TY - JOUR A1 - Wendler, Petra A1 - Enenkel, Cordula T1 - Nuclear Transport of Yeast Proteasomes JF - Frontiers in molecular biosciences N2 - 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. KW - proteasome KW - nuclear transport KW - importin KW - karyopherin KW - Blm10 KW - proteasome storage granules Y1 - 2019 U6 - https://doi.org/10.3389/fmolb.2019.00034 SN - 2296-889X VL - 6 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Möser, Christin A1 - Lorenz, Jessica S. A1 - Sajfutdinow, Martin A1 - Smith, David M. T1 - Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence JF - International journal of molecular sciences N2 - 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. KW - DNA nanostructure KW - ephrin KW - EphA2 KW - SWL KW - PC-3 cells KW - multivalence Y1 - 2018 U6 - https://doi.org/10.3390/ijms19113482 SN - 1422-0067 VL - 19 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schwanhold, Nadine A1 - Iobbi-Nivol, Chantal A1 - Lehmann, Angelika A1 - Leimkühler, Silke T1 - Same but different BT - Comparison of two system-specific molecular chaperones for the maturation of formate dehydrogenases JF - PLoS one N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1371/journal.pone.0201935 SN - 1932-6203 VL - 13 IS - 11 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Siddiqui, Tarique Adnan A1 - Maute, Astrid A1 - Pedatella, Nick A1 - Yamazaki, Yosuke A1 - Lühr, Hermann A1 - Stolle, Claudia T1 - On the variability of the semidiurnal solar and lunar tides of the equatorial electrojet during sudden stratospheric warmings JF - Annales geophysicae N2 - 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. Y1 - 2018 U6 - https://doi.org/10.5194/angeo-36-1545-2018 SN - 0992-7689 SN - 1432-0576 VL - 36 IS - 6 SP - 1545 EP - 1562 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Warditz, Vladislava Maria T1 - Русское имянаречение Нового времени BT - социально-культурные и политико� идеологические механизмы антропонимических сдвигов BT - Socio-cultural and political ideological mechanisms of anthroponymic shifts JF - Voprosy onomastiki N2 - 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. T2 - Russian Name-Giving of the New Time KW - Russian name giving KW - causes of anthroponymic shifts KW - Europeization KW - archaization KW - New Time KW - cultural paradigm KW - identity Y1 - 2018 U6 - https://doi.org/10.15826/vopr_onom.2019.16.2.018 SN - 1994-2400 SN - 1994-2451 VL - 16 IS - 2 SP - 129 EP - 144 PB - Uralʹskij federalʹnyj universitet CY - Ekaterinenburg ER - TY - JOUR A1 - Rosenbaum, Benjamin A1 - Raatz, Michael A1 - Weithoff, Guntram A1 - Fussmann, Gregor F. A1 - Gaedke, Ursula T1 - Estimating parameters from multiple time series of population dynamics using bayesian inference JF - Frontiers in ecology and evolution N2 - 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. KW - Bayesian inference KW - chemostat experiments KW - ordinary differential equation KW - parameter estimation KW - population dynamics KW - predator prey KW - time series analysis KW - trait variability Y1 - 2019 U6 - https://doi.org/10.3389/fevo.2018.00234 SN - 2296-701X VL - 6 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Kruse, Julia A1 - Kummer, Volker A1 - Shivas, Roger G. A1 - Thines, Marco T1 - The first smut fungus, Thecaphora anthemidis sp nov (Glomosporiaceae), described from Anthemis (Asteraceae) JF - MycoKeys N2 - 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. KW - Glomosporiaceae KW - host specificity KW - internal transcribed spacer KW - molecular phylogenetics KW - smut fungi Y1 - 2018 U6 - https://doi.org/10.3897/mycokeys.41.28454 SN - 1314-4057 SN - 1314-4049 IS - 41 SP - 39 EP - 50 PB - Pensoft Publ. CY - Sofia ER - TY - JOUR A1 - Perkins, Daniel M. A1 - Perna, Andrea A1 - Adrian, Rita A1 - Cermeno, Pedro A1 - Gaedke, Ursula A1 - Huete-Ortega, Maria A1 - White, Ethan P. A1 - Yvon-Durocher, Gabriel T1 - Energetic equivalence underpins the size structure of tree and phytoplankton communities JF - Nature Communications N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-018-08039-3 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Wickert, Andrew D. A1 - Schildgen, Taylor F. T1 - Long-profile evolution of transport-limited gravel-bed rivers JF - Earth surface dynamics N2 - 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. Y1 - 2019 U6 - https://doi.org/10.5194/esurf-7-17-2019 SN - 2196-6311 SN - 2196-632X VL - 7 IS - 1 SP - 17 EP - 43 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Uber, Magdalena A1 - Vandervaere, Jean-Pierre A1 - Zin, Isabella A1 - Braud, Isabelle A1 - Heistermann, Maik A1 - Legout, Cedric A1 - Molinie, Gilles A1 - Nord, Guillaume T1 - How does initial soil moisture influence the hydrological response? A case study from southern France JF - Hydrology and earth system sciences : HESS N2 - 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. Y1 - 2018 U6 - https://doi.org/10.5194/hess-22-6127-2018 SN - 1027-5606 SN - 1607-7938 VL - 22 IS - 12 SP - 6127 EP - 6146 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Milewski, Robert A1 - Chabrillat, Sabine A1 - Behling, Robert T1 - Analyses of Recent Sediment Surface Dynamic of a Namibian Kalahari Salt Pan Based on Multitemporal Landsat and Hyperspectral Hyperion Data JF - Remote Sensing N2 - This study combines spaceborne multitemporal and hyperspectral data to analyze the spatial distribution of surface evaporite minerals and changes in a semi-arid depositional environment associated with episodic flooding events, the Omongwa salt pan (Kalahari, Namibia). The dynamic of the surface crust is evaluated by a change-detection approach using the Iterative-reweighted Multivariate Alteration Detection (IR-MAD) based on the Landsat archive imagery from 1984 to 2015. The results show that the salt pan is a highly dynamic and heterogeneous landform. A change gradient is observed from very stable pan border to a highly dynamic central pan. On the basis of hyperspectral EO-1 Hyperion images, the current distribution of surface evaporite minerals is characterized using Spectral Mixture Analysis (SMA). Assessment of field and image endmembers revealed that the pan surface can be categorized into three major crust types based on diagnostic absorption features and mineralogical ground truth data. The mineralogical crust types are related to different zones of surface change as well as pan morphology that influences brine flow during the pan inundation and desiccation cycles. These combined information are used to spatially map depositional environments where the more dynamic halite crust concentrates in lower areas although stable gypsum and calcite/sepiolite crusts appear in higher elevated areas. KW - salt pan KW - playa KW - hyperspectral KW - multitemporal KW - change detection KW - evaporite minerals Y1 - 2016 U6 - https://doi.org/10.3390/rs9020170 SN - 2072-4292 VL - 9 IS - 2 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schinköth, Michaela A1 - Brand, Ralf T1 - Automatic associations and the affective valuation of exercise BT - disentangling the type-1 process of the affective–reflective theory of physical inactivity and exercise JF - German Journal of Exercise and Sport Research N2 - The decision to exercise is not only bound to rational considerations but also automatic affective processes. The affective–reflective theory of physical inactivity and exercise (ART) proposes a theoretical framework for explaining how the automatic affective process (type‑1 process) will influence exercise behavior, i.e., through the automatic activation of exercise-related associations and a subsequent affective valuation of exercise. This study aimed to empirically test this assumption of the ART with data from 69 study participants. A single-measurement study, including within-subject experimental variation, was conducted. Automatic associations with exercise were first measured with a single-target implicit association test. The somato-affective core of the participants’ automatic valuation of exercise-related pictures was then assessed via heart rate variability (HRV) analysis, and the affective valence of the valuation was tested with a facial expression (FE; smile and frown) task. Exercise behavior was assessed via self-report. Multiple regression (path) analysis revealed that automatic associations predicted HRV reactivity (β = −0.24, p = .044); the signs of the correlation between automatic associations and the smile FE score was in the expected direction but remained nonsignificant (β = −0.21, p = .078). HRV reactivity predicted self-reported exercise behavior (β = −0.28, p = .013) (the same pattern of results was achieved for the frown FE score). The HRV-related results illustrate the potential role of automatic negative affective reactions to the thought of exercise as a restraining force in exercise motivation. For better empirical distinction between the two ART type‑1 process components, automatic associations and the affective valuation should perhaps be measured separately in the future. The results support the notion that automatic and affective processes should be regarded as essential aspects of the motivation to exercise. KW - Heart rate variability KW - Facial expression KW - Somatic KW - Dual-process KW - Motivation Y1 - 2019 U6 - https://doi.org/10.1007/s12662-020-00664-9 SN - 2509-3150 SN - 2509-3142 VL - 50 IS - 654 SP - 366 EP - 376 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Mardoukhi, Yousof A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Spurious ergodicity breaking in normal and fractional Ornstein–Uhlenbeck process JF - New Journal of Physics N2 - The Ornstein–Uhlenbeck process is a stationary and ergodic Gaussian process, that is fully determined by its covariance function and mean. We show here that the generic definitions of the ensemble- and time-averaged mean squared displacements fail to capture these properties consistently, leading to a spurious ergodicity breaking. We propose to remedy this failure by redefining the mean squared displacements such that they reflect unambiguously the statistical properties of any stochastic process. In particular we study the effect of the initial condition in the Ornstein–Uhlenbeck process and its fractional extension. For the fractional Ornstein–Uhlenbeck process representing typical experimental situations in crowded environments such as living biological cells, we show that the stationarity of the process delicately depends on the initial condition. KW - Ornstein–Uhlenbeck process KW - stationary stochastic process KW - ensemble and time averaged mean squared displacement Y1 - 2020 U6 - https://doi.org/10.1088/1367-2630/ab950b SN - 1367-2630 VL - 22 PB - IOP CY - London ER - TY - JOUR A1 - Lonsdorf, Tina B. A1 - Klingelhöfer-Jens, Maren A1 - Andreatta, Marta A1 - Beckers, Tom A1 - Chalkia, Anastasia A1 - Gerlicher, Anna A1 - Jentsch, Valerie L. A1 - Drexler, Shira Meir A1 - Mertens, Gaetan A1 - Richter, Jan A1 - Sjouwerman, Rachel A1 - Wendt, Julia A1 - Merz, Christian J. T1 - Navigating the garden of forking paths for data exclusions in fear conditioning research JF - eLife N2 - 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. Y1 - 2019 U6 - https://doi.org/10.7554/eLife.52465 SN - 2050-084X VL - 8 PB - eLife Sciences Publications CY - Cambridge ER - TY - JOUR A1 - Lonsdorf, Tina B. A1 - Klingelhöfer-Jens, Maren A1 - Andreatta, Marta A1 - Beckers, Tom A1 - Chalkia, Anastasia A1 - Gerlicher, Anna Maria Veronika A1 - Jentsch, Valerie L. A1 - Drexler, Shira Meir A1 - Mertens, Gaetan A1 - Richter, Jan A1 - Sjouwerman, Rachel A1 - Wendt, Julia A1 - Merz, Christian J. T1 - Navigating the garden of forking paths for data exclusions in fear conditioning research JF - eLife Y1 - 2019 U6 - https://doi.org/10.7554/eLife.52465 SN - 2050-084X VL - 8 PB - eLife Sciences Publications CY - Cambridge ER - TY - JOUR A1 - Günther, Erika A1 - Klauß, André A1 - Toro-Nahuelpan, Mauricio A1 - Schüler, Dirk A1 - Hille, Carsten A1 - Faivre, Damien T1 - The in vivo mechanics of the magnetotactic backbone as revealed by correlative FLIM-FRET and STED microscopy JF - Scientific reports N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-55804-5 SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Thomas, Jessica E. A1 - Carvalho, Gary R. A1 - Haile, James A1 - Rawlence, Nicolas J. A1 - Martin, Michael D. A1 - Ho, Simon Y. W. A1 - Sigfusson, Arnor P. A1 - Josefsson, Vigfus A. A1 - Frederiksen, Morten A1 - Linnebjerg, Jannie F. A1 - Castruita, Jose A. Samaniego A1 - Niemann, Jonas A1 - Sinding, Mikkel-Holger S. A1 - Sandoval-Velasco, Marcela A1 - Soares, Andre E. R. A1 - Lacy, Robert A1 - Barilaro, Christina A1 - Best, Juila A1 - Brandis, Dirk A1 - Cavallo, Chiara A1 - Elorza, Mikelo A1 - Garrett, Kimball L. A1 - Groot, Maaike A1 - Johansson, Friederike A1 - Lifjeld, Jan T. A1 - Nilson, Goran A1 - Serjeanston, Dale A1 - Sweet, Paul A1 - Fuller, Errol A1 - Hufthammer, Anne Karin A1 - Meldgaard, Morten A1 - Fjeldsa, Jon A1 - Shapiro, Beth A1 - Hofreiter, Michael A1 - Stewart, John R. A1 - Gilbert, M. Thomas P. A1 - Knapp, Michael T1 - Demographic reconstruction from ancient DNA supports rapid extinction of the great auk JF - eLife N2 - 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. Y1 - 2019 U6 - https://doi.org/10.7554/eLife.47509 SN - 2050-084X VL - 8 PB - eLife Sciences Publications CY - Cambridge ER - TY - JOUR A1 - Bröker, Katharine A1 - Sinelnikov, Evgeny A1 - Gustavus, Dirk A1 - Schumacher, Udo A1 - Pörtner, Ralf A1 - Hoffmeister, Hans A1 - Lüth, Stefan A1 - Dammermann, Werner T1 - Mass Production of Highly Active NK Cells for Cancer Immunotherapy in a GMP Conform Perfusion Bioreactor JF - Frontiers in Bioengineering and Biotechnology N2 - 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. KW - natural killer cells (NK cells) KW - cytotoxicity KW - tumor immunity KW - immunotherapy KW - perfusion bioreactor KW - GMP KW - mass production process Y1 - 2019 U6 - https://doi.org/10.3389/fbioe.2019.00194 SN - 2296-4185 VL - 7 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Löpfe, Moira A1 - Duss, Anja A1 - Zafeiropoulou, Katerina-Alexandra A1 - Bjoergvinsdottir, Oddny A1 - Eglin, David A1 - Fortunato, Giuseppino A1 - Klasen, Jürgen A1 - Ferguson, Stephen J. A1 - Würtz-Kozak, Karin A1 - Krupkova, Olga T1 - Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc JF - Pharmaceutics N2 - 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. KW - degenerative disc disease KW - inflammation KW - drug delivery KW - EGCG KW - microparticles KW - injectable biomaterial KW - electrospraying Y1 - 2019 U6 - https://doi.org/10.3390/pharmaceutics11090435 SN - 1999-4923 VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Miele, Vincent A1 - Guill, Christian A1 - Ramos-Jiliberto, Rodrigo A1 - Kéfi, Sonia T1 - Non-trophic interactions strengthen the diversity-functioning relationship in an ecological bioenergetic network model JF - PLoS Computational Biology : a new community journal N2 - Ecological communities are undeniably diverse, both in terms of the species that compose them as well as the type of interactions that link species to each other. Despite this long recognition of the coexistence of multiple interaction types in nature, little is known about the consequences of this diversity for community functioning. In the ongoing context of global change and increasing species extinction rates, it seems crucial to improve our understanding of the drivers of the relationship between species diversity and ecosystem functioning. Here, using a multispecies dynamical model of ecological communities including various interaction types (e.g. competition for space, predator interference, recruitment facilitation in addition to feeding), we studied the role of the presence and the intensity of these interactions for species diversity, community functioning (biomass and production) and the relationship between diversity and functioning. Taken jointly, the diverse interactions have significant effects on species diversity, whose amplitude and sign depend on the type of interactions involved and their relative abundance. They however consistently increase the slope of the relationship between diversity and functioning, suggesting that species losses might have stronger effects on community functioning than expected when ignoring the diversity of interaction types and focusing on feeding interactions only. Y1 - 2020 U6 - https://doi.org/10.1371/journal.pcbi.1007269 SN - 1553-7358 VL - 15 IS - 8 PB - PLoS CY - San Fransisco ER -