@article{PaulyHelleMiramontetal.2018, author = {Pauly, Maren and Helle, Gerhard and Miramont, Cecile and Buentgen, Ulf and Treydte, Kerstin and Reinig, Frederick and Guibal, Frederic and Sivan, Olivier and Heinrich, Ingo and Riedel, Frank and Kromer, Bernd and Balanzategui, Daniel and Wacker, Lukas and Sookdeo, Adam and Brauer, Achim}, title = {Subfossil trees suggest enhanced Mediterranean hydroclimate variability at the onset of the Younger Dryas}, series = {Scientific reports}, volume = {8}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-018-32251-2}, pages = {8}, year = {2018}, abstract = {Nearly 13,000 years ago, the warming trend into the Holocene was sharply interrupted by a reversal to near glacial conditions. Climatic causes and ecological consequences of the Younger Dryas (YD) have been extensively studied, however proxy archives from the Mediterranean basin capturing this period are scarce and do not provide annual resolution. Here, we report a hydroclimatic reconstruction from stable isotopes (delta O-18, delta C-13) in subfossil pines from southern France. Growing before and during the transition period into the YD (12 900-12 600 cal BP), the trees provide an annually resolved, continuous sequence of atmospheric change. Isotopic signature of tree sourcewater (delta O-18(sw)) and estimates of relative air humidity were reconstructed as a proxy for variations in air mass origin and precipitation regime. We find a distinct increase in inter-annual variability of sourcewater isotopes (delta O-18(sw)), with three major downturn phases of increasing magnitude beginning at 12 740 cal BP. The observed variation most likely results from an amplified intensity of North Atlantic (low delta O-18(sw)) versus Mediterranean (high delta O-18(sw)) precipitation. This marked pattern of climate variability is not seen in records from higher latitudes and is likely a consequence of atmospheric circulation oscillations at the margin of the southward moving polar front.}, language = {en} } @article{HuckWohlwendCoimbraetal.2017, author = {Huck, Stefan and Wohlwend, Stephan and Coimbra, Rute and Christ, Nicolas and Weissert, Helmut}, title = {Disentangling shallow-water bulk carbonate carbon isotope archives with evidence for multi-stage diagenesis}, series = {The depositional record}, volume = {3}, journal = {The depositional record}, publisher = {Wiley}, address = {Hoboken}, issn = {2055-4877}, doi = {10.1002/dep2.35}, pages = {233 -- 257}, year = {2017}, abstract = {Disentangling shallow-water bulk carbonate carbon isotope archives into primary and diagenetic components is a notoriously difficult task and even diagenetically screened records often provide chemostratigraphic patterns that significantly differ from global signals. This is mainly caused by the polygenetic nature of shallow-water carbonate substrates, local carbon cycle processes causing considerable neritic-pelagic isotope gradients and the presence of hiatal surfaces resulting in extremely low carbonate preservation rates. Provided here is an in-depth petrographic and geochemical evaluation of different carbonate phases of a mid-Cretaceous (Barremian-Aptian) shallow-water limestone succession (Jabal Madar section) deposited on the tropical Arabian carbonate platform in Oman. The superposition of stable isotope signatures of identified carbonate phases causes a complex and often noisy bulk carbon isotope pattern. Blocky sparite cements filling intergranular pores and bioclastic voids evidence intermediate to (arguably) deep burial diagenetic conditions during their formation, owing to different timing or differential faulting promoting the circulation of fluids from variable sources. In contrast, sparite cements filling sub-vertical veins reveal a rock-buffered diagenetic fluid composition with an intriguing moderate enrichment in 13C, probably due to fractionation during pressure release in the context of the Miocene exhumation of the carbonate platform under study. The presence of abundant, replacive dedolomite in mud-supported limestone samples forced negative carbon and oxygen isotope changes that are either associated with the thermal breakdown of organic matter in the deep burial realm or the expulsion of buried meteoric water in the intermediate burial realm. Notwithstanding the documented stratigraphically variable and often facies-related impact of different diagenetic fluids on the bulk-rock stable isotope signature, the identification of diagenetic end-members defined δ13C and δ18O threshold values that allowed the most reliable 'primary' bulk carbon isotope signatures to be extracted. Most importantly, this approach exemplifies how to place regional shallow-water stable isotope patterns with evidence for a complex multi-stage diagenetic history into a supraregional or even global context.