Histamine increases sphingosine kinase-1 expression and activity in the human arterial endothelial cell line EA.hy 926 by a PKC-alpha-dependent mechanism

Sphingosine 1-phosphate (S1P) is a potent mitogenic signal generated from sphingosine by the action of sphingosine kinases (SKs). In this study, we show that in the human arterial endothelial cell line EA.hy 926 histamine induces a time-dependent upregulation of the SK-1 mRNA and protein expression which is followed by increased SK-1 activity. A similar upregulation of SK-1 is also observed with the direct protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast, SK-2 activity is not affected by neither histamine nor TPA. The increased SK-1 protein expression is due to stimulated de novo synthesis since cycloheximide inhibited the delayed SK-1 protein upregulation. Moreover, the increased SK-1 mRNA expression results from an increased promoter activation by histamine and TPA. In mechanistic terms, the transcriptional upregulation of SK-1 is dependent on PKC and the extracellular signal-regulated protein kinase (ERK) cascade since staurosporine and the MEK inhibitor U0126 abolish the TPA-induced SK-1 induction. Furthermore, the histamine effect is abolished by the H1-receptor antagonist diphenhydramine, but not by the H2-receptor antagonist cimetidine. Parallel to the induction of SK-1, histamine and TPA stimulate an increased migration of endothelial cells, which is prevented by depletion of the SK-1 by small interfering RNA (siRNA). To appoint this specific cell response to a specific PKC isoenzyme, siRNA of PKC-alpha, -delta, and -epsilon were used to selectively downregulate the respective isoforms. Interestingly, only depletion of PKC-alpha leads to a complete loss of TPA- and histamine-triggered SK-1 induction and cell migration. In summary, these data show that PKC-alpha activation in endothelial cells by histamine-activated H1-receptors, or by direct PKC activators leads to a sustained upregulation of the SK-1 protein expression and activity which, in turn, is critically involved in the mechanism of endothelial cell migration.

Building Up: A history of Montana Tech Library 1900 - 2006

This paper traces the history of the Library of the Montana State School of Mines from its inception in 1900 to 2006. The history includes sketches of the library directors over 106 years, and the library’s various campus locations and emerging collections and services.

Materialien zum Zivilgesetzbuch. Die Erläuterungen von Eugen Huber / Text des Vorentwurfs von 1900

Das Werk eröffnet eine Serie von Bänden, die sich die Publikation der wichtigsten Materialien zum Schweizerischen Zivilgesetzbuch zum Ziel gesetzt hat. Sie sollen den Berner Kommentar zum Schweizerischen Privatrecht um eine kodifikationshistorische Dimension ergänzen und den Ausgangspunkt für die Erläuterungen zum geltenden Recht bilden. Der erste Band ist eigens auf die Centenarfeier des ZGB am 10. Dezember 2007 hin fertig gestellt worden. Er enthält mit den Erläuterungen zum Vorentwurf des Eidg. Justiz- und Polizeidepartements von 1900 das vielleicht schönste und anregendste, sicher aber das monumentalste Werk der Materialien. Es zeugt vom magistralen Überblick Eugen Hubers über den zivilrechtlichen Rechtsstoff und einer Weitsicht, die noch heute Vorbild jeder Gesetzgebungsarbeit sein sollte. Erstmals seit Jahrzehnten wird es wieder einem breiteren Publikum in originalgetreuer Form zugänglich gemacht. Zwecks prägnanter Zitierbarkeit sind Randnoten hinzugefügt worden. Ein Stichwortverzeichnis garantiert die schnelle Auffindbarkeit der Textstellen.

Empowering Interactions. Political Cultures and the Emergence of the State. in Europe 1300-1900

The emergence of the state in Europe is a topic that has engaged historians since the establishment of the discipline of history. Yet the primary focus of has nearly always been to take a top-down approach, whereby the formation and consolidation of public institutions is viewed as the outcome of activities by princes and other social elites. Yet, as the essays in this collection show, such an approach does not provide a complete picture. By investigating the importance of local and individual initiatives that contributed to state building from the late middle ages through to the nineteenth century, this volume shows how popular pressure could influence those in power to develop new institutional structures. By not privileging the role of warfare and of elite coercion for state building, it is possible to question the traditional top-down model and explore the degree to which central agencies might have been more important for state representation than for state practice. The studies included in this collection treat many parts of Europe and deal with different phases in the period between the late middle ages and the nineteenth century. Beginning with a critical review of state historiography, the introduction then sets out the concept of 'empowering interactions' which is then explored in the subsequent case studies and a number of historiographical, methodological and theoretical essays. Taken as a whole this collection provides a fascinating platform to reconsider the relationships between top-down and bottom-up processes in the history of the European state.