TY - JOUR A1 - Leimkühler, Silke A1 - Mendel, Ralf-Rainer T1 - Molybdenum Cofactor Biosynthesis JF - Molybdenum and tungsten enzymes: biochemistry N2 - The biosynthesis of the molybdenum cofactor (Moco) is highly conserved among all kingdoms of life. In all molybdoenzymes with the exception of nitrogenase, the molybdenum atom is coordinated to a dithiolene group present in the pterin-based 6-alkyl side chain of molybdopterin (MPT). In general, the biosynthesis of Moco can be divided into three steps in eukaryotes, and four steps in bacteria and archaea: (i) the starting point is the formation of the cyclic pyranopterin monophosphate (cPMP) from 5′GTP, (ii) in the second step the two sulfur molecules are inserted into cPMP leading to the formation of MPT, (iii) in the third step the molybdenum atom is inserted into molybdopterin to form Moco and (iv) additional modification of Moco occurs in bacteria and archaea with the attachment of a nucleotide (CMP or GMP) to the phosphate group of MPT, forming the dinucleotide variants of Moco. This review will focus on the biosynthesis of Moco in bacteria, humans and plants. Y1 - 2016 SN - 978-1-78262-391-5 SN - 978-1-78262-089-1 SN - 978-1-78262-881-1 U6 - https://doi.org/10.1039/9781782623915 VL - 5 SP - 100 EP - 116 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Li, Zhengdong A1 - Xu, Xun A1 - Wang, Weiwei A1 - Kratz, Karl A1 - Sun, Xianlei A1 - Zou, Jie A1 - Deng, Zijun A1 - Jung, Friedrich Wilhelm A1 - Gossen, Manfred A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells. KW - Mesenchymal stem cells KW - precondition KW - microstructure KW - migration KW - FAK-MAPK Y1 - 2017 U6 - https://doi.org/10.3233/CH-179208 SN - 1386-0291 SN - 1875-8622 VL - 67 SP - 267 EP - 278 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Reeg, Jette A1 - Schad, Thorsten A1 - Preuss, Thomas G. A1 - Solga, Andreas A1 - Körner, Katrin A1 - Mihan, Christine A1 - Jeltsch, Florian T1 - Modelling direct and indirect effects of herbicides on non-target grassland communities JF - Ecological modelling : international journal on ecological modelling and engineering and systems ecolog N2 - Natural grassland communities are threatened by a variety of factors, such as climate change and increasing land use by mankind. The use of plant protection products (synthetic or organic) is mandatory in agricultural food production. To avoid adverse effects on natural grasslands within agricultural areas, synthetic plant protection products are strictly regulated in Europe. However, effects of herbicides on non-target terrestrial plants are primarily studied on the level of individual plants neglecting interactions between species. In our study, we aim to extrapolate individual-level effects to the population and community level by adapting an existing spatio-temporal, individual-based plant community model (IBC-grass). We analyse the effects of herbicide exposure for three different grassland communities: 1) representative field boundary community, 2) Calthion grassland community, and 3) Arrhenatheretalia grassland community. Our simulations show that herbicide depositions can have effects on non-target plant communities resulting from direct and indirect effects on population level. The effect extent depends not only on the distance to the field, but also on the specific plant community, its disturbance regime (cutting frequency, trampling and grazing intensity) and resource level. Mechanistic modelling approaches such as IBC-grass present a promising novel approach in transferring and extrapolating standardized pot experiments to community level and thereby bridging the gap between ecotoxicological testing (e.g. in the greenhouse) and protection goals referring to real world conditions. KW - Plant community modelling KW - Herbicide exposure KW - Landscape KW - Non-target terrestrial plants KW - Field margins Y1 - 2017 U6 - https://doi.org/10.1016/j.ecolmodel.2017.01.010 SN - 0304-3800 SN - 1872-7026 VL - 348 SP - 44 EP - 55 PB - Elsevier CY - Amsterdam ER - TY - THES A1 - Knecht, Volker T1 - Modeling Biomolecular Association Y1 - 2017 ER - TY - JOUR A1 - Groth, Detlef T1 - Modeling a secular trend by Monte Carlo simulation of height biased migration in a spatial network JF - Anthropologischer Anzeiger : journal of biological and clinical anthropology ; Mitteilungsorgan der Gesellschaft für Anthropologie N2 - Background: In a recent Monte Carlo simulation, the clustering of body height of Swiss military conscripts within a spatial network with characteristic features of the natural Swiss geography was investigated. In this study I examined the effect of migration of tall individuals into network hubs on the dynamics of body height within the whole spatial network. The aim of this study was to simulate height trends. Material and methods: Three networks were used for modeling, a regular rectangular fishing net like network, a real world example based on the geographic map of Switzerland, and a random network. All