TY - JOUR A1 - Singh, Jasbir A1 - Dani, Harinder M. A1 - Sharma, Reeta A1 - Steinberg, Pablo T1 - Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B-1 can disrupt protein targeting JF - Cell biochemistry and function N2 - Cell culture and western blotting studies revealed that aflatoxin B-1 (AFB(1)) inhibits the biosynthesis of two of the constituent polypeptides of signal recognition particle (SRP) (SRP54 and 72). SRP escorts polyribosomes carrying signal peptides from free form in the cytosol to the bound form on endoplasmic reticulum (ER) membrane during protein targeting. These effects of AFB(1) on SRP biosynthesis may inhibit the formation of functional SRP Our experiments have further shown that AFB(1) also inhibits the biosynthesis/translocation of a secretory protein, preprolactin, which fails to appear in the lumen of ER consequent to the treatment with this hepatocarcinogen. The results of the experiments presented in this article therefore enable us to infer for the first time that aflatoxin B-1 may inhibit the functioning of SRP as an escort and deplete the ER of polyribosomes for secretory protein synthesis. As these secretory proteins are important components of the plasma membrane, gap junctions and intercellular matrix, their absence from these locations could disturb cell to cell communication leading to tumorigenesis. KW - aflatoxin B-1 KW - SRP KW - protein targeting KW - protein translocation KW - western blotting Y1 - 2005 U6 - https://doi.org/10.1027/cbf.1285 SN - 0263-6484 VL - 24 SP - 507 EP - 510 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Kath, Nadja J. A1 - Boit, Alice A1 - Guill, Christian A1 - Gaedke, Ursula T1 - Accounting for activity respiration results in realistic trophic transfer efficiencies in allometric trophic network (ATN) models JF - Theoretical ecology N2 - Allometric trophic network (ATN) models offer high flexibility and scalability while minimizing the number of parameters and have been successfully applied to investigate complex food web dynamics and their influence on food web diversity and stability. However, the realism of ATN model energetics has never been assessed in detail, despite their critical influence on dynamic biomass and production patterns. Here, we compare the energetics of the currently established original ATN model, considering only biomass-dependent basal respiration, to an extended ATN model version, considering both basal and assimilation-dependent activity respiration. The latter is crucial in particular for unicellular and invertebrate organisms which dominate the metabolism of pelagic and soil food webs. Based on metabolic scaling laws, we show that the extended ATN version reflects the energy transfer through a chain of four trophic levels of unicellular and invertebrate organisms more realistically than the original ATN version. Depending on the strength of top-down control, the original ATN model yields trophic transfer efficiencies up to 71% at either the third or the fourth trophic level, which considerably exceeds any realistic values. In contrast, the extended ATN version yields realistic trophic transfer efficiencies 30% at all trophic levels, in accordance with both physiological considerations and empirical evidence from pelagic systems. Our results imply that accounting for activity respiration is essential for consistently implementing the metabolic theory of ecology in ATN models and for improving their quantitative predictions, which makes them more powerful tools for investigating the dynamics of complex natural communities. KW - Food web KW - Trophic transfer efficiency KW - Allometric trophic network model KW - Allometry KW - Energy transfer KW - Activity respiration Y1 - 2018 U6 - https://doi.org/10.1007/s12080-018-0378-z SN - 1874-1738 SN - 1874-1746 VL - 11 IS - 4 SP - 453 EP - 463 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Fritz, Michael Andre A1 - Rosa, Stefanie A1 - Sicard, Adrien T1 - Mechanisms Underlying the Environmentally Induced Plasticity of Leaf Morphology JF - Frontiers in genetics N2 - The primary function of leaves is to provide an interface between plants and their environment for gas exchange, light exposure and thermoregulation. Leaves have, therefore a central contribution to plant fitness by allowing an efficient absorption of sunlight energy through photosynthesis to ensure an optimal growth. Their final geometry will result from a balance between the need to maximize energy uptake while minimizing the