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The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Einleitung vor § 1297
(2014)
Vorbemerkung vor § 1297
(2014)
Vorbemerkung vor § 1353
(2014)
Vor dem Hintergrund zunehmender gesellschaftlicher Veränderungen bei den Lebens- und Familienformen hat es sich die Commission on European Family Law (CEFL) seit 2001 zum Ziel gesetzt, unverbindliche Regelungsvorschläge für ein europaweit einheitliches Familienrecht zu schaffen. Die Vorstellung und Diskussion dieser auf rechtsvergleichender Basis erstellten Principles erfolgt auf den regelmäßig veranstalteten Tagungen der CEFL. Die nunmehr fünfte Konferenz zum Thema „Family Law and Culture in Europe – Developments, Challenges and Opportunities“ fand erstmals in Deutschland statt. Ausgerichtet wurde die Veranstaltung, zu der ca. 200 Teilnehmerinnen und Teilnehmern aus Wissenschaft und Praxis aus insgesamt 33 Ländern angereist waren, von Nina Dethloff (Direktorin des Instituts für Deutsches, Europäisches und Internationales Familienrecht an der Universität Bonn), Katharina Boele-Woelki (Direktorin des Utrecht Centre for European Research into Family Law und Preisträgerin des Anneliese Maier-Forschungspreises der Alexander von Humboldt-Stiftung) und Werner Gephart (Direktor des Käte Hamburger Kollegs „Recht als Kultur“).
Does stiffer electoral competition reduce political shirking? For a micro-analysis of this question, I construct a new data set spanning the years 2005 to 2012 covering biographical and political information about German Members of Parliament (MPs), including their attendance rates in voting sessions. For the parliament elected in 2009, I show that indeed opposition party MPs who expect to face a close race in their district show significantly and relevantly lower absence rates in parliament beforehand. MPs of governing parties seem not to react significantly to electoral competition. These results are confirmed by an analysis of the parliament elected in 2005, by several robustness checks, and also by employing an instrumental variable strategy exploiting convenient peculiarities of the German electoral system. The study also shows how MPs elected via party lists react to different levels of electoral competition.
This paper investigates the extent to which corporate governance affects the cost of debt and equity capital of German exchange-listed companies. I examine corporate governance along three dimensions: financial information quality, ownership structure and board structure. The results suggest that firms with high levels of financial transparency and bonus compensations face lower cost of equity. In addition, block ownership is negatively related to firms' cost of equity when the blockholders are other firms, managers or founding-family members. Consistent with the conjecture that agency costs increase with firm size, I find significant cost of debt effects only in the largest German companies. Here, the creditors demand lower cost of debt from firms with block ownerships held by corporations or banks. My findings demonstrate that a uniform set of governance attributes is unlikely to satisfy suppliers of debt and equity capital equally.