networks contained between 144 and 148 districts and between 265-307 road connections. Around 100,000 agents were initially released with average height of 170 cm, and height standard deviation of 6.5 cm. The simulation was started with the a priori assumption that height variation within a district is limited and also depends on height of neighboring districts (community effect on height). In addition to a neighborhood influence factor, which simulates a community effect, body height dependent migration of conscripts between adjacent districts in each Monte Carlo simulation was used to re-calculate next generation body heights. In order to determine the direction of migration for taller individuals, various centrality measures for the evaluation of district importance within the spatial network were applied. Taller individuals were favored to migrate more into network hubs, backward migration using the same number of individuals was random, not biased towards body height. Network hubs were defined by the importance of a district within the spatial network. The importance of a district was evaluated by various centrality measures. In the null model there were no road connections, height information could not be delivered between the districts. Results: Due to the favored migration of tall individuals into network hubs, average body height of the hubs, and later, of the whole network increased by up to 0.1 cm per iteration depending on the network model. The general increase in height within the network depended on connectedness and on the amount of height information that was exchanged between neighboring districts. If higher amounts of neighborhood height information were exchanged, the general increase in height within the network was large (strong secular trend). The trend in the homogeneous fishnet like network was lowest, the trend in the random network was highest. Yet, some network properties, such as the heteroscedasticity and autocorrelations of the migration simulation models differed greatly from the natural features observed in Swiss military conscript networks. Autocorrelations of district heights for instance, were much higher in the migration models. Conclusion: This study confirmed that secular height trends can be modeled by preferred migration of tall individuals into network hubs. However, basic network properties of the migration simulation models differed greatly from the natural features observed in Swiss military conscripts. Similar network-based data from other countries should be explored to better investigate height trends with Monte Carlo migration approach. KW - secular trend KW - body height KW - simulation KW - community effect KW - Monte Carlo method KW - network Y1 - 2017 U6 - https://doi.org/10.1127/anthranz/2017/0703 SN - 0003-5548 SN - 2363-7099 VL - 74 IS - 1 SP - 81 EP - 88 PB - Schweizerbart CY - Stuttgart ER - TY - JOUR A1 - Schmidt, Marco F. T1 - miRNA Targeting Drugs BT - the next blockbusters? JF - Drug Target miRNA: Methods and Protocols N2 - Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. Addressing miRNAs as drug targets may enable the cure, or at least the treatment of diseases, which presently seems impossible. However, due to miRNAs’ chemical structure, generation of potential drug molecules with necessary pharmacokinetic properties is still challenging and requires a re-thinking of the drug discovery process. Therefore, this chapter highlights the potential of miRNAs as drug targets, discusses the challenges, and tries to give a complete overview of recent strategies in miRNA drug discovery. KW - miRNA KW - Drug discovery KW - microRNA-induced silencing complex KW - Antisense agents KW - Small-molecule miRNA modulators KW - Argonaute 2 protein Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 U6 - https://doi.org/10.1007/978-1-4939-6563-2_1 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - 3 EP - 22 PB - Springer CY - New York ER - TY - JOUR A1 - Eckert, Ester M. A1 - Di Cesare, Andrea A1 - Kettner, Marie Therese A1 - Arias-Andres, Maria A1 - Fontaneto, Diego A1 - Grossart, Hans-Peter A1 - Corno, Gianluca T1 - Microplastics increase impact of treated wastewater on freshwater microbial community JF - Environmental pollution N2 - Plastic pollution is a major global concern with several million microplastic particles entering every day freshwater ecosystems via wastewater discharge. Microplastic particles stimulate biofilm formation (plastisphere) throughout the water column and have the potential to affect microbial community structure if they accumulate in pelagic waters, especially enhancing the proliferation of biohazardous bacteria. To test this scenario, we simulated the inflow of treated wastewater into a temperate lake using a continuous culture system with a gradient of concentration of microplastic particles. We followed the effect of microplastics on the microbial community structure and on the occurrence of integrase 1 (intl), a marker associated