damage caused by environmental stresses. This intimate relationship between leaf and its surroundings has led to an enormous diversification in leaf forms. Leaf shape varies between species, populations, individuals or even within identical genotypes when those are subjected to different environmental conditions. For instance, the extent of leaf margin dissection has, for long, been found to inversely correlate with the mean annual temperature, such that Paleobotanists have used models based on leaf shape to predict the paleoclimate from fossil flora. Leaf growth is not only dependent on temperature but is also regulated by many other environmental factors such as light quality and intensity or ambient humidity. This raises the question of how the different signals can be integrated at the molecular level and converted into clear developmental decisions. Several recent studies have started to shed the light on the molecular mechanisms that connect the environmental sensing with organ-growth and patterning. In this review, we discuss the current knowledge on the influence of different environmental signals on leaf size and shape, their integration as well as their importance for plant adaptation. KW - plants KW - leaf morphology KW - environment KW - developmental plasticity KW - gene regulatory networks KW - sensory system KW - gene responsiveness Y1 - 2018 U6 - https://doi.org/10.3389/fgene.2018.00478 SN - 1664-8021 VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Maes, Sybryn L. A1 - Perring, Michael P. A1 - Vanhellemont, Margot A1 - Depauw, Leen A1 - Van den Bulcke, Jan A1 - Brumelis, Guntis A1 - Brunet, Jorg A1 - Decocq, Guillaume A1 - den Ouden, Jan A1 - Härdtle, Werner A1 - Hedl, Radim A1 - Heinken, Thilo A1 - Heinrichs, Steffi A1 - Jaroszewicz, Bogdan A1 - Kopecký, Martin A1 - Malis, Frantisek A1 - Wulf, Monika A1 - Verheyen, Kris T1 - Environmental drivers interactively affect individual tree growth across temperate European forests JF - Global change biology N2 - Forecasting the growth of tree species to future environmental changes requires abetter understanding of its determinants. Tree growth is known to respond to global‐change drivers such as climate change or atmospheric deposition, as well as to localland‐use drivers such as forest management. Yet, large geographical scale studiesexamining interactive growth responses to multiple global‐change drivers are relativelyscarce and rarely consider management effects. Here, we assessed the interactiveeffects of three global‐change drivers (temperature, precipitation and nitrogen deposi-tion) on individual tree growth of three study species (Quercus robur/petraea, Fagus syl-vatica and Fraxinus excelsior). We sampled trees along spatial environmental gradientsacross Europe and accounted for the effects of management for Quercus. We collectedincrement cores from 267 trees distributed over 151 plots in 19 forest regions andcharacterized their neighbouring environment to take into account potentially confounding factors such as tree size, competition, soil conditions and elevation. Wedemonstrate that growth responds interactively to global‐change drivers, with species ‐specific sensitivities to the combined factors. Simultaneously high levels of precipita-tion and deposition benefited Fraxinus, but negatively affected Quercus’ growth, high-lighting species‐specific interactive tree growth responses to combined drivers. ForFagus, a stronger growth response to higher temperatures was found when precipita-tion was also higher, illustrating the potential negative effects of drought stress underwarming for this species. Furthermore, we show that past forest management canmodulate the effects of changing temperatures on Quercus’ growth; individuals in plotswith a coppicing history showed stronger growth responses to higher temperatures.Overall, our findings highlight how tree growth can be interactively determined by glo-bal‐change drivers, and how these growth responses might be modulated by past for-est management. By showing future growth changes for scenarios of environmentalchange, we stress the importance of considering multiple drivers, including past man-agement and their interactions, when predicting tree growth. KW - basal area increment KW - climate change KW - Fagus KW - Fraxinus KW - historical ecology KW - nitrogen deposition KW - Quercus KW - tree-ring analysis Y1 - 2018 U6 - https://doi.org/10.1111/gcb.14493 SN - 1354-1013 SN - 1365-2486 VL - 25 IS - 1 SP - 201 EP - 217 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Coloma, Sebastian A1 - Gaedke, Ursula A1 - Sivonen, Kaarina A1 - Hiltunen, Teppo T1 - Frequency of virus-resistant hosts determines experimental community dynamics JF - Ecology : a publication of the Ecological Society of America N2 - Parasites, such as bacterial viruses (phages), can have large effects on host populations both at the ecological and evolutionary levels. In the case of cyanobacteria, phages can reduce primary production and infected hosts release intracellular nutrients influencing planktonic food web structure, community dynamics, and biogeochemical cycles. Cyanophages may be of great importance in aquatic food webs during large cyanobacterial blooms unless the host population becomes resistant to phage infection. The consequences on plankton community dynamics of the evolution of phage resistance in bloom forming cyanobacterial populations are still poorly studied. Here, we examined the effect of different frequencies of a phage-resistant genotype within a filamentous nitrogen-fixing Nodularia spumigena population on an experimental plankton community. Three Nodularia populations with different initial frequencies (0%, 5%, and 50%) of phage-resistant genotypes were inoculated in separate treatments with the phage 2AV2, the green alga Chlorella vulgaris, and the rotifer Brachionus plicatilis, which formed the experimental plankton community subjected to either nitrogen-limited or nitrogen-rich conditions. We found that the frequency of the phage-resistant Nodularia genotype determined experimental community dynamics. Cyanobacterial populations with a high frequency (50%) of the phage-resistant genotype dominated the cultures despite the presence of phages, retaining most of the intracellular nitrogen in the plankton community. In contrast, populations with low frequencies (0% and 5%) of the phage-resistant genotype were lysed and reduced to extinction by the phage, transferring the intracellular nitrogen held by Nodularia to Chlorella and rotifers, and allowing Chlorella to dominate the communities and rotifers to survive. This study shows that even though phages represent minuscule biomass, they can have key effects on community composition and eco-evolutionary feedbacks in plankton communities. KW - cyanobacteria KW - eco-evolutionary feedbacks KW - experimental evolution KW - host-parasite interaction KW - phage resistance KW - predator-prey interaction Y1 - 2018 U6 - https://doi.org/10.1002/ecy.2554 SN - 0012-9658 SN - 1939-9170 VL - 100 IS - 1 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Ryo, Masahiro A1 - Jeschke, Jonathan M. A1 - Rillig, Matthias C. A1 - Heger, Tina T1 - Machine learning with the hierarchy-of-hypotheses (HoH) approach discovers novel pattern in studies on biological invasions JF - Research synthesis methods N2 - Research synthesis on simple yet general hypotheses and ideas is challenging in scientific disciplines studying highly context-dependent systems such as medical, social, and biological sciences. This study shows that machine learning, equation-free statistical modeling of artificial intelligence, is a promising synthesis tool for discovering novel patterns and the source of controversy in a general hypothesis. We apply a decision tree algorithm, assuming that evidence from various contexts can be adequately integrated in a hierarchically nested structure. As a case study, we analyzed 163 articles that studied a prominent hypothesis in invasion biology, the enemy release hypothesis. We explored if any of the nine attributes that classify each study can differentiate conclusions as classification problem. Results corroborated that machine learning can be useful for research synthesis, as the algorithm could detect patterns that had been already focused in previous narrative reviews. Compared with the previous synthesis study that assessed the same evidence collection based on experts' judgement, the algorithm has newly proposed that the studies focusing on Asian regions mostly supported the hypothesis, suggesting that more detailed investigations in these regions can enhance our understanding of the hypothesis. We suggest that machine learning algorithms can be a promising synthesis tool especially where studies (a) reformulate a general hypothesis from different perspectives, (b) use different methods or variables, or (c) report insufficient information for conducting meta-analyses. KW - artificial intelligence KW - hierarchy-of-hypotheses approach KW - machine learning KW - meta-analysis KW - synthesis KW - systematic review Y1 - 2019 U6 - https://doi.org/10.1002/jrsm.1363 SN - 1759-2879 SN - 1759-2887 VL - 11 IS - 1 SP - 66 EP - 73 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Schaub, Tonio A1 - Klaassen, Raymond H. G. A1 - Bouten, Willem A1 - Schlaich, Almut E. A1 - Koks, Ben J. T1 - Collision risk of Montagu’s Harriers Circus pygargus with wind turbines derived from high-resolution GPS tracking JF - Ibis : the international journal of avian science ; the journal of the British Ornithologists' Union N2 - Flight behaviour characteristics such as flight altitude and avoidance behaviour determine the species-specific collision risk of birds with wind turbines. However, traditional observational methods exhibit limited positional accuracy. High-resolution GPS telemetry represents a promising method to overcome this drawback. In this study, we used three-dimensional GPS tracking data including high-accuracy tracks recorded at 3-s intervals to investigate the collision risk of breeding male Montagu's Harriers Circus pygargus in the Dutch–German border region. Avoidance of wind turbines was quantified by a novel approach comparing observed flights to a null model of random flight behaviour. On average, Montagu's Harriers spent as much as 8.2 h per day in flight. Most flights were at low altitude, with only 7.1% within the average rotor height range (RHR; 45–125 m). Montagu's Harriers showed significant avoidance behaviour, approaching turbines less often than expected, particularly when flying within the RHR (avoidance rate of 93.5%). For the present state, with wind farms situated on the fringes of the regional nesting range, collision risk models based on our new insights on flight behaviour indicated 0.6–2.0 yearly collisions of adult males (as compared with a population size of c. 40 pairs). However, the erection of a new wind farm inside the core breeding area could markedly increase mortality (up to 9.7 yearly collisions). If repowering of the wind farms was carried out using low-reaching modern turbines (RHR 36–150 m), mortality would more than double, whereas it would stay approximately constant if higher turbines (RHR 86–200 m) were used. Our study demonstrates the great potential of high-resolution GPS tracking for collision risk assessments. The resulting information on collision-related flight behaviour allows for performing detailed scenario analyses on wind farm siting and turbine design, in contrast to current environmental assessment practices. With regard to Montagu's Harriers, we conclude that although the deployment of higher wind turbines represents an opportunity to reduce collision risk for this species, precluding wind energy developments in core breeding areas remains the most important mitigation measure. KW - avoidance rate KW - environmental impact KW - flight height KW - human-wildlife conflict KW - mitigation KW - raptors KW - renewable energy KW - wind energy Y1 - 2019 U6 - https://doi.org/10.1111/ibi.12788 SN - 0019-1019 SN - 1474-919X VL - 162 IS - 2 SP - 520 EP - 534 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Voigt, Christian A1 - Scholl, Julia M. A1 - Bauer, Juliane A1 - Teige, Tobias A1 - Yovel, Yossi A1 - Kramer-Schadt, Stephanie A1 - Gras, Pierre T1 - Movement responses of common noctule bats to the illuminated urban landscape JF - Landscape ecology N2 - Context Cities are a challenging habitat for obligate nocturnal mammals because of the ubiquitous use of artificial light at night (ALAN). How nocturnal animals move in an urban landscape, particularly in response to ALAN is largely unknown. Objectives We studied the movement responses, foraging and commuting, of common noctules (Nyctalus noctula) to urban landscape features in general and ALAN in particular. Methods We equipped 20 bats with miniaturized GPS loggers in the Berlin metropolitan area and related spatial positions of bats to anthropogenic and natural landscape features and levels of ALAN. Results Common noctules foraged close to ALAN only next to bodies of water or well vegetated areas, probably to exploit swarms of insects lured by street lights. In contrast, they avoided illuminated roads, irrespective of vegetation cover nearby. Predictive maps identified most of the metropolitan area as non-favoured by this species because of high levels of impervious surfaces and ALAN. Dark corridors were used by common noctules for commuting and