}, language = {en} } @article{WendlerEnenkel2019, author = {Wendler, Petra and Enenkel, Cordula}, title = {Nuclear Transport of Yeast Proteasomes}, series = {Frontiers in molecular biosciences}, volume = {6}, journal = {Frontiers in molecular biosciences}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2296-889X}, doi = {10.3389/fmolb.2019.00034}, pages = {12}, year = {2019}, abstract = {Proteasomes are key proteases in regulating protein homeostasis. Their holo-enzymes are composed of 40 different subunits which are arranged in a proteolytic core (CP) flanked by one to two regulatory particles (RP). Proteasomal proteolysis is essential for the degradation of proteins which control time-sensitive processes like cell cycle progression and stress response. In dividing yeast and human cells, proteasomes are primarily nuclear suggesting that proteasomal proteolysis is mainly required in the nucleus during cell proliferation. In yeast, which have a closed mitosis, proteasomes are imported into the nucleus as immature precursors via the classical import pathway. During quiescence, the reversible absence of proliferation induced by nutrient depletion or growth factor deprivation, proteasomes move from the nucleus into the cytoplasm. In the cytoplasm of quiescent yeast, proteasomes are dissociated into CP and RP and stored in membrane-less cytoplasmic foci, named proteasome storage granules (PSGs). With the resumption of growth, PSGs clear and mature proteasomes are transported into the nucleus by Blm10, a conserved 240 kDa protein and proteasome-intrinsic import receptor. How proteasomes are exported from the nucleus into the cytoplasm is unknown.}, language = {en} } @article{MoeserLorenzSajfutdinowetal.2018, author = {M{\"o}ser, Christin and Lorenz, Jessica S. and Sajfutdinow, Martin and Smith, David M.}, title = {Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence}, series = {International journal of molecular sciences}, volume = {19}, journal = {International journal of molecular sciences}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms19113482}, pages = {19}, year = {2018}, abstract = {DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized binding and/or signaling interactions. Here, the efficacy of SWL, an ephrin-mimicking peptide that binds specifically to EphrinA2 (EphA2) receptors, increased by presenting up to three of these peptides on small DNA nanostructures in an oligovalent manner. Ephrin signaling pathways play crucial roles in tumor development and progression. Moreover, Eph receptors are potential targets in cancer diagnosis and treatment. Here, the quantitative impact of SWL valency on binding, phosphorylation (key player for activation) and phenotype regulation in EphA2-expressing prostate cancer cells was demonstrated. EphA2 phosphorylation was significantly increased by DNA trimers carrying three SWL peptides compared to monovalent SWL. In comparison to one of EphA2's natural ligands ephrin-A1, which is known to bind promiscuously to multiple receptors, pinpointed targeting of EphA2 by oligovalent DNA-SWL constructs showed enhanced cell retraction. Overall, we show that DNA scaffolds can increase the potency of weak signaling peptides through oligovalent presentation and serve as potential tools for examination of complex signaling pathways.}, language = {en} } @article{SchwanholdIobbiNivolLehmannetal.2018, author = {Schwanhold, Nadine and Iobbi-Nivol, Chantal and Lehmann, Angelika and Leimk{\"u}hler, Silke}, title = {Same but different}, series = {PLoS one}, volume = {13}, journal = {PLoS one}, number = {11}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0201935}, pages = {24}, year = {2018}, abstract = {The maturation of bacterial molybdoenzymes is a complex process leading to the insertion of the bulky bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor into the apoenzyme. Most molybdoenzymes were shown to contain a specific chaperone for the insertion of the bis-MGD cofactor. Formate dehydrogenases (FDH) together with their molecular chaperone partner seem to display an exception to this specificity