@article{GratwohlPfirrmannZanderetal.2016, author = {Gratwohl, A and Pfirrmann, M and Zander, A and Kr{\"o}ger, N and Beelen, D and Novotny, J and Nerl, C and Scheid, C and Spiekermann, K and Mayer, J and Sayer, HG and Falge, C and Bunjes, D and D{\"o}hner, H and Ganser, A and Schmidt-Wolf, I and Schwerdtfeger, R and Baurmann, H and Kuse, R and Schmitz, N and Wehmeier, A and Fischer, J Th and Ho, AD and Wilhelm, M and Goebeler, M-E and Lindemann, HW and Bormann, M and Hertenstein, B and Schlimok, G and Baerlocher, GM and Aul, C and Pfreundschuh, M and Fabian, M and Staib, P and Edinger, M and Schatz, M and Fauser, A and Arnold, R and Kindler, T and Wulf, G and Rosselet, A and Hellmann, A and Sch{\"a}fer, E and Pr{\"u}mmer, O and Schenk, M and Hasford, J and Heimpel, H and Hossfeld, DK and Kolb, H-J and B{\"u}sche, G and Haferlach, C and Schnittger, S and M{\"u}ller, MC and Reiter, A and Berger, U and Saußele, S and Hochhaus, A and Hehlmann, R}, title = {Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment}, series = {Leukemia}, volume = {30}, journal = {Leukemia}, doi = {10.1038/leu.2015.281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150368}, pages = {562-569}, year = {2016}, abstract = {Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95\% confidence interval (CI): 0.69-0.82) vs 0.69 (95\% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56\% vs 39\%; P = 0.005) and free of drug treatment (56\% vs 6\%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.}, language = {en} } @article{SchueleinVoelkWolfZhuetal.2014, author = {Sch{\"u}lein-V{\"o}lk, Christina and Wolf, Elmar and Zhu, Jing and Xu, Wenshan and Taranets, Lyudmyla and Hellmann, Andreas and J{\"a}nicke, Laura A. and Diefenbacher, Markus E. and Behrens, Axel and Eilers, Martin and Popov, Nikita}, title = {Dual Regulation of Fbw7 Function and Oncogenic Transformation by Usp28}, series = {CELL REPORTS}, volume = {9}, journal = {CELL REPORTS}, number = {3}, issn = {2211-1247}, doi = {10.1016/j.celrep.2014.09.057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118219}, pages = {1099-1109}, year = {2014}, abstract = {Fbw7, the substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, mediates the turnover of multiple proto-oncoproteins and promotes its own degradation. Fbw7-dependent substrate ubiquitination is antagonized by the Usp28 deubiquitinase. Here, we show that Usp28 preferentially antagonizes autocatalytic ubiquitination and stabilizes Fbw7, resulting in dose-dependent effects in Usp28 knockout mice. Monoallelic deletion of Usp28 maintains stable Fbw7 but drives Fbw7 substrate degradation. In contrast, complete knockout triggers Fbw7 degradation and leads to the accumulation of Fbw7 substrates in several tissues and embryonic fibroblasts. On the other hand, overexpression of Usp28 stabilizes both Fbw7 and its substrates. Consequently, both complete loss and ectopic expression of Usp28 promote Ras-driven oncogenic transformation. We propose that dual regulation of Fbw7 activity by Usp28 is a safeguard mechanism for maintaining physiological levels of proto-oncogenic Fbw7 substrates, which is equivalently disrupted by loss or overexpression of Usp28.}, language = {en} } @article{TimmermansvanderTolTimmermansetal.2015, author = {Timmermans, Wim J. and van der Tol, Christiaan and Timmermans, Joris and Ucer, Murat and Chen, Xuelong and Alonso, Luis and Moreno, Jose and Carrara, Arnaud and Lopez, Ramon and Fernando de la Cruz, Tercero and Corcoles, Horacio L. and de Miguel, Eduardo and Sanchez, Jose A. G. and Perez, Irene and Belen, Perez and Munoz, Juan-Carlos J. and Skokovic, Drazen and Sobrino, Jose and Soria, Guillem and MacArthur, Alasdair and Vescovo, Loris and Reusen, Ils and Andreu, Ana and Burkart, Andreas and Cilia, Chiara and Contreras, Sergio and Corbari, Chiara and Calleja, Javier F. and Guzinski, Radoslaw and Hellmann, Christine and Herrmann, Ittai and