@article{AllanManningAltetal.2015, author = {Allan, Eric and Manning, Pete and Alt, Fabian and Binkenstein, Julia and Blaser, Stefan and Bl{\"u}thgen, Nico and B{\"o}hm, Stefan and Grassein, Fabrice and H{\"o}lzel, Norbert and Klaus, Valentin H. and Kleinebecker, Till and Morris, E. Kathryn and Oelmann, Yvonne and Prati, Daniel and Renner, Swen C. and Rillig, Matthias C. and Schaefer, Martin and Schloter, Michael and Schmitt, Barbara and Sch{\"o}ning, Ingo and Schrumpf, Marion and Solly, Emily and Sorkau, Elisabeth and Steckel, Juliane and Steffen-Dewenter, Ingolf and Stempfhuber, Barbara and Tschapka, Marco and Weiner, Christiane N. and Weisser, Wolfgang W. and Werner, Michael and Westphal, Catrin and Wilcke, Wolfgang and Fischer, Markus}, title = {Land use intensification alters ecosystem multifunctionality via loss of biodiversity and changes to functional composition}, series = {Ecology letters}, volume = {18}, journal = {Ecology letters}, number = {8}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1461-023X}, doi = {10.1111/ele.12469}, pages = {834 -- 843}, year = {2015}, abstract = {Global change, especially land-use intensification, affects human well-being by impacting the delivery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is a major component of global change effects on multifunctionality in real-world ecosystems, as in experimental ones, remains unclear. Therefore, we assessed biodiversity, functional composition and 14 ecosystem services on 150 agricultural grasslands differing in land-use intensity. We also introduce five multifunctionality measures in which ecosystem services were weighted according to realistic land-use objectives. We found that indirect land-use effects, i.e. those mediated by biodiversity loss and by changes to functional composition, were as strong as direct effects on average. Their strength varied with land-use objectives and regional context. Biodiversity loss explained indirect effects in a region of intermediate productivity and was most damaging when land-use objectives favoured supporting and cultural services. In contrast, functional composition shifts, towards fast-growing plant species, strongly increased provisioning services in more inherently unproductive grasslands.}, language = {en} } @article{SoliveresvanderPlasManningetal.2016, author = {Soliveres, Santiago and van der Plas, Fons and Manning, Peter and Prati, Daniel and Gossner, Martin M. and Renner, Swen C. and Alt, Fabian and Arndt, Hartmut and Baumgartner, Vanessa and Binkenstein, Julia and Birkhofer, Klaus and Blaser, Stefan and Bl{\"u}thgen, Nico and Boch, Steffen and B{\"o}hm, Stefan and B{\"o}rschig, Carmen and Buscot, Francois and Diek{\"o}tter, Tim and Heinze, Johannes and H{\"o}lzel, Norbert and Jung, Kirsten and Klaus, Valentin H. and Kleinebecker, Till and Klemmer, Sandra and Krauss, Jochen and Lange, Markus and Morris, E. Kathryn and M{\"u}ller, J{\"o}rg and Oelmann, Yvonne and Overmann, J{\"o}rg and Pasalic, Esther and Rillig, Matthias C. and Schaefer, H. Martin and Schloter, Michael and Schmitt, Barbara and Sch{\"o}ning, Ingo and Schrumpf, Marion and Sikorski, Johannes and Socher, Stephanie A. and Solly, Emily F. and Sonnemann, Ilja and Sorkau, Elisabeth and Steckel, Juliane and Steffan-Dewenter, Ingolf and Stempfhuber, Barbara and Tschapka, Marco and T{\"u}rke, Manfred and Venter, Paul C. and Weiner, Christiane N. and Weisser, Wolfgang W. and Werner, Michael and Westphal, Catrin and Wilcke, Wolfgang and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Fischer, Markus and Allan, Eric}, title = {Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality}, series = {Nature : the international weekly journal of science}, volume = {536}, journal = {Nature : the international weekly journal of science}, publisher = {Nature Publ. Group}, address = {London}, issn = {0028-0836}, doi = {10.1038/nature19092}, pages = {456 -- +}, year = {2016}, language = {en} } @article{SoliveresManningPratietal.2016, author = {Soliveres, Santiago and Manning, Peter and Prati, Daniel and Gossner, Martin M. and Alt, Fabian and Arndt, Hartmut and Baumgartner, Vanessa and Binkenstein, Julia and Birkhofer, Klaus and Blaser, Stefan and Bluethgen, Nico and Boch, Steffen and Boehm, Stefan and Boerschig, Carmen and Buscot, Francois and