rule, since the chaperone FdhD has been proven to be involved in the maturation of all three FDH enzymes present in Escherichia colt. Multiple roles have been suggested for FdhD-like chaperones in the past, including the involvement in a sulfur transfer reaction from the L-cysteine desulfurase IscS to bis-MGD by the action of two cysteine residues present in a conserved CXXC motif of the chaperones. However, in this study we show by phylogenetic analyses that the CXXC motif is not conserved among FdhD-like chaperones. We compared in detail the FdhD-like homologues from Rhodobacter capsulatus and E. colt and show that their roles in the maturation of FDH enzymes from different subgroups can be exchanged. We reveal that bis-MGDbinding is a common characteristic of FdhD-like proteins and that the cofactor is bound with a sulfido-ligand at the molybdenum atom to the chaperone. Generally, we reveal that the cysteine residues in the motif CXXC of the chaperone are not essential for the production of active FDH enzymes.}, language = {en} } @article{SiddiquiMautePedatellaetal.2018, author = {Siddiqui, Tarique Adnan and Maute, Astrid and Pedatella, Nick and Yamazaki, Yosuke and L{\"u}hr, Hermann and Stolle, Claudia}, title = {On the variability of the semidiurnal solar and lunar tides of the equatorial electrojet during sudden stratospheric warmings}, series = {Annales geophysicae}, volume = {36}, journal = {Annales geophysicae}, number = {6}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {0992-7689}, doi = {10.5194/angeo-36-1545-2018}, pages = {1545 -- 1562}, year = {2018}, abstract = {The variabilities of the semidiurnal solar and lunar tides of the equatorial electrojet (EEJ) are investigated during the 2003, 2006, 2009 and 2013 major sudden stratospheric warming (SSW) events in this study. For this purpose, ground-magnetometer recordings at the equatorial observatories in Huancayo and Fuquene are utilized. Results show a major enhancement in the amplitude of the EEJ semidiurnal lunar tide in each of the four warming events. The EEJ semidiurnal solar tidal amplitude shows an amplification prior to the onset of warmings, a reduction during the deceleration of the zonal mean zonal wind at 60 degrees N and 10 hPa, and a second enhancement a few days after the peak reversal of the zonal mean zonal wind during all four SSWs. Results also reveal that the amplitude of the EEJ semidiurnal lunar tide becomes comparable or even greater than the amplitude of the EEJ semidiurnal solar tide during all these warming events. The present study also compares the EEJ semidiurnal solar and lunar tidal changes with the variability of the migrating semidiurnal solar (SW2) and lunar (M2) tides in neutral temperature and zonal wind obtained from numerical simulations at E-region heights. A better agreement between the enhancements of the EEJ semidiurnal lunar tide and the M2 tide is found in comparison with the enhancements of the EEJ semidiurnal solar tide and the SW2 tide in both the neutral temperature and zonal wind at the E-region altitudes.}, language = {en} } @article{Warditz2018, author = {Warditz, Vladislava Maria}, title = {Русское имянаречение Нового времени}, series = {Voprosy onomastiki}, volume = {16}, journal = {Voprosy onomastiki}, number = {2}, publisher = {Uralʹskij federalʹnyj universitet}, address = {Ekaterinenburg}, issn = {1994-2400}, doi = {10.15826/vopr_onom.2019.16.2.018}, pages = {129 -- 144}, year = {2018}, abstract = {The author stems from the premise that modern anthroponymy effectively incorporates data from related fields of knowledge, primarily those of cultural and political history, thus getting enlarged through interdisciplinary research. An integrated approach allows one to deduce the extra-linguistic mechanisms which lay behind anthroponymic changes. In the same vein, the present paper focuses on the dynamics within the Russian anthroponymic paradigm caused by the changing vectors of political, ideological, cultural, and religious identity in the historical perspective of the New Time (1700-1920s). The study aims to establish the connection between specific trends in naming and the precedent names, events, and texts of political, cultural, and religious life. The mechanisms of anthroponymic shifts are illustrated by the cases of individual names becoming socially significant in a particular historical context. Using interdisciplinary methods of cultural anthropology, the study builds on