@article{NoonanTuckerFlemingetal.2018, author = {Noonan, Michael J. and Tucker, Marlee A. and Fleming, Christen H. and Akre, Thomas S. and Alberts, Susan C. and Ali, Abdullahi H. and Altmann, Jeanne and Antunes, Pamela Castro and Belant, Jerrold L. and Beyer, Dean and Blaum, Niels and Boehning-Gaese, Katrin and Cullen Jr, Laury and de Paula, Rogerio Cunha and Dekker, Jasja and Drescher-Lehman, Jonathan and Farwig, Nina and Fichtel, Claudia and Fischer, Christina and Ford, Adam T. and Goheen, Jacob R. and Janssen, Rene and Jeltsch, Florian and Kauffman, Matthew and Kappeler, Peter M. and Koch, Flavia and LaPoint, Scott and Markham, A. Catherine and Medici, Emilia Patricia and Morato, Ronaldo G. and Nathan, Ran and Oliveira-Santos, Luiz Gustavo R. and Olson, Kirk A. and Patterson, Bruce D. and Paviolo, Agustin and Ramalho, Emiliano Estero and Rosner, Sascha and Schabo, Dana G. and Selva, Nuria and Sergiel, Agnieszka and da Silva, Marina Xavier and Spiegel, Orr and Thompson, Peter and Ullmann, Wiebke and Zieba, Filip and Zwijacz-Kozica, Tomasz and Fagan, William F. and Mueller, Thomas and Calabrese, Justin M.}, title = {A comprehensive analysis of autocorrelation and bias in home range estimation}, series = {Ecological monographs : a publication of the Ecological Society of America.}, volume = {89}, journal = {Ecological monographs : a publication of the Ecological Society of America.}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {0012-9615}, doi = {10.1002/ecm.1344}, pages = {21}, year = {2018}, abstract = {Home range estimation is routine practice in ecological research. While advances in animal tracking technology have increased our capacity to collect data to support home range analysis, these same advances have also resulted in increasingly autocorrelated data. Consequently, the question of which home range estimator to use on modern, highly autocorrelated tracking data remains open. This question is particularly relevant given that most estimators assume independently sampled data. Here, we provide a comprehensive evaluation of the effects of autocorrelation on home range estimation. We base our study on an extensive data set of GPS locations from 369 individuals representing 27 species distributed across five continents. We first assemble a broad array of home range estimators, including Kernel Density Estimation (KDE) with four bandwidth optimizers (Gaussian reference function, autocorrelated-Gaussian reference function [AKDE], Silverman's rule of thumb, and least squares cross-validation), Minimum Convex Polygon, and Local Convex Hull methods. Notably, all of these estimators except AKDE assume independent and identically distributed (IID) data. We then employ half-sample cross-validation to objectively quantify estimator performance, and the recently introduced effective sample size for home range area estimation ( N̂ area ) to quantify the information content of each data set. We found that AKDE 95\% area estimates were larger than conventional IID-based estimates by a mean factor of 2. The median number of cross-validated locations included in the hold-out sets by AKDE 95\% (or 50\%) estimates was 95.3\% (or 50.1\%), confirming the larger AKDE ranges were appropriately selective at the specified quantile. Conversely, conventional estimates exhibited negative bias that increased with decreasing N̂ area. To contextualize our empirical results, we performed a detailed simulation study to tease apart how sampling frequency, sampling duration, and the focal animal's movement conspire to affect range estimates. Paralleling our empirical results, the simulation study demonstrated that AKDE was generally more accurate than conventional methods, particularly for small N̂ area. While 72\% of the 369 empirical data sets had >1,000 total observations, only 4\% had an N̂ area >1,000, where 30\% had an N̂ area <30. In this frequently encountered scenario of small N̂ area, AKDE was the only estimator capable of producing an accurate home range estimate on autocorrelated data.