TY - GEN A1 - Weisser, Karin A1 - Stübler, Sabine A1 - Matheis, Walter A1 - Huisinga, Wilhelm T1 - Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products T2 - Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology N2 - As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved. KW - Aluminium KW - Aluminium adjuvants KW - Absorption kinetics KW - Toxicokinetic modelling KW - In vitro dissolution Y1 - 2017 U6 - https://doi.org/10.1016/j.yrtph.2017.02.018 SN - 0273-2300 SN - 1096-0295 VL - 88 SP - 310 EP - 321 PB - Elsevier CY - San Diego ER - TY - THES A1 - Martínez Jaime, Silvia T1 - Towards the understanding of protein function and regulation BT - organization of the mitochondrial protein complexome under different conditions and the role of SUM03 in Arabidopsis thaliana Y1 - 2017 ER - TY - JOUR A1 - Bühning, Martin A1 - Valleriani, Angelo A1 - Leimkühler, Silke T1 - The role of SufS is restricted to Fe-S cluster biosynthesis in escherichia coli JF - Biochemistry N2 - In Escherichia coli, two different systems that are important for the coordinate formation of Fe–S clusters have been identified, namely, the ISC and SUF systems. The ISC system is the housekeeping Fe–S machinery, which provides Fe–S clusters for numerous cellular proteins. The IscS protein of this system was additionally revealed to be the primary sulfur donor for several sulfur-containing molecules with important biological functions, among which are the molybdenum cofactor (Moco) and thiolated nucleosides in tRNA. Here, we show that deletion of central components of the ISC system in addition to IscS leads to an overall decrease in Fe–S cluster enzyme and molybdoenzyme activity in addition to a decrease in the number of Fe–S-dependent thiomodifications of tRNA, based on the fact that some proteins involved in Moco biosynthesis and tRNA thiolation are Fe–S-dependent. Complementation of the ISC deficient strains with the suf operon restored the activity of Fe–S-containing proteins, including the MoaA protein, which is involved in the conversion of 5′GTP to cyclic pyranopterin monophosphate in the fist step of Moco biosynthesis. While both systems share a high degree of similarity, we show that the function of their respective l-cysteine desulfurase IscS or SufS is specific for each cellular pathway. It is revealed that SufS cannot play the role of IscS in sulfur transfer for the formation of 2-thiouridine, 4-thiouridine, or the dithiolene group of molybdopterin, being unable to interact with TusA or ThiI. The results demonstrate that the role of the SUF system is exclusively restricted to Fe–S cluster assembly in the cell. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biochem.7b00040 SN - 0006-2960 VL - 56 SP - 1987 EP - 2000 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Heim, Olga A1 - Lenski, Johannes A1 - Schulze, Jelena A1 - Jung, Kirsten A1 - Kramer-Schadt, Stephanie A1 - Eccard, Jana A1 - Voigt, Christian C. T1 - The relevance of vegetation structures and small water bodies for bats foraging above farmland JF - Basic and applied ecology : Journal of the Gesellschaft für Ökologie N2 - Bats are known to forage and commute close to vegetation structures when moving across the agricultural matrix, but the role of isolated landscape elements in arable fields for bat activity is unknown. Therefore, we investigated the influence of small isolated ponds which lie within arable fields close to vegetation structures on the flight and foraging activity of bats. Additionally, we compared species-specific activity measures between forest edges and linear structures such as hedgerows. We repeatedly recorded bat activity using passive acoustic monitoring along 20 transects extending from the vegetation edge up to 200 m into the arable field (hereafter: edge-field interface) with a small pond present at five transects per edge type (linear vs. forest). Using generalized linear mixed effect models, we analyzed the effects of edge type, pond presence and the season on species-specific flight and foraging activity within the edge-field interface. We found a higher flight activity of Nyctalus noctula and Pipistrellus pygmaeus above the arable field when a pond was present. Furthermore, Pipistrellus nathusii and Pipistrellus pipistrellus foraged more frequently at forest edges than at linear structures (e.g. hedgerows). Additionally, we found three major patterns of seasonal variation in the activity of bats along the edge-field interface. This study highlights the species-specific and dynamic use of forest and hedgerow or tree line edges by bats and their importance for different bat species in the agricultural landscape. Further, additional landscape elements such as small isolated ponds within arable fields might support the activity of bats above the open agricultural landscape, thereby facilitating agroecosystem functioning. Therefore, additional landscape elements within managed