textual sources, primarily name indexes to the collections of works by outstanding cultural figures and scholars, and biographical dictionaries. Some examples of pragmatic naming strategies in works of art (literature, opera, cinema) are also provided. Preliminary findings reveal some major trends in the Russian anthroponymic system of the New Age such as Europeization vs. Russification, modernization vs. archaization, as well as their synthesis. These tendencies remain key up to the present day and can be traced and characteristically defined within a set (or corpus) of names relating to the particular epoch, in terms of their frequency and the parameters of the sociolinguistic distribution. The diachronic perspective of the study also supports the sociolinguistic observation that the newly introduced names, which are currently in use, have a pronounced social resonance, which is getting neutralized as their frequency increases. Further development of the topic implies, among other things, statistical verification of preliminary findings.}, language = {ru} } @article{RosenbaumRaatzWeithoffetal.2019, author = {Rosenbaum, Benjamin and Raatz, Michael and Weithoff, Guntram and Fussmann, Gregor F. and Gaedke, Ursula}, title = {Estimating parameters from multiple time series of population dynamics using bayesian inference}, series = {Frontiers in ecology and evolution}, volume = {6}, journal = {Frontiers in ecology and evolution}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2296-701X}, doi = {10.3389/fevo.2018.00234}, pages = {14}, year = {2019}, abstract = {Empirical time series of interacting entities, e.g., species abundances, are highly useful to study ecological mechanisms. Mathematical models are valuable tools to further elucidate those mechanisms and underlying processes. However, obtaining an agreement between model predictions and experimental observations remains a demanding task. As models always abstract from reality one parameter often summarizes several properties. Parameter measurements are performed in additional experiments independent of the ones delivering the time series. Transferring these parameter values to different settings may result in incorrect parametrizations. On top of that, the properties of organisms and thus the respective parameter values may vary considerably. These issues limit the use of a priori model parametrizations. In this study, we present a method suited for a direct estimation of model parameters and their variability from experimental time series data. We combine numerical simulations of a continuous-time dynamical population model with Bayesian inference, using a hierarchical framework that allows for variability of individual parameters. The method is applied to a comprehensive set of time series from a laboratory predator-prey system that features both steady states and cyclic population dynamics. Our model predictions are able to reproduce both steady states and cyclic dynamics of the data. Additionally to the direct estimates of the parameter values, the Bayesian approach also provides their uncertainties. We found that fitting cyclic population dynamics, which contain more information on the process rates than steady states, yields more precise parameter estimates. We detected significant variability among parameters of different time series and identified the variation in the maximum growth rate of the prey as a source for the transition from steady states to cyclic dynamics. By lending more flexibility to the model, our approach facilitates parametrizations and shows more easily which patterns in time series can be explained also by simple models. Applying Bayesian inference and dynamical population models in conjunction may help to quantify the profound variability in organismal properties in nature.}, language = {en} } @article{KruseKummerShivasetal.2018, author = {Kruse, Julia and Kummer, Volker and Shivas, Roger G. and Thines, Marco}, title = {The first smut fungus, Thecaphora anthemidis sp nov (Glomosporiaceae), described from Anthemis (Asteraceae)}, series = {MycoKeys}, journal = {MycoKeys}, number = {41}, publisher = {Pensoft Publ.