thus likely improved the permeability of the city landscape. Conclusions We conclude that the spatial use of common noctules, previously considered to be more tolerant to light than other bats, is largely constrained by ALAN. Our study is the first individual-based GPS tracking study to show sensitive responses of nocturnal wildlife to light pollution. Approaches to protect urban biodiversity need to include ALAN to safeguard the larger network of dark habitats for bats and other nocturnal species in cities. KW - Urbanization KW - GPS tracking KW - Artificial light at night KW - ALAN KW - Habitat use KW - Preference KW - Movement KW - Common noctule bat Y1 - 2019 U6 - https://doi.org/10.1007/s10980-019-00942-4 SN - 0921-2973 SN - 1572-9761 VL - 35 IS - 1 SP - 189 EP - 201 PB - Springer CY - Dordrecht ER - TY - GEN A1 - Albers, Philip A1 - Uestuen, Suayib A1 - Witzel, Katja A1 - Bornke, Frederik T1 - Identification of a novel target of the bacterial effector HopZ1a T2 - Phytopathology N2 - The plant pathogen Pseudomonas syringae is a gram-negative bacterium which infects a wide range of plant species including important crops plants. To suppress plant immunity and cause disease P.syringae injects type-III effector proteins (T3Es) into the plant cell cytosol. In this study, we identified a novel target of the well characterized bacterial T3E HopZ1a. HopZ1a is an acetyltransferase that was shown to disrupt vesicle transport during innate immunity by acetylating tubulin. Using a yeast-two-hybrid screen approach, we identified a REMORIN (REM) protein from tobacco as a novel HopZ1a target. HopZ1a interacts with REM at the plasma membrane (PM) as shown by split-YFP experiments. Interestingly, we found that PBS1, a well-known kinase involved in plant immunity also interacts with REM in pull-down assays, and at the PM as shown by BiFC. Furthermore, we confirmed that REM is phosphorylated by PBS1 in vitro. Overexpression of REM provokes the upregulation of defense genes and leads to disease-like phenotypes pointing to a role of REM in plant immune signaling. Further protein-protein interaction studies reveal novel REM binding partners with a possible role in plant immune signaling. Thus, REM might act as an assembly hub for an immune signaling complex targeted by HopZ1a. Taken together, this is the first report describing that a REM protein is targeted by a bacterial effector. How HopZ1a might mechanistically manipulate the plant immune system through interfering with REM function will be discussed. Y1 - 2018 SN - 0031-949X SN - 1943-7684 VL - 108 IS - 10 PB - American Phytopathological Society CY - Saint Paul ER - TY - JOUR A1 - Franco-Obregon, Alfredo A1 - Cambria, Elena A1 - Greutert, Helen A1 - Wernas, Timon A1 - Hitzl, Wolfgang A1 - Egli, Marcel A1 - Sekiguchi, Miho A1 - Boos, Norbert A1 - Hausmann, Oliver A1 - Ferguson, Stephen J. A1 - Kobayashi, Hiroshi A1 - Würtz-Kozak, Karin T1 - TRPC6 in simulated microgravity of intervertebral disc cells JF - European Spine Journal N2 - Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies. KW - Intervertebral disc KW - Simulated microgravity KW - Senescence KW - TRP channels KW - Mechanotransduction KW - Gene expression Y1 - 2018 U6 - https://doi.org/10.1007/s00586-018-5688-8 SN - 0940-6719 SN - 1432-0932 VL - 27 IS - 10 SP - 2621 EP - 2630 PB - Springer CY - New York ER - TY - JOUR A1 - Götz, Klaus-Peter A1 - Naher, Jobadatun A1 - Fettke, Jörg A1 - Chmielewski, Frank M. T1 - Changes of proteins during dormancy and bud development of sweet cherry (Prunus avium L.) JF - Scientia horticulturae : an international journal sponsored by the International Society for Horticultural Science N2 - Trees control the flowering processes in response to both environmental and endogenous (mechanisms at cellular/tissue level) conditions. Dormancy of flower buds is characterized by the reduction of growth and the enhancement of frost and desiccation resistance. The release of endodormancy and the beginning of ontogenetic development, as two important dates for developing reliable phenological models, escape from any visible signs. Thus, we identified - to our knowledge as first - relevant proteins in sweet cherry buds occurring during these phenological phases at high time resolution in three seasons (2012/13–2014/15) under natural conditions in Northeast Germany. The protein content of buds from the first week of October to leaf fall, from leaf fall to the end of endodormancy (t1), from t1 to the beginning of