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- ItemIntegrating Biophysics in Toxicology(Basel : MDPI, 2020) Del Favero, G.; Kraegeloh, A.Integration of biophysical stimulation in test systems is established in diverse branches of biomedical sciences including toxicology. This is largely motivated by the need to create novel experimental setups capable of reproducing more closely in vivo physiological conditions. Indeed, we face the need to increase predictive power and experimental output, albeit reducing the use of animals in toxicity testing. In vivo, mechanical stimulation is essential for cellular homeostasis. In vitro, diverse strategies can be used to model this crucial component. The compliance of the extracellular matrix can be tuned by modifying the stiffness or through the deformation of substrates hosting the cells via static or dynamic strain. Moreover, cells can be cultivated under shear stress deriving from the movement of the extracellular fluids. In turn, introduction of physical cues in the cell culture environment modulates differentiation, functional properties, and metabolic competence, thus influencing cellular capability to cope with toxic insults. This review summarizes the state of the art of integration of biophysical stimuli in model systems for toxicity testing, discusses future challenges, and provides perspectives for the further advancement of in vitro cytotoxicity studies.
- ItemCharge isomers of myelin basic protein: Structure and interactions with membranes, nucleotide analogues, and calmodulin(San Francisco, CA : Public Library of Science, 2011) Wang, C.; Neugebauer, U.; Bürck, J.; Myllykoski, M.; Baumgärtel, P.; Popp, J.; Kursula, P.As an essential structural protein required for tight compaction of the central nervous system myelin sheath, myelin basic protein (MBP) is one of the candidate autoantigens of the human inflammatory demyelinating disease multiple sclerosis, which is characterized by the active degradation of the myelin sheath. In this work, recombinant murine analogues of the natural C1 and C8 charge components (rmC1 and rmC8), two isoforms of the classic 18.5-kDa MBP, were used as model proteins to get insights into the structure and function of the charge isomers. Various biochemical and biophysical methods such as size exclusion chromatography, calorimetry, surface plasmon resonance, small angle X-ray and neutron scattering, Raman and fluorescence spectroscopy, and conventional as well as synchrotron radiation circular dichroism were used to investigate differences between these two isoforms, both from the structural point of view, and regarding interactions with ligands, including calmodulin (CaM), various detergents, nucleotide analogues, and lipids. Overall, our results provide further proof that rmC8 is deficient both in structure and especially in function, when compared to rmC1. While the CaM binding properties of the two forms are very similar, their interactions with membrane mimics are different. CaM can be used to remove MBP from immobilized lipid monolayers made of synthetic lipids - a phenomenon, which may be of relevance for MBP function and its regulation. Furthermore, using fluorescently labelled nucleotides, we observed binding of ATP and GTP, but not AMP, by MBP; the binding of nucleoside triphosphates was inhibited by the presence of CaM. Together, our results provide important further data on the interactions between MBP and its ligands, and on the differences in the structure and function between MBP charge isomers.
- ItemA new climate dataset for systematic assessments of climate change impacts as a function of global warming(München : European Geopyhsical Union, 2012) Heinke, J.; Ostberg, S.; Schaphoff, S.; Frieler, K.; Müller, C.; Gerten, D.; Meinshausen, M.; Lucht, W.Interactions between food demand, biomass energy and forest preservation are driving both food prices and land-use changes, regionally and globally. This study presents a new model called Nexus Land-Use version 1.0 which describes these interactions through a generic representation of agricultural intensification mechanisms within agricultural lands. The Nexus Land-Use model equations combine biophysics and economics into a single coherent framework to calculate crop yields, food prices, and resulting pasture and cropland areas within 12 regions inter-connected with each other by international trade. The representation of cropland and livestock production systems in each region relies on three components: (i) a biomass production function derived from the crop yield response function to inputs such as industrial fertilisers; (ii) a detailed representation of the livestock production system subdivided into an intensive and an extensive component, and (iii) a spatially explicit distribution of potential (maximal) crop yields prescribed from the Lund-Postdam-Jena global vegetation model for managed Land (LPJmL). The economic principles governing decisions about land-use and intensification are adapted from the Ricardian rent theory, assuming cost minimisation for farmers. In contrast to the other land-use models linking economy and biophysics, crops are aggregated as a representative product in calories and intensification for the representative crop is a non-linear function of chemical inputs. The model equations and parameter values are first described in details. Then, idealised scenarios exploring the impact of forest preservation policies or rising energy price on agricultural intensification are described, and their impacts on pasture and cropland areas are investigated.