}, language = {en} } @article{GarbusowSchadSeboldetal.2016, author = {Garbusow, Maria and Schad, Daniel and Sebold, Miriam and Friedel, Eva and Bernhardt, Nadine and Koch, Stefan P. and Steinacher, Bruno and Kathmann, Norbert and Geurts, Dirk E. M. and Sommer, Christian and Mueller, Dirk K. and Nebe, Stephan and Paul, Soeren and Wittchen, Hans-Ulrich and Zimmermann, Ulrich S. and Walter, Henrik and Smolka, Michael N. and Sterzer, Philipp and Rapp, Michael A. and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence}, series = {Addiction biology}, volume = {21}, journal = {Addiction biology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12243}, pages = {719 -- 731}, year = {2016}, abstract = {In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.}, language = {en} } @article{PiontekWinklerBaletal.2004, author = {Piontek, J. and Winkler, Lars and Bal, M. S. and Lassowski, Birgit and Mueller, Sandra L. and Gast, Klaus and Blasig, Ingolf E.}, title = {Investigating of homophilic interactions of the tight junction proteins occludin and claudin-5}, year = {2004}, language = {en} } @misc{ScarpeciZanorCarrilloetal.2007, author = {Scarpeci, Telma E. and Zanor, Mar{\´i}a I. and Carrillo, N{\´e}stor and Mueller-Roeber, Bernd and Valle, Estela M.}, title = {Generation of superoxide anion in chloroplasts of Arabidopsis thaliana during active photosynthesis}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, number = {866}, issn = {1866-8372}, doi = {10.25932/publishup-43425}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-434254}, pages = {361 -- 378}, year = {2007}, abstract = {The antioxidant defense system involves complex functional coordination of multiple components in different organelles within the plant cell. Here, we have studied the Arabidopsis thaliana early response to the generation of superoxide anion in chloroplasts during active photosynthesis. We exposed plants to methyl viologen (MV), a superoxide anion propagator in the light, and performed biochemical and expression profiling experiments using Affymetrix ATH1 GeneChip(R) microarrays under conditions in which photosynthesis and antioxidant enzymes were active. Data analysis identified superoxide-responsive genes that were compared with available microarray results. Examples include genes encoding proteins with unknown function, transcription factors and signal transduction components. A common GAAAAGTCAAAC motif containing the W-box consensus sequence of WRKY transcription factors, was found in the promoters of genes highly up-regulated by superoxide. Band shift assays showed that oxidative treatments enhanced the specific binding of leaf protein extracts to this motif. In addition, GUS reporter gene fused to WRKY30 promoter, which contains this binding motif, was induced by MV and H2O2. Overall, our study suggests that genes involved in signalling pathways and with unknown functions are rapidly activated by superoxide anion generated in photosynthetically active chloroplasts, as part of the early antioxidant response of Arabidopsis leaves.}, language = {en} } @article{GronauWildemannZaehetal.2006, author = {Gronau, Norbert and Wildemann, H. and Zaeh, M. F. and Mueller, N. and L{\"a}mmer, Anne and Andresen, Katja}, title = {Tools zur Ermittlung der Wandlungsf{\"a}higkeit}, year = {2006}, language = {de} } @article{SpeckRaeuberKuekenshoeneretal.2013, author = {Speck, Janina and R{\"a}uber, Christina and K{\"u}kensh{\"o}ner, Tim and Niem{\"o}ller, Christoph and Mueller, Katelyn J. and Schleberger, Paula and Dondapati, Padmarupa and Hecky, Jochen and Arndt, Katja Maren and M{\"u}ller, Kristian M.}, title = {TAT hitchhiker selection expanded to folding helpers, multimeric interactions and combinations with protein fragment complementation}, series = {Protein engineering design \& selection}, volume = {26}, journal = {Protein engineering design \& selection}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1741-0126}, doi = {10.1093/protein/gzs098}, pages = {225 -- 242}, year = {2013}, abstract = {The twin-arginine translocation (TAT) pathway of the bacterial cytoplasmic membrane mediates translocation only of proteins that accomplished a native-like conformation. We deploy this feature in modular selection systems for directed evolution, in which folding helpers as well as dimeric or oligomeric proteinprotein