TY  - JOUR
A1  - Kuekenshoener, Tim
A1  - Wohlwend, Daniel
A1  - Niemoeller, Christoph
A1  - Dondapati, Padmarupa
A1  - Speck, Janina
A1  - Adeniran, Adebola V.
A1  - Nieth, Anita
A1  - Gerhardt, Stefan
A1  - Einsle, Oliver
A1  - Mueller, Kristian M.
A1  - Arndt, Katja Maren
T1  - Improving coiled coil stability while maintaining specificity by a bacterial hitchhiker selection system
JF  - Journal of structural biology
N2  - The design and selection of peptides targeting cellular proteins is challenging and often yields candidates with undesired properties. Therefore we deployed a new selection system based on the twin-arginine translocase (TAT) pathway of Escherichia coli, named hitchhiker translocation (HiT) selection. A pool of alpha-helix encoding sequences was designed and selected for interference with the coiled coil domain (CC) of a melanoma-associated basic-helix-loop-helix-leucine-zipper (bHLHLZ) protein, the microphthalmia associated transcription factor (MITF). One predominant sequence (iM10) was enriched during selection and showed remarkable protease resistance, high solubility and thermal stability while maintaining its specificity. Furthermore, it exhibited nanomolar range affinity towards the target peptide. A mutation screen indicated that target-binding helices of increased homodimer stability and improved expression rates were preferred in the selection process. The crystal structure of the iM10/MITF-CC heterodimer (2.1 angstrom) provided important structural insights and validated our design predictions. Importantly, iM10 did not only bind to the MITF coiled coil, but also to the markedly more stable HLHLZ domain of MITF. Characterizing the selected variants of the semi-rational library demonstrated the potential of the innovative bacterial selection approach. (C) 2014 Elsevier Inc. All rights reserved.
KW  - Basic helix-loop-helix leucine zipper
KW  - Coiled coils
KW  - Microphthalmia associated transcription factor
KW  - Selection and design
KW  - Twin arginine translocation pathway
Y1  - 2014
U6  - https://doi.org/10.1016/j.jsb.2014.03.002
SN  - 1047-8477
SN  - 1095-8657
VL  - 186
IS  - 3
SP  - 335
EP  - 348
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Holldack, Karsten
A1  - Ovsyannikov, Ruslan
A1  - Kuske, P.
A1  - Mueller, R.
A1  - Schaelicke, A.
A1  - Scheer, M.
A1  - Gorgoi, Mihaela
A1  - Kuehn, D.
A1  - Leitner, T.
A1  - Svensson, S.
A1  - Martensson, N.
A1  - Föhlisch, Alexander
T1  - Single bunch X-ray pulses on demand from a multi-bunch synchrotron radiation source
JF  - Nature Communications
N2  - Synchrotron radiation facilities routinely operate in a multi-bunch regime, but applications relying on time-of-flight schemes require single bunch operation. Here we show that pulse picking by resonant excitation in a storage ring creates in addition to the multi-bunch operation a distinct and separable single bunch soft X-ray source. It has variable polarization, a photon flux of up to 10(7)-10(9) ph s(-1)/0.1%BW at purity values of 10(4)-10(2) and a repetition rate of 1.25 MHz. The quasi-resonant excitation of incoherent betatron oscillations of electrons allows horizontal pulse separation at variable (also circular) polarization accessible for both, regular 30 ps pulses and ultrashort pulses of 2-3 ps duration. Combined with a new generation of angularly resolving electron spectrometers this creates unique opportunities for time-resolved photoemission studies as confirmed by time-of-flight spectra. Our pulse picking scheme is particularly suited for surface physics at diffraction-limited light sources promising ultimate spectral resolution.
Y1  - 2014
U6  - https://doi.org/10.1038/ncomms5010
SN  - 2041-1723
VL  - 5
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Weiz, Annika R.
A1  - Ishida, Keishi
A1  - Quitterer, Felix
A1  - Meyer, Sabine
A1  - Kehr, Jan-Christoph
A1  - Mueller, Kristian M.
A1  - Groll, Michael
A1  - Hertweck, Christian
A1  - Dittmann-Thünemann, Elke
T1  - Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions
JF  - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition
N2  - Understanding and controlling proteolysis is an important goal in therapeutic chemistry. Among the natural products specifically inhibiting proteases microviridins are particularly noteworthy. Microviridins are ribosomally produced and posttranslationally modified peptides that are processed into a unique, cagelike architecture. Here, we report a combined rational and random mutagenesis approach that provides fundamental insights into selectivity-conferring moieties of microviridins. The potent variant microviridin J was co-crystallized with trypsin, and for the first time the three-dimensional structure of microviridins was determined and the mode of inhibition revealed.