}, address = {Sofia}, issn = {1314-4057}, doi = {10.3897/mycokeys.41.28454}, pages = {39 -- 50}, year = {2018}, abstract = {There are 63 known species of Thecaphora (Glomosporiaceae, Ustilaginomycotina), a third of which occur on Asteraceae. These smut fungi produce yellowish-brown to reddish-brown masses of spore balls in specific, mostly regenerative, plant organs. A species of Thecaphora was collected in the flower heads of Anthemis chia (Anthemideae, Asteraceae) on Rhodes Island, Greece, in 2015 and 2017, which represents the first smut record of a smut fungus on a host plant species in this tribe. Based on its distinctive morphology, host species and genetic divergence, this species is described as Thecaphora anthemidis sp. nov. Molecular barcodes of the ITS region are provided for this and several other species of Thecaphora. A phylogenetic and morphological comparison to closely related species showed that Th. anthemidis differed from other species of Thecaphora. Thecaphora anthemidis produced loose spore balls in the flower heads and peduncles of Anthemis chia unlike other flower-infecting species.}, language = {en} } @misc{ManzoniCapekPoradaetal.2018, author = {Manzoni, Stefano and Capek, Petr and Porada, Philipp and Thurner, Martin and Winterdahl, Mattias and Beer, Christian and Bruchert, Volker and Frouz, Jan and Herrmann, Anke M. and Lindahl, Bjorn D. and Lyon, Steve W. and Šantrůčkov{\´a}, Hana and Vico, Giulia and Way, Danielle}, title = {Reviews and syntheses}, series = {Biogeosciences}, volume = {15}, journal = {Biogeosciences}, number = {19}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {1726-4170}, doi = {10.5194/bg-15-5929-2018}, pages = {5929 -- 5949}, year = {2018}, abstract = {The cycling of carbon (C) between the Earth surface and the atmosphere is controlled by biological and abiotic processes that regulate C storage in biogeochemical compartments and release to the atmosphere. This partitioning is quantified using various forms of C-use efficiency (CUE) - the ratio of C remaining in a system to C entering that system. Biological CUE is the fraction of C taken up allocated to biosynthesis. In soils and sediments, C storage depends also on abiotic processes, so the term C-storage efficiency (CSE) can be used. Here we first review and reconcile CUE and CSE definitions proposed for autotrophic and heterotrophic organisms and communities, food webs, whole ecosystems and watersheds, and soils and sediments using a common mathematical framework. Second, we identify general CUE patterns; for example, the actual CUE increases with improving growth conditions, and apparent CUE decreases with increasing turnover. We then synthesize > 5000CUE estimates showing that CUE decreases with increasing biological and ecological organization - from uni-cellular to multicellular organisms and from individuals to ecosystems. We conclude that CUE is an emergent property of coupled biological-abiotic systems, and it should be regarded as a flexible and scale-dependent index of the capacity of a given system to effectively retain C.}, language = {en} } @misc{RisbeyLewandowskyCowtanetal.2018, author = {Risbey, James S. and Lewandowsky, Stephan and Cowtan, Kevin and Oreskes, Naomi and Rahmstorf, Stefan and Jokim{\"a}ki, Ari and Foster, Grant}, title = {A fluctuation in surface temperature in historical context}, series = {Environmental research letters}, volume = {13}, journal = {Environmental research letters}, number = {12}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {1748-9326}, doi = {10.1088/1748-9326/aaf342}, pages = {23}, year = {2018}, abstract = {This work reviews the literature on an alleged global warming 'pause' in global mean surface temperature (GMST) to determine how it has been defined, what time intervals are used to characterise it, what data are used to measure it, and what methods used to assess it. We test for 'pauses', both in the normally understood meaning of the term to mean no warming trend, as well as for a 'pause' defined as a substantially slower trend in GMST. The tests are carried out with the historical versions of GMST that existed for each pause-interval tested, and with current versions of each of the GMST datasets. The tests are conducted following the common (but questionable) practice of breaking the linear fit at the start of the trend interval ('broken' trends), and also with trends that are continuous with the data bordering the trend interval. We also compare results when appropriate allowance is made for the selection bias problem. The results show that there is little or no statistical evidence for a lack of trend or slower trend in GMST using either the historical data or the current data. The perception that there was a 'pause' in GMST was bolstered by earlier biases in the data in combination with incomplete statistical testing.