Diekoetter, Tim and Heinze, Johannes and Hoelzel, Norbert and Jung, Kirsten and Klaus, Valentin H. and Klein, Alexandra-Maria and Kleinebecker, Till and Klemmer, Sandra and Krauss, Jochen and Lange, Markus and Morris, E. Kathryn and Mueller, Joerg and Oelmann, Yvonne and Overmann, J{\"o}rg and Pasalic, Esther and Renner, Swen C. and Rillig, Matthias C. and Schaefer, H. Martin and Schloter, Michael and Schmitt, Barbara and Schoening, Ingo and Schrumpf, Marion and Sikorski, Johannes and Socher, Stephanie A. and Solly, Emily F. and Sonnemann, Ilja and Sorkau, Elisabeth and Steckel, Juliane and Steffan-Dewenter, Ingolf and Stempfhuber, Barbara and Tschapka, Marco and Tuerke, Manfred and Venter, Paul and Weiner, Christiane N. and Weisser, Wolfgang W. and Werner, Michael and Westphal, Catrin and Wilcke, Wolfgang and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Fischer, Markus and Allan, Eric}, title = {Locally rare species influence grassland ecosystem multifunctionality}, series = {Philosophical transactions of the Royal Society of London : B, Biological sciences}, volume = {371}, journal = {Philosophical transactions of the Royal Society of London : B, Biological sciences}, publisher = {Royal Society}, address = {London}, issn = {0962-8436}, doi = {10.1098/rstb.2015.0269}, pages = {3175 -- 3185}, year = {2016}, abstract = {Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6\% of the species tested. Species specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.}, language = {en} } @article{EdlichGereckeGiulbudagianetal.2016, author = {Edlich, Alexander and Gerecke, Christian and Giulbudagian, Michael and Neumann, Falko and Hedtrich, Sarah and Schaefer-Korting, Monika and Ma, Nan and Calderon, Marcelo and Kleuser, Burkhard}, title = {Specific uptake mechanisms of well-tolerated thermoresponsive polyglycerol-based nanogels in antigen-presenting cells of the skin}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.12.016}, pages = {155 -- 163}, year = {2016}, abstract = {Engineered nanogels are of high value for a targeted and controlled transport of compounds due to the ability to change their chemical properties by external stimuli. As it has been indicated that nanogels possess a high ability to penetrate the stratum corneum, it cannot be excluded that nanogels interact with dermal dendritic cells, especially in diseased skin. In this study the potential crosstalk of the thermore-sponsive nanogels (tNGs) with the dendritic cells of the skin was investigated with the aim to determine the immunotoxicological properties of the nanogels. The investigated tNGs were made of dendritic polyglycerol (dPG) and poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)), as polymer conferring thermoresponsive properties. Although the tNGs were taken up, they displayed neither cytotoxic and genotoxic effects nor any induction of reactive oxygen species in the tested cells. Interestingly, specific uptake mechanisms of the tNGs by the dendritic cells were depending on the nanogels cloud point temperature (Tcp), which determines the phase transition of the nanoparticle. The study points to caveolae-mediated endocytosis as being the major tNGs uptake mechanism at 37 degrees C, which is above the Tcp of the tNGs. Remarkably, an additional uptake mechanism, beside caveolae-mediated endocytosis, was observed at 29 degrees C, which is the Tcp of the tNGs. At this temperature, which is characterized by two different states of the tNGs, macropinocytosis was involved as well. In summary, our study highlights the impact of thermoresponsivity on the cellular uptake mechanisms which has to be taken into account if the tNGs are used as a drug delivery system.