ontogenetic development (t1*), and from t1* until swollen bud, was comparable in each of the seasons. The increase of the protein content began after swollen bud and markedly differences occurred at side green, green tip, tight and open cluster. SDS gel electrophoresis followed by peptide mass fingerprinting accomplished by MALDI-TOF MS was applied for protein identification. ‘Volume intensity’ has been used to demonstrate the pattern and changes of proteins. None of the analysed proteins like for cell proliferation/differentiation (Phytosulfokines 3), carbon fixation (Rubisco), and defense against pathogenes (Major allergen Pru sv 1) indicates the date of endodormancy release or the beginning of the (invisible) ontogenetic development. The stages around green tip, tight, and open cluster resulted in markedly increase of the volume intensity of the protein for cell proliferation/differentiation and the carbon fixation, whereas the volume intensity of a protein for defense against pathogens markedly decreased. The pattern and changes of the volume intensity of neoxanthin synthase (NXS) in sweet cherry buds followed the increasing demand during endo- and ecodormancy to produce neoxanthin, which is a prominent member of the group of reactive oxygen species (ROS) scavengers. KW - Dormancy phases KW - Buds KW - Prunus avium L. KW - Peptide mass fingerprinting Y1 - 2018 U6 - https://doi.org/10.1016/j.scienta.2018.05.016 SN - 0304-4238 SN - 1879-1018 VL - 239 SP - 41 EP - 49 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Navarro-Retamal, Carlos A1 - Bremer, Anne A1 - Ingolfsson, Helgi I. A1 - Alzate-Morales, Jans A1 - Caballero, Julio A1 - Thalhammer, Anja A1 - Gonzalez, Wendy A1 - Hincha, Dirk K. T1 - Folding and Lipid Composition Determine Membrane Interaction of the Disordered Protein COR15A JF - Biophysical journal N2 - Plants from temperate climates, such as the model plant Arabidopsis thaliana, are challenged with seasonal low temperatures that lead to increased freezing tolerance in fall in a process termed cold acclimation. Among other adaptations, this involves the accumulation of cold-regulated (COR) proteins, such as the intrinsically disordered chloroplast-localized protein COR15A. Together with its close homolog COR15B, it stabilizes chloroplast membranes during freezing. COR15A folds into amphipathic alpha-helices in the presence of high concentrations of low-molecular-mass crowders or upon dehydration. Under these conditions, the (partially) folded protein binds peripherally to membranes. In our study, we have used coarse-grained molecular dynamics simulations to elucidate the details of COR15A-membrane binding and its effects on membrane structure and dynamics. Simulation results indicate that at least partial folding of COR15A and the presence of highly unsaturated galactolipids in the membranes are necessary for efficient membrane binding. The bound protein is stabilized on the membrane by interactions of charged and polar amino acids with galactolipid headgroups and by interactions of hydrophobic amino acids with the upper part of the fatty acyl chains. Experimentally, the presence of liposomes made from a mixture of lipids mimicking chloroplast membranes induces additional folding in COR15A under conditions of partial dehydration, in agreement with the simulation results. Y1 - 2018 U6 - https://doi.org/10.1016/j.bpj.2018.08.014 SN - 0006-3495 SN - 1542-0086 VL - 115 IS - 6 SP - 968 EP - 980 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Fedders, Ronja A1 - Muenzner, Matthias A1 - Weber, Pamela A1 - Sommerfeld, Manuela A1 - Knauer, Miriam A1 - Kedziora, Sarah A1 - Kast, Naomi A1 - Heidenreich, Steffi A1 - Raila, Jens A1 - Weger, Stefan A1 - Henze, Andrea A1 - Schupp, Michael T1 - Liver-secreted RBP4 does not impair glucose homeostasis in mice JF - The journal of biological chemistry N2 - Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis. KW - liver KW - retinoid-binding protein KW - glucose metabolism KW - insulin resistance KW - mouse KW - TTR Y1 - 2018 U6 - https://doi.org/10.1074/jbc.RA118.004294 SN - 1083-351X VL - 293 IS - 39 SP - 15269 EP - 15276 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER - TY - JOUR A1 - Guerrero-Ramirez, Nathaly Rokssana A1 - Craven, Dylan A1 - Reich, Peter B. A1 - Ewel, John J. A1 - Isbell, Forest A1 - Koricheva, Julia A1 - Parrotta, John A. A1 - Auge, Harald A1 - Erickson, Heather E. A1 - Forrester, David I. A1 - Hector, Andy A1 - Joshi, Jasmin Radha A1 - Montagnini, Florencia