}, language = {en} } @article{PerkinsPernaAdrianetal.2019, author = {Perkins, Daniel M. and Perna, Andrea and Adrian, Rita and Cermeno, Pedro and Gaedke, Ursula and Huete-Ortega, Maria and White, Ethan P. and Yvon-Durocher, Gabriel}, title = {Energetic equivalence underpins the size structure of tree and phytoplankton communities}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-018-08039-3}, pages = {8}, year = {2019}, abstract = {The size structure of autotroph communities - the relative abundance of small vs. large individuals - shapes the functioning of ecosystems. Whether common mechanisms underpin the size structure of unicellular and multicellular autotrophs is, however, unknown. Using a global data compilation, we show that individual body masses in tree and phytoplankton communities follow power-law distributions and that the average exponents of these individual size distributions (ISD) differ. Phytoplankton communities are characterized by an average ISD exponent consistent with three-quarter-power scaling of metabolism with body mass and equivalence in energy use among mass classes. Tree communities deviate from this pattern in a manner consistent with equivalence in energy use among diameter size classes. Our findings suggest that whilst universal metabolic constraints ultimately underlie the emergent size structure of autotroph communities, divergent aspects of body size (volumetric vs. linear dimensions) shape the ecological outcome of metabolic scaling in forest vs. pelagic ecosystems.}, language = {en} } @article{WickertSchildgen2019, author = {Wickert, Andrew D. and Schildgen, Taylor F.}, title = {Long-profile evolution of transport-limited gravel-bed rivers}, series = {Earth surface dynamics}, volume = {7}, journal = {Earth surface dynamics}, number = {1}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {2196-6311}, doi = {10.5194/esurf-7-17-2019}, pages = {17 -- 43}, year = {2019}, abstract = {Alluvial and transport-limited bedrock rivers constitute the majority of fluvial systems on Earth. Their long profiles hold clues to their present state and past evolution. We currently possess first-principles-based governing equations for flow, sediment transport, and channel morphodynamics in these systems, which we lack for detachment-limited bedrock rivers. Here we formally couple these equations for transport-limited gravel-bed river long-profile evolution. The result is a new predictive relationship whose functional form and parameters are grounded in theory and defined through experimental data. From this, we produce a power-law analytical solution and a finite-difference numerical solution to long-profile evolution. Steady-state channel concavity and steepness are diagnostic of external drivers: concavity decreases with increasing uplift rate, and steepness increases with an increasing sediment-to-water supply ratio. Constraining free parameters explains common observations of river form: to match observed channel concavities, gravel-sized sediments must weather and fine - typically rapidly - and valleys typically should widen gradually. To match the empirical square-root width-discharge scaling in equilibrium-width gravel-bed rivers, downstream fining must occur. The ability to assign a cause to such observations is the direct result of a deductive approach to developing equations for landscape evolution.}, language = {en} } @article{UberVandervaereZinetal.2018, author = {Uber, Magdalena and Vandervaere, Jean-Pierre and Zin, Isabella and Braud, Isabelle and Heistermann, Maik and Legout, Cedric and Molinie, Gilles and Nord, Guillaume}, title = {How does initial soil moisture influence the hydrological response? A case study from southern France}, series = {Hydrology and earth system sciences : HESS}, volume = {22}, journal = {Hydrology and earth system sciences : HESS}, number = {12}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {1027-5606}, doi = {10.5194/hess-22-6127-2018}, pages = {6127 -- 6146}, year = {2018}, abstract = {The phi(ev) is calculated from high-resolution discharge and precipitation data for several rain events with a cumulative precipitation P-cum ranging from less than 5mm to more than 80 mm. Because of the high uncertainty of phi(ev) associated with the hydrograph separation method, phi(ev) is calculated with several methods, including graphical methods, digital filters and a