@article{SchenkeSchjeidePuescheletal.2020, author = {Schenke, Maren and Schjeide, Brit-Maren and P{\"u}schel, Gerhard Paul and Seeger, Bettina}, title = {Analysis of motor neurons differentiated from human induced pluripotent stem cells for the use in cell-based Botulinum neurotoxin activity assays}, series = {Toxins}, volume = {12}, journal = {Toxins}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {2072-6651}, doi = {10.3390/toxins12050276}, pages = {20}, year = {2020}, abstract = {Botulinum neurotoxins (BoNTs) are potent neurotoxins produced by bacteria, which inhibit neurotransmitter release, specifically in their physiological target known as motor neurons (MNs). For the potency assessment of BoNTs produced for treatment in traditional and aesthetic medicine, the mouse lethality assay is still used by the majority of manufacturers, which is ethically questionable in terms of the 3Rs principle. In this study, MNs were differentiated from human induced pluripotent stem cells based on three published protocols. The resulting cell populations were analyzed for their MN yield and their suitability for the potency assessment of BoNTs. MNs produce specific gangliosides and synaptic proteins, which are bound by BoNTs in order to be taken up by receptor-mediated endocytosis, which is followed by cleavage of specific soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) proteins required for neurotransmitter release. The presence of receptors and substrates for all BoNT serotypes was demonstrated in MNs generated in vitro. In particular, the MN differentiation protocol based on Du et al. yielded high numbers of MNs in a short amount of time with high expression of BoNT receptors and targets. The resulting cells are more sensitive to BoNT/A1 than the commonly used neuroblastoma cell line SiMa. MNs are, therefore, an ideal tool for being combined with already established detection methods.}, language = {en} } @article{KocPetrowThieken2020, author = {Koc, Gamze and Petrow, Theresia and Thieken, Annegret}, title = {Analysis of the most severe flood events in Turkey (1960-2014)}, series = {Water / Molecular Diversity Preservation International (MDPI)}, volume = {12}, journal = {Water / Molecular Diversity Preservation International (MDPI)}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2073-4441}, doi = {10.3390/w12061562}, pages = {32}, year = {2020}, abstract = {The most severe flood events in Turkey were determined for the period 1960-2014 by considering the number of fatalities, the number of affected people, and the total economic losses as indicators. The potential triggering mechanisms (i.e., atmospheric circulations and precipitation amounts) and aggravating pathways (i.e., topographic features, catchment size, land use types, and soil properties) of these 25 events were analyzed. On this basis, a new approach was developed to identify the main influencing factor per event and to provide additional information for determining the dominant flood occurrence pathways for severe floods. The events were then classified through hierarchical cluster analysis. As a result, six different clusters were found and characterized. Cluster 1 comprised flood events that were mainly influenced by drainage characteristics (e.g., catchment size and shape); Cluster 2 comprised events aggravated predominantly by urbanization; steep topography was identified to be the dominant factor for Cluster 3; extreme rainfall was determined as the main triggering factor for Cluster 4; saturated soil conditions were found to be the dominant factor for Cluster 5; and orographic effects of mountain ranges characterized Cluster 6. This study determined pathway patterns of the severe floods in Turkey with regard to their main causal or aggravating mechanisms. Accordingly, geomorphological properties are of major importance in large catchments in eastern and northeastern Anatolia. In addition, in small catchments, the share of urbanized area seems to be an important factor for the extent of flood impacts. This paper presents an outcome that could be used for future urban planning and flood risk prevention studies to understand the flood mechanisms in different regions of Turkey.