with mobile genetic elements known as a proxy for anthropogenic effects on the spread of antimicrobial resistance genes. The abundance of intl increased in the plastisphere with increasing microplastic particle concentration, but not in the water surrounding the microplastic particles. Likewise, the microbial community on microplastic was more similar to the original wastewater community with increasing microplastic concentrations. Our results show that microplastic particles indeed promote persistence of typical indicators of microbial anthropogenic pollution in natural waters, and substantiate that their removal from treated wastewater should be prioritised. (C) 2017 Elsevier Ltd. All rights reserved. KW - Microplastics KW - Anthropogenic pollution KW - Treated wastewater KW - Freshwater microbial communities KW - Integrase 1 KW - Biofilm Y1 - 2017 U6 - https://doi.org/10.1016/j.envpol.2017.11.070 SN - 0269-7491 SN - 1873-6424 VL - 234 SP - 495 EP - 502 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Raatz, Michael A1 - Weikl, Thomas R. T1 - Membrane Tubulation by Elongated and Patchy Nanoparticles JF - Advanced materials interfaces N2 - Advances in nanotechnology lead to an increasing interest in how nanoparticles interact with biomembranes. Nanoparticles are wrapped spontaneously by biomembranes if the adhesive interactions between the particles and membranes compensate for the cost of membrane bending. In the last years, the cooperative wrapping of spherical nanoparticles in membrane tubules has been observed in experiments and simulations. For spherical nanoparticles, the stability of the particle-filled membrane tubules strongly depends on the range of the adhesive particle-membrane interactions. In this article, it is shown via modeling and energy minimization that elongated and patchy particles are wrapped cooperatively in membrane tubules that are highly stable for all ranges of the particle-membrane interactions, compared to individual wrapping of the particles. The cooperative wrapping of linear chains of elongated or patchy particles in membrane tubules may thus provide an efficient route to induce membrane tubulation, or to store such particles in membranes. Y1 - 2016 U6 - https://doi.org/10.1002/admi.201600325 SN - 2196-7350 VL - 4 IS - 1 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Cabral, Juliano Sarmento A1 - Valente, Luis A1 - Hartig, Florian T1 - Mechanistic simulation models in macroecology and biogeography BT - state-of-art and prospects JF - Ecography : pattern and diversity in ecology N2 - Macroecology and biogeography are concerned with understanding biodiversity patterns across space and time. In the past, the two disciplines have addressed this question mainly with correlative approaches, despite frequent calls for more mechanistic explanations. Recent advances in computational power, theoretical understanding, and statistical tools are, however, currently facilitating the development of more system-oriented, mechanistic models. We review these models, identify different model types and theoretical frameworks, compare their processes and properties, and summarize emergent findings. We show that ecological (physiology, demographics, dispersal, biotic interactions) and evolutionary processes, as well as environmental and human-induced drivers, are increasingly modelled mechanistically; and that new insights into biodiversity dynamics emerge from these models. Yet, substantial challenges still lie ahead for this young research field. Among these, we identify scaling, calibration, validation, and balancing complexity as pressing issues. Moreover, particular process combinations are still understudied, and so far models tend to be developed for specific applications. Future work should aim at developing more flexible and modular models that not only allow different ecological theories to be expressed and contrasted, but which are also built for tight integration with all macroecological data sources. Moving the field towards such a ‘systems macroecology’ will test and improve our understanding of the causal pathways through which eco-evolutionary processes create diversity patterns across spatial and temporal scales. Y1 - 2016 U6 - https://doi.org/10.1111/ecog.02480 SN - 0906-7590 SN - 1600-0587 VL - 40 IS - 2 SP - 267 EP - 280 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Bhat, Javaid Y. A1 - Milicic, Goran A1 - Thieulin-Pardo, Gabriel A1 - Bracher, Andreas A1 - Maxwell, Andrew A1 - Ciniawsky, Susanne A1 - Müller-Cajar, Oliver A1 - Engen, John R. A1 - Hartl, F. Ulrich A1 - Wendler, Petra A1 - Hayer-Hartl, Manajit T1 - Mechanism of Enzyme Repair by the AAA(+) Chaperone Rubisco Activase JF - Molecular cell N2 - How AAA(+) chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA(+) protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Y1 - 2017 U6 - https://doi.org/10.1016/j.molcel.2017.07.004 SN - 1097-2765 SN - 1097-4164 VL - 67 SP - 744 EP - 756 PB - Cell Press CY - Cambridge ER -