@phdthesis{Kempa2004, author = {Kempa, Stefan}, title = {Analysen zur Stressantwort von Arabidopsis thaliana unter Schwefelmangelbedingungen : Studien zur Funktion der Dehydroascorbatreduktase in vivo}, address = {Potsdam}, pages = {123 S. : graph. Darst.}, year = {2004}, language = {de} } @article{KempaHummelSchwemmeretal.2009, author = {Kempa, Stefan and Hummel, Jan and Schwemmer, Thorsten and Pietzke, Matthias and Strehmel, Nadine and Wienkoop, Stefanie and Kopka, Joachim and Weckwerth, Wolfram}, title = {An automated GCxGC-TOF-MS protocol for batch-wise extraction and alignment of mass isotopomer matrixes from differential C-13-labelling experiments : a case study for photoautotrophic-mixotrophic grown Chlamydomonas reinhardtii cells}, issn = {0233-111X}, doi = {10.1002/jobm.200800337}, year = {2009}, abstract = {Two dimensional gas chromatography coupled to time-of-flight mass spectrometry (GCxGC-TOF-MS) is a promising technique to overcome limits of complex metabolome analysis using one dimensional GC-TOF-MS. Especially at the stage of data export and data mining, however, convenient procedures to cope with the complexity of GCxGC-TOF-MS data are still in development. Here, we present a high sample throughput protocol exploiting first and second retention index for spectral library search and subsequent construction of a high dimensional data matrix useful for statistical analysis. The method was applied to the analysis of 13 C-labelling experiments in the unicellular green alga Chlamydomonas reinhardtii. We developed a rapid sampling and extraction procedure for Chlamydomonas reinhardtii laboratory strain (CC503), a cell wall deficient mutant. By testing all published quenching protocols we observed dramatic metabolite leakage rates for certain metabolites. To circumvent metabolite leakage, samples were directly quenched and analyzed without separation of the medium. The growth medium was adapted to this rapid sampling protocol to avoid interference with GCxGC-TOF-MS analysis. To analyse batches of samples a new software tool, MetMax, was implemented which extracts the isotopomer matrix from stable isotope labelling experiments together with the first and second retention index (RI1 and RI2). To exploit RI1 and RI2 for metabolite identification we used the Golm metabolome database (GMD [1] with RI1/ RI2-reference spectra and new search algorithms. Using those techniques we analysed the dynamics of (CO2)-C-13 and C-13- acetate uptake in Chlamydomonas reinhardtii cells in two different steady states namely photoautotrophic and mixotrophic growth conditions.}, language = {en} } @article{SteinfathGaertnerLisecetal.2009, author = {Steinfath, Matthias and G{\"a}rtner, Tanja and Lisec, Jan and Meyer, Rhonda Christiane and Altmann, Thomas and Willmitzer, Lothar and Selbig, Joachim}, title = {Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers}, series = {Theoretical and applied genetics : TAG ; international journal of plant breeding research}, volume = {120}, journal = {Theoretical and applied genetics : TAG ; international journal of plant breeding research}, publisher = {Springer}, address = {Berlin}, issn = {0040-5752}, doi = {10.1007/s00122-009-1191-2}, pages = {239 -- 247}, year = {2009}, abstract = {A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80\% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected.}, language = {en} } @article{PrasadBaier2014, author = {Prasad, Sushma and Baier, Janina}, title = {Tracking the impact of mid- to late Holocene climate change and anthropogenic activities on Lake Holzmaar using an updated Holocene chronology}, series = {Global and planetary change}, volume = {122}, journal = {Global and planetary change}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0921-8181}, doi = {10.1016/j.gloplacha.2014.08.020}, pages = {251 -- 264}, year = {2014}, abstract = {The mid- to late Holocene interval is characterised by a highly variable climate in response to a gradual change in orbital insolation. The seasonal impact of these changes on the Eifel Maar region is not yet well documented largely due to uncertainties about the completeness of this archive ("missing varves" in the well known Lake Holzmaar) and a limited understanding of the factors (e.g. temperature, precipitation) influencing the seasonality archived within the lamination/varves. In this study we approach these challenges