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When, some two centuries ago, German Romantics turned their backs on modernity – industrialisation, urbanisation, commerce and secularisation – they turned to ancient India. For them, India exemplified the primordial unity of mankind with this and the afterworld. For sections of the emerging nationalist movement in Germany, found the deployment of India handy to question the cultural hegemony, and eventually break the political dominance, of France. They tried to surpass the French, who claimed the ancient Roman heritage, by claiming an even older heritage for the Germans. Friedrich Schlegel for example suggested that the German language, and not the French, stood in unbroken continuity with ancient Sanskrit. For Romantics such as he, Sanskrit, the oldest surviving Indo-European language, was closest to the language of original divine revelation. This lead Schlegel to romanticise India in a way that stood in marked contrast to the Orientalist clichés current in other parts of Europe at the time. For him, the link between Sanskrit and German made Germany the true oriental self of Europe. The importance of this particular representation of India for the German national movement is underlined by the great number of university chairs that sprang up in the course of the nineteenth century: twenty two in Germany as opposed to only three in the United Kingdom. This paper explores the particular kind of ‘inverse’ Orientalism of the Germans in the context of its recent post-colonial critique.
Background: The interferon-inducible immunity-related GTPases (IRG proteins/p47 GTPases) are a distinctive family of GTPases that function as powerful cell-autonomous resistance factors. The IRG protein, Irga6 (IIGP1), participates in the disruption of the vacuolar membrane surrounding the intracellular parasite, Toxoplasma gondii, through which it communicates with its cellular hosts. Some aspects of the protein's behaviour have suggested a dynamin-like molecular mode of action, in that the energy released by GTP hydrolysis is transduced into mechanical work that results in deformation and ultimately rupture of the vacuolar membrane. Results: Irga6 forms GTP-dependent oligomers in vitro and thereby activates hydrolysis of the GTP substrate. In this study we define the catalytic G-domain interface by mutagenesis and present a structural model, of how GTP hydrolysis is activated in Irga6 complexes, based on the substrate-twinning reaction mechanism of the signal recognition particle (SRP) and its receptor (SRalpha). In conformity with this model, we show that the bound nucleotide is part of the catalytic interface and that the 3'hydroxyl of the GTP ribose bound to each subunit is essential for trans-activation of hydrolysis of the GTP bound to the other subunit. We show that both positive and negative regulatory interactions between IRG proteins occur via the catalytic interface. Furthermore, mutations that disrupt the catalytic interface also prevent Irga6 from accumulating on the parasitophorous vacuole membrane of T. gondii, showing that GTP-dependent Irga6 activation is an essential component of the resistance mechanism. Conclusions: The catalytic interface of Irga6 defined in the present experiments can probably be used as a paradigm for the nucleotide-dependent interactions of all members of the large family of IRG GTPases, both activating and regulatory. Understanding the activation mechanism of Irga6 will help to explain the mechanism by which IRG proteins exercise their resistance function. We find no support from sequence or G-domain structure for the idea that IRG proteins and the SRP GTPases have a common phylogenetic origin. It therefore seems probable, if surprising, that the substrate-assisted catalytic mechanism has been independently evolved in the two protein families.
Background: The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods: A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. Results: The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions: Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
Ein Vordenker, der in der internationalen Diskussion um « cultural translation » so gut wie nie diskutiert wird, ist Antonio Gramsci. Der Philosoph aus Sardinien, von Kindes Tagen an in Zweisprachigkeit (Sardisch-Italienisch) geübt, hat ein feines Sensorium für kulturelle Differenzen ausgebildet. In seinen Gefängnisjahren übersetzt er – als intellektuelles Training – aus dem Russischen und dem Deutschen ins Italienische, und in den Gefängnisheften setzt er sich wiederholt mit dem Begriff der traducibilità (Übersetzbarkeit) auseinander: Übersetzbarkeit von Sprachen, aber auch von Kulturen. Der Artikel geht den Linien nach, die von Gramscis Überlegungen zu der aktuellen Diskussion gezogen werden können, und diskutiert am Ende vergleichend die Positionen Homi K. Bhabhas und Gayatri Spivaks.