areas should be restored and protected against the conversion into arable land and better linked to surrounding landscape elements in order to efficiently support bats within the agroecosystem. KW - Hedgerow KW - Forest edge KW - Pond KW - European bats KW - Agricultural landscape KW - Wind turbines Y1 - 2017 U6 - https://doi.org/10.1016/j.baae.2017.12.001 SN - 1439-1791 SN - 1618-0089 VL - 27 SP - 9 EP - 19 PB - Elsevier GMBH CY - München ER - TY - JOUR A1 - Skłodowski, Kamil A1 - Riedelsberger, Janin A1 - Raddatz, Natalia A1 - Riadi, Gonzalo A1 - Caballero, Julio A1 - Chérel, Isabelle A1 - Schulze, Waltraud A1 - Graf, Alexander A1 - Dreyer, Ingo T1 - The receptor-like pseudokinase MRH1 interacts with the voltage-gated potassium channel AKT2 JF - Scientific reports N2 - The potassium channel AKT2 plays important roles in phloem loading and unloading. It can operate as inward-rectifying channel that allows H+-ATPase-energized K+ uptake. Moreover, through reversible post-translational modifications it can also function as an open, K+-selective channel, which taps a ‘potassium battery’, providing additional energy for transmembrane transport processes. Knowledge about proteins involved in the regulation of the operational mode of AKT2 is very limited. Here, we employed a large-scale yeast two-hybrid screen in combination with fluorescence tagging and null-allele mutant phenotype analysis and identified the plasma membrane localized receptor-like kinase MRH1/MDIS2 (AT4G18640) as interaction partner of AKT2. The phenotype of the mrh1-1 knockout plant mirrors that of akt2 knockout plants in energy limiting conditions. Electrophysiological analyses showed that MRH1/MDIS2 failed to exert any functional regulation on AKT2. Using structural protein modeling approaches, we instead gathered evidence that the putative kinase domain of MRH1/MDIS2 lacks essential sites that are indispensable for a functional kinase suggesting that MRH1/MDIS2 is a pseudokinase. We propose that MRH1/MDIS2 and AKT2 are likely parts of a bigger protein complex. MRH1 might help to recruit other, so far unknown partners, which post-translationally regulate AKT2. Additionally, MRH1 might be involved in the recognition of chemical signals. Y1 - 2017 U6 - https://doi.org/10.1038/srep44611 SN - 2045-2322 VL - 7 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Falk, Thomas A1 - Kirk, Michael A1 - Lohmann, Dirk A1 - Kruger, Bertus A1 - Hüttich, Christian A1 - Kamukuenjandje, Richard T1 - The profits of excludability and transferability in redistributive land reform in central Namibia JF - Development Southern Africa N2 - Policies which redistribute property rights to land can improve the well-being of rural households and can have overall growth effects. In many cases, however, land reforms are driven mainly by politically justified objectives. Under such circumstances, little emphasis is placed on whether and, if so, how property rights can increase productivity. Following 18 years of land reform implementation in Namibia, we evaluated 65 beneficiaries in Namibia. We assess to which degree land rights affects their farm income. The study focuses on Namibia’s two main commercial land reform instruments, namely the Farm Unit Resettlement Scheme and the Affirmative Action Loan Scheme. We find evidence that the majority of land reform projects are not profitable. Further, our study confirms the importance of the right to restrict land access compared with the right to transfer. The long-term leasehold contract seemingly provides sufficient incentives to make productive use of the land. KW - Redistributive land reform KW - property rights KW - farm productivity KW - pastoralism KW - Namibia Y1 - 2017 U6 - https://doi.org/10.1080/0376835X.2016.1269633 SN - 0376-835X SN - 1470-3637 VL - 34 SP - 314 EP - 329 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Ruelens, Philip A1 - Zhang, Zhicheng A1 - van Mourik, Hilda A1 - Maere, Steven A1 - Kaufmann, Kerstin A1 - Geuten, Koen T1 - The Origin of Floral Organ Identity Quartets JF - The plant cell N2 - The origin of flowers has puzzled plant biologists ever since Darwin referred to their sudden appearance in the fossil record as an abominable mystery. Flowers are considered to be an assembly of protective, attractive, and reproductive male and female leaf-like organs. Their origin cannot be understood by a morphological comparison to gymnosperms, their closest relatives, which develop separate male or female cones. Despite these morphological differences, gymnosperms and angiosperms possess a similar genetic toolbox consisting of phylogenetically related MADS domain proteins. Using ancestral MADS domain protein reconstruction, we trace the evolution of organ identity quartets along the stem lineage of crown angiosperms. We provide evidence that current floral quartets specifying male organ identity, which consist of four types of subunits, evolved from ancestral