from a different perspective. Using detailed microfacies investigations we: (1) demonstrate that the ambiguity about the "missing varves" is related to the climate induced complex biotic and abiotic laminations that led to mis-identification of varves; (2) use a combination of detailed microfacies investigations (varve structure, seasonality of biotic and abiotic signals), lamination quality, varve counts on multiple cores, published and new radiocarbon dates to develop a continuous master chronology based on the Bayesian modelling approach. The dates of major climate, volcanic, and archaeological event(s) determined using our model are in good agreement with the independently determined ages of the same events from other archives, confirming the accuracy of our age model; (3) test the sensitivity of the seasonal proxies to the available data on mid-Holocene changes in temperature and precipitation; (4) demonstrate that the changes in lake eutrophicity are correlative with temperature changes in NW Europe and probably triggered by solar variability; and (5) show that the early Iron Age onset of eutrophication in Lake Holzmaar was climate induced and began several decades before the impact of anthropogenic activity was seen in the form of intensified detrital erosion in the catchment area. Our work has implications for understanding the impact of climate change and anthropogenic activities on limnological systems. (C) 2014 Elsevier B.V. All rights reserved.}, language = {en} } @article{ScheckWenderothCacaceMaystrenkoetal.2014, author = {Scheck-Wenderoth, Magdalena and Cacace, Mauro and Maystrenko, Yuriy Petrovich and Cherubini, Yvonne and Noack, Vera and Kaiser, Bjoern Onno and Sippel, Judith and Bjoern, Lewerenz}, title = {Models of heat transport in the Central European Basin System: Effective mechanisms at different scales}, series = {Marine and petroleum geology}, volume = {55}, journal = {Marine and petroleum geology}, publisher = {Elsevier}, address = {Oxford}, issn = {0264-8172}, doi = {10.1016/j.marpetgeo.2014.03.009}, pages = {315 -- 331}, year = {2014}, abstract = {Understanding heat transport in sedimentary basins requires an assessment of the regional 3D heat distribution and of the main physical mechanisms responsible for the transport of heat. We review results from different 3D numerical simulations of heat transport based on 3D basin models of the Central European Basin System (CEBS). Therefore we compare differently detailed 3D structural models of the area, previously published individually, to assess the influence of (1) different configurations of the deeper lithosphere, (2) the mechanism of heat transport considered and (3) large faults dissecting the sedimentary succession on the resulting thermal field and groundwater flow. Based on this comparison we propose a modelling strategy linking the regional and lithosphere-scale to the sub-basin and basin-fill scale and appropriately considering the effective heat transport processes. We find that conduction as the dominant mechanism of heat transport in sedimentary basins is controlled by the distribution of thermal conductivities, compositional and thickness variations of both the conductive and radiogenic crystalline crust as well as the insulating sediments and by variations in the depth to the thermal lithosphere-asthenosphere boundary. Variations of these factors cause thermal anomalies of specific wavelength and must be accounted for in regional thermal studies. In addition advective heat transport also exerts control on the thermal field on the regional scale. In contrast, convective heat transport and heat transport along faults is only locally important and needs to be considered for exploration on the reservoir scale. The general applicability of the proposed workflow makes it of interest for a broad range of application in geosciences including oil and gas exploration, geothermal utilization or carbon capture and sequestration issues. (C) 2014 Elsevier Ltd. All rights reserved.