}, language = {en} } @article{KocPetrowThieken2020, author = {Ko{\c{c}}, Gamze and Petrow, Theresia and Thieken, Annegret}, title = {Analysis of the Most Severe Flood Events in Turkey (1960-2014)}, series = {Water}, volume = {12}, journal = {Water}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2073-4441}, doi = {10.3390/w12061562}, pages = {32}, year = {2020}, abstract = {The most severe flood events in Turkey were determined for the period 1960-2014 by considering the number of fatalities, the number of affected people, and the total economic losses as indicators. The potential triggering mechanisms (i.e., atmospheric circulations and precipitation amounts) and aggravating pathways (i.e., topographic features, catchment size, land use types, and soil properties) of these 25 events were analyzed. On this basis, a new approach was developed to identify the main influencing factor per event and to provide additional information for determining the dominant flood occurrence pathways for severe floods. The events were then classified through hierarchical cluster analysis. As a result, six different clusters were found and characterized. Cluster 1 comprised flood events that were mainly influenced by drainage characteristics (e.g., catchment size and shape); Cluster 2 comprised events aggravated predominantly by urbanization; steep topography was identified to be the dominant factor for Cluster 3; extreme rainfall was determined as the main triggering factor for Cluster 4; saturated soil conditions were found to be the dominant factor for Cluster 5; and orographic effects of mountain ranges characterized Cluster 6. This study determined pathway patterns of the severe floods in Turkey with regard to their main causal or aggravating mechanisms. Accordingly, geomorphological properties are of major importance in large catchments in eastern and northeastern Anatolia. In addition, in small catchments, the share of urbanized area seems to be an important factor for the extent of flood impacts. This paper presents an outcome that could be used for future urban planning and flood risk prevention studies to understand the flood mechanisms in different regions of Turkey.}, language = {en} } @article{MunyaevSmirnovKostinetal.2020, author = {Munyaev, Vyacheslav O. and Smirnov, Lev A. and Kostin, Vasily A. and Osipov, Grigory V. and Pikovskij, Arkadij}, title = {Analytical approach to synchronous states of globally coupled noisy rotators}, series = {New journal of physics : the open-access journal for physics}, volume = {22}, journal = {New journal of physics : the open-access journal for physics}, number = {2}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {1367-2630}, doi = {10.1088/1367-2630/ab6f93}, pages = {14}, year = {2020}, abstract = {We study populations of globally coupled noisy rotators (oscillators with inertia) allowing a nonequilibrium transition from a desynchronized state to a synchronous one (with the nonvanishing order parameter). The newly developed analytical approaches resulted in solutions describing the synchronous state with constant order parameter for weakly inertial rotators, including the case of zero inertia, when the model is reduced to the Kuramoto model of coupled noise oscillators. These approaches provide also analytical criteria distinguishing supercritical and subcritical transitions to the desynchronized state and indicate the universality of such transitions in rotator ensembles. All the obtained analytical results are confirmed by the numerical ones, both by direct simulations of the large ensembles and by solution of the associated Fokker-Planck equation. We also propose generalizations of the developed approaches for setups where different rotators parameters (natural frequencies, masses, noise intensities, strengths and phase shifts in coupling) are dispersed.}, language = {en} } @article{MunyaevSmirnovKostinetal.2020, author = {Munyaev, Vyacheslav and Smirnov, Lev A. and Kostin, Vasily and Osipov, Grigory V. and Pikovskij, Arkadij}, title = {Analytical approach to synchronous states of globally coupled noisy rotators}, series = {New Journal of Physics}, volume = {22}, journal = {New Journal of Physics}, number = {2}, publisher = {Springer Science}, address = {New York}, pages = {15}, year = {2020}, abstract = {We study populations of globally coupled noisy rotators (oscillators with inertia) allowing a nonequilibrium transition from a desynchronized state to a synchronous one (with the nonvanishing order parameter). The newly developed analytical approaches resulted in solutions describing the synchronous state with constant order parameter for weakly inertial rotators, including the case of zero inertia, when the model is reduced to the Kuramoto model of coupled noise oscillators. These approaches provide also analytical criteria distinguishing supercritical and subcritical transitions to the desynchronized state and indicate the universality of such transitions in rotator ensembles. All the obtained analytical results are confirmed by the numerical ones, both by direct simulations of the large ensembles and by solution of the associated Fokker-Planck equation. We also propose generalizations of the developed approaches for setups where different rotators parameters (natural frequencies, masses, noise intensities, strengths and phase shifts in coupling) are dispersed.