KW  - cyanobacteria
KW  - peptide engineering
KW  - protease inhibitors
KW  - RiPPs
KW  - structure elucidation
Y1  - 2014
U6  - https://doi.org/10.1002/anie.201309721
SN  - 1433-7851
SN  - 1521-3773
VL  - 53
IS  - 14
SP  - 3735
EP  - 3738
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Kuekenshoener, Tim
A1  - Hagemann, Urs B.
A1  - Wohlwend, Daniel
A1  - Raeuber, Christina
A1  - Baumann, Tobias
A1  - Keller, Sandro
A1  - Einsle, Oliver
A1  - Mueller, Kristian M.
A1  - Arndt, Katja Maren
T1  - Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies
JF  - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences
N2  - D-Peptides have been attributed pharmacological advantages over regular L-peptides, yet design rules are largely unknown. Based on a designed coiled coil-like D/L heterotetramer, named L-Base/D-Acid, we generated a library offering alternative residues for interaction with the D-peptide. Phage display selection yielded one predominant peptide, named HelixA, that differed at 13 positions from the scaffold helix. In addition to the observed D-/L-heterotetramers, ratio-dependent intermediate states were detected by isothermal titration calorimetry. Importantly, the formation of the selected HelixA/D-Acid bundle passes through fewer intermediate states than L-Base/D-Acid. Back mutation of HelixA core residues to L-Base (HelixLL) revealed that the residues at e/g-positions are responsible for the different intermediates. Furthermore, a Val-core variant (PeptideVV) was completely devoid of binding D-Acid, whereas an Ile-core helix (HelixII) interacted with D-Acid in a significantly more specific complex than L-Base.
Y1  - 2014
U6  - https://doi.org/10.1021/bm5006883
SN  - 1525-7797
SN  - 1526-4602
VL  - 15
IS  - 9
SP  - 3296
EP  - 3305
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Raber, Georg
A1  - Ebert, Franziska
A1  - Leffers, L.
A1  - Mueller, Sandra Maria
A1  - Taleshi, M. S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites
JF  - Toxicology research
N2  - Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMA(V), DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at mu M concentrations. DMA(V) causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMA(V) in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.
Y1  - 2015
U6  - https://doi.org/10.1039/c5tx00122f
SN  - 2045-452X
SN  - 2045-4538
VL  - 4
IS  - 5
SP  - 1289
EP  - 1296
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - GEN
A1  - Moser, Othmar
A1  - Mueller, Alexander
A1  - Tschakert, Gerhard
A1  - Koehler, Gerd
A1  - Lawrence, Jimmy B.
A1  - Groeschl, Werner
A1  - Pieber, Thomas R.
A1  - Bracken, Richard M.
A1  - Hofmann, Peter
T1  - Exercise Prescription in Type 1 Diabetes: Should We Use Percentages of Maximum Heart Rate?
T2  - Medicine and science in sports and exercise : official journal of the American College of Sports Medicine
Y1  - 2017
U6  - https://doi.org/10.1249/01.mss.0000519798.35679.cf
SN  - 0195-9131
SN  - 1530-0315
VL  - 49
SP  - 1020
EP  - 1020
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Hoffmann, Stefan A.
A1  - Wohltat, Christian
A1  - Mueller, Kristian M.
A1  - Arndt, Katja Maren
T1  - A user-friendly, low-cost turbidostat with versatile growth rate estimation based on an extended Kalman filter
JF  - PLoS one
N2  - For various experimental applications, microbial cultures at defined, constant densities are highly advantageous over simple batch cultures. Due to high costs, however, devices for continuous culture at freely defined densities still experience limited use. We have developed a small-scale turbidostat for research purposes, which is manufactured from inexpensive components and 3D printed parts. A high degree of spatial system integration and a graphical user interface provide user-friendly operability. The used optical density feedback control allows for constant continuous culture at a wide range of densities and offers to vary culture volume and dilution rates without additional parametrization. Further, a recursive algorithm for on-line growth rate estimation has been implemented. The employed Kalman filtering approach based on a very general state model retains the flexibility of the used control type and can be easily adapted to other bioreactor designs. Within several minutes it can converge to robust, accurate growth rate estimates. This is particularly useful for directed evolution experiments or studies on metabolic challenges, as it allows direct monitoring of the population fitness.
Y1  - 2017
U6  - https://doi.org/10.1371/journal.pone.0181923
SN  - 1932-6203
VL  - 12
SP  - 5944
EP  - 5952
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Kienzler, Sarah
A1  - Pech, Ina
A1  - Kreibich, Heidi
A1  - Mueller, M.
A1  - Thieken, Annegret
T1  - After the extreme flood in 2002: changes in preparedness, response and recovery of flood-affected residents in Germany between 2005 and 2011
JF  - Natural hazards and earth system sciences
N2  - After the flood in 2002, the level of private precautions taken increased considerably. One contributing factor is the fact that, in general, a larger proportion of people knew that they were at risk of flooding. The best level of precaution was found before the flood events in 2006 and 2011. The main reason for this might be that residents had more experience with flooding than residents affected in 2005 or 2010. Yet, overall, flood experience and knowledge did not necessarily result in building retrofitting or flood-proofing measures, which are considered as mitigating damages most effectively. Hence, investments still need to be stimulated in order to reduce future damage more efficiently.
Y1  - 2015
U6  - https://doi.org/10.5194/nhess-15-505-2015
SN  - 1561-8633
VL  - 15
IS  - 3
SP  - 505
EP  - 526
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Soliveres, Santiago
A1  - Manning, Peter
A1  - Prati, Daniel
A1  - Gossner, Martin M.
A1  - Alt, Fabian
A1  - Arndt, Hartmut
A1  - Baumgartner, Vanessa
A1  - Binkenstein, Julia
A1  - Birkhofer, Klaus
A1  - Blaser, Stefan
A1  - Bluethgen, Nico
A1  - Boch, Steffen
A1  - Boehm, Stefan
A1  - Boerschig, Carmen
A1  - Buscot, Francois
A1  - Diekoetter, Tim
A1  - Heinze, Johannes
A1  - Hoelzel, Norbert
A1  - Jung, Kirsten
A1  - Klaus, Valentin H.
A1  - Klein, Alexandra-Maria
A1  - Kleinebecker, Till
A1  - Klemmer, Sandra
A1  - Krauss, Jochen
A1  - Lange, Markus
A1  - Morris, E. Kathryn
A1  - Mueller, Joerg
A1  - Oelmann, Yvonne
A1  - Overmann, Jörg
A1  - Pasalic, Esther
A1  - Renner, Swen C.
A1  - Rillig, Matthias C.
A1  - Schaefer, H. Martin
A1  - Schloter, Michael
A1  - Schmitt, Barbara
A1  - Schoening, Ingo
A1  - Schrumpf, Marion
A1  - Sikorski, Johannes
A1  - Socher, Stephanie A.
A1  - Solly, Emily F.
A1  - Sonnemann, Ilja
A1  - Sorkau, Elisabeth
A1  - Steckel, Juliane
A1  - Steffan-Dewenter, Ingolf
A1  - Stempfhuber, Barbara
A1  - Tschapka, Marco
A1  - Tuerke, Manfred
A1  - Venter, Paul
A1  - Weiner, Christiane N.
A1  - Weisser, Wolfgang W.
A1  - Werner, Michael
A1  - Westphal, Catrin
A1  - Wilcke, Wolfgang
A1  - Wolters, Volkmar
A1  - Wubet, Tesfaye
A1  - Wurst, Susanne
A1  - Fischer, Markus
A1  - Allan, Eric
T1  - Locally rare species influence grassland ecosystem multifunctionality
JF  - Philosophical transactions of the Royal Society of London : B, Biological sciences
N2  - Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
KW  - biodiversity
KW  - common species
KW  - ecosystem function
KW  - identity hypothesis
KW  - land use
KW  - multitrophic
Y1  - 2016
U6  - https://doi.org/10.1098/rstb.2015.0269
SN  - 0962-8436
SN  - 1471-2970
VL  - 371
SP  - 3175
EP  - 3185
PB  - Royal Society
CY  - London
ER  - 
TY  - JOUR
A1  - Nebe, Stephan
A1  - Kroemer, Nils B.
A1  - Schad, Daniel
A1  - Bernhardt, Nadine
A1  - Sebold, Miriam
A1  - Mueller, Dirk K.
A1  - Scholl, Lucie
A1  - Kuitunen-Paul, Sören
A1  - Heinz, Andreas
A1  - Rapp, Michael A.
A1  - Huys, Quentin J. M.
A1  - Smolka, Michael N.
T1  - No association of goal-directed and habitual control with alcohol consumption in young adults
JF  - Addiction biology
N2  - Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se.
KW  - alcohol
KW  - goal-directed
KW  - reinforcement learning
Y1  - 2017
U6  - https://doi.org/10.1111/adb.12490
SN  - 1355-6215
SN  - 1369-1600
VL  - 23
IS  - 1
SP  - 379
EP  - 393
PB  - Wiley
CY  - Hoboken
ER  -