}, language = {en} } @article{FuehrerSchlaad2014, author = {Fuehrer, Felix N. and Schlaad, Helmut}, title = {ADMET polymerization of amino-acid-based diene}, series = {Macromolecular chemistry and physics}, volume = {215}, journal = {Macromolecular chemistry and physics}, number = {22}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1352}, doi = {10.1002/macp.201400166}, pages = {2268 -- 2273}, year = {2014}, abstract = {1,4-Di(homo)allyl-2,5-diketopiperazines are synthesized and polymerized via ADMET using the Hoveyda-Grubbs 2nd generation catalyst. The but-3-enylated diketopiperazine can be converted into unsaturated tertiary polyamide with molar mass of <3000 g mol(-1), whereas the allylated diketopiperazine cannot. Double-bond isomerization occurs regardless of whether or not benzoquinone is present. A polyesteramide with a higher molar mass of ca. 4800 g mol(-1) is obtained by the alternating copolymerization (ALTMET) of 1,4-di(but-3-enyl)-2,5-di ketopiperazine and ethylene glycol diacrylate. A post-polymerization modification of the poly(ester)amides via radical thiol-ene chemistry, however, fails.}, language = {en} } @article{GambaJonesTeasdaleetal.2014, author = {Gamba, Cristina and Jones, Eppie R. and Teasdale, Matthew D. and McLaughlin, Russell L. and Gonz{\´a}lez-Fortes, Gloria M. and Mattiangeli, Valeria and Domboroczki, Laszlo and Kovari, Ivett and Pap, Ildiko and Anders, Alexandra and Whittle, Alasdair and Dani, Janos and Raczky, Pal and Higham, Thomas F. G. and Hofreiter, Michael and Bradley, Daniel G. and Pinhasi, Ron}, title = {Genome flux and stasis in a five millennium transect of European prehistory}, series = {Nature Communications}, volume = {5}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms6257}, pages = {9}, year = {2014}, abstract = {The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (similar to 22x) and seven to similar to 1x coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence.}, language = {en} } @article{LehmannCoumouFrieleretal.2014, author = {Lehmann, Jascha and Coumou, Dim and Frieler, Katja and Eliseev, Alexey V. and Levermann, Anders}, title = {Future changes in extratropical storm tracks and baroclinicity under climate change}, series = {Environmental research letters}, volume = {9}, journal = {Environmental research letters}, number = {8}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {1748-9326}, doi = {10.1088/1748-9326/9/8/084002}, pages = {8}, year = {2014}, abstract = {The weather in Eurasia, Australia, and North and South America is largely controlled by the strength and position of extratropical storm tracks. Future climate change will likely affect these storm tracks and the associated transport of energy, momentum, and water vapour. Many recent studies have analyzed how storm tracks will change under climate change, and how these changes are related to atmospheric dynamics. However, there are still discrepancies between different studies on how storm tracks will change under future climate scenarios. Here, we show that under global warming the CMIP5 ensemble of coupled climate models projects only little relative changes in vertically averaged mid-latitude mean storm track activity during the northern winter, but agree in projecting a substantial decrease during summer. Seasonal changes in the Southern Hemisphere show the opposite behaviour, with an intensification in winter and no change during summer. These distinct seasonal changes in northern summer and southern winter storm tracks lead to an amplified seasonal cycle in a future climate. Similar changes are seen in the mid-latitude mean Eady growth rate maximum, a measure that combines changes in vertical shear and static stability based on baroclinic instability theory. Regression analysis between changes in the storm tracks and changes in the maximum Eady growth rate reveal that most models agree in a positive association between the two quantities over mid-latitude regions.}, language = {en} } @article{JonesGonzalezFortesConnelletal.2015, author = {Jones, Eppie R. and Gonz{\´a}lez-Fortes, Gloria M. and Connell, Sarah and Siska, Veronika and Eriksson, Anders and Martiniano, Rui and McLaughlin, Russell L. and Llorente, Marcos Gallego and Cassidy, Lara M. and Gamba, Cristina and Meshveliani, Tengiz and Bar-Yosef, Ofer and Mueller, Werner and Belfer-Cohen, Anna and Matskevich, Zinovi and Jakeli, Nino and Higham, Thomas F. G. and Currat, Mathias and Lordkipanidze, David and Hofreiter, Michael and Manica, Andrea and Pinhasi, Ron and Bradley, Daniel G.