A1 - Palmborg, Cecilia A1 - Piotto, Daniel A1 - Potvin, Catherine A1 - Roscher, Christiane A1 - van Ruijven, Jasper A1 - Tilman, David A1 - Wilsey, Brian A1 - Eisenhauer, Nico T1 - Diversity-dependent temporal divergence of ecosystem functioning in experimental ecosystems JF - Nature ecology & evolution N2 - The effects of biodiversity on ecosystem functioning generally increase over time, but the underlying processes remain unclear. Using 26 long-term grassland and forest experimental ecosystems, we demonstrate that biodiversity-ecosystem functioning relationships strengthen mainly by greater increases in functioning in high-diversity communities in grasslands and forests. In grasslands, biodiversity effects also strengthen due to decreases in functioning in low-diversity communities. Contrasting trends across grasslands are associated with differences in soil characteristics. Y1 - 2017 U6 - https://doi.org/10.1038/s41559-017-0325-1 SN - 2397-334X VL - 1 IS - 11 SP - 1639 EP - 1642 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Berry, Scott A1 - Rosa, Stefanie A1 - Howard, Martin A1 - Buhler, Marc A1 - Dean, Caroline T1 - Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression JF - Genes & Development N2 - Epigenetic maintenance of gene repression is essential for development. Polycomb complexes are central to this memory, but many aspects of the underlying mechanism remain unclear. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binds Polycomb-deposited H3K27me3 and is required for repression of many Polycomb target genes in Arabidopsis. Here we show that LHP1 binds RNA in vitro through the intrinsically disordered hinge region. By independently perturbing the RNA-binding hinge region and H3K27me3 (trimethylation of histone H3 at Lys27) recognition, we found that both facilitate LHP1 localization and H3K27me3 maintenance. Disruption of the RNAbinding hinge region also prevented formation of subnuclear foci, structures potentially important for epigenetic repression. KW - chromatin KW - epigenetics KW - plant biology KW - Polycomb KW - RNA Y1 - 2017 U6 - https://doi.org/10.1101/gad.305227.117 SN - 0890-9369 SN - 1549-5477 VL - 31 SP - 2115 EP - 2120 PB - Cold Spring Harbor Laboratory Press CY - Cold Spring Harbor, NY ER - 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 - Reil, Daniela A1 - Binder, Florian A1 - Freise, Jona A1 - Imholt, Christian A1 - Beyrers, Konrad A1 - Jacob, Jens A1 - Krüger, Detlev H. A1 - Hofmann, Jörg A1 - Dreesman, Johannes A1 - Ulrich, Rainer Günter T1 - Hantaviren in Deutschland BT - Aktuelle Erkenntnisse zu Erreger, Reservoir, Verbreitung und Prognosemodellen JF - Berliner und Münchener tierärztliche Wochenschrift N2 - Hantaviruses are small mammal-associated pathogens that are found in rodents but also in shrews, moles and bats. Aim of this manuscript is to give a current overview of the epidemiology and ecology of hantaviruses in Germany and to discuss respective models for the prediction of virus outbreaks. In Germany the majority of human disease cases are caused by the Puumala virus (PUUV), transmitted by the bank vole (Myodes glareolus). PUUV is associated with the Western evolutionary lineage of the bank vole and is not present in the eastern and northern parts of Germany. A second human pathogenic hantavirus is the Dobrava-Belgrade virus (DOBV), genotype Kurkino; its reservoir host, the striped field mouse (Apodemus agrarius), is mostly occurring in the eastern part of Germany. A PUUV-related hantavirus is the rarely pathogenic Tula virus (TULV), that is associated with the common vole (Microtus arvalis). In addition, Seewis virus, Asikkala virus, and Bruges virus are shrew- and mole-associated hantaviruses with still unknown pathogenicity in humans. Human disease cases are associated with the different hantaviruses according to their regional distribution. The viruses can cause mild to severe but also subclinical courses of the respective disease. The number of human PUUV disease cases in 2007, 2010, 2012, 2015 and 2017 correlates with the occurrence of high levels of seed production of beech trees ("beech mast") in the preceding year. Models based on weather parameters for the prediction of PUUV disease clusters as developed in recent years need further validation and optimisation. in addition to the abundance of infected reservoir rodents, the exposure behaviour of humans affects the risk of human infection. The application of robust forecast models can assist the public