complexes of two types of subunits through gene duplication and integration of SEPALLATA proteins just before the origin of flowering plants. Our results suggest that protein interaction changes underlying this compositional shift were the result of a gradual and reversible evolutionary trajectory. Modeling shows that such compositional changes may have facilitated the evolution of the perfect, bisexual flower. Y1 - 2017 U6 - https://doi.org/10.1105/tpc.16.00366 SN - 1040-4651 SN - 1532-298X VL - 29 IS - 2 SP - 229 EP - 242 PB - American Society of Plant Physiologists CY - Rockville ER - TY - JOUR A1 - Edenius, Lars A1 - Choi, Chang-Yong A1 - Heim, Wieland A1 - Jaakkonen, Tuomo A1 - De Jong, Adriaan A1 - Ozaki, Kiyoaki A1 - Roberge, Jean-Michel T1 - The next common and widespread bunting to go? BT - global population decline in the Rustic Bunting Emberiza rustica JF - Bird conservation international N2 - Populations of several long-distance migratory songbirds in Eurasia are in peril, drastically illustrated by the recent range-wide population collapse in the Yellow-breasted Bunting Emberiza aureola. There are signals of a strong decline also in the Rustic Bunting E. rustica, but no range-wide assessment of population trends in this superabundant and widespread bunting species has yet been undertaken. The conservation status of Rustic Bunting is ‘Least Concern’ on the global IUCN Red List, but it has recently been upgraded to ‘Vulnerable’ on the European Red List. To assess the Rustic Bunting’s global conservation status we compiled, for the first time, population data across its breeding and wintering ranges. The analysis reveals a 75–87% decline in overall population size over the last 30 years and a 32–91% decline over the last 10 years. The trend estimates indicate that the long-term (30-year) range-wide population decline in the Rustic Bunting is of similar magnitude to two well-known examples of declining species within the same genus, the Yellow-breasted Bunting and the Ortolan Bunting E. hortulana. The magnitude of the range-wide population decline over the last 10 years suggests that the Rustic Bunting could be upgraded from ‘Least Concern’ to ‘Vulnerable’ or ‘Endangered’ on the IUCN global Red List. Agricultural intensification in the wintering range and intensified levels of disturbance, including logging and fire, in the breeding range could be important drivers of the range-wide population decline, and persecution could also contribute. Untangling threat factors and their interactions on Rustic Bunting is necessary for conservation, but hampered by our currently limited understanding of the relationships between population dynamics and different threats. Y1 - 2016 U6 - https://doi.org/10.1017/S0959270916000046 SN - 0959-2709 SN - 1474-0001 VL - 27 IS - 1 SP - 35 EP - 44 PB - Cambridge Univ. Press CY - New York ER - TY - GEN A1 - Gonzalez-Fortes, Gloria M. A1 - Tassi, Francesca A1 - Ghirotto, Silvia A1 - Henneberger, Kirstin A1 - Hofreiter, Michael A1 - Barbujani, Guido T1 - The Neolithic transition at the Western edge of Europe T2 - American journal of physical anthropology Y1 - 2017 SN - 0002-9483 SN - 1096-8644 VL - 162 SP - 198 EP - 198 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Friemel, Martin A1 - Marelja, Zvonimir A1 - Li, Kuanyu A1 - Leimkühler, Silke T1 - The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with L-Cysteine Desulfurase NFS1 JF - Biochemistry N2 - Assembly of iron sulfur (FeS) clusters is an important process in living cells. The initial sulfur mobilization step for FeS cluster biosynthesis is catalyzed by L-cysteine desulfurase NFS1, a reaction that is localized in mitochondria in humans. In humans, the function of NFS1 depends on the ISD11 protein, which is required to stabilize its structure. The NFS1/ISD11 complex further interacts with scaffold protein ISCU and regulator protein frataxin, thereby forming a quaternary complex for FeS cluster formation. It has been suggested that the role of ISD11 is not restricted to its role in stabilizing the structure of NFS1, because studies of single-amino acid variants of ISD11 additionally demonstrated its importance for the correct assembly of the quaternary complex. In this study, we are focusing on the N-terminal region of ISD11 to determine the role of N-terminal amino acids in the formation of the complex with NFS1 and to reveal the mitochondria) targeting sequence for subcellular localization. Our in vitro studies with the purified proteins and in vivo studies in a cellular system show that the first 10 N-terminal amino acids of ISD11 are indispensable for the activity of NFS1 and especially the conserved "LYR" motif is essential for the role of ISD11 in forming a stable and active complex with NFS1. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biochem.6b01239 SN - 0006-2960 VL - 56 SP - 1797 EP - 1808 PB - American Chemical Society CY - Washington ER -