}, language = {en} } @article{ZhangYangJomaaetal.2020, author = {Zhang, Xiaolin and Yang, Xiaoqiang and Jomaa, Seifeddine and Rode, Michael}, title = {Analyzing impacts of seasonality and landscape gradient on event-scale nitrate-discharge dynamics based on nested high-frequency monitoring}, series = {Journal of hydrology}, volume = {591}, journal = {Journal of hydrology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-1694}, doi = {10.1016/j.jhydrol.2020.125585}, pages = {12}, year = {2020}, abstract = {Increasingly available high-frequency data during storm events, when hydrological dynamics most likely activate nitrate storage-flux exchanges, reveal insights into catchment nitrate dynamics. In this study, we explored impacts of seasonality and landscape gradients on nitrate concentration-discharge (C-Q) hysteresis patterns in the Selke catchment, central Germany, which has heterogeneous combinations of meteorological, hydrogeological and land use conditions. Three nested gauging stations established along the main Selke River captured flow and nitrate export dynamics from the uppermost subcatchment (mixed forest and arable land), middle subcatchment (pure steep forest) and lowermost subcatchment (arable and urban land). We collected continuous high-frequency (15-min) discharge and nitrate concentration data from 2012 to 2017 and analyzed the 223 events detected at all three stations. A dominant hysteresis pattern in the uppermost and middle subcatchments was counter-clockwise and combined with an accretion effect, indicating many proximal and mobilized distal nitrate sources. However, 66\% of all events at the catchment outlet experienced a dilution effect, possibly due to mechanisms that vary seasonally. During wetting/wet periods (October-March), it was combined mainly with a counter-clockwise pattern due to the dominance of event runoff volume from the uppermost and middle subcatchments. During drying/dry periods (April-September), however, it was combined mainly with a clockwise pattern due to occasional quick surface flows from lowland near-stream urban areas. In addition, the clockwise hysteresis occurred mainly from May-October during mostly drying/dry periods at all three sites, indicating little distal nitrate transport in response to the low terrestrial hydrological connectivity, especially in the lowermost dry and flat sub-catchment. This comprehensive analysis (i.e., clockwise vs. counter-clockwise, accretion vs. dilution) enables in-depth analysis of nitrate export mechanisms during certain periods under different landscape conditions. Specific combination of C-Q relationships could identify target locations for agricultural management actions that decrease nitrate output. Therefore, we strongly encourage long-term multisite and high-frequency monitoring strategies in heterogeneous nested catchment(s), which can help understand process mechanisms, generate data for physical-based water-quality modeling and provide guidance for water and agricultural management.}, language = {en} } @article{PaijmansBarlowHennebergeretal.2020, author = {Paijmans, Johanna L. A. and Barlow, Axel and Henneberger, Kirstin and Fickel, J{\"o}rns and Hofreiter, Michael and Foerste, Daniel W. G.}, title = {Ancestral mitogenome capture of the Southeast Asian banded linsang}, series = {PLoS ONE}, volume = {15}, journal = {PLoS ONE}, number = {6}, publisher = {PLOS}, address = {San Francisco, California, US}, issn = {1932-6203}, doi = {10.1371/journal.pone.0234385}, pages = {12}, year = {2020}, abstract = {Utilising a reconstructed ancestral mitochondrial genome of a clade to design hybridisation capture baits can provide the opportunity for recovering mitochondrial sequences from all its descendent and even sister lineages. This approach is useful for taxa with no extant close relatives, as is often the case for rare or extinct species, and is a viable approach for the analysis of historical museum specimens. Asiatic linsangs (genus Prionodon) exemplify this situation, being rare Southeast Asian carnivores for which little molecular data is available. Using ancestral capture we recover partial mitochondrial genome sequences for seven banded linsangs (P. linsang) from historical specimens, representing the first intraspecific genetic dataset for this species. We additionally assemble a high quality mitogenome for the banded linsang using shotgun sequencing for time-calibrated phylogenetic analysis. This reveals a deep divergence between the two Asiatic linsang species (P. linsang, P. pardicolor), with an estimated divergence of ~12 million years (Ma). Although our sample size precludes any robust interpretation of the population structure of the banded linsang, we recover two distinct matrilines with an estimated tMRCA of ~1 Ma. Our results can be used as a basis for further investigation of the Asiatic linsangs, and further demonstrate the utility of ancestral capture for studying divergent taxa without close relatives.