshock-induced efflux in both control and vanadate-pretreated cells, while not affecting calcium-activated 86Rb+ efflux. Potentiation of the RVD response by vanadate was confirmed by direct measurements of hypotonicity-induced changes in cell volume. Hypotonic shock alone triggered a rapid and transient increase in tyrosine phosphorylation of several proteins as well as phosphorylation of mitogen-activated protein kinase. Furthermore, the potentiating effects of vanadate on hypotonicity-induced ion efflux and mitogen-activated protein (MAP) kinase phosphorylation were mimicked by epidermal growth factor. Neither vanadate nor epidermal growth factor provoked a RVD-like ionic response under isotonic conditions. These results indicate that tyrosine phosphorylation is an essential step in the RVD response and suggest a novel role of growth factors in the cellular defense against osmotic stress

Political Regimes and Sovereign Credit Risk in Europe, 1750-1913

This article uses a new panel data set to perform a statistical analysis of political regimes and sovereign credit risk in Europe from 1750 to 1913. Old Regime polities typically suffered from fiscal fragmentation and absolutist rule. By the start of World War I, however, many such countries had centralized institutions and limited government. Panel regressions indicate that centralized and?or limited regimes were associated with significant improvements in credit risk relative to fragmented and absolutist ones. Structural break tests also reveal close relationships between major turning points in yield series and political transformations

A molecular communication channel consisting of a single reversible chain of hydrogen bonds in a conformationally flexible oligomer

Communication of information through the global switching of conformation in synthetic molecules has hitherto entailed the inversion of chirality. Here, we report a class of oligomer through which information may be communicated through a global reversal of polarity. Ethylene-bridged oligoureas are constitutionally symmetrical, conformationally flexible molecules organized by a single chain of hydrogen bonds running the full length of the oligomer. NMR reveals that this hydrogen-bonded chain may undergo a coherent reversal of directionality. The directional uniformity of the hydrogen-bond chain allows it to act as a channel for the spatial communication of information on a molecular scale. A binding site at the terminus of an oligomer detects local information about changes in pH or anion concentration and transmits that information—in the form of a directionality switch in the hydrogen-bond chain—to a remote polarity-sensitive fluorophore. This propagation of polarity-encoded information provides a new mechanism for molecular communication

P38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level

The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling cascade in human umbilical vein endothelial cells. TNFalpha increased the activity of the p38 substrate MAP kinase-activated-protein (MAPKAP) kinase 2 and the subsequent phosphorylation of the small heat shock protein Hsp27 about two to three fold. This stimulation was blocked almost completely by the specific p38 MAP kinase inhibitor SB203580. This inhibitor also suppressed the TNFalpha-induced surface expression of the endothelial adhesion molecule vascular cell adhesion molecule (VCAM)-1. In contrast, inhibition of p38 MAP kinase had no effect on the stimulated surface expression of the intercellular cell adhesion molecule (ICAM)-1. VCAM-1 mRNA accumulation induced by TNFalpha was not affected by SB203580, suggesting that the p38 MAP kinase signalling cascade regulates the endothelial expression of VCAM-1 at the post-transcriptional level

The perspectives of people with intellectual disabilities on their experience of voting in UK general elections

Background: People with intellectual disabilities' voting rate within the United Kingdom remains significantly below the population average despite government enacted voting promotion measures. No published academic literature directly involves people with intellectual disabilities when considering their UK general election experiences – this study aims to address this omission. Methods: Semi-structured interviews were conducted with people with intellectual disabilities (N = 20) about their election experiences during the 2017 (n = 18) and 2019 (n = 8) general elections. Six participants were interviewed around both elections. Data was analysed with template analysis. Results: Eight themes were produced – election information, political knowledge, political opinions, voting choice process, polling station experience, voting outcome, capacity and support. Theme interactions impacted on election experiences. Conclusions: While acknowledging diverse experiences, voting outcomes and experiences were particularly impacted by factor interactions concerning election information and/or polling station accessibility, capacity and support. Voting promotion interventions and future research should consider these areas

Understanding the rift, the (still) uneasy bedfellows of History and Organization Studies

Although the use of History has become increasingly discussed and more widely applied within Organization Studies (OS), its relevance for OS still remains far from centrally accepted. This article historicizes the relationship between Sociology and History as a means of better understanding the tensions, perceived and real, that exist between History and Organization Studies. In particular we analyse three differences of epistemological standpoint (method, objectivity and usefulness) that are commonly seen as the foundation stones to incompatibility. Perhaps surprisingly for an analysis of apparent disciplinary differences, we find that these distinctions in terms of approach, once closely examined, are rarely clear-cut and historians and OS scholars are frequently closer in intention and method than they are distant. However, despite their large intersection of interests, we argue that important distinctions between the two fields should be acknowledged. Our contribution to the debates over the need for more historical approaches within OS therefore centrally rests on abandoning aspirations for fully integrative models of working together, in favour of cooperative modes that concede the fields’ differences. This subtle shift of emphasis will, we believe, greatly benefit OS scholars who hope to include historical perspectives in their work