@misc{WeisserStueblerMatheisetal.2017, author = {Weisser, Karin and St{\"u}bler, Sabine and Matheis, Walter and Huisinga, Wilhelm}, title = {Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products}, series = {Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology}, volume = {88}, journal = {Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology}, publisher = {Elsevier}, address = {San Diego}, issn = {0273-2300}, doi = {10.1016/j.yrtph.2017.02.018}, pages = {310 -- 321}, year = {2017}, abstract = {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.}, language = {en} } @phdthesis{MartinezJaime2017, author = {Mart{\´i}nez Jaime, Silvia}, title = {Towards the understanding of protein function and regulation}, school = {Universit{\"a}t Potsdam}, pages = {131}, year = {2017}, language = {en} } @article{BuehningVallerianiLeimkuehler2017, author = {B{\"u}hning, Martin and Valleriani, Angelo and Leimk{\"u}hler, Silke}, title = {The role of SufS is restricted to Fe-S cluster biosynthesis in escherichia coli}, series = {Biochemistry}, volume = {56}, journal = {Biochemistry}, publisher = {American Chemical Society}, address = {Washington}, issn = {0006-2960}, doi = {10.1021/acs.biochem.7b00040}, pages = {1987 -- 2000}, year = {2017}, abstract = {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.}, language = {en} } @article{HeimLenskiSchulzeetal.2017, author = {Heim, Olga and Lenski, Johannes and Schulze, Jelena and Jung, Kirsten and Kramer-Schadt, Stephanie and Eccard, Jana and Voigt, Christian C.}, title = {The relevance of vegetation structures and small water bodies for bats foraging above farmland}, series = {Basic and applied ecology : Journal of the Gesellschaft f{\"u}r {\"O}kologie}, volume = {27}, journal = {Basic and applied ecology : Journal of the Gesellschaft f{\"u}r {\"O}kologie}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {1439-1791}, doi = {10.1016/j.baae.2017.12.001}, pages = {9 -- 19}, year = {2017}, abstract = {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.}, language = {en} } @article{SkłodowskiRiedelsbergerRaddatzetal.2017, author = {Skłodowski, Kamil and Riedelsberger, Janin and Raddatz, Natalia and Riadi, Gonzalo and Caballero, Julio and Ch{\´e}rel, Isabelle and Schulze, Waltraud and Graf, Alexander and Dreyer, Ingo}, title = {The receptor-like pseudokinase MRH1 interacts with the voltage-gated potassium channel AKT2}, series = {Scientific reports}, volume = {7}, journal = {Scientific reports}, publisher = {Nature Publishing Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep44611}, pages = {12}, year = {2017}, abstract = {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.}, language = {en} } @article{FalkKirkLohmannetal.2017, author = {Falk, Thomas and Kirk, Michael and Lohmann, Dirk and Kruger, Bertus and H{\"u}ttich, Christian and Kamukuenjandje, Richard}, title = {The profits of excludability and transferability in redistributive land reform in central Namibia}, series = {Development Southern Africa}, volume = {34}, journal = {Development Southern Africa}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {0376-835X}, doi = {10.1080/0376835X.2016.1269633}, pages = {314 -- 329}, year = {2017}, abstract = {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.}, language = {en} } @article{RuelensZhangvanMouriketal.2017, author = {Ruelens, Philip and Zhang, Zhicheng and van Mourik, Hilda and Maere, Steven and Kaufmann, Kerstin and Geuten, Koen}, title = {The Origin of Floral Organ Identity Quartets}, series = {The plant cell}, volume = {29}, journal = {The plant cell}, number = {2}, publisher = {American Society of Plant Physiologists}, address = {Rockville}, issn = {1040-4651}, doi = {10.1105/tpc.16.00366}, pages = {229 -- 242}, year = {2017}, abstract = {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.}, language = {en} } @article{EdeniusChoiHeimetal.2017, author = {Edenius, Lars and Choi, Chang-Yong and Heim, Wieland and Jaakkonen, Tuomo and De Jong, Adriaan and Ozaki, Kiyoaki and Roberge, Jean-Michel}, title = {The next common and widespread bunting to go?}, series = {Bird conservation international}, volume = {27}, journal = {Bird conservation international}, number = {1}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {0959-2709}, doi = {10.1017/S0959270916000046}, pages = {35 -- 44}, year = {2017}, abstract = {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.}, language = {en} } @misc{GonzalezFortesTassiGhirottoetal.2017, author = {Gonzalez-Fortes, Gloria M. and Tassi, Francesca and Ghirotto, Silvia and Henneberger, Kirstin and Hofreiter, Michael and Barbujani, Guido}, title = {The Neolithic transition at the Western edge of Europe}, series = {American journal of physical anthropology}, volume = {162}, journal = {American journal of physical anthropology}, publisher = {Wiley}, address = {Hoboken}, issn = {0002-9483}, pages = {198 -- 198}, year = {2017}, language = {en} } @article{FriemelMareljaLietal.2017, author = {Friemel, Martin and Marelja, Zvonimir and Li, Kuanyu and Leimk{\"u}hler, Silke}, title = {The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with L-Cysteine Desulfurase NFS1}, series = {Biochemistry}, volume = {56}, journal = {Biochemistry}, publisher = {American Chemical Society}, address = {Washington}, issn = {0006-2960}, doi = {10.1021/acs.biochem.6b01239}, pages = {1797 -- 1808}, year = {2017}, abstract = {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.}, language = {en} }