}, language = {en} } @article{Lehnert2020, author = {Lehnert, Gertrud}, title = {Andere R{\"a}ume : Pupenh{\"a}user}, series = {Materielle Miniaturen : zur {\"A}sthetik der Verkleinerung}, journal = {Materielle Miniaturen : zur {\"A}sthetik der Verkleinerung}, publisher = {K{\"o}nigshausen \& Neumann}, address = {W{\"u}rzburg}, isbn = {978-3-8260-6679-5}, pages = {57 -- 74}, year = {2020}, language = {de} } @article{Steinroetter2020, author = {Steinr{\"o}tter, Bj{\"o}rn}, title = {Anforderungen an die Einwilligung des Internetnutzers beim Setzen und Auslesen von Cookies}, series = {Zeitschrift f{\"u}r das Privatrecht der Europ{\"a}ischen Union}, volume = {17}, journal = {Zeitschrift f{\"u}r das Privatrecht der Europ{\"a}ischen Union}, number = {3}, publisher = {Dr. Otto Schmidt}, address = {K{\"o}ln}, issn = {2364-7205}, doi = {10.9785/gpr-2020-170303}, pages = {106 -- 111}, year = {2020}, language = {de} } @article{DuffusSchrapersSchuthetal.2020, author = {Duffus, Benjamin R. and Schrapers, Peer and Schuth, Nils and Mebs, Stefan and Dau, Holger and Leimk{\"u}hler, Silke and Haumann, Michael}, title = {Anion binding and oxidative modification at the molybdenum cofactor of formate dehydrogenase from Rhodobacter capsulatus studied by X-ray absorption spectroscopy}, series = {Inorganic chemistry}, volume = {59}, journal = {Inorganic chemistry}, number = {1}, publisher = {American Chemical Society}, address = {Washington, DC}, issn = {0020-1669}, doi = {10.1021/acs.inorgchem.9b01613}, pages = {214 -- 225}, year = {2020}, abstract = {Formate dehydrogenase (FDH) enzymes are versatile catalysts for CO2 conversion. The FDH from Rhodobacter capsulatus contains a molybdenum cofactor with the dithiolene functions of two pyranopterin guanine dinucleotide molecules, a conserved cysteine, and a sulfido group bound at Mo(VI). In this study, we focused on metal oxidation state and coordination changes in response to exposure to O-2, inhibitory anions, and redox agents using X-ray absorption spectroscopy (XAS) at the Mo K-edge. Differences in the oxidative modification of the bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor relative to samples prepared aerobically without inhibitor, such as variations in the relative numbers of sulfido (Mo=S) and oxo (Mo=O) bonds, were observed in the presence of azide (N-3(-)) or cyanate (OCN-). Azide provided best protection against O-2, resulting in a quantitatively sulfurated cofactor with a displaced cysteine ligand and optimized formate oxidation activity. Replacement of the cysteine ligand by a formate (HCO2-) ligand at the molybdenum in active enzyme is compatible with our XAS data. Cyanide (CN-) inactivated the enzyme by replacing the sulfido ligand at Mo(VI) with an oxo ligand. Evidence that the sulfido group may become protonated upon molybdenum reduction was obtained. Our results emphasize the role of coordination flexibility at the molybdenum center during inhibitory and catalytic processes of FDH enzymes.}, language = {en} } @article{GlatzelNoackSchanzenbachetal.2020, author = {Glatzel, Julia and Noack, Sebastian and Schanzenbach, Dirk and Schlaad, Helmut}, title = {Anionic polymerization of dienes in 'green' solvents}, series = {Polymer international}, volume = {70}, journal = {Polymer international}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {0959-8103}, doi = {10.1002/pi.6152}, pages = {181 -- 184}, year = {2020}, abstract = {Isoprene and beta-myrcene were polymerized by anionic polymerization in bulk and in the 'green' ether solvents cyclopentyl methyl ether and 2-methyltetrahydrofuran and, for comparison, in cyclohexane and tetrahydrofuran. The polydienes produced in bulk and in cyclohexane contained high amounts of 1,4 units (>90\%) whereas those produced in ether solvents were rich in 1,2 and 3,4 units (36\%-86\%). Comparison of the microstructures and glass transition temperatures of the polydienes obtained in the various solvents suggests that conventionally used solvents can be substituted by environmentally more friendly alternatives.