tracer-based method. The results indicate that the hydrological response depends on (theta) over bar (ini): during dry conditions phi(ev) is consistently below 0.1, even for events with high and intense precipitation. Above a threshold of (theta) over bar (ini) = 34 vol \% phi(ev) can reach values up to 0.99 but there is a high scatter. Some variability can be explained with a weak correlation of phi(ev) with P-cum and rain intensity, but a considerable part of the variability remains unexplained. It is concluded that threshold-based methods can be helpful to prevent overestimation of the hydrological response during dry catchment conditions. The impact of soil moisture on the hydrological response during wet catchment conditions, however, is still insufficiently understood and cannot be generalized based on the present results.}, language = {en} } @article{LonsdorfKlingelhoeferJensAndreattaetal.2019, author = {Lonsdorf, Tina B. and Klingelh{\"o}fer-Jens, Maren and Andreatta, Marta and Beckers, Tom and Chalkia, Anastasia and Gerlicher, Anna and Jentsch, Valerie L. and Drexler, Shira Meir and Mertens, Gaetan and Richter, Jan and Sjouwerman, Rachel and Wendt, Julia and Merz, Christian J.}, title = {Navigating the garden of forking paths for data exclusions in fear conditioning research}, series = {eLife}, volume = {8}, journal = {eLife}, publisher = {eLife Sciences Publications}, address = {Cambridge}, issn = {2050-084X}, doi = {10.7554/eLife.52465}, pages = {36}, year = {2019}, abstract = {In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradigms with a learning element. We illustrate this empirically through case examples from human fear conditioning research, in which the exclusion of 'non-learners' and 'non-responders' is common - despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria identified in a systematic literature search and highlight the potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. On the basis of these studies, we propose a consensus on evidence-based rather than idiosyncratic criteria, including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.}, language = {en} } @article{LonsdorfKlingelhoeferJensAndreattaetal.2019, author = {Lonsdorf, Tina B. and Klingelh{\"o}fer-Jens, Maren and Andreatta, Marta and Beckers, Tom and Chalkia, Anastasia and Gerlicher, Anna Maria Veronika and Jentsch, Valerie L. and Drexler, Shira Meir and Mertens, Gaetan and Richter, Jan and Sjouwerman, Rachel and Wendt, Julia and Merz, Christian J.}, title = {Navigating the garden of forking paths for data exclusions in fear conditioning research}, series = {eLife}, volume = {8}, journal = {eLife}, publisher = {eLife Sciences Publications}, address = {Cambridge}, issn = {2050-084X}, doi = {10.7554/eLife.52465}, pages = {36}, year = {2019}, language = {en} } @article{GuentherKlaussToroNahuelpanetal.2019, author = {G{\"u}nther, Erika and Klauß, Andr{\´e} and Toro-Nahuelpan, Mauricio and Sch{\"u}ler, Dirk and Hille, Carsten and Faivre, Damien}, title = {The in vivo mechanics of the magnetotactic backbone as revealed by correlative FLIM-FRET and STED microscopy}, series = {Scientific reports}, volume = {9}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-019-55804-5}, pages = {9}, year = {2019}, abstract = {Protein interaction and protein imaging strongly benefit from the advancements in time-resolved and superresolution fluorescence microscopic techniques. However, the techniques were typically applied separately and ex vivo because of technical challenges and the absence of suitable fluorescent protein pairs. Here, we show correlative in vivo fluorescence lifetime imaging microscopy Forster resonance energy transfer (FLIM-FRET) and stimulated emission depletion (STED) microscopy to unravel protein mechanics and structure in living cells. We use magnetotactic bacteria as a model system where two proteins, MamJ and MamK, are used to assemble magnetic particles called magnetosomes. The filament polymerizes out of MamK and the magnetosomes are connected via the linker MamJ. Our system reveals that bacterial filamentous structures are more fragile than the connection of biomineralized particles to this filament. More importantly, we anticipate the technique to find wide applicability for the study and quantification of biological processes in living cells and at high resolution.