}, language = {en} } @article{HeneghanWardPereraetal.2012, author = {Heneghan, Carl and Ward, Alison and Perera, Rafael and Bankhead, Clare and Fuller, Alice and Stevens, Richard and Bradford, Kairen and Tyndel, Sally and Alonso-Coello, Pablo and Ansell, Jack and Beyth, Rebecca and Bernardo, Artur and Christensen, Thomas Decker and Cromheecke, Manon and Edson, Robert G and Fitzmaurice, David and Gadisseur, Alain PA and Garcia-Alamino, Josep M and Gardiner, Chris and Hasenkam, Michael and Jacobson, Alan and Kaatz, Scott and Kamali, Farhad and Khan, Tayyaba Irfan and Knight, Eve and Kortke, Heinrich and Levi, Marcel and Matchar, David Bruce and Menendez-Jandula, Barbara and Rakovac, Ivo and Schaefer, Christian and Siebenhofer, Andrea and Souto, Juan Carlos and Sunderji, Rubina and Gin, Kenneth and Shalansky, Karen and V{\"o}ller, Heinz and Wagner, Otto and Zittermann, Armin}, title = {Self-monitoring of oral anticoagulation systematic review and meta-analysis of individual patient data}, series = {The lancet}, volume = {379}, journal = {The lancet}, number = {9813}, publisher = {Elsevier}, address = {New York}, organization = {Self-Monitoring Trialist Collabora}, issn = {0140-6736}, doi = {10.1016/S0140-6736(11)61294-4}, pages = {322 -- 334}, year = {2012}, abstract = {Background Uptake of self-testing and self-management of oral coagulation has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. Methods We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. Findings Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12 800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0.51; 95\% CI 0.31-0.85) but not for major haemorrhagic events (0.88, 0.74-1.06) or death (0.82, 0.62-1.09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0.33, 95\% CI 0.17-0.66), as did participants with mechanical heart valve (0.52, 0.35-0.77). Analysis of major outcomes in the very elderly (age >= 85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. Interpretation Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up.}, language = {en} } @article{MayerSchauenburgThompsonSteckeletal.2016, author = {Mayer, Magnus C. and Schauenburg, Linda and Thompson-Steckel, Greta and Dunsing, Valentin and Kaden, Daniela and Voigt, Philipp and Schaefer, Michael and Chiantia, Salvatore and Kennedy, Timothy E. and Multhaup, Gerhard}, title = {Amyloid precursor-like protein 1 (APLP1) exhibits stronger zinc-dependent neuronal adhesion than amyloid precursor protein and APLP2}, series = {Journal of neurochemistry}, volume = {137}, journal = {Journal of neurochemistry}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0022-3042}, doi = {10.1111/jnc.13540}, pages = {266 -- 276}, year = {2016}, abstract = {The amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominently for APLP1, and (ii) by reducing the concentrations of neurotrophic soluble APP/APLP ectodomains.}, language = {en} } @article{KralemannFruehwirthPikovskijetal.2013, author = {Kralemann, Bjoern and Fruehwirth, Matthias and Pikovskij, Arkadij and Rosenblum, Michael and Kenner, Thomas and Schaefer, Jochen and Moser, Maximilian}, title = {In vivo cardiac phase response curve elucidates human respiratory heart rate variability}, series = {Nature Communications}, volume = {4}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms3418}, pages = {9}, year = {2013}, abstract = {Recovering interaction of endogenous rhythms from observations is challenging, especially if a mathematical model explaining the behaviour of the system is unknown. The decisive information for successful reconstruction of the dynamics is the sensitivity of an oscillator to external influences, which is quantified by its phase response curve. Here we present a technique that allows the extraction of the phase response curve from a non-invasive observation of a system consisting of two interacting oscillators-in this case heartbeat and respiration-in its natural environment and under free-running conditions. We use this method to obtain the phase-coupling functions describing cardiorespiratory interactions and the phase response curve of 17 healthy humans. We show for the first time the phase at which the cardiac beat is susceptible to respiratory drive and extract the respiratory-related component of heart rate variability. This non-invasive method for the determination of phase response curves of coupled oscillators may find application in many scientific disciplines.}, language = {en} } @article{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calderon, Marcelo and Hedtrich, Sarah and Schaefer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, series = {Nanotoxicology}, volume = {11}, journal = {Nanotoxicology}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1743-5390}, doi = {10.1080/17435390.2017.1292371}, pages = {267 -- 277}, year = {2017}, abstract = {Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.}, language = {en} }