}, title = {Upper Palaeolithic genomes reveal deep roots of modern Eurasians}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms9912}, pages = {8}, year = {2015}, abstract = {We extend the scope of European palaeogenomics by sequencing the genomes of Late Upper Palaeolithic (13,300 years old, 1.4-fold coverage) and Mesolithic (9,700 years old, 15.4-fold) males from western Georgia in the Caucasus and a Late Upper Palaeolithic (13,700 years old, 9.5-fold) male from Switzerland. While we detect Late Palaeolithic-Mesolithic genomic continuity in both regions, we find that Caucasus hunter-gatherers (CHG) belong to a distinct ancient clade that split from western hunter-gatherers similar to 45 kya, shortly after the expansion of anatomically modern humans into Europe and from the ancestors of Neolithic farmers similar to 25 kya, around the Last Glacial Maximum. CHG genomes significantly contributed to the Yamnaya steppe herders who migrated into Europe similar to 3,000 BC, supporting a formative Caucasus influence on this important Early Bronze age culture. CHG left their imprint on modern populations from the Caucasus and also central and south Asia possibly marking the arrival of Indo-Aryan languages.}, language = {en} } @phdthesis{Friese2016, author = {Friese, Viviane A.}, title = {Solvato-, vapo, mechanochromic and luminescent behavior of Rhodium, Platinum and Gold complexes and their coordination polymers}, school = {Universit{\"a}t Potsdam}, pages = {100 S.}, year = {2016}, language = {en} } @phdthesis{Swart2017, author = {Swart, Corn{\´e}}, title = {Managing protein activity in A. thaliana}, school = {Universit{\"a}t Potsdam}, pages = {160}, year = {2017}, language = {en} } @phdthesis{Radloff2018, author = {Radloff, Katrin}, title = {The role of the fatty acid profile and its modulation by cytokines in the systemic inflammation in cancer cachexia}, school = {Universit{\"a}t Potsdam}, pages = {156}, year = {2018}, abstract = {Systemic inflammation is a hallmark of cancer cachexia. Among tumor-host interactions, the white adipose tissue (WAT) is an important contributor to inflammation as it suffers morphological reorganization and lipolysis, releasing free fatty acids (FA), bioactive lipid mediators (LM) and pro-inflammatory cytokines, which accentuate the activation of pro-inflammatory signaling pathways and the recruitment of immune cells to the tissue. This project aimed to investigate which inflammatory factors are involved in the local adipose tissue inflammation and what is the influence of such factors upon enzymes involved in FA or LM metabolism in healthy individuals (Control), weight stable gastro-intestinal cancer patients (WSC) and cachectic cancer patients (CC). The results demonstrated that the inflammatory signature of systemic inflammation is different from local adipose tissue inflammation. The systemic inflammation of the cachectic cancer patients was characterized by higher levels of circulating saturated fatty acids (SFA), tumor-necrosis-factor-α (TNF-α), interleukins IL-6, IL-8 and CRP while levels of polyunsaturated fatty acids (PUFAs), especially n3-PUFAs, were lower in CC than in the other groups. In vitro and in adipose tissue explants, pro-inflammatory cytokines and SFAs were shown to increase the chemokines IL-8 and CXCL10 that were found to be augmented in adipose tissue inflammation in CC which was more profound in the visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT). Systemic inflammation was negatively associated with the expression of PUFA synthesizing enzymes, though gene and protein expression did hardly differ between groups. The effects of inflammatory factors on enzymes in the whole tissue could have been masked by differentiated modulation of the diverse cell types in the same tissue. In vitro experiments showed that the expression of FA-modifying enzymes such as desaturases and elongases in adipocytes and macrophages was regulated into opposing directions by TNF-α, IL-6, LPS or palmitate. The higher plasma concentration of the pro-resolving LM resolvin D1 in CC cannot compensate the overall inflammatory status and the results indicate that inflammatory cytokines interfere with synthesis pathways of pro-resolving LM. In summary, the data revealed a complex inter-tissue and inter-cellular crosstalk mediated by pro-inflammatory cytokines and lipid compounds enhancing inflammation in cancer cachexia by feed-forward mechanisms.