- ItemMAgPIE 4-a modular open-source framework for modeling global land systems(Göttingen : Copernicus GmbH, 2019) Dietrich, J.P.; Bodirsky, B.L.; Humpenöder, F.; Weindl, I.; Stevanović, M.; Karstens, K.; Kreidenweis, U.; Wang, X.; Mishra, A.; Klein, D.; Ambrósio, G.; Araujo, E.; Yalew, A.W.; Baumstark, L.; Wirth, S.; Giannousakis, A.; Beier, F.; Meng-Chuen, Chen, D.; Lotze-Campen, H.; Popp, A.The open-source modeling framework MAgPIE (Model of Agricultural Production and its Impact on the Environment) combines economic and biophysical approaches to simulate spatially explicit global scenarios of land use within the 21st century and the respective interactions with the environment. Besides various other projects, it was used to simulate marker scenarios of the Shared Socioeconomic Pathways (SSPs) and contributed substantially to multiple IPCC assessments. However, with growing scope and detail, the non-linear model has become increasingly complex, computationally intensive and non-transparent, requiring structured approaches to improve the development and evaluation of the model. Here, we provide an overview on version 4 of MAgPIE and how it addresses these issues of increasing complexity using new technical features: modular structure with exchangeable module implementations, flexible spatial resolution, in-code documentation, automatized code checking, model/output evaluation and open accessibility. Application examples provide insights into model evaluation, modular flexibility and region-specific analysis approaches. While this paper is focused on the general framework as such, the publication is accompanied by a detailed model documentation describing contents and equations, and by model evaluation documents giving insights into model performance for a broad range of variables. With the open-source release of the MAgPIE 4 framework, we hope to contribute to more transparent, reproducible and collaborative research in the field. Due to its modularity and spatial flexibility, it should provide a basis for a broad range of land-related research with economic or biophysical, global or regional focus.
- ItemThe Nexus Land-Use model version 1.0, an approach articulating biophysical potentials and economic dynamics to model competition for land-use(München : European Geopyhsical Union, 2012) Souty, F.; Brunelle, T.; Dumas, P.; Dorin, B.; Ciais, P.; Crassous, R.; Müller, C.; Bondeau, A.Interactions between food demand, biomass energy and forest preservation are driving both food prices and land-use changes, regionally and globally. This study presents a new model called Nexus Land-Use version 1.0 which describes these interactions through a generic representation of agricultural intensification mechanisms within agricultural lands. The Nexus Land-Use model equations combine biophysics and economics into a single coherent framework to calculate crop yields, food prices, and resulting pasture and cropland areas within 12 regions inter-connected with each other by international trade. The representation of cropland and livestock production systems in each region relies on three components: (i) a biomass production function derived from the crop yield response function to inputs such as industrial fertilisers; (ii) a detailed representation of the livestock production system subdivided into an intensive and an extensive component, and (iii) a spatially explicit distribution of potential (maximal) crop yields prescribed from the Lund-Postdam-Jena global vegetation model for managed Land (LPJmL). The economic principles governing decisions about land-use and intensification are adapted from the Ricardian rent theory, assuming cost minimisation for farmers. In contrast to the other land-use models linking economy and biophysics, crops are aggregated as a representative product in calories and intensification for the representative crop is a non-linear function of chemical inputs. The model equations and parameter values are first described in details. Then, idealised scenarios exploring the impact of forest preservation policies or rising energy price on agricultural intensification are described, and their impacts on pasture and cropland areas are investigated.