}, language = {en} } @article{Lampart2020, author = {Lampart, Fabian}, title = {Anmerkungen zum Konzept der Funktionslosigkeit in Lyrikdebatten der 1950er und 1960er Jahre}, series = {Grundfragen der Lyrikologie. Bd. 2. Begriffe, Methoden und Analysedimensionen}, journal = {Grundfragen der Lyrikologie. Bd. 2. Begriffe, Methoden und Analysedimensionen}, editor = {Hillebrandt, Claudia and Klimek, Sonja and M{\"u}ller, Ralph and Zymner, R{\"u}diger}, publisher = {de Gruyter}, address = {Berlin, Boston}, isbn = {978-3-11-045687-5}, pages = {177 -- 195}, year = {2020}, language = {de} } @article{HartmannPreickAbeltetal.2020, author = {Hartmann, Stefanie and Preick, Michaela and Abelt, Silke and Scheffel, Andr{\´e} and Hofreiter, Michael}, title = {Annotated genome sequences of the carnivorous plant Roridula gorgonias and a non-carnivorous relative, Clethra arborea}, series = {BMC Research Notes}, volume = {13}, journal = {BMC Research Notes}, publisher = {Biomed Central}, address = {London}, issn = {1756-0500}, doi = {10.1186/s13104-020-05254-4}, pages = {6}, year = {2020}, abstract = {Objective Plant carnivory is distributed across the tree of life and has evolved at least six times independently, but sequenced and annotated nuclear genomes of carnivorous plants are currently lacking. We have sequenced and structurally annotated the nuclear genome of the carnivorous Roridula gorgonias and that of a non-carnivorous relative, Madeira's lily-of-the-valley-tree, Clethra arborea, both within the Ericales. This data adds an important resource to study the evolutionary genetics of plant carnivory across angiosperm lineages and also for functional and systematic aspects of plants within the Ericales. Results Our assemblies have total lengths of 284 Mbp (R. gorgonias) and 511 Mbp (C. arborea) and show high BUSCO scores of 84.2\% and 89.5\%, respectively. We used their predicted genes together with publicly available data from other Ericales' genomes and transcriptomes to assemble a phylogenomic data set for the inference of a species tree. However, groups of orthologs showed a marked absence of species represented by a transcriptome. We discuss possible reasons and caution against combining predicted genes from genome- and transriptome-based assemblies.}, language = {en} } @article{BrunelloAndermannMarcetal.2020, author = {Brunello, Camilla Francesca and Andermann, Christoff and Marc, Odin and Schneider, Katharina A. and Comiti, Francesco and Achleitner, Stefan and Hovius, Niels}, title = {Annually resolved monsoon onset and withdrawal dates across the Himalayas derived from local precipitation statistics}, series = {Geophysical research letters}, volume = {47}, journal = {Geophysical research letters}, number = {23}, publisher = {American Geophysical Union}, address = {Washington}, issn = {0094-8276}, doi = {10.1029/2020GL088420}, pages = {12}, year = {2020}, abstract = {A local and flexible definition of the monsoon season based on hydrological evidence is important for the understanding and management of Himalayan water resources. Here, we present an objective statistical method to retrieve seasonal hydrometeorological transitions. Applied to daily rainfall data (1951-2015), this method shows an average longitudinal delay of similar to 15 days, with later monsoon onset and earlier withdrawal in the western Himalaya, consistent with the continental progression of wet air masses. This delay leads to seasons of different length along the Himalaya and biased precipitation amounts when using uniform calendric monsoon boundaries. In the Central Himalaya annual precipitation has increased, due primarily to an increase of premonsoon precipitation. These findings highlight issues associated with a static definition of monsoon boundaries and call for a deeper understanding of nonmonsoonal precipitation over the Himalayan water tower.