interactions enable TAT-dependent translocation of the resistance marker TEM -lactamase (L). Specifically, we demonstrate and analyze selection of (i) enhancers for folding by direct TAT translocation selection of a target protein interposed between the TorA signal sequence and L, (ii) dimeric or oligomeric proteinprotein interactions by hitchhiker translocation (HiT) selection of proteins fused to the TorA signal sequence and to the L, respectively and (iii) heterotrimeric proteinprotein interactions by combining HiT with protein fragment complementation selection of proteins fused to two split L fragments and TorA, respectively. The lactamase fragments were additionally engineered for improved activity and stability. Applicability was benchmarked with interaction partners of known affinity and multimerization whereby cellular fitness correlated well with biophysical protein properties. Ultimately, the HiT selection was employed to identify peptides, which specifically bind to leukemia- and melanoma-relevant target proteins (MITF and ETO) by coiled-coil or tetra-helix-bundle formation with high affinity. The various versions of TAT selection led to inhibiting peptides (iPEPs) of disease-promoting interactions and enabled so far difficult to achieve selections.}, language = {en} } @article{HagenBaumannWagneretal.2014, author = {Hagen, Sven and Baumann, Tobias and Wagner, Hanna J. and Morath, Volker and Kaufmann, Beate and Fischer, Adrian and Bergmann, Stefan and Schindler, Patrick and Arndt, Katja Maren and Mueller, Kristian M.}, title = {Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy}, series = {Scientific reports}, volume = {4}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep03759}, pages = {11}, year = {2014}, abstract = {The pre-clinical and clinical development of viral vehicles for gene transfer increased in recent years, and a recombinant adeno-associated virus (rAAV) drug took center stage upon approval in the European Union. However, lack of standardization, inefficient purification methods and complicated retargeting limit general usability. We address these obstacles by fusing rAAV-2 capsids with two modular targeting molecules (DARPin or Affibody) specific for a cancer cell-surface marker (EGFR) while simultaneously including an affinity tag (His-tag) in a surface-exposed loop. Equipping these particles with genes coding for prodrug converting enzymes (thymidine kinase or cytosine deaminase) we demonstrate tumor marker specific transduction and prodrug-dependent apoptosis of cancer cells. Coding terminal and loop modifications in one gene enabled specific and scalable purification. Our genetic parts for viral production adhere to a standardized cloning strategy facilitating rapid prototyping of virus directed enzyme prodrug therapy (VDEPT).}, language = {en} } @article{MuellerRailaAltenkampetal.2012, author = {Mueller, K. and Raila, Jens and Altenkamp, Rainer and Schmidt, D. and Dietrich, R. and Hurtienne, Andrea and Wink, M. and Krone, O. and Brunnberg, Leo and Schweigert, Florian J.}, title = {Concentrations of retinol, 3,4-didehydroretinol, and retinyl esters in plasma of free-ranging birds of prey}, series = {Journal of animal physiology and animal nutrition}, volume = {96}, journal = {Journal of animal physiology and animal nutrition}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0931-2439}, doi = {10.1111/j.1439-0396.2011.01219.x}, pages = {1044 -- 1053}, year = {2012}, abstract = {This study investigated vitamin A compounds in the plasma of healthy free-ranging Central European raptors with different feeding strategies. Plasma samples of nestlings of white-tailed sea eagle [white-tailed sea eagle (WTSE), Haliaeetus albicilla) (n = 32), osprey (Pandion haliaetus) (n = 39), northern goshawk (Accipiter gentilis) (n = 25), common buzzard (Buteo buteo) (n = 31), and honey buzzard (Pernis apivorus) (n = 18) and adults of WTSE (n = 10), osprey (n = 31), and northern goshawk (n = 45) were investigated with reversed-phase-high-performance liquid chromatography (RP-HPLC). In WTSE, northern goshawks and common buzzards retinol were the main plasma component of vitamin A, whilst in ospreys and honey