health service to develop and communicate spatially and temporally targeted information. Thus, further recommendations to mitigate infection risk for the public may be provided. N2 - Hantaviren sind Kleinsäuger-assoziierte Krankheitserreger, die vor allem in Nagetieren, aber auch in Spitzmäusen, Maulwürfen und Fledermäusen vorkommen. Ziel dieser Arbeit ist es, einen aktuellen Überblick zur Epidemiologie und Ökologie der Hantaviren in Deutschland zu geben und Modelle zur Vorhersage von Virusausbrüchen zu diskutieren. In Deutschland werden die meisten humanen Erkrankungsfälle beim Menschen durch das von der Rötelmaus (Myodes glareolus) übertragene Puumalavirus (PUUV) verursacht. PUUV ist mit der westlichen evolutionären Linie der Rötelmaus assoziiert und fehlt im östlichen und nördlichen Teil Deutschlands. Ein zweites humanpathogenes Hantavirus ist das Dobrava-Belgrad-Virus (DOBV), Genotyp Kurkino, dessen Reservoir die vor allem im östlichen Teil Deutschlands vorkommende Brandmaus (Apodemus agrarius) ist. Ein PUUV-verwandtes Hantavirus ist das selten humanpathogene Tulavirus (TULV), das mit der Feldmaus (Microtus arvalis) assoziiert ist. Darüber hinaus wurden mit dem Seewis-, Asikkala- und Brugesvirus Spitzmaus- und Maulwurf-assoziierte Hantaviren mit noch unklarer Humanpathogenität gefunden. Die humanen Erkrankungen sind jeweils mit den verschiedenen Hantaviren in deren regionaler Verteilung assoziiert und können mild bis schwer, aber auch subklinisch verlaufen. Das Auftreten von Häufungen humaner, durch PUUV verursachter Erkrankungen in den Jahren 2007, 2010, 2012, 2015 und 2017 korreliert mit dem Auftreten einer starken Fruktifikation der Buche („Buchenmast“) im jeweiligen Vorjahr. Auf der Basis von Wetterparametern sind Modelle zur Vorhersage von PUUV-Erkrankungshäufungen entwickelt worden, die zukünftig validiert und optimiert werden müssen. Neben dem Ausmaß des Virusvorkommens im Reservoir wird das Risiko humaner Infektionen durch das Expositionsverhalten des Menschen beeinflusst. Durch die Anwendung von Prognosemodellen soll der öffentliche Gesundheitsdienst in die Lage versetzt werden, räumlich und zeitlich gezielte und sachgerechte Präventionsempfehlungen für die Bevölkerung abzugeben. T2 - Hantaviruses in Germany: current knowledge on pathogens, reservoirs, distribution and forecast models KW - early warning system KW - hantavirus KW - hantavirus disease KW - rodents KW - population dynamics KW - Frühwarn-System KW - Hantavirus KW - Hantavirus-Erkrankung KW - Nagetiere KW - Populationsdynamik Y1 - 2018 U6 - https://doi.org/10.2376/0005-9366-18003 SN - 0005-9366 SN - 1439-0299 VL - 131 IS - 11-12 SP - 453 EP - 464 PB - Schlütersche Verlagsgesellschaft mbH & Co. KG. CY - Hannover ER - TY - JOUR A1 - Sperber, Hannah Sabeth A1 - Welke, Robert-William A1 - Petazzi, Roberto Arturo A1 - Bergmann, Ronny A1 - Schade, Matthias A1 - Shai, Yechiel A1 - Chiantia, Salvatore A1 - Herrmann, Andreas A1 - Schwarzer, Roland T1 - Self-association and subcellular localization of Puumala hantavirus envelope proteins JF - Scientific reports N2 - Hantavirus assembly and budding are governed by the surface glycoproteins Gn and Gc. In this study, we investigated the glycoproteins of Puumala, the most abundant Hantavirus species in Europe, using fluorescently labeled wild-type constructs and cytoplasmic tail (CT) mutants. We analyzed their intracellular distribution, co-localization and oligomerization, applying comprehensive live, single-cell fluorescence techniques, including confocal microscopy, imaging flow cytometry, anisotropy imaging and Number&Brightness analysis. We demonstrate that Gc is significantly enriched in the Golgi apparatus in absence of other viral components, while Gn is mainly restricted to the endoplasmic reticulum (ER). Importantly, upon co-expression both glycoproteins were found in the Golgi apparatus. Furthermore, we show that an intact CT of Gc is necessary for efficient Golgi localization, while the CT of Gn influences protein stability. Finally, we found that Gn assembles into higher-order homo-oligomers, mainly dimers and tetramers, in the ER while Gc was present as mixture of monomers and dimers within the Golgi apparatus. Our findings suggest that PUUV Gc is the driving factor of the targeting of Gc and Gn to the Golgi region, while Gn possesses a significantly stronger self-association potential. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-018-36879-y SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER -