TY  - JOUR
A1  - Kastl, Johanna
A1  - Braun, Joachim
A1  - Prestel, Andreas
A1  - Möller, Heiko Michael
A1  - Huhn, Thomas
A1  - Mayer, Thomas U.
T1  - Mad2 Inhibitor-1 (M2I-1): A Small Molecule Protein-Protein Interaction Inhibitor Targeting the Mitotic Spindle Assembly Checkpoint
JF  - ACS chemical biology
N2  - The genetic integrity of each organism depends on the faithful segregation of its genome during mitosis. To meet this challenge, a cellular surveillance mechanism, termed the spindle assembly checkpoint (SAC), evolved that monitors the correct attachment of chromosomes and blocks progression through mitosis if corrections are needed. While the central role of the SAC for genome integrity is well established, its functional dissection has been hampered by the limited availability of appropriate small molecule inhibitors. Using a fluorescence polarization-based screen, we identify Mad2 inhibitor-1 (M2I-1), the first small molecule inhibitor targeting the binding of Mad2 to Cdc20, an essential protein-protein interaction (PPI) within the SAC. Based on computational and biochemical analyses, we propose that M2I-1 disturbs conformational dynamics of Mad2 critical for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens the SAC response, indicating that the compound might be active in cells. Thus, our study identifies the SAC specific complex formation between Mad2 and Cdc20 as a protein-protein interaction that can be targeted by small molecules.
Y1  - 2015
U6  - https://doi.org/10.1021/acschembio.5b00121
SN  - 1554-8929
SN  - 1554-8937
VL  - 10
IS  - 7
SP  - 1661
EP  - 1666
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Beerenwinkel, Niko
A1  - Sing, Tobias
A1  - Lengauer, Thomas
A1  - Rahnenfuhrer, Joerg
A1  - Roomp, Kirsten
A1  - Savenkov, Igor
A1  - Fischer, Roman
A1  - Hoffmann, Daniel
A1  - Selbig, Joachim
A1  - Korn, Klaus
A1  - Walter, Hauke
A1  - Berg, Thomas
A1  - Braun, Patrick
A1  - Faetkenheuer, Gerd
A1  - Oette, Mark
A1  - Rockstroh, Juergen
A1  - Kupfer, Bernd
A1  - Kaiser, Rolf
A1  - Daeumer, Martin
T1  - Computational methods for the design of effective therapies against drug resistant HIV strains
N2  - The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data
Y1  - 2005
ER  - 
TY  - JOUR
A1  - Koshkina, Olga
A1  - Westmeier, Dana
A1  - Lang, Thomas
A1  - Bantz, Christoph
A1  - Hahlbrock, Angelina
A1  - Würth, Christian
A1  - Resch-Genger, Ute
A1  - Braun, Ulrike
A1  - Thiermann, Raphael
A1  - Weise, Christoph
A1  - Eravci, Murat
A1  - Mohr, Benjamin
A1  - Schlaad, Helmut
A1  - Stauber, Roland H.
A1  - Docter, Dominic
A1  - Bertin, Annabelle
A1  - Maskos, Michael
T1  - Tuning the Surface of Nanoparticles: Impact of Poly(2-ethyl-2-oxazoline) on Protein Adsorption in Serum and Cellular Uptake
JF  - Macromolecular bioscience
N2  - Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asymmetrical flow field-flow fractionation, gel electrophoresis, and liquid chromatography-mass spectrometry, it is demonstrated that protein adsorption on PEtOxylated nanoparticles is extremely low, similar as on PEGylated nanoparticles. Moreover, quantitative microscopy reveals that PEtOxylation significantly reduces the non-specific cellular uptake, particularly by macrophage-like cells. Collectively, studies demonstrate that PEtOx is a very effective alternative to PEG for stealth modification of the surface of nanoparticles.
KW  - cellular uptake
KW  - nanoparticles
KW  - poly(2-ethyl-2oxazoline)
KW  - poly(ethylene glycol)
KW  - protein adsorption
Y1  - 2016
U6  - https://doi.org/10.1002/mabi.201600074
SN  - 1616-5187
SN  - 1616-5195
VL  - 16
SP  - 1287
EP  - 1300
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Alkemeyer, Thomas
A1  - Braun, Sebastian
A1  - Gebauer, Gunther
T1  - Spitzensport, soziale Ungleichheit und soziale Reproduktion im deutsch-französischen Vergleich
Y1  - 1998
ER  - 
TY  - JOUR
A1  - Jedrusik-Bode, Monika
A1  - Studencka, Maja
A1  - Smolka, Christian
A1  - Baumann, Tobias
A1  - Schmidt, Henning
A1  - Kampf, Jan
A1  - Paap, Franziska
A1  - Martin, Sophie
A1  - Tazi, Jamal
A1  - Müller, Kristian M.
A1  - Krüger, Marcus
A1  - Braun, Thomas
A1  - Bober, Eva
T1  - The sirtuin SIRT6 regulates stress granule formation in C. elegans and mammals
JF  - Journal of cell science
N2  - SIRT6 is a NAD(+)-dependent deacetylase that modulates chromatin structure and safeguards genomic stability. Until now, SIRT6 has been assigned to the nucleus and only nuclear targets of SIRT6 are known. Here, we demonstrate that in response to stress, C. elegans SIR-2.4 and its mammalian orthologue SIRT6 localize to cytoplasmic stress granules, interact with various stress granule components and induce their assembly. Loss of SIRT6 or inhibition of its catalytic activity in mouse embryonic fibroblasts impairs stress granule formation and delays disassembly during recovery, whereas deficiency of SIR-2.4 diminishes maintenance of P granules and decreases survival of C. elegans under stress conditions. Our findings uncover a novel, evolutionary conserved function of SIRT6 in the maintenance of stress granules in response to stress.
KW  - C. elegans
KW  - G3BP
KW  - SIRT6
KW  - Sirtuins
KW  - Stress
KW  - Stress granules
Y1  - 2013
U6  - https://doi.org/10.1242/jcs.130708
SN  - 0021-9533
SN  - 1477-9137
VL  - 126
IS  - 22
SP  - 5166
EP  - +
PB  - Company of Biologists Limited
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Reusswig, Fritz
A1  - Braun, Florian
A1  - Heger, Ines
A1  - Ludewig, Thomas
A1  - Eichenauer, Eva
A1  - Lass, Wiebke
T1  - Against the wind: Local opposition to the German Energiewende
JF  - Utilities Policy
N2  - A growing number of local energy conflicts around wind power and power-grid extensions are slowing down the deployment of the German Energiewende. In this paper, a local conflict on wind energy in the state of Baden-Württemberg is analysed in detail. In the little community of Engelsbrand, local opposition against a planned wind park was able to turn around a set of favourable a priori conditions, such as a supporting state government planning process, a local supporter group, a transparent planning process, including a majority vote pro wind energy, and a round table discussion. Distancing itself from the NIMBY-explanation (‘Not In My Back Yard’), the paper applies insights from discourse network analysis and micro-sociology in order to study the local conflict dynamics. Special attention is given to the resource mobilisation strategies of the opponents, including social networks, mass and social media use. The paper ends by drawing some general conclusions for the German Energiewende.
KW  - Energy conflicts
KW  - Acceptance of wind energy
KW  - Discourse networks
KW  - Conflict dynamics
Y1  - 2016
U6  - https://doi.org/10.1016/j.jup.2016.02.006
SN  - 0957-1787
SN  - 1878-4356
VL  - 41
SP  - 214
EP  - 227
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - INPR
A1  - Braun, Karl-Heinz
A1  - Brechenmacher, Thomas
A1  - Damberg, Wilhelm
A1  - Felten, Franz J.
A1  - Kampmann, Christoph
A1  - Koerner, Hans-Michael
A1  - Schindling, Anton
T1  - Editiorial
T2  - Historisches Jahrbuch
Y1  - 2014
SN  - 0018-2621
VL  - 134
SP  - IX
EP  - IX
PB  - Alber
CY  - Freiburg Breisgau
ER  - 
TY  - JOUR
A1  - Cesca, Simone
A1  - Braun, Thomas
A1  - Maccaferri, Francesco
A1  - Passarelli, Luigi
A1  - Rivalta, Eleonora
A1  - Dahm, Torsten
T1  - Source modelling of the M5-6 Emilia-Romagna, Italy, earthquakes (2012 May 20-29)
JF  - Geophysical journal international
N2  - On 2012 May 20 and 29, two damaging earthquakes with magnitudes M-w 6.1 and 5.9, respectively, struck the Emilia-Romagna region in the sedimentary Po Plain, Northern Italy, causing 26 fatalities, significant damage to historical buildings and substantial impact to the economy of the region. The earthquake sequence included four more aftershocks with M-w, >= 5.0, all at shallow depths (about 7-9 km), with similar WNW-ESE striking reverse mechanism. The timeline of the sequence suggests significant static stress interaction between the largest events. We perform here a detailed source inversion, first adopting a point source approximation and considering pure double couple and full moment tensor source models. We compare different extended source inversion approaches for the two largest events, and find that the rupture occurred in both cases along a subhorizontal plane, dipping towards SSW Directivity is well detected for the May 20 main shock, indicating that the rupture propagated unilaterally towards SE. Based on the focal mechanism solution, we further estimate the co-seismic static stress change induced by the May 20 event. By using the rate-and-state model and a Poissonian earthquake occurrence, we infer that the second largest event of May 29 was induced with a probability in the range 0.2-0.4. This suggests that the segment of fault was already prone to rupture. Finally, we estimate peak ground accelerations for the two main events as occurred separately or simultaneously. For the scenario involving hypothetical rupture areas of both main events, we estimate M-w = 6.3 and an increase of ground acceleration by 50 per cent. The approach we propose may help to quantify rapidly which regions are invested by a significant increase of the hazard, bearing the potential for large aftershocks or even a second main shock.
KW  - Earthquake dynamics
KW  - Earthquake source observations
Y1  - 2013
U6  - https://doi.org/10.1093/gji/ggt069
SN  - 0956-540X
VL  - 193
IS  - 3
SP  - 1658
EP  - 1672
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Dahm, Torsten
A1  - Cesca, Simone
A1  - Hainzl, Sebastian
A1  - Braun, Thomas
A1  - Krüger, Frank
T1  - Discrimination between induced, triggered, and natural earthquakes close to hydrocarbon reservoirs: A probabilistic approach based on the modeling of depletion-induced stress changes and seismological source parameters
JF  - Journal of geophysical research : Solid earth
N2  - Earthquakes occurring close to hydrocarbon fields under production are often under critical view of being induced or triggered. However, clear and testable rules to discriminate the different events have rarely been developed and tested. The unresolved scientific problem may lead to lengthy public disputes with unpredictable impact on the local acceptance of the exploitation and field operations. We propose a quantitative approach to discriminate induced, triggered, and natural earthquakes, which is based on testable input parameters. Maxima of occurrence probabilities are compared for the cases under question, and a single probability of being triggered or induced is reported. The uncertainties of earthquake location and other input parameters are considered in terms of the integration over probability density functions. The probability that events have been human triggered/induced is derived from the modeling of Coulomb stress changes and a rate and state-dependent seismicity model. In our case a 3-D boundary element method has been adapted for the nuclei of strain approach to estimate the stress changes outside the reservoir, which are related to pore pressure changes in the field formation. The predicted rate of natural earthquakes is either derived from the background seismicity or, in case of rare events, from an estimate of the tectonic stress rate. Instrumentally derived seismological information on the event location, source mechanism, and the size of the rupture plane is of advantage for the method. If the rupture plane has been estimated, the discrimination between induced or only triggered events is theoretically possible if probability functions are convolved with a rupture fault filter. We apply the approach to three recent main shock events: (1) the M-w 4.3 Ekofisk 2001, North Sea, earthquake close to the Ekofisk oil field; (2) the M-w 4.4 Rotenburg 2004, Northern Germany, earthquake in the vicinity of the Sohlingen gas field; and (3) the M-w 6.1 Emilia 2012, Northern Italy, earthquake in the vicinity of a hydrocarbon reservoir. The three test cases cover the complete range of possible causes: clearly human induced, not even human triggered, and a third case in between both extremes.
KW  - induced seismicity
KW  - probabilistic discrimination
KW  - hydrocarbon field
KW  - triggered earthquake
KW  - seismic hazard
KW  - earthquake
Y1  - 2015
U6  - https://doi.org/10.1002/2014JB011778
SN  - 2169-9313
SN  - 2169-9356
VL  - 120
IS  - 4
SP  - 2491
EP  - 2509
PB  - American Geophysical Union
CY  - Washington
ER  - 
TY  - JOUR
A1  - Hofman, Maarten P. G.
A1  - Hayward, M. W.
A1  - Heim, M.
A1  - Marchand, P.
A1  - Rolandsen, C. M.
A1  - Mattisson, Jenny
A1  - Urbano, F.
A1  - Heurich, M.
A1  - Mysterud, A.
A1  - Melzheimer, J.
A1  - Morellet, N.
A1  - Voigt, Ulrich
A1  - Allen, B. L.
A1  - Gehr, Benedikt
A1  - Rouco Zufiaurre, Carlos
A1  - Ullmann, Wiebke
A1  - Holand, O.
A1  - Jorgensen, n H.
A1  - Steinheim, G.
A1  - Cagnacci, F.
A1  - Kroeschel, M.
A1  - Kaczensky, P.
A1  - Buuveibaatar, B.
A1  - Payne, J. C.
A1  - Palmegiani, I
A1  - Jerina, K.
A1  - Kjellander, P.
A1  - Johansson, O.
A1  - LaPoint, S.
A1  - Bayrakcismith, R.
A1  - Linnell, J. D. C.
A1  - Zaccaroni, M.
A1  - Jorge, M. L. S.
A1  - Oshima, J. E. F.
A1  - Songhurst, A.
A1  - Fischer, C.
A1  - Mc Bride, R. T.
A1  - Thompson, J. J.
A1  - Streif, S.
A1  - Sandfort, R.
A1  - Bonenfant, Christophe
A1  - Drouilly, M.
A1  - Klapproth, M.
A1  - Zinner, Dietmar
A1  - Yarnell, Richard
A1  - Stronza, A.
A1  - Wilmott, L.
A1  - Meisingset, E.
A1  - Thaker, Maria
A1  - Vanak, A. T.
A1  - Nicoloso, S.
A1  - Graeber, R.
A1  - Said, S.
A1  - Boudreau, M. R.
A1  - Devlin, A.
A1  - Hoogesteijn, R.
A1  - May-Junior, J. A.
A1  - Nifong, J. C.
A1  - Odden, J.
A1  - Quigley, H. B.
A1  - Tortato, F.
A1  - Parker, D. M.
A1  - Caso, A.
A1  - Perrine, J.
A1  - Tellaeche, C.
A1  - Zieba, F.
A1  - Zwijacz-Kozica, T.
A1  - Appel, C. L.
A1  - Axsom, I
A1  - Bean, W. T.
A1  - Cristescu, B.
A1  - Periquet, S.
A1  - Teichman, K. J.
A1  - Karpanty, S.
A1  - Licoppe, A.
A1  - Menges, V
A1  - Black, K.
A1  - Scheppers, Thomas L.
A1  - Schai-Braun, S. C.
A1  - Azevedo, F. C.
A1  - Lemos, F. G.
A1  - Payne, A.
A1  - Swanepoel, L. H.
A1  - Weckworth, B.
A1  - Berger, A.
A1  - Bertassoni, Alessandra
A1  - McCulloch, G.
A1  - Sustr, P.
A1  - Athreya, V
A1  - Bockmuhl, D.
A1  - Casaer, J.
A1  - Ekori, A.
A1  - Melovski, D.
A1  - Richard-Hansen, C.
A1  - van de Vyver, D.
A1  - Reyna-Hurtado, R.
A1  - Robardet, E.
A1  - Selva, N.
A1  - Sergiel, A.
A1  - Farhadinia, M. S.
A1  - Sunde, P.
A1  - Portas, R.
A1  - Ambarli, Hüseyin
A1  - Berzins, R.
A1  - Kappeler, P. M.
A1  - Mann, G. K.
A1  - Pyritz, L.
A1  - Bissett, C.
A1  - Grant, T.
A1  - Steinmetz, R.
A1  - Swedell, Larissa
A1  - Welch, R. J.
A1  - Armenteras, D.
A1  - Bidder, O. R.
A1  - Gonzalez, T. M.
A1  - Rosenblatt, A.
A1  - Kachel, S.
A1  - Balkenhol, N.
T1  - Right on track?
BT  - Performance of satellite telemetry in terrestrial wildlife research
JF  - PLoS one
N2  - Satellite telemetry is an increasingly utilized technology in wildlife research, and current devices can track individual animal movements at unprecedented spatial and temporal resolutions. However, as we enter the golden age of satellite telemetry, we need an in-depth understanding of the main technological, species-specific and environmental factors that determine the success and failure of satellite tracking devices across species and habitats. Here, we assess the relative influence of such factors on the ability of satellite telemetry units to provide the expected amount and quality of data by analyzing data from over 3,000 devices deployed on 62 terrestrial species in 167 projects worldwide. We evaluate the success rate in obtaining GPS fixes as well as in transferring these fixes to the user and we evaluate failure rates. Average fix success and data transfer rates were high and were generally better predicted by species and unit characteristics, while environmental characteristics influenced the variability of performance. However, 48% of the unit deployments ended prematurely, half of them due to technical failure. Nonetheless, this study shows that the performance of satellite telemetry applications has shown improvements over time, and based on our findings, we provide further recommendations for both users and manufacturers.
Y1  - 2019
U6  - https://doi.org/10.1371/journal.pone.0216223
SN  - 1932-6203
VL  - 14
IS  - 5
PB  - PLoS
CY  - San Fransisco
ER  -