buzzards, 3,4-didehydroretinol predominated. The median of the retinol plasma concentration in the nestlings group ranged from 0.12 to 3.80 mu M and in the adult group from 0.15 to 6.13 mu M. Median plasma concentrations of 3,4-didehydroretinol in nestlings ranged from 0.06 to 3.55 mu M. In adults, northern goshawks had the lowest plasma concentration of 3,4-didehydroretinol followed by WTSE and ospreys. The plasma of all investigated species contained retinyl esters (palmitate, oleate, and stearate). The results show considerable species-specific differences in the vitamin A plasma concentrations that might be caused by different nutrition strategies.}, language = {en} } @article{SollySchoeningBochetal.2013, author = {Solly, Emily and Sch{\"o}ning, Ingo and Boch, Steffen and Mueller, J. and Socher, S. A. and Trumbore, S. E. and Schrumpf, M.}, title = {Mean age of carbon in fine roots from temperate forests and grasslands with different management}, series = {Biogeosciences}, volume = {10}, journal = {Biogeosciences}, number = {7}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {1726-4170}, doi = {10.5194/bg-10-4833-2013}, pages = {4833 -- 4843}, year = {2013}, abstract = {Fine roots are the most dynamic portion of a plant's root system and a major source of soil organic matter. By altering plant species diversity and composition, soil conditions and nutrient availability, and consequently belowground allocation and dynamics of root carbon (C) inputs, land-use and management changes may influence organic C storage in terrestrial ecosystems. In three German regions, we measured fine root radiocarbon (C-14) content to estimate the mean time since C in root tissues was fixed from the atmosphere in 54 grassland and forest plots with different management and soil conditions. Although root biomass was on average greater in grasslands 5.1 +/- 0.8 g (mean +/- SE, n = 27) than in forests 3.1 +/- 0.5 g (n = 27) (p < 0.05), the mean age of C in fine roots in forests averaged 11.3 +/- 1.8 yr and was older and more variable compared to grasslands 1.7 +/- 0.4 yr (p < 0.001). We further found that management affects the mean age of fine root C in temperate grasslands mediated by changes in plant species diversity and composition. Fine root mean C age is positively correlated with plant diversity (r = 0.65) and with the number of perennial species (r = 0.77). Fine root mean C age in grasslands was also affected by study region with averages of 0.7 +/- 0.1 yr (n= 9) on mostly organic soils in northern Germany and of 1.8 +/- 0.3 yr (n = 9) and 2.6 +/- 0.3 (n = 9) in central and southern Germany (p < 0.05). This was probably due to differences in soil nutrient contents and soil moisture conditions between study regions, which affected plant species diversity and the presence of perennial species. Our results indicate more long-lived roots or internal redistribution of C in perennial species and suggest linkages between fine root C age and management in grasslands. These findings improve our ability to predict and model belowground C fluxes across broader spatial scales.}, language = {en} } @article{HagenMattayRaeuberetal.2014, author = {Hagen, Sven and Mattay, Dinah and Raeuber, Christina and Mueller, Kristian M. and Arndt, Katja Maren}, title = {Characterization and inhibition of AF10-mediated interaction}, series = {Journal of peptide science}, volume = {20}, journal = {Journal of peptide science}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1075-2617}, doi = {10.1002/psc.2626}, pages = {385 -- 397}, year = {2014}, abstract = {The non-random chromosomal translocations t(10;11)(p13;q23) and t(10;11)(p13;q14-21) result in leukemogenic fusion proteins comprising the coiled coil domain of the transcription factor AF10 and the proteins MLL or CALM, respectively, and subsequently cause certain types of acute leukemia. The AF10 coiled-coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma. Using sequential synthetic peptides, we mapped the potential AF10/GAS41 interaction site, which was subsequently be used as scaffold for a library targeting the AF10 coiled-coil domain. Using phage display, we selected a peptide that binds the AF10 