}, language = {en} } @article{DvornikovLeibmanHeimetal.2018, author = {Dvornikov, Yury and Leibman, Marina and Heim, Birgit and Bartsch, Annett and Herzschuh, Ulrike and Skorospekhova, Tatiana and Fedorova, Irina and Khomutov, Artem and Widhalm, Barbara and Gubarkov, Anatoly and R{\"o}ßler, Sebastian}, title = {Terrestrial CDOM in lakes of Yamal Peninsula}, series = {Remote Sensing}, volume = {10}, journal = {Remote Sensing}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2072-4292}, doi = {10.3390/rs10020167}, pages = {21}, year = {2018}, abstract = {In this study, we analyze interactions in lake and lake catchment systems of a continuous permafrost area. We assessed colored dissolved organic matter (CDOM) absorption at 440 nm (a(440)(CDOM)) and absorption slope (S300-500) in lakes using field sampling and optical remote sensing data for an area of 350 km(2) in Central Yamal, Siberia. Applying a CDOM algorithm (ratio of green and red band reflectance) for two high spatial resolution multispectral GeoEye-1 and Worldview-2 satellite images, we were able to extrapolate the a()(CDOM) data from 18 lakes sampled in the field to 356 lakes in the study area (model R-2 = 0.79). Values of a(440)(CDOM) in 356 lakes varied from 0.48 to 8.35 m(-1) with a median of 1.43 m(-1). This a()(CDOM) dataset was used to relate lake CDOM to 17 lake and lake catchment parameters derived from optical and radar remote sensing data and from digital elevation model analysis in order to establish the parameters controlling CDOM in lakes on the Yamal Peninsula. Regression tree model and boosted regression tree analysis showed that the activity of cryogenic processes (thermocirques) in the lake shores and lake water level were the two most important controls, explaining 48.4\% and 28.4\% of lake CDOM, respectively (R-2 = 0.61). Activation of thermocirques led to a large input of terrestrial organic matter and sediments from catchments and thawed permafrost to lakes (n = 15, mean a(440)(CDOM) = 5.3 m(-1)). Large lakes on the floodplain with a connection to Mordy-Yakha River received more CDOM (n = 7, mean a(440)(CDOM) = 3.8 m(-1)) compared to lakes located on higher terraces.}, language = {en} } @phdthesis{Robalo2018, author = {Robalo, Jo{\~a}o Ramiro Alavedra Mendes}, title = {Investigating the role of fluorinated amino acids on protein structure and function using simulation}, school = {Universit{\"a}t Potsdam}, pages = {84}, year = {2018}, language = {en} } @phdthesis{Mubeen2018, author = {Mubeen, Umarah}, title = {Regulation of central carbon and nitrogen metabolism by Target of Rapamycin (TOR) kinase in Chlamydomonas reinhardtii}, school = {Universit{\"a}t Potsdam}, pages = {vii, 153}, year = {2018}, abstract = {The highly conserved protein complex containing the Target of Rapamycin (TOR) kinase is known to integrate intra- and extra-cellular stimuli controlling nutrient allocation and cellular growth. This thesis describes three studies aimed to understand how TOR signaling pathway influences carbon and nitrogen metabolism in Chlamydomonas reinhardtii. The first study presents a time-resolved analysis of the molecular and physiological features across the diurnal cycle. The inhibition of TOR leads to 50\% reduction in growth followed by nonlinear delays in the cell cycle progression. The metabolomics analysis showed that the growth repression is mainly driven by differential carbon partitioning between anabolic and catabolic processes. Furthermore, the high accumulation of nitrogen-containing compounds indicated that TOR kinase controls the carbon to nitrogen balance of the cell, which is responsible for biomass accumulation, growth and cell cycle progression. In the second study the cause of the high accumulation of amino acids is explained. For this purpose, the effect of TOR inhibition on Chlamydomonas was examined under different growth regimes using stable 13C- and 15N-isotope labeling. The data clearly showed that an increased nitrogen uptake is induced within minutes after the inhibition of TOR. Interestingly, this increased N-influx is accompanied by increased activities of nitrogen assimilating enzymes. Accordingly, it was concluded that TOR inhibition induces de-novo amino acid synthesis in Chlamydomonas. The recognition of this novel process opened an array of questions regarding potential links between central metabolism and TOR signaling. Therefore a detailed phosphoproteomics study was conducted to identify the potential substrates of TOR pathway regulating central metabolism. Interestingly, some of the key enzymes involved in carbon metabolism as well as amino acid synthesis exhibited significant changes in the phosphosite intensities immediately after TOR inhibition. Altogether, these studies provide a) detailed insights to metabolic response of Chlamydomonas to TOR inhibition, b) identification of a novel process causing rapid upshifts in amino acid levels upon TOR inhibition and c) finally highlight potential targets of TOR signaling regulating changes in central metabolism. Further biochemical and molecular investigations could confirm these observations and advance the understanding of growth signaling in microalgae.