Plain Language Summary Precipitation in the Himalayas determines water availability for the Indian foreland with large socioeconomic implications. Despite its importance, spatial and temporal patterns of precipitation are poorly understood. Here, we estimate the long-term average and trends of seasonal precipitation at the scale of individual catchments draining the Himalayas. We apply a statistical method to detect the timing of hydrometeorological seasons from local precipitation measurements, focusing on monsoon onset and withdrawal. We identify longitudinal and latitudinal delays, resulting in seasons of different length along and across the Himalayas. These spatial patterns and the annual variability of the monsoon boundaries mean that oft-used, fixed calendric dates, for example, 1 June to 30 September, may be inadequate for retrieving monsoon rainfall totals. Moreover, we find that, despite its prominent contribution to annual rainfall totals, the Indian summer monsoon cannot explain the increase of the annual precipitation over the Central Himalayas. Instead, this appears to be mostly driven by changes in premonsoon and winter rainfall. So far, little attention has been paid to premonsoon precipitation, but governed by evaporative processes and surface water availability, it may be enhanced by irrigation and changed land use in the Gangetic foreland.}, language = {en} } @article{WangCherstvyLiuetal.2020, author = {Wang, Wei and Cherstvy, Andrey G. and Liu, Xianbin and Metzler, Ralf}, title = {Anomalous diffusion and nonergodicity for heterogeneous diffusion processes with fractional Gaussian noise}, series = {Physical review : E, Statistical, nonlinear and soft matter physics}, volume = {102}, journal = {Physical review : E, Statistical, nonlinear and soft matter physics}, number = {1}, publisher = {American Physical Society}, address = {College Park}, issn = {2470-0045}, doi = {10.1103/PhysRevE.102.012146}, pages = {012146-1 -- 012146-16}, year = {2020}, abstract = {Heterogeneous diffusion processes (HDPs) feature a space-dependent diffusivity of the form D(x) = D-0|x|(alpha). Such processes yield anomalous diffusion and weak ergodicity breaking, the asymptotic disparity between ensemble and time averaged observables, such as the mean-squared displacement. Fractional Brownian motion (FBM) with its long-range correlated yet Gaussian increments gives rise to anomalous and ergodic diffusion. Here, we study a combined model of HDPs and FBM to describe the particle dynamics in complex systems with position-dependent diffusivity driven by fractional Gaussian noise. This type of motion is, inter alia, relevant for tracer-particle diffusion in biological cells or heterogeneous complex fluids. We show that the long-time scaling behavior predicted theoretically and by simulations for the ensemble-and time-averaged mean-squared displacements couple the scaling exponents alpha of HDPs and the Hurst exponent H of FBM in a characteristic way. Our analysis of the simulated data in terms of the rescaled variable y similar to |x|(1/(2/(2-alpha)))/t(H) coupling particle position x and time t yields a simple, Gaussian probability density function (PDF), PHDP-FBM(y) = e(-y2)/root pi. Its universal shape agrees well with theoretical predictions for both uni- and bimodal PDF distributions.}, language = {en} } @article{Bezzenberger2020, author = {Bezzenberger, Tilman}, title = {Anschauungsf{\"a}lle zur Unm{\"o}glichkeit der Leistung im gegenseitigen Vertrag}, series = {Jura : juristische Ausbildung}, volume = {42}, journal = {Jura : juristische Ausbildung}, number = {4}, publisher = {De Gruyter}, address = {Berlin}, issn = {0170-1452}, doi = {10.1515/jura-2019-2350}, pages = {378 -- 383}, year = {2020}, abstract = {Die folgenden Fallstudien wollen Standardwissen zu klassischen Themen des allgemeinen Schuldrechts in Erinnerung rufen und vor allem die Systematik der Falll{\"o}sung deutlich machen. Man darf sich nicht dazu verleiten lassen, alles auf einmal l{\"o}sen zu wollen, sondern muss auf die einzelnen Anspr{\"u}che blicken und sich fragen: (1) Was wird aus dem prim{\"a}ren Erf{\"u}llungsanspruch auf die gest{\"o}rte Leistung? (2) Gibt es Schadensersatzanspr{\"u}che, die als Sekund{\"a}ranspr{\"u}che an die Stelle des Prim{\"a}ranspruchs oder neben ihn treten? Und schließlich (3): Was ist mit dem Anspruch auf die Gegenleistung? Vom Schwierigkeitsgrad her ist das Folgende ungef{\"a}hr im Bereich einer gehobenen Zwischenpr{\"u}fungsklausur anzusiedeln.}, language = {de} } @article{LinkeWoesleHarder2020, author = {Linke, Christian and W{\"o}sle, Markus and Harder, Anja}, title = {Anti-cancer agent 3-bromopyruvate reduces growth of MPNST and inhibits metabolic pathways in a representative in-vitro model}, series = {BMC cancer}, volume = {20}, journal = {BMC cancer}, number = {1}, publisher = {BioMed Central}, address = {London}, issn = {1471-2407}, doi = {10.1186/s12885-020-07397-w}, pages = {11}, year = {2020}, abstract = {Background Anticancer compound 3-bromopyruvate (3-BrPA) suppresses cancer cell growth via targeting glycolytic and mitochondrial metabolism. The malignant peripheral nerve sheath tumor (MPNST), a very aggressive, therapy resistant, and Neurofibromatosis type 1 associated neoplasia, shows a high