coiled-coil domain with higher affinity than the respective coiled-coil region of wild-type GAS41, as demonstrated by phage ELISA, CD, and PCAs. Furthermore, we were able to successfully deploy the inhibitory peptide in a mammalian cell line to lower the expression of Hoxa genes that have been described to be overexpressed in these leukemias. This work dissects molecular determinants mediating AF10-directed interactions in leukemic fusions comprising the N-terminal parts of the proteins MLL or CALM and the C-terminal coiled-coil domain of AF10. Furthermore, it outlines the first steps in recognizing and blocking the leukemia-associated AF10 interaction in histiocytic lymphoma cells and therefore, may have significant implications in future diagnostics and therapeutics. Copyright (c) 2014 European Peptide Society and John Wiley \& Sons, Ltd.}, language = {en} } @article{KuekenshoenerWohlwendNiemoelleretal.2014, author = {Kuekenshoener, Tim and Wohlwend, Daniel and Niemoeller, Christoph and Dondapati, Padmarupa and Speck, Janina and Adeniran, Adebola V. and Nieth, Anita and Gerhardt, Stefan and Einsle, Oliver and Mueller, Kristian M. and Arndt, Katja Maren}, title = {Improving coiled coil stability while maintaining specificity by a bacterial hitchhiker selection system}, series = {Journal of structural biology}, volume = {186}, journal = {Journal of structural biology}, number = {3}, publisher = {Elsevier}, address = {San Diego}, issn = {1047-8477}, doi = {10.1016/j.jsb.2014.03.002}, pages = {335 -- 348}, year = {2014}, abstract = {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.}, language = {en} } @article{HolldackOvsyannikovKuskeetal.2014, author = {Holldack, Karsten and Ovsyannikov, Ruslan and Kuske, P. and Mueller, R. and Schaelicke, A. and Scheer, M. and Gorgoi, Mihaela and Kuehn, D. and Leitner, T. and Svensson, S. and Martensson, N. and F{\"o}hlisch, Alexander}, title = {Single bunch X-ray pulses on demand from a multi-bunch synchrotron radiation source}, series = {Nature Communications}, volume = {5}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms5010}, pages = {7}, year = {2014}, abstract = {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.}, language = {en} } @article{WeizIshidaQuittereretal.2014, author = {Weiz, Annika R. and Ishida, Keishi and Quitterer, Felix and Meyer, Sabine and Kehr, Jan-Christoph and Mueller, Kristian M. and Groll, Michael and Hertweck, Christian and Dittmann-Th{\"u}nemann, Elke}, title = {Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions}, series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, volume = {53}, journal = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, number = {14}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1433-7851}, doi = {10.1002/anie.201309721}, pages = {3735 -- 3738}, year = {2014}, abstract = {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.}, language = {en} } @article{KuekenshoenerHagemannWohlwendetal.2014, author = {Kuekenshoener, Tim and Hagemann, Urs B. and Wohlwend, Daniel and Raeuber, Christina and Baumann, Tobias and Keller, Sandro and Einsle, Oliver and Mueller, Kristian M. and Arndt, Katja Maren}, title = {Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies}, series = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences}, volume = {15}, journal = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences}, number = {9}, publisher = {American Chemical Society}, address = {Washington}, issn = {1525-7797}, doi = {10.1021/bm5006883}, pages = {3296 -- 3305}, year = {2014}, abstract = {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.}, language = {en} } @article{MeyerRaberEbertetal.2015, author = {Meyer, S{\"o}ren and Raber, Georg and Ebert, Franziska and Leffers, L. and Mueller, Sandra Maria and Taleshi, M. S. and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites}, series = {Toxicology research}, volume = {4}, journal = {Toxicology research}, number = {5}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2045-452X}, doi = {10.1039/c5tx00122f}, pages = {1289 -- 1296}, year = {2015}, abstract = {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.