}, language = {en} } @article{ThomasCarvalhoHaileetal.2019, author = {Thomas, Jessica E. and Carvalho, Gary R. and Haile, James and Rawlence, Nicolas J. and Martin, Michael D. and Ho, Simon Y. W. and Sigfusson, Arnor P. and Josefsson, Vigfus A. and Frederiksen, Morten and Linnebjerg, Jannie F. and Castruita, Jose A. Samaniego and Niemann, Jonas and Sinding, Mikkel-Holger S. and Sandoval-Velasco, Marcela and Soares, Andre E. R. and Lacy, Robert and Barilaro, Christina and Best, Juila and Brandis, Dirk and Cavallo, Chiara and Elorza, Mikelo and Garrett, Kimball L. and Groot, Maaike and Johansson, Friederike and Lifjeld, Jan T. and Nilson, Goran and Serjeanston, Dale and Sweet, Paul and Fuller, Errol and Hufthammer, Anne Karin and Meldgaard, Morten and Fjeldsa, Jon and Shapiro, Beth and Hofreiter, Michael and Stewart, John R. and Gilbert, M. Thomas P. and Knapp, Michael}, title = {Demographic reconstruction from ancient DNA supports rapid extinction of the great auk}, series = {eLife}, volume = {8}, journal = {eLife}, publisher = {eLife Sciences Publications}, address = {Cambridge}, issn = {2050-084X}, doi = {10.7554/eLife.47509}, pages = {35}, year = {2019}, abstract = {The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species' geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.}, language = {en} } @article{BroekerSinelnikovGustavusetal.2019, author = {Br{\"o}ker, Katharine and Sinelnikov, Evgeny and Gustavus, Dirk and Schumacher, Udo and P{\"o}rtner, Ralf and Hoffmeister, Hans and L{\"u}th, Stefan and Dammermann, Werner}, title = {Mass Production of Highly Active NK Cells for Cancer Immunotherapy in a GMP Conform Perfusion Bioreactor}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {7}, journal = {Frontiers in Bioengineering and Biotechnology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2296-4185}, doi = {10.3389/fbioe.2019.00194}, pages = {17}, year = {2019}, abstract = {NK cells have emerged as promising candidates for cancer immunotherapy, especially due to their ability to fight circulating tumor cells thereby preventing metastases formation. Hence several studies have been performed to generate and expand highly cytotoxic NK cells ex vivo, e.g., by using specific cytokines to upregulate both their proliferation and surface expression of distinct activating receptors. Apart from an enhanced activity, application of NK cells as immunotherapeutic agent further requires sufficient cell numbers and a high purity. All these parameters depend on a variety of different factors including the starting material, additives like cytokines as well as the culture system. Here we analyzed PBMC-derived NK cells of five anonymized healthy donors expanded under specific conditions in an innovative perfusion bioreactor system with respect to their phenotype, IFN gamma production, and cytotoxicity in vitro. Important features of the meander type bioreactors used here are a directed laminar flow of medium and control of relevant process parameters. Cells are cultivated under "steady state" conditions in perfusion mode. Our data demonstrate that expansion of CD3(+) T cell depleted PBMCs in our standardized system generates massive amounts of highly pure (>85\%) and potent anticancer active NK cells. These cells express a variety of important receptors driving NK cell recruitment, adhesion as well as activation. More specifically, they express the chemokine receptors CXCR3, CXCR4, and CCR7, the adhesion molecules L-selectin, LFA-1, and VLA-4, the activating receptors NKp30, NKp44, NKp46, NKG2D, DNAM1, and CD16 as well as the death ligands TRAIL and Fas-L. Moreover, the generated NK cells show a strong IFN gamma expression upon cultivation with K562 tumor cells and demonstrate a high cytotoxicity toward leukemic as well as solid tumor cell lines in vitro. Altogether, these characteristics promise a high clinical potency of thus produced NK cells awaiting further evaluation.}, language = {en} } @article{LoepfeDussZafeiropoulouetal.2019, author = {L{\"o}pfe, Moira and Duss, Anja and Zafeiropoulou, Katerina-Alexandra and Bjoergvinsdottir, Oddny and Eglin, David and Fortunato, Giuseppino and Klasen, J{\"u}rgen and Ferguson, Stephen J. and W{\"u}rtz-Kozak, Karin and Krupkova, Olga}, title = {Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc}, series = {Pharmaceutics}, volume = {11}, journal = {Pharmaceutics}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {1999-4923}, doi = {10.3390/pharmaceutics11090435}, pages = {15}, year = {2019}, abstract = {Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.}, language = {en} }