}, language = {en} } @phdthesis{GraberMajchrzak2018, author = {Graber Majchrzak, Sarah}, title = {Arbeit - Produktion - Protest}, series = {Zeithistorische Studien}, journal = {Zeithistorische Studien}, number = {62}, publisher = {B{\"o}hlau}, address = {K{\"o}ln}, isbn = {978-3-412-51917-9}, school = {Universit{\"a}t Potsdam}, pages = {563 S.}, year = {2018}, abstract = {Am 14. August 1980 begannen die Arbeiter*innen auf der Danziger Leninwerft einen Besetzungsstreik, in deren Folge die erste unabh{\"a}ngige Gewerkschaft Solidarność gegr{\"u}ndet wurde. Einen Monat sp{\"a}ter am 17. September 1980 gingen auf der anderen Seite des „Eisernen Vorhangs" die Arbeiter*innen der „AG Weser" Werft in Bremen auf die Straße, um gegen den Verlust ihrer Arbeitspl{\"a}tze zu protestieren. Die vorliegende Studie zeigt aus einer Perspektive „von unten", wie seit den 1970er Jahren Betriebe in zwei unterschiedlichen politisch-{\"o}konomischen Systeme auf technische Ver{\"a}nderungen und die versch{\"a}rfte Konkurrenz auf dem Weltmarkt reagierten und verweist darauf, dass die Krisen in Ost und West Ende der 1970er Jahre eng miteinander verbunden waren.}, language = {de} } @article{PornsawadSapsakulBoeckmann2019, author = {Pornsawad, Pornsarp and Sapsakul, Nantawan and B{\"o}ckmann, Christine}, title = {A modified asymptotical regularization of nonlinear ill-posed problems}, series = {Mathematics}, volume = {7}, journal = {Mathematics}, edition = {5}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2227-7390}, doi = {10.3390/math7050419}, pages = {19}, year = {2019}, abstract = {In this paper, we investigate the continuous version of modified iterative Runge-Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))-𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.}, language = {en} } @article{KotthoffLisecSchwerdtleetal.2019, author = {Kotthoff, Lisa and Lisec, Jan and Schwerdtle, Tanja and Koch, Matthias}, title = {Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis}, series = {Molecules}, volume = {24}, journal = {Molecules}, number = {15}, publisher = {MDPI}, address = {Basel}, issn = {1420-3049}, doi = {10.3390/molecules24152732}, pages = {12}, year = {2019}, abstract = {The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.}, language = {en} } @phdthesis{Yishai2019, author = {Yishai, Oren}, title = {Engineering the reductive glycine pathway in Escherichia coli}, school = {Universit{\"a}t Potsdam}, pages = {86}, year = {2019}, language = {en} } @phdthesis{RuizRodriguez2019, author = {Ruiz Rodriguez, Janete Lorena}, title = {Osmotic pressure effects on collagen mimetic peptides}, school = {Universit{\"a}t Potsdam}, pages = {139}, year = {2019}, abstract = {Collagen is the most abundant protein in mammals. In many tissues, collagen molecules assemble to form a hierarchical structure. In the smallest supramolecular unit, named fibril, each molecule is displaced in the axial direction with respect to its neighbors. This staggering creates a periodic gap and overlap regions, where the gap regions exhibit 20\% less density. These fibril-forming collagens play an essential role in the strength of connective tissues. Despite much effort, directed at understanding collagen function and regulation, the influence of the chemical environment on the local structural and mechanical properties remains poorly understood. Recent studies, aimed at elucidating the effect of osmotic pressure, showed that collagen contracts upon water removal. This observation highlights the importance of water for the stabilization and mechanics of the collagen molecule. Using collagen mimetic peptides (CMPs), which fold into triple helical structures reminiscent of natural collagen, the primary goal of this work was to investigate the effect of the osmotic pressure on specific