Kerr, Gregoire and Lazar, Adina-Laura and Leutner, Benjamin and Mendiguren, Gorka and Nasilowska, Sylwia and Nieto, Hector and Pachego-Labrador, Javier and Pulanekar, Survana and Raj, Rahul and Schikling, Anke and Siegmann, Bastian and von Bueren, Stefanie and Su, Zhongbo (Bob)}, title = {An Overview of the Regional Experiments for Land-atmosphere Exchanges 2012 (REFLEX 2012) Campaign}, series = {Acta Geophysica}, volume = {63}, journal = {Acta Geophysica}, number = {6}, doi = {10.2478/s11600-014-0254-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136491}, pages = {1465-1484}, year = {2015}, abstract = {The REFLEX 2012 campaign was initiated as part of a training course on the organization of an airborne campaign to support advancement of the understanding of land-atmosphere interaction processes. This article describes the campaign, its objectives and observations, remote as well as in situ. The observations took place at the experimental Las Tiesas farm in an agricultural area in the south of Spain. During the period of ten days, measurements were made to capture the main processes controlling the local and regional land-atmosphere exchanges. Apart from multi-temporal, multi-directional and multi-spatial space-borne and airborne observations, measurements of the local meteorology, energy fluxes, soil temperature profiles, soil moisture profiles, surface temperature, canopy structure as well as leaf-level measurements were carried out. Additional thermo-dynamical monitoring took place at selected sites. After presenting the different types of measurements, some examples are given to illustrate the potential of the observations made.}, language = {en} } @article{DiestelReschMeinhardtetal.2013, author = {Diestel, Uschi and Resch, Marcus and Meinhardt, Kathrin and Weiler, Sigrid and Hellmann, Tina V. and Mueller, Thomas D. and Nickel, Joachim and Eichler, Jutta and Muller, Yves A.}, title = {Identification of a Novel TGF-beta-Binding Site in the Zona Pellucida C-terminal (ZP-C) Domain of TGF-\(\beta\)-Receptor-3 (TGFR-3)}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0067214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130904}, pages = {e67214}, year = {2013}, abstract = {The zona pellucida (ZP) domain is present in extracellular proteins such as the zona pellucida proteins and tectorins and participates in the formation of polymeric protein networks. However, the ZP domain also occurs in the cytokine signaling co-receptor transforming growth factor beta (TGF-\(\beta\)) receptor type 3 (TGFR-3, also known as betaglycan) where it contributes to cytokine ligand recognition. Currently it is unclear how the ZP domain architecture enables this dual functionality. Here, we identify a novel major TGF-beta-binding site in the FG loop of the C-terminal subdomain of the murine TGFR-3 ZP domain (ZP-C) using protein crystallography, limited proteolysis experiments, surface plasmon resonance measurements and synthetic peptides. In the murine 2.7 angstrom crystal structure that we are presenting here, the FG-loop is disordered, however, well-ordered in a recently reported homologous rat ZP-C structure. Surprisingly, the adjacent external hydrophobic patch (EHP) segment is registered differently in the rat and murine structures suggesting that this segment only loosely associates with the remaining ZP-C fold. Such a flexible and temporarily-modulated association of the EHP segment with the ZP domain has been proposed to control the polymerization of ZP domain-containing proteins. Our findings suggest that this flexibility also extends to the ZP domain of TGFR-3 and might facilitate co-receptor ligand interaction and presentation via the adjacent FG-loop. This hints that a similar C-terminal region of the ZP domain architecture possibly regulates both the polymerization of extracellular matrix proteins and cytokine ligand recognition of TGFR-3.}, language = {en} }