metabolic activity and affected patients may therefore benefit from 3-BrPA treatment. To elucidate the specific mode of action, we used a controlled cell model overexpressing proteasome activator (PA) 28, subsequently leading to p53 inactivation and oncogenic transformation and therefore reproducing an important pathway in MPNST and overall tumor pathogenesis. Methods Viability of MPNST cell lines S462, NSF1, and T265 in response to increasing doses (0-120 mu M) of 3-BrPA was analyzed by CellTiter-Blue (R) assay. Additionally, we investigated viability, reactive oxygen species (ROS) production (dihydroethidium assay), nicotinamide adenine dinucleotide dehydrogenase activity (NADH-TR assay) and lactate production (lactate assay) in mouse B8 fibroblasts overexpressing PA28 in response to 3-BrPA application. For all experiments normal and nutrient deficient conditions were tested. MPNST cell lines were furthermore characterized immunohistochemically for Ki67, p53, bcl2, bcl6, cyclin D1, and p21. Results MPNST significantly responded dose dependent to 3-BrPA application, whereby S462 cells were most responsive. Human control cells showed a reduced sensitivity. In PA28 overexpressing cancer cell model 3-BrPA application harmed mitochondrial NADH dehydrogenase activity mildly and significantly failed to inhibit lactate production. PA28 overexpression was associated with a functional glycolysis as well as a partial resistance to stress provoked by nutrient deprivation. 3-BrPA treatment was not associated with an increase of ROS. Starvation sensitized MPNST to treatment. Conclusions Aggressive MPNST cells are sensitive to 3-BrPA therapy in-vitro with and without starvation. In a PA28 overexpression cancer cell model leading to p53 inactivation, thereby reflecting a key molecular feature in human NF1 associated MPNST, known functions of 3-BrPA to block mitochondrial activity and glycolysis were reproduced, however oncogenic cells displayed a partial resistance. To conclude, 3-BrPA was sufficient to reduce NF1 associated MPNST viability potentially due inhibition of glycolysis which should lead to the initiation of further studies and promises a potential benefit for NF1 patients.}, language = {en} } @article{Holl2020, author = {Holl, Bernhard}, title = {Antij{\"u}dische Polemik unter falscher Flagge}, series = {Zeitschrift f{\"u}r Religions- und Geistesgeschichte}, volume = {72}, journal = {Zeitschrift f{\"u}r Religions- und Geistesgeschichte}, number = {4}, publisher = {Brill}, address = {Leiden}, issn = {0044-3441}, doi = {10.1163/15700739-07204004}, pages = {412 -- 424}, year = {2020}, abstract = {For the longest time historians have treated the infamous Libelo de Sevilla (1480) as an authentic document of the heresy of "Judaizing" allegedly wide spread among the so-called marrano or converso population. However, a closer look however reveals that the pamphlet is much more likely to be the fabrication of Old Christian agitators aiming to discredit both converts from Judaism and their allies.}, language = {de} } @article{ChepkiruiOchiengSarkaretal.2020, author = {Chepkirui, Carolyne and Ochieng, Purity J. and Sarkar, Biswajyoti and Hussain, Aabid and Pal, Chiranjib and Yang, Li Jun and Coghi, Paolo and Akala, Hoseah M. and Derese, Solomon and Ndakala, Albert and Heydenreich, Matthias and Wong, Vincent K. W. and Erdelyi, Mate and Yenesew, Abiy}, title = {Antiplasmodial and antileishmanial flavonoids from Mundulea sericea}, series = {Fitoterapia}, volume = {149}, journal = {Fitoterapia}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0367-326X}, doi = {10.1016/j.fitote.2020.104796}, pages = {6}, year = {2020}, abstract = {Five known compounds (1-5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6-8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC50 of 2.0 mu M against chloroquine-resistant W2, and 6.6 mu M against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC50 values of 9.0 and 5.0 mu M, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 mu M) and HePG2 (IC50 10.8 mu M) human cell lines. All the other compounds showed low cytotoxicity (IC50 > 30 mu M) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2)}, language = {en} } @article{AscheArnold2020, author = {Asche, Matthias and Arnold, Matthieu}, title = {Anton Schindling (1947-2020)}, series = {Francia : Forschungen zur westeurop{\"a}ischen Geschichte}, journal = {Francia : Forschungen zur westeurop{\"a}ischen Geschichte}, number = {47}, publisher = {Thorbecke}, address = {Ostfildern}, isbn = {978-3-7995-8147-9}, doi = {10.11588/fr.2020.0.75750}, pages = {501 -- 503}, year = {2020}, language = {de} }