collagen-mimetic sequences. CMPs were used as the model system as they provide sequence control, which is essential for discriminating local from global structural changes and for relating the observed effects to existing knowledge about the full-length collagen molecule. Of specific interest was the structure of individual collagen triple helices as well as their organization into self-assembled higher order structures. These key structural features were monitored with infrared spectroscopy (IR) and synchrotron X-ray scattering, while varying the osmotic pressure. For controlling the osmotic pressure, CMP powder samples were incubated in air of defined relative humidity, ranging from dry conditions to highly "humid". In addition, to obtain more biologically relevant conditions, the CMPs were measured in ultrapure water and in solutions containing small molecule osmolytes. Using the sequences (Pro-Pro-Gly)10, (Pro-Hyp-Gly)10 and (Hyp-Hyp-Gly)10, it was shown that CMPs with different degrees of proline hydroxylation (Hyp = hydroxyproline) exhibit a sequence-specific response to osmotic pressure. IR spectroscopy revealed that osmotic pressure changes affect the strength of the triple helix stabilizing, interchain hydrogen bond and that the extent of this change depends on the degree of hydroxylation. X-ray scattering experiments further showed that changes in osmotic pressure affect both the molecular length as well as the higher order organization of CMPs. Starting from a pseudo-hexagonal packing in the dry state, all three CMPs showed isotropic swelling when increasing the water content to approximately 1.2 water molecules per amino acid, again to different extents depending on the degree of hydroxylation. When increasing the water content further, this pseudo-hexagonal arrangement breaks down. In the fully hydrated state, each CMP is characterized by its own specific and more complex packing geometry. While these changes in the lateral packing arrangement suggest swelling upon hydration, an overall decrease of the molecular length (i.e. contraction) was observed in the axial direction. Also for this structural feature, a strong dependency on the specific amino acid sequence was found. Interestingly, the observed contraction is the opposite of what has been reported for natural collagen. As (Pro-Pro-Gly)n, (Pro-Hyp-Gly)n and (Hyp-Hyp-Gly)n repeat units are found in collagen with a relatively high abundance, this suggests that other collagen sequence fragments need to respond to hydration in the opposite way to obtain a net elongation of the full-length collagen molecule. To test this hypothesis, sequences predicted to be sensitive to osmotic pressure were considered. One such sequence, consisting of two repeat units (Ala-Arg-Gly-Ser-Asp-Gly), was inserted as a guest into a (Pro-Pro-Gly) host. When compared to the canonical CMP sequences investigated earlier, the lateral helix packing follows a similar trend with increasing hydration; however, the host-guest CMP axially elongates with increasing water content. This behavior is more similar to what has been found for natural collagen and suggests that different sequences do determine the molecular length of collagen sequences differently. Interestingly, the canonical sequences are more abundant in the overlap region while the guest sequence is found in the gap region. This allows to speculate that sequences in the gap and overlap regions possess a specifically fine-tuned local response to osmotic pressure changes. Clearly, more experiments with additional sequences are needed to confirm this. In conclusion, the results obtained in this work indicate a highly sequence specific interaction between collagen and water. Osmotic pressure-induced conformational changes mostly originate from local geometries and bonding patterns and affect both the structure of individual triple helices as well as higher order assemblies. One key remaining question is how these conformational changes affect the local mechanical properties of the collagen molecule. As a first step, the stiffness (persistence length) of full-length collagen was determined using atomic force microscopy. In the future, experimental strategies need to be developed that allow for investigating the mechanical properties of specific collagen sequences, e.g. performing single-molecule force spectroscopy of CMPs.}, language = {en} }