The Forgotten Archduke: The Funeral Monument for Ernest of Austria in Brussels

Archduke Ernest of Austria (1553–1595), second son of Emperor Maximilian II and younger brother of Emperor Rudolf II, was in his youth a possible candidate for the thrones of the Empire or the Spanish Kingdom. Instead, he became Governor-General of the Netherlands in 1593 and relocated to Brussels in 1594 where he was welcomed with lavish festivities as the bearer of hope and prosperity. Unfortunately, Ernest died only thirteen months later without having achieved any political success. His brother and successor Albert of Austria commissioned the funeral monument for Ernest in 1600 after it was settled that he would be buried in Brussels and not Vienna. Focusing on this monument, which draws stylistically from various dynasty-related models, it will be shown that Albert intended to use this monument – and thus his brother’s memoria – to make the Brussels Cathedral the primary location of Habsburg dynastic memory in the Low Countries.

Dsh homolog DVL3 mediates resistance to IGFIR inhibition by regulating IGF-RAS signaling

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.

The Johann Jacob Wepfer Award 2012 of the European Stroke Conference to Professor Louis R. Caplan

No abstract available.

Renewal of Religious Leadership According to an Ancient Model. Bishop Joseph Hubert Reinkens and Bishop Martin of Tours

Im Jahr 1866 verfasste der damals in Breslau lehrende römisch-katholische Kirchenhistoriker Joseph Hubert Reinkens eine der ersten historisch-kritischen Studien in deutscher Sprache über Martin von Tours, in der er sich u.a. mit Martins bischöflichem Leitungsdienst befasste. Nach dem Ersten Vatikanischen Konzil (1870) wurde Reinkens 1873 der erste Bischof für die Alt-Katholiken im Deutschen Reich. Der Beitrag beschreibt den Einfluss, den Reinkens' Martin-Rezeption auf sein theologisches und praktisches Verständnis des Bischofsamts hatte.