}, language = {en} } @misc{MoserMuellerTschakertetal.2017, author = {Moser, Othmar and Mueller, Alexander and Tschakert, Gerhard and Koehler, Gerd and Lawrence, Jimmy B. and Groeschl, Werner and Pieber, Thomas R. and Bracken, Richard M. and Hofmann, Peter}, title = {Exercise Prescription in Type 1 Diabetes: Should We Use Percentages of Maximum Heart Rate?}, series = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine}, volume = {49}, journal = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0195-9131}, doi = {10.1249/01.mss.0000519798.35679.cf}, pages = {1020 -- 1020}, year = {2017}, language = {en} } @article{HoffmannWohltatMuelleretal.2017, author = {Hoffmann, Stefan A. and Wohltat, Christian and Mueller, Kristian M. and Arndt, Katja Maren}, title = {A user-friendly, low-cost turbidostat with versatile growth rate estimation based on an extended Kalman filter}, series = {PLoS one}, volume = {12}, journal = {PLoS one}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0181923}, pages = {5944 -- 5952}, year = {2017}, abstract = {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.}, language = {en} } @article{KienzlerPechKreibichetal.2015, author = {Kienzler, Sarah and Pech, Ina and Kreibich, Heidi and Mueller, M. and Thieken, Annegret}, title = {After the extreme flood in 2002: changes in preparedness, response and recovery of flood-affected residents in Germany between 2005 and 2011}, series = {Natural hazards and earth system sciences}, volume = {15}, journal = {Natural hazards and earth system sciences}, number = {3}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {1561-8633}, doi = {10.5194/nhess-15-505-2015}, pages = {505 -- 526}, year = {2015}, abstract = {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.}, language = {en} } @article{SoliveresManningPratietal.2016, author = {Soliveres, Santiago and Manning, Peter and Prati, Daniel and Gossner, Martin M. and Alt, Fabian and Arndt, Hartmut and Baumgartner, Vanessa and Binkenstein, Julia and Birkhofer, Klaus and Blaser, Stefan and Bluethgen, Nico and Boch, Steffen and Boehm, Stefan and Boerschig, Carmen and Buscot, Francois and Diekoetter, Tim and Heinze, Johannes and Hoelzel, Norbert and Jung, Kirsten and Klaus, Valentin H. and Klein, Alexandra-Maria and Kleinebecker, Till and Klemmer, Sandra and Krauss, Jochen and Lange, Markus and Morris, E. Kathryn and Mueller, Joerg and Oelmann, Yvonne and Overmann, J{\"o}rg and Pasalic, Esther and Renner, Swen C. and Rillig, Matthias C. and Schaefer, H. Martin and Schloter, Michael and Schmitt, Barbara and Schoening, Ingo and Schrumpf, Marion and Sikorski, Johannes and Socher, Stephanie A. and Solly, Emily F. and Sonnemann, Ilja and Sorkau, Elisabeth and Steckel, Juliane and Steffan-Dewenter, Ingolf and Stempfhuber, Barbara and Tschapka, Marco and Tuerke, Manfred and Venter, Paul and Weiner, Christiane N. and Weisser, Wolfgang W. and Werner, Michael and Westphal, Catrin and Wilcke, Wolfgang and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Fischer, Markus and Allan, Eric}, title = {Locally rare species influence grassland ecosystem multifunctionality}, series = {Philosophical transactions of the Royal Society of London : B, Biological sciences}, volume = {371}, journal = {Philosophical transactions of the Royal Society of London : B, Biological sciences}, publisher = {Royal Society}, address = {London}, issn = {0962-8436}, doi = {10.1098/rstb.2015.0269}, pages = {3175 -- 3185}, year = {2016}, abstract = {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.}, language = {en} } @article{NebeKroemerSchadetal.2017, author = {Nebe, Stephan and Kroemer, Nils B. and Schad, Daniel and Bernhardt, Nadine and Sebold, Miriam and Mueller, Dirk K. and Scholl, Lucie and Kuitunen-Paul, S{\"o}ren and Heinz, Andreas and Rapp, Michael A. and Huys, Quentin J. M. and Smolka, Michael N.}, title = {No association of goal-directed and habitual control with alcohol consumption in young adults}, series = {Addiction biology}, volume = {23}, journal = {Addiction biology}, number = {1}, publisher = {Wiley}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12490}